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CAN WE PREDICT ATRIAL FIBRILLATION?<br />

1603 Left atrial asynchrony is a major predictor of<br />

recurrence of atrial fibrillation after electrical<br />

cardioversion<br />

G. Dell’era, E. Rondano, G. De Luca, C. Piccinino, G. Bellomo,<br />

P.N. Marino on behalf of NAIF. University of Eastern Piedmont,<br />

Cardiology, Novara, Italy<br />

Background: Dispersed conduction due to atrial fibrillation (AF) is linked to cavity<br />

remodelling and loss of filling and emptying properties, mostly consequence of<br />

atrial fibrosis. The aim of the current study was to evaluate whether left atrial<br />

asynchrony (LAS) is a predictor of recurrence of atrial fibrillation after electrical<br />

cardioversion (EC)<br />

Methods: Atrial volume was calculated from anteroposterior diameter and area<br />

according to the formula: 4.2*diameter/ 2*area/2. 2D strain (speckle tracking technique)<br />

was used to estimate peak and standard deviation (SD) of the time-to-peak<br />

(% of R-R’ interval) of the deformation of 6 segments arbitrarily identified along the<br />

septum, the roof and the lateral wall of the atrial cavity, as imaged in a 4-chamber<br />

view. LAS was quantified according to the SD of the time-to-peak. Patients were<br />

divided in quartiles according to the extent of LAS.<br />

Results: A total of 130 patients undergoing electrical cardioversion for AF were<br />

prospectively enrolled. LAS was linearly related with left atrial dimension (p =<br />

0.052) and left ventricular mass (p = 0.073). No differences were observed between<br />

the groups in terms of clinical and additional echocardiographic variables.<br />

At 1 year follow-up a recurrence of atrial fibrillation was observed in 53.1% of<br />

patients. LAS was linearly related with the rate of recurrence of atrial fibrillation<br />

at 1 year follow-up (Figure). At multivariate analysis only LAS (OR [95 CI] = 1.49<br />

[1.07-2.09], p = 0.019) and left ventricular end-diastolic volume (OR [95 CI] =<br />

1.033 [1.004-1.062], p = 0.025) were identified as independent predictors of recurrence<br />

of AF.<br />

Conclusion: This is the first study showing that left atrial asynhrony before EC<br />

is a major and independent predictor of recurrence of atrial fibrillation in patients<br />

undergoing EC.<br />

1604 Obstructive sleep apnea is an independent predictor of<br />

recurrences after circumferential pulmonary vein<br />

ablation for atrial fibrillation<br />

M. Matiello, A. Berruezo, D. Tamborero, L. Mont, B. Daga, J. Brugada.<br />

Hospital Clinic University, Arrhythmias Section, Barcelona, Spain<br />

Obstructive Sleep Apnea (OSA) has been associated with atrial fibrillation (AF).<br />

However, the efficacy of AF ablation in patients with this condition has not been<br />

evaluated. The aim of this study was to evaluate whether OSA influence the ablation<br />

outcome.<br />

Methods: A series of 120 consecutive patients submitted to circumferential pulmonary<br />

vein (CPVA) ablation were included in the study. All patients underwent<br />

a complete echocardiographic and clinical evaluation, including body mass index<br />

(BMI). Diagnosis of OSA was based on the results of the Berlin questionnaire. The<br />

use of continuos positive airway pressure (CPAP) was also recorded. Follow-up<br />

consisted of outpatient visits and 24-h Holter monitoring at one, four and seven<br />

months, and every six months thereafter if the patient remained asymptomatic.<br />

Any documented episode of AF or left atrial flutter presenting after the threemonths<br />

blanking period was considered as a recurrence.<br />

Results: OSA was diagnosed in 37 patients (30%). Of them, 12 (27%) were<br />

diagnosed through a polisomnography, and 9 (24%) were under treatment with<br />

CPAP. At one year follow-up, 36% of OSA patients were arrhythmia free against<br />

67% of the remaining patients (p=0.005). Obesity and BMI were not related with<br />

procedure failure. At the multivariable Cox analysis, anteroposterior left atrial diameter<br />

(HR= 1.090, 95% CI 1.03-1.16; p=0.005) and OSA (HR= 2.20, 95% CI<br />

1.14-4.26; p=0.019) were identified as independent predictors of arrhythmia recurrence.<br />

Treatment with CPAP did not improve ablation results.<br />

Conclusion: OSA is an independent predictor of CPVA failure.<br />

Can we predict atrial fibrillation? 257<br />

1605 Isolated atrial microvascular dysfunction in patients<br />

with lone recurrent atrial fibrillation<br />

E.I. Skalidis, M.I. Hamilos, I.K. Karalis, G. Chlouverakis, E. Pouli,<br />

E. Koutalas, N.E. Igoumenidis, E.A. Zacharis, G.E. Kochiadakis,<br />

P.E. Vardas. Heraklion University Hospital, Department of Cardiology,<br />

Heraklion, Greece<br />

Aim: Although acute atrial ischemia has been implicated in the pathogenesis of<br />

atrial fibrillation, there are few data concerning human atrial myocardial perfusion<br />

and none for patients with lone recurrent atrial fibrillation (LRAF). The purpose of<br />

this study was to assess atrial myocardial perfusion in patients with LRAF.<br />

Methods: Sixteen patients with LRAF and fifteen control subjects with suitable<br />

coronary anatomy underwent time-averaged peak coronary blood flow velocity<br />

measurements (APV cm/s), using a Doppler guidewire in the proximal left circumflex<br />

coronary artery (LCx) and in the left atrial circumflex branch (LACB), at<br />

baseline (b) and after adenosine administration to achieve maximal hyperemia<br />

(h). Coronary flow reserve was defined as h-APV/b-APV.<br />

Results: Although there were no statistically significant differences in b-APV<br />

between patients with LRAF and control subjects nor between the LACB and<br />

LCx, there were significant group (p=0.002), artery (p=0.001) and interaction<br />

(p


258 Can we predict atrial fibrillation? / Thromboembolic risks and therapeutic approaches in atrial fibrillation<br />

patients with paroxysmal AF, (11.90±4.79 ng/ml vs. 14.98±6.28 ng/ml, p=0.03<br />

and 154.90±44.91 ng/ml vs. 129.75±37.92 ng/ml, p


Thromboembolic risks and therapeutic approaches in atrial fibrillation / Healthy bone marrow for a healthy heart 259<br />

Conclusions: In patients with short-term AF TEE revealed left atrial thrombi in<br />

1.4% and dense spontaneous echo contrast in 10% of patients. Patients with<br />

TEE-guided cardioversion of short-term AF had an 8-fold reduced incidence of<br />

stroke/death after 1 month than patients undergoing conventional approach without<br />

TEE. Thus, in patients with AF < 48 hours, TEE-guided electrical cardioversion<br />

might be useful to reduce the embolic risk.<br />

1612 Beta-fibrinogen 455 G/A gene polymorphism is<br />

associated with the left atrial thrombus and severe<br />

spontaneous echo contrast in atrial fibrillation<br />

V. Bozdemir, O. Kirimli, B. Akdeniz, A. Aslan, V. Kala, E. Ozel,<br />

O. Senaslan, S. Guneri. Dokuz Eylul University Cardiology, Cardiology,<br />

Izmir, Turkey<br />

Purpose: The detection of genetically abnormalities related with the thrombogenic<br />

factors may aid to determine the risk of thromboembolism and mechanism<br />

of thrombus formation in atrial fibrillation (AF). In this study, we aimed to investigate<br />

the effect of the presence of beta fibrinogen gene polymorphism or glycoprotein<br />

IIIa gene polymorphism on the development left atrial (LA) thrombus or<br />

spontaneous echo contrast (SEC) in patients with atrial fibrillation.<br />

Methods: Forty-seven patients with persistent AF, which were scheduled for cardioversion,<br />

in whom transesophageal echocardiography was performed for the<br />

detection of LA thrombus and SEC were included in the study. Patients were divided<br />

in two groups; those with LA thrombus or severe SEC (n=27) consisted to<br />

group I and those without thrombus or severe SEC were in group II (n=20). All<br />

patients were also evaluated in terms of mitral regurgitation (grading were made<br />

according to ASE criteria) and presence of mild to moderate SEC and gene polymorphism.<br />

DNA analysis was conducted to determine the beta-fibrinogen 455<br />

G/A polymorphism and glycoprotein IIIa PlA1/A2 polymorphism, blood samples<br />

were taken from the peripheral venous route.<br />

Results: There were no significance difference regarding to demographic (age,<br />

sex) and clinical characteristics (LA size, LVEF, the prevalence of hypertension,<br />

diabetes etc.) between groups. The frequency of beta-fibrinogen 455 G/A polymorphism<br />

was significantly higher (44.4%) in group I compared to group II (10%)<br />

(p=0.01). Glycoprotein IIIa Pl A1/A2 polymorphism was not different between<br />

groups (22.2% in group I and 25% group II; p=0.82). In patients with left atrial<br />

thrombus, comparing to those without thrombus, mitral regurgitation score was<br />

tend to be lower (p=0.08) and the prevalence of SEC (mild to severe) was found<br />

to be significantly higher (p=0.03).<br />

Conclusion: This cross-sectional study revealed that, beta-fibrinogen 455 G/A<br />

gene polymorphism in patients with atrial fibrillation is associated with the presence<br />

of left atrial thrombus and severe SEC, whereas the glycoprotein IIIa<br />

PlA1/A2 polymorphism is not. Beta-fibrinogen 455 G/A gene polymorphism may<br />

be a promising marker for the prediction of thromboembolism risk in patients with<br />

atrial fibrillation.<br />

1613 Prevalence and clinical impact of left atrial thrombus<br />

and dense spontaneous echo contrast in patients with<br />

atrial fibrillation and low CHADS2 score<br />

T. Kleemann, T. Becker, M. Strauss, S. Schneider, K. Seidl.<br />

Herzzentrum Ludwigshafen, Medizinische Klinik B, Ludwigshafen,<br />

Germany<br />

Aim of the study was to evaluate the prevalence and clinical impact of left atrial<br />

thrombus and dense spontaneous echo contrast (SEC) in patients with atrial fibrillation<br />

(AF) and low CHADS2 score.<br />

Methods and results: A total of 295 consecutive patients with nonvalvular AF<br />

and a CHADS2 score of 0 or 1 from the prospective single center registry ANTIK<br />

who underwent transoesophageal echocardiography (TEE) before cardioversion<br />

were analysed. Median follow-up was 5 years. Left atrial thrombus was present in<br />

3% and dense SEC in 8% of patients.<br />

Independent predictors for the presence of thrombus or dense SEC were ejection<br />

fraction (EF) < 40% and left atrial diameter > 50mm. In anticoagulated patients<br />

thrombus and dense SEC were not independently associated with an increased<br />

risk for stroke or death during the 5-year follow-up (OR 1.73, 95% CI<br />

0.65-4.63).<br />

Table 1. Clinical characteristics of patients with AF and CHADS2 score of 0/1: left atrial thrombus<br />

or dense SEC versus no thrombus/SEC<br />

Thrombus or dense SEC No thrombus and no dense SEC p-value<br />

(n=30) (n=265)<br />

Age (years) 62 (55-72) 61 (54-68) 0.23<br />

Male 77% 78% 0.86<br />

NYHA II+ 50% 21% 0.01<br />

Hypertension 23% 31% 0.41<br />

Diabetes 3% 0.8% 0.18<br />

EF < 40% 30% 11% < 0.01<br />

LA dimension > 50mm 30% 8% < 0.001<br />

LVEDD > 60mm 11% 7% 0.56<br />

Conclusions: Despite a low CHADS2 score of 0/1 3% of patients have left atrial<br />

thrombus and 8% dense SEC. Independent predictors for the presence of thrombus<br />

and dense SEC were EF < 40% and left atrial dimension > 50mm. Thus,<br />

echocardiography might be a useful tool for further risk stratification in patients<br />

with low CHADS2 score.<br />

1614 Thromboembolic risk assessment in persistent atrial<br />

flutter: is it different from atrial fibrillation? A singlecenter<br />

TEE study on 483 consecutive patients<br />

A. Cresti, G. Miracapillo, F. Cesareo, A. Costoli, L. Addonisio,<br />

S. Severi. Division of Cardiology, Misericordia Hospital, Cardiology,<br />

Grosseto, Italy<br />

Objectives: despite a lack of clear evidence, risk assessment and embolic prophylactic<br />

treatment of atrial flutter (AFL) is similar to that of atrial fibrillation (AF).<br />

Recent studies evidenced lower embolic risk in AFL and Transesophageal Echocardiography<br />

(TEE) has been recently considered redundant before cardioversion<br />

(CV) in unselected pts. Aim of our study was to evaluate the presence of auricular<br />

thrombosis risk by TEE in a large series of AFL pts.<br />

Methods: in the period 2000-07, 483 consecutive pts, referred for multiplane TEE<br />

before medical or electrical CV for AF (Group 1, N=382, 79%) or AFL (Group 2,<br />

N=101, 21%), were included. Basal clinical characteristics were the following:<br />

male 60%, mean age 70±10 yrs, hearth disease: valvular 49.4%, hypertensive<br />

25%, ischemic 18.5%, idiophatic dilatative 5.4%, others 1.7%; EF 50±11%, left<br />

ventricular end diastolic diameter (LVED) 52±6 mm, left atrial parasternal diameter<br />

(LA) 49±7 mm, history of cerebral accidents 5.2%, type of arrhythmia: persistent<br />

85.3%, paroxysmal 4.8%, permanent 9.9%. Anticoagulation was recommended<br />

according to standard protocols. Thrombosis risk assessment was evaluated<br />

according to the presence of left or right atrial thrombus, severe spontaneous<br />

echocontrast (SSE) in the left atrium or in the auricle and left atrial appendage<br />

Doppler velocities (LAADV) < 20 cm/sec.<br />

Results: TEE was performed in all pts without complications. Basal clinical<br />

characteristics of Group 1 (AF) vs Group 2 (AFL) were the following: male<br />

56 vs 75%(p=0.000), mean age 69±10 vs 72±9 yrs (p=0.005), EF 52±11 vs<br />

46±11%(p=0.002), LVED 52±6 vs53±7mm (p=0.54), LA 49±7 vs48±6 mm<br />

(p=0.34), hearth disease: valvular 50.8 vs 44.7%(p=0.59), hypertensive 26.9<br />

vs 18.4%(p=0.33), ischemic 14.6 vs 31.6%(p=0.04), idiophatic dilatative 6.2 vs<br />

2.6%(p=0.39), others 1.5 vs 2.6%(p=0.67); history of cerebral accidents 5.8 vs<br />

3.0%(p=0.26); type of arrhythmia: persistent 82.4 vs 95.9%(p=0.29), paroxysmal<br />

5.4 vs 2.7%(p=0.36), permanent 12.3 vs 1.4% (p=0.009); LAADV: 36.1±15.8 vs<br />

46.1±10.8 cm/sec (p=0.000). Thrombosis risk factors of Group 1 vs Group 2 resulted<br />

respectively: presence of left or right atrial thrombus 9.8 vs. 2.0%(p=0.012),<br />

SSE in the left atrium or in the auricle 4.6 vs 3.0%(p=0.49), LAADV


260 Healthy bone marrow for a healthy heart<br />

MI and left ventricular dysfunction. This may contribute to a better outcome after<br />

acute event.<br />

1632 Vascular oxidative stress inhibits mobilization of<br />

circulating stem cells with endothelial progenitor<br />

capacity in mice<br />

T. Suvorava1 ,S.Kumpf1 ,V.Adams2 ,G.Kojda1 . 1Heinrich Heine<br />

University, Institute of Pharmacology, Duesseldorf, Germany;<br />

2University of Leipzig, <strong>Heart</strong> Center Leipzig, Leipzig, Germany<br />

Purpose: The number of circulating stem cells with endothelial progenitor capacity<br />

(EPCs) was reported to inversely correlate with the number of cardiovascular<br />

risk factors and is reduced in cardiovascular disease. Despite recent advances<br />

in EPC studies, the molecular mechanisms of EPC mobilization remain unclear.<br />

We sought to investigate the effects of increased vascular oxidative stress on<br />

exercise-induced EPCs mobilization.<br />

Methods: Transgenic mice with a vascular-specific overexpression of catalase<br />

and reduced vascular levels of oxidative stress (cat++) and their transgene negative<br />

littermates (catn) were assigned to a sedentary group and a group undergoing<br />

moderate forced exercise training (15 m/min, 30 min, 5 days a week, 3<br />

weeks). The number of EPCs in peripheral blood was measured by Fluorescence-<br />

Activated Cell Sorting (FACS) using anti-mouse CD3, Flk-1 and CD34, CD133 or<br />

Sca-1 antibodies. Additionally, the effects of different amounts of physical activity<br />

on EPC mobilization were investigated in sedentary (singularized), freely moving<br />

(6 mice per cage), voluntary (9.8±0.7 km/night) and forced (15 m/min, 5 days, 30<br />

min/day) running C57BL/6 mice.<br />

Results: There was no difference in circulating EPCs between sedentary and<br />

freely moving C57BL/6 mice (p>0.05, n=5). Three weeks of forced exercise training<br />

failed to mobilize EPCs defined as double positive for Flk-1 and CD34 or more<br />

immature hematopoeitic stem marker CD133 (p>0.05, n=5-9). Similarly, the number<br />

of EPCs was not different between sedentary and voluntary exercised groups<br />

(n=5-8, all p>0.05). FACS analysis of cat++ and catn peripheral blood revealed no<br />

effect of catalase overexpression on the basal level of circulating EPCs (p=0.68,<br />

n=8). Inhibition of catalase by 3 week treatment with catalase inhibitor aminotriazole<br />

(670 mg/kg in drinking water) strongly reduced the number of endothelial progenitors<br />

in blood of sedentary catn, and to a lesser extend also in cat++(p


Healthy bone marrow for a healthy heart / Exercise testing in athletes: new answers from an old test 261<br />

1636 Modifications of reticulocytes and reticulated platelets<br />

in sedentary healthy men after an acute episode of<br />

strenuous exercise<br />

F. Cesari 1 ,F.Sofi 2 , A. Capalbo 1 , N. Pucci 1 ,A.M.Gori 1 , R. Caporale 3 ,<br />

A. Fanelli 3 ,R.Abbate 1 ,G.F.Gensini 1 . 1 University of Florence, Med.<br />

& Surgical Critical Care, Florence, Italy; 2 University of Florence, Faculty of<br />

Medicine, Med. & Surgical Critical Care, Thrombosis Cen., Florence, Italy;<br />

3 Azienda Ospedaliero-Universitaria Careggi, Central Laboratory, Florence, Italy<br />

Introduction: Exercise is considered a physiological stimulus for cells’ release by<br />

the bone marrow. In particular, maximal exercise, carried out under hypoxic conditions,<br />

has been reported to determine reticulocytes’ release, probably due to<br />

the augmented levels of erythropoietin. We aimed to investigate whether physical<br />

exercise can determine, together with reticulocytes, also the release of reticulated<br />

platelets (RP), immature and more reactive platelets that reflect platelet production<br />

from megakariocytes.<br />

Methods: Haematological parameters (red blood count, white blood count,<br />

haematocrit, haemoglobin, platelets), reticulocytes, and RP were measured in<br />

20 healthy sedentary men (median age: 34 years) by using the Sysmex XE-<br />

2100 haematology analyzer (Sysmex, Kobe, Japan). Reticulocytes and RP were<br />

counted according to the measurement of scatter and RNA content was analyzed<br />

using oxazine. The reticulocytes’ fractions with low (L), medium (M), and high (H)<br />

RNA contents were assessed, the M and H fraction being immature reticulocytes.<br />

All subjects performed a maximal incremental graded treadmill test and blood<br />

samples were drawn before (T0), at the end (T1), and 30 minutes after the test<br />

(T2).<br />

Results: All the haematological parameters showed a significant (p=0.002) increase<br />

at T1 with respect to T0, by returning similar to baseline at T2. Reticulocytes<br />

demonstrated a significant trend of increase at T1 with respect to T0<br />

[52,650 (35,900-99,500) vs. 51,000(26,800-105,000) ret/microL; p


262 Exercise testing in athletes: new answers from an old test<br />

The amplitude and duration of the P, Q, R, S, and T waves was measured. Specific<br />

note was made of the presence of deep (>-0.2mV) T-wave inversions (excluding<br />

V1, aVr, isolated III or isolated aVl), pathological q waves (> 40 ms in<br />

duration and > 25% of the height of the proceeding R wave). The Romhilt-Estes<br />

points’ score and Sokolow-Lyon voltage criterion for LVH were calculated in each<br />

athlete.<br />

Results: None of the athletes exhibited features consistent with HCM at echocardiography.<br />

Of the 1719 males, 35 (2%) exhibited deep T wave inversions, 15<br />

(0.9%) showed q waves and 172 (10%) fulfilled the Romhilt-Estes points score of<br />

≥ 5 to indicate LVH. In contrast, none of the females demonstrated deep T wave<br />

inversions, pathological q waves or the Romhilt-Estes points score ≥ 5. Males<br />

exhibited a significantly higher prevalence of the Sokolow-Lyon voltage criterion<br />

for LVH compared with females (41.9%vs 14.7%; p


NEW PROGNOSTIC MARKERS IN ACUTE<br />

CARDIAC CARE<br />

1643 Impact of anemia and reduced left ventricular ejection<br />

fraction on in-hospital outcome of acute coronary<br />

syndromes. Euro heart survey ACS III registry<br />

(2006-2007)<br />

W. Wojakowski1 , M. Tendera1 , M. Tubaro2 ,M.Gierlotka3 , H. Bueno4 ,<br />

B. Lindahl5 , M. Hochadel6 ,Y.Hasin7 , J.P. Bassand8 ,A.K.Gitt6 .<br />

1 2 3 Katowice, Poland; III Division of Cardiology, Rome, Italy; III Division of<br />

Cardiology, Zabrze, Poland; 4III Division of Cardiology, Madrid, Spain; 5III Division<br />

of Cardiology, Uppsala, Sweden; 6III Division of Cardiology, Ludwigshafen,<br />

Germany; 7III Division of Cardiology, Haifa, Israel; 8Besancon, France<br />

Aim: of the study was to examine the impact of anemia and reduced left ventricular<br />

ejection fraction (LVEF) on in-hospital outcome in acute coronary syndromes<br />

(ACS).<br />

Methods: Euro <strong>Heart</strong> Survey on Acute Coronary Syndromes analyzed 6498<br />

patients (69% males) admitted across Europe in 2006-2007 with diagnosis of<br />

ACS [56.4% NSTE-ACS (29.6% NSTEMI, 26.8% unstable angina) and 43.6%<br />

STEMI/LBBB]. LVEF was assessed during hospitalization in 93% of patients.<br />

Results: LVEF was normal in 57.1% pts, slightly reduced in 22.5%, moderately<br />

reduced in 13.5% and severely reduced in 6.9% of pts. Anemia (Hb


264 New prognostic markers in acute cardiac care / Resuscitation resuscitated!<br />

Conclusion: Patients presenting with acute dyspnea at the ED, with a positive<br />

cTnT were at a very high risk of in-hospital death. Cardiac troponin T positivity<br />

was an independent predictor of in-hospital death, whereas NT pro-BNP was not.<br />

1647 N-terminal pro-B-type natriuretic peptide changes in<br />

patients with acute coronary syndromes<br />

K. Shreyder, R. Shakhnovich, E. Bosikh, M. Ruda. National Cardiology<br />

Research Center, Intensive Cardiology, Moscow, Russian Federation<br />

The purpose of the study was to determine NT-proBNP dynamics in<br />

different treatment strategies in patients with acute coronary syndromes (ACS).<br />

Materials and methods: 52 patients with ST-elevation myocardial infarction<br />

(STEMI) and 61 patients with non-ST-elevation ACS (NSTACS) were included<br />

into the study. NT-proBNP was measured in admission, on the 3d day and before<br />

discharge (7-12 days).<br />

Results: In NSTACS baseline concentration of NT-proBNP was higher than<br />

in STEMI group (751,1 vs. 449,9pg/ml, p=0,05). NT-proBNP level increases<br />

markedly in STEMI during hospitalization and achieves peak at discharge. In<br />

NSTACS baseline concentration of NT-proBNP is the highest and decreases towards<br />

discharge (figure). In STEMI patients with pre-hospital thrombolysis baseline<br />

NT-proBNP level is lower than in cases with in-hospital treatment (140,9 vs.<br />

543,1 pg/ml, p=0,05). The peak concentration of NT-proBNP at discharge was<br />

in the facilitated PTCA group, when compared with pre-hospital thrombolysis, inhospital<br />

thrombolysis and primary PTCA. NT-proBNP was lower in patients with<br />

reperfusion before 4 hours than in cases with later reperfusion (1150,5 vs 2130,2<br />

pg/ml, p


CI 0.2-1.6, p=0.32) after epinephrine and atropine (compared with epinephrine).<br />

On the other hand, the epinephrine and atropine group had significantly higher<br />

rate of return of spontaneous circulation (ROSC) than the epinephrine group<br />

(35% vs. 23%, p


266 Resuscitation resuscitated! / Risk assessment: strengths and weaknesses<br />

resuscitated from cardiac arrest and those without this complication. The higher<br />

mortality rate among resuscitated patients is explained by noncardiac complications.<br />

RISK ASSESSMENT:<br />

STRENGTHS AND WEAKNESSES<br />

1762 Aortic augmentation index: reference values and<br />

association with known cardiovascular risk factors in a<br />

Danish population<br />

J.H. Janner1 , N.S. Godtfredsen2 , P. Lange1 ,J.Vestbo1 ,E.Prescott2 .<br />

1Hvidovre University Hospital, Cardiology and Respiratory Medicine,<br />

Copenhagen, Denmark; 2Bispebjerg University Hospital, Department of<br />

Respiratory Medicine, Copenhagen, Denmark<br />

Background: It has been proposed that aortic augmentation index (AIx) – a measure<br />

of arterial wave reflection – can be used as a surrogate measure of arterial<br />

stiffness. In a selected patient group (end stage renal disease) AIx has been<br />

shown to be a predictor of all-cause mortality. AIx has also been shown to predict<br />

cardiovascular events in patients with hypertension and patients undergoing PCI.<br />

Studies of reference values of AIx are scarce.<br />

Objective: 1) To report reference values of AIx in a population at low risk of CVD<br />

according to <strong>Heart</strong>score. 2) To investigate the association between AIx and known<br />

CVD risk factors in a large cohort of the Danish population.<br />

Methods: This population-study is based on 4700 subjects from the Copenhagen<br />

City <strong>Heart</strong> Study. In those with the lowest risk of CVD as defined by <strong>Heart</strong>score<br />

we analysed AIx adjusted for heart-rate and its dependency of sex, age and<br />

height using linear regression. Multivariate linear regression was used to examine<br />

the association between AIx and the following risk factors for CVD – systolic<br />

and diastolic blood pressure, total-cholesterol, LDL cholesterol, HDL cholesterol,<br />

triglycerides, high-sensitive C-reactive protein (hs-CRP), smoking status, years of<br />

smoking, alcohol consumption, diabetes, medication for hypertension, heart disease<br />

or high cholesterol, physical inactivity, familiar history of CVD and education.<br />

All analyses were stratified by sex.<br />

Results: AIx was positively associated with age and negatively with height in<br />

those with lowest risk of CVD in the following manner: Woman: AIx = 26.56 +<br />

0.76 (age) – 0.004 (age 2 ) – 0.19 (height (cm)). Men: AIx = 59.52 + 0.42 (age)<br />

– 0.38 (height (cm)). We found increasing AIx with increasing risk of CVD as<br />

defined by the <strong>Heart</strong>score index. In the multivariate analyses AIx was positively<br />

associated with systolic and diastolic blood pressure, hs-CRP and current smoking<br />

and – negatively with weight for both sexes, and positively associated with<br />

total cholesterol for men only. AIx was not associated with other CVD risk factors,<br />

including diabetes.<br />

Conclusions: We propose a novel equation including age, height and sex to<br />

calculate reference values for AIx - based on a large general population sample<br />

with low risk of CVD. AIx is highly dependent on age and both systolic and<br />

diastolic blood pressure, positively associated with hs-CRP and current smoking.<br />

This study is the largest to date evaluating the association between AIx and<br />

known CVD risk factors. We plan to examine AIx as independent predictor for cardiovascular<br />

events and mortality in the Copenhagen City <strong>Heart</strong> Study – a cohort<br />

with low risk of CVD.<br />

1763 Increased cardiovascular mortality in women with<br />

normal weight obesity<br />

A. Romero-Corral1 , V.K. Somers1 , S. Boarin 2 , J. Sierra-Johnson3 ,<br />

Y. Korenfeld4 , J. Korinek4 , G. Parati 5 , F. Lopez-Jimenez1 . 1Mayo Clinic, Cardiovascular, Rochester, United States of America; 2Mayo Clinic and Istituto Auxologico Italiano, Cardiovascular, Milan, Italy; 3Mayo Clinic<br />

and Karolinska Institute, Cardiovascular, Stockholm, Sweden; 4Mayo Clinic,<br />

Cardiovascular, Rochester, United States of America; 5Istituto Auxologico<br />

Italiano, Cardiovascular, Milan, Italy<br />

Background: We hypothesized that subjects with normal weight obesity (NWO),<br />

defined as those with normal BMI but high body fat (BF) content, in whom we<br />

have previously reported a higher prevalence of metabolic syndrome and cardiovascular<br />

(CV) risk factors, are at higher risk for total and CV mortality.<br />

Methods: We analyzed 2,127 subjects ≥ 20 years of age from the Third National<br />

Health and Nutrition Examination Survey (NHANES III) and mortality study with<br />

normal BMI (18.5-24.9 kg/m 2 ), body composition assessment, fasting morning<br />

blood measurements and CV risk factors data. Survival information was available<br />

for all subjects after 8.7 years of follow-up. We divided our sample into three<br />

groups: low BF (35% in women), defined as NWO. We compared total and<br />

CV mortality across groups.<br />

Results: NWO comprised ∼20% of all subjects with a normal BMI. Table displays<br />

the total and CV mortality rate in men and women according to BF. As BF<br />

increased in men, there was a non-significant increased risk for total and CV mortality.<br />

However, as BF increased in women, there was a significant increased risk<br />

for total and CV mortality. When compared to the low BF group, NWO women<br />

showed a trend towards higher total mortality (HR=1.52; 95%CI, 0.83-2.77), and<br />

after adjustment for age, dyslipidemia, hypertension, diabetes, CV disease and<br />

Total and cardiovascular deaths by BF<br />

Men (n=1,1036) Body fat 25% Age and race adjusted<br />

(n=378) (n=400) (n=248) p-value for trend<br />

Total deaths 39 (5.63%) 42 (6.36%) 37 (12.5%) 0.21<br />

Cardiovascular deaths 15 (2.52%) 20 (2.63%) 13 (4.94%) 0.59 †<br />

Women (n=1,101) Body fat 35%<br />

(n=428) (n=427) (n=246)<br />

Total deaths 20 (3.03%) 31 (5.55%) 22 (8.25%) 0.038<br />

Cardiovascular deaths 5 (0.87%) 12 (2.12%) 12 (4.37%)* 0.044 †<br />

*p-value


Risk assessment: strengths and weaknesses / Prognosis in heart failure: surveys and clinical markers 267<br />

11 <strong>European</strong> countries and represents over 2.7 million person years of observation,<br />

of these 6,687 from 5 countries were aged 65 or over. Cox proportional hazards<br />

model was used to derive SCORE ELD. Only data from those aged ≥65 were<br />

used and the following variables were included: age, TC, SBP, smoking, HDL-C.<br />

The baseline survival was calculated separately in men and women and in high<br />

and low risk countries. The performance of the two functions was compared using<br />

AUROC (area under receiver operated curve) and NRI (net reclassification<br />

indices), sensitivity, specificity and goodness of fit. The performance of SCORE<br />

ELD was also compared to that of the Framingham function (CVD version, <strong>2008</strong>).<br />

Results: AUROC for SCORE ELD was 0.73, superior to that of Framingham<br />

(0.68, p 10%) by the<br />

SCORE high risk chart, are not at high risk according to the Dutch equation. On<br />

the other hand, 80% of those identified to be at high risk by the Dutch equation,<br />

are not identified by the SCORE low risk charts.<br />

Classification by diff. risk equations<br />

SCORE high risk Dutch equation SCORE low risk<br />

< 5% 5-10% > 10% < 5% 5-10% > 10%<br />

30,277 1509 0 < 5% 31,786 0 0<br />

4 645 292 5–10% 653 288 0<br />

0 1 210 > 10% 1 170 40<br />

Conclusions: The number of Dutch patients eligible for drug therapy is overestimated<br />

by SCORE risk charts for high risk regions and underestimated by SCORE<br />

risk charts for low risk regions. This illustrates the need for the use of proper risk<br />

equations in primary prevention of CVD.<br />

1767 Body mass index and total mortality<br />

A. Dudina, M.T. Cooney, I.M. Graham on behalf of SCORE<br />

investigators. Dublin, Ireland<br />

Purpose: The SCORE data set comprises data from 12 <strong>European</strong> cohort<br />

studies. There were 205 178 persons (88 080 women and 117 098<br />

men) representing 2.7 million person years of follow-up. Data on BMI was available<br />

for 110,902 men and 84,451 women. These data are sufficiently powered<br />

to allow detailed examination of relationships between body weight and prognosis.<br />

We have previously reported the relationship with cardiovascular mortality,<br />

but relation with total mortality may be of more public health importance. We now<br />

examine this aspect.<br />

Methods: The relationship between increasing BMI and total mortality was examined<br />

using Cox proportional hazards model. Hazard ratios were calculated for<br />

each body mass index (BMI) category (under 20, 25-30, 30-35, 35-40 and over<br />

39), compared to normal weight (20-25), for the total mortality endpoint. Analyses<br />

were performed separately in men and women and stratified by country.<br />

The following covariates were introduced into the model in a stepwise manner:<br />

age, smoking, systolic blood pressure (SBP), total cholesterol, diabetes and HDL-<br />

Cholesterol (HDL-C).<br />

Results: The table shows that after adjustment for age and current smoking, BMI<br />

was strongly related to total mortality, especially in women. This relationship was<br />

attenuated by adjustment for cholesterol, systolic blood pressure and diabetes.<br />

Further adjustment for HDL-C resulted minor further attenuation but BMI greater<br />

than 35 remained significant.<br />

Table 1. HR for total Mortality in BMI<br />

BMICategory Males Females<br />

Age, smoking +chol, SBP, diabetes Age, smoking +chol, SBP, diabetes<br />

adjustment adjustment adjustment adjustment<br />

Underweight 40 2.06*** 1.48* 2.39*** 1.79***<br />

HR: Hazard Ratio; BMI: Body Mass Index; ***p


268 Prognosis in heart failure: surveys and clinical markers<br />

the AF group (46.7%) and 11,737 deaths in the SR group (32.3%). As shown<br />

in the figure, meta-analysis of these 13 studies demonstrated an adverse effect<br />

of AF on mortality in these 42,510 patients, with a hazard ratio of 1.29 (95% CI<br />

1.26-1.33; p


Prognosis in heart failure: surveys and clinical markers / Prognostic predictors in acute heart failure 269<br />

in patients post-AMI and in HF. RFP represents an important prognostic marker<br />

among patients with diabetes and cardiovascular disease.<br />

PROGNOSTIC PREDICTORS IN ACUTE<br />

HEART FAILURE<br />

1778 Relationship between body weight change following<br />

hospital discharge and risk for death/rehospitalization:<br />

an EVEREST analysis<br />

M. Gheorghiade1 , C. Zimmer2 , J. Burnett3 ,L.Grinfeld4 ,<br />

A.P. Maggioni5 , K. Swedberg6 , F. Zannad7 , G.C. Fonarow 8 ,T.Cook9 ,<br />

M. Konstam10 on behalf of the EVEREST Investigators. 1Northwestern University, Chicago, United States of America; 2Otsuka Maryland Research<br />

Institute, Rockville, United States of America; 3Mayo Clinic, Rochester, United<br />

States of America; 4TANGO, Buenos Aires, Argentina; 5ANMCO Research<br />

Center, Firenze, Italy; 6Sahlgrenska University Hospital, Goteborg, Sweden;<br />

7 8 CIC-INSERM-CHU, Toul, France; UCLA, Los Angeles, United States of<br />

America; 9University of Wisconsin SDAC, Madison, United States of America;<br />

10Tufts New England Medical Center, Boston, United States of America<br />

Purpose: In patients with chronic heart failure (HF), increases in body weight<br />

(BW) have been shown to begin several weeks prior to hospitalization, and may<br />

identify a period during which intervention may be beneficial. We explored the<br />

relationship between change in BW and subsequent risk for all-cause mortality/cardiovascular<br />

(CV) re-hospitalization following hospitalization for worsening<br />

HF in the EVEREST trial.<br />

Methods: The EVEREST trial randomized 4133 patients (EF


270 Prognostic predictors in acute heart failure / Restenosis: is there an alternative to drug-eluting stents?<br />

the degree of oedema showed no correlation to the duration of dyspnea prior to<br />

presentation (r=-0.168, p=0.393).<br />

Conclusion: Lower extremity oedema in ADHF is not primarily caused by an<br />

elevation of the hydrostatic pressure as depicted by the CVP but might mirror<br />

disease severity depicted by BNP levels. Interestingly, the extent of lower oedema<br />

can not be used as a bedside measurement of disease severity.<br />

1782 Prognostic value and changes in renal function in<br />

patients admitted with acute heart failure - results from<br />

the EVEREST program<br />

J. Blair 1 , J.C. Burnett2 ,M.A.Konstam3 , L. Grinfield4 , A.P. Maggioni5 ,<br />

K. Swedberg6 ,J.E.Udelson3 , F. Znnad7 ,T.Cook8 , M. Gheorghiade1 on behalf of the EVEREST investigators. 1Northwestern University, Internal<br />

Medicine, Division of Cardiology, Chicago, United States of America; 2Mayo Clinic, Rochester, United States of America; 3Tufts New England Medical Center,<br />

Boston, United States of America; 4Hospital Italiano, Buenos Aires, Argentina;<br />

5 6 Associazione Nazionale Medici Cardioligi, Florence, Italy; Sahlgrenska<br />

University Hospital/Oestra, Gothenburg, Sweden; 7INSERM, Nancy, France;<br />

8University of Wisconsin, Madison, United States of America<br />

Introduction: The prognostic value of admission and changes in renal function<br />

has not been well studied in patients admitted with acute heart failure.<br />

Methods: EVEREST was a prospective, international, placebo controlled trial<br />

evaluating the effects of tolvaptan, an oral vasopressin antagonist, in pts admitted<br />

with worsening heart failure and LVEF £ 40%. Pts with a Cr > 3.5 mg/dL or on<br />

hemodialysis were excluded. Pts were receiving standard medical therapy including<br />

ACE inhibitors/ARBs, beta blockers, and diuretics. The 4133 enrolled patients<br />

were grouped into quartiles of baseline BUN, Cr, eGFR, and BUN/Cr ratio, and<br />

outcomes for each quartile were reported. BUN and Cr levels were obtained during<br />

hospitalization and over the course of the study (median 9.9 months)<br />

Results: After adjustment for non-renal baseline characteristics (age, race, SBP,<br />

EF, beta blocker use, geographic region, BNP, and QRS), all four measures of<br />

renal function were highly predictive of 3-month and 1-year mortality (p 24 mg/dL) was 47% on admission,<br />

53% at discharge, and 39% at one year. Similarly, the percentage of pts with<br />

abnormal Cr (>1.1 mg/dL) was 39% on admission, 41% at discharge, and 39%<br />

at one year.<br />

One Year Unadjusted Mortality<br />

Quartile BUN Cr eGFR BUN/Cr<br />

Range Mortality Range Mortality Range Mortality Range Mortality<br />

1 ≤20 16.3% ≤1.0 16.8% >75 16.4% ≤17 19.7%<br />

2 21-26 17.4% 1.0-1.3 21.1% 59-75 21.1% 18-21 21.7%<br />

3 27-35 27.2% 1.4-1.6 29.6% 44-58 26.1% 22-25 24.6%<br />

4 >35 42.8% >1.6 40.3% ≤44 39.2% >25 37.2%<br />

Conclusion: In pts admitted with acute heart failure and reduced LVEF, baseline<br />

renal dysfunction is common, tended to worsen during hospitalization, and is an<br />

independent predictor of short- and long- term mortality.<br />

1783 The presence of an S3 is associated with an increase<br />

rate of all- cause-mortality after one year<br />

M. Potocki, T. Breidthardt, T. Klima, M. Noveanu, T. Reichlin, K. Laule,<br />

C. Stelzig, T. Boldanova, M. Christ, C. Mueller. University Hospital,<br />

Internal Medicine, Basel, Switzerland<br />

Purpose: The S3 heart sound has been shown to be diagnostic in patients presenting<br />

with acute decompensated heart failure (ADHF). We investigated the utility<br />

of the S3 heart sound to predict one year all-cause-mortality in patients presenting<br />

with dyspnea to the emergency department (ED).<br />

Methods: We analyzed the data of 287 consecutive patients with dyspnea enrolled<br />

from April 2006 to March 2007 in our emergency department. The patients<br />

received a clinical evaluation with an S3 evaluation by Audicor ® (Inovise Medical,<br />

Inc, Portland, USA). The diagnosis of ADHF was adjudicated by two independent<br />

cardiologists using all available clinical data including BNP.<br />

Results: Audicor ® results were available in 275 patients. The mean age was<br />

74±12 years and 52% were male. The median follow-up time was 372 days<br />

[IQR 153-430 days]. Hypertension, coronary artery disease, chronic kidney disease<br />

and diabetes was present in 183 (67%), 75 (27%), 72 (26%) and 51 (19%).<br />

ADHF was the adjudicated final diagnosis in 145 patients (53%). Median BNP levels<br />

were significantly higher in patients with an S3 compared to patients without<br />

S3 detection (1081 vs. 263pmol/L, p < 0.001). In the Kaplan-Meier and log-rank<br />

analyses, those patients with an S3 detected had a significantly higher one year<br />

mortality compared to the patients without an S3 (37% vs. 23%, p = 0.046). The<br />

sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy<br />

of an electronic S3 for detection of ADHF were 26%, 92%, 79%, 53% and<br />

57% and for an S3 detected by physician auscultation 9%, 99%, 93%, 49% and<br />

52%. The odds ratio for one year mortality was 2.02 (p = 0.036) for the electronic<br />

detection of an S3, whereas S3 detection by physician failed to reach statistically<br />

significance.<br />

Conclusions: The presence of an electronically detected S3 is a significant predictor<br />

of one year mortality in patients presenting with dyspnea to the emergency<br />

department. The detection of S3, both by auscultation or by electronical devices,<br />

is highly specific for the diagnosis of ADHF and may improve early diagnostic<br />

accuracy in the emergency department.<br />

RESTENOSIS: IS THERE AN ALTERNATIVE TO<br />

DRUG-ELUTING STENTS?<br />

1784 Oral cilostazol prevents restenosis and repeat<br />

revascularization after percutaneous coronary<br />

stenting: A meta-analysis of 15 randomized trials and<br />

4897 patients<br />

G. Biondi-Zoccai1 ,C.Moretti1 , M. Lotrionte2 , P. Agostoni3 ,F.Sciuto1 ,<br />

P. Omede1 , A. Abbate4 ,G.Trevi1 , I. Sheiban1 . 1Turin, Italy; 2Rome, Italy; 3Antwerp, Belgium; 4Richmond, United States of America<br />

Purpose: Drug-eluting stents reduce the risk of restenosis after percutaneous<br />

coronary intervention (PCI), but may pose a risk of thrombosis. Cilostazol, an oral<br />

antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia,<br />

could hold the promise of preventing both restenosis and thrombosis. We<br />

systematically reviewed randomized clinical trials on the angiographic and clinical<br />

impact of cilostazol after percutaneous coronary stenting.<br />

Methods: Pertinent randomized trials were searched in BioMedCentral, CEN-<br />

TRAL, clinicaltrials.gov, EMBASE, and PubMed (January 2007). Co-primary<br />

end-points were binary angiographic restenosis and repeat revascularization,<br />

abstracted and pooled by means of random-effect relative risks (RR). Small<br />

study/publication bias was appraised with multiple methods.<br />

Results: A total of 15 randomized clinical trials were included (4897 patients,<br />

2453 randomized to oral cilostazol for 1-6 months, and 2444 randomized to control<br />

therapy or placebo), with median follow-up of 6 months. Pooled analysis<br />

showed that cilostazol was associated with statistically significant reductions in binary<br />

angiographic restenosis (18.8% for cilostazol vs 26.8% for control, RR=0.60<br />

[0.49-0.73], p


Restenosis: is there an alternative to drug-eluting stents? / Confonding factors influencing outcome after stenting 271<br />

1786 Comparison of efficacy of low (80mg) and high-dose<br />

(160-320mg) valsartan in the prevention of in-stent<br />

restenosis after implantation of bare-metal stents in<br />

type B2/C lesions<br />

S. Peters. Klinikum D. Erxleben Quedlinburg, Innere Medizin I -<br />

Kardiologie, Quedlinburg, Germany<br />

The VALVACE trial suggests that prevention of in-stent restenosis after implantation<br />

of bare-metal stents in type B2/C lesions is possible by administration of<br />

80mg valsartan. A 1:1 matched comparison to higher dosage valsartan (160-<br />

320mg) was initiated in a prospective controlled registry on a case-controlled<br />

basis. 450 patients (241 males, mean age 62.7±9.1 years) with matched demographic<br />

and angiographic characteristics to patients of the VALVACE trial were<br />

treated with high-dose valsartan (160 to 320mg) over 6 months until control angiography.<br />

Angiographic restenosis rate, TLR and TVR rates, MACE rate (death,<br />

myocardial infarction and stent thrombosis) and mean lumen late loss were analysed<br />

after 6 months. Results were compared to the results of the VALVACE<br />

trial. In the whole collective with vlasartan at different doses gender- and dosedependancy<br />

was analysed. In the high-dose group angiographic restenosis rate<br />

in 368 patients with control angiography was 7.3% in comparison to 19.5% in the<br />

low-dose group (VALVACE) with a p value < 0.0001. Mean lumen late loss was<br />

0.37±0.3 mm and in VALVACE 0.53±0.31% (p < 0.01). TLR and TVR rate was<br />

4.3% in comparison to 9% (p < 0.01) and MACE rate was 0% in comparison to<br />

1.5% (p < 0.01). Taking all data with valsartan together in-stent restenosis rate<br />

in males was 23.8% under 80mg, 13.6% under 160mg, 5.7% under 240mg and<br />

4.9% under 320mg. In females restenosis rate was 13.3% under 80mg and 6.3%<br />

under 160mg; no restenosis appeared under higher doses. High-dose administration<br />

of oral valsartan after bare-metal stent implantation in type B2/C lesions<br />

is able to reduce angiographic in-stent restenosis rate, TLR and TVR rate, late<br />

lumen loss and MACE rate more effectively than low-dose (80mg) valsartan.<br />

1787 Do we need DES in all patients? Results of a strategy<br />

combining a simple selection process and the use of<br />

thin strut cobalt chromium bare metal stents<br />

P. Stella, H. Nathoe, S. Hoseyni, T. Wildbergh, H. Meijburg, E. Van<br />

Belle. University Medical Center, Cardiology, Utrecht, Netherlands<br />

Background: The introduction of drug eluting stents (DES) has been a breakthrough<br />

in the prevention of restenosis following PCI. However, the high rates of<br />

late stent thrombosis observed with these devices make alternative preventive<br />

strategies mandatory. The use of thin struts cobalt chromium (TSCC) bare metal<br />

stents has been associated with promising clinical results. We hypothesized that<br />

the use of a strategy combining a simple selection of clinical indications and the<br />

use of TSCC BM stents could achieve very low restenosis rates without compromising<br />

safety.<br />

Methods: From <strong>September</strong> 2005 to June 2006, among patients referred for a PCI<br />

procedure in our centre, we prospectively selected those in which at least one of<br />

the 2 inclusion criteria was met: 1) de novo coronary lesion not exceeding 20<br />

mm in length; 2) vessel diameter more than 2.6 mm; and excluded 3) those with<br />

diabetes mellitus unless vessel diameter > 3.5 mm; to undergo implantation of<br />

TSCC bare metal stents. Twelve months follow-up was obtained in all patients.<br />

Results: 511 patients; 30% of the total population referred for PCI; matched the<br />

selection criterions and were part of the study. Despite the selection process, the<br />

study population was at relatively high risk including 22% of patients with a history<br />

of MI, 50% with multivessel coronary artery disease and 59% undergoing PCI for<br />

an acute coronary syndrome.<br />

A single TSCC MB-stent was implanted in 88% of patients. The procedural success<br />

rate was 99.6%. A peri-procedural myocardial infarction occurred in 7 (1.4%)<br />

patients.<br />

Clinically driven TLR and TVR at 12 months were observed in 8 (1.6%) and 13<br />

(2.5%) patients, respectively. Cumulative In stent-thrombosis at 1 and 12 months<br />

occurred in 4 (0.08%) and 6 (0.1%) patients, respectively.<br />

Conclusion: Our results demonstrate that a simple selection process, applying<br />

to 30% of a routine PCI population, combined with the use of TSCC bare metal<br />

stents can be associated with a very favourable long-term clinical outcome. The<br />

use of TSCC bare metal stents is an attractive alternative to DES in such a population.<br />

1788 In stent restenosis - benign or dangerous? Clinical<br />

presentation of in-stent restenosis in Sweden<br />

E. Omerovic1 , T. Ramunddal2 , G. Matejka2 ,P.Albertsson2 .<br />

1Wallenberg Laboratory at Sahlgrenska Academy, Departement of<br />

Cardiology, Gothenburg, Sweden; 2Dpt of Cardiology, Sahlgrenska<br />

Univ. Hosp., Gothenburg, Sweden<br />

Background: Restenosis after percutaneous coronary intervention (PCI) is traditionally<br />

thought to be a benign event clinically manifested as stable exertional<br />

angina. However, the presentation of in-stent restenosis (ISR) in "real-life" patients<br />

is not well-studied. The aim of this study was to evaluate to which extent<br />

patients with bare metal (BMS) ISR present as acute coronary syndromes in Sweden.<br />

Methods: We searched Swedish Coronary Angiography and Angioplasty Reg-<br />

istry (SCAAR) data. All cases of PCI for BMS ISR occurring between 1998 and<br />

2004 in Sweden were scrutinized. Both multivessel and single vessel interventions<br />

were included. ISR presentation was classified into three categories: (1) myocardial<br />

infarction, (2) unstable angina requiring hospitalization and (3) exertional<br />

angina. ISR episodes were based on patient’s symptoms and therefore were defined<br />

clinically rather than angiographically as routine angiographic screening after<br />

initial stent placement was not performed.<br />

Results: We identified 4729 cases of bare-metal ISR, 3462 in men and 1267<br />

in women. Of the ISR episodes, 52% (2466) were presented as either unstable<br />

angina or myocardial infarction. Almost 10% of these patients presented as STsegment<br />

elevation MI. Minority of pts with ISR presented as exertional angina<br />

(48%). Women had higher incidence of unstable angina and myocardial infarctions<br />

(49%) at ISR presentation compared to men (55%) (p


272 Confonding factors influencing outcome after stenting<br />

able on the independent role of chronic and acute post procedural renal failure<br />

in predicting mortality in patients with ST-elevation myocardial infarction (STEMI)<br />

treated with primary coronary angioplasty (PCI).<br />

Methods:We studied 453 consecutive patients with STEMI without cardiogenic<br />

shock treated at our institution with primary angioplasty and stent between January<br />

2002 and December 2006. Demographic, clinical, angiographic and hemodynamic<br />

variables were collected prospectively by independent clinicians. Creatinine<br />

concentration and glomerular filtration rate (GFR, estimated by MDRD<br />

equation) were determined at hospital admission (baseline) and 6h, 24h, 48h and<br />

72 h after the procedure. Contrast-induced nephropathy (CIN) was defined as<br />

the increase of creatinine of more than 25% from baseline value within 48h after<br />

the procedure. The mortality rate at 1 and 12 months was obtained by clinical<br />

interview or review of death certificates.<br />

Results:22 (4.8%) patients died within the first month after the procedure, 44<br />

(10.2%) within 1 year. Both 1 month and 1 year mortality were significantly associated<br />

with age, baseline creatinine and GFR, CIN and pre-procedural ejection<br />

fraction (EF) (all p


Confonding factors influencing outcome after stenting / New vessels and changed vessels: angiogenesis and vascular remodelling 273<br />

Interval late luminal loss.<br />

procedure may be observed following DES therapy. There appears to exist a<br />

device-specificity in this late reduction in anti-restenotic efficacy in favour of a<br />

platform devoid of permanent polymer.<br />

1795 Comparison of 18 month clinical outcome of<br />

endothelial progenitor cell capture stent versus drug<br />

eluting and bare metal stents in patients undergoing<br />

primary percutaneous coronary intervention<br />

E. Chong, Liang Shen, K.K. Poh, S.G. Teo, A. Low, C.H. Lee, H.C. Tan.<br />

National University Hospital, The <strong>Heart</strong> Institute, Singapore, Singapore<br />

Purpose: Endothelial progenitor cell (EPC) capture stent (Genous stent), is designed<br />

to promote rapid endothelization and is potentially most useful in patients<br />

undergoing primary percutaneous coronary intervention (PPCI) for acute<br />

ST-segment elevation myocardial infarction (STEMI). We compare its long-term<br />

clinical efficacy and safety with a sirolimus-eluting (SES) bioabsorbable polymercoated<br />

stent (Cura stent) and a bare metal stent (BMS) (Liberte stent) in patients<br />

with STEMI.<br />

Methods: All patients who presented to our center with STEMI and received PPCI<br />

with either EPC, SES or BMS stents between Jan 2004 and June 2006 were<br />

enrolled in this cohort study. The study endpoints were cumulative major adverse<br />

cardiac events (MACE) defined as a composite end point of death, myocardial<br />

infarction (MI) and target vessel revascularization (TVR) at 18 months.<br />

Results: A total of 365 patients (EPC=95, SES=53, BMS 218) were enrolled.<br />

Baseline demographics in terms of age, gender, diabetes mellitus, baseline renal<br />

impairment, pre-discharge left ventricular ejection fraction, cardiogenic shock<br />

were comparable between the 3 groups. Procedural success rate was high at<br />

a mean of 99.5%. Post-procedural TIMI 3 flow was achieved in EPC 91.6%,<br />

SES 96.2% and BMS 88.5%. The MACE results and stent thrombosis rate at<br />

18-months are shown in table.<br />

Table 1. 18 month clinical outcome<br />

Events EPC (n=95) SES (n=53) BMS (n=218) p value<br />

MACE (%) 13(13.7%) 8(15.1%) 35(16.1%) 0.865<br />

Death (%) 9(9.5%) 2(3.8%) 25(11.5%) 0.208<br />

Non-fatal MI (%) 1(1.1%) 1(1.9%) 4(1.8%) 0.916<br />

TVR 3(3.2%) 5(9.4%) 6(2.8%) 0.070<br />

Acute stent thrombosis 1 (1%) 0 (0%) 0 (0%) ns<br />

Subacute stent thrombosis (SAT) 0 (0%) 0 (0%) 0 (0%) ns<br />

Late stent thrombosis (LST) 0 (0%) 0 (0%) 2 (0.9%) ns<br />

Conclusion: The MACE rates among patients who underwent PPCI were similar<br />

in all 3 stent groups at 18 months follow-up. There was no difference in TVR rate<br />

and stent thrombosis remains a low event occurrence.<br />

NEW VESSELS AND CHANGED VESSELS:<br />

ANGIOGENESIS AND VASCULAR REMODELLING<br />

1814 Neuropilin-1 expressing mononuclear cells (NEMs)<br />

deriving from the bone marrow promote vessel<br />

maturation during therapeutic angiogenesis<br />

S. Zacchigna1 , L. Pattarini1 , L. Zentilin1 , A. Carrer1 ,S.Moimas1 ,<br />

S. Tafuro 1 , M. Sinigaglia1 , G.F. Sinagra 2 , M. Giacca1 . 1ICGEB, Molecular Medicine, Trieste, Italy; 2Unita di Cardiologia Ospedali Riuniti TS,<br />

Trieste, Italy<br />

Purpose: The possibility that bone marrow (BM)-derived cells promote new blood<br />

vessel formation through transdifferentiation has recently aroused much excitement.<br />

Recent evidence however indicates that these cells have less plasticity than<br />

predicted and that their effect is essentially paracrine. To exactly define the role of<br />

BM cells during neovascularization, here we exploited a gene transfer approach<br />

and characterized the in vivo effect of various factors, differing in their capacity to<br />

recruit BM cells and to promote angiogenesis.<br />

Methods: Adeno-Associated Virus (AAV) vectors were used to sustain the longterm<br />

expression of VEGF121, VEGF165 and Sema3A in the mouse skeletal muscle.<br />

Treated muscles were harvested at different times after transduction and the<br />

angiogenic effect was assessed by histological and functional examinations. BM<br />

transplantation, immunoFISH, siRNA-mediated silencing and clodronate depletion<br />

were used to explore the in vivo role of BM cells.<br />

Results: The injection of a vector expressing VEGF165 determined the formation<br />

of an impressive number of new arterioles, paralleled by a massive infiltration<br />

of CD11b+ BM cells. In contrast, VEGF121 induced a potent capillary sprouting,<br />

but neither cellular infiltrates nor arterial vessels were evident. Leading from<br />

the consideration that the main difference between these two VEGF isoforms is<br />

their ability to bind the receptor neuropilin-1 (NP-1), we examined the effect of<br />

semaphorin-3A (Sema3A), another ligand for NP-1. Strikingly, an AAV vector expressing<br />

Sema3A, although not angiogenic, was able to recruit CD11b+ BM cells<br />

similar to VEGF165. Consistent with these findings, we found that CD11b+ cells<br />

migrated in vitro in response to both VEGF and Sema3A, and that their migration<br />

was impaired after NP- 1 silencing both in vitro and in vivo. These CD11b+,NP-1expressing<br />

mononuclear cells (NEMs) were in no case directly incorporated in the<br />

newly formed vasculature nor they were arteriogenic per se, but contributed to arterial<br />

formation through a paracrine effect ensuing in the activation and proliferation<br />

of tissue-resident mural cells in order to promote the maturation of VEGF121induced<br />

capillaries to acquire an arterial phenotype. Consistently, NEM depletion<br />

by clodronate significantly impaired the formationof new arterial vessels.<br />

Conclusions: These findings show that the different isoforms of VEGF are not<br />

redundant, and that BM-derived NEMs, although not directly incorporated into the<br />

newly formed vasculature, are essential for proper arterial formation, thus playing<br />

a key role during therapeutic angiogenesis.<br />

1815 Interferon-beta attenuates collateral artery growth by<br />

inducing monocyte apoptosis and inhibiting smooth<br />

muscle cell proliferation<br />

S.H. Schirmer 1 , P.T.G. Bot 2 , J.O. Fledderus 3 , A.J.G. Horrevoets 4 ,<br />

J.J. Piek 2 , I.E. Hoefer 3 ,N.VanRoyen 2 . 1 Universitaetsklinikum des<br />

Saarlandes, Klinik fuer Innere Medizin III, Homburg/Saar, Germany; 2 Academic<br />

Medical Center, Department of Cardiology, Amsterdam, Netherlands; 3 University<br />

Medical Center, Department of Vascular Medicine, Utrecht, Netherlands; 4 VU<br />

University Medical Center, Department of Molecular Cell Biology and Immu,<br />

Amsterdam, Netherlands<br />

Purpose: Circulating monocytes orchestrate collateral artery growth (arteriogenesis).<br />

In a recent study we demonstrated that monocytes from patients with insufficient<br />

coronary collateral artery growth show increased expression of the interferon<br />

(IFN)-beta pathway compared to patients with well developed collateral<br />

arteries, pointing to an inhibitory role of the IFNbeta-pathway in arteriogenesis<br />

(EHJ suppl. 2007). Here, we investigated the underlying mechanisms of the putative<br />

inhibitory effect of IFNbeta on arteriogenesis and hypothesized that we could<br />

stimulate arteriogenesis by blocking IFNbeta-signaling.<br />

Methods: Three groups of mice (control (129Sv/Ev, n=25), IFNalpha/betareceptor<br />

knockout mice (IFNAR /-, n=25) and IFNbeta treated mice (105 IU/kg s.c,<br />

n=25) underwent unilateral femoral artery ligation. Collateral dependent hindlimb<br />

perfusion was assessed after one week by infusing fluorescent microspheres under<br />

conditions of maximal vasodilation. Hindlimb tissue was analyzed immunohistochemically<br />

for the presence of IFNAR. Both hindlimb tissue and stimulated<br />

peripheral blood monocytes were subjected to gene expression analysis using<br />

RT-PCR. Smooth muscle cells (SMCs) and THP1 monocytes were treated with<br />

interferon-beta to assess the effects of IFNbeta on apoptosis and proliferation<br />

in-vitro.<br />

Results: IFN-beta treatment significantly reduced perfusion restoration compared<br />

to control mice, expressed as percentage ligated/non-ligated hindlimb<br />

(31.46±4.12% vs. 41.88±8.2%, p=0.01), while mice lacking the IFNbeta-receptor<br />

showed significantly increased hindlimb perfusion (54.29±6.55%, p


274 New vessels and changed vessels: angiogenesis and vascular remodelling<br />

Notch ligand Delta-like (Dll) 4 regulates arterial differentiation in embryonic development,<br />

but the key ligand in mature CA remains elusive. Here we identify the<br />

Notch ligand Dll1 as an essential regulator of postnatal coronary arteriogenesis,<br />

which is protective after myocardial infarction.<br />

Methods and Results: To characterize expression and role of Dll1 in adult hearts<br />

we analyzed heterozygous Dll1-lacZ/+ reporter mice, in which one allele of Dll1<br />

has been replaced by lacZ. X-gal staining revealed selective Dll1 expression in<br />

the endocardium and in endothelium of coronary arteries (CA), but not in veins or<br />

capillaries. Interestingly, hearts from Dll1 heterozygous mice were smaller (heart<br />

weight (g)/femur length (cm), wt: 0.13±0.02 vs. het: 0.09±0.02, n=10, p20 um) but an increased number of<br />

small arterioles


New vessels and changed vessels: angiogenesis and vascular remodelling / Syncope: still a lot to learn 275<br />

due to prevention of platelet aggregation. In contrast, complete loss of platelets<br />

appears to be detrimental, suggesting a supportive role for platelet recruitment in<br />

the arteriogenic process. These findings establish the platelet as a major player<br />

in arteriogenesis.<br />

1820 A critical role of platelet function in arteriogenesis<br />

M.L. Von Bruehl1 , J. Pagel2 , W. Schaper3 , E. Deindl2 ,S.Massberg1 .<br />

1Deutsches Herzzentrum, Experimental Cardiology, Muenchen,<br />

Germany; 2Walter-Brendel-Center for Exp. Medicine, Ludwig-<br />

Maximilians-University, Muenchen, Germany; 3Max-Planck-Insitute, Bad Nauheim, Germany<br />

Background: The compensatory growth of blood vessels after major arterial<br />

occlusions (arteriogenesis) describes the remodelling of pre-existing arterioarteriolar<br />

anastomoses to large functional arteries. The growth is triggered by<br />

fluid shear stress initiating endothelial activation and modulating processes, which<br />

control attraction of circulating cells. Although recruitment of monocytes and Tcells<br />

has been identified during arteriogenesis, the exact cellular mechanisms<br />

underlying the arteriogenic process are still ill defined. Platelets play a pivotal<br />

role not only in hemostasis but also in acute and chronic inflammatory processes<br />

of the vascular wall; however, their contribution to arteriogenesis remains unclear.<br />

Methods: To examine the arteriogenic role of the platelets, male or female GPIIb<br />

(αIIb integrin)-deficient mice (n=7) underwent right femoral artery ligation to induce<br />

arteriogenesis. The left femoral artery was sham operated. WT littermates<br />

served as controls. In separate experiments, thrombocytopenia (


276 Syncope: still a lot to learn / Science Hot Line<br />

Figure 1<br />

SS). In conclusion the outcome was similar among pts with high likelihood of neurally<br />

mediated syncope,despite the different modalities of clinical presentation of<br />

spontaneous syncope; HUT results were not helpful in the prediction of syncope<br />

recurrence.<br />

1824 A 1166C polymorphism in angiotensin II receptor gene<br />

is associated with hemodynamic and autonomic<br />

changes during head- up tilt test in patients with<br />

vasovagal syncope<br />

P. Mitro 1 , K. Mudrakova 1 , H. Mickova2 , J. Dudas2 , P. Kirsch2 ,<br />

G. Valocik 2 . 1University Hospital, 3rd Department of Internal Medicine III, Kosice,<br />

Slovak Republic; 2Medical Faculty, Department of Medical Biology, Kosice,<br />

Slovak Republic<br />

Purpose: A familiar occurrence and genetic predisposition may exist in vasovagal<br />

syncope (VVS). Aim of the study was to evaluate the influence of gene polymorphisms<br />

of renin – angiotensin system and serotonin transporter (SERT) gene on<br />

hemodynamic and autonomic changes during head- up tilt test (HUT) in patients<br />

with syncope.<br />

Methods: DNA was collected from 191 patients (mean age 44+ 18 years, 61<br />

men, 130 women). Following genetic polymorphisms were determined in genomic<br />

DNA using the PCR method: ACE insertion/deletion polymorphism (I/D ACE),<br />

angiotensinogen gene polymorphism (M 235), angiotensin II receptor (ATR1)<br />

polymorphism (A 11666C) and polymorphism of serotonin transporter gene (S/L<br />

SERT). Changes in autonomic tone were assessed by the method of heart rate<br />

variability (time – domain- and frequency- domain analysis) in 5 minutes intervals<br />

during HUT. Following parameters were recorded: LF, HF, SDNN a rMSSD.<br />

Results: Only A 1166C polymorphism in ATR1 gene was associated with hemodynamic<br />

and autonomic changes during HUT. A/A genotype of A 1166C polymorphism<br />

was associated with enhanced decline in systolic and diastolic blood<br />

pressure during HUT (minimal systolic BP: AA 59,6±21,8, AC 79,9±22,7, CC<br />

65,4±22,7 mmHg, p=0,007), (minimal diastolic BP AA 36,4±22,7, AC 52,3±22,9,<br />

CC 45,4±19,5 mmHg, p=0,007). A/A genotype of A 1166C polymorphism in ATR1<br />

gene was also associated with higher SDNN in early phase of HUT (SDNN in 5<br />

minute: AA 59,7±24,6 AC 50,6±20,6, CC 46,0±13,2, p=0,01) and at syncope<br />

occurrence (SDNN: AA 71,0±20,9, AC 58,2±17,9, CC 58±1 0, p=0,04) when<br />

compared to other genotypes of A 1166C polymorphism in ATR1 gene.<br />

Conclusion: A/A genotype of A 1166C polymorphism in ATR1 gene is associated<br />

with more pronounced fall in blood pressure and enhanced decline in sympathetic<br />

tone during HUT in syncopal patients. It may play a role in genetic predisposition<br />

to vasovagal syncope.<br />

1825 Atrioventricular block during tilt testing<br />

J. Gajek, D. Zysko, W. Mazurek. Medical University of Wroclaw,<br />

Department of Cardiology, Wroclaw, Poland<br />

Atrioventricular block (AVB) is a rare result during tilt testing (TT) in<br />

patients with vasovagal syncope. Its clinical importance is not known.<br />

Clinical data and tilt testing (TT) findings could differ between patients with and<br />

without AVB during TT. The aim of the study was to compare the medical history<br />

as well TT findings between the patients with and without AVB during positive<br />

TT. The study group consisted of 521 pts with positive TT. The medical history<br />

about the syncope number, traumatic injuries related to syncope, hospitalization<br />

due to these injuries, jerks during spontaneous syncope have been obtained. The<br />

following TT data: necessity for NTG provocation, duration of heart rate slowing<br />

during neurocardiogenic reaction, outcome of TT assessed as total loss of consciousness<br />

(TLOC) or presyncope have been collected.<br />

Results: The patients characteristics and results are shown in table:<br />

The stepwise logistic regression analysis revealed that AVB occurrence have<br />

been independently associated with TLOC (OR - 5.5, CI 1.3-23.5, p


(n=574) served as the cohort where plaque osteopontin levels were examined in<br />

relation to their outcome during follow up. Plaques obtained from patients undergoing<br />

femoral endarterectomy (n=151) served as an external validation cohort.<br />

Results: The primary and secondary endpoints were reached in 137 and 66 patients<br />

respectively. Endpoints involved the cerebral circulation (17%), coronary<br />

circulation (40%) and peripheral circulation (43%) The mean carotid plaque osteopontin<br />

levels differed consistently between plaques obtained from patients who<br />

suffered from any cardiovascular event during follow up (mean level 15.0±1.0<br />

ng/ml) and patients who had no event (mean level 9.2±0.4 ng/ml). Patients were<br />

divided in quartiles based on the carotid plaque osteopontin levels. Comparing the<br />

highest quartile of carotid plaque osteopontin levels with quartile 1+2 showed a<br />

hazard ratio for the primary outcome of 4.0 [95% Confidence Interval (CI) 2.5-6.5].<br />

In quartile 4 >50% of the patients reached a primary endpoint within 3 years compared<br />

with 13% in quartiles 1+2. The outcome did not change after adjustment<br />

for plaque characteristics and traditional risk factors [hazard ratio 4.3, 95%CI 2.7-<br />

6.8]. In subgroup analyses, carotid plaque osteoptin levels were predictive for all<br />

single endpoints of cerebral, myocardial and peripheral origin. Multivariate analyses<br />

revealed that age and plaque osteopontin levels were the only independent<br />

predictors for outcome (both p


278 Science Hot Line / Stress echo in clinical practice<br />

1843 High density lipoprotein (HDL) loses major<br />

vasoprotective properties in patients with stable<br />

coronary disease and acute coronary syndrome as<br />

compared to HDL from healthy subjects - important<br />

novel implications for HDL-targeted treatment<br />

strategies<br />

C. Besler, K. Yonekawa, C. Doerries, Y. Shi, T.F. Luescher, U. Landmesser.<br />

Zurich, Switzerland<br />

Background: Reduced high density lipoprotein (HDL) represents a major cardiovascular<br />

risk factor. HDL isolated from healthy subjects exerts direct vasoprotective<br />

effects, i.e. stimulates endothelial nitric oxide (NO) production, exerts antioxidant<br />

and anti-inflammatory effects. HDL-targeted treatment approaches are<br />

therefore currently intensely studied as a potential novel strategy for cardiovascular<br />

protection. However, the vascular effects of HDL from patients with stable<br />

coronary artery disease (CAD) or an acute coronary syndrome (ACS) remain to<br />

be characterized. This is a critical question because only raising HDL with vasoprotective<br />

properties can be expected to exert beneficial effects.<br />

Methods: HDL was isolated from patients with stable CAD or ACS (n=24) and<br />

age- and sex-matched healthy subjects (n=10) by sequential ultracentrifugation.<br />

The effects of HDL on endothelial cell nitric oxide (NO) and superoxide production<br />

were determined by electron spin resonance (ESR) spectroscopy using the<br />

spin-traps Fe-DETC and CM-H, respectively. The effect of HDL on endothelial repair<br />

was examined by injection of HDL into nude mice with carotid artery injury<br />

and measurement of the re-endothelialized area after 3 days. Anti-inflammatory<br />

properties of HDL were tested by using an endothelial monocyte adhesion assay.<br />

Furthermore, lipid peroxidation and activity of paraoxonase, an important HDLassociated<br />

anti-oxidant enzyme system, were determined.<br />

Results: Whereas HDL isolated from healthy subjects stimulated endothelial NO<br />

production, HDL from both, patients with stable CAD or acute coronary syndrome,<br />

had the opposite effect and inhibited endothelial NO production. Endothelial superoxide<br />

production was markedly reduced by HDL from healthy subjects, an<br />

effect that was largely lost when HDL from patients with stable CAD or ACS was<br />

examined. Importantly, HDL from healthy subjects markedly accelerated endothelial<br />

repair after carotid injury, that was not observed with HDL isolated from patients<br />

with stable CAD or ACS. Moreover, HDL from healthy subjects, but not from<br />

patients with stable CAD and ACS inhibited monocyte adhesion on TNF-alphastimulated<br />

endothelial cells, suggesting a loss of anti-inflammatory effects of HDL<br />

in coronary artery disease. Lipid peroxidation was increased in patients with stable<br />

CAD or ACS as compared to healthy subjects, likely at least in part due to a<br />

profoundly reduced HDL-associated paraoxonase activity in patients with stable<br />

CAD or ACS.<br />

Conclusion: The findings of the present study provide the first evidence suggesting<br />

that HDL from patients with stable coronary artery disease or an acute<br />

coronary syndrome loses important endothelial-protective effects. In particular<br />

HDL from patients with coronary artery disease had lost the beneficial effects on<br />

endothelial NO production, endothelial repair, anti-oxidant and anti-inflammatory<br />

properties. These findings have likely important implications for designing HDLtargeted<br />

therapeutic approaches and suggest that the impact of HDL-targeted<br />

treatments on vascular effects of HDL needs to be characterized, since only raising<br />

HDL with vasoprotective properties can be expected to exert cardiovascular<br />

protective effects.<br />

1844 In vivo measurement of regional and local<br />

aortic pulse-wave velocity in mice with MRI at 17.6<br />

Tesla<br />

M. Parczyk, V. Herold, G. Klug, W. Bauer, E. Rommel, P.M. Jakob.<br />

Wuerzburg, Germany<br />

Background: Aortic stiffness increases in an early state of arteriosclerosis,<br />

assessable by pulse wave velocity (PWV) MR-measurements. Up to now<br />

only studies in larger animals and humans have been reported in literature. As<br />

part of a comprehensive measuring protocol to examine vessel morphology and<br />

function in the mouse two non-invasive MR-imaging techniques measuring the<br />

pulse wave velocity in the murine aorta were developed.<br />

Methods: All measurements were performed on a 17.6 Tesla Bruker AVANCE<br />

scanner equipped with a 1T/m gradient insert and a 27mm TEM resonator. Regional<br />

aortic PWV was measured with a transit time method based on a highresolution<br />

CINE-sequence with flow compensating gradients (TR: 5.0ms, TE:<br />

1.6ms, in plane resolution: 80x80μm 2 , slice thickness: 1mm). Cross-sectional areas<br />

were measured at the descending thoracic aorta and the abdominal aorta.<br />

Local PWV in the ascending aorta and the abdominal aorta was measured using<br />

the QA-method based on the assumption of a unidirectional and reflection-free<br />

incident pulse wave. In this case the pulse wave velocity is given as PWV=dQ/dA<br />

where Q denotes the volume flow through the aorta and A is the cross-sectional<br />

area of the aorta. A PC-Cine-FLASH-sequence was applied to measure the time<br />

dependant parameters Q and A.<br />

Results: Our preliminary studies confirmed the feasibility of MR-PWV measurements<br />

in murine aortas. In vivo regional measurements indicated PWVs of 5.5<br />

m/s. Local PWV were measured to be 2.8 m/s in the ascending aorta and 3.2 m/s<br />

in the thoracic aorta.<br />

Conclusion: This study demonstrates the feasibility of high-field-MRI to measure<br />

local and regional PWV in the murine aorta. After further validation protocols are<br />

incorporated into a comprehensive MR protocol to image mechanisms of plaque<br />

progression and regression in atherosclerotic mice.<br />

STRESS ECHO IN CLINICAL PRACTICE<br />

1845 Positive predictive value of stress echocardiography in<br />

the chest pain unit: what does this test add to a clinical<br />

score?<br />

A. Estevez, M. Martinez-Selles, H. Bueno, R. Del Castillo, J. De<br />

Miguel, J. Andueza, J. Ortiz, L. Gallego, M.A. Garcia-Fernandez,<br />

F. Fernandez-Aviles. hospital general universitario gregorio maran, cardiology,<br />

Madrid, Spain<br />

Introduction: Patients admitted to chest pain units are usually classified on the<br />

basis of the results of non-invasive tests. However, the large number of potential<br />

patients places a strain on limited resources. Thus, we have previously reported<br />

a clinical index (UDT-65) to stratify the risk of coronary artery disease (CAD) of<br />

these patients. The aim of the present study was to evaluate the positive predictive<br />

value of the stress echocardiography when added to the clinical features.<br />

Methods: We studied 700 consecutive patients admitted to the Chest Pain Unit<br />

at our institution, all of whom had an ECG without changes in repolarization and<br />

normal troponin. Chest pain was shorter than 60 minutes in all cases. CAD was<br />

defined as stenosis > 70% of the lumen. We performed coronary angiography to<br />

all patients with a definite positive result on the stress echocardiography.<br />

Results: We performed coronary angiography to 50 patients with positive result<br />

on stress echocardiography. Mean age was 66.1±12.9 years and 74.7% were<br />

male. Chest pain was described as typical in 41.6%, doubtful in 39.3% and atypical<br />

in 19.1%. Stress echocardiography was clinically positive in 25 patients; electrically<br />

positive in 19 and 40 showed worsening in the segment contractility. 17<br />

patients (37.8%) did not have significant CAD. So, the Positive Predictive Value<br />

(PPV) for the stress echocardiography was 0.62. When we only considered the<br />

result of patients with a positive clinical, electrical and echocardiographic test, the<br />

PPV increased to 0.89. Moreover, when we analysed the PPV adjusted to the<br />

clinical index (UDT-65) composed by use of aspirin, diabetes, typical chest pain<br />

and age over 64, scored from 0 to 4, it increased from 0.40 when the score was<br />

0-1 to 0.88 when the score was 3-4.<br />

Conclusions: Our previously described clinical index UDT-65 correlates with the<br />

presence of CAD. Our present study shows that stress echocardiography has a<br />

reduced power to detect CAD in those patients in a Chest Pain Unit with low<br />

clinical risk. The PPV was only high in those patients with high clinical pre-test<br />

probability of CAD. We conclude that the usefulness of the stress ecocardiography<br />

in the chest pain unit to predict CAD is uncertain.<br />

1846 Risk stratification in diabetics by left anterior<br />

descending flow reserve: evidence for shorter warranty<br />

period compared to nondiabetics<br />

G. Athanassopoulos1 , G. Hatzigeorgiou2 ,A.Motsi2 , M. Marinou2 ,<br />

G. Karatasakis2 ,D.V.Cokkinos2 . 1Pireas, Greece; 2Athens, Greece<br />

Background: Non-invasive evaluation of left anterior descending artery (LAD)<br />

flow reserve (CFR) is feasible using transthoracic Doppler echo. LAD CFR, despite<br />

its proven accuracy for LAD patency diagnosis, has not been extensively<br />

validated for prognosis. CFR evaluation has still undefined prognostic value in<br />

diabetics compared to nondiabetics.<br />

Methods: 518 consecutive pts with chronic CAD were studied for LAD CFR (age<br />

62+11, ejection fraction 48+10, 18% with anterior MI, 20% with CABG, 13% with<br />

diabetes). Coronary angiography had 47% of pts with 29% having>70% LAD<br />

diameter stenosis. CFR was estimated using bolus adenosine infusion at<br />

140μg/kg/min.<br />

Results: During a follow up of 9+4.5 months (range 1-26), 52 pts had a cardiac<br />

event (CE): 3 died, 25 had revascularization, and 24 acute coronary syndromes.<br />

UsingROCforpredictionofCE,aCFRvalue>1.8 had sensitivity 0.65, specificity<br />

0.83(p


Using Cox’s proportional hazards model including age, sex, ejection fraction, CFR<br />

and diabetes, then only ejection fraction (exp(b): 0.95, p=0.01) and CFR>1.8<br />

(exp(b):1.87p=0.04) had independent prognostic value for CE in the presence of<br />

diabetes.<br />

With Kaplan Meier analysis, nondiabetics with CFR >1.8 had a sustained decrease<br />

of CE during follow up (log rank: 24.6, p1.8 showed a better outcome only in short term (70% was related with CE only in nondiabetics (log rank=15,<br />

p=0.001)<br />

Conclusion: In diabetics:<br />

1. Noninvasive LAD CFR provides important but mid term diagnostic yield for<br />

cardiac events, independently from the severity of LAD stenosis.<br />

2. Since warranty period does not exceed 9 months, a periodical assessment<br />

of iscemia should be encoureged, especially in the presence of left ventricular<br />

dysfunction.<br />

1847 Synchronicity indexes during exercise are associated<br />

to functional capacity and left ventricular function in<br />

patients with left bundle branch block<br />

P. Pazos, J. Peteiro, A. Bouzas, E. Barge, D. Perez, A. Castro-Beiras.<br />

Juan Canalejo Hospital, Cardiology, A Coruna, Spain<br />

Alterations in synchronicity are commonly seen in patients with left bundle branch<br />

block (LBBB). We hypothesized that synchronicity may improve during exercise<br />

in some of these pts and that such improvement may increase their functional<br />

capacity. 89 pts with LBBB referred for exercise echocardiography were studied<br />

by color Doppler tissue velocity (TV) at rest (R) and in the immediate postexercise<br />

(PE) period (within 45 secs). The time from the onset of the Q or R wave to peak<br />

TV in 9 locations (basal, mid, and apical septum; basal and mid lateral; basal and<br />

mid posterior; basal and mid anterior) were measured to derive a synchronicity<br />

index (SI=mean of the deviation of the 9 locations/9). 27 pts were classified as<br />

having coronary artery disease (CAD, ≥50% stenosis, G1), 5 had non-ischemic<br />

dilated cardiomyopathy (G2) and 57 without dilated cardiomyopathy or CAD were<br />

considered normal subjects (G3, 18 with normal coronary arteries and 39 asymptomatic<br />

with low pre-test probability). At rest the SI (ms) was similar in the 3<br />

groups: G1 35±19, G2 39±11, G3 39±12 (p=NS), despite significant differences<br />

in resting ejection fraction (EF) between groups (G1 46±10, G2 34±4, G3 56±5,<br />

p


280 Stress echo in clinical practice / Non-invasive testing for arrhythmias<br />

chaemia. Therefore, we developed a three-dimensional (3D) analysis tool that<br />

makes it possible to anatomically align 3D rest and stress data systematically,<br />

to generate optimal, non-foreshortened standard anatomical cross sections and<br />

to analyse the images synchronised and side-by-side. The aim of the present<br />

study was to investigate whether this 3D analysis tool could improve interobserver<br />

agreement on myocardial ischaemia during 3D DSE.<br />

Methods: The study comprised 34 consecutive patients (22 men, mean age<br />

57±13 years) with stable chest pain who underwent both non-contrast and contrast<br />

3D DSE. Two observers scored segmental wall motion using a conventional<br />

analysis and the novel analysis with the new 3D tool.<br />

Results: At peak stress, 434 of the 578 segments (76%) could be analysed during<br />

noncontrast 3D imaging. With contrast-enhanced 3D imaging, the number of<br />

available left ventricular segments increased to 526 (91%). The two observers<br />

agreed on the presence of myocardial ischemia in 81 of 102 coronary territories<br />

(agreement 79%, kappa 0.28) during noncontrast 3D imaging and 92 of 102<br />

coronary territories (agreement 90%, kappa 0.65) during contrast-enhanced 3D<br />

imaging. With the new 3D analysis software these numbers improved to 98 of 102<br />

coronary territories (agreement 96%, kappa 0.69) during noncontrast 3D imaging<br />

and 98 of 102 coronary territories (agreement 96%, kappa 0.82) during contrastenhanced<br />

3D imaging.<br />

Conclusion: The use of a 3D DSE analysis tool improves interobserver agreement<br />

for myocardial ischaemia both for non-contrast and contrast images.<br />

NON-INVASIVE TESTING FOR ARRHYTHMIAS<br />

1851 T-wave variability detects abnormalities in ventricular<br />

repolarisation: a prospective study comparing healthy<br />

persons and olympic athletes<br />

L. Heinz1 ,A.Sax2 , F. Robert 2 , A. Urhausen2 , D. Luhm3 ,<br />

R. Ocklenburg3 ,J.O.Schwab4 . 1Bonn, Germany; 2Luxembourg, Luxembourg; 3Muenchen, Germany; 4University of Bonn, Department of<br />

Medicine-Cardiology, Bonn, Germany<br />

Introduction: Sudden cardiac death in athletes is more common than in the general<br />

population. Routine screening procedures are performed to identify competitors<br />

at risk. A new, Holter based parameter, analyses variation of the ventricular<br />

repolarization (TVAR). The aim of the present study was to evaluate differences in<br />

ECG, Echo, and Holter (H) in competitive athletes compared to a healthy control<br />

group consisting of medical students (MS).<br />

Methods: 40 athletes (19 female, Olympic Team, Luxembourg) and 40 MS (22<br />

female) were examined by means of a resting ECG, treadmill exercise (TE),<br />

echocardiogram (Echo), as well as H recordingsduring a routine screening visit.<br />

To analyze TVAR, a 20 min H recording at rest (sampling rate 2000 s -1 )was<br />

performed.<br />

Results: No differences in demographic variables were detected. The Table illustrate<br />

the findings of echo and H computations.<br />

Parameters of Echocardiography/Holter<br />

Parameter Athletes (mean±SD) Students (mean±SD) P-value<br />

<strong>Heart</strong> rate (bpm) 66±8 77±7


hibitory response, or in pts with positive HUTT during passive or active phases.<br />

At multivariate analysis, the presence of a number of syncopes > 4inthelast12<br />

months before HUTT was a risk factor for syncopal recurrence either in pts with<br />

positive HUTT (p = 0.028; HR: 1.83; CI (95%) = 1.07-3.17) or in all the pts that<br />

evaluated by HUTT (p = 0.023; HR: 1.7; CI (95%) = 1.07-2.69).<br />

Conclusions: This study shows that HUTT results are poorly predictive of syncopal<br />

recurrences. The history of syncope (number of previous syncopal episodes)<br />

is associated to different outcomes in terms of syncopal recurrences. Indeed, a<br />

number of previous syncopal episodes > 4 in the 12 months before HUTT represents<br />

an important risk factor for syncopal recurrence during long-term f-up,<br />

either in pts with a positive HUTT or in all the pts evaluated in this study.<br />

1855 Increased beat to beat variability of QT intervals as an<br />

additional diagnostic marker in long QT Syndrome<br />

B.M. Beckmann1 , M. Hinterseer1 ,M.B.Thomsen2 ,R.Dalla-Pozza1 ,<br />

M. Loeff1 , A. Pfeufer3 ,H.Netz1 , S. Kaab1 . 1Universitaetsklinikum Grosshadern, Medizinische Klinik I, Munich, Germany; 2Columbia University, Department of Pharmacology, New York, United States of America;<br />

3Helmholtz Center Neuherberg and Technical Uni, Institut fuer Humangenetik,<br />

Munich, Germany<br />

Long QT syndrome (LQTS) is one of the most common inheritedcardiac arrhythmias,<br />

and it may serve a a model disease for an impaired repolarisation reserve<br />

as seen in aquired or drug induced LQTS. Usually diagnosis and risk stratification<br />

in LQTS is based on the length of QT interval. Studies indicate that not only<br />

prolongation of QT interval but also an enhanced beat-to-beat variability of the<br />

QT-intervals measured as short-term variabiliy of the QT-interval, is a marker for<br />

a decreased repolarization reserve. In the absence of QTc prolongation, baseline<br />

STVQT characterized patients with documented drug-induced proarrhythmia.<br />

Purpose: To evaluate if LQT mutation carriers (MC) have an increased beat-tobeat<br />

variability of the QT interval measured as STVQT, and if so, to explore if<br />

STVQT could contribute to distinguish mutation carriers from healthy controls.<br />

Methods and Results: 60 MC of a mutation in one of the major LQT disease<br />

genes were compared to 60 age- and sex-matched controls. Lead-II or lead-<br />

V5 RR, and QT intervals from 30 consecutive beats were manually measured.<br />

STVQT was determined from Poincaré plots of QT intervals (STVQT=�|QTn+1-<br />

QTn|/[30* √ 2]). In addition QTc of 3 cycles was determined using Bazett’s formula.<br />

MC had longer QTc intervals and STVQT (461±52 and 6.9±2 ms, respectively)<br />

than controls (408±28 and 4.3±2 ms, respectively; both P50% (n=8), nonstenosing coronary<br />

plaque (n=11), and coronary anomaly (n=1). Effective radiation dose was<br />

2.2±0.7, 2.2±0.1, and 6.2±0.2 mSv for CTCA, stress-SPECT, and rest-SPECT,<br />

respectively. Thus, total radiation dose was significantly lower for CTCA/stress-<br />

SPECT (4.4±0.7 vs 8.5±0.3 mSv for standard stress/rest SPECT, p


282 Multimodality imaging of coronary heart disease<br />

Table 1. Main long-term mortality predictors<br />

Without previous infarction With previous infarction<br />

HR (95% CI) P HR (95% CI) P<br />

Age 1.07 (1.04-1.09)


Multimodality imaging of coronary heart disease / Optimisation of techniques and adjunct therapy in cardiac surgery 283<br />

sitivity, specifity, negative predictive and positive predictive value, and accuracy<br />

for GRE-MRI analysis of myocardial perfusion in the detection of flow-limiting<br />

epicardial coronary artery lesions, as defined as diameter stenosis >50%, were<br />

72%,100%, 54%, 100% and 73%, respectively.<br />

Conclusions: These preliminary results indicate a moderate diagnostic accuracy<br />

of cardiac GRE-MRI perfusion imaging at least during dipyridamole-induced coronary<br />

flow increases in the detection of flow-limiting epicardial artery lesions. The<br />

concordance between 201TI-SPECT and cardiac GRE-MRI imaging in the detection<br />

of stress-induced perfusion defects was relatively low, and 39% of 201TI-<br />

SPECT-determined perfusion defects were not identified by cardiac GRE-MRI,<br />

that deserves further investigations.<br />

P1880 Myocardial T2* estimation techniques in iron overload<br />

disease: relationship with left ventricular function<br />

M. Leung, G. Brown, A. Carbone, S. Worthley. Royal Adelaide<br />

Hospital, Adelaide, Australia<br />

Objectives: Myocardial T2* relaxometry has been proposed as a<br />

measure of myocardial iron accumulation and is associated with fatal heart failure.<br />

Its estimation can be observer dependent, limiting its clinical utility. We developed<br />

explicit rules for data acquisition and analysis and assessed their impact<br />

on myocardial T2* estimate (myoT2*), its reproducibility and relationship with left<br />

ventricular function.<br />

Methods: Mid-septum short-axis segmented FLASH images with 11 TE values<br />

(3.6-18ms) were acquired on 30 patients with congenital haemoglobinopathy.<br />

Mean pixel values at the inter-ventricular septum were graphed against TE.<br />

myoT2* was derived from exponential regression analysis. Comparison between<br />

11 and standard 9 TE values (5.6-18ms), and the inclusion/exclusion of myocardial<br />

signal indistinguishable (signal-1SD < noise+1SD) from background noise<br />

(noise test) was performed by Bland-Altman analysis. Intra-, inter-observer and<br />

inter-study variability were assessed by % coefficient of variation (%CV) and<br />

Bland-Altman analysis.<br />

Results: Observed myoT2* was 16.4±12.2ms (mean±SD). 11 versus 9 TE<br />

demonstrated a myoT2* mean difference (95% limits of agreement) of -0.4ms<br />

(-6.2, 5.4ms), and with/without noise test of 0.3ms (-2.6, 3.2ms). With 11 TE and<br />

noise test, intra-, inter-observer and inter-study %CV were 6.4%, 8.1% and 5%<br />

respectively. Mean difference between observations (95% limits of agreement) for<br />

all myoT2*, myoT2*>20ms (normal) and ≤20ms (abnormal) are shown in Table<br />

1. Logn myoT2* correlated with LVEF (P=0.021, R=0.433).<br />

Table 1. Reproducibility of myoT2*<br />

Reproducibility myoT2* range Mean Difference 95% Limits of Agreement<br />

Intra-observer all myoT2* 0.3ms -5.0 to 5.7ms<br />

myoT2*≤ 20 ms -0.08ms -3.5 to 3.3ms<br />

myoT2*> 20 ms 0.8ms -6.5 to 8.2ms<br />

Inter-observer all myoT2* 0.5ms -3.6 to 4.7ms<br />

myoT2*≤ 20 ms 0.6ms -1.7 to 2.9ms<br />

myoT2*> 20 ms 0.5ms -6.0 to 7.0ms<br />

Inter-study all myoT2* 0.1ms -4.0 to 4.3ms<br />

myoT2*≤ 20 ms 0.1ms -2.2 to 2.5ms<br />

myoT2*> 20 ms 0.08ms -6.9 to 7.1ms<br />

Conclusions: This myoT2* methodology demonstrated high reproducibility and<br />

correlated with left ventricular function.<br />

P1881 Variables associated with contrast enhanced<br />

cardiovascular magnetic resonance in hypertrophic<br />

cardiomyopathy: importance of quantification and<br />

pattern of enhancement<br />

F. Marin Ortuno1 , J. Gonzalez1 , A. Garcia Honrubia2 , A. Romero1 ,<br />

V. Climent2 , F. Ruiz Espejo1 , V. Roldan3 ,J.R.Gimeno1 , G. De La Morena1 ,<br />

M. Valdes1 . 1Hospital Virgen de la Arrixaca, Murcia, Murcia, Spain; 2Hospital General Universitario, Cardiology, Alicante, Spain; 3Universidad de Murcia,<br />

Centro Regional de Hemodonacion, Murcia, Spain<br />

Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and<br />

disarray. Late gadolinium-enhancement (LGE) in cardiovascular magnetic resonance<br />

(CMR) is observed in regions of increased myocardial collagen. The extent<br />

of LGE has been associated with higher prevalence of risk factors of sudden<br />

death. The aim of the present study was to describe the clinical characteristics<br />

and the presence of risk factors for sudden death in a series of patients from two<br />

referral centres for HCM in relation to LGE in CMR.<br />

Methods: 120 patients (47±16 years) were included. All patients fulfilled conventional<br />

criteria for HCM. Risk factors for sudden death were evaluated. A blinded<br />

CMR was performed with LGE in the left ventricular short-axis orientation. Quantification<br />

of LGE was performed by Mass Suite software. A qualitative analysis<br />

of the presence of LGE was also done. NT-proBNP and C-reactive protein were<br />

determined in serum samples.<br />

Results: 83 patients (69%) showed LGE. These patients had higher maximal left<br />

ventricular wall thickness (22±5vs.17±3 mm,p


284 Optimisation of techniques and adjunct therapy in cardiac surgery<br />

dure. Demographic profiles, operative data, long term survival and quality of life<br />

by the Short Form 36 Health Survey questionnaire were analysed.<br />

The 30 day mortality was 14.7% in the reoperation group and 8.5% (p=0.43)<br />

in the control group. Average time between previous operation and reoperation<br />

was 10.8±5.6 (range 1.7–30.6 years). Actuarial survival at 1, 3 and 6<br />

years was 77.2±5%, 58.3±6.3% and 36.3±7.8% for patients with reoperation<br />

and 71±5.5%, 58.3±6.3% and 30±8.1% for matched patients with primary cardiac<br />

surgery (p=0.68) (figure). No significant differences regarding the physical<br />

(40.7±9.4 vs. 39.1±10, p=0.55) and the mental health summarized-score<br />

(51.9±10.9 vs. 48±12.9, p=0.24) of the SF-36 were found between groups.<br />

Octogenarians exhibit a similar mortality, long-term survival and quality of life following<br />

primary and redo cardiac surgery. Therefore, this kind of surgery should<br />

not be reserved for younger patients alone.<br />

P1885 Mass-III: a randomized study comparing on-pump and<br />

off-pump coronary artery bypass graft surgery: 3-year<br />

results<br />

N.H. Lopes1 , A.F.T. Gois2 ,F.S.Paulitsch2 , C.L. Garzillo2 ,L.Dallan2 ,<br />

L.A.M. Cesar2 , N.A.G. Stolf2 , W. Hueb2 on behalf of MASS. 1<strong>Heart</strong> Institute - INCOR, Chronic Coronary Disease Department, Sao Paulo, Brazil;<br />

2<strong>Heart</strong> Institute, Sao Paulo, Brazil<br />

Introduction: In recent decades, concern has been increasing regarding reducing<br />

mortality and morbidity related to coronary artery bypass graft (CABG)<br />

surgery, particularly related to on-pump procedures. In this scenario, the development<br />

of off-pump techniques might provide advantages.<br />

Objectives: We compared the results of on-pump and off-pump procedures, regarding<br />

data during surgery, clinical evolution after surgery, and mortality and<br />

morbidity at 3-year follow-up.<br />

Methods: Patients with multivessel chronic coronary artery disease (CAD) and<br />

preserved left ventricular function who needed a CABG procedure and were suitable,<br />

according to surgeon’s assessment, for either on-pump or off-pump revascularization<br />

techniques were randomized and followed up. The duration of the<br />

surgery and need of a ventilator, intensive care unit (ICU) and hospital stay, clinical<br />

problems, and need of a blood transfusion were analyzed. The primary endpoints<br />

were cardiac death, myocardial infarction, and refractory angina requiring<br />

a new intervention.<br />

Results: 279 patients were randomized: 140 to on-pump and 139 to off-pump<br />

CABG. Baseline profiles were similar between the groups. Of those in the offpump<br />

group, a significant reduction occurred in the duration of surgery (4,08h vs.<br />

5,04h, p


Conclusions: EVH is a strong independent predictor of VGF in patients who undergo<br />

CABG surgery. The clinical significance of and mechanism behind this observation<br />

requires further investigation. These findings should be weighed against<br />

potential benefits of EVH.<br />

P1888 Incidence and risk factors of early thromboembolic<br />

events after mitral mechanical heart valve<br />

replacement in patients treated with intravenous<br />

unfractionated heparin<br />

N. Allou1 , P. Piednoir2 , C. Berroeta2 , S. Provenchere2 , H. Ibrahim2 ,<br />

L. Etchegoyen2 ,P.Montravers2 ,B.Iung2 , I. Philip2 , N. Ajzenberg2 . 1CHU Bichat-Claude - Bernard, Postcardiac intensive care unit, Paris, France; 2CHU Bichat-Claude -Bernard, Postcardiac intensive care unit, Paris, France<br />

Purpose: The management of postoperative anticoagulation (AC) after mechanical<br />

heart valve replacement (MHVR) remains controversial, even in recent guidelines.<br />

The aim of our study was to evaluate incidence and risk factors of early<br />

thromboembolic events (TE) after MHVR in patients (pts) treated with intravenous<br />

unfractionated heparin (IVUH).<br />

Methods: This study included all patients undergoing MHVR between December<br />

2005 and May 2007. Postoperative AC was performed with IVUH and started the<br />

4th postoperative hour with 100/IU/kg/day and regularly increased to target an<br />

APTT ratio of 2 to 3 on day 2, according to a standardized protocol. Vitamin K<br />

antagonist was started on the second postoperative day. The endpoint was the<br />

occurrence of arterial TE from day 1 to 30. We also collected major bleeding<br />

complications.<br />

Results: 300 pts were studied. Mitral (M) or double MHVR were performed in 149<br />

pts, and aortic (A) MHVR in 151 pts. 24 pts (8%) had an early TE: 11 nonobstructive<br />

prosthetic valve thrombosis, 2 obstructive valve thrombosis, 3 thrombi in the<br />

left atrium and 8 ischemic strokes. Twenty-two (14.8%) TE occurred after a M or<br />

double MHVR and 2 (1.3%) after an A-MHVR (P=0.005).Consequently, we studied<br />

risk factors of TE only in pts with M or double MHVR. In multivariate analysis<br />

diabetes mellitus (OR [95% CI]: 3.9 [1.2-12.9]; p=0.04) and a none effective AC<br />

on day 3 (3.5 [1.1-10.5]; p=0.02) were independent risk factors for TE. 12 major<br />

bleeding events (8.3%) occurred in pts with M or double MHVR. We did not find<br />

any association between the timing of effective AC and bleeding complication.<br />

Conclusion: This study using systematic early post-operative AC with IVUH<br />

shows that: 1) TE rate remains high after mitral MHVR; 2) inadequate AC at day 3<br />

was a predictor of post-operative TE, suggesting that early effective AC is mandatory;<br />

3) patients with diabetes seem at higher risk of TE and might benefit from<br />

more aggressive treatment.<br />

P1889 Bridging therapy to chronic anticoagulant treatment<br />

in patients undergoing cardiac surgery: comparison<br />

between low-molecular-weight heparin and<br />

subcutaneous unfranctionated heparin. A pilot study<br />

C. Rostagno, S. Romagnoli, S. Bevilacqua, F. Puggelli, G. Rosso,<br />

G. Giunti, G.F. Montesi, L. Ghilli, S. Caciolli, P.L. Stefano. AOU Careggi,<br />

Cardiologia 1, Firenze, Italy<br />

Purpose: At present no clear evidence has been provided regarding the superiority<br />

of various heparin regimens as bridging treatment to chronic anticoagulation.<br />

Aim of present pilot investigation was to prospectively compare the safety of<br />

weight adjusted enoxaparin and subcutaneous unfractionated heparin in patents<br />

undergoing valvular heart surgery.<br />

Methods: One hundred and four patients undergoing heart valve surgery between<br />

January 1 and March 31 2007 were randomized to weight adjusted<br />

enoxaparin (group I) or comparable weight adjusted subcutaneous unfractionated<br />

heparin (group II). Treatment was started 12 hours after ICU admission and<br />

maintained until therapeutic range of oral anticoagulation was obtained. Hemorrhagic<br />

and thromboembolic complications, the need for blood transfusions, total<br />

drainage fluid, haemoglobin values and presence and degree of pericardial effusion<br />

at discharge were evaluated.<br />

Results: A total of 104 patients was included, 52 for each group. We did not<br />

find any thromboembolic event in the two groups. Average fluid drainage after<br />

24 hours was similar with the two regimens (401 group I vs 411 ml group II)<br />

while the need of blood unit transfusion in ICU after starting heparin therapy was<br />

higher in patients treated with enoxaparin vs. s.c. unfractionated heparin (40 vs<br />

30% p


286 Atrial fibrillation<br />

P1893 Right ventricular rhythmic cardiomyopathy: about<br />

patients treated by catheter ablation for atrial<br />

fibrillation<br />

R. Ollivier, E. Donal, D. Veillard, D. Pavin, J.-C. Daubert, P. Mabo.<br />

Rennes, France<br />

Background: Left ventricular systolic dysfunction is frequent and is a<br />

well-known problem in atrial fibrillation (AF) patients. No data exist in regard to the<br />

potential involvement of the right ventricle (RV) in that rhythmic cardiomyopathy.<br />

Aims: To determine in witch extent AF affects RV-function and -remodelling and,<br />

if pulmonary vein isolation is efficient to improve them.<br />

Method: We prospectively studied 30 patients (mean age: 58±10 y.o., 77% men<br />

(23)) with paroxysmal (n=22) or persistent (n=8) AF, referred for pulmonary vein<br />

isolation. A control group of 15 patients without any cardiac disease, matched in<br />

age and sex, was also studied. All patients had echocardiographic study at baseline,<br />

at discharge and at 3-months follow-up (f/u). Right ventricle study included<br />

minimal and maximal areas, systolic excursion of the tricuspid annular plane in<br />

M-mode (TAPSE), RV’s lateral wall peak-velocity (Sa) measured by DTI and maximal<br />

longitudinal shortening measured by strain (ε) on RV’s lateral wall.<br />

Results: RV’s areas weren’t different between AF patients and controls, at baseline,<br />

nor at 3-months f/u. AF may not induce significant RV morphological remodelling.<br />

At baseline, AF patients had lower TAPSE than controls (21.2±6.5 mm vs. 28.3±4<br />

mm, p


any antiarrhythmic drug (AAD), Group 2: 62pt class II agent: Amiodarone 30pt,<br />

32pt with Sotalol due to contraindications to Amiodarone, Group 3: 58pt - last ineffective<br />

drug (1pt quinidine, 1pt werapamil+metoprolol, 9pt propafenone + metoprolol,<br />

29pt metoprolol, 15pt propafenone, 3 pt bisoprolol). During 2months of<br />

follow-up after ARF 24-hour ECG recording was performed twice, and standard<br />

ECG was performed each time any symptoms of arrhythmia occurred.<br />

Results: There were no significant differences in coronary artery disease, hypertension,<br />

diabetes mellitus, persistent AF rates among groups. 88pt (48,9%) were<br />

free of any AF episodes. In 36pt (20%) single episode occurred. More than one<br />

episode, but reduction in duration and severity of AF episodes was observed in<br />

41pt (22,7%), no improvement was observed in 15pt (8,4%).<br />

Results in subgroups: G1: no recurrence 34pt (56,7%), 1 AF episode 9pt (15%),<br />

reduction 13pt (21,7%), no improvement: 4pt (6,6%); G2: no recurrence – 28pt<br />

(45,2%), 1 AF episode: 10pt (16,1%), reduction – 17pt (27,4%), no improvement:<br />

7pt (11,3%); G3: no recurrence – 26pt (44,8%), 1 AF episode: 17pt (29,3%),reduction<br />

– 11pt (18,97%), no improvement: 4pt (6,9%). X2 test: G1 vs G2: p=0,32;<br />

G1vsG3: p=0,98; G1vsG3: p=0,42; G1vsG2vsG3: p=0,34. There is no significant<br />

difference between results in subgroups. Proarrhythmia: increase in number of<br />

AF episodes and severity of AF occurred in 1 pt (1,6%) without AAD, new atypical<br />

atrial flutter occurred in 1pt (1,7%) with propafenone and 2pt (3,2%) with sotalol.<br />

Long QT >460ms occured in 2pt (3,2%) with sotalol.<br />

Conclusions: Antiarrhythmic prophylaxis do not improve clinical outcome during<br />

blanking period in patients after radiofrequency ablation due to atrial fibrillation.<br />

P1897 Pill-in-the-pocket strategy on-top of chronic<br />

antiarrhythmic therapy for conversion of recent onset<br />

atrial fibrillation to sinus rhythm<br />

G.L. Botto1 ,M.Luzi2 ,G.Russo2 , B. Mariconti 2 ,F.Ruffa3 ,<br />

G. Cappelletti 2 ,P.L.Pina2 ,K.Sielert2 , M. Guanziroli 2 ,<br />

S.C. Zerboni2 . 1Sant’ Anna Hospital, Cardiology Department, Como, Italy;<br />

2 3 Sant’Anna Hospital, Cardiology, Como, Italy; Manzoni Hospital, Cardiology,<br />

Como, Italy<br />

Background: Data about the use of oral loading of 1C antiarrhythmic drugs (1C-<br />

AADs) on-top of chronic antiarrhythmic therapy to convert atrial fibrillation (AF)<br />

relapses to sinus rhythm (SR), are lacking.<br />

Methods: The study group consisted of 241 patients (pts) with history of paroxysmal<br />

AF without heart failure, coronary heart disease and conduction disturbances,<br />

chronically treated with class 1C-AADs as prophylaxis. When recent onset<br />

(


288 Atrial fibrillation<br />

modelling characterised by interstitial fibrosis, atrial enlargement, slowed and<br />

heterogenous conduction, increased effective refractory periods and a greater<br />

propensity for AF. These findings highlight the importance of early and aggressive<br />

therapy for hypertension to prevent the development of arrhythmogenic substrates.<br />

P1902 Incidence of atrial fibrillation after percutaneous<br />

closure of patent foramen ovale and small atrial<br />

septal defects in patients presenting with cryptogenic<br />

stroke: a case-control study<br />

R. Bonvini, R. Sztajzel, M. Righini, P.A. Dorsaz, J. Alibegovic,<br />

C. Bonvin, U. Sigwart, E. Camenzind, V. Verin, J. Sztajzel on behalf of NA.<br />

University Hospital of Geneva, Cardiology, Geneva, Switzerland<br />

Background and Purpose: The occurrence of atrial fibrillation (AF) after percutaneous<br />

closure of a patent foramen ovale (PFO) for cryptogenic stroke has been<br />

reported in a variable percentage of patients. However, its precise incidence and<br />

mechanism are presently unclear and remain to be elucidated.<br />

Methods and Results: We started from 2002 onwards an arrhythmia follow-up<br />

(FU) protocol performing a 7-day event-loop-recording (ELR) at day 1, after 6 and<br />

12 months in patients who underwent a percutaneous PFO closure procedure for<br />

cryptogenic stroke. Ninety-two patients (Closure Group) were so far followed and<br />

then compared to a similar Control Group of 51 patients who did not undergo the<br />

PFO closure for several reasons. The incidence of AF was similar in both study<br />

groups during a FU of 12 months, including 7.6% (95% CI: 3.1%-15.0%) in the<br />

Closure Group and 7.8% (95% CI: 2.18%-18.9%) in the Control Group (p=1.0).<br />

The presence of a large PFO was the only significant risk factor for the occurrence<br />

of AF irrespective of the type of the administered treatment (i.e. interventional or<br />

medical). The odds ratio was 6.596 (95% CI, 1.660–26.21; P=0.0051).<br />

Conclusions: Patients with cryptogenic stroke and PFO had a rather high incidence<br />

of AF during a FU of 12 months, irrespective if the PFO was percutaneously<br />

closed or medically managed. The presence of a large PFO was the only<br />

significant predictor of AF occurrence during FU. Meticulous AF detection protocols<br />

should be performed in all cryptogenic stroke patients, especially in those<br />

scheduled for PFO-closure.<br />

P1903 Combined anatomical and electrogram-guided<br />

approach in catheter ablation of atrial fibrillation<br />

G.B. Nam, K.M. Park, K.J. Choi, Y.H. Kim. Asan Medical Center,<br />

Univ Ulsan Coll Med, Cardiology, Seoul, Korea, Republic of<br />

Purpose: Current catheter ablation of atrial fibrillation (AF) is focused<br />

on the elimination of pulmonary vein (PV) potentials. Tailored approach based on<br />

complex fractionated electrograms (CFE) has been proposed. Additive effect of<br />

this electrogram-guided approach in addition to the anatomical PV antral isolation<br />

has not been reported.<br />

Methods: 1. Patients with symptomatic, drug-refractory AF (paroxysmal, 76, persistent,<br />

29 pts) were included. 2. Catheter ablation was guided by fluoroscopy<br />

or 3D mapping system (NavX or CARTO). 3. PV antral isolation (PVAI) was<br />

performed targeting elimination or dissociation of PV potentials. After PVAI,<br />

electrogram-guided ablation was continued targeting CFEs or high-frequency activity<br />

relative to the surrounding areas. 4. End-point of the procedure was noninducibility<br />

of AF in pts with paroxysmal AF (PAF), termination into sinus rhythm<br />

in pts with persistent AF (PeAF).<br />

Results: 1. In PAF, PVAI alone rendered AF non-inducible in 42 of 79 pts (55%).<br />

After electrogram-guided ablation, AF became non-inducible in additional 12 pts<br />

(16%), while only atrial flutters (AFL) were induced in 16 pts (21%). AF persisted<br />

in 6 pts (8%) after this combined ablation procedure. In 16 pts with inducible<br />

AFL (27 AFLs), mechanisms of tachycardia included right isthmus dependent in<br />

5/27, perimitral in 4/27, roof-dependent in 4/27, focal in 8/27, and unknown in<br />

6/27 AFLs. 2. In PeAF, PVAI restored sinus rhythm in 0/29 pts. After electrogramguided<br />

ablation, AF converted directly into sinus rhythm in 2(7%) and into AFLs<br />

in 19 pts (65%), while AF persisted in 8 pts (28%). In 19 pts with AFLs (38 AFLs)<br />

converted from AF, mechanisms of tachycardia were right isthmus dependent in<br />

12/38, perimitral in 11/38, roof-dependent in 5/38, focal in 6/38, and unknown in<br />

4/38 AFLs.<br />

Conclusions: Electrogram-guided ablation targeting CFEs after PVAI resulted in<br />

non-inducibility of AF in pts with PAF, or conversion of AF into AFL in pts with<br />

PeAF. The major mechanism of the induced or converted AFLs during this combined<br />

procedure was macroreentry around the large anatomic obstacles such as<br />

tricuspid/mitral annulus or PVs.<br />

P1905 Anatomical differences in the coronary venous<br />

system in patients with persistent atrial fibrillation<br />

compared to patients in sinus rhythm<br />

E. Arbelo Lainez, E. Caballero Dorta, J. Novoa Medina, A. Garcia<br />

Quintana, A. Delgado Espinosa, C. Amador Gil, M.C. Rios Diaz,<br />

A. Medina Fernandez-Aceytuno. Hospital de Gran Canaria Dr. Negrin, Servicio<br />

de Cardiologia, Las Palmas De Gran Canaria, Spain<br />

Introduction and Objective: The coronary sinus (CS) muscle sleeves have been<br />

suggested to have role in the genesis of atrial fibrillation (AF), having been described<br />

a higher probability of conversion to sinus rhythm (SR) by ablating at that<br />

level in patients (p) with persistent AF. The aim was to describe the anatomy of<br />

the coronary venous system in p with persistent AF.<br />

Methods: The anatomy of the CS and its tributaries was studied by hyperemic<br />

coronary venous return angiography and/or occlusive retrograde senovenography<br />

in 319 p, 47 (15%) of which were in persistent AF (70% male, 64,8±10,5 years<br />

left atrial diameter 47,5±6,6 mm).<br />

Results: The diameter of the CS ostium was 17,3±5 mm with the presence of a<br />

Thebesian valve in 37 p (79%) that covered 45,9±33,8% of the orifice and left an<br />

opening into the right atrium of 12,1±6,3mm. The length of the CS was 42,3±12,8<br />

mm and its diameter 13,3±2,7 mm, whereas that of the great cardiac vein (GCV)<br />

was 10,7±2,7 mm. The oblique vein of Marshall was observed in 27 p (57%) and<br />

the Vieussens valve (ViV) in 33 (70%), being the two associated in 25 p (53%). In<br />

4 p an aneurismatic dilatation of the proximal CS (8,5%) was seen and in 32 (68%)<br />

diastolic compression of the CS was present, 12 of which (25,5%) consisted of<br />

a discrete muscular sleeve of 3 to 7 mm width. 4 p (8,5%) additionally showed<br />

muscular sleeves over the tributary veins of the CS. The mean diameter of the<br />

lateral vein was 4,2±1,4 mm. When comparing this group in persistent AF to the<br />

272 p in SR, statistically significant differences were found in terms of diameter<br />

of the CS ostium, the CS and GCV. The VoM were also more prevalent, with a<br />

greater length and diameter. Finally, the ViV and an aneurismatic dilatation of the<br />

proximal CS were also more frequent.<br />

Conclusions: The anatomy of the CS and its tributaries has differential characteristics<br />

in patients with persistent AF. This might play a role in the mechanisms<br />

of AF or have implications in the design of the ablation procedure.<br />

P1906 Time-dependent regional differences in sources of<br />

oxidative stress in atrial fibrillation-induced<br />

remodelling<br />

S.N. Reilly1 , U. Schotten2 ,N.J.Alp1 , B. Casadei1 . 1University of Oxford, Cardiovascular Medicine, Oxford, United Kingdom;<br />

2University of Maastricht, Physiology, Maastricht, Netherlands<br />

Purpose: Atrial fibrillation (AF) is associated with electrical and structural atrial<br />

remodelling and with increased myocardial oxidative stress, leading to reduced<br />

nitric oxide (NO) bioavailability and NOS uncoupling. To date, it is unclear whether<br />

oxidative stress is a trigger or a by-product of atrial remodeling. We evaluated the<br />

time course and sources of superoxide (O2-) production in the right (RA) and left<br />

(LA) atria of a goat model of pacing-induced AF.<br />

Methods: Atrial O2- was assessed (lucigenin-enhanced chemiluminescence and<br />

2-OH ethidium detection by HPLC) 14 days after the onset of AF (i.e. only electrical<br />

remodeling presents) and after 6 months (electrical and structural remodeling).<br />

The NOS cofactor BH4 and NOS activity were assessed by HPLC.<br />

Results: In early AF O2- release was significanty increased in the LA only (Figure,<br />

n=4). Inhibition of NADPH oxidases normalized O2- production in LA-AF but<br />

had no effect in the RA or in SR. Atrial NOS activity and nNOS protein expression<br />

but not BH4 level were reduced in both atria in AF.<br />

In late AF, O2- release was greater in both atria (Figure). NADPH oxidase inhibition<br />

did not affect O2- production, whereas inhibition of NOS or mitochondrial<br />

Abstract P1905 – Characteristics of the CS in AF and SR<br />

N Diameter Effective orifice Aneurismatic Diameter Diameter Presence of Diameter Presence of<br />

of the CS ostium (mm) of the CS (mm) proximal CS (%) of the CS (mm) of the GCV (mm) VoM (%) of VoM (mm) ViV (%)<br />

AF 47 17,3±5 12,1±6,3 8,5% 13,3±2,7 10,7±2,7 61% 2,04±0,7 75%<br />

SR 272 13,4±4,4 8,9±4,1 2% 10,6±2,8 9,1±2,2 36% 1,6±0,8 57%<br />

p


oxidases decreased O2- by 16±3.1% and 38.1±4.1%, respectively (P


290 Atrial fibrillation<br />

cardioverted episode of persistent LAF, appear to be early and reliable predictors<br />

of SR maintenance during the following year.<br />

P1911 Transoesophageal echocardiographic findings in<br />

patients with persistent atrial fibrillation at low risk for<br />

stroke (CHADS 0 or 1)<br />

I. Karnialiuk, I. Aliakseyeuskaya, M. Belskaya, Y. Persidskikh. The<br />

Center of Cardiology, Minsk, Belarus<br />

Purpose: Atrial fibrillation (AF) promotes the development of atrial thrombus (AT),<br />

which can be revealed by transoesophageal echocardiography (TOE). This study<br />

was aimed to compare various echocardiografic parameters, assessed during<br />

transthoracic (TTE) and TOE in two groups of patients divided according to the<br />

detection of thrombus in left atrial appendage (LAA).<br />

Methods: TTE and TOE were performed in 56 patients with persistent nonrheumatic<br />

AF at low risk for stroke (CHADS 0-1), who were planned to undergo<br />

electrical cardioversion. The following parameters were analyzed: left atrial diameter<br />

(LA), left ventricular endsystolic and enddiastolic diameter (LVes, LVed),<br />

ejection fraction (EF). The presences of spontaneous echocontrast (SEC), LAA<br />

area and flow velocity in the LAA (LAAa, LAA-flow) were measured during TOE.<br />

Results: A thrombus was detected in 20 patients (35.7%) in the LAA. Out of<br />

these patients, 85.0% vs. 16.7% of patients without thrombus showed moderate<br />

or severe SEC (p


Fig. 1. Five types of merge errors.<br />

nical match errors (10 errors, 43%), position change due to movement (5 errors,<br />

21.7%), volume discrepancy with the CT and 3D map (4 errors, 17.4%), rotational<br />

disarrangement (3 errors, 13.0%), and a bad CT image (1 error, 4.3%) (Figure 1).<br />

A significant correlation between the LA size and match statistic data was determined<br />

(r = 0.382, p = 0.01). Excluding patient movement, the match statistic<br />

data showed a significant correlation with the LA size (r = 0.382, p = 0.002) and<br />

practical match accuracy (r = -0.276, p = 0.026).<br />

Conclusion: Although CARTO-Merge is very useful tool for AF ablation, for accurate<br />

integration, more detailed mapping needs to be performed in order to attempt<br />

to prevent movement, and to consider the position of patients, the CT image and<br />

the LA size.<br />

P1917 Coagulation dysfunction can be improved by statin in<br />

atrial fibrillation regardless of cholesterol level<br />

H.W. Park, N.S. Yoon, K.H. Kim, Y.J. Hong, J.H. Kim, Y.K. Ahn,<br />

M.H. Jeong, J.G. Cho, J.C. Park, J.C. Kang. Chonnam National<br />

University Hospital, Cardiovascular Medicine, Gwangju, Korea,<br />

Republic of<br />

Background: Circulating lipids appear to have prothrombotic and endotheliumaltering<br />

properties. Atrial fibrillation is associated with thromboembolism, endothelial<br />

dysfunction and abnormalities in coagulation system. However, it is not<br />

certain whether statin may reverse prothombotic condition in atrial fibrillation.<br />

Methods: Consecutive 306 atrial fibrillation patients were enrolled. Patients of<br />

group I had dyslipidemia and received statin for more than 6 months (n=122,<br />

59±11 years) and group II had not dyslipidemia and did not receive statin (n=184,<br />

56±17 years). Markers for endothelial function (von-Willebrand factor, vWF; factor<br />

8 related antigen and ristocetin cofactor), inflammation [WBCs, ESR, quantitative<br />

and high sensitivity C-reactive protein] and coagulation system (fibrinogen, fibrinogen<br />

degradation product, fibrin d-dimer) and platelet activity (p-selectin) were<br />

measured.<br />

Results: There were no significant differences in levels of markers for endothelial<br />

dysfunction or inflammation between 2 groups. Total and LDL-cholesterol levels<br />

were significantly higher in group I than in group II (185±44 mg/dL vs 169±35<br />

mg/dL, p=0.001; 124±45mg/dL vs 102±29mg/dL, p=0.001). Even though fibrinogen<br />

level was not different between 2 groups (group I; 303±88 mg/dL, group II;<br />

287±84 mg/dL, p=0.107), fibrinogen degradation product level was significantly<br />

lower in group I (1.1±1.7 ug/mL vs 2.2±4.6 ug/mL, p=0.024). D-dimer level also<br />

was significantly lower in group I than group II (0.19±0.19 mg/L vs 0.27±0.29<br />

mg/L, p= 0.013).<br />

Conclusion: Statin showed beneficial effect on coagulation system in patients<br />

with atrial fibrillation regardless of their cholesterol level and statin may reduce<br />

thromboembolism in patients with atrial fibrillation<br />

P1918 Pulmonary veins remodeling and transcatheter<br />

ablation of atrial fibrillation<br />

V. Scarabeo, G. De Simone, F. De Conti, P. Turrini, R. Verlato,<br />

N. Lafisca, A. Zampiero, P. Piovesana. Camposampiero Hospital,<br />

Cardiology, Camposampiero (Pd), Italy<br />

Introduction: Radiofrequency circumferential isolation of the pulmonary veins is<br />

a recently introduced ablation technique for the treatment of atrial fibrillation.<br />

This study evaluated pulmonary veins remodeling at long term follow-up after<br />

transcatheter ablation of atrial fibrillation.<br />

Methods: 81 patients undergoing pulmonary veins isolation procedure were included.<br />

All patients underwent transoesophageal echocardiogram before and<br />

three months after the procedure. Anatomical and functional study of the pulmonary<br />

veins was assessed. In case of abnormal pulmonary veins flow detection<br />

the exam was repeated at 12 months follow-up.<br />

Results: In 80 patients (98,7% of cases) visualization of veno-atrial junction was<br />

successfully done. Before ablation mean diameter of the left superior pulmonary<br />

vein resulted 1,19±0,64cm; left inferior pulmonary vein was 1,07±0,57cm;<br />

right superior pulmonary vein 1,28±0,69cm and right inferior pulmonary vein<br />

0,69±0,52cm. During follow-up there was a significant size reduction only of the<br />

left inferior pulmonary vein (p=0,02), corresponding to a 10% lumen reduction, defined<br />

as a mild stenosis. Venous flow analysis revealed increased flow velocity in<br />

20 patients (≥100cm/s); in 4 patients flow velocity resulted >150 cm/s. Increased<br />

flow velocity involved the left superior pulmonary vein and the right superior pulmonary<br />

vein in the same number of patients (12 patients, 14,8%). 10 patients<br />

Atrial fibrillation 291<br />

(12,3%) had two vessels with increased flow velocity, 5 patients (6,1%) had one<br />

vessel and 3 patients (3,7%) three vessels. One patient presented a 62,5% lumen<br />

reduction compared to baseline value, resulting in a moderate stenosis, not<br />

requiring interventional treatment. All patients were asymptomatic, and didn’t develop<br />

pulmonary hypertension after procedure.<br />

Conclusions: Study of pulmonary veins remodeling after ablation procedure<br />

showed a significant lumen reduction (narrowing by 10%) only in the left inferior<br />

pulmonary vein and a flow velocity increase of one or more vessels, but not<br />

requiring treatment.<br />

P1919 Have the same significance prior or acute atrial<br />

fibrillation in octogenarian patients with acute<br />

myocardial infarction?<br />

J. Galcera Tomas1 , A. Melgarejo-Moreno2 , A. Padilla-Serrano3 ,<br />

N. Alonso-Fernandez2 , J.H. De Egea-Garcia 3 , D. Martinez-Bano3 ,<br />

A. Ortin-Freire3 , R. Jimenez-Sanchez3 , G. Escudero2 , P. Rodriguez-Garcia3 .<br />

1 2 Murcia, Spain; Hospital Universitario Santa Maria del Rosell, Cartagena,<br />

Spain; 3Hospital Universitario Virgen de la Arrixaca, Murcia, Spain<br />

Purpose: To study peculiarities and prognostic significance of atrial fibrillation<br />

(AF) depending of being previous (PAF) or presumed new appearance (NAAF) in<br />

octogenarian patients (OP) with acute myocardial infraction (MI).<br />

Methods: Prospectively in all OP admitted with acute MI from October 1997 to<br />

October 2007 to the Coronary Unit of two hospital of Murcia Region of Spain,<br />

incidence of AF and its classification as PAF or NAAF was established. Survival<br />

was studied by Kaplan-Meier curves and their association with mortality by multivariable<br />

analysis.<br />

Results: Among 775 OP-patients, 211 had AF: PAF N=77 and NAAF N=134. Patients<br />

with PAF were older (84±3 vs82±4, pI (64 vs 38% pII (21 vs 36%, p


292 Atrial fibrillation<br />

Results: LA ejection fraction and fractional shortening were significantly decreased<br />

in PAF. However, LA dimension, A-wave of transmitral flow, and LA emptying<br />

volume were comparable between two groups. The parameters of atrial<br />

dyssynchrony were summarized in Table.<br />

Table 1. Atrial dyssynchrony<br />

Control<br />

Reservoir period<br />

PAF p-value<br />

Ts-SD 16.0±11.4 19.2±15.0 0.258<br />

Tst-SD 29.7±11.9 39.7±15.8 0.001<br />

Tsr-SD<br />

Atrial contraction period<br />

37.3±18.7 41.8±14.1 0.262<br />

Ts-SD 25.9±16.3 33.6±18.6 0.035<br />

Tsr-SD 29.5±14.1 36.9±17.1 0.084<br />

Conclusions: In patients with recent onset PAF, atrial dyssynchrony was present.<br />

Of all parameters, dyssynchronous atrial lengthening assessed by strain during<br />

reservoir period showed the greatest difference between two groups.<br />

P1921 Predictors of mortality in atrial fibrillation<br />

T. Potpara1 ,M.Grujic2 ,J.Marinkovic2 , B. Vujisic2 ,N.Mujovic2 ,<br />

M. Polovina2 . 1Institute for Cardiovascular Diseases, cardiology,<br />

Belgrade, Serbia; 2Institute for Cardiovascular Diseases,KCS,<br />

Belgrade, Serbia<br />

The aim of the study was to assess mortality of patients treated for atrial fibrillation<br />

(AF).<br />

Out of 1100 pts with recently diagnosed AF, aged 52.7±12.0 years, 389 pts<br />

(35.4%) were females, 442 pts (40.2%) had lone AF, 939 pts (85.4%) had normal<br />

left ventricular systolic function and 33 pts (3.0%) had mitral annulus calcification<br />

(MAC), while 104 pts (9.5%) had dilated cardiomyopathy and 58 pts (4.8%)<br />

had coronary disease. AF was permanent from the beggining in 210 pts (19.1%).<br />

Treatment of AF was in concordance with current recommendations, aiming to<br />

control rhythm wherever possible, with 629 pts (57.2%) receiving beta blockers<br />

at some point of the follow up, 656 pts (59.6%) treated with amiodarone, 524 pts<br />

(47.6%) using digoxin at some point of the study, 841 pts (76.5%) received aspirin<br />

for the different time lenght and 677 pts (61.5%) were antikoagulated either<br />

continuously or periodically. We have also administered verapamil to total of 641<br />

pts (58.3%), propafenon to 333 pts (30.3%), sotalol to 82 pts (7.5%) or various<br />

drug combinations to total of 591 pts (53.7%) during the study.<br />

During total follow up of 9.9±12.1 years (prospective 5.7±4.3), 297 pts (27.0%)<br />

developed new cardiac disease and 112 pts (10.2%) noncardiac disorders. Hear<br />

failure was evident in 155 pts (14.1%), 64 pts (5.8%) developed coronary disease<br />

and thromboembolic events occured in 88 pts (8.0%). Total of 531 pts (48.3%) had<br />

permanent AF until the end of the study. There were 85 deaths (7.7%) and 62 of<br />

them (5.6%) were cardiovascular, including 25 sudden cardiac deaths. Mean age<br />

of pts at time of death was 68.0±10.9 years and 10.7±6.6 years elapsed from first<br />

episode of AF. In the time of death 18 pts (21.2%) were in sinus rhythm. Cumulative<br />

5-year survival rate in our study group was 98.1% (95%CI, 97.3-98.9%) and<br />

Cox proportional hazard regression model identified age at diagnosis of AF (HR<br />

1.8, 95%CI 1.4-2.5), reduction of LVEF during follow up (HR 2.0, 95%CI 1.1-3.5),<br />

heart failure during follow up (HR 2.7, 95% CI 1.5-4.6), thromboembolic events<br />

(HR 1.8, 95%CI 1.0-3.3) and MAC (HR 3.8, 95%CI 1.5-9.6) as risk predictors of<br />

all-cause death in patients with AF, while lone AF, use of beta blockers and use<br />

of aspirin had protective impact on mortality (HR 0.2, 95% CI 0.1-0.5, HR 0.5,<br />

95%CI 0.3-0.9 and HR 0.4, 95%CI 0.3-0.5, respectively), adjusted for sex, age<br />

and initial differences among pts with paroxysmal, persistent and permanent AF.<br />

The type of AF at the beggining and during the follow up had no independent,<br />

significant relation to death in our study population.<br />

P1922 Inflammation in lone atrial fibrillation: new insights by<br />

coronary sinus thermography<br />

E. Tsiamis1 , K. Toutouzas2 , M. Drakopoulou1 ,P.Dilaveris1 ,<br />

K. Gatzoulis1 , J. Karabelas1 , S. Vaina1 , E. Stefanadi1 ,K.Vlassis1 ,<br />

C. Stefanadis1 . 1Hippokration Hospital, Athens, Greece;<br />

2Hippokration Hospital, First Department of Cardiology, Athens, Greece<br />

Background: In the clinical setting there are conflicting results regarding the role<br />

of inflammatory activation in atrial fibrillation (AF). Coronary sinus (CS) thermography<br />

assesses myocardial heat production and is correlated with inflammatory<br />

states. We investigated in patients with AF whether 1) there is increased CS blood<br />

temperature and 2) the correlation of heat production with systemic inflammation.<br />

Methods: We included patients with AF and subjects with sinus rhythm. Creactive<br />

protein (CRP) levels were measured in all patients. CS and right atrium<br />

(RA) blood temperature measurements were performed by a dedicated 7F thermography<br />

catheter. �T was calculated by subtracting RA from CS blood temperature.<br />

Results: We included 47 patients with AF and 23 subjects with sinus rhythm. We<br />

stratified patients with AF into two groups: normotensive (AFN) and hypertensive<br />

(AFH). �T was lower in the RA compared with the CS in AFH (37.27±0.52°C vs<br />

37.47±0.54°C, p


manent AF were studied. The number of nerve fiber sections/mm 2 did not differ<br />

in SR and AF pulmonary vein ostial regions (0.29±0.21 versus 0.28±0.20). Immunohistochemical<br />

staining revealed mixed staining (adrenergic and cholinergic<br />

staining) in 62% of all nerve fibers in SR and 56% in AF. Predominantly adrenergic<br />

fibers were documented in 10% in SR and 39% in AF. 28% of nerve fibers<br />

were predominantly stained for cholinergic fibers in SR and 5% in AF. There is a<br />

significant difference in predominantly adrenergic nerve fibers in the left atrium of<br />

patients with SR (0.02±0.17 versus 0.19±0.28, p=0.003) compared to permanent<br />

AF<br />

Conclusions: In patients with SR or AF mixed staining (adrenergic and cholinergic)<br />

appears to be the predominant feature of autonomic nerves. Nerve densitiy<br />

was similar in SR and AF. There are significantly more adrenergic nerve fibers<br />

documented in permanent AF indicating a predmoninance of the adrenergic autonomic<br />

nerve system on the cellular level. In addition there appears to be relative<br />

partial atrial vagal denervation in permanent AF.<br />

P1925 Long-term success of intraoperative ablation of<br />

permanent atrial fibrillation<br />

T. Deneke, K. Khargi, B. Lemke, D. Voss, T. Lawo, A. Laczkovics,<br />

A. Muegge, M. Fritz. University <strong>Heart</strong> Center Bochum, Bg Klinik<br />

Bergmannsheil, Med. Klinik Ii, Bochum, Germany<br />

Short- and medium term rhythm success rates of intraoperative radiofrequency<br />

ablation to treat permanent atrial fibrillation (AF) are well documented. Is conversion<br />

to sinus rhythm (SR) long-term stable during follow-up of over 3 years?<br />

Methods: 122 patients who had undergone intraoperative radiofrequency cooledtip<br />

endocardial ablation (SICTRA) of permanent AF (> 1 year AF-duration) concomitant<br />

to open heart surgery more than 3 years ago were followed up using<br />

ECG and echocardiography. In 55% of patients only the left atrium and in 45%<br />

both atria were treated using SICTRA. Stable SR was documented based on<br />

ECG and atrial contraction based on atrio-ventricular Doppler-echo profile.<br />

Results: 122 patients underwent mitral valve replacement in 18, mitral valve reconstruction<br />

in 24, aortic valve replacement in 14, CABG procedures in 48 (including<br />

10 patients with additional mitral valve surgery) and complex procedures<br />

in 22 patients 52±14 (range 36-91) months ago. 69% of patients (84/122) were in<br />

stable SR whereas 28% (34/122) were in AF and 3% (4/122) were in atrial flutter.<br />

During the follow-up period 9 patients (7%) converted to AF after having documented<br />

SR and 2 patients (2%) converted to atrial flutter. Comparing patients<br />

after left to biatrial SICTRA no significant difference in rhythm success (74% versus<br />

60%) was documented (p=0.59). Echocardiography revealed 67% of patients<br />

in SR to have biatrial contraction.<br />

Conclusions: SICTRA effectively restores long-term stable SR in 69% of patients.<br />

9% of patients reconverted back to atrial arrhythmia more than 2 years<br />

after first documentation of SR. There is no difference in long-term rhythm efficacy<br />

when limiting the SICTRA to the left atrium alone.<br />

P1926 Outcome after limited ablation concepts to treat long<br />

lasting persistent AF: how much ablation is<br />

necessary?<br />

C. Piorkowski, A. Bollmann, M. Esato, P. Sommer, T. Gaspar,<br />

A.Arya,C.Staab,G.Hindricks.<strong>Heart</strong> Center Universitiy Leipzig,<br />

Electrophysiology, Leipzig, Germany<br />

Background: Patients with persistent AF often need additional atrial ablation lesions<br />

to modify the extensive substrate in addition to the trigger elimination. Current<br />

treatment approaches tend to extensive procedures with partly biatrial ablations,<br />

defragmentation, CS ablation, SVC isolation and different linear lesions.<br />

The present prospective study analyzed the rhythm outcome after a limited left<br />

atrial ablation concept in patients with persistent AF.<br />

Methods: 48 consecutive patients with highly symptomatic AF (57±10 years,<br />

83% male, AF history for 60 [24;95] months, 13% prior AF ablation, 52% lone<br />

AF, LA size 48±7 mm) received a left atrial ablation. After cardioversion patients<br />

were treated in SR with circumferential left atrial PV ablation. Additionally the<br />

posterior LA was electrically isolated through placement of a "Box lesion", and a<br />

mitral isthmus line was applied without enforcing line continuity through epicardial<br />

ablations.<br />

Results: Procedure, radiation and RF time measured 201±35, 38±15 and<br />

65±20 min, respectively. In 46/48 (96%) patients all PVs and the posterior LA<br />

were sucessfully isolated. In 14/48 (29%) patients ablation of the right atrial inferior<br />

isthmus was performed due to clinically documented typical atrial flutter. At<br />

the end of the procedure 22/48 (46%) patients were inducible for AF and atrial<br />

macroreentrant tachycardia (MRT) on aggressive Burst stimulation at the atrial<br />

refractory period. Postinterventional antiarrhythmic drug treatment was used in<br />

case of symptomatic recurrences of AF/MRT only. Three months after ablation<br />

7/48 (15%) patients received class Ic or class III antiarrhythmic drug treatment.<br />

During 7-day-Holter after 3 and 6 months freedom from AF and/or MRT was documented<br />

in 35/48 (73%) and 34/48 (71%) of the patients.<br />

Conclusions: Using a limited left atrial ablation concept aiming on truly continuous<br />

ablation lesions with electrophysiologically defined endpoints (complete PV<br />

isolation + complete Box-lesion + mitral isthmus line) more than 70% of the patients<br />

with previously persistent AF were free from recurrences of AF and/or MRT<br />

after a single intervention with 3 and 6 months of follow-up. The value of addi-<br />

Atrial fibrillation 293<br />

tional extensive ablation approaches such as atrial defragmentation, CS ablation<br />

and SVC isolation has to be judged against these results.<br />

P1927 Combination method of 3D mapping (CARTO-Merge)<br />

and the use of a large sized-lasso for atrial fibrillation<br />

ablation<br />

Y.S. Oh 1 ,J.H.Kim2 ,W.S.Shin2 ,S.W.Jang2 , Y.S. Choi2 ,C.S.Park2 ,<br />

S.W. Jin 2 , H.J. Youn2 , M.Y. Lee2 ,T.H.Rho2 . 1St. Mary’s Hospital,<br />

Internal Medicine, Seoul, Korea, Republic of; 2Seoul, Korea, Republic of<br />

Background: It is well known that catheter ablation is very effective treatment<br />

modality for the treatment of atrial fibrillation (AF). However many different treatment<br />

strategies have been developed to improve the success rate. We have<br />

produced good results with the combination method of a 3D mapping system<br />

(CARTO) and the use of a large-sized-lasso.<br />

Materials and Methods: A total of 154 patients were enrolled in the study. AF<br />

ablation was performed due to drug refractory paroxysmal, persistent and permanent<br />

AF. Sixty-nine patients underwent segmental pulmonary vein isolation<br />

(PVI) (Group 1), 21 patients received 3D mapping guided circumferential ablation<br />

(Group 2) and 64 patients were treated with the combination method of conventional<br />

electroanatomic mapping (CARTO) or electroanatomic mapping and CT<br />

imaging (CARTO-Merge) and the use of a large-sized (30–35 mm) lasso (Group<br />

3). In the combination method, both a continous antral line on the CARTO map<br />

and electrical conduction block at the antrum was confirmed by the use of the<br />

lasso. We compared the recurrence rates of AF for each group and analyzed<br />

factors affecting recurrence.<br />

Results: There were 97 male patients and the mean age was 57±10 years. The<br />

recurrence rate of paroxysmal AF in group 1, 2, and 3 patients was 29.6%, 23.1%,<br />

and 15.1%, respectively, and recurrence rate of persistent AF was 40.0%, 33.3%,<br />

and 223%, respectively. A significant decrease of recurrence between group 1<br />

and group 3 patients (p = 0.042) was seen, but was not seen for patients in group<br />

2 and group 3 (p = 0.053). The paroxysmal or the chronic AF group of patients<br />

did not show any significant difference for recurrence among the three groups.<br />

By multiple logistic regression, the use of a large sized-lasso was the strongest<br />

predictable factor of recurrence (odds ratio: 2.18, 95% CI: 1.099–7.118) and the<br />

LV ejection fraction was also a predictable factor for recurrence (p = 0.049).<br />

Conclusion: The combination method of CARTO merge and the use of a large<br />

sized-lasso might be a more effective strategy than segmental PVI and conventional<br />

3D mapping guided circumferential ablation.<br />

P1928 Development of depression and quality of life in<br />

patients with atrial fibrillation<br />

N. Rueb, M. Eberle, A. Henning, R. Laszlo, H.J. Weig, M. Gawaz,<br />

J. Schreieck. Tubingen, Germany<br />

Objectives: The development of individual quality of life (QOL) in patients<br />

with atrial fibrillation (AF) considerably varies. This fact has been recognized<br />

in controlled trials but remains poorly understood in clinical practice.<br />

Methods: In a specialized cardiological center 103 consecutive patients (78 m,<br />

25 f, mean age 66 years) with AF were registered and followed. QOL was measured<br />

by the WHO modules "WHO-Five Well Being Index" (WHO-5) and "Major<br />

Depression Inventory" (MDI). In a follow-up visit after 6 months these parameters<br />

were collected again and compared to baseline. The following parameters<br />

were collected at baseline: age, sex, symptoms of AF, type of AF, CAD, valvular<br />

heart disease >II°, cardiomyopathy, left ventricular function, left ventricular hypertrophy,<br />

left atrial dilation, pulmonary hypertension, QRS width, Diabetes, BMI,<br />

physical activity, arterial hypertension, medication. The data presented here have<br />

been documented within the scientific research projects of the Competence Network<br />

on atrial fibrillation in Germany (AFNET). The results are not results of the<br />

AFNET but only represent data of our institution.<br />

Results: Most of the patients showed unchanged levels of their QOL and depression<br />

(40% and 76%). A similar portion of the remaining patients revealed an improvement<br />

or a deterioration respectively: concerning QOL 33% improvement vs.<br />

27% deterioration, concernig depression 14% vs. 10%, respectively. None of the<br />

collected parameters was a statistically significant predictor for an improvement of<br />

QOL or depression. The following parameters were predictors for a deterioration<br />

of QOL or depression:<br />

QRS-width: 44% (12 out of 27) of patients with a wide QRS revealed a deterioration<br />

in WHO-5 versus 21% (16 out of 76) with a narrow QRS (p=0.025).<br />

LA-Dilation: 20% (9 out of 44) of patients with a dilated LA worsened in respect of<br />

the MDI versus 2% (1 out of 42) of patients with normal LA-diameters (p=0.015).<br />

Left ventricular hypertrophy (LVH): 18% (9 out of 51) of patients with LVH showed<br />

a deterioration in respect of the MDI after 6 months versus 3% (1 out of 34) of<br />

patients without LVH.<br />

Severe pulmonary hypertension: All patients (2 out of 2) with PAP sys >60mmHg<br />

got worse in the MDI.<br />

Conclusions: Only a few of the clinical and echocardiographic parameters of<br />

our patients with AF have a predictive significance for the development of well<br />

being and depression in the following 6 months. A widened QRS goes along<br />

with a deterioration in well being, a dilated left atrium, left ventricular hypertrophy<br />

and severe pulmonary hypertension more frequently leads to an increase in the<br />

degree of depression.<br />

Downloaded from<br />

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294 Atrial fibrillation<br />

P1929 Effect of rate or rhythm control on quality of life in<br />

persistent atrial fibrillation. Results from the HOT<br />

CAFE study<br />

D.A. Kosior 1 , G. Opolski 1 , J. Kochanowski 1 , D. Rabczenko 2 .<br />

1 Medical University of Warsaw, I Chair And Department of<br />

Cardiology, Warsaw, Poland; 2 National Institute of Hygiene, Warsaw, Poland<br />

Objectives: We studied the influence of rate control or rhythm control in patients<br />

with persistent atrial fibrillation (AF) on quality of life (QoL).<br />

Background: Atrial fibrillation may cause symptoms like fatigue and dyspnea,<br />

which could impair QoL. Treatment of AF with either rate or rhythm control may<br />

influence QoL.<br />

Method: Investigators of HOT CAFE study enrolled 239 pts. (mean age 62,1±8,1<br />

years; 36.0% female) in 7 centers; 62,8% had HT, 43,5% CAD, 17,6% diabetes<br />

and 20,9% lone AF. In 60.3% pts. AF was the first episode of arrhythmia. Mean AF<br />

duration was 165,2±73,2 days. Pts. were assigned randomly to rate-controlling<br />

drugs, allowing AF to persist, or rhythm-controlling antiarrhythmic drugs, to maintain<br />

sinus rhythm. Quality of life and arrhythmia related symptoms intensity was<br />

assessed at initial and one year. Quality of life was studied using the Short Form<br />

(SF)-36 health survey questionnaire. At baseline, QoL was compared with that<br />

of healthy control subjects. Patient characteristics related to QoL changes were<br />

determined.<br />

Results: At baseline, QoL was lower in pts. with AF than in age-matched healthy<br />

controls. Female (p


P1933 Left atrial appendage dominant frequency predicts<br />

termination of atrial fibrillation during pulmonary vein<br />

disconnection<br />

L.F. Atea, A. Arenal, T. Datino, F. Atienza, L. Castilla, E. Gonzalez-<br />

Torrecilla, J. Almendral, F. Fernandez-Aviles. Hospital Universitario<br />

Gregorio Maranon, Cardiology Department, Madrid, Spain<br />

Background: Termination of Atrial fibrillation (AF) during pulmonary vein (PV)<br />

disconnection suggests a single firing pulmonary focus with fibrillatory conduction<br />

to the rest of the atrium as AF mechanism. The left atrium dominant frequencies<br />

(DF) characteristics during fibrillatory conduction from a rapid firing site are not<br />

established yet.<br />

Purpose: The aim of this study was to establish the effect of left atrium DF on PV<br />

disconnection.<br />

Methods: DF analysis was performed in 22 patients (8 women, 54±9 years) with<br />

paroxysmal AF during spontaneous or induced episodes. DF were determined at<br />

each PV antrum, posterior, lateral, septal, superior, inferior walls and at the left<br />

atrial appendage (LAA). During left atrial circumferential ablation around both ipsilateral<br />

PV with the end point of PV disconnection AF terminated in 13 patients<br />

(Group I) in the remaining patients Group II AF continued despite all PV were disconnected.<br />

No differences between groups I and II were found regarding maximal<br />

DF (7,8±1,5 vs. 8,2±1,5 Hz p= ns) and minimal DF (4,6±,57 vs.4,7±,9 Hz p=ns).<br />

In group II DF was significantly higher at the superior wall (6,3±1,1 vs. 5,3±, 5<br />

Hz p 6 Hz at the LAA suggests the presence of extra pulmonary focus maintaining<br />

AF.<br />

P1934 Automatic measurement of fractionated electrograms<br />

and their changes after pulmonary vein antral<br />

isolation in patients with atrial fibrillation<br />

G.B. Nam, K.M. Park, K.J. Choi, Y.H. Kim. Asan Medical Center,<br />

Univ Ulsan Coll Med, Cardiology, Seoul, Korea, Republic of<br />

Purpose: Tailored approach in atrial fibrillation (AF) ablation can be guided by<br />

complex fractionated electrograms (CFE). Role of 3-dimentional mapping system<br />

in the identification of the CFE and the changes of CFE after pulmonary vein (PV)<br />

antral isolation (PVAI) have not been reported.<br />

Methods: 1. NavX CFE map was obtained in 19 patients with AF (paroxysmal,<br />

9, persistent, 10). 2. CFE was defined as electrograms with a mean cycle length<br />

(CL) < 85ms in an 8-second window (P-P sensitivity 0.1mV, width slider 24ms,<br />

refractory period 49ms). 3. To evaluate the reproducibility and validation of the<br />

automatic measurement, CFE maps were repeated twice with each point at least<br />

10 minutes apart, and CFE CLs of the individual points were compared with visual<br />

determination of the fractionation in 260 points (6 patients). 4. PVAI was<br />

performed targeting elimination or dissociation of PV potentials. In 7 patients,<br />

post-PVAI CFE map was created to observe the changes in CFE after antral isolation.<br />

After PVAI, defragmentation was continued at the CFE areas.<br />

Results: 1. CFE maps were highly sensitive (80%) and specific (78%) for identification<br />

of the visually determined fractionated electrograms. 2. Areas of fractionated<br />

electrograms were spatially and temporally stable. CLs of the two CFE reproducibility<br />

maps were highly correlated (correlation coefficient, 0.88) 3. In 5 patients<br />

with paroxysmal AF, pre-ablation CFEs were recorded remote from the PV<br />

antrum, but AF was not inducible after PVAI. In 7 patients (2 paroxysmal AF with<br />

inducible AF after PVAI, 5 persistent AF) with pre/post-PVAI CFE maps, CFEs<br />

that were present remote from the antrum were either abolished or markedly attenuated<br />

after antral isolation.<br />

Conclusions: 1. NavX CFE map was sensitive, specific and reproducible for automatic<br />

identification of the fractionated electrograms. 2. Marked attenuation of<br />

the remote CFEs after PVAI suggests CFE-CFE interaction or dependence of<br />

CFE on the autonomic nervous system activity.<br />

P1935 Effect of Renin-Angiotensin- System blockers on<br />

maintenance of sinus rhythm in patients with<br />

hypertension and atrial fibrillation after pulmonary<br />

vein isolation<br />

A. Berkowitsch, T. Neumann, M. Kuniss, S. Zaltsberg, R. Brand,<br />

C. Hamm, H.F. Pitschner. Kerckhoff-Klinik, Cardiology Department,<br />

Bad Nauheim, Germany<br />

There is little known about the effect of the Renin-Angiotensin- System-blockers<br />

(RASB) on maintenance of sinus rhythm after pulmonary vein isolation (PVI) in<br />

pts with AF. The aim of this retrospective analysis was to detect possible differences<br />

in outcome after PVI in pts with hypertension and AF receiving RASB and<br />

those treated with other antihypertensive drugs. The secondary objective was<br />

identification of patients who may potentially benefit from RASB after PVI. A total<br />

of 182 consecutive pts with symptomatic AF and hypertension (paroxysmal<br />

AF=137, male=113, age=58 yrs, LVEF=60%, CAD=23, median LA size 39x55<br />

mm) were enrolled in the study: 82 pts were treated with a cryoballoon (Cryocath)<br />

and 100 pts were ablated with an irrigated tip catheter (Cordis-Webster). A 7-day<br />

continuous Holter ECG was performed after discharge and every three months.<br />

Atrial fibrillation 295<br />

Follow-up was 2 years. Antihypertensive drug therapy included: β-blockers =142,<br />

50=diuretics, 32=Ca-antagonists, 64=ACE and 46=ARB. AF burden (total duration<br />

of AF episodes within the last 3 months prior to PVI) was stratified as follows:<br />

pts with PAF and AFB< 500 h/3 months were assigned a score of 1; pts with<br />

PAF and AFB≥500 h – score 2; pts with PersAF – score 3. We also stratified patients<br />

according to LA size: LA size< 45x60mm (score 0) and LA size ≥45x60mm<br />

(score 1). Overall risk score was defined based on a scale of 1 to 4, expressed as<br />

sum of individual AF burden and LA size scores. Analysis was based on multivariate<br />

Cox-regression model and subgroup analysis Multivariate analysis showed<br />

that the calculated risk score and the use of RASB were predictors of outcome.<br />

Out of 91 pts with a risk score of 1, 52 pts received RASB. During follow-up, 44 pts<br />

(85%) in this group were in sinus rhythm, compared with only 19 (49%) out of 39<br />

patients with the same risk score who did not receive RASB (p


296 Atrial fibrillation<br />

ment. Platelet P-selectin, platelet-leukocyte conjugates and leukocyte activation<br />

markers were measured by flow-cytometry in basal conditions and after in vitro<br />

ADP/collagen challenge. Plasma D-dimer, soluble P-selectin, IL-6 and ICAM-1<br />

were measured by ELISA.<br />

Results: In AF patients before parnaparin, platelet count and platelet P-selectin<br />

expression were lower than in controls, while both soluble P-selectin and D-dimer<br />

higher. Both basal and stimulated platelet-leukocyte conjugates were lower in<br />

AF; leukocyte activation markers and cytokines were unchanged (Table). Parnaparin<br />

significantly reduced D-dimer (to 192±7, p


hydrolysable, it would dissipate before the more tonic, proarrhythmic effects could<br />

take hold.<br />

Methods: Sustained AF episodes, lasted on average 8.6±2.2 min (n=32), were<br />

elicited in anesthetized Wistar rats by programmed electrical stimulation via transesophageal<br />

catheter. Rats were randomly and blindly assigned with a model drug,<br />

acetylcholine (ACh, n=17), or saline injection (n=15) either via the tail vein or into<br />

the right ventricular cavity, three minutes after the AF initiation.<br />

Results: Intravenous injection of a model hydrolysable muscarinic agonist,<br />

acetylcholine (0.2 mg/kg body weight), converted AF into sinus rhythm within<br />

8.4±1.9 sec (n=10, p < 0.0001). The termination of AF episode was always accompanied<br />

with transient bradycardia; the sinus rhythm gradually accelerated and<br />

reached its pre-AF values within 10-20 sec following the injection.<br />

Conclusion: Our evidence indicates that bolus administration of rapidly hydrolysable<br />

muscarinic agonist could be an effective way for pharmacological conversion<br />

of atrial fibrillation into the sinus rhythm.<br />

P1942 Non-linear heart rate dynamics before sudden-onset<br />

episodes of paroxysmal atrial fibrillation<br />

H. Bonnemeier1 ,F.Kurz2 , M. Barantke 2 , U.K. Wiegand2 ,<br />

H. Schunkert 2 . 1Universitaet zu Luebeck, Medizinische Klinik II,<br />

Luebeck, Germany; 2Luebeck, Germany<br />

Introduction: Beside bradycardia-, tachycardia- and ectopy-related initiation of<br />

paroxysmal atrial fibrillation (pAF), those episodes without preceding rate or<br />

rhythm changes (i.e. sudden onset (SO) episodes) are particulary interesting for<br />

the investigation of autonomic fluctuations before spontaneous onset of pAF. We<br />

hypothesized that there are significant alterations of beat-to-beat RR-interval fluctuations<br />

before SO-pAF and tested this assumption in a large patient population<br />

using parameters of non-linear heart-rate dynamics.<br />

Methods: From a total of 20.546 consecutive Holter-recordings, 715 episodes of<br />

pAF were identified in 350 patients. Detrended fluctuation analysis (DFA), approximate<br />

entropy (APEn), and parameters of heart rate variability (HRV) were analysed<br />

in 5-minute-segments before SO-pAF, and during AF-free day- and nighttime.<br />

Results: A dominant portion of pAF onsets were SO-episodes (n=276; 39%),<br />

299 (41%) ectopy-related, and 140 (20%) heart rate related. Time domain HRV<br />

(SDNNi, SDANN, rMSSD, TI) significantly increased before pAF-onset. The low<br />

frequency component (LF), the LF/HF-ratio, the Poincaré-SD2, and DFA also increased<br />

before pAF-onset, whereas APEn significantly decreased.<br />

Conclusions: In this first study providing detailed analysis of heart-rate dynamics<br />

preceding SO-pAF-episodes, we were able to demonstrate that there are significant<br />

pertubations of autonomic modulation preceding SO-pAF. These transient<br />

abnormal changes of cardiac autonomic nervous control may predispose to the<br />

development of pAF.<br />

P1943 Analysis of atrial fibrillation episode after catheter<br />

ablation of atrial fibrillation: long-term results of<br />

received technology<br />

A. Romanov, E. Pokuschalov, A. Turov, S. Artemenko, P. Shugaev,<br />

V. Shabanov, I. Stenin, D. Elesin, N. Shirokova, V. Selina. Research<br />

Institute of Circulation Pathology, Novosibirsk, Russian Federation<br />

Purpose: The objective of this study was to assess the time course of atrial fibrillation<br />

(AF) episodes before and after left atrial ablation and the percentage of<br />

patients with complete freedom from AF after ablation by using continuously monitors<br />

a patient’s ECG.<br />

Methods: A total of 45 consecutive patients with highly symptomatic drug refractory<br />

PAF (age, 52±10 years) underwent catheter ablation. The Insertable Cardiac<br />

Monitor was implanted to all patients at least 5 days immediately before the ablation.<br />

14 patients underwent PV isolation by segmental ostial catheter ablation<br />

(SOCA), 16 patients underwent left atrial catheter ablation (LACA) to encircle the<br />

Atrial fibrillation / Perspectives in heart failure treatment 297<br />

PVs and 15 patients underwent left atrial GP ablation. During SOCA, ostial PV<br />

potentials recorded with a ring catheter were targeted. LACA was performed by<br />

encircling the left- and right-sided PVs 1 to 2 cm from the ostia and was guided<br />

by an electroanatomic mapping system; ablation lines also were created in the<br />

mitral isthmus and posterior left atrium. Target sites for GP ablation were defined<br />

using the data of their anatomical location. Symptom-based monitoring was approximated<br />

by analyzing days when patients indicated symptoms with an external<br />

activator.<br />

Results: A total of 4119 days were monitored. Out of the total 390 events triggered<br />

by patient’s symptoms, 31% were confirmed as AF events (89) and 69%<br />

were confirmed as non-AF events (198). Before ablation, 36 of 45 patients (80%)<br />

had documented AF episodes. All episodes were symptomatic in 15 patients<br />

(41,7%). In 20 patients (44,4%), both symptomatic and asymptomatic episodes<br />

were recorded, whereas in 1 patients (2,7%) all documented AF episodes were<br />

asymptomatic. After ablation, the percentage of patients with only asymptomatic<br />

AF recurrences increased to 42% (P


298 Perspectives in heart failure treatment<br />

P1945 Intravenous mildronate improves flow-mediated<br />

vasodilatory response in stable chronic heart failure:<br />

double-blind placebo-controlled crossover study<br />

L. Voronkov, I. Shkurat, O. Lutsak. Institute of Cardiology, <strong>Heart</strong><br />

Failure, Kiev, Ukraine<br />

Background: Taking to account recently established independent role of endothelial<br />

dysfunction (ED) in chronic heart failure (CHF) progression and mortality,<br />

normalization of ED may be considered as an important therapeutic goal in<br />

CHF. Mildronate (trimethylhydrazinium propionate dihydrate) is a new, now clinically<br />

tested in stable angina, partial fatty acids oxidation inhibitor with concomitant<br />

experimentally established potent endothelium-mediated vasorelaxation properties.<br />

Objective: To evaluate the ability of mildronate to modulate flow-mediated vasodilatory<br />

response (FMVR) in stable CHF.<br />

Method: 30 pts with stable CHF (NYHA II-III, left ventricular EF ≤ 40%) at<br />

chronic (≥ 2 months) ACE-inhibitor/β-blocker/diuretic therapy were examined. All<br />

pts signed informed consent for the participation in trial. A. brachialis diameter<br />

was detected ultrasonographically at Sonoline Omnia system before (D1) and<br />

after (D2) standard forearm cuff test (200 mm Hg during 5 min). FMVR was calculated<br />

by formula: (D2 – D1)/D1 x 100%. Forearm cuff test also was performed<br />

in 30 healthy age-matched controls. Placebo protocol (PP) was represented by<br />

initial FMVR test (A), 30 min recovery period (B), 100 ml saline (0,85% NaCl)<br />

infusion during 30 min (C), repeated FMVR test 30 min after end of infusion (D).<br />

Points A, B and D of active drug protocol (ADP) were similar to PP; C point was<br />

represented by mildronate 1000 mg infusion in 100 ml of saline during 30 min.<br />

The interval between PP and ADP was 48 hours, at that in one group (15 pts) PP<br />

was performed first and in other group (15 pts) – the ADP first. Neither pts nor<br />

FMVR performer knew about presence/absence of active drug in infused solution.<br />

Groups FMVR, % p A vs B<br />

Baseline (A) After infusion (B)<br />

CHF placebo protocol (I) 9,6±0,7 10,4±0,8 NS<br />

CHF active drug protocol (II) 8,3±0,8 14,4±0,9 < 0,001<br />

Controls 11,1±0,8 –<br />

pIvsII NS < 0,001<br />

p I vs controls < 0,01 –<br />

p II vs contols < 0,001 –<br />

Conclusion: Intravenous mildronate dramatically improves impaired FMVR in<br />

conventionally treated stable CHF patients.<br />

P1946 Influence of regeneration of heart muscle by<br />

intracoronary autologous bone marrow cell<br />

transplantation on the BNP levels in patients with<br />

chronic ischemic heart disease<br />

R. Turan, M. Brehm, M. Koestering, S. Steiner, T. Zeus, T. Bartsch,<br />

S. Yokus, C.M. Schannwell, B.E. Strauer. Heinrich Heine University Duesseldorf,<br />

Cardiology, Pneumology And Angiology, Duesseldorf, Germany<br />

Introduction: We recently demonstrated in patients with chronic myocardial infarction<br />

by intracoronary transplantation of autologous bone marrow mononuclear<br />

cells (BMCs) after 3 months follow-up that the infarct size was reduced by 30%,<br />

whereas the global LV ejection fraction increased by 15% and regional infarct wall<br />

movement velocity by 57%. (The IACT Study)<br />

We analyzed the influence of regeneration of human infarcted heart muscle by<br />

intracoronary cell therapy after 3 months follow up on the BNP levels in PB<br />

Methods and Results: Peripheral blood levels of BNP were measured by BNPassay<br />

in 40 patients with chronic ischemic heart disease pre intracoronary cell<br />

therapy as well as 3 months after intracoronary cell therapy. We showed in patients<br />

with chronic myocardial infarction by intracoronary transplantation of autologous<br />

bone marrow cells (BMC) after 3 months follow up a significant reduced<br />

of infarct size and increase of global LV-ejection fraction as well as infarct wall<br />

movement velocity. Clinically we observed significant improvement in NYHA classification<br />

3 months after intracoronary stem cell therapy as compared to before<br />

(p=0.002). Furthermore we found a significant decrease of the BNP levels in peripheral<br />

blood 3 months after intracoronary stem cell therapy as compared to<br />

before (p=0.002)<br />

Conclusion: Selective intracoronary transplantation of autologous bone marrow<br />

mononuclear cells reduces infarct size and improves LV-Function. In Addition<br />

this intracoronary cell transplantation improves clinical symptoms in patients with<br />

chronic ischemic heart disease<br />

P1947 Clinical effects and safety profile of initial<br />

monotherapy with bisoprolol versus enalapril in<br />

elderly patients with heart failure<br />

D. Dobre 1 , D.J. Van Veldhuisen 1 , M.A. Goulder 2 ,H.Krum 3 ,<br />

R. Willenheimer 4 . 1 University Medical Centre Groningen, Clinical<br />

Pharmacology, Groningen, Netherlands; 2 Nottingham Clinical Research Limited,<br />

Nottingham, United Kingdom; 3 Monash University/Alfred Hospital, Melbourne,<br />

Australia; 4 <strong>Heart</strong> Health Group and Lund University, Cardiology, Malmo, Sweden<br />

Purpose: To assess the clinical effects and safety profile of initial monotherapy<br />

with either bisoprolol or enalapril in elderly patients with heart failure (HF).<br />

Methods: In CIBIS III, 1010 patients with mild to moderate HF, age ≥ 65 years<br />

and left ventricular ejection fraction ≤ 35% were randomized to monotherapy with<br />

bisoprolol or enalapril for 6 months. We evaluated the effect on the combined endpoint<br />

of all-cause mortality or hospitalization, each individual end-point, causes of<br />

death, signs and symptoms of HF, and safety profile. The primary end point of allcause<br />

mortality or hospitalization, and mortality and hospitalizations separately,<br />

were analyzed by Cox proportional hazards model with treatment as the only<br />

independent variable.<br />

Results: Bisoprolol had a similar effect as enalapril regarding the combined endpoint<br />

of all-cause mortality or hospitalization (hazard ratio [HR] 1.02; 95% confidence<br />

interval [CI] 0.78 to 1.33, p=0.90). Slightly fewer patients died on bisoprolol<br />

than on enalapril (23 vs. 32, p=0.24) which was related to the number of sudden<br />

deaths (8 vs. 16; p=0.11). On the other hand, more cases of worsening HF requiring<br />

hospitalization or occurring while in hospital were observed in the bisoprolol<br />

group (HR 1.67; 95% CI 1.04 to 2.70, P=0.03). The two groups were similar with<br />

regard to treatment cessations (7% vs. 10%, p=0.11) and early introduction of the<br />

second drug (8% vs. 7%, p=0.81).<br />

Conclusions: Bisoprolol and enalapril had a similar effect on the combined endpoint<br />

of mortality or hospitalization during 6 months monotherapy. Although a<br />

trend to fewer deaths was observed with bisoprolol, this was offset by more HF<br />

hospitalizations.<br />

P1948 Antithrombotic drugs in patients with chronic heart<br />

failure<br />

M. Lainscak1 , L. Hodoscek-Majc2 , S. Von Haehling3 , W. Doehner3 ,<br />

S.D. Anker 3 . 1University Clinic of Respiratory Diseases, Division<br />

of Cardiology, Golnik, Slovenia; 2General Hospital Murska Sobota,<br />

Department of Internal Medicine, Murska Sobota, Slovenia; 3Charite Campus<br />

Virchow-Klinikum, Division of Applied Cachexia Research, Berlin, Germany<br />

Background: Limited data supports the use of antithrombotic drugs (antiplatelets<br />

and anticoagulants) in patients with chronic heart failure (CHF). According to recent<br />

CHF guidelines, only patients with concomitant atrial fibrillation (AF) could be<br />

treated, whereas AF guidelines suggest risk stratification (e.g. CHADS2 score).<br />

Our aim was to investigate the prevalence and predictors of antithrombotic drugs<br />

prescription in patients with CHF and their prognostic impact.<br />

Methods: In our population based survey, we screened all discharges and deaths<br />

from our community hospital (population 125.000) from 2001 to 2003. We identified<br />

638 patients (73±10 years, 48% men, 74% NYHA class III) who were discharged<br />

alive and had diagnosis of CHF according to ICD 10. Medical charts and<br />

ECG recordings were reviewed in detail, and vital status was obtained from a<br />

Central Population Registry.<br />

Results: AF was present in 330 (52%) patients with CHF, who were older (74±10<br />

vs 72±11 years, p=0.021), had lower eGFR (50±18 vs 53±21 mL/min, p=0.044)<br />

and total cholesterol (4.6±1.6 vs 5.0±1.5 mmol/L, p=0.002) and higher uric acid<br />

(434±145 vs 406±132 mmol/L, p=0.020). At discharge, patients with AF were<br />

prescribed with more optimal treatment: ACE inhibitors (83% vs 75%, p=0.019,<br />

OR 1.60, 95% CI 1.08-2.35), beta-blockers (31% vs 20%, p=0.003, OR 1.71,<br />

95% CI 1.21-2.50), and spironolactone (49% vs 37%, p=0.003, OR 1.63, 95%<br />

CI 1.19-2.24). Overall, antithrombotic drugs and warfarin were prescribed in 430<br />

(67%) and 197 (31%) patients, respectively. CHADS2 score was ≥2 in 85% of<br />

patients with AF. Patients with AF were more likely to receive antithrombotics<br />

(n=274 [83%], OR 4.77, 95% CI 3.31-6.86) and warfarin (n=168 [51%], OR 9.98,<br />

95% CI 6.43-15.48). AF was not associated with higher disk of death (HR 1.13,<br />

95% CI 0.93-1.37). Kaplan-Meier and univariate Cox proportional hazard analysis<br />

showed that use of warfarin (log rank test p=0.0008, HR 0.62, 95%CI 0.47-0.81)<br />

but not of antiplatelet drugs (log rank test, p=0.34, HR 1.16, 95%CI 0.85-1.59)<br />

was associated with reduced mortality in patients with AF. In a Cox proportional<br />

hazard model, adjusted for age, gender, eGFR, total cholesterol, uric acid, and<br />

treatment with ACE inhibitors, beta blockers, and spironolactone, the finding for<br />

warfarin was borderline: HR 0.74, 95% CI 0.53-1.05.<br />

Conclusions: In large unselected cohort of patients with CHF from a community<br />

hospital, AF was very prevalent but it was not predictive of mortality. According to<br />

CHADS2 score, warfarin was underprescribed. Warfarin but not antiplatelet drugs<br />

were associated with better outcome in patients with AF.<br />

Downloaded from<br />

http://eurheartj.oxfordjournals.org/ by guest on December 8, 2012


P1949 A first-in-human clinical trial of a novel chimeric<br />

natriuretic peptide, CD-NP, in healthy subjects<br />

C.Y. Lee, H.H. Chen, O. Lisy, S.M. Sandberg, D.M. Heublein,<br />

J.C. Burnett Jr. Mayo Clinic & Mayo Clinic College of Medicine,<br />

Medicine, Physiology, and Pharmacology, Rochester, Minnesota,<br />

United States of America<br />

Objectives: CD-NP is a novel Mayo-designed chimeric natriuretic peptide (NP)<br />

which consists of the full-length 22 amino acids (AA) of human C-type NP (CNP)<br />

and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale of its design<br />

was to transform CNP, which is a ligand for the natriuretic peptide receptor (NPR)-<br />

B and a venodilating peptide with minimal hypotensive and natriuretic effects, into<br />

a CNP-like peptide with enhanced renal actions without inducing hypotension.<br />

Preclinical canine studies have indeed demonstrated the augmented renal actions<br />

of CD-NP with minimal effects on systemic blood pressure. We conducted a<br />

first-in-human clinical trial to evaluate CD-NP for the first time in healthy subjects.<br />

Methods: This phase I clinical trial consisted of 2 stages: an open-label sequential<br />

dose-escalation study (stage 1) and a randomized, double-blind, placebo<br />

(PLB)-controlled study (stage 2). For stage 1, three cohorts of 4 subjects each<br />

were enrolled in the dose-escalation study (10, 17.5, or 25 ng/kg/min i.v. for 4<br />

hours). For stage 2, ten subjects were randomized in the double-blind study (6:4<br />

for CD-NP vs PLB) which evaluated the maximum tolerated dose (MTD, as determined<br />

in stage 1) of CD-NP vs PLB i.v. for 4 hours. Mean±SE, P


300 Perspectives in heart failure treatment<br />

of negative inotropy which increases FMR through coaptation force reduction.<br />

After 3 month effects of B and I on FMR were comparable, but after 6 month FMR<br />

incidence and severity were less in B with better exercise tolerability probably due<br />

to improved contractility through better myocardial response to catecholamines<br />

after long term use.<br />

P1953 Rapid carvedilol up-titration in hospitalized patients<br />

with systolic heart failure<br />

M. Martinez-Selles, T. Datino, M. Alhama, F. Fernandez-Aviles.<br />

Madrid, Spain<br />

Background: Carvedilol rapid up-titration in patients with systolic<br />

heart failure could have important clinical benefits, however its safety is unknown.<br />

Methods: To evaluate if carvedilol can be safely up-titrated before hospital discharge,<br />

we studied 372 consecutive patients, with left ventricular ejection fraction<br />

(LVEF) 50 mg. Variables related to the discharge dose were also<br />

related to the dose at the end of follow-up except in the case of previous betablockers<br />

use.<br />

Table 1. Discharge dose and dose at the end of follow-up<br />

Carvedilol discharge dose* Carvedilol dose at p Carvedilol >50 mg daily at p<br />

mg daily (n – %) the end of follow-up** the end of follow-up**<br />

(mean±SD, mg daily) n (%)<br />

0 (23 – 6%) 22.7±20.3 50% were randomized to 3 groups (n=40) in order to receive ramipril 10<br />

mg/day (R), losartan 50 mg/day (LL) or losartan 100 mg/day (LH). Transmitral E<br />

wave deceleration time (EDT), IVRT, duration of reversal in the pulmonary vein<br />

(RPV) and transmitral A wave (RPV – A), index of left atrial volumes (LAVI) and<br />

EF (LAEF) were obtained by TEE in 1, 30, 180 day follow up.<br />

Results: Baseline characteristics were comparable between groups. In 30 day<br />

EDT, IVRT and RPV - A were better in R, compare to LL and LH (EDT: R 133±11<br />

ms* vs LL 122±10 ms vs LH 124±9 ms,*p< 0.05; IVRT R 52±6 ms* vs LL<br />

42±4 msvs45±3 ms,*p< 0,05, RPV – A: 24±5 ms* vs 32±3 msvs29±2 ms;<br />

*p < 0.05). In 180 day all parameters were better in LH and comparable between<br />

R and LL (EDT: R 132±12 ms vs LL 129±13 ms vs LH 138±9 ms*,*p< 0.05;<br />

IVRT R 52±6 msvsLL48±4 msvsLH58±5 ms*,*p< 0,05, RPV – A: R 22±4<br />

ms vs LL 26±3 msvsLH18±3 ms*;*p< 0.05, LAVI: R 28±5 ml/m 2 vs LL 32±4<br />

ml/m 2 vs LH 21±5 ml/m 2 *; *p < 0.01, LAEF: R 35±16% vs LL 33±12% vs LH<br />

41±12%*, *p < 0.01)<br />

Conclusion: Thus higher doses of L favorably alter diastolic function parameters<br />

in DHF with decreased compliance probably through better RAAS control.<br />

P1955 Medication adherence and aspects of heart failure<br />

management-a cross sectional study in South Africa<br />

V. Ruf 1 ,S.Stewart2 ,S.Pretorius3 , M. Kubheka3 ,<br />

C. Lautenschlaeger1 ,P.Presek1 , K. Sliwa3 . 1Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany; 2Baker <strong>Heart</strong><br />

Research Institute, Melbourne, Australia; 3Soweto Cardiovascular Research<br />

Unit, Department of Cardiology, Soweto, Johannesburg, South Africa<br />

Purpose: Despite its clinical importance there is a paucity of data on treatment<br />

adherence in patients with heart failure (HF) in the African context. We examined<br />

the pattern of treatment adherence in a large cohort of HF patients from Soweto,<br />

South Africa.<br />

Material and methods: The "Patient Compliance and Knowledge on <strong>Heart</strong> Failure<br />

Survey" was initially developed, validated and then applied to 200 consecutive<br />

HF patients with a left ventricular ejection fraction


P1957 Electrophysiological effects of levosimendan<br />

administration in patients with advanced heart failure<br />

secondary to ischemic or dilated cardiomyopathy<br />

E.M. Kanoupakis, E.M. Kallergis, H.E. Mavrakis, G.M. Lyrarakis,<br />

E.P. Koutalas, C. Goudis, E.G. Manios, P.E. Vardas. Heraklion<br />

University Hospital, Department of Cardiology, Heraklion, Greece<br />

Purpose: Levosimendan administration exerts favourable effects on systolic and<br />

diastolic cardiac function, as well as on neurohormonal and inflammatory activation<br />

of pts with CHF. However, this calcium sensitizing inotrope may have proarrhythmic<br />

effects. The purpose of the present study was to evaluate the effects of<br />

levosimendan infusion, on human cardiac electrophysiological properties.<br />

Methods: In 11 stable pts (68±4.5 years) with left ventricular dysfunction<br />

(EF20 mm Hg)<br />

or heart rate (>20 beats/min), and improvement in quality of life, which would all<br />

correspond to clinical effects of carvedilol, were more likely to be prescribed with<br />

carvedilol target dose. In univariate analysis, patients with baseline NYHA class<br />

III (OR 0.42, 95% CI 0.29-0.60) and with no change in NYHA class during survey<br />

(OR 0.60, 95% CI 0.49-0.74) had lower chance to receive carvedilol target dose at<br />

six months. In multivariate analysis, male gender, treatment with diuretics, arterial<br />

hypertension, and blood pressure drop >20mm Hg were associated with higher<br />

chance of receiving carvedilol target dose at six months. Same model showed,<br />

that treatment with ACEI or angiotensin receptor blockers, arrhytmia, baseline<br />

NYHA class III, no change in NYHA class during survey, experience of any side<br />

effect and hospitalization significantly reduced the chance of receiving carvedilol<br />

target dose at six months.<br />

Conclusions: Carvedilol was well tolerated and improved well-being in patients<br />

with CHF. Titration scheme was not followed in most of the patients and only 29%<br />

of patients were treated with carvedilol target dose after six months of titration<br />

period. Our results suggest that advanced stages of CHF, associated with deteri-<br />

Perspectives in heart failure treatment 301<br />

oration due to CHF severity or treatment side effects may be the main reason for<br />

inadequate implementation of guidelines in clinical practice.<br />

P1959 Blockade of the urotensin II receptor does not<br />

attenuate cardiac remodeling in a model of<br />

pressure-overload hypertrophy: functional and<br />

histological assessment<br />

A.R. Kompa1 , A. Phrommintikul2 , S.A. Douglas3 ,H.Krum1 .<br />

1 2 Monash University, Medicine, Prahran, Australia; Chiang Mai<br />

University, Internal Medicine, Chiang Mai, Thailand; 3GlaxoSmithKline, King of<br />

Prussia, United States of America<br />

Objective: Urotensin-II (UII) has been implicated in heart failure and hypertension.<br />

Studies have shown that UII receptor (UTR) blockade improves survival and<br />

attenuates functional and structural changes in a model of myocardial infarction.<br />

However, there are limited studies examining UTR inhibition in models of cardiac<br />

disease. In this study we examined the functional and histological effect of UTR<br />

inhibition in a model of pressure-overload hypertrophy (POH).<br />

Methods: POH was induced by constriction of the abdominal aorta above both<br />

renal arteries, sham animals did not have their aorta constricted. Treatment with a<br />

UTR antagonist, SB657510 (SB, 1500ppm in food) commenced the following day<br />

and continued for 20 weeks. Cardiac function was assessed by echocardiography<br />

(echo) and catheterization. Immunohistochemistry examined expression of left<br />

ventricular (LV) collagen I and III.<br />

Results: In POH animals, SB did not reduce hypertrophy on echo, or heart<br />

weight, nor did it attenuate measures of diastolic function as assessed by Doppler<br />

indices of E-wave deceleration time and isovolumic relaxation time. Furthermore,<br />

SB did not reduce systemic and intra-cardiac (LV end diastolic and LV end systolic)<br />

pressures. No change was observed in measures of systolic and diastolic<br />

function obtained from pressure-volume (PV) loops (table). LV collagen I and I/III<br />

ratio was significantly increased after POH; SB treatment did not attenuate these<br />

measures (table).<br />

Sham+ Veh Sham+ SB POH+ Veh POH+ SB<br />

End systolic PV relationship (mmHg/μl) 0.74±0.08 0.52±0.07 0.41±0.06* 0.40±0.04<br />

End diastolic PV relationship (mmHg/μl) 0.023±0.005 0.022±0.005 0.037±0.008 0.036±0.006<br />

Preload recruitable stroke work (mmHg) 92.07±11.41 82.70±14.43 71.66±10.69 66.70±12.46<br />

Tau – logistic (msec) 7.45±0.52 7.06±0.34 9.48±0.45* 8.50±0.41*<br />

Collagen I (%age area) 12.27±1.34 12.88±0.86 17.62±1.20* 17.06±1.46*<br />

Collagen III (%age area) 4.71±1.08 4.93±0.69 3.31±0.43 3.21±0.37*<br />

Collagen I/III 3.06±0.58 2.94±0.34 5.82±0.98* 5.87±0.72**<br />

Data presented as mean ± SEM, *p


302 Perspectives in heart failure treatment<br />

P1961 Registry of <strong>Heart</strong> Failure (HF) and Acute Myocardial<br />

Infarction (AMI) for andalucia: incidence of hf in acute<br />

myocardial infarction and treatment with<br />

antialdosteronic drugs<br />

A. Martinez1 , M. Anguita2 , M. Jimenez Mena3 , J. Fenandez De<br />

Bobadilla4 , R. Munoz4 on behalf of RAICIAM. 1Hospital Universitario Virgen<br />

del Rocio, Sevilla, Spain; 2Hospital Universitario Reina Sofia, Cordoba, Spain;<br />

3 4 Hospital Clinico Virgen de la Victoria, Malaga, Spain; Pfizer, Madrid, Spain<br />

Objective: There is an interest in determining the incidence of <strong>Heart</strong> Failure (HF)<br />

in patients suffering Acute Myocardial Infarction (AMI), and in assessing the therapeutic<br />

approach, after the publication of the EPHESUS trial (Eplerenone Post-<br />

Acute Myocardial Infarction <strong>Heart</strong> Failure Efficacy and Survival Study) in which a<br />

mortality benefit for Eplerenone in patients with AMI, left ventricular ejection fraction<br />

(LVEF) ≤ 0.40 and clinical signs of HF/diabetes mellitus was demonstrated.<br />

The objective of the analysis was to determine the incidence of HF in AMI, the<br />

profile of this HF subpopulation, the proportion of patients fitting in EPHESUS<br />

profile and the use of antialdosteronic drugs.<br />

Methods: The first 20 patients admitted with AMI in every hospital participating in<br />

the registry were included. Analysed variables: gender, age, cardiovascular risk<br />

factors, previous morbidities, variables related to the acute event, analytic data,<br />

revascularization procedures and therapeutic approach. Follow-up six months after<br />

discharge was also registered. Incidence of HF at admission and during admission<br />

was evaluated. Profile of HF patients was assessed and compared with<br />

the non-HF population. Prevalence of EPHESUS criteria and the use of antialdosteronic<br />

drugs in this population was assessed.<br />

Results: 906 patients, 71% males, 29% females; age: 67±13 years were included<br />

in the registry. Incidence of HF was 20,4% (n=184 out of 902) and 13,7%<br />

(n=119 out of 866 patients) at admission and at discharge respectively. HF was<br />

more frequent for women (40%) than for men (25%) and HF patients were older<br />

(73 vs 64). Previous HF was more prevalent in those with present heart failure<br />

(21% vs 3%: p


for the population of Tayside, Scotland (400,000 people) was employed. Subjects<br />

with incident CHF (n=774) between 1994 -2003 were identified through administrative<br />

medical records based on ICD-9 code 428, ICD-10 code-50 and through<br />

use of combined CHF medications of loop diuretics and ACE inhibitors. Subjects<br />

were grouped according to oral hypoglycemic agents into three study cohorts:<br />

metformin monotherapy (n= 90), sulfonylurea monotherapy (n= 381) and<br />

combination (n= 303). Cox regression model was used to assess differences in<br />

all–cause mortality, all-cause hospitalization and combination of all-cause hospitalization<br />

or mortality by estimation of relative risks.<br />

Results: Average age of subjects was (75±9.79 yrs), 55% were male. Compared<br />

to sulfonylurea monotherapy, fewer deaths occurred in patients receiving<br />

metformin only: 295 (77.4%) for sulfonylurea monotherapy versus 54 (60.0%) for<br />

metformin monotherapy unadjusted risk ratio (R.R= 0.78, 95% CI 0.57 - 1.06). After<br />

adjusting for differences between groups (age, sex, Creatinine and medication)<br />

the risk ratio was (R.R= 0.90, 95% CI 0.63 - 1.28) and 201(66.3%) for combination<br />

therapy (R.R= 0.72, 95% CI 0.58-0.88). One year mortality was also observed:<br />

fewer deaths occurred in metformin and combination group compared with sulfonylurea<br />

monotherapy the adjusted risk ratio for metformin was (R.R=0.48, 95%<br />

CI 0.24-0.96) and (R.R= 0.66, 95% CI 0.46-0.96) for combination group.<br />

A reduction of hospitalizations was also observed: 346(90.8%) for sulfonylurea<br />

monotherapy versus 70 (77.8%) for metformin (R.R=0.74, 95% CI 0.57 to 0.96)<br />

and 264(87.1%) for combination group (R.R=0.88, 95%CI 0.74-1.04). Combined<br />

end points (all-cause hospitalization or mortality) was lower in metformin group<br />

compared to sulfonylurea monotherapy (R.R= 0.74, 95% CI 0.56-0.99) and (R.R=<br />

0.92, 95% CI 0.77-1.10) for combination group.<br />

Conclusion: In this large observational of CHF patients treated with oral hypoglycemic<br />

agents, those treated with metformin alone or in combination were associated<br />

with a markedly lower risk of morbidity and mortality when compared to<br />

those receiving sulfonylurea alone.<br />

P1966 Effects of levosimendan versus dobutamine on left<br />

atrial function in decompensated heart failure<br />

D. Duman 1 ,F.Palit2 ,E.Simsek1 , B. Karadag3 ,S.Atalay4 ,<br />

F. Akdogan4 ,A.Ozgultekin4 , R. Demirtunc4 . 1Haydarpasa Numune Training and Research Hosp, Cardiology, Istanbul, Turkey;<br />

2 3 Haydarpasa Numune Training and Research Hosp, Istanbul, Turkey; University<br />

of Istanbul, Cerrahpasa Sc. of Med, Cardiology, Istanbul, Turkey; 4Haydarpasa Numune Training and Research Hos, Istanbul, Turkey<br />

Background: Although the effects of levosimendan on the left ventricle (LV) have<br />

been studied, its effect on LA function is poorly understood despite its key role<br />

in optimizing LV function. This study compared the effects of levosimendan and<br />

dobutamine on left atrial (LA) and left ventricular (LV) functions in patients with<br />

decompensated heart failure (DHF).<br />

Methods: Seventy-four patients (mean age 64±10 yrs) with DHF and LV ejection<br />

fraction (EF) ≤ 0.35 were randomized to levosimendan (n=37) and dobutamine<br />

(n= 37) groups. LA active emptying fraction (AEF) and LA passive emptying fraction<br />

(PEF), the ratio of mitral inflow early diastolic velocity to annulus velocity (E/e)<br />

were evaluated with with pulsed wave and tissue Doppler together with plasma<br />

B-type natriuretic peptide (BNP) levels measurements before and after drug infusion.<br />

Results: The mean BNP, AEF and EF decreased in both the levosimendan and<br />

dobutamine groups although, the reductions of BNP and AEF were significantly<br />

greater in levosimendan group (-624±666 pg/ml vs. -281±276, P


304 Perspectives in heart failure treatment / <strong>Heart</strong> failure: peripheral mechanisms<br />

Afterload-lowering therapy significantly reduced BNP levels during the first 6hours<br />

(1336pg/ml [788-2302] initial vs 1136pg/ml [704-2273] 6hours, p=0.034) and continued<br />

to significantly decrease BNP levels every 6hours until 36hours. Overall,<br />

afterload-lowering therapy decreased BNP levels by 33% (p


P1973 Effect of ursodeoxycholic acid on peripheral blood<br />

flow, immune function & markers of neurohormonal<br />

activation in chronic heart failure: a randomised,<br />

placebo-controlled, double-blind cross-over study<br />

S. Von Haehling 1 ,E.A.Jankowska2 ,A.Vazir1 ,P.R.Kalra1 ,<br />

A. Sandek3 , W. Doehner3 ,H.D.Volk3 , P.A. Poole-Wilson1 , S.D. Anker3 .<br />

1National <strong>Heart</strong> & Lung Institute, Clinical Cardiology, London, United Kingdom;<br />

2 3 Military Hospital, Wroclaw, Poland; Charite Medical School, Applied Cachexia<br />

Research, Dept. Cardiology, Berlin, Germany<br />

Background: Inflammation contributes to increased mortality and to the development<br />

of endothelial dysfunction in patients with chronic heart failure (CHF). Endotoxin,<br />

a bacterial cell wall component, which enters the circulation through the<br />

oedematous gut wall, could be the responsible trigger. We tested the hypothesis<br />

that ursodeoxycholic acid (UDCA), a bile acid that inhibits endotoxin absorption<br />

through the gut wall, would improve endothelial and immune function in CHF patients.<br />

Methods: In a placebo-controlled, double-blind, cross-overstudy, 16 male CHF<br />

patients (age 66±3y, 75% ischaemic aetiology, NYHA class 2.4±0.1, LVEF<br />

31±2%[all 0.7). UDCA decreased WBC (6.9±0.4<br />

vs 7.6±0.4,p=0.0075), absolute neutrophil (4.6±0.4 vs 5.1±0.4, p=0.025), and<br />

lymphocyte count (1.5±0.1 vs 1.7±0.1, p=0.013) compared to placebo. UDCA<br />

decreased plasma values of aspartate aminotransferase (AST, 19±2 vs22±1,<br />

p=0.025) and gamma-glutamyl transpeptidase (gGT, 29±3 vs37±6,p=0.0094)<br />

compared to placebo.<br />

Conclusions: UDCA administration is safe in patients with CHF. UDCA improves<br />

endothelial function, possibly by micell formation around endotoxin. Furthermore,<br />

UDCA improves liver function and decreases the number of neutrophils and lymphocytes<br />

in patients with CHF.<br />

P1974 The impact of irbesartan on impaired insulin<br />

sensitivity in chronic heart failure - results from a<br />

placebo-controlled, double blinded, randomized proof<br />

of concept-trial<br />

W. Doehner1 , T. Karhausen1 , C. Kennecke 1 , J. Todorovic 1 ,<br />

M. Rauchhaus1 , A. Sandek1 , M. Lainscak2 , S. Von Haehling1 , S.D. Anker1 .<br />

1Charite Medical School Campus Virchow Hosp., Applied Cachexia Research,<br />

Dpt of Cardiology, Berlin, Germany; 2General Hospital Murska Sobota, Internal<br />

Medicine, Murska Sobota, Slovenia<br />

Background: Impaired insulin sensitivity (Si) is common in chronic heart failure<br />

(CHF), contributes to symptomatic status and independently predicts prognosis.<br />

The angiotensin II-receptor antagonist irbesartan (ARA) has been observed to<br />

improve insulin sensitivity via peroxisome proliferator-activated receptor gamma<br />

(PPAR gamma). Whether this effect can be detected in the clinical setting of<br />

chronic heart failure has not been investigated.<br />

Methods: In a placebo-controlled, double-blinded, 2:1-randomized study design<br />

we investigated 36 ambulatory patients with stable ischaemic CHF (age 63±9y,<br />

BMI 28.2±3.9kg/m 2 , peakVO2 16.6±4.8mL/kg/min all mean ±SD). All patients<br />

were free of diabetes and without antidiabetic therapy. Irbesartan or placebo was<br />

given on top of standard optimum CHF therapy including ACE inhibitor (target<br />

dose 300mg/d) for 16 weeks including a 4-week up-titration period. Si (primary<br />

endpoint) was assessed at baseline and after therapy using the minimal modelling<br />

technique from glucose and insulin profiles of a frequently sampled intravenous<br />

glucose tolerance test.<br />

Results: At baseline both groups were similar for age, NYHA class, peak<br />

VO2, BMI, body composition (DEXA scan), and main clinical characteristics.<br />

Si was 2.51±1.58 min-1.μU.mL-1.104 in the study population, which is 30%<br />

lower than in healthy controls of similar age (P


306 <strong>Heart</strong> failure: peripheral mechanisms<br />

P1977 Skeletal muscle alterations in chronic heart failure:<br />

Differential effects of left ventricular dysfunction on<br />

catabolic activation in the quadriceps and the<br />

diaphragm<br />

N. Mangner1 ,S.Gielen1 ,B.Weikert1 , M. Sandri 1 , R. Hoellriegel1 ,<br />

V. Adams1 , R. Hambrecht2 , G. Schuler1 . 1University Leipzig - <strong>Heart</strong><br />

Center, Department for Cardiology, Leipzig, Germany; 2Klinik Links der Weser -<br />

<strong>Heart</strong> Center, Bremen, Germany<br />

Progressive muscle wasting is recognized as major cause of exercise intolerance<br />

in chronic heart failure (CHF). The catabolic process is in part mediated by the<br />

muscle specific E3-Ligase Murf-1 via activation of the ubiquitin proteasome system.<br />

It is, however, unclear if respiratory muscles are equally affected by muscle<br />

catabolism as compared to peripheral skeletal muscles: Aim of this study was<br />

therefore to examine the differential effects of left ventricular dysfunction on expression<br />

of E3-Ligase Murf-1 and the activity of manganese superoxiddismutase<br />

(Mn-SOD) in quadriceps muscle (Qua) and diaphragm (Dia) in LAD-ligated rats<br />

(MI).<br />

Methods: Twelve weeks after operation left ventricular function was assessed in<br />

MI (n=12) and sham operated (C, n=9) rats using echocardiography and Millarcatheter.<br />

Murf-1 protein expression was quantified using Western Blot and Mn-<br />

SOD activity was measured in Qua and Dia.<br />

Results: Compared to C, LAD-Ligation resulted in a severe left ventricular dysfunction<br />

(EF: 33.4±3.3 vs. 64.8±2.6% (p


=0.31, p=0.0003) and QUICKI (r=0.29, p=0.0008). HOMA identified impaired insulin<br />

sensitivity in CHF vs controls (3.45±0.29 vs 1.39±0.19) as did FIRI (3.10 vs<br />

0.26) and QUICKI (0.34±0.01 vs 0.39±0.004, all p


308 Cardiac surgery and transplantation<br />

P1985 Cellular implant follow-up in chronic cardiopathy<br />

produced by American trypanosomiasis (Chagas’<br />

disease)<br />

J.C. Trainini 1 , N. Lago 2 , J. Bordone 2 , J. Mouras 2 , J. Barisani 2 ,<br />

A. Riarte 2 ,A.Ruiz 2 , J.C. Chachques 3 . 1 Presidente Peron Hospital,<br />

Cardiac Surgery Department, Buenos Aires, Argentina; 2 Presidente<br />

Peron Hospital, Cardiovascular Surgery, Avellaneda, Argentina; 3 Pompidou<br />

Hospital, Cardiovascular Surgery, Paris, France<br />

Objectives: Chagas’disease is presented in very important number of transplantation<br />

candidates in South America. Your etiology is the Cruzi trypanosoma, which<br />

produces in the heart severe arrhythmias, dilated cardiomyopathy, heart failure<br />

with death prognostic. The purpose of this clinical study was to evaluate the performance<br />

of the bone marrow stem cells implant in heart failure for Chagas-Mazza<br />

disease.<br />

Methods: Over 70 patients implanted with bone marrow stem cells 7 had chronic<br />

chagasic cardiopathy. About these last, 5 consecutive patients had a follow-up of<br />

22.8±13.3 months. These patients with an age of 55.8±8.1 years, presented left<br />

ventricular failure. The preoperative data showed an average of functional class:<br />

2.6±0.5 (NYHA), left ventricular ejection fraction: 26.4±5.7%, left ventricular diastolic<br />

diameter: 61.6±5.6 mm and the left ventricular systolic diameter: 46.9±6.3<br />

mm. Enriched suspension of mononuclear stem cells diluted in autologous serum<br />

containing (average) 10.6±7 mlwith1.43±0.6 (E+08) cells; CD34+: 5.07±9.51<br />

(E+06); CD133+: 5.11±4.3 (E+06). The approach was made by intracoronary<br />

way.<br />

Results: There was one mortality at 17 months by arrhythmia. Blind echocardiography<br />

and radioisotopic analysis showed that ejection fraction improved<br />

from 26.4±5.7% to 35.6±5.3% (p=0.05) and the class functional decrease from<br />

2.6±0.5 to 1±0 (p


P1989 Hormonal mechanisms of cachexia in heart failure<br />

and weight gain after heart transplantation<br />

L.H. Lund1 , J.J. Williams2 ,P.Freda2 , J.J. Lamanca3 ,<br />

S.B. Heymsfield4 , T.H. Lejemtel5 , D.M. Mancini 2 . 1Karolinska University Hospital, Cardiology Department, Stockholm, Sweden;<br />

2 3 Columbia University, New York, United States of America; Salisbury University,<br />

Salisbury, United States of America; 4Merck Pharmaceuticals, New Jersey,<br />

United States of America; 5Tulane University, New Orleans, United States of<br />

America<br />

Objectives: <strong>Heart</strong> failure (HF) is associated with cachexia and heart transplantation<br />

(HTx) with weight gain independent of steroid therapy. The mechanisms may<br />

be related to hormonal changes.<br />

Methods: We examined anabolic (insulin, growth hormone (GH) and its downstream<br />

mediator insulin-like growth factor-1 (IGF-1)), anorexic (leptin) and<br />

appetite-stimulating/anabolic (ghrelin) hormones, hunger and caloric intake, and<br />

body composition in 12 HF patients awaiting HTx, 12 patients who had gained<br />

18±8 kgover13±9 months since HTx and 7 obese controls (Ctrl). Seven of the<br />

12 HF patients were followed for longitudinal analysis post HTx.<br />

Results: Insulin resistance was present in HF and HTx and correlated with BMI<br />

in HTx but not in HF. GH was elevated in HF and IGF-1 in HTx. Leptin was higher<br />

in HTx. Ghrelin over 5 hours prior to a test meal was elevated in HF, hunger was<br />

equal and caloric intake was lower in HF (table). The longitudinal study confirmed<br />

these findings.<br />

Ctrl (n=7) HF (n=12) HTx (n=12) p<br />

Age (years) 42±14 52±16 47±18 0.46<br />

Male/Female (n) 5/2 10/2 11/1 0.54<br />

BMI (kg/m2 ) 28±4 23±3 32±6


310 Cardiomyopathy<br />

death rates in the 2 cohorts were similar in all pts: 2, 5, 7, 10% vs 3, 7, 14, 17%,<br />

p=NS.<br />

Conclusions: An early diagnosis, secondary to the screening program of familial<br />

cases is associated to a better outcomes with respect to sporadic forms. However<br />

the sudden death rate and the overall outcome were similar after risk stratification<br />

between familial and sporadic forms.<br />

P1993 Septic cardiomyopathy: role of iNOS and eNOS in a<br />

murine model of sepsis<br />

A. Van De Sandt1 , A. Goedecke 2 , R. Windler3 , S. Becher1 ,<br />

T. Rassaf3 , C. Weber4 ,M.Kelm3 , J. Schrader2 ,M.W.Merx3 . 1IZKF Biomat RWTH, Aachen, Germany; 2Physiology, University Hospital,<br />

Duesseldorf, Germany; 3Cardiology Dep., University Hospital RWTH, Aachen,<br />

Germany; 4IMCAR, RWTH Aachen, Aachen, Germany<br />

Purpose: Nitric oxide (NO) plays a central role in the pathogenesis of septic cardiomyopathy.<br />

However, the relative contribution of inducible nitric oxide synthase (iNOS) and<br />

endothelial nitric oxide synthase (eNOS) as high-capacity NO-producing enzymes<br />

and their involvement in the detrimental cardiac alterations in the setting<br />

of septic cardiomyopathy remain unclear. Having demonstrated an absence of<br />

hypotension resulting in a significantly improved survival in septic eNOS-/- mice.<br />

The aim of this study is to elucidate the influence of eNOS and iNOS on cardiac<br />

parameters in the clinically relevant polymicrobial cecum ligation and puncture<br />

(CLP) model of sepsis.<br />

Methods: B6/c57 wildtype (WT) and eNOS-/- mice were rendered septic by<br />

CLP or sham-operated. Immediately, treatment with the selective iNOS-inhibitor<br />

1400W (6,6 mg/kg BW i.p. and s.c.) or placebo was initiated. At 12 hours after<br />

sepsis induction heart function was assessed by pressure-volume loops using a<br />

1.4 Fr Millar catheter placed in the left ventricle of anesthetized mice.<br />

Results: dPdTmax was diminished only in septic wildtype (WT clp, n=6 vs.<br />

wt sham, n=7: dPdtmax: 10981±1100,14mmHg vs. dPdtmax: 13408±826,64<br />

mmHg, p


or more of the following ECG changes: repolarization ST/T abnormalities in 209<br />

(80%), pathologic Q waves (Q waves ≥0.04 s in duration or ≥25% of the height of<br />

the ensuing R wave) in 103 (39.6%); left atrial enlargement in 75 (28.8%), intraventricular<br />

conduction abnormalities (QRS duration ≥90 ms) in 71 (27.3%) and<br />

left axis deviation in 9 (3.5%). ECG tracings showed isolated increase of QRS<br />

voltages in 5 HCM patients (1.9%) and were completely normal in 14 (5.4%).<br />

Compared with patients with HCM, trained athletes significantly more often had<br />

isolated voltage criteria for LVH (403, 40%; p


312 Cardiomyopathy<br />

P2000 Cardiac fibrosis and low QRS amplitudes are<br />

mutation specific clinical features in subjects with<br />

hereditary DCM due to mutations in phospholamban<br />

M.G. Posch 1 ,A.Perrot 1 , C. Geier 1 ,G.Schmidt 2 , H.B. Lehmkuhl 2 ,<br />

R. Hetzer 2 ,R.Dietz 1 , M. Gutberlet 3 ,W.Haverkamp 1 , C. Ozcelik 1 .<br />

1 Charite - Universitaetsmedizin Berlin, Cardiogenetic Lab (Haus 129), Berlin,<br />

Germany; 2 German <strong>Heart</strong> Institute Berlin, Cardiothoracic and Vascular Surgery,<br />

Berlin, Germany; 3 University of Leipzig, Diagnostic and Interventional Radiology,<br />

Berlin, Germany<br />

Purpose: Mutations in phospholamban (PLN) were reported as a rare cause for<br />

familial DCM (FDCM). Low-voltage ECG (LVE) was described as a clinical feature<br />

of PLN mutation carriers in one greek family. Yet, previous reports are inconsistent<br />

about a specific phenotype. The purpose of this study was to assess a specific<br />

cardiac phenotype of subjects affected by FDCM due to a mutation in PLN.<br />

Methods: We prospectively studied twenty relatives of a large German FDCM<br />

family with LVE. The phenotyping protocol included ECG, Holter-ECG, echocardiography<br />

(including TDI), cardiac magnetic resonance imaging (CMR) and<br />

75-lead body surface potential mapping (BSPM). Medical charts of four deceased<br />

family members were reviewed. The coding region of PLN was directly<br />

sequenced.<br />

Results: We identified a heterozygous in frame deletion of codon 14 in the PLN<br />

gene (PLN-R14Del) in seven family subjects. The mutation was previously shown<br />

to be pathogenic for human DCM and cosegregated with the disease in the pedigree.<br />

Penetrance of DCM was age and gender dependent. Affected individuals<br />

suffer from severe heart failure associated with cardiac deaths between ages of<br />

26-50. Interestingly, we identified LVE as an early sign for the disease. Three dimensional<br />

reconstructions of cardiac electrical currents by use of BSPM allowed<br />

us to link LVE to regions of extensive cardiac fibrosis as assessed by Gadolinium<br />

late enhancement (LE) in CMR. Therefore, cardiac fibrosis constitutes the<br />

pathogenic substrate for LVE in patients with the PLN-R14Del mutation.<br />

Conclusion: We present a family suffering from a severe form of fDCM associated<br />

with cardiac fibrosis and LVE due to the PLN-R14Del mutation. According to<br />

our results LVE is a specific phenotype in FDCM patients with the PLN-R14 Del<br />

mutation. Therefore, it is highly recommendable to screen patients with DCM and<br />

LVE in the gene encoding PLN.<br />

P2001 Right ventricular involvement in Fabry Disease<br />

G. Dostalova 1 , T. Palecek2 , P. Kuchynka2 ,D.Karetova2 ,J.Bultas2 ,<br />

M. Elleder2 , A. Linhart 2 on behalf of Cardiovascular research<br />

project of the Charles University Prague, nr. 0021620817. 1General Teaching Hospital, 2nd Department of Internal Medicine, Prague 2,<br />

Czech Republic; 2Prague, Czech Republic<br />

Background: Fabry disease (FD) is characterized by intracellular deposition of<br />

neutral glycosphingolipids. Left ventricular hypertrophy (LVH) is a hallmark cardiac<br />

manifestation of FD, however right ventricular (RV) involvement is far less<br />

known.<br />

Objectives: The purpose of this study was to describe RV structural and functional<br />

changes in FD.<br />

Methods: A detailed echocardiographic examination including the assessment of<br />

RV size, thickness, systolic function and filling pressure together with the evaluation<br />

of right atrial (RA) size was performed in 58 patients with proven FD (mean<br />

age 40±16 years, 24 males).<br />

Results: RV hypertrophy was present in 40% of affected subjects with similar<br />

prevalence in both genders. Almost two thirds of patients with LVH also exhibited<br />

RV hypertrophy. RV dilatation was not present in any subject. RV systolic dysfunction<br />

was noted only in one female. Elevation of RV filling pressure was found<br />

in 9% of the patients. RA dilatation was noted in 48% of subjects, and was frequently<br />

associated with RV hypertrophy. A significant correlation between RV wall<br />

thickness and age (r=0.52, p


P2004 Association between cardiovascular risk factors,<br />

impaired myocardial blood flow and ventricular<br />

remodelling in patients with idiopathic left ventricular<br />

dysfunction<br />

D. Neglia1 ,D.Rovai1 ,E.Rizza2 ,F.Bigazzi1 ,S.Masi1 ,C.Simi1 ,<br />

T. Sampietro 1 ,A.L’abbate1 . 1Pisa, Italy; 2Bologna, Italy<br />

Background: In patients with idiopathic left ventricular (LV) systolic dysfunction,<br />

absolute myocardial blood flow (MBF) is frequently impaired due to coronary microvascular<br />

disease and may predict progressive deterioration of cardiac function.<br />

Purpose: We tested the hypothesis that abnormal MBF and LV dysfunction in<br />

these patients are related with coronary risk factors as combined in the Framingham<br />

estimated coronary heart disease (CHD) risk.<br />

Methods: A group of 64 patients with systolic LV dysfunction (48 males, age<br />

61±9 yrs,LVEF38±9%, range 20-53%) and angiographically normal coronary<br />

arteries were studied. Absolute MBF (ml/min/g) was measured by positron emission<br />

tomography, using 13N-Ammonia as a flow tracer, at rest and during i.v.<br />

dipyridamole infusion (0.56 mg/kg over 4 min). LV function was assessed by 2D-<br />

Echo measurements of LVEF, LV end-diastolic diameter (LVEDD, mm) and LV<br />

mass index (LVMI, g/m 2 ). The estimated Framingham CHD risk was based on<br />

age, sex, blood pressure, cigarette smoking, LDL and HDL cholesterol and diabetes.<br />

Results: CHD risk ranged from 4% to 56%. With increasing tertiles of CHD risk,<br />

MBF decreased, both at rest (P=0.043) and during vasodilation (P=0.026) (Figure).<br />

With increasing CHD risk, LVEDD and LVMI increased (for LVEDD 58±5,<br />

63±9 and 65±6, P=0.010; for LVMI 128±31, 141±29 and 154±26, P=0.037)<br />

while LVEF did not significantly change.<br />

MBF values and CHD risk tertiles.<br />

Conclusion: In patients with idiopathic LV dysfunction, an increase in CHD risk<br />

is associated with a reduction in MBF and an increase in LV dimensions, suggesting<br />

that cardiovascular risk factors are related with the extent of coronary<br />

microvascular dysfunction and LV functional remodelling.<br />

P2005 Preamplification techniques for real-time RT-PCR<br />

analyses of endomyocardial biopsies<br />

M. Noutsias1 , M. Rohde1 , K. Klippert 2 , K. Blunert 1 ,M.Hummel1 ,<br />

R. Hetzer3 , U. Kuehl1 , H.P. Schultheiss1 ,H.D.Volk2 ,K.Kotsch2 .<br />

1Charite - Campus Benjamin Franklin, Department of Cardiology &<br />

Pneumonology, Berlin, Germany; 2Charite - Campus Mitte, Institute of Medical<br />

Immunology, Berlin, Germany; 3German <strong>Heart</strong> Institute Berlin, Cardiovascular<br />

Surgery, Berlin, Germany<br />

Background: Due to the limited RNA amounts from endomyocardial biopsies<br />

(EMBs) and low expression levels of certain genes, gene expression analyses by<br />

conventional real-time RT-PCR are restrained in EMBs. We applied two preamplification<br />

techniques, the TaqMan ® PreAmp Master Mix (T-PreAmp) and a multiplex<br />

preamplification following a sequence specific reverse transcription (SSRT-<br />

PreAmp).<br />

Results: T-PreAmp encompassing 92 gene assays with 14 cycles resulted<br />

in a mean improvement of 7.24+0.33 Ct values. The coefficients for inter-<br />

(1.89+0.48%) and intra-assay variation (0.85+0.45%) were low for all gene assays<br />

tested (40ms in 11%). At signal averaged ECG late potentials were<br />

present in 58% of pts. At 2D echocardiography, mean right ventricle (RV) enddiastolic<br />

area was 30±8 cm 2 , and RV fractional area contraction (FAC) 30±13%;<br />

RV aneurysms were present in 67%. RV systolic dysfunction (FAC


314 Cardiomyopathy<br />

(11%) experienced death/heart transplantation (D/HTx), 6 (3%) died for refractory<br />

HF; 4 pts (2%) underwent status one heart transplantation; 6 pts (3%) died<br />

suddenly; one (0.5%) for extracardiac disease and 3 (1.6%) for unknown reason.<br />

Conclusions: ARVC is a relatively uncommon disease, frequently with familial<br />

transmission. The disease tipically begins in the early age, clinical presentation<br />

with symptomatic or sustained ventricular arrhythmias is frequent; LV involvement<br />

is present in one third of cases at enrolment. The overall prognosis is not severe<br />

in the long term.<br />

P<strong>2008</strong> Changing mortality in dilated cardiomyopathy in the<br />

last 30 years<br />

A. Di Lenarda1 ,M.Merlo1 , G. Barbati 2 ,A.Pivetta1 ,S.Pyxaras1 ,<br />

A. Magagnin1 ,G.Finocchiaro1 , L. Dell’angela1 , G. Sabbadini1 ,<br />

G. Sinagra 1 on behalf of <strong>Heart</strong> Muscle Disease Study Group.<br />

1Ospedali Riuniti and University, Cardiovascular Department, Trieste, Italy;<br />

2University of Torino, Department of Public Health and Microbiology, Torino, Italy<br />

Purpose: Dilated cardiomyopathy (IDC) is a myocardial disease, characterized<br />

by left and/or right ventricular dilatation and dysfunction and poor outcome.<br />

Evidence-based treatment with ACE inhibitors and beta-blockers (BB) and, in the<br />

last decade, implantable cardioverter defibrillator (ICD) have been demonstrated<br />

to improve significantly heart failure symptoms and prognosis. The aim of this<br />

study was to evaluate the effect of different strategies developed in IDC patients<br />

(pts).<br />

Methods: We analysed the data from 631 patients (pts) (males 75%, mean age<br />

45±15 years, NYHA III-IV 26%, LV ejection fraction 30±10%) with IDC enrolled<br />

in the <strong>Heart</strong> Muscle Disease Registry from January 1978 to December 2002. Our<br />

population was divided in three groups on the basis of time of enrolment and<br />

therapeutic strategies: group 1 (110 pts) enrolled from 1978 to 1987, group 2<br />

(361) from 1988 to 1997 (pharmacological therapy "era") and group 3 (160 pts)<br />

from 1998 to 2002 (pharmacological and device-therapy "era").<br />

Results: Pts of the three groups did not differ significantly for age, sex, NYHA<br />

class, left ventricular ejection fraction and presence of left bundle branch block.<br />

ACE inhibitors were used in 22 vs 92 vs 96% (p


P2012 Correlations between the degree of portal<br />

hypertension, cardiovascular complications and<br />

some biochemical markers in patients with hepatic<br />

cirrhosis<br />

E.I. Manov1 , H.N. Velinov2 ,M.D.Apostolova2 ,T.I.Donova1 ,<br />

K.G. Tchernev 1 . 1medical university, clinic of cardiology, Sofia,<br />

Bulgaria; 2Institute of Molecular Biology, Medical and Biological Research Lab,<br />

Sofia, Bulgaria<br />

objective: 1.To study correlations between the degree of portal hypertension in<br />

patients with hepatic cirrhosis, cardiovascular complications and levels of endothelin,<br />

brain natriuretic peptide and aldosteron. 2. To establish the predictive<br />

ratio of these biochemical markers for development of cardiovascular complications.<br />

methods: We include 91 men and 35 women at the age of 54±10 years with<br />

histologically documented hepatic cirrhosis (postviral:n=82, alcocholic:n=44) and<br />

different levels of portal hypertension: stage 1- with varices, no ascites (n=50);<br />

2. ascites and varices (n=65); 3. resistant ascites or bleeding episode (n=11).<br />

Ascites were proved by abdominal echography or computer tomography, varicesby<br />

endoscopy. Cardiovascular complications were detected by electrocardiography<br />

and echocardiography. We excluded patients with cardiovascular risk factors<br />

and data for cardiovascular diseases. ELISA was used to detect the biochemical<br />

markers in all patients and healthy subjects (n= 71). Data were analyzed by<br />

ANOVA, Turky’s post-hoc analysis, Pearson, Spearman and Fisher tests.<br />

results: Compromised cardiac function in most of our patients was characterized<br />

mainly as diastolic dysfunction in stage 1 and 2 of portal hypertension. Patients<br />

in stage 3 had mostly systolic disfunction with globally reduced left-ventricle ejection<br />

fraction. The levels of biochemical markers in patients studied were significant<br />

increased (p30 mmHg, vs 8% among those without syncope; p=0.02); moreover,<br />

they showed a trend toward greater prevalence of associated moderate-tosevere<br />

or severe mitral regurgitation (40% vs 16%, respectively; p=0.118), and<br />

pulmonary edema or cardiogenic shock on admission (40% vs 14%, respectively;<br />

p=0.117). In addition, patients presenting with syncope had higher admission Troponin<br />

I values (8±5 ng/ml vs 3±4 ng/ml; p=0.05), and more often required intraaortic<br />

balloon pumping (40% vs 8%, p=0.02). All patients with LV outflow tract<br />

obstruction received beta-blocker therapy with subsequent early regression of the<br />

dinamic obstruction. There were no differences between the 2 groups in terms of<br />

baseline LV ejection fraction (35±10% vs 35±8%, respectively; p=0.991), time<br />

to recovery of normal systolic function (7±4 daysvs7±3 days, respectively;<br />

p=0.872), and one-year mortality (0% vs. 4.5%, respectively; p=0.622). At Cox<br />

analysis the only independent predictor of death was age (p=0.034).<br />

Conclusions: Syncope is an unusual presentation of TTC and it is more common<br />

in the subset developing LV outflow tract obstruction. These data suggest<br />

the need for the assessment of LV outflow tract obstruction in all TTC patients,<br />

in particular in those presenting with syncope, and for beta-blocker therapy of<br />

dinamic obstruction.<br />

P2015 Risk factor profiles in South African patients with<br />

hypertrophic cardiomyopathy caused by distinct<br />

founder mutations<br />

M. Heradien1 ,M.Revera2 , A. Goosen3 ,P.A.Brink3 , J.C. Moolman-<br />

Smook3 . 1University of Stellenbosch, Internal Medicine, Cape<br />

Town, South Africa; 2University of Pavia, Cardiology, Pavia, Italy; 3University of<br />

Stellenbosch, Intenal Medicine, Cape Town, South Africa<br />

Background: Implantable cardioverter defibrillators are increasingly used to prevent<br />

sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) patients<br />

deemed to be at high risk. Risk stratification assesses a number of factors, including<br />

a family history of multiple SCDs, unexplained syncope, non-sustained<br />

ventricular tachycardia on Holter ECG, maximal left ventricular wall thickness<br />

(mLVWT) ≥30mm and abnormal blood pressure response during exercise testing.<br />

Early genetic studies also suggested that correlations exist between genetic<br />

mutation and survival.<br />

Purpose: The aim of this study was to compare risk factor profiles between three<br />

South African HCM founder mutation groups, to assess whether genotype correlated<br />

with risk profile.<br />

Methods: Twenty-one South African families in which one of three HCM<br />

founder mutations segregated participated in this study. Thirty R92WTNNT2, 24<br />

R403WMYH7, and 27 A797TMYH7 HCM mutation-bearing individuals as well<br />

as 67 of their non-carrier relatives were investigated with 2D and M-mode echocardiography<br />

and exercised under a modified Bruce protocol. Patient and family<br />

histories were obtained.<br />

Results: Significantly more R92WTNNT2 individuals failed to increase systolic<br />

blood pressure by more than 20mmHg than did individuals from either the control<br />

or other mutation groups (p=0.015). R92WTNNT2 individuals also demonstrated<br />

more syncope (p=0.007) than did the control or other mutation groups. On the<br />

other hand, significantly more A797TMYH7 individuals demonstrated overt hypertrophy<br />

(mLVWT≥30mm). Most SCDs occurred in R92WTNNT2 families, while<br />

A797TMYH7 families suffered more SCDs than R403WMYH7 families.<br />

Conclusion: Mechanisms underlying SCD for the different mutations are not<br />

clear, but may involve alterations in calcium-handling and/or alterations in autonomic<br />

tone.<br />

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316 Imaging in cardiomyopathy<br />

IMAGING IN CARDIOMYOPATHY<br />

P2016 Prevalence and clinical significance of chronic left<br />

ventricular systolic dysfunction in adolescents<br />

G. Limongelli 1 , G. Pacileo2 , P. Calabro’ 2 , R. Ancona2 , A. D’andrea2 ,<br />

M. Romano2 , G. Romano2 ,G.DiSalvo2 ,A.Rea2 , R. Calabro’ 2 .<br />

1Second University of Naples-Monaldi Hospital, Napoli, Italy;<br />

2Cardiothoracic Sciences, Second University of Naples-Monaldi Hospital, Napoli,<br />

Italy<br />

Aim: Prevalence, etiology and clinical course of progressive left ventricular dysfunction<br />

leading to heart failure (HF) have been widely described in children and<br />

adults with cardiomyopathies. To date, few is known concerning left ventricular<br />

systolic dysfunction developing during adolescence. Here, we sought to analyse<br />

etiology, clinical course and outcome of chronic systolic dysfunction in adolescents<br />

with different type of cardiomyopathies.<br />

Methods: Fifty-two patients (median age 16) who had been diagnosed with<br />

systolic dysfunction (ejection fraction


disease. Familial study was recomended because of a proband diagnosed of: Hypertrophic<br />

Cardiomyopathy (HCM) in 289 (57%), Dilated (DCM) in 69 (14%), Arrhythmogenic<br />

right ventricular (ARVC) in 14 (3%), Left ventricular non-compation<br />

in 14 (3%), Brugada in 77 (15%), SADS in 15 (3%) and LongQT in 12 (3%), other<br />

conditions in 15 (3%). Familial disease was considered when at least 2 individuals<br />

of the same family were clearly affected. 79 (16%) had a family history of sudden<br />

cardiac death.<br />

Results: Familial disease was confirmed in 161 (40%); 45% in HCM, 50% in<br />

DCM, 25% in ARVC, 27% in LVNC, 23% in Brugada, 33% in LongQT.<br />

190 (0.47 per family; 43±20 years old; 60% male) affected relatives were identified<br />

(127 of whom were new diagnosed cases). The new cases were 63 HCM,<br />

39 DCM, 2 ARVC, 5 LVNC, 14 Brugada and 2 LongQT, in whom appropriate risk<br />

stratification and medication if needed was iniciated (5 affected relatives underwent<br />

ICD implantation for primary prevention). 161 individuals (0.4 per family)<br />

were found to have some non-diagnostic features (possibles) and further reviews<br />

were recommended.<br />

Conclusions: The prevalence of familial disease in inherited cardic diseases<br />

is high. Systematic familial study identify asymptomatic affected individuals that<br />

could benefit from early treatments in order to prevent complications. Dedicated<br />

clinics and multidisciplinary teams are needed for proper screening programs.<br />

P2020 Hypercholesterolemia causes systolic and diastolic<br />

dysfunction<br />

J. Rubinstein 1 , A. Vedre2 , R. Huang2 , G.S. Abela2 . 1Michigan State University, Cardiology Dept., East Lansing, United States of<br />

America; 2Michigan State University, Cardiology, East Lansing,<br />

United States of America<br />

Background: <strong>Heart</strong> failure affects both systolic and diastolic function. We sought<br />

to establish a link between hypercholesterolemia and myocardial dysfunction by<br />

both standard echocardiographic examination and tissue Doppler imaging (TDI).<br />

Methods: 27 rabbits were studied; Group I (GI; n=7) were fed normal chow; GII<br />

(n=10) were fed a high cholesterol diet; GIII (n=10) high cholesterol diet with ezetimibe<br />

(1mg/kg/day). Echocardiographic examination included 2-D echo, Doppler<br />

flow and TDI under anesthesia. Serum cholesterol levels were obtained at baseline<br />

and 3 months. Myocardial tissue cholesterol levels were measured post euthanasia.<br />

Results: A full echocardiographic study was obtainable in 24/27 rabbits. No significant<br />

differences were noted in chamber sizes or ejection fraction among the<br />

groups. E/A was lower in the GII compared to both GI and GIII respectively<br />

(1.55±0.49 vs. 1.89±0.51 and 1.92±0.37; p=0.05). By TDI (picture), E’/A’ was<br />

higher in GPI and GIII compared to GII respectively (1.93±0.42 and 1.89±0.22<br />

vs.1.26±0.62; p=0.01). Also, GI and GIII had higher S’ measurements reflecting<br />

better systolic function compared to GII respectively (6.42±2.5 and 6.55±1.66 vs.<br />

4.6±0.69 p=0.05). In GII serum cholesterol was significantly higher in comparison<br />

to GI and GIII respectively (1073mg/dl±539 vs. 87mg/dl±37 and 179mg/dl±81;<br />

p


318 Imaging in cardiomyopathy<br />

P2023 Myocardial trabeculation in healthy volunteers.<br />

Cardiovascular magnetic resonance study<br />

A.M. Maceira Gonzalez1 , J. Cosin-Sales2 ,S.K.Prasad3 ,<br />

P.J. Kilner3 . 1ERESA - Hospital Arnau de Vilanova, CMR Unit,<br />

Valencia, Spain; 2Hospital Arnau de Vilanova, Cardiology, Valencia,<br />

Spain; 3Royal Brompton Hospital, CMR Unit, London, United Kingdom<br />

Purpose: Isolated non-compaction of the left ventricle (INCLV) is a rare but potentially<br />

lethal cause of LV dysfunction and arrhythmias. In healthy subjects a<br />

certain amount of myocardial trabeculation, especially in the lateral wall, may exist.<br />

Also, the apical myocardium is usually thin and apical trabeculations can be<br />

misdiagnosed as pathological. Cardiac magnetic resonance (CMR) can detect<br />

hypertrabeculation in cases in which this finding is not obvious with echocardiography.<br />

Our aim was to study with CMR the presence and range of normality of<br />

myocardial trabeculation in healthy volunteers.<br />

Methods: 120 healthy volunteers were included (60 males), 20 in each age decile<br />

(20-29, 30-39, 40-49, 50-59, 60-69, 70-79 yrs). They were studied with medical<br />

history, physical examination, ECG, BP measurement and conventional blood<br />

tests. CMR acquisitions were at 1.5T using retrospective gating. Breath-hold cine<br />

sequences were acquired in the 2, 4, and 3-chamber views, and SA stack of the<br />

ventricles (slice thickness/gap/temporal resolution: 7mm/3mm/22ms). Ventricular<br />

mass and volumes were measured. Trabeculation was considered to be present<br />

where muscular bands 5% was observed<br />

in 70% of subjects, and %Trab>10% in 41% of subjects. The most frequent localization<br />

of trabeculation was the lateral wall (in 72% of subjects), followed by the<br />

anterior wall (51%) and apex (38%), while this finding was very infrequent in the<br />

septum (2.5% of subjects). Table shows %Trab (median; p25-p75) in males and<br />

females according to age.<br />

20-29yrs 30-39yrs 40-49yrs 50-59yrs 60-69yrs 70-79yrs All<br />

Males 6; 4-12 7; 0-11 9; 5-16 8; 4-15 11; 8-17 11; 6-14 10; 6-14<br />

Females 3; 0-7 6; 6-11 8; 0-13 8; 0-11 10; 8-14 9; 6-14 9; 5-14<br />

Conclusions: In healthy subjects with normal LV dimensions and systolic function<br />

CMR can detect myocardial trabeculations within a range of normality. These<br />

trabeculations are mainly seen in the lateral wall. This finding may be important<br />

for the accurate diagnosis of INCLV.<br />

P2024 The relationship between echocardiographic<br />

parameters and plasma N-terminal pro-brain<br />

natriuretic peptide levels in patients with dilated<br />

cardiomyopathy<br />

C. Mornos, A. Ionac, D. Cozma, L. Petrescu, D. Maximov, A. Mornos,<br />

D. Popa, A. Lupu, S.I. Dragulescu. Institute of Cardiovascular<br />

Diseases, Timisoara, Romania<br />

The myocardial performance index (MPI), defined as the sum of isovolumic contraction<br />

and relaxation times divided by ejection time, and N-terminal pro-brain<br />

natriuretic peptide (NTproBNP) have been utilised to express global left ventricular<br />

(LV) function. The ratio between early diastolic transmitral velocity (E, using<br />

pulsed Doppler) and early mitral annular diastolic velocity (Ea, using tissue<br />

Doppler imaging) has been proposed as the best Doppler predictor for evaluating<br />

LV filling pressures in a variety of cardiac diseases.<br />

Purpose: to assess the relationship between echocardiographic parameters<br />

(conventional echocardiography and Tissue Doppler imaging) and NTproBNP in<br />

patients with dilated cardiomyopathy (DCM) in sinus rhythm.<br />

Methods: Conventional echocardiography and tissue Doppler imaging were performed<br />

in 50 consecutive patients (age 63±13 years) with DCM, in sinus rhythm,<br />

concomitent with NTproBNP determination. Patients with inadequate echocardiographic<br />

images, paced rhythm, mitral prosthesis, severe mitral annular calcification<br />

or renal failure were not included. Ea and Sa (peak systolic mitral annular<br />

velocity during ejection) were determined at the lateral site of mitral annulus. MPI<br />

(using conventional echocardiography) and E/Ea were calculated.<br />

Results: The simple regression analysis demonstrated the strongest statistically<br />

significant linear correlation between MPI and NTproBNP (r=0.70, p 3 segments or a LGE score >4<br />

predicted a RC with a sensitivity of 70 and 73%, a specificity of 88 and 75%, a<br />

negative predictive value of 44 and 43% and a positive predictive value of 95 and<br />

91% respectively. Regarding LGE, its presence was significantly correlated with<br />

left ventricular posterior (p= 0.012), septal (p=0.07) wall and interatrial (p=0,032)<br />

thickness, left atrium diameter (p= 0,004).<br />

Conclusions: Restrictive filling pattern on cardiac catheterization and LGE on<br />

CMR are common findings in FAP patients without sign of heart failure. LGE has<br />

a very good positive predictive value for RC but absence of LGE cannot rule out<br />

RC.<br />

P2026 Cardiomyopathy in the course of laminopathy and<br />

emerinopathy, echocardiographic and biochemical<br />

features<br />

M. Marchel 1 , A. Madej 2 , V. Stepien 1 ,R.Steckiewicz 1 ,<br />

J. Kochanowski 1 ,P.Scislo 1 ,R.Piatkowski 1 , K.J. Filipiak 1 ,<br />

I. Hausmanowa-Petrusewicz 2 ,G.Opolski 1 . 1 Medical University of Warsaw, 1St<br />

Dept of Cardiology, Warsaw, Poland; 2 Polish Academy of Science, Warsaw,<br />

Poland<br />

Purpose: Emery-Dreifuss muscular dystrophy (EDMD) is characterized by musculoskeletal<br />

abnormalities, accompanied by cardiac defects (conduction disturbances<br />

and systolic dysfunction). Sudden cardiac death is the most common<br />

mechanism of death in this group. The genetic background of EDMD is a mutation<br />

in nuclear proteins: lamin A/C and emerin. The aim of the study was an<br />

analysis of left ventricular (LV) dysfunction in EDMD patients with the use of tissue<br />

Doppler imaging (TDI) and plasma natriuretic peptides measurements.<br />

Methods: In the present study we included 25 pts with genetically confirmed<br />

EDMD (17 pts with an X-linked inheritance [defect in the STA gene, emerinopathy]<br />

and 8 pts with an autosomal dominant form [defect in LMNA, laminopathy]).<br />

Conventional echocardiography, TDI, and natriuretic peptide levels were measured<br />

in all patients and controls (25 healthy volunteers). Diastolic function was<br />

measured by TDI derived parameter E/E’. For each wall, the peak strain (%) and<br />

strain rate - SR (s -1 ) were assessed in basal and mid LV segments.<br />

Results: The mean left ventricular ejection fraction (LVEF) was 51,3±9,1% and<br />

65,5±2,6 for EDMD pts and for controls respectively (p


P2027 MRI for the detection of restrictive cardiomyopathy in<br />

familial amyloid polyneuropathy<br />

O. De Sauniere1 ,A.Resten1 , M. Mabille1 , S. Bennani1 ,<br />

V. Algalarrondo1 , F. Rouzet2 , S. Dinanian1 , D. Adams3 , D. Musset1 ,<br />

M.S. Slama1 . 1Clamart, France; 2Paris, France; 3Le Kremlin Bicetre,<br />

France<br />

Purpose: To determine cardiac magnetic resonance (CMR) imaging signs predictive<br />

of restrictive cardiomyopathy (RC), as diagnosed by cardiac catheterization,<br />

in patients with familial amyloid polyneuropathy (FAP).<br />

Methods: 38 consecutive patients with FAP without heart failure symptoms<br />

screened for liver transplantation underwent cardiac catheterization, CMR with<br />

study of late gadolinium enhancement (LGE) assessed by phase-sensitive inversion<br />

recovery sequence (PSIR). Patients demonstrating the following criteria were<br />

considered as having a RC: right atrial pressure> 5 mmHg or pulmonary capillary<br />

wedge pressure>15 mmHg or dip and plateau on right ventricular pressure<br />

curve, before or after overload with 500 cc of colloid solution, or decrease of cardiac<br />

output after overload. LGE was quantified by number of segments involved<br />

(16-segment model) and by extension within wall thickness (4 scale score), providing<br />

an individual score. CMR data also comprised LV septal and posterior wall,<br />

right ventricular free wall, interatrial septum thicknesses and left atrium diameter.<br />

Results: 79% of patients had RC and 76% exhibited LGE. We found no correlation<br />

between RC and left atrium diameter or right ventricular thickness. The<br />

posterior wall thickness (p= 0,012), number of segments (p=0,017) and individual<br />

score (p=0,012) of LGE were positively correlated with the presence of RC. In the<br />

9 patients without LGE, 6 (66%) had RC and only 3 (33%) had a normal hemodynamic<br />

profile. In ROC curve analysis, LGE in > 3 segments or a LGE score >4<br />

predicted a RC with a sensitivity of 70 and 73%, a specificity of 88 and 75%, a<br />

negative predictive value of 44 and 43% and a positive predictive value of 95 and<br />

91% respectively. Regarding LGE, its presence was significantly correlated with<br />

left ventricular posterior (p= 0.012), septal (p=0.07) wall and interatrial (p=0,032)<br />

thickness, left atrium diameter (p= 0,004).<br />

Conclusions: Restrictive filling pattern on cardiac catheterization and LGE on<br />

CMR are common findings in FAP patients without sign of heart failure. LGE has<br />

a very good positive predictive value for RC but absence of LGE cannot rule out<br />

RC.<br />

P2028 Myocardial performance index combined with tissue<br />

Doppler imaging could help prediction of early<br />

anthracycline-induced cardiotoxicity<br />

A.A.M. Farrag, M. Meshref. Cairo University, Cardiology, Cairo,<br />

Egypt<br />

Background: Doxorubicin is a known active agent for treatment of various malignancies.<br />

Its subclinical toxicity after lower doses is not fully understood. The<br />

present study was designed to evaluate the diagnostic role of myocardial performance<br />

index (MPI) combined with tissue Doppler imaging (TDI) in asymptomatic<br />

adults receiving chemotherapy regimen including low-dose doxorubicin.<br />

Methods: Twenty four patients (mean age 32±13 years), newly diagnosed as<br />

Hodgkin’s or non-Hodgkin’s lymphoma were eligible for our study. All had baseline<br />

echo-Doppler study within normal limits and all patients were treated with<br />

doxorubicin cumulative dose ≤ 300 mg/m 2 . Left ventricular ejection fraction (EF)<br />

and MPI [(isovolumic relaxation time + isovolumic contraction time)/ ejection time]<br />

were measured. Peak systolic (Sm), early (Em) and late (Am) diastolic myocardial<br />

velocities as well as contraction time (CTm) were recorded at lateral mitral annulus<br />

before (study 1), after completion of therapy (study 2) and at one year follow<br />

up (study 3). We considered MPI >0.4 represent early myocardial dysfunction.<br />

Results: None of our patients developed clinical manifestations of heart failure<br />

after one year. Sm and Em were decreased significantly in studies 2 and 3 when<br />

compared to study 1. The inverse was true regarding Am and MPI (table). MPI<br />

at study 1 had a significant positive correlation with left ventricular end systolic<br />

volume of study 3 (r= 0.770, p= 0.0001), however, a significant inverse correlation<br />

was observed with Em (r= -0.622, p= 0.001). The area under the curve (AUC)<br />

and 95% confidence interval (CI) of the receiver operating characteristic (ROC)<br />

curves for the examined parameters to predict MPI > 0.4 showed that the Am of<br />

study 2 yielded the largest area (AUC 0.757, 95% CI 0.512-0.938, p= 0.035).<br />

Echocardiographic and TDI parameters<br />

Variable Study 1 Study 2 Study 3 p 1 vs. 2 p 1 vs. 3<br />

LVEF 62±5.8 58±5.7 56±5.1 0.002 0.0001<br />

MPI 0.33±0.08 0.38±0.08 0.39±0.07 0.01 0.0001<br />

Sm (cm/sec) 12.7±2.2 11.2±1.9 10.5±1.6 0.0001 0.0001<br />

Em (cm/sec) 15.9±2.6 14.4±2.7 13.5±2.4 0.001 0.006<br />

Am (cm/sec) 8.6±1.7 10.3±2.2 11.0±2.2 0.0001 0.0001<br />

Conclusion: The cardiotoxic manifestations of low dose anthracyclines are frequently<br />

subclinical and could be highlighted by myocardial performance index.<br />

Imaging in cardiomyopathy / Non ST-elevation myocardial infarction 319<br />

P2029 Late gadolinium enhancement detected by<br />

cardiovascular magnetic resonance imaging is<br />

associated with increased inducibility of ventricular<br />

tachyarrhythmias in patients with hypertrophic<br />

cardiomyopathy<br />

S. Fluechter1 , J. Kuschyk1 , C. Wolpert 1 , D. Haghi2 , C. Doesch1 ,<br />

D. Dinter2 , S. Schoenberg1 , T. Sueselbeck2 , M. Borggrefe 2 , T. Papavassiliu2 .<br />

1University Hospital Mannheim, 1st Medical Department, Mannheim, Germany;<br />

2Universitiy Hospital Mannheim, 1st Medical Department, Mannheim, Germany<br />

Purpose: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are established<br />

as the principal mechanisms of sudden death in patients with hypertrophic<br />

cardiomyopathy (HCM). However risk stratification of patients with HCM still remains<br />

a challenge. Myocardial replacement scarring is probably an important<br />

anatomic component of the arrhythmogenic substrate in patients with HCM and<br />

can be assessed by late gadolinium-enhancement (LGE) CMR. Thus, we hypothesized<br />

that myocardial scarring detected by LGE CMR might be associated<br />

with an increased likelihood of inducibility of ventricular tachyarrhythmias in patients<br />

with HCM. The aim of this retrospective study was to investigate whether<br />

presence, extent and location of myocardial scarring assessed by LGE CMR correlates<br />

with the inducibility of ventricular tachyarrhythmias during programmed<br />

ventricular stimulation (PVS) in patients with HCM.<br />

Methods: 67 patients with HCM underwent LGE CMR. 32 of these patients (22<br />

males and 10 females; mean age 56±15 years) were also examined by electrophysiologic<br />

study including PVS. LV function, volumes, myocardial thickness, and<br />

the extent of LGE, were assessed with respect to the inducibility of ventricular<br />

tachyarrhythmias during PVS.<br />

Results: 21 of the 32 patients (66%) showed LGE, 11 patients did not (34%).<br />

Overall, in 11 patients (34%) ventricular tachyarrhythmias were inducible during<br />

PVS. Patients with inducible ventricular tachyarrhythmias showed significantly<br />

more extent of LGE as compared to patients with normal electophysiologic findings<br />

(23% vs. 10%, p=0.037).<br />

Conclusions: The extent of LGE is associated with the inducibility of ventricular<br />

tachyarrhythmias in patients with HCM. Future studies are needed to assess the<br />

potential role of LGE CMR for risk stratification of patients with HCM.<br />

NON ST-ELEVATION MYOCARDIAL INFARCTION<br />

P2030 Cardiogenic shock in NSTEMI and STEMI -<br />

differences in treatment and outcomes in clinical<br />

practice. Results from PL-ACS registry<br />

M. Gasior1 ,M.Gierlotka1 , W. Ruzyllo2 ,R.Gil3 , D. Dudek4 ,<br />

S. Grajek5 ,M.Trusz-Gluza6 ,J.Kubica7 , M. Zembala1 ,<br />

L. Polonski1 . 1Silesian Centre For <strong>Heart</strong> Diseases, Zabrze, Poland; 2Institute of Cardiology, Warsaw, Poland; 3MSWiA Hospital, Warsaw, Poland; 4Collegium Medicum, Jagiellonian University, Cracow, Poland; 5Institute of Cardiology,<br />

Poznan, Poland; 6Medical University of Silesia, Katowice, Poland; 7Medical University, Bydgoszcz, Poland<br />

The aim of this analysis was to assess differences in treatment and outcomes of<br />

patients with cardiogenic shock (CS) and NSTEMI or STEMI in clinical practice.<br />

Methods: From 10.2003 to 08.2006, a total of 71290 consecutive patients with<br />

NSTEMI (N=33392) and STEMI (N=37898) have been enrolled into the ongoing,<br />

prospective, registry of acute coronary syndromes (PL-ACS). Follow-up deaths<br />

were acquired from the government database.<br />

Results: CS on admission was present in 1158 (3.5%) pts with NSTEMI and in<br />

2986 (7.9%) pts with STEMI. Pts with CS and NSTEMI were younger, less frequently<br />

smokers, more frequently had prior MI, and had higher heart rate than<br />

STEMI patients. The rates of invasive treatment was low in NSTEMI (17%) as<br />

compared to STEMI (41%). One-year mortality was higher in NSTEMI as a consequence<br />

of lower rates of invasive treatment as well as higher mortality after<br />

coronary angiography compared to STEMI patients.<br />

NSTEMI STEMI P value<br />

Age, years 71.0±11.2 67.9±12.2


320 Non ST-elevation myocardial infarction<br />

P2031 Patterns of use and effectiveness of early invasive<br />

strategy in non-ST-segment elevation acute coronary<br />

syndromes<br />

I. Ferreira Gonzalez 1 , G. Permanyer-Miralda 2 , M. Heras 2 ,<br />

J. Cunyat 3 ,E.Civeira 4 ,F.Aros 5 , P.L. Sanchez 6 , J. Marrugat 2 ,<br />

H. Bueno 6 on behalf of MASCARA study group. 1 Vall d’Hebron Hospital,<br />

Cardiology Department, Barcelona, Spain; 2 Barcelona, Spain; 3 Valencia, Spain;<br />

4 Zaragoza, Spain; 5 Vitoria, Spain; 6 Madrid, Spain<br />

Aims: To assess the patterns of use and the benefit of an early invasive strategy<br />

(EIS) in non-ST-segment elevation acute coronary syndrome (NSTEACS)<br />

patients in real life.<br />

Methods: All consecutive patients hospitalized by NSTEACS between November<br />

2004 and June, 2005 in 32 randomly selected hospitals were prospectively<br />

included. Patients were stratified by their baseline risk profile using the GRACE<br />

risk score in two groups. In-hospital mortality, one and six month mortality or rehospitalisation<br />

for acute coronary syndromes were analyzed. To ensure optimal<br />

adjustment logistic regression, propensity score and Cox regression were employed.<br />

Results: Of 2,856 patients 1616 (56%) had low/intermediate risk (GRACE ≤ 140)<br />

and 1,240 high risk (GRACE >140). Patients who underwent EIS had lower risk<br />

than those who did not (GRACE score: 128.2±41 vs 138.5±43; p 0.01-0.07<br />

μg/l) MI groups. Patients with no elevation of troponin above the "new" cutoff values<br />

were classified as unstable angina. Starting in 2005, post-discharge follow-up<br />

information was collected for all patients who provided consent from a subgroup<br />

of 44 hospitals.<br />

Results:<br />

"Classic" MI (n=8701) "New" MI (n=489)<br />

Age 66.4±13.7 y 67.2±13.7 y NS<br />

Male gender 6140/8701 (70.6%) 351/489 (71.8%) NS<br />

Prior history of CAD 2845/7470 (38.1%) 254/447 (56.8%)


P2035 Oxidized low density lipoprotein levels associate with<br />

culprit vessel in ST-elevation myocardial infarction<br />

P. Napoleao1 ,M.Selas2 , A. Andreozzi3 , A. Turkman3 , A. Viegas-<br />

Crespo3 ,A.Toste2 , R. Cruz Ferreira2 , T. Pinheiro4 . 1Instituto Tecnologico e Nuclear, Sacavem, Portugal; 2Hospital St Marta,<br />

CH Lisboa Central, Servico Cardiologia, Lisboa, Portugal; 3Universidade de<br />

Lisboa, Centro de Estatistica Aplicada, Lisboa, Portugal; 4Instituto Tecnologico e<br />

Nuclear, Sacavem, Portugal<br />

Objectives: To study the variations of oxidized LDL (ox-LDL) at the onset of acute<br />

myocardial infarction (AMI) and along the recovery period and explore the relation<br />

with disease severity.<br />

Methods: A follow-up of 30 ST-elevation AMI patients was evaluated against 16<br />

patients with angiographically normal coronary arteries (controls, CTR) and 24<br />

healthy volunteers (reference group, REF). The AMI patients were evaluated at 3<br />

time points: at admission before the administration of IIb/IIIa and angioplasty (day<br />

0), two (day 2) and 40 (day 40) days after intervention. Plasma concentration of<br />

ox-LDL was measured by ELISA.<br />

Results: Plasma levels of ox-LDL were significantly higher in AMI patients<br />

(103±8 U/l) than in healthy subjects (57±6 U/l,p


322 Non ST-elevation myocardial infarction<br />

P2039 Coronary revascularization improves prognosis in<br />

diabetic patients with non-ST-segment elevation<br />

acute coronary syndromes; results from the<br />

Euro<strong>Heart</strong> survey on ACS-II<br />

R. Parma1 , H. Bueno2 ,A.Gitt3 ,A.Battler4 , N. Danchin5 ,<br />

G. Filippatos6 , D. Hasdai4 ,Y.Hasin7 , J. Marrugat8 ,F.VanDeWerf9on behalf of Euro<strong>Heart</strong> Survey on ACS-II investigators. 1Medical University of<br />

Silesia, 3rd Division of Cardiology, Katowice, Poland; 2Hospital Universitario<br />

Gregorio Maranon, Department of Cardiology, Madrid, Spain; 3Herzzentrum Ludwigshafen, Institut fur Herzinfarktorschung, Ludwigshafen, Germany;<br />

4 5 Sheba Medical Center, Tel Hashomer, Israel; Hopital Europeen Georges-<br />

Pompidou, Department of Cardiologie, Paris, France; 6Atticon University<br />

Hospital, Department of Cardiology, Athens, Greece; 7Poriah Medical Center,<br />

Cardiovascular Institute, Tiberias, Israel; 8Institut Municipal Investigacio Medica,<br />

Lipids and Cardiovascular Epidemiology Unit, Barcelona, Spain; 9University Hospital Gasthuisberg, Department of Cardiology, Leuven, Belgium<br />

Background: Diabetes mellitus (DM) is an independent predictor of mortality in<br />

patients with non-ST-segment elevation acute coronary syndromes (NSTEACS),<br />

but coronary revascularisation seems to improve prognosis in these patients.<br />

Aims: To evaluate the influence of DM on the use and outcomes of coronary<br />

revascularisation in patients with NSTEACS.<br />

Methods: We analysed data of 3046 patients with NSTEACS enrolled in Euro<strong>Heart</strong><br />

Survey on ACS-II registry in years 2004 and 2005, regarding their DM<br />

status (27%) and hospital revascularisation (44%). The outcome measure was<br />

mortality at 1-year.<br />

Results: Coronary revascularization was performed in 40% of patients with DM<br />

and 45% without DM (NS). Revascularised patients were younger, had lower<br />

prevalence of risk factors, comorbidities, and troponin elevation, and similar ECG<br />

presentation in both groups. One-year mortality was significantly lower among<br />

revascularised patients, but the difference was higher in the DM group (2.4%<br />

vs 13.5%, p


P2042 Persistent under representation of the circumflex<br />

artery as infarct related vessel in patients treated with<br />

acute reperfusion therapy<br />

C. Willemse, S. Rasoul, J.P. Ottervanger, E. Kolkman,<br />

J.H.E. Dambrink, M.J. De Boer, J.C.A. Hoorntje, H. Suryapranata,<br />

A.T.M. Gosselink, A.W.J. Van ’T Hof. Isala Klinieken Zwolle, Cardiology, Zwolle,<br />

Netherlands<br />

Background: It is unlikely that the chance of plaque rupture in the circumflex (CX)<br />

artery is lower than plaque rupture in the RCA or LAD coronary artery. Therefore<br />

one would expect an equal distribution of infarct artery involvement between the<br />

three coronary arteries in patients with an acute coronary syndrome. We hypothesized<br />

that the involvement of the CX artery might increase over time with better<br />

recognition of an acute CX occlusion using either electro- (V7-V9) or echocardiographic<br />

diagnostic tools.<br />

Methods: All patients who presented with symptoms suggestive of an acute myocardial<br />

infarction (MI) and who underwent immediate coronary angiography were<br />

included. The 12 lead ECG on admission was analysed by an independent corelab.<br />

The culprit infarct related vessel (IRV) was determined by the intervening<br />

physician. Patients with non-STEMI were defined as having less than 1 mm cumulated<br />

ST segment elevation.<br />

Results: From January 1, 2000 until December 31, 2005, 2.985 patients were<br />

included. Overall 179 patients (6.0%) were diagnosed with non-STEMI. The CX<br />

was the infarct related vessel (IRV) in 13.2%, versus 44.9 and 39.2% for the LAD<br />

and RCA respectively. From the CX related MI, 14% presented as a non-STEMI<br />

as compared to 4.6% of RCA or LAD related MI (p


324 Non ST-elevation myocardial infarction<br />

Figure 1<br />

tively, despite their higher risk profile, were less likely to receive recommended<br />

secondary prevention treatments at discharge than those who underwent PCI.<br />

P2046 Considering criteria for left ventricular hypertrophy in<br />

a continuous manner augments their ability to predict<br />

adverse events in patients with NSTEMI<br />

J.A. Barrabes, J. Figueras, J. Cortadellas, R.M. Lidon, S. Ibars.<br />

Hospital Universitari Vall d’Hebron, Cardiology, Barcelona, Spain<br />

Purpose: Left ventricular hypertrophy (LVH) is associated with a worse outcome<br />

in patients with acute coronary syndromes, but dichotomous categorization of<br />

patients into those having or not LVH has limitations irrespective of the definition<br />

used. We aimed to explore whether considering the components of LVH criteria in<br />

a continuous manner has incremental value to predict in-hospital adverse events<br />

in patients with non-ST elevation acute myocardial infarction (NSTEMI).<br />

Methods: We evaluated 451 consecutive patients with a first NSTEMI. LVH was<br />

defined by Sokolow-Lyon and Cornell (voltage and product) criteria on the admission<br />

ECG and, in 296 of them, by echocardiography (corrected American Society<br />

of Echocardiography [ASE] formula). The association of in-hospital adverse<br />

events (death, reinfarction, severe heart failure, or angina with ECG changes)<br />

with these criteria for LVH, either considered as dichotomous variables or across<br />

quintiles of their components, was assessed.<br />

Results: Patients with LVH (5 to 6% by ECG criteria and 24% by echocardiography)<br />

had more adverse events than those without: 41.7 vs 26.0%, respectively<br />

(P=0.09), by Sokolow-Lyon; 50.0 vs 25.6% (P=0.01) by Cornell voltage;<br />

50.0 vs 25.3% (P=0.004) by Cornell product; and 38.0 vs 22.2% (P=0.008) by the<br />

ASE formula. However, a progressive increase in the rate of events was observed<br />

across quintiles of the components of all LVH criteria (Table). This increase was<br />

not paralleled by differences in the prevalence of multivessel disease or in CK-<br />

MB peak, and was also present after excluding patients with LVH according to<br />

the dichotomous criteria.<br />

Rates of major adverse events (%)<br />

Criterion (units) Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5 P value for trend<br />

Sokolow-Lyon (mV) 17.8 21.8 26.7 28.7 41.8


P2049 Addition of B-type natriuretic peptide to the<br />

Thrombolysis in Myocardial Infarction (TIMI) risk<br />

score enhances risk stratification in acute coronary<br />

syndrome<br />

S. Ang 1 ,L.Wei2 , C. Lang2 , A. Struthers2 . 1University of Dundee,<br />

Division of Medicine And Therapeutics, Dundee, United Kingdom;<br />

2University of Dundee, Division of Medicine and Therapeutics, Dundee, United<br />

Kingdom<br />

Purpose: In acute coronary syndrome (ACS), both the TIMI (Thrombolysis In<br />

Myocardial Infarction) risk score and B-type natriuretic peptide (BNP) predict adverse<br />

prognosis. However, it is unknown whether the addition of BNP to the TIMI<br />

risk score would enhance risk stratification in ACS.<br />

Methods: We recruited 329 consecutive non ST elevation ACS patients and measured<br />

admission TIMI risk score and bedside BNP levels. The main outcome<br />

measure was either all cause mortality, readmission with ACS or congestive heart<br />

failure, (defined as a cardiovascular event) at 10 months from presentation.<br />

Results: Of the 329 patients, 93 patients presented with unstable angina (28%).<br />

There were 72 cardiovascular events at 10 months. Both higher TIMI risk terciles<br />

and higher BNP terciles predicted cardiovascular events. There was a significant<br />

but partial correlation between the TIMI risk score and LOG BNP (R=0.439,<br />

P80 pg/ml) were more likely to experience cardiovascular<br />

events at 10 months [RR 9.91 (95% CI, 3.56-27.62] compared to<br />

those with low TIMI risk score-high BNP [RR 5.11 (95% CI, 1.72-15.17] or high<br />

TIMI risk score-low BNP [RR 3.52 (95% CI, 1.03-12.02)].<br />

Conclusion: In ACS, BNP predicts cardiovascular events over and above the<br />

TIMI risk score. This suggests that both methods reflect different risk attributes<br />

when predicting adverse prognosis in ACS. In addition, the combined use of both<br />

the TIMI risk score and BNP further identifies a subset of ACS patients at a particularly<br />

high risk. Therefore the synergistic use of both modalities has the potential<br />

to enhance risk stratification in ACS.<br />

P2050 Routine invasive strategy for women with NSTEMI<br />

myocardial infarction? - Results of the Berliner<br />

Herzinfarktregister (BHIR)<br />

J. Ebbinghaus1 ,C.Graf-Bothe2 ,R.Thieme3 ,R.Schoeller2 ,<br />

B. Maier 4 , S. Behrens1 on behalf of Berliner Herzinfarktregister.<br />

1 2 Vivantes Humboldt Klinikum, Berlin, Germany; DRK Kliniken Westend,<br />

Berlin, Germany; 3Juedisches Krankenhaus, Berlin, Germany; 4Zig, Technische<br />

Universitaet Berlin, Berlin Myocardial Infarction Registry, Berlin, Germany<br />

Background: The benefit of a routine invasive strategy for male and female<br />

STEMI patients and for male NSTEMI patients is known. It is<br />

under discussion whether female NSTEMI patients may also benefit from routine<br />

invasive procedures. Therefore we analysed our data concerning the effect of a<br />

routine invasive strategy in consecutive female patients with NSTEMI and STEMI.<br />

Methods: The BHIR is an ongoing myocardial infarction registry which<br />

collected data from 775 female AMI patients (STEMI n=449, NSTEMI n=326)<br />

who were treated between 1.1.04-31.7.06 in Berlin in hospitals with a cath-lab.<br />

The data were analysed stratified for STEMI and NSTEMI. Differences between<br />

patients with a statistically significant influence on hospital mortality for both<br />

STEMI and NSTEMI were adjusted for age, renal failure, diabetes mellitus, CHF,<br />

and cardiogenic shock on admission.<br />

Results: NSTEMI (72.6 years) and STEMI patients (71.3 years) did not show a<br />

significant difference in age (p=0.358). Patients with NSTEMI<br />

showed more concomitant diseases, i.e. diabetes mellitus (NSTEMI: 38.7%;<br />

STEMI: 30.2% p=0.015), previous AMI (NSTEMI: 25.0%; STEMI: 14.9%<br />

p=0.001), atrial fibrillation (NSTEMI: 13.3%; STEMI: 7.8% p=0.013).<br />

NSTEMI patients reached a hsopital only in 49.8% of cases with the physician<br />

escorted rescue system (compared to 62.0% for STEMI p=0.001). NSTEMI received<br />

primary PCI (66.9%) less often than STEMI patients (75.9%) (p=0.006).<br />

There were no major differences in the initial therapy with ASA, beta-blockers,<br />

ace-inhibitors, and cse-inhibitors. Hospital mortality was 5.7% for NSTEMI and<br />

13.1.% for STEMI patients (p=0.001).<br />

The influence of PCI on hospital mortality for STEMI patients was OR=0.33 (95%<br />

CI: 0.15-0.73) after adjustment, the results for NSTEMI patients were not significant<br />

and showed an OR=0.86 (95% CI: 0.21-3.52).<br />

Conclusion: The data of our clinical registry did not show a benefit of a routine<br />

invasive strategy for NSTEMI in comparison to STEMI female<br />

patients. The results should be validated in other studies and registries. Further<br />

research may be needed to determine an appropriate and optimal strategy for<br />

female NSTEMI patients.<br />

Non ST-elevation myocardial infarction 325<br />

P2051 Low use of combined clopidogrel aspirin therapy in<br />

patients undergoing CABG or cardiac rehabilitation<br />

after non ST-elevation ACS. The S-temoin registry<br />

N. Danchin 1 ,F.Dievart 2 , J.F. Thebaut 3 , O. Grenier 3 ,<br />

M.A. Herrmann 3 , J. Ferrieres 4 on behalf of S-Temoin investigators.<br />

1 Hopital Europeen Georges Pompidou (Hegp), Service De Cardiologie, Paris,<br />

France; 2 Dunkerque, France; 3 Paris, France; 4 Toulouse, France<br />

Background: the CURE trial has shown the efficacy of prolonged administration<br />

of clopidogrel and aspirin in the year following an acute coronary syndrome<br />

(ACS).<br />

Aim: to evaluate correlates of prolonged use of combined antiplatelet therapy<br />

versus monotherapy in patients discharged after non ST-elevation ACS.<br />

Population and methods: 512 cardiologists included 2,121 patients seen at their<br />

outpatient clinics 2-13 months after an episode of non ST-elevation ACS. Of those,<br />

2,081 were on either antiplatelet monotherapy (544 patients, 26%) or combination<br />

therapy (aspirin + clopidogrel, 1,537 patients, 74%).<br />

Results: By univariate analysis, combined antiplatelet therapy was more frequently<br />

used in patients


326 Non ST-elevation myocardial infarction / Antithrombotic agent<br />

P2053 Microvascular damage prevention with<br />

thrombaspiration during primary percutaneous<br />

intervention in acute myocardial infarction<br />

A. Berger-Kucza, M. Turski, A. Rybicka-Musialik, K. Wita,<br />

M. Trusz-Gluza. Katowice, Poland<br />

Background: Despite rapid and complete recanalization of infarct related artery<br />

(IRA) with percutaneous coronary intervention (PCI) microvascular integrity is not<br />

often preserved. Several mechanical devices have been proposed to prevent distal<br />

embolization, but the impact of these devices on myocardial perfusion remains<br />

controversial.<br />

The aim of our study was to assess microvascular damage reduction with quantitative<br />

myocardial contrast perfusion echocardiography (QMCE) among patients<br />

with the first anterior AMI treated with thromboaspiration during PCI.<br />

Methods: 42 patients (57,4±10 yrs, 74% males) with first anterior AMI were randomized<br />

1:1 to intracoronary thromboaspiration followed by stenting, or to a conventional<br />

strategy of stenting alone ECHO and quantitative contrast echocardiography<br />

(QMCE) were performed 7 days and one month later (ECHO).Parameter<br />

A (reflecting MBV), β (reflecting velocity MBF) and product of A and β as indicator<br />

of MBF were analysed. For each patient mean value of A, β and A x β from all<br />

dysfunctional segments was calculated.<br />

Results: The study population was divided into two groups: thromboaspiration<br />

(group I, 19 pts) and stenting alone (group II, 23 pts). There was no difference<br />

between the both groups in demographic, clinical, echocardiographic and angiographic<br />

data. Parameter A and Axβ were significantly higher in group I than<br />

in group II: 8,58±2,54 dB vs 5,29±3,18 dB (p


P2058 Genetic variation in CYP2C19 affects exposure to the<br />

active metabolite and P2Y12 inhibition for clopidogrel<br />

but not prasugrel in patients with atherosclerosis<br />

C. Varenhorst 1 ,S.James 1 ,D.Erlinge 2 , O.O. Braun 2 ,K.J.Winters 3 ,<br />

M. Man 3 , A. Siegbahn 4 ,J.Walker 5 , L. Wallentin 1 ,S.L.Close 3 .<br />

1 Uppsala Clinical Research Center, Dept Internal Medicine, Cardiology, Uppsala,<br />

Sweden; 2 Dept of Cardiology, Lund, Sweden; 3 Lilly Research Laboratories,<br />

Indianapolis, United States of America; 4 Coagulation Laboratory, Dept Medical<br />

Sciences, Uppsala, Sweden; 5 Daiichi Sankyo Inc., Parsippany, United States of<br />

America<br />

Purpose: Clopidogrel is a prodrug that is hydrolyzed by esterases to an inactive<br />

metabolite, with only a minor fraction converted to the active metabolite (AM) in<br />

two CYP-dependent steps, compared to prasugrel that requires only one CYPdependent<br />

step to form the AM. We hypothesized that a decrease in CYP2C19<br />

activity affects generation of clopidogrel AM but not prasugrel AM, which results<br />

in a corresponding decrease in the pharmacodynamic response to clopidogrel.<br />

Methods: Samples for genetic analysis were obtained from 98 patients with<br />

coronary artery disease participating in a randomized, double blind comparison<br />

of clopidogrel 600 mg versus prasugrel 60 mg loading doses (LD) on a background<br />

of 75 mg aspirin. DNA was extracted from peripheral blood and genotyped<br />

for CYP2C19. Subjects were grouped into two CYP2C19 genotype functional<br />

groups: normal function metabolizers (EM) and reduced function metabolizers<br />

(RM). Plasma AM concentrations were measured. VASP phosphorylation<br />

(PRI, %) was measured pre-dose and 24h post-LD.<br />

Results: The genotype frequencies were similar in both groups. For prasugrel,<br />

there was no statistically significant difference in the total exposure to<br />

the prasugrel AM or VASP-PRI between groups. For clopidogrel, the exposure<br />

to AM was statistically significantly lower (p0.2), and ST elevation resolution >70%<br />

60 minutes after PPCI (70.7% vs. 68.8%, P>0.2) were not significantly better in<br />

the Early group. MRI data (Table) showed no significant differences in initial and<br />

6-month infarct size between the 2 groups (P>0.20).<br />

Cardiac MRI results<br />

Pre-discharge 6 months<br />

DE, % of Transmurality DE, % of Transmurality Change in DE,<br />

myocardium of DE, % myocardium of DE, % %<br />

Early (n=44) 21±11 26±15 14±9 17±13 -7±6<br />

Late (n=32) 18±12 21±14 12±9 14±13 -6±6<br />

P value >0.20 >0.20 >0.20 >0.20 >0.20<br />

DE = Delayed Enhancement; Early = early abciximab administration; Late = abciximab administration<br />

in Cath Lab.<br />

Conclusions: Our study shows that early abciximab administration is not associated<br />

with either smaller infarct size or greater myocardial salvage after 6 months.<br />

These findings might be explained by the non-significant increase in recanalization<br />

of the infarct-related artery with early abciximab administration, possibly due<br />

to the short time from randomization to angiography.<br />

P2062 Long-term net clinical benefit in favor of fondaparinux<br />

compared with enoxaparin in <strong>European</strong> patients with<br />

non-ST elevation acute coronary syndromes:<br />

a subgroup analysis of OASIS-5<br />

J.-P. Bassand 1 , A. Budaj 2 ,K.A.A.Fox 3 , S.R. Mehta 4 ,<br />

R.J.G. Peters 5 , P.G. Steg 6 ,L.Wallentin 7 , S. Yusuf 4 on behalf of Oasis-5<br />

Investigators. 1 University Hospital Jean Minjoz, Department of Cardiology,<br />

Besancon, France; 2 Grochowski Hospital, Cardiology, Warsaw, Poland;<br />

3 University of Edinburgh, Cardiovascular Research Division, Edinburgh, United<br />

Kingdom; 4 Hamilton General Hospital, McMaster Clinic, Hamilton, Canada;<br />

5 Academic Medical Centre, Cardiology, Amsterdam, Netherlands; 6 Bichat<br />

Hospital, Cardiology, Paris, France; 7 University Hospital, Uppsala Clinical<br />

Research Centre, Uppsala, Sweden<br />

Purpose: The randomized, double-blind OASIS-5 trial demonstrated a better net<br />

clinical benefit of fondaparinux (fonda) 2.5mg once daily compared to enoxaparin<br />

(enox) in patients (pts) with non-ST elevation acute coronary syndromes<br />

(NSTEACS). Since this trial was performed in 41 countries and because of possible<br />

differences in practice patterns between countries, we analyzed the benefitrisk<br />

ratio of fonda in the subgroup of pts recruited in <strong>European</strong> Community (EC)<br />

countries.<br />

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328 Antithrombotic agent<br />

Methods: Pts with NSTEACS were randomly assigned to fonda (2.5mg once<br />

daily) or enox (1mg/kg twice daily). Rates of death, myocardial infarction (MI),<br />

refractory ischemia (RI) and major bleeds were efficacy and safety endpoints.<br />

Follow-up was 180 days.<br />

Results: Of 20,078 pts, 11,695 (58.2%) were recruited in EC; 4447 of them<br />

(38.0%) underwent a percutaneous coronary intervention (PCI) procedure. Overall<br />

findings were consistent with data obtained in the total population. The rates<br />

of primary efficacy outcome (death/MI/RI) at 9 days were similar (p=0.79) in pts<br />

treated with fonda (6.1%) or enox (6.0%), irrespective of whether patients underwent<br />

PCI. There was a significant risk reduction for death with fonda at 30<br />

days (HR [95%CI]: 0.80 [0.65-0.99]; p=0.042) and 180 days (HR: 0.86 [0.73-<br />

1.00]; p=0.051). A significant reduction of major bleeding was observed at 9 days,<br />

1.9% with fonda vs 4.3% with enox (HR [95%CI]: 0.43 [0.35-0.54], p


p=0.003). Minor bleeding was also less common in these pts (4.9% vs 19%; p=<br />

0.03). The optimal ROC-defined INR value for all bleeding was 2.6. This value<br />

had a specificity of 89%, a sensitivity of 66%, a negative predictive value of 95%,<br />

and a positive predictive value of 44%. INR > 2.6 was the only independent predictor<br />

of bleeding. There were no significant differences in MACE between groups<br />

(5.8% vs 3.9%; p=0.1).<br />

Conclusions: In pts undergoing coronary stenting, long term triple therapy is<br />

associated with an increased bleeding risk which can be reduced by careful monitoring<br />

and targeting low INR values.<br />

P2066 Fondaparinux administration according to its<br />

<strong>European</strong> labeling improves outcome in patients with<br />

ST elevation acute myocardial infarction (STEMI): a<br />

subanalysis of the OASIS-6 study<br />

R.J.G. Peters1 ,J.Oldgren2 ,S.R.Mehta3 , L. Wallentin2 , S. Yusuf3 on behalf of The OASIS-6 Investigators. 1Nieuwer Ter Aa, Netherlands;<br />

2University Hospital, Uppsala Clinical Research Centre, Uppsala, Sweden;<br />

3Hamilton General Hospital, McMaster Clinic, Hamilton, Canada<br />

Purpose: In OASIS-6 in patients with STEMI, fondaparinux 2.5 mg once daily was<br />

significantly more effective in preventing death (D) or reinfarction (RI) than control<br />

treatment (unfractionated heparin [UFH] or placebo) without increasing severe<br />

bleeding (SB). We investigated the value of fondaparinux administered according<br />

to its <strong>European</strong> labeling, i.e. in the subgroup of patients receiving thrombolytics<br />

or non-reperfused.<br />

Methods: 12,092 STEMI patients were randomized to fondaparinux (2.5 mg once<br />

daily for up to 8 days) or control treatment consisting of either UFH for 48 hours<br />

or placebo in patients with no UFH indication. Follow-up was up to 180 days<br />

(minimum 90 days).<br />

Results: 8294 (68.6%) patients did not undergo primary percutaneous coronary<br />

intervention, but received either thrombolytics (n=5437, 45.0%) or were nonreperfused<br />

(n=2857, 23.6%). According to local practice, 5641 patients did not<br />

have an indication for UFH and 2653 did. D or RI at 30 days (primary endpoint)<br />

was reduced from 14.1% in the control group to 11.4% in the fondaparinux group<br />

(hazard ratio 0.80 [95% CI: 0.70 to 0.90]; p


330 Antithrombotic agent<br />

dial infarction (MI), repeat revascularization at 30 days; b) individual components<br />

of the composite end-point (death, MI, death + MI, repeat revascularization); c)<br />

major bleeding; d) minor bleeding. Data were extracted by 2 independent reviewers.<br />

Studies evaluating eptifibatide in the setting of primary PCI were excluded.<br />

Results: A total of 4 trials, including 6297 patients, were found. Triple composite<br />

end-point occurred in 9% of patients receiving eptifibatide vs 11% of those receiving<br />

placebo (pooled OR 0.73, 0.62-0.87; P=0.0003). Patients randomized to<br />

eptifibatide showed 28% risk reduction in the occurrence of death + MI (OR 0.72,<br />

0.59-0.88; P=0.001), decreased incidence of MI (6% vs 8%; P=0.001), a trend<br />

towards a reduction in mortality (0.5% vs 0.7%, OR 0.58, 0.30-1.10; P=0.09) and<br />

lower repeat revascularization (3% vs 4%, OR 0.73, 0.56-0.97; P=0.03). Major<br />

bleeding incidence was not different in the 2 arms (4% vs 3%, OR 1.17, 0.87-<br />

1.56; P=0.29), whereas the eptifibatide group had higher risk of minor bleeding<br />

(OR 1.55, 1.36-1.77; P


Avidin, a protein found in hen eggs, has a high- and specific-affinity for biotin and<br />

can immediately neutralize the anticoagulant activity of biotinylated idraparinux.<br />

This study was designed to evaluate whether a second administration of avidin,<br />

several months after the first administration, is able to rapidly and safely reverse<br />

the pharmacological activity of biotinylated idraparinux.<br />

Methods: In a previous study, TDU5307, the efficacy and safety of a single intravenous<br />

(IV) injection of avidin following a single SC dose of biotinylated idraparinux,<br />

was demonstrated in 40 healthy, young, male subjects. Of these subjects,<br />

8 then underwent the same protocol administration of study drugs 9–13 months<br />

later; SC injection of biotinylated idraparinux (3 mg), followed 4 hours later (tmax<br />

of biotinylated idraparinux) by an IV infusion of avidin (100 mg). The pharmacodynamic<br />

activity (inhibition of Factor Xa without an excess of antithrombin III) was<br />

assessed using a validated chromogenic method.<br />

Results: The large, rapid, and sustained neutralization of biotinylated idraparinux<br />

anti-Xa activity was observed in all 8 subjects who had a second administration<br />

of avidin (including those who presented positive antibody titers). Anti-Xa activity<br />

decreased by 93% (range: 85–100%) within 30 minutes of the avidin infusion,<br />

a decrease similar to that obtained in the first study (87% [range: 86–89%]). In<br />

both studies, there was no evidence of a rebound phase of anti-Xa activity for up<br />

to 14 days after avidin administration (the last sampling time). Total antibodies<br />

against avidin were detectable at baseline in 4 of the 8 subjects, and the titer<br />

increased by 2–3-times in 3 of 4 of these subjects. Among the 4 subjects without<br />

baseline antibodies, 2 became antibody positive after the second avidin injection<br />

and 2 remained negative. More importantly, none of the subjects had a positive<br />

prick or RAST test reaction to egg allergen 1 month after the administration of<br />

avidin and biotinylated idraparinux. Total IgE, circulating immune complex and<br />

complement activation markers did not show relevant changes during the study,<br />

and no hypersensitivity reactions were observed.<br />

Conclusions: A second administration of 100 mg avidin is safe and efficient for<br />

the neutralization of a single dose of biotinylated idraparinux. This allows the<br />

consideration of multiple administrations of avidin in patients receiving long-term<br />

treatment with biotinylated idraparinux.<br />

P2074 Thrombin generation is a possible marker for a<br />

haemostatic action of recombinant factor VIIa to<br />

shorten prolonged bleeding time provoked by a high<br />

dose of a direct factor Xa inhibitor in rats<br />

Y. Morishima, Y. Honda, C. Matsumoto, T. Fukuda, T. Shibano.<br />

Daiichi Sankyo Co., Ltd., Biological Research Laboratories I, Tokyo, Japan<br />

Purpose: Warfarin is the current standard of care for patients requiring chronic<br />

anticoagulation. Direct factor Xa (FXa) inhibitors are in development as a replacement<br />

for warfarin. A key clinical need for all anticoagulants regardless of mechanism<br />

of action is the availability of an antidote. The objective of this study is to<br />

evaluate thrombin generation (TG) assay as a potential biomarker to monitor the<br />

reversal of a direct FXa inhibitor-induced bleeding by recombinant FVIIa (rFVIIa).<br />

Methods: A rat model of template bleeding was used. Rats were anesthetized<br />

with thiopental. An incision was made on the planta with a knife. Blood was blotted<br />

every 30 sec, and bleeding time was defined as the time from the incision to the<br />

first arrest of bleeding. The maximum observation period was 30 min. We used<br />

DU-176b as a direct FXa inhibitor. DU-176b (1 mg/kg/h, a supratherapeutic dose)<br />

was administered by intravenous infusion 2 h before the induction of bleeding to<br />

the end of experiment. Recombinant FVIIa was given as a bolus injection 8 min<br />

before the bleeding induction. Blood samples were collected 3 min before and<br />

30 min after the incision and plasma was prepared. TG in plasma was assayed<br />

by means of the calibrated automated thrombography with the thrombinoscope<br />

software. Plasma sample, 5 pM tissue factor (TF) and 4 μM phospholipids were<br />

mixed, and the reaction was initiated by addition of 16.7 mM CaCl2 and 417 μM<br />

of a fluorogenic substrate. Lag-time of TG and the maximum concentration of<br />

thrombin (peak) were analyzed. Prothrombin time (PT) was also measured.<br />

Results: DU-176b significantly prolonged bleeding time and PT at a supratherapeutic<br />

dose, and suppressed TG (i.e. prolongation of lag-time and decrease<br />

in peak thrombin concentration). Recombinant FVIIa (0.3, 1 and 3 mg/kg, i.v.)<br />

reversed DU-176b-induced prolongation of bleeding time in a dose dependent<br />

manner. Significant shortening of bleeding time was observed at 1 and 3 mg/kg.<br />

Lag-time of TG and PT were completely reversed to control levels at 0.3 mg/kg,<br />

the dose which did not significantly affect bleeding time. Peak thrombin concentration<br />

of TG was dose dependently increased toward control level by rFVIIa. The<br />

dose response relationship of rFVIIa for increase in peak thrombin concentration<br />

corresponded well with that for suppression of bleeding time.<br />

Conclusion: The present study suggests that the peak concentration of TG is a<br />

possible marker to monitor the haemostatic action of rFVIIa in case of accidental<br />

haemorrhage by overdoses of direct FXa inhibitors.<br />

P2075 The reversible oral P2Y12 antagonist AZD6140<br />

inhibits ADP-induced vascular smooth muscle<br />

contractions in mouse and man<br />

D. Erlinge, C. Hogberg, H. Svensson, A. Eyjolfsson, R. Gustafsson.<br />

Lund University Hospital, Cardiology, Lund, Sweden<br />

AZD6140, the first reversible oral P2Y12 antagonist, is currently in a Phase 3<br />

clinical trial (PLATO) for acute coronary syndromes (ACS). P2Y12 receptors are<br />

Antithrombotic agent / Development of new start technology 331<br />

distributed on vascular smooth muscle cells and mediate a contractile function<br />

after ADP stimulation, which may contribute to local vasospasm seen in patients<br />

with ACS or hypertension (Wihlborg et al., ATVB, 2004). We investigated whether<br />

AZD6140, compared to clopidogrel (CLOP), could inhibit ADP-mediated arterial<br />

contractions. Mice were treated with CLOP 50 mg/kg 24h and 2h before the experiment<br />

was begun. Thoracic parts of aorta were used from both CLOP (n=5)<br />

and untreated (n=4) mice. Vessels were dissected free from connective tissue and<br />

denuded. Ring segments were mounted into temperature-controlled tissue baths<br />

containing physiological Krebs buffer. The segments were precontracted with a<br />

submaximal dose of norepinephrine and AZD6140 1 μM was added 20 min before<br />

contraction was stimulated by the stable ADP analog 2-MeSADP. CLOP treatment<br />

per os did not inhibit 2-MeSADP–induced contractions in mice. However,<br />

AZD6140 inhibited 2-MeSADP contraction both in the mice not treated with systemic<br />

CLOP, from 59% to 33% (% of maximal contraction induced by 60 mM K+,<br />

p=0.015), and in the systemic CLOP-treated mice, from 64% to 32% (p=0.002).<br />

AZD6140 also inhibited 2-MeSADP-induced contractions in both human left internal<br />

mammary arteries (52±10% to 29±7%, p < 0.05) and human resistance<br />

arteries (12±3% to 2±1%, p < 0.01), obtained during thoracic surgery.<br />

These data demonstrate that AZD6140 may have an effect on large and small<br />

arteries by blocking the contractile effect of ADP via P2Y12 receptors. These<br />

effects could be beneficial in the prevention of local vasospasm and possibly in<br />

more generalized conditions such as hypertension.<br />

DEVELOPMENT OF NEW START TECHNOLOGY<br />

P2076 Comparison of paclitaxel coated PACCOCATH and<br />

DIOR drug eluting balloon catheters in the porcine<br />

coronary restenosis model<br />

B. Cremers1 , M. Biedermann2 , D. Mahnkopf3 , M. Boehm1 ,<br />

B. Scheller1 . 1Universitaetsklinikum des Saarlandes, Klinik fuer<br />

Innere Medizin III, Homburg, Germany; 2Charite, Campus Mitte, Institut fuer<br />

Radiologie, Berlin, Germany; 3IMTM GmbH, Rottmersleben, Germany<br />

Background: Paclitaxel-coated drug eluting balloon (DEB) catheters based on<br />

the PACCOCATH matrix technology have shown surprising effects in the treatment<br />

and prevention of restenosis in the porcine coronary overstretch model<br />

and recently also in clinical trials. The DIOR balloon is a recently introduced<br />

paclitaxel-coated PTCA catheter. However, no experimental and clinical data regarding<br />

safety and efficacy have been published yet. The aim of the present study<br />

was to compare the safety and efficacy of PACCOCATH and DIOR DEB in<br />

respect of the inhibition of neointimal proliferation in the porcine coronary overstretch<br />

model.<br />

Methods: Twenty-eight stainless steel stents (diameters, 3.0 and 3.5 mm; length,<br />

18 mm) were implanted in LAD and Cx of 14 domestic pigs either with PAC-<br />

COCATH (n=8) or DIOR (n=9) DEB. Uncoated conventional PTCA catheters<br />

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332 Development of new start technology<br />

served as control (n=11). After 28 days, quantitative angiography and histomorphometry<br />

of the stented arteries was performed.<br />

Results: Paclitaxel coated DEB based on the PACCOCATH matrix technology<br />

led to a highly significant (p


flow, and


334 Development of new start technology / Clinical issues after heart transplantation<br />

high-pressure postdilatation with a short, bigger balloon in both groups. Dual<br />

antiplatelet treatment was administered for 30 days in both groups. An inhospital<br />

and 30-day follow-up rates of MACEs (death, myocardial infarction, reintervention<br />

and heart failure) were assessed in both groups.<br />

Results: Baseline demographic, angiographic and procedural characteristics<br />

were well balanced in both groups. All procedures have been performed without<br />

complication in both groups. There were 2 in-hospital deaths (one cardiogenic<br />

shock and one stroke) in the Genous group and 1 in-hospital death ("coma vigile"<br />

after prolonged cardio-pulmonary resuscitation) in the chromium-cobalt group<br />

(p=NS). Furthermore, there was not difference regarding in-hospital heart failure<br />

(12% versus 10%; p=NS) or ejection fraction (55% versus 55%; p=NS). There<br />

was not stent thrombosis neither in the Genous nor in the chromium-cobalt group.<br />

The rate of MACEs at 30-day was comparable in both groups.<br />

Conclusion: The use of EPC capture stent for treatment of STEMI is feasible and<br />

safe. Furthermore, immediate and 30-day outcome is comparable to chromiumcobalt<br />

stents.<br />

CLINICAL ISSUES AFTER HEART TRANSPLANTATION<br />

P2087 Predictors of mortality and major events in heart<br />

transplant recipients treated by bare metal or drug<br />

elting stents for transplant vasculopathy<br />

F. Beygui1 , S. Varnous2 , F. Fernandez2 , G. Montalescot2 ,<br />

P. Leprince2 , C. Aubailly2 ,A.Pavie2 ,C.LeFeuvre1 , J.P. Metzger2 ,<br />

I. Gandjbakhch2 . 1Aphp, Pitie-Salpetriere University Hospital, Cardiology Dept<br />

& INSERM U856, Paris, France; 2Aphp, pitie-Salpetriere university hospital,<br />

Cardiac surgery, Paris, France<br />

Purpose: To assess the correlates of mortality and major acute coronary events<br />

in patients treated by coronary stents for transplant vasculopathy.<br />

Methods: From <strong>September</strong> 1996 to December 2006, 94 consecutive patients<br />

underwent a first coronary stenting on 105 lesions. On routine basis, all transplant<br />

recipients received drug eluting stents (DES, n=55) from January 2002, while<br />

all received bare metal stents (BMS, n=50) prior to this date. The patients were<br />

followed-up for a mean time of 3.4 years. Multivarible cox analysis, including donor<br />

and recipient parameters was performed to identify correlates of death and major<br />

events.<br />

Results: The mean time between transplantation and stenting was 8.7 years.<br />

During the follow-up 54 major events -33 deaths, 2 myocardial infarctions, 34<br />

coronary revsacularizations of which 17 target lesion revascularization- were reported.<br />

Univariable correlates of death were absence of aspirin treatment, left<br />

ventricular ejection fraction (LVEF), CMV infection, hypertension and transplantation<br />

to PCI time. Univariable correlates of major events were similar except for the<br />

aspirin use.<br />

Multivariable analysis identified LVEF (HR 0.63, p=0.0005), hypertension (HR<br />

4.48, p=0.00004) and transplantation to PCI time (HR 1.1 per year, p=0.04) and,<br />

LVEF (HR 0.80, p=0.04) and hypertension (HR 2.71, p=0.005) as independent<br />

correlates of death and major events respectively. Compared to BMS the use of<br />

DES was associated with lower rates of target lesion revascularization (6.3% vs<br />

30.4% p=0.002), but total revascularization rates were statistically comparable<br />

(43.5% vs 29.2%).<br />

Conclusions: Rates of major events remain high after coronary artery stenting in<br />

heart transplant recipients. The dramatic reduction in rates of target lesion revascularization<br />

by DES contrasts with high rates of remote lesion revascularization<br />

and absence of effect on outcome. The preservation of LVEF and hypertension<br />

control, the major correlates of outcome, may be considered as specific targets<br />

of the management of such patients.<br />

P2088 Coronary flow reserve by contrast-enhanced<br />

transthoracic echocardiography predicts maximal<br />

epicardial intimal thickening in transplant coronary<br />

artery disease<br />

E. Osto1 , F. Tona1 , G. Tarantini1 , M. Napodano1 ,R.Montisci2 ,<br />

A. Gambino1 , A. Ramondo1 , G. Gerosa1 , A.L.P. Caforio1 ,<br />

S. Iliceto1 . 1University of Padova, Cardiology, Padova, Italy; 2University of<br />

Cagliari, Cardiology, Cagliari, Italy<br />

Cardiac allograft vasculopathy (CAV) is the main limiting factor of long-term survival<br />

after heart transplantation (HT). Several noninvasive tests have proven<br />

unsatisfactory in CAV diagnosis. We assessed the role of contrast-enhanced<br />

transthoracic echocardiography (CE-TTE) during adenosine infusion, a new noninvasive<br />

method for determination of coronary flow reserve (CFR).<br />

Methods: CAV was defined as maximal intimal thickness (MIT) assessed by intravascular<br />

ultrasound (IVUS) ≥0.5 mm. CFR was assessed in the left anterior<br />

descending coronary artery by CE-TTE in 12 HT recipients (11 male, aged 55±7<br />

yearsatHT),at6±4 years post-HT. CFR measurements were taken blindly within<br />

24 hours from diagnostic IVUS.<br />

Results: CAV was diagnosed in 5 patients (group A), 8 had normal coronaries<br />

(group B). The median MIT was 0.6 mm (range 0-1.8). MIT was higher in group<br />

A(1.3±0.3 mm vs 0.2±0.1 mm, p


(PCWP) were recorded. In 16 patients, an initial examination was performed 1<br />

month and a follow-up measurement 1 year after heart transplantation (HTX).<br />

Results: Simple regression analysis revealed IMR to directly correlate with<br />

PCWP (r=0.34; p12<br />

mmHg, pulmonary vascular resistance >4 UW]; donor (female gender, age>30<br />

years) and procedural (ischemic time > 240 minutes). Multivariate analysis identified<br />

6 independent predictors shown in Table 1.<br />

Table 1<br />

Prevalence Relative risk CI (95%) p<br />

Recipient age > 60 years 20% 1.99 1.04-3.8 0.037<br />

Recipent diabetes mellitus 12% 2.26 1.08-4.69 0.029<br />

Recipent inotrope therapy 39% 1.94 1.06-3.53 0.029<br />

Recipent RAP > 10 mmHg 42% 2.53 1.30-4.80 0.006<br />

Recipient PSAP > 50 mmHg 37% 1.88 1.01-3.51 0.045<br />

Donor female gender 24% 2.15 1.16-3.96 0.014<br />

Conclusion: Univariate analysis showed multiple recipient, donor and procedural<br />

variables associated to the incidence of PGD, what is consistent with a multifactorial<br />

origin of this syndrome. Multivariate analysis identified 6 independent<br />

predictors with narrow confidence intervals that could be useful for prediction of<br />

the risk of PGD. We hypothesize that these results could help to design strategies<br />

for prevention or early therapy of PGD whenever risk for its development is high.<br />

Further studies on this issue are warranted.<br />

Clinical issues after heart transplantation / Factors influencing outcome after stent placement 335<br />

FACTORS INFLUENCING OUTCOME AFTER STENT<br />

PLACEMENT<br />

P2092 Early endothelialization and neointimal proliferation<br />

in pigs up to 6 months after implantation of BMS by<br />

paclitaxel-coated balloon catheters, Cypher- and<br />

Taxus-stents<br />

B. Cremers1 , M. Braeutigam2 , N. Kaufels3 , D. Mahnkopf4 ,<br />

U. Speck3 , M. Boehm1 , B. Scheller1 . 1Universitaetsklinikum des Saarlandes,<br />

Klinik fuer Innere Medizin III, Homburg, Germany; 2Bayer Schering Pharma<br />

AG, Berlin, Germany; 3Charite, Campus Mitte, Institut fuer Radiologie, Berlin,<br />

Germany; 4IMTM GmbH, Rottmersleben, Germany<br />

Background: Concerns have been raised that sustained drug release by DES<br />

by delaying endothelialization may be associated with an increased incidence of<br />

late thrombotic complications. In contrast, drug-eluting balloon catheters (DEB)<br />

allow for rapid dilution and elimination of antiproliferative active substances after<br />

the short inflation time of the balloon. This study investigated for the first time<br />

endothelialization and neointimal proliferation in the porcine coronary overstretch<br />

model after implan-tation of DEB in combination with bare metal stents (BMS)<br />

compared to Cypher- and Taxus-DES.<br />

Methods: 196 stents were implanted in LAD and Cx of 98 domestic pigs: Control<br />

(BMS, implanted with uncoated PTCA catheter, n=46); DEB+BMS (BMS, implanted<br />

with paclitaxel-coated (3 μg/mm 2 ) PTCA catheter, n=50); Taxus stent<br />

(n=50); Cypher stent (n=50). After 3 and 7 days, as well as after 1, 3 and 6<br />

months quantitative angiography and histomorphometry of the stented arteries<br />

was performed.<br />

Results: DEB+BMS led to early endothelialization with no difference compared<br />

to control. However, Cypher stents showed delayed healing. After one month,<br />

DEB+BMS resulted in a highly significant reduction in neointimal proliferation<br />

compared to control and Taxus stents. At 3 and 6 months follow-up, both DES<br />

showed accelerated neointimal proliferation. In contrast, this effect was considerably<br />

extenuated in coronary arteries, treated with DEB+BMS.<br />

Conclusion: Coronary angioplasty with DEB+BMS resulted in early endothelialization,<br />

effective inhibition of neointimal proliferation and no adverse effects at<br />

later points in time in the porcine coronary overstretch model. This new concept<br />

of local drug delivery could avoid suspected risks of DES in treatment and prevention<br />

of restenosis.<br />

P2093 Risk score for survival after left main percutaneous<br />

coronary intervention<br />

J.A. Gomez Hospital 1 , A. Cequier1 , J. Rondan2 , I. Lozano2 ,<br />

J. Gomez-Lara1 , A. Carro2 , L.M. Teruel Gila 1 , P. Avanzas2 ,<br />

E. Esplugas1 ,C.Moris2 . 1IDIBELL. Hospital Universitari Bellvitge,<br />

Interventional Cardiology Dept., Barcelona, Spain; 2Hospital Central Asturias,<br />

Cardiology, Oviedo, Spain<br />

Background: Left main (LM) percutaneous coronary intervention (PCI) is more<br />

frequently performed due to an increase in revascularization indications, mainly<br />

in patients (pt) with surgical high risk.<br />

Objectives: A series of consecutive pt with significant stenosis in the LM treated<br />

with PCI with stent implantation were included. Pt in cardiogenic shock or treated<br />

during primary angioplasty were excluded. To identify predictive factors associated<br />

to the outcome, a series of clinical, angiographic and procedural variables<br />

were collected. The primary end point was cardiac mortality. The risk score was<br />

derived by selection of the independent prognostic variables identified in the multivariate<br />

logistic regression analysis. To develop the score, the OR values were<br />

assigned to each independent variable identified in the multivariate analysis.<br />

Results: Two hundred seventy seven consecutive pt were included. Mean age<br />

was 71±10 years, 70% male and 35% diabetics. Creatinine Clearance (CrCl)<br />

< 60 ml/min was observed in 45%, previous MI in 40% and previous CABG in<br />

28%. A left ventricular ejection fraction (LVEF) < 45% was documented in 30.7%.<br />

LM bifurcation was involved in 68%. The in-hospital mortality was 4.3%. After<br />

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336 Factors influencing outcome after stent placement<br />

a follow-up of 46±8 months, 53 pt died (19.1%) and 19 pt required additional<br />

additional revascularization procedures (CABG 1%, and re-PCI 6.5%).The independent<br />

predictive factors associated with long-term mortality were expressed in<br />

the table.<br />

The following risk score assignment was developed: LVEF < 45, 3 points; ClCr<br />

< 60, 3 points and Bare Metal Use, 2 points. A progressive increase in mortality<br />

was observed when the risk score increases: Score 0-1, mortality 6.3%; Score<br />

2-4, mortality 24.2% and Score 5-8, mortality 50.49%.<br />

Predictive Factors of Mortality<br />

OR CI 95%<br />

LVEF< 45% 2.8 (1.7-4.5)<br />

ClCr < 60 ml/min 2.5 (1.2-4.9)<br />

Bare Metal Stent 2.3 (1.1-3.2)<br />

Conclusion: In pt with LM stenosis with a PCI indication, the long term prognosis<br />

can be categorized with a simple risk score.<br />

P2094 The acute and three-year clinical outcome according<br />

to gender after sirolimus-eluting stent in the arterial<br />

revascularization therapy study (ARTS) II;<br />

comparison with ARTS I patients<br />

V. Voudris 1 , F.-W. Amann2 , D.V. Cokkinos1 , J. Daemen3 ,<br />

M.-C. Morice4 ,P.Rioux5 , S. Vaina1 ,M.Pieters6 ,H.-P.Stoll6 ,P.-W.Serruys3 on behalf of ARTS II investigators. 1Athens, Greece; 2Zurich, Switzerland;<br />

3 4 5 6 Rotterdam, Netherlands; Massy, France; Nimes, France; Waterloo, Belgium<br />

Background: Compared to men (M), women (W) undergoing percutaneous coronary<br />

interventions (PCI) have a higher rate of in-hospital complications. To determine<br />

whether W have an unfavorable long-term outcome after PCI or surgical<br />

revascularization (CABG) we assessed patients (pts) undergoing revascularization<br />

within the Arterial Revascularization Therapies Studies (ARTS) I and II.<br />

Methods: ARTSI was a randomized multicenter trial of 1205 pts with multivessel<br />

disease (MVD), comparing surgery (ARTSI-CABG, n=605, W=24%) with<br />

bare metal stenting (ARTSI-PCI, n=600, W=23%). ARTSII is a multicenter, nonrandomized<br />

open-label trial of 607 pts (W=23%) with MVD treated with sirolimuseluting<br />

stent (SES). Primary aim was to compare the effectiveness of SES with<br />

ARTSI-CABG (measured as freedom from major cardiac and cerebrovascular<br />

events (MACCE) at 1 year. The clinical presentation, in-hospital complications,<br />

and freedom from MACCE at 1 and 3 year were assessed.<br />

Results: W in ARTSII had a statistically significant higher prevalence of diabetes,<br />

hypertension and 3-vessel disease, compared to ARTSI-PCI and ARTSI-CABG;<br />

the mean number of significant lesions was 3.4 in ARTSII vs. 2.7 in ARTSI-PCI<br />

and 2.7 in ARTSI-CABG (both p


Methods: A prospective, consecutive enrollment study was conducted to gather<br />

demographic, procedural, and discharge data of patients being treated with<br />

a novel "plug-and-play" pCPB system. Patient’s diagnostic codes, procedural<br />

codes, hemodynamic data, and survival rate were analyzed. Femoral arterial and<br />

venous cannulation (15-21F) was used to connect the patient’s circulation to the<br />

device which automatically eliminates air. Up to 6 l/min flow can be provided without<br />

any specially trained personnel.<br />

Results: We included 14 patients with severe coronary artery disease who underwent<br />

high-risk PCI in 2 centers (mean age 79±9 years) under pCPB. 12 patients<br />

(86%) had a history of NYHA Class III or IV, left ventricular ejection fraction<br />

was 44% (± 19%), 9 patients (64%) had an AMI, and 8 patients (57%) were in<br />

cardiogenic shock. 5 patients (36%) were scheduled for elective high-risk PCI for<br />

left main disease. 2 patients also underwent aortic valvuoplasty. Cardiac resuscitation<br />

was unsuccessful in 1 patient prior to receiving PCI. Mean pCPB time<br />

was 187 minutes (range 20-918 minutes). Mean arterial blood pressure was preserved<br />

throughout the intervention (76±25 mmHg before, 79±18 mmHg after 30<br />

minutes, and 77±21 mmHg at procedure end). 13 patients survived, 12 patients<br />

were either discharged or survived seven days after treatment. One cardiogenic<br />

shock patient died during intensive care stay after being successfully treated in<br />

the cath lab. No relevant bleeding complications were reported.<br />

Conclusion: In this early experience, pCPB provided a safe and effective bridge<br />

for interventional therapy and improved survival for these high risk patients. Further<br />

studies should evaluate the appropriate indications and algorithms for use of<br />

pCPB in the catheter laboratory.<br />

P2098 Optical coherence tomographic analysis of<br />

neointimal coverage of sirolimus-eluting stent in<br />

pateints with acute coronary syndrome<br />

M. Habara, M. Terashima, K. Nasu, M. Kimura, Y. Kinoshita,<br />

E. Tsuchikane, T. Matsubara, H. Asakura, O. Kato, T. Suzuki.<br />

Toyohashi <strong>Heart</strong> Center, Cardiovascular Medicine, Toyohashi, Japan<br />

Back ground: Drug eluting stent in lesions with acute coronary syndrome (ACS)<br />

is one of the major predictors of late stent thrombosis (LST). Whereas, delayed<br />

arterial healing should be responsible for LST. Optical coherence tomography<br />

(OCT) is a high-resolution (approximately10μm) imaging technique. The aim of<br />

this study was to evaluate arterial healing following implantation of Sirolimus-<br />

Eluting-Stent (SES) in ACS lesion, compared to non-ACS lesion.<br />

Method: Motorized OCT pullback (1mm/s) was performed in 10 ACS patients<br />

with 14 SESs and in 12 non-ACS patients with 15 SESs. Neointimal coverage of<br />

stent struts and stent malapposition were evaluated in every observed strut.<br />

Result: In total, 3677 struts analyzed (1728 with ACS and 1949 with non-ACS).<br />

Uncovered struts and malapposed struts were observed more frequently in SES<br />

in ACS patients than in non-ACS patients (22.4% vs 7.1%, p


338 Factors influencing outcome after stent placement<br />

(12.1% vs 17.3%, p=0.2), but a significantly lower target bifurcation revascularization<br />

(TBR) (5.0% vs 12.7%, p=0.003). MC group compared to T-prov 1-stent<br />

group had a similar main branch restenosis (6.4% vs 13.6%, p=0.053) but a significantly<br />

lower side branch restenosis (5.7% vs 18.3%, p=0.002).<br />

Conclusions: Both techniques of bifurcation treatment achieved high procedural<br />

success with low complication rates and similar MACE mid-term outcome. However,<br />

the MC technique yields a lower TBR and restenosis rate at side branch.<br />

These results may confirm the advantage of using two stents technique to give<br />

complete coverage of the ostium of side branches.<br />

P2103 Histological evidence of impaired vascular healing of<br />

restenotic sirolimus-eluting coronary stents: an<br />

antemortem clinical study<br />

H. Jneid, I. Palacios, A.O. Maree, I. Cruz-Gonzalez, R. Cubeddu,<br />

N. Silva, S. Vigo, E. Pomerantsev, S. Houser. MGH-Harvard Medical<br />

School, Cardiology, Boston, United States of America<br />

Purpose: We describe the antemortem histology of drug-eluting stent (DES)<br />

restenosis in patients undergoing directional coronary atherectomy (DCA).<br />

Methods: DCA was performed in 10 patients presenting with clinical restenosis<br />

of sirolimus-eluting stents. Specimens were fixed, paraffin-embedded, cut in<br />

5μm sections, stained and examined with light microscopy. Histological prevalence<br />

of morphologic features was graded as 0 (absent), trace to 1+ (50%). Morphometric analysis was used to<br />

quantify areas of α-smooth muscle actin (SMA)-positive cells and macrophages.<br />

Results: The median time from DES implantation to DCA was 271 days. Nine<br />

specimens were characterized as fibrous, and one contained a lipid pool. The<br />

neointima consisted of mature collagen (2.1+) and acidic proteoglycan mucosubstance<br />

(2.5+), while elastic tissue was scarce (0.6+). Fibrin deposition was noted<br />

in 8 of the 10 specimens (1.3+). No endothelial cells were identified by CD31,<br />

CD34 and Factor VIII stains in any of the DES specimens. T cells ranged from<br />

0 to 1+, and a trace of B cells was identified in 1 specimen. Macrophage staining<br />

accounted for 0.2-13.6% of the total tissue area. SMA-positive spindle cells<br />

accounted for 1.1-65.7% of the total tissue. Ki-67 (0.1+) and PCNA (0.6+) demonstrated<br />

a paucity of active cellular proliferation.<br />

Endothelium of a BMS (A-B) vs. DES (C-E).<br />

Conclusions: The persistence of fibrin deposition and absence of endothelial<br />

staining in neointimal tissue confirm previous reports showing impaired vascular<br />

healing following DES implantation.<br />

P2104 Impact of incomplete stent apposition on long-term<br />

clinical outcome after drug-eluting stent implantation:<br />

an intravascular ultrasound study<br />

P. Eshtehardi1 , S. Cook2 , S. Wandel1 , L. Raeber1 , P. Wenaweser1 ,<br />

R. Corti 1 ,G.Suetsch1 ,F.Eberli1 , P. Jueni1 ,S.Windecker1 .<br />

1 2 Bern, Switzerland; Swiss Cardiovascular Center Bern University H, Invasive<br />

Cardiology, Bern, Switzerland<br />

Background: Late acquired incomplete stent apposition (ISA) is more common<br />

after DES than BMS. However, the impact of ISA on clinical outcome after DES<br />

implantation is not well established. The aim of thepresent study was therefore to<br />

compare long-term clinical outcome in patientswith and without ISA as assessed<br />

by intravascular ultrasound (IVUS) 8 months after implantation of sirolimus-eluting<br />

(SES) or paclitaxel-eluting stents (PES).<br />

Methods and Results: A total of 196 patients underwent IVUS 8 months after<br />

implantation ofDES (SES: 92 patients, PES: 104 patients) and were followed<br />

prospectively for 3 years. IVUS imaging was performed using motorized pullback<br />

(0.5 mm/s) and images were analyzed offline by blinded outcome assessors. ISA<br />

was defined as 1 or more stent struts separated from the vessel wall with evidence<br />

of blood speckles behind the strut. ISA was present in 37 pts (19%) at 8-month<br />

with a higher rate for SES than PES treated pts (14% vs. 6% p=0.001). Baseline<br />

clinical and procedural characteristics were similar for both groups except for<br />

stent length, which was longer in ISA pts (22.1±11.6mm vs. 18.0±8.7,p=0.01).<br />

Clinical outcome at 3 years is summarized in the table below. Therewere no significant<br />

differences regarding death, MI, or repeat revascularization. Late definite<br />

stent thrombosis was encountered in 3 pts (8.1%) with ISA and no patient without<br />

ISA (0%, p


over paclitaxel-eluting stent (PES) was observed with commercially available<br />

stent diameter (≤3.5mm). However whether its efficacy will be maintained in<br />

the treatment of large coronary vessels (≥4.0mm) using overdilatation has not<br />

to been well studied.<br />

Method: We identified 186 consecutive patients who underwent percutaneous<br />

coronary interventions using SESs or PESs and completed follow-up intravascular<br />

ultrasound (IVUS). Patients were divided into 4 groups based on stent diameters<br />

(2.75, 3.0, 3.5, and 4.0/3.5mmSES overdilated with 4.0mm adjuvant balloon<br />

was designated with SES4.0mm). IVUS parameters, including EEM area (EEM),<br />

luminal area (LA), stent area (SA), neointimal hyperplasia area (NIHA) and calculated<br />

percentage of NIH (NIH%=NIHA/MSAx100), were measured at minimal LA<br />

site and compared between SES vs. PES.<br />

Results: 186 patients (92 SES, 94 PES), including nine SES4.0mm and nine<br />

PES4.0mm were enrolled in this study. Baseline clinical and angiographic characteristics<br />

were similar between SES vs. PES in all groups. At 9 months followup,<br />

LA was larger (5.79±1.63mm 2 vs. 4.97±1.89mm 2 , P=0.003) and NIHA was<br />

smaller (0.61±1.18mm 2 vs. 2.31±1.85mm 2 ,P


340 Factors influencing outcome after stent placement / Clinical assessment of new stent technology<br />

on the procedure type, but not on the access site (P = NS). The decline of ORE<br />

was more distinctive in CA as compared to PCI.<br />

Conclusion: Deployment of FPS leads to a markedly reduced radiation exposure<br />

of both operators and patients independent from the access site. Therefore<br />

advantages of transradial approach can be used without increased radiation exposure<br />

P2111 Intravascular ultrasound findings and captured<br />

materials by filtraptm distal protection device at<br />

percutaneous coronary intervention<br />

T. Lee 1 ,T.Kakuta 1 , T. Yonetsu 1 , K. Handa 1 , A. Suzuki 1 ,Y.Iesaka 1 ,<br />

H. Fujiwara 1 ,M.Isobe 2 . 1 Tsuchiura Kyodo Hospital, Division of<br />

Cardiology, Cardiovascular Center, Tsuchiura-Shi, Japan; 2 Tokyo Medical and<br />

Dental University, Division of Cardiology, Tokyo, Japan<br />

Background and Purpose: A new filter-based distal protection device (FiltrapTM)<br />

was investigated with respect to the relation between decreased plaque<br />

volume by PCI and angiographic outcome.<br />

Methods: FiltrapTM was used in 50 consecutive patients (AMI: 21, UAP: 13, SAP:<br />

16). Aspiration thrombectomy was performed before FiltrapTM insertion in ACS<br />

at the operator’s discretion. All patients underwent pre- and post-PCI IVUS and<br />

qualitative and quantitative analyses were performed at the lesion segment. The<br />

difference between pre- and post-PCI plaque volume was defined as the index of<br />

the decrease in plaque volume (�PV). Amount of debris captured by FiltrapTM<br />

was visually inspected first and graded into one of two categories (group E: debris<br />

easily detected, group D: difficult to detected visually). FiltrapTM no reflow (FNR)<br />

was defined as a phenomenon showing final TIMI 3 flow after PCI with TIMI 0-2<br />

flow before FiltrapTM retrieval.<br />

Results: In all cases, FiltrapTM was successfully inserted. Echo signal attenuation<br />

(EA) by IVUS was observed in 35 (70%) patients, and FNR was observed<br />

in 21 (42%) patients. In EA group, �PV was significantly greater (EA: 51.6±17.6<br />

vs. non-EA: 33.0±13.3mm 3 ,p


which proved to be safe and effective in proximal simple lesions resulting in significantly<br />

reduced procedural duration and lower contrast consumption compared<br />

to conventional PCI.<br />

P2115 Efficacy of very short-term exposure to a<br />

paclitaxel-coated balloon in restenosis inhibition<br />

B. Cremers1 , M. Kuehler2 , N. Kaufels3 , D. Mahnkopf4 , U. Speck3 ,<br />

M. Boehm1 ,B.Scheller1 . 1Universitaetsklinikum des Saarlandes,<br />

Innere Medizin III, Homburg, Germany; 2B. Braun Melsungen<br />

AG, Vascular Systems, Berlin, Germany; 3Charite, Campus Mitte, Institut fuer<br />

Radiologie, Berlin, Germany; 4IMTM GmbH, Rottmersleben, Germany<br />

Background: Paclitaxel-coated SeQuent Please balloon catheters based<br />

on the PACCOCATH technology have shown promising effects in inhibiting<br />

restenosis in the porcine coronary overstretch model and recently also in clinical<br />

trials. Nevertheless, little is known about the risk of overdose due to overlapping<br />

balloons and the required duration of contact with the vessel wall. The aim of the<br />

present study was to evaluate the influence of the shortest possible inflation time<br />

and higher doses than those tested in clinical trials.<br />

Methods and results: Fifty-six stainless steel stents (diameters, 3.0 and 3.5 mm;<br />

length, 19 mm) were implanted in the left anterior descending and circumflex<br />

coronary arteries of 28 domestic pigs. Both conventional uncoated and paclitaxelcoated<br />

DEB (5 μg/mm 2 balloon surface) PTCA balloon catheters were used. The<br />

animals were randomized to 5 different treatments with a range of short (10 seconds<br />

inflation using 1 DEB) to extended (2x60 seconds inflation using 2 DEB)<br />

intima contact time; uncoated balloons (60 seconds inflation time) were used<br />

as control. After 28 days, quantitative angiography and histomorphometry of the<br />

stented arteries was performed. Paclitaxel balloon coating led to a marked reduction<br />

of parameters characterizing in-stent stenosis (reduction of neointimal area<br />

up to 61%) independent of inflation time or dose. Despite the marked reduction of<br />

neointimal proliferation, endothelialization of stent struts was present in all samples.<br />

Conclusion: Paclitaxel-coated SeQuent Please balloon catheters were found<br />

to effectively reduce neointimal proliferation regardless of inflation time and dose<br />

within the tested range. No adverse reactions were seen as dose was increased<br />

to more than 3 times the clinically tested dose.<br />

P2116 Magnetic Navigation significantly reduces the<br />

contrast needed to cross a lesion<br />

S. Ramcharitar, R.J. Van Geuns, M.S. Patterson, M. Van Der<br />

Ent, R.T. Van Domburg, P.W. Serruys. Thoraxcenter, Rotterdam,<br />

Netherlands<br />

Magnetic navigation is an innovative technology that can accurately control the<br />

positioning of a guidewire or a catheter in vivo. We conducted the first randomised<br />

comparison of the performance of the Magnetic Navigation System (MNS) versus<br />

conventional wire technique in native coronary arteries. In 111 consecutive<br />

patients admitted with stable and unstable angina, 151 lesions were randomised<br />

to cross the culprit lesion twice, either firstly using a conventional or a magnetically<br />

enabled guidewire. The amount of contrast (ml) used was measured after<br />

first placing a guidewire at the tip of a guide catheter engaged at the ostium and<br />

following the wire passage distal to the lesion. The guidewire was then withdrawn<br />

and the comparative guidewire was then used to coincide with the start and end<br />

position of the first wire. The crossing with the MNS was achieved using a virtual<br />

3-dimensional roadmap superimposed on the live fluoroscopic image. This map<br />

was created from 2 angiographic images using a dedicated software. Lesions<br />

were classified according to the AHA/ACC criteria and comprised of 15 Type A<br />

(10%), 30 Type B1 (20%), 95 Type B2 (63%) and 11 Type C (7%). The operators<br />

had unrestricted access to the choice of either magnetic or conventional<br />

guidewires. All were interventional cardiologists who were also trained with the<br />

MNS. Student T-test was used to determine if there were significant differences<br />

between the parameters assessed using both techniques.<br />

The results showed that in crossing type A lesions there was no significant differ-<br />

Clinical assessment of new stent technology 341<br />

ence in contrast usage (ml) between the magnetic or conventional wires (1.5±1.8<br />

vs. 1.9±2.3 p = 0.59 respectively). However, as lesion complexity increased significantly<br />

less contrast (ml) was needed when the MNS was employed:- Type B1<br />

(2.5±3.2 vs. 4.0±2.6 p = 0.01); Type B2 (2.3±3.8 vs. 4.9±4.9 p < 0.001); Type C<br />

(2.9±3.4 vs. 5.9±4.9 p = 0.03). In addition, no contrast was required when crossing<br />

59 lesions (39%) with the MNS in comparison to 21 lesions (14%) using the<br />

the conventional wire approach<br />

Overall the MNS gave a small but significant reduction in contrast usage (2.3±3.5<br />

vs. 4.5±4.4 p < 0.001) relative to the conventional wire technique. Moreover by<br />

superimposing a virtual roadmap of the vessel on the live fluoroscopic image 39%<br />

of the lesions were crossed without the need for any contrast.<br />

P2117 Implantation of zotarolimus-eluting stent could not be<br />

associated with significant long-term coronary<br />

endothelial dysfunction: the prospective randomized<br />

study between ZES and SES implantation<br />

D.I. Shin, K.B. Seung, P.J. Kim, M.J. Kim, D.S. Jeon, M.Y. Lee. The<br />

Catholic University of Korea, Internal Medicine, Seoul, Korea, Republic of<br />

Purpose: Sirolimus-eluting stent (SES) has been associated with endothelial<br />

dysfunction in recent studies. However, the endothelial function after zotarolimuseluting<br />

stent (ZES) implantation remains largely unknown. We assessed coronary<br />

endothelial function 6 months after ZES implantation compared with SES implantation.<br />

Methods: Thirty patients who had one stent implantation for single de novo lesion<br />

in left anterior descending artery were enrolled to this prospective randomized<br />

study. They were classified into two groups according to the type of the<br />

stents; 15 patients of SES and 15 patients of ZES group. We assessed endothelial<br />

function only in patients who showed no in-stent restenosis on 6 month-follow<br />

up angiography. Endothelium-dependent vasomotion was determined by measuring<br />

the change of diameter after selective intracoronary injection of acetylcholine<br />

(Ach, 10-6 mol/L). Endothelium-independent vasomotion was assessed after injection<br />

of 2mg-nitrates. The measuring was done at 5 segments; near proximal<br />

and proximal, distal and far distal, and stented segments by quantitative coronary<br />

angiography. The endothelial dysfunction was defined as abnormal vasoconstriction<br />

of more than 20% in vessel diameter change from the baseline after infusion<br />

of Ach at any measuring points.<br />

Results: The assessment was performed in total 22 patients (10 of ZES, 12 of<br />

SES). The baseline characteristics were all well matched. In stented segments,<br />

no vasomotion was observed in both groups. In distal and far distal segments,<br />

SES group showed significant vasoconstriction by Ach, but ZES group did not<br />

(SES vs ZES: -36.1% vs 0.6% for distal;p=0.002, -34.7% vs 0.5% for far distal;p=0.001).<br />

In proximal portion, no significant difference was seen between two<br />

groups (SES vs ZES: 1.6% vs 2.4% for near proximal;p=0.26, 1.1% vs 0.6% for<br />

proximal;p=0.39). When comparing change of diameter between near proximal<br />

and far distal segments and between proximal and distal segments after Ach injection,<br />

ZES group showed no differences (p=0.19, 0.98) while SES showed significant<br />

decrease of diameter in distal compared to proximal portion (p=0.001,<br />

0.001). The pattern of vasodilatation by nitrates was similar between the two<br />

groups.<br />

Conclusion: The impairment of endothelium-dependent vasodilatation in the<br />

distal portion was observed in SES group but not in ZES group. Endotheliumindependent<br />

vasodilatation was intact in both groups. The results suggest that<br />

the ZES implantation could not be associated with the long-term coronary endothelial<br />

dysfunction, while it was significant after SES implantation.<br />

P2118 Angiographic late loss in the overlapping site of<br />

multiple overlapping cypher sirolimus-eluting stents<br />

Y. Takamiya 1 , Y. Tsuchiya2 , Y. Fukuda1 , T. Kuwano1 ,A.Ike1 ,<br />

D. Yanagi1 , K. Kubota1 , B. Zhang1 ,K.Shirai1 ,K.Saku1 . 1Fukuoka University Hospital, Department of Cardiology, Fukuoka, Japan;<br />

2Fukuoka University Chikushi Hospital, Department of Cardiology, Fukuoka,<br />

Japan<br />

Background: It has been reported that the overlapping Cypher Sirolimus-Eluting<br />

Stents (SESs) are associated with a greater late lumen loss in stent and more<br />

angiographic restenosis. The purpose of this study is to evaluate whether the<br />

overlapped site in overlapping SES would increase neointimal hyperplasia or be<br />

rather decrease it.<br />

Methods: Between October 2004 and November 2007, SESs were implanted<br />

electively in 297 patients with coronary artery disease. We compared sevenmonth<br />

angiographic late loss of the overlapped site in overlapped-stent-treated<br />

patients (overlapping SES group, N=50) to that in single-stent-treated patients<br />

(single SES group, N=247). Patients with either stable or unstable angina were<br />

included but acute myocardial infarction was excluded.<br />

Results: Baseline clinical and angiographic characteristics of the overlapping and<br />

the single SES groups were similar except longer lesion length in the overlapping<br />

SES group. The length of overlapped stent segment by quantitative coronary angiogram<br />

(QCA) was 4.00±1.72mm. There was no significant difference in death<br />

and myocardial infarction between the two groups. Overlapping SES group was<br />

not associated with the increase of binary restenosis (17% vs. 23%, respectively,<br />

P=0.32) and taget lesion revascularization compared with single SES group (10%<br />

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342 Clinical assessment of new stent technology<br />

vs. 12%, respectively, P=0.76). In-stent late lumen loss did not differ significantly<br />

between the two groups (0.10±0.57mm vs. 0.20±0.61mm, respectively, P=0.34).<br />

Furthermore, the overlapped site in overlapping SES group had lower late lumen<br />

loss (0.10±0.47mm).<br />

Conclusions: The overlapped site of the overlapping SES was not associated<br />

with a greater late lumen loss, nor higher in-stent binary restenosis rate compared<br />

to non-overlapped site. The overlapping of SES itself did not increase neointimal<br />

hyperplasia.<br />

P2119 Is systemic inflammation a main determining factor<br />

for neointimal hyperplasia after drug-eluting stent<br />

implantation?<br />

W.C. Kang1 ,T.H.Ahn1 , C.I. Moon1 ,J.S.Kim2 , D. Choi2 ,Y.Jang2 ,<br />

B.K. Kim3 ,S.J.Oh3 , D.W. Jeon3 ,J.Y.Yang3 . 1Gachon University,<br />

Interventional Cardiology, Incheon, Korea, Republic of; 2Yonsei University,<br />

Interventional Cardiology, Seoul, Korea, Republic of; 3NHIC Ilsan Hospital,<br />

Interventional Cardiology, Koyang, Korea, Republic of<br />

Introduction: Inflammation plays a crucial role in determining in-stent restenosis<br />

via neointimal proliferation. Although DES reduce restenosis by inhibition of<br />

neointimal hyperplasia (NIH), paclitaxel-eluting stent (PES) and silorimus-eluting<br />

stent (SES) showed different effect on suppression of NIH in several studies. So<br />

we compared degree of inflammation, as measured by hs-CRP, IL-6 levels and<br />

NIH volume after PES and SES implantation.<br />

Method: We performed PCI with a single DES in 99 stable angina patients (PES,<br />

n=51; SES, n=48). The hs-CRP and IL-6 levels were determined before and at<br />

24, 72 hours, 4 weeks after PCI. Angiography and IVUS were performed at pre,<br />

post PCI and 9 months after PCI.<br />

Results: There was no difference in the clinical and angiographic baseline characteristics<br />

between the two groups. The hs-CRP and IL-6 levels at baseline did<br />

not differ between the two groups. The hs-CRP increased significantly from baselineat24hr(p


Comparison of neointimal growth among BM.<br />

SES also had less NIT, compared to other stents (52.7±35.6μm, 175.5±43.8μm,<br />

212.2±86.8μm, p 80%.<br />

Results: Data were collected prospectively in 38 patients aged 67.2±12.4 yrs,<br />

diabetic 36%, acute coronary syndrome 31%, in whom 60 stents (length 19.6±6.8<br />

mm; diameter 2.92±0.48 mm) were deployed at a mean pressure of 13.6±2.2<br />

atm. Lesion reference diameter was 3.06±0.50 mm.<br />

5 sec 15 sec 25 sec Deflation<br />

Minimal stent diameter (mm) 2.41+0.47 2.54+0.46 2.58+0.47 2.52+0.48<br />

Mean stent diameter (mm) 2.75+0.45 2.84+0.47 2.90+0.47 2.83+0.49<br />

Maximal stent diameter (mm) 3.06+0.48 3.15+0.50 3.19+0.49 3.15+0.54<br />

Optimal stent expansion (%) 58.3 93.3 95.0 88.3<br />

Conclusion: Better stent implantation may be achieved by increasing the duration<br />

of stent deployment. This may influence the risk of stent thrombosis.<br />

P2124 The vascular pro-healing potential of 17beta-estradiol<br />

drug eluting stent: a pre-clinical study<br />

J.F. Tanguay, P. Geoffroy, I. Cloutier. Institut de Cardiologie de<br />

Montreal, Biomedical Science, Universite de Montreal, Montreal,<br />

Canada<br />

Purpose and objectives: First to evaluate the efficacy of stents<br />

coated with two concentrations (300μg and 500μg) of 17-beta estradiol (E2) to<br />

improve vascular healing and reduce restenosis at 24 hours, 14 days and 28 days<br />

after stent implantation. Their safety and efficacy were compared to control bare<br />

metallic (BM) and polymer-only coated stents. Secondly, to evaluate the reendothelialization<br />

process, a scanning electron microscopy (SEM) analysis was performed<br />

at 28 days following the implantation of E2 coated stents (500μg), taxus<br />

or cypher drug eluting stents.<br />

Methods: Stainless steel (BM) stents were spray coated with 300ug or 500ug<br />

of E2 matrixed with the poly (ester-amide) (MVPEA.I.(Ac)) tempo polymer with a<br />

200ug topcoat of polymer only. cypher and taxus stents were also used. For the<br />

efficacy study, E2 and control stents were implanted in 75 swine following balloon<br />

dilation. For the reendothelialization study, 7 swine distributed into 3 groups<br />

received PEA/500ug E2 stents (n=3), cypher (n=2) or taxus (n=2) stents with 2<br />

stents per animal.<br />

Results: The healing process on the luminal side of the arteries was reflected<br />

by a complete reendothelialization as determined by immunohistology analysis<br />

using an anti-CD31 specific antibody. The reendothelialization was significantly<br />

faster in the 300ug E2 group as compared with the BM group with greater than<br />

90% of reendothelialization at 2 weeks post stent implantation. However, no dif-<br />

Clinical assessment of new stent technology 343<br />

ference in the score of macrophage infiltration (Mac-2 staining) was detected. By<br />

SEM, the best reendothelialization profile was obtained with the PEA/E2 500ug<br />

stent. A more complete coverage of all the struts with tightly connected endothelial<br />

cells was observed with the E2 stents when compared to the cypher stents.<br />

Also, adhesion of platelets and leukocytes on the endothelium was comparable<br />

or even lower with the 500ug E2 stent than with the taxus or cypher stents. At the<br />

28-days time point, the 500 ug E2 stents reduced the expansion of the neointima<br />

(Ni) when compared with the PEA stents.<br />

Conclusions: The healing process of coronaries occurs rapidly in the E2 treated<br />

groups when compared with the BM group with >90% of reendothelialization after<br />

2 weeks. In the reendothelialization study, the PEA/E2 500ug stents gave the<br />

best reendothelialization profile with a more complete coverage of all stent struts<br />

than the cypher stents and less adhesion of platelets and leukocytes to the endothelium<br />

than the taxus stents. At 28 days, the 300ug and 500ug E2 stents had<br />

no significant difference in Ni formation compared with the BM, PEA, taxus and<br />

cypher stents.<br />

P2125 German stereotaxis-guided percutaneuous coronary<br />

intervention study group: first multicenter real world<br />

experience<br />

R. Blindt1 , U. Adamu1 , M. Weber2 ,K.Hertting3 ,C.Hamm2 ,<br />

K.H. Kuck3 ,R.Hoffmann1 ,M.Kelm1 ,K.Krause3 . 1University Hospital RWTH Aachen, Cardiology Dept., Aachen, Germany; 2Kerckhoff-Klinik Bad Nauheim, Cardiology Dept., Bad Nauheim, Germany; 3Asklepios Klinik St.<br />

Georg St. Hamburg, Cardiology Dept., Hamburg, Germany<br />

Introduction: Aim of this observational multicenter study was to systematically<br />

evaluate the capability of the Stereotaxis Niobe Magnetic Navigation system to<br />

facilitate wire navigation during percutaneous coronary intervention (PCI). The<br />

Niobe Stereotaxis system consists of two .8 Tesla magnets and a navigation<br />

software allowing to move specially-designed coronary wires guided by remote<br />

control. The aim of the study was to determine the success rate of magneticallyguided<br />

PCIs in a real-world setting and to analyse procedure-related variables<br />

influencing the results.<br />

Methods: 157 patients underwent magnetically-guided PCI in 3 German centres.<br />

Demographic variables of the patients, lesion quality determined by quantitative<br />

coronary angiography, success rate of the procedure as well as radiation time<br />

were analyzed. A subanalysis was performed for two periods (06/04 - 10/06 and<br />

10/06 - 10/07) owing to a second generation of wires which was introduced at<br />

the beginning of the second period and procured-related learning curves of the<br />

operators.<br />

Results: Mean age of the patients was 66±0.4 years (82% male, 18% female).<br />

34% of the patients were diabetics, 12% had an impaired left ventricular function<br />

(< 45%). The lesions were characterized by high complexity (11% AHA type<br />

A, 25% type B1, 38% type B2, 25% type C). Mean percent lesion stenosis was<br />

85±26%. The overall success rate of the magnetically-guided approach was 87%.<br />

The total fluoroscopy time was 12.4±0.46 min. All failures occurred within the first<br />

period (84 pts) while the success rate between 10/06 -10/07 was 100% (73 pts).<br />

In the first period, 80% of the failures could be successfully treated after switching<br />

to conventional wires. On the other hand, between 10/06 - 10/07 three conventional<br />

PCI failures could be could be successfully treated following utilization of<br />

the Stereotaxis system.<br />

Conclusions: Magnetically-guided PCI represents an interesting tool for the<br />

treatment of dedicated lesions. There is a marked difference in the success rates<br />

of the method between the two different time periods which were analyzed, reflecting<br />

advances in the wire development and learning curves of the respective<br />

operators. Randomized controlled trials are required to determine the method’s<br />

overall value and to identify subgroups that may particularly benefit.<br />

P2126 MAHOROBA I, first-in-man study: four-months results<br />

of a biodegradable polymer taclorimus-eluting stent<br />

in de-novo coronary stenosis<br />

Y. Onuma 1 ,N.Kukreja1 ,S.Tanimoto1 ,P.Smits2 ,P.DenHeijer3 ,<br />

K. Fukaya4 , H. Maeda4 , H. Sakurai4 ,P.W.Serruys. 1Thorax Center,<br />

Erasmus MC, Interventional Cardiology, Rotterdam, Netherlands; 2Medisch centrum Rijnmond-Zuid, Rotterdam, Netherlands; 3Amphia Ziekenhuis,<br />

Research Cardiologie Interventie, Breda, Netherlands; 4Kaneka corporation,<br />

Osaka, Japan<br />

Objective: Tacrolimus is one of the potential pharmacological candidates for<br />

drug-eluting stents. The results of cell culture studies imply that the inhibitory<br />

concentration value 50 (IC 50) of tacrolimus for endothelial cells (EC) is markedly<br />

higher than that for smooth muscle cells (SMC), while the IC50 of sirolimus for EC<br />

is remarkably lower than that for SMC. Accordingly, tacrolimus may have a preferential<br />

effect on ECs as opposed to SMCs if equivalent concentrations for suppressing<br />

SMC are used. Furthermore, unlike sirolimus or paclitaxel, tacrolimus<br />

does not affect tissue factor and e-NOS expression, which might contribute to a<br />

lower risk of stent thrombosis. The combination of tacrolimus with a biodegradeable<br />

polymer coating may produce a safer drug-eluting stent. The aim of the MA-<br />

HOROBA I study is to report angiographic and clinical follow-up at 4 months after<br />

implantation of the second-generation tacrolimus-eluting bioabsorbable PLGA<br />

polymer- coated stent (strut thickness 75μm).<br />

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344 Clinical assessment of new stent technology<br />

Methods: Patients having stable or unstable angina or silent myocardial ischemia<br />

with a de-novo coronary lesion of a length that could be covered by a single 18<br />

mm stent in a native coronary artery of diameter between 3.0 mm and 3.5 mm<br />

were enrolled at 3 sites. The primary endpoints were in-stent and in-segment late<br />

loss at 4 months. Secondary clinical endpoints included major adverse cardiac<br />

events and stent thrombosis at 4 months. Clinical follow-up was planned at 30<br />

days and 4-months with angiographic follow-up at 4 months.<br />

Results: Forty-seven patients (mean age 61.3 years, 63% males and 20% diabetics)<br />

were enrolled between May and November 2007. The majority of patients<br />

had stable angina (75%). Within 30 days, one patient (2.1%) experienced a myocardial<br />

infarction due to subacute stent thrombosis at 4 days after procedure. No<br />

additional events occurred at 30 days follow-up<br />

Conclusion: Tacrolimus-eluting stents are feasible for the treatment of de-novo<br />

coronary artery lesions, with low short-term adverse event rates. The results of<br />

angiographic and clinical follow-up at 4 months are currently being collected and<br />

will be presented at the time of the meeting.<br />

P2127 Culotte stenting technique in coronary bifurcation<br />

disease. Angiographic follow up using dedicated<br />

quantative coronary angiographic analysis and<br />

12-month clinical outcomes<br />

R. Byrne, T. Adriaenssens, R. Iijima, J. Mehilli, A. Dibra, O. Bruskina,<br />

J. Pache, A. Schoemig, A. Kastrati. Deutsches Herzzentrum Muenchen, Munich,<br />

Germany<br />

Background: Percutaneous treatment of coronary bifurcation disease remains<br />

a challenge for the interventional cardiologist. In patient subsets in which a 2stent<br />

strategy is necessary, the culotte technique is a widely used method. We<br />

sought to examine the clinical and angiographic outcomes of patients treated<br />

in this manner at our institution. As quantitative coronary angiographic analysis<br />

using standard measurement programmes is problematic, we used a dedicated<br />

bifurcation analysis system.<br />

Methods: We prospectively enrolled patients undergoing culotte stenting with<br />

drug-eluting stents in 2 German centers. The technique consists of stenting one<br />

of both branches of the bifurcation lesion first, and after balloon dilatation of the<br />

stent meshes, stenting the uncovered branch through the first stent and leaving<br />

the main vessel covered with two overlapped stents. All bifurcation lesions<br />

were classified according to the Medina classification. Angiographic follow-up was<br />

scheduled between 6 and 12 months after the index procedure. Clinical follow-up<br />

was available up to 12 months.<br />

Results: The culotte technique was used in 134 lesions in 132 patients. Of these,<br />

124 (92.5%) represented a true bifurcation lesion morphology, defined as Medina<br />

classification (1,1,1), (1,0,1) or (0,1,1). The median patient age was 64±11<br />

years. Reference vessel diameter was 3.09±0.39 mm in the proximal main vessel,<br />

2.75±0.33 mm in the distal vessel and 2.57±0.42 mm in the side branch.<br />

Kissing balloon inflation was used in 62% of patients. Procedural angiographic<br />

success was achieved in all lesions. Follow-up coronary angiography was performed<br />

in 108 (81.8%) patients. Late lumen loss was 0.15±0.40 mm in the proximal<br />

main vessel, 0.37±0.55 mm in the distal main branch and 0.38±0.64 mm<br />

in the side branch. The incidence of binary angiographic restenosis was 22% for<br />

the whole bifurcation lesion, 0% in the proximal main vessel, 9.1% in the distal<br />

main branch and 16% in the side branch. At 12 months, 26 of 132 (19%) patients<br />

had undergone target lesion revascularization. The incidence of stent thrombosis<br />

(at 1 year) was 1.5%. Predictors of angiographic restenosis were older age<br />

(p=0.01), bifurcation angle larger than 52° (p= 0.03), more severe stenosis in the<br />

distal main branch (p= 0.032), and smaller reference diameter of the side branch<br />

(p= 0.02); kissing balloon postdilation tended to have a protective effect (p=0.07).<br />

Conclusions: The culotte stenting technique is associated with high procedural<br />

success and a relatively low risk of angiographic restenosis. Safety results in our<br />

cohort were favourable in terms of a low risk of stent thrombosis.<br />

P2128 Factors determining use of stents in patients<br />

presenting with acute coronary syndrome and<br />

undergoing PCI: results from the antiplatelet<br />

treatment observational registry (APTOR)<br />

A. Iniguez 1 , A. Bakhai 2 , J. Ferrieres 3 , M. Belger 4 ,C.Schmitt 4 ,<br />

T. Huete 5 ,U.Zeymer 6 on behalf of the APTOR investigators. 1 Vigo, Spain;<br />

2 London, United Kingdom; 3 Toulouse, France; 4 Windlesham, United Kingdom;<br />

5 Madrid, Spain; 6 Ludwigshafen, Germany<br />

Purpose: To identify clinical factors explaining variations in use of stent type in<br />

patients presenting with ACS, the most common cardiac cause of hospital admissions.<br />

Methods: A prospective observational registry in 3 countries, recruited ACS patients<br />

undergoing PCI, Jan – Aug 2007, capturing practice patterns, resource use<br />

and QoL.<br />

Results: 1525 ACS pts (Spain-538, UK-504, France-483), mean age 62 (SD<br />

12), mean wt 80kg (SD 15), 22% female were recruited with co-morbidities<br />

of hypertension-53%, dyslipidemia-52%, diabetes-20% and prior MI-23%. Index<br />

diagnosis: Unstable angina (UA) and non ST-elevation myocardial infarction<br />

(NSTEMI)-62%; ST-elevation myocardial infarction (STEMI)-38%. 95% of 1491<br />

pts with procedural data had PCI with stent implantation (see table). Of the overall<br />

ACS population undergoing PCI with stent implantation, 635 (45%) pts received<br />

a bare metal stent (BMS), 603 (43%) a drug eluting stent (DES) and 160 (11%)<br />

both. The use of DES varied by country: Spain 375 (72%), UK 236 (56%), France<br />

152 (33%). GP IIb/IIIa inhibitor use: abciximab-22%, tirofiban-9%, eptifibatide-<br />

2%. 173 (60%) pts with diabetes received DES compared with 430 (39%) nondiabetics.<br />

DES was used in 125 (56%) pts reporting previous PCI and in 478<br />

(41%) pts with no previous PCI. 95% stent pts received dual antiplatelet therapy<br />

at discharge (94% BMS, 95% DES, 96% BMS+DES). France was the only country<br />

with more than 1% use of a clopidogrel discharge dose > 75mg: 57 (19%) pts<br />

with BMS, 35 (35%) pts with DES, and 14 (29%) pts with both (24% of total stent<br />

pts) (1 pt in each of Spain and UK had >75mg).<br />

Spain % UK % France % UA/NSTEMI% STEMI % Pooled%<br />

(533) (477) (481) (914) (577) (1491)<br />

PCI with stent 98 90 96 94 95 95<br />

PCI with >1 stent 47 42 36 44 38 42<br />

PCI with BMS + DES 16 6 11 13 9 11<br />

PCI with BMS only 28 44 67 37 59 45<br />

PCI with DES only 56 49 23 50 32 43<br />

Conclusions: These high international variations do not seem to be explained by<br />

patient baseline characteristics or by disease epidemiology. These data provide<br />

a useful benchmark for comparison with <strong>European</strong> ACS management guidelines,<br />

and further results from our registry will provide key information on these patients<br />

in clinical practice.<br />

P2129 Balloon folding, the underestimated cause of<br />

neointimal hyperplasia?<br />

M. De Beule 1 ,P.Mortier 1 , D. Van Loo 2 , P. Segers 1 , Y. Taeymans 3 ,<br />

B. Verhegghe 1 , P. Verdonck 1 . 1 IBiTech, Ghent University, Gent,<br />

Belgium; 2 UGCT, Ghent University, Gent, Belgium; 3 UZGent, Ghent<br />

University, Gent, Belgium<br />

Purpose: Restenosis after (drug-eluting) stent implantation is correlated with<br />

non-uniform stent strut distribution. This observation is related to the protrusion<br />

of the tissue between the struts of the stent (prolapse) and the local drug concentrations<br />

and gradients, resulting from inhomogeneous strut placement. Therefore<br />

efforts should target optimization of the uniformity of the stent strut distribution<br />

upon stent deployment. We hypothesize that the folding pattern of the delivery<br />

balloon contributes to the non-uniform strut distribution.<br />

Methods: We developed an innovative computer tool that allows inflation of balloons<br />

and expansion of stents to predict and optimize stent strut distribution during<br />

the procedure. The procedure was applied to a commercially available and<br />

widely used last generation drug-eluting stent, which was expanded virtually with<br />

both a tri- and six-folded balloon configuration. As validation, the tri-folded scenario<br />

was compared with micro-CT images at the end of the transient expansion<br />

phase.<br />

Results: There was an excellent correspondence between the simulations and<br />

the micro-CT images of the real expansion. For the three-folded balloon (its regular<br />

application), a non-uniform strut distribution pattern was observed (left panel:<br />

simulation; center panel: experiment), whereas a six-folded balloon (right panel:<br />

simulation) results in a homogeneous strut distribution.<br />

Conclusions: The balloon folding pattern is a major factor contributing to nonuniform<br />

stent strut distribution. Our virtual tool allows to assess the most appropriate<br />

balloon folding for a specific stent to minimize stent strut non-uniformity<br />

attributable to balloon unfolding.<br />

P2130 Off-label use of drug-eluted stents: demographic,<br />

clinical and angiographic predictors influencing the<br />

election of DES in real-world practice<br />

J.L. Gutierrez-Chico, A. Ortiz Saez, S. Vazquez Fernandez,<br />

J.A. Baz-Alonso, A. Iniguez-Romo. Complejo Hospitalario<br />

Universitario de Vigo, Unidad de Cardiologia Intervencionista, Vigo (Pontevedra),<br />

Spain<br />

Background: Although DES are approved for some limited indications, their efficacy<br />

to prevent restenosis has widened their use for the most challenging cases,<br />

with worse clinical-angiographic profile. Recent data have raised concern however<br />

about DES safety. Off-label indication should be taken into consideration to<br />

understand the controversial results of trials and metaanalysis.<br />

Methods: We retrospectively analyzed data of 3822 stents implanted in 2101<br />

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patients between October 2006 and January <strong>2008</strong>. Demographic, clinical and angiographic<br />

variables were analyzed with step backward logistic regression (likelihood<br />

ratio) to determine their influence in the choice for DES vs. bare metal stent<br />

(dependent variable).<br />

Results: The strongest predictors of DES election were: unprotected left main<br />

PCI (OR 6.023, CI 95% 3.022 – 12.004), chronic total occlusion (OR 5.718, CI<br />

95% 2.243 – 14.579), Diabetes (OR 3.219, CI 95% 2.420 – 4.280), bifurcation<br />

lesion (OR 2.039, CI 95% 1.438 – 2,893), 3-vessels disease (OR 1.598, CI 95%<br />

1.061 – 2,407) and lesion length (OR 1.064, CI 95% 1.049 – 1.079). Variables<br />

preventing the option for DES were prior surgical revascularization (OR 0.173, CI<br />

95% 0.075 – 0.397) and % stenosis (OR 0.983, CI 95% 0.972 – 0.994). Variables<br />

included in the final regression model, but with weak predictive value were hypercholesterolemia,<br />

prior PCI, completeness of revascularization and 2-vessels disease.<br />

No predictive value was found for hypertension, smoke, familiar history of<br />

ischemia, prior infarction, heart failure, age, total length treated in the procedure,<br />

vessel diameter, TIMI flow or type of vessel (native, saphene graft or mammary<br />

artery).<br />

Conclusions: Variables influencing the choice for DES in real practice differ by<br />

far from on-label admitted indications. This fact should be contemplated in the<br />

current debate about the controversial use of these devices.<br />

LIPIDS: STATINS AND BEYOND<br />

P2131 Effects of rosuvastatin and atorvastatin on the<br />

ApoB/ApoA1 ratio in patients with acute coronary<br />

syndrome (CENTAURUS trial)<br />

J.M. Lablanche 1 ,J.C.Tardif 2 , A. Leone 3 ,B.Merkely 4 , J. Morais 5 ,<br />

J. Alonso 6 , M. Santini 7 ,J.Eha 8 ,N.Demil 9 , M. Licour 9 on behalf<br />

of CENTAURUS investigators. 1 Hopital Cardiologique, Lille, France; 2 Montreal<br />

<strong>Heart</strong> Institute and Universite, Montreal, Canada; 3 Hopital CHU Tivoli, La<br />

Louviere, Belgium; 4 Cardiology, Budapest, Hungary; 5 Hospital de Santo Andre,<br />

Leiria, Portugal; 6 Hospital De Fuenlabrada, Spain; 7 Ospedale S. Filippo Neri,<br />

Roma, Italy; 8 Tartu, Estonia; 9 Astrazeneca, Medical Cardiology Dept., Rueil<br />

Malmaison, France<br />

Background: Recent studies have shown that the ApoB/ApoA1 ratio could be<br />

one of the strongest predictors of acute fatal myocardial infarction. CENTAURUS<br />

is the first study to evaluate the change in ApoB/ApoA1 ratio during the acute<br />

phase of acute coronary syndrome (ACS). Objectives: To assess the efficacy and<br />

safety of rosuvastatin 20 mg (R20) versus atorvastatin 80 mg (A80) in patients<br />

with ACS.<br />

Methods: A randomized, double-blind, international, 2-parallel groups trial that<br />

included patients with non-ST elevation ACS and no cholesterol-lowering medications<br />

during the preceding month. The primary objective was to compare the<br />

efficacy of R20 vs A80 initiated at hospital discharge, in reducing the ApoB/ApoA1<br />

ratio at 3 months. The secondary objective was to demonstrate the non-inferiority<br />

of R20 compared to A80 for percentage reduction in LDL-cholesterol (LDL-C) levels<br />

at 1 and 3 months. The non-inferiority analysis for LDL-C was performed with<br />

the upper limit of 95% IC for the difference between R20 and A80 being less than<br />

3%, on both the Intent To Treat (ITT) and Per Protocol (PP) populations.<br />

Results: Among the 829 patients who took at least one dose of study drug after<br />

hospital discharge, 369 patients in R20 group and 384 patients in A80 group<br />

were included in the ITT analysis, 226 and 252 respectively in PP analysis. At<br />

baseline, median ApoB/ApoA1 ratio was 0.90 and median LDL-C 1.26 g/l (3.3<br />

mmol/l). R20 was more effective in decreasing ApoB/ApoA1 ratio at 1 month but<br />

not at 3 months. LDL-C decreased by nearly 50% after 1 and 3 months in each<br />

group. The non-inferiority of R20 versus A80 was demonstrated after 1 month with<br />

a difference of -0.3% [-2.7; +2.1] [95%CI] in favour of greater reduction in the R20<br />

group. This hypothesis couldn’t be shown after 3 months (+1.0% [-1.6; 3.5]) in<br />

ITT analysis. However, the non-inferiority of R20 was demonstrated both at 1 and<br />

3 months in the PP analysis (-0.7% [-3.5; 2.0] and -0.5% [-3.5;2.5] respectively).<br />

The 2 treatments were well tolerated.<br />

% Change in ApB/ApoA1 R20 median A80 median Estimated difference p<br />

(mean ± std)* (mean ± std)* Median [95% CI]*<br />

At 1 month -44.4 (-43.1±16.5) -42.9 (-40.5±16.3) -2.6 [-4.5;-0,0] 0.02<br />

At 3 months -44.4 (-41.2±20.1) -44.4 (-41.7±17.1) 0.0 [-2.5;+1.7] 0.87<br />

*Data distribution was not normal.<br />

Conclusion: In patients with non-ST elevation ACS, R20 significantly decreases<br />

ApoB/ApoA1 ratio at 1 month compared to A80 whereas no difference is shown<br />

at 3 months.<br />

Clinical assessment of new stent technology / Lipids: statins and beyond 345<br />

P2132 High density lipoprotein cholesterol, low high density<br />

lipoprotein cholesterol and major cardiovascular<br />

events among patients with coronary heart disease in<br />

the scandinavian simvastatin survival study<br />

Q. Zhang1 , V. Sazonov1 ,Y.Cui1 , D.L. Maccubbi 1 , T.J. Cook1 ,<br />

T.R. Pedersen2 . 1Merck & Co, Inc, Whitehouse Station, United States of<br />

America; 2University of Oslo, Oslo, Norway<br />

Purpose: Many coronary heart disease (CHD) patients fail to attain low density<br />

lipoprotein cholesterol (LDL-C) goal despite statin therapy. Over one-third also<br />

have low high density lipoprotein cholesterol (HDL-C). We examined the risk of<br />

major cardiovascular events (MCEs) including revascularization, in statin treated<br />

CHD patients with low HDL-C and elevated LDL-C compared to patients with<br />

elevated LDL-C only.<br />

Methods: This is a post-hoc analysis of the 4S, a 5-year trial of simvastatin<br />

vs. placebo in CHD patients. Patients from the simvastatin arm with LDL-C<br />

≥100mg/dL at year 1 of treatment were included. Patients with MCEs or with<br />

missing LDL-C or HDL-C at year 1 were excluded. MCEs were evaluated over<br />

4 years on average, from year 1 to the end of follow-up. Low HDL-C at year 1<br />

was defined as


346 Lipids: statins and beyond<br />

baseline in Total C/HDL-C, LDL-C/HDL-C, ApoB/ApoA-I and Non-HDL-C/HDL-C<br />

at 24 wks, compared to N and E/S (p


P2139 Inverse relation of baseline LDL levels to clinical<br />

response to HDL rise in patients with coronary heart<br />

disease<br />

I. Goldenberg, U. Goldbourt, V. Boyco, M. Benderly, S. Behar<br />

on behalf of the BIP Study Group. Sheba Medical Center, <strong>Heart</strong><br />

Institute, Tel Hashomer, Israel<br />

Purpose: Recent studies have shown that high-density lipoprotein cholesterol<br />

(HDL-C) levels are a strong inverse predictor of cardiovascular events, and that<br />

this association is maintained in patients with low levels of low-density lipoprotein<br />

cholesterol (LDL-C). The present study was designed to assess clinical response<br />

to HDL-C rise in coronary heart disease (CHD) patients with varying degrees of<br />

baseline LDL-C levels.<br />

Methods: The risk of a major cardiac event (defined as cardiac death or nonfatal<br />

myocardial infarction) during a median 7.9-year follow-up of 3020 CHD patients<br />

enrolled in the Bezafibrate Infarction Prevention trial was related to changes in<br />

lipid levels during the study. Baseline LDL-C levels were categorized according to<br />

National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP<br />

III) criteria.<br />

Results: After multivariable adjustment for baseline clinical variables and lipid levels,<br />

the benefit of HDL-C rise was shown to be most pronounced among patients<br />

with baseline LDL-C levels ≤129 mg/dL (29% risk reduction per 5 mg/dL HDL-C<br />

increment [p=0.02]), intermediate in patients with LDL-C levels of 130-159 mg/dL<br />

(13% risk reduction per 5 mg/dL HDL-C increment [p=0.03]), and non-significant<br />

in patients with LDL-C ≥160 mg/dL (HR=0.94 [p=0.57]; Table). A similar relationship<br />

was shown for risk reduction associated triglyceride (TG) decrements,<br />

whereas the benefit of LDL-C reduction was more pronounced in patients with<br />

baseline LDL-C ≥130 mg/dL (Table).<br />

≤129<br />

Baseline LDL-C Levels (mg/dL)<br />

130-159 ≥160<br />

HDL increase (per 5 mg/dL)<br />

Hazard Ratio<br />

TG reduction (per 50 mg/dL)<br />

0.71 0.87 0.94<br />

Hazard Ratio<br />

LDL reduction (per 20 mg/dL)<br />

0.81 0.84 0.96<br />

Hazard Ratio 1.01 0.75 0.81<br />

Conclusions: The current study demonstrates that the clinical response to HDL-<br />

C rise is inversely related to baseline LDL-C levels. These findings suggest that<br />

more focus should be directed at combined assessment of both HDL-C and LDL-<br />

C levels in CHD patients.<br />

P2140 Pitavastatin improves lipid profiles and reduces<br />

high-sensitivity CRP in Japanese subjects with<br />

hypercholesterolemia-KISHIMEN multi-center<br />

prospective study<br />

N. Kume1 ,Y.Fujioka2 , A. Taniguchi3 , S. Kagimoto4 ,K.Hirata2 ,<br />

Y. Nakamura 5 , T. Yamamoto4 , N. Inagaki4 ,Y.Seino3 ,H.Koshiyama3 on behalf of KISHIMEN Investigators. 1Kyoto University, Cardiovascular Medicine<br />

Dept., Kyoto, Japan; 2Kobe, Japan; 3Osaka, Japan; 4Kyoto, Japan; 5Amagasaki, Japan<br />

Background: Pitavastatin is a synthetic statin whose anti-inflammatory effects<br />

have not been explored yet.<br />

Methods: Effects of pitavastatin (1-2mg, for 12 months) on lipid profiles and highsensitivity<br />

C-reactive protein (hs-CRP) levels were examined in 178 Japanese<br />

hypercholesterolemic subjects, including those with type 2 diabetes (DM; n=103,<br />

58%) by a multi-center prospective open-label study.<br />

Results: Serum low-density lipoprotein cholesterol (LDL-C) levels were significantly<br />

decreased by 30.3 and 31.0% in total and DM subjects, respectively.<br />

Remnant-like particle cholesterol (RLP-C) levels were significantly decreased<br />

by 22.8% and 14.0% in total and DM subjects, respectively. In subjects previously<br />

not treated with other statins, pitavastatin (2mg) lowered LDL-C by 39.9%.<br />

In subjects with basal high-density lipoprotein cholesterol (HDL-C) levels below<br />

40mg/dL, pitavastatin significantly raised HDL-C levels by 19.0% and 24.5% in<br />

total and DM subjects, respectively. Pitavastatin significantly lowered hs-CRP levels<br />

(median: 0.69 to 0.45mg/L, -34.8%, p


348 Lipids: statins and beyond<br />

P2143 Hypolipidemic treatment increases blood apelin in<br />

patients with isolated LDL-cholesterol elevation<br />

I. Tasci, G. Erdem, S. Tapan, G. Ozgur, T. Dogru, C. Acikel,<br />

A. Sonmez. Gulhane School of Medicine, Department of Internal<br />

Medicine, Ankara, Turkey<br />

Purpose: Apelin, a newly described peptide with various favorable effects in cardiovascular<br />

system, is associated with insulin resistance and inflammation. We<br />

have recently reported significantly reduced plasma apelin levels in people with<br />

elevated LDL-cholesterol who had no additional disorder or drug usage. In the<br />

presents study, we searched whether plasma apelin increases after hypolipidemia<br />

is attained either with an intensive lifestyle management or statin treatment.<br />

Methods: 134 subjects with LDL-cholesterol >160 mg/dL were enrolled. 116 of<br />

them finished a successful 12 weeks period of therapeutic lifestyle change (TLC)<br />

intervention according to ATPIII Report. Among them, 54 patients achieved target<br />

LDL-cholesterol levels. The remaining 62 were treated with rosuvastatin for an additional<br />

12 weeks, and 56 patients achieved a target LDL-cholesterol level. Blood<br />

apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were measured<br />

at each time point.<br />

Results: The patients who achieved target LDL-cholesterol levels by the end<br />

of TLC period had significantly higher levels of apelin (p=.000) and adiponectin<br />

(p=.001), and lower leptin (p=.023 for woman and p=.042 for men) and insulin<br />

(p=.031) levels, whereas TNF-alpha (p=.902) and hsCRP (p=.126) levels as well<br />

as HOMA values (p=.109) remained the same compared to baseline. The subjects<br />

who received a statin treatment for 12 weeks because of unresponsiveness<br />

to TLC in terms of LDL-cholesterol reduction also had significantly higher levels<br />

of apelin (p=.020) and adiponectin (p=.011), and lower TNF-alpha (p=.000) and<br />

hsCRP (p=.023) levels, whereas leptin (p=.134 for woman and P=.959 for men)<br />

and insulin (p=.865) levels as well as HOMA values (p=.855) remained the same<br />

compared to the results before treatment. Besides, blood apelin levels remained<br />

the same when LDL-cholesterol reduction did not happen.<br />

Conclusions: Reduced circulating apelin levels in patients with hypercholesterolemia<br />

increases either with TLC intervention or hypolipidemic treatment.<br />

Though it was previously shown that, at least in adipocytes, synthesis of apelin<br />

is positively stimulated by TNF-alpha, in the present study, the patients with increased<br />

TNF-alpha levels and LDL-cholesterol concentrations had lower blood<br />

apelin levels which reversed after LDL-cholesterol reduction. Moreover, serum<br />

apelin concentration behaves in the same direction with adiponectin and leptin.<br />

The association of apelin with atherosclerosis seems to be complex and linked to<br />

dyslipidemia, insulin resistance and/or inflammation.<br />

P2144 <strong>Heart</strong> rate variability and plasma lipids before and<br />

after treatment with rosuvastatin in<br />

hypercholesterolaemic patients without coronary<br />

artery disease<br />

E.A. Zacharis, M.E. Marketou, E.I. Skalidis, I.K. Karalis,<br />

H.E. Mavrakis, A.P. Patrianakos, G.F. Diakakis, E. Ganotakis,<br />

F.I. Parthenakis, P.E. Vardas. Heraklion University Hospital, Department of<br />

Cardiology, Heraklion, Greece<br />

Purpose: Decreased 24-h heart rate variability (HRV) is associated with increased<br />

risk of cardiovascular morbidity and mortality. The objective of this study<br />

is to examine the relation between plasma lipids and HRV in hypercholesterolaemic<br />

subjects without coronary artery disease (CAD) before and after treatment<br />

with 10 mg rosuvastatin.<br />

Methods: We included 35 hyperlipidaemic subjects (20 men, aged 58±10 years).<br />

Inclusion criteria were hypercholesterolaemia (TCHOL >240 mg/dl) and low density<br />

lipoprotein (LDL-C) cholesterol>160 mg/dl. All had a normal echocardiogram<br />

and no signs of coronary artery disease. Holter recording and fasting blood samples<br />

were performed in all subjects. The subjects were randomized to receive 10<br />

mg/day rosuvastatin (n=25 or placebo n=10) for 1 year and reevaluated.<br />

Total cholesterol and LDL-C levels were significantly reduced (from 287±102<br />

mg/dl and 170±65 mg/dl to 190±64mg/dl and 98±27 mg/dl respectively, p


tive. We sought to determine the effects of low levels of HDL-C on endothelial<br />

function.<br />

Methods:A total of 31 students attending a military school with isolated low HDL-<br />

C(< 40 mg/dL) was taken as a study group. Control group consisted of 31 students<br />

with high HDL-C (>60 mg/dL). Exclusion criteria were smoking, high total<br />

cholesterol (>200 mg/dL), high triglyceride (>150 mg/dL) levels and arterial blood<br />

pressure > 130/85 mmHg. Endothelial function was determined by brachial artery<br />

flow mediated dilatation.<br />

Results: Both groups were similar in terms of age (20.9±1.5 vs 21±1.6) and<br />

body mass index (22.4±1.6 vs 22.3±1.7). Serum lipids and blood glucose are<br />

depicted in the table.<br />

Flow mediated dilatation was less in low HDL-C group compared to controls<br />

(10.4±4.3 vs. 15.3±5.1, p


350 Lipids: statins and beyond<br />

P2151 Modification of in-hospital lipid lowering drug therapy<br />

in primary and secondary<br />

F. Towae 1 , C. Juenger1 , K. Bestehorn2 , M.G. Gottwik1 , R. Zahn1 ,<br />

J. Senges1 ,A.K.Gitt1on behalf of 2L-Study-Group. 1Institut fuer Herzinfarktforschung, Ludwigshafen, Germany; 2Institut fuer<br />

klinische Pharmakologie, Dresden, Germany<br />

Background: Current practice guidelines recommend LDL-cholesterol levels<br />

100 mg/dl<br />

105 111 < 0.01<br />

Increase of statin dose [%] 26.9 24.6 n.s.<br />

Adding ezetemibe [%] 5.9 3.3 < 0.05<br />

Increase of statin dose + ezetemibe [%] 10.2 9.4 n.s<br />

Conclusion: About 40% of high risk patients admitted to hospital already had<br />

achieved the recommended LDL


P2155 A very high prevalence of low HDL-cholesterol in<br />

Spanish patients with acute coronary syndromes<br />

X. Pinto1 ,E.Corbella1 , A. Munoz2 , J.C. Pedro Botet3 ,<br />

A. Hernandez-Mijares 4 , A. Zuniga5 , A. Mangas6 , J. Millan7 on<br />

behalf of Spanish HDL Forum. 1Unitat de lipids Risc CV. Hospital<br />

Bellvitge, Internal Medicine, L’hospitalet Ll. Barcelona, Spain; 2Solvay Pharma,<br />

Medical department, Barcelona, Spain; 3Medicina Interna. Hospital del Mar,<br />

Medicina interna, Barcelona, Spain; 4Servicio Endocrinologia. Hospital Peset,<br />

Valencia, Spain; 5Medicina Interna. Hospital Marques Valdecilla, Santander,<br />

Spain; 6Medicina Interna. Hospital Puerta de Mar, Cadiz, Spain; 7Medicina Interna. H U Gregorio Maranon, Madrid, Spain<br />

The aim of our study was to know the prevalence of low HDL-C in Spanish patients<br />

with acute coronary syndromes and the main factors related with this disorder.<br />

Material and Methods: We examined 648 medical records of patients who were<br />

admitted at the coronary care units of 6 Spanish tertiary hospitals. Clinical and<br />

laboratory data were retrospectively investigated. Blood analyses were done before<br />

the sixth day of the hospital stay. Low HDL-C was defined as a serum concentration<br />

< 1,04 mmol/L in men and < 1,3 mmol/L in women.<br />

Results: Low HDL-C was observed in 404 (62,3%) patients. A decrease of 0,157<br />

mmol/L of HDL-C was estimated (lineal regression) for the every day of time<br />

elapsed from hospital admission until the lipid measurements were done. Patients<br />

with low HDL-C have a higher body weight and triglycerides concentrations, and<br />

a higher prevalence of smoking, hypertension and diabetes. No differences were<br />

observed in the number of patients taking statins or fibrates between those who<br />

had a low HDL-C and those who had not. Only a small percentage of patients<br />

with low HDL-C were on fibrate therapy.<br />

No Low HDL-C244 (37.7%) Low HDL-C404 (62.3%) p<br />

Female 33 (13.5%) 99 (24.5%) 0.001<br />

Age (years) 64±12 62±12 0.080<br />

Body Mass Index 27.98±4.1 28.71±4.2 0.041<br />

Previous Ischemic Disease 100 (41.5%) 174 (44.4%) 0.476<br />

Smokers<br />

Former Smokers<br />

83 (34.9%)<br />

95 (39.9%)<br />

169 (42.5%)<br />

120 (30.2%)<br />

0.036<br />

Hypertension 133 (55.4%) 254 (64.3%) 0.026<br />

Diabetes Mellitus 65 (27.2%) 142 (36.4%) 0.017<br />

Total Cholesterol (mmol/L) 5.06±1.17 4.76±1.19 0.002<br />

LDL-C (mmol/L) 3.14±1.1 3.16±1.1 0.869<br />

Triglyceride (mmol/L) 1.41±0.7 1.87±1.0


352 Lipids: statins and beyond / Gender matters<br />

P2159 Enhancement of angiotensin II forming activity in<br />

mononuclear cells by free fatty acids<br />

Y. Azekosi1 , M. Kobayashi2 ,K.Yamakawa2 ,T.Yasu2 , Y. Tagomori 3 ,<br />

S. Abe 3 ,H.Urata4 ,S.Ueda2 . 1University of Ryukyus School of<br />

Medicine, Clinical Pharmacology And Therpeutics, Nakagami,<br />

Japan; 2University of Ryukyus School of Medicine, Clinical pharmacology and<br />

theraperutics, Nakagami, Japan; 3Fukuoka University, Second Department of<br />

Internal Medicine, Fukuoka, Japan; 4Fukuoka University Chikushi Hospital,<br />

Department of Cardiology, Fukuoka, Japan<br />

Objective: Free fatty acids appear to be a pivotal adipocytokine that are closely<br />

associated with insulin resistance and endothelial dysfunction. We have previously<br />

shown that an elevated free fatty acid (FFA) impairs endothelial function<br />

through activation of renin-angiotensin system (RAS) in human. However, elevated<br />

FFA did not affect any circulating components of RAS. We investigated<br />

effect of elevated FFA on angiotensin II forming activity in human mononuclear<br />

cells ex vivo.<br />

Method and Results: Blood samples were obtained before and after systemic<br />

infusion of lipid/heparin (1 lipid: 20% intralipid, 100ml/hr + heparin: 0.3U/kg/min<br />

for 3hr) or saline in 8 healthy subjects. Angiotensin II forming activities in isolated<br />

mononuclear cells were measured by immunofluorescence technique. Elevated<br />

FFA after lipid/heparin infusion significantly enhanced angiotensin II forming<br />

activities {Total: before: 3253.7±2830.2, after: 11657.0±8686.5 (p


P2163 The influence of estradiol on Bone Morphogenetic<br />

Protein signal pathway in pulmonary vascular<br />

endothelial cells<br />

H. Ichimori, S. Kogaki, J. Narita, H. Ishida, T. Uchikawa, S. Nasuno,<br />

Y. Okada, Y. Yoshida, K. Ozono. Osaka University, Pediatrics, Suita,<br />

Japan<br />

Background: Gender differences in the development of Pulmonary Artery Hypertension<br />

(PAH) have been documented in both human and animal studies. Idiopathic<br />

PAH is predominantly a disease of young women in their child-bearing<br />

years, which suggests a rule of sex hormones in pathogenesis of PAH. However,<br />

the influence of sex hormones in pulmonary vasculatures and the development<br />

of PAH have not been fully understood. Recent advance in understanding IPAH<br />

has revealed genetic predisposition such as BMPR (Bone Morphogenetic Protein<br />

Receptor) and ALK-1.<br />

Purpose: The aim of the present study is to investigate the effect of β-estradiol<br />

(E2) upon BMPR signal pathway in pulmonary vascular endothelial cells in vitro.<br />

Materials and methods: Isolated rat lung vascular endothelial cell (RLEC) were<br />

cultured and we examined the expression of BMPR2, BMP-regulated Smads,<br />

and Id1 under normoxia and hypoxia with BMP2 stimulation. Then, we investigate<br />

changes in the expression of these molecules in the presence of E2 with or<br />

without estrogen receptor antagonist (ICI 182.780.).<br />

Results: First, we confirmed that estrogen receptor α and β were expressed in<br />

RLEC. In exposure to 24 hours’ hypoxia, the expression of mRNA transcripts for<br />

BMPR2, Id1, and Smad6 in RLEC was reduced. In addition, we demonstrated that<br />

E2 decreased the expression of phosphorylated Smad1/5/8 in a dose-dependent<br />

manner and phosphorylated Smad1/5/8 were decreased about 80% by E2 of 10-<br />

7M. The attenuation of phosphorylated Smad1/5/8 was rescued by ICI182.780.<br />

The attenuation of phosphorylated Smads.<br />

Discussion: Under hypoxic condision, the presence of E2 attenuate the BMPR<br />

signal pathway in the endothelium of pulmonary vasculatures. Our observations<br />

provide the first evidence that sex hormone on BMPR signal pathway can offer<br />

new strategies for the treatment of PAH.<br />

P2164 The-129A allele within myeloperoxidase promoter<br />

region exerts a protective role towards myocardial<br />

infarction in women<br />

B. Gigante, E. Zotova, L. Lyrenas, U. De Faire, R. Morgenstern,<br />

A. Bennet. Karolinska Institutet, Division of Cardiovascular<br />

Epidemiology, Stockholm, Sweden<br />

It has recently been shown that myeloperoxidase (MPO) serum levels, a prooxidant<br />

enzyme that converts LDL into the oxidized-LDL, are inversely related to<br />

the presence of coronary artery disease. Genetic factors are known to modulate<br />

MPO serum levels, in particular it has been shown that the rare allele at two genetic<br />

loci -463G/A and -129G/A within the MPO promoter region are associated<br />

with lower MPO serum levels, while male sex, older age and hormone replacement<br />

therapy (HRT) are associated with increased MPO serum levels and activity.<br />

The aim of the present study was to investigate the potential role of the two genetic<br />

variants -463G/A and -129G/A for the occurrence of myocardial infarction<br />

(MI) in the Stockholm <strong>Heart</strong> Epidemiology Program (SHEEP) a case-control population<br />

recruited in the Stockholm area. SHEEP cases (n=1213) were identified<br />

as non fatal MI patients and controls (n=1561) were sex and age-matched subjects.The<br />

two genetic variants -463G/A and -129G/A have been genotyped by the<br />

RFLP and DASH platform, respectively. Differences in genotype and allele frequencies<br />

were tested by chi2square test. Crude and adjusted odds ratios (OR)<br />

and relative 95%confidence intervals (CI) were estimated by logistic regression<br />

analysis. According to the SHEEP design, data were analyzed in male and female<br />

separately. The two variants were in high linkage disequilibrium (D’=0.9).<br />

The -129A allele was prevalent in women cases 0.09 vs 0.06 (p


354 Gender matters<br />

ders in Finland. However, among young women the decline in case fatality has<br />

been slower than among men or among older women. The reasons for this less<br />

favorable development warrant further research.<br />

P2167 Pronounced adverse effect of abdominal obesity on<br />

hypertensive cardiac sequelae in the female gender.<br />

Insights from the Hippokration Hellenic Hypertension<br />

(3H) Study<br />

D. Tsiachris, C. Tsioufis, C. Thomopoulos, K. Dimitriadis, M. Selima,<br />

E. Andrikou, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of<br />

Athens, Hippokration Hospital, Athens, Greece<br />

Purpose: Obesity and hypertension deteriorate left ventricular (LV) structure<br />

and function in an additive manner increasing the risk of congestive heart failure.<br />

Whether there is a sex-specific role of excess visceral fat accumulation in<br />

hypertension-induced cardiac adaptations is not well clarified. Our aim was to assess<br />

the differential effect of waist circumference on LV structural and functional<br />

alterations, in hypertensive males and females.<br />

Methods: 1789 consecutive, non-diabetic, essential hypertensives (aged<br />

55.8±13.5 years, 966 females) that were included in the 3H Study, an ongoing<br />

registry of hypertension related target organ damage, were classified to obese<br />

and non-obese according to ATP III criteria regarding waist circumference value<br />

(>88 cm for obese women and > 102 cm for obese men). In all participants, LV<br />

mass index (LVMI) and relative wall thickness were determined, while LV diastolic<br />

function was evaluated by means of conventional Doppler and tissue Doppler<br />

imaging (TDI), averaging early and late diastolic mitral annular peak velocities<br />

(Em, Am, Em/Am ratio) from four separate sites of measurement (septal, lateral,<br />

anterior and inferior walls).<br />

Results: Hypertensive obese women (n=599) compared with non-obese (n=367)<br />

exhibited significantly greater LVMI and a higher prevalence of LV hypertrophy<br />

(by 5.5gr/m 2 and 8.8%, p=0.003 and 0.005, respectively), while such differences<br />

were not present between hypertensive obese (n=415) and non-obese (n=408)<br />

men. Among hypertensive women, obese compared to non-obese were accompanied<br />

by significantly lower ratios of transmitral E/A (by 0.08 p


2nd year of follow-up, respectively). There was an improvement in HRQoL at 2<br />

years for both groups, as compared with baseline, the pattern was however, different<br />

for men and women. Among women, significant improvement was observed<br />

only in domains referring to physical health whereas men reported improvement<br />

in domains referring also to mental health. Despite differences in baseline characteristics,<br />

female gender was independently associated with worse outcome in the<br />

following domains, respectively after the 1st and 2nd year of observation: Physical<br />

Functioning - PE (parameter estimate) = -8.13 [95CI, -12.26 to -3.99, p=0.0002]<br />

and PE = -8.85 [95 CI, -12.74 to -4.96, p


356 Gender matters<br />

Conclusions: HT is associated with increased PWV independently of arterial<br />

atherosclerosis, indicating a direct impact of this immunological disorder on arterial<br />

stiffening. This effect may be masked in postmenopausal women possibly due<br />

to their more adverse cardiovascular risk profile.<br />

P2175 Evidence based care for women: big effort small<br />

result<br />

O. Manfrini1 ,E.Rossi1 ,G.DeVitis1 ,M.DeRosa1 ,A.Berti1 ,<br />

F. Fedele2 , F. Romeo2 , R. Bugiardini3 . 1Bologna, Italy; 2Roma, Italy; 3University of Bologna, Dip. Med. Interna, Cardioangiologia,<br />

Bologna, Italy<br />

Purpose: In the past two years the Italian Society of Cardiology launched a campaign<br />

aimed at raising awareness of risk of ischemic heart disease in women.<br />

The current study examined the rates of treatment of acute myocardial infarction<br />

(AMI) in women, to assess the relation between prevention efforts and results<br />

since the campaign settlement.<br />

Methods: We evaluated medical records of 4073 consecutive patients (1475<br />

women) survived from AMI between January 1st 2005 and December 31st 2006.<br />

They were discharged from 5 hospitals located in the North Italy (the CINECA-<br />

ARNO survey). Post-discharge use of aspirin, beta-blocker, angiotensin converting<br />

enzyme (ACE) inhibitor and statin during 10 months follow-up was compared<br />

between women discharged in 2005 and those in 2006.<br />

Results: The rate of consecutive women with discharged diagnosis of AMI was<br />

higher in 2006 than in 2005 (743/1990, 37.3% versus 732/2084, 35.1%). Female<br />

sex was associated with lower use of aspirin (OR, 0.58; 95% CI, 0.49-0.69;<br />

p


P2179 Symptoms of atrial fibrillation by gender and age<br />

classes in a setting of emergency telecardiology<br />

N.D. Brunetti 1 , L. De Gennaro1 ,G.Amodio2 , G. Dellegrottaglie3 ,<br />

M. Di Biase1 , G. Antonelli 2 . 1University of Foggia, Cardiology<br />

Department, Foggia, Italy; 2Azienda Ospedaliera Policlinico,<br />

Emergency Cardiology Department, Bari, Italy; 3Cardio-on-line Europe, Bari,<br />

Italy<br />

Aim: To analyze symptoms of patients with atrial fibrillation (AF) diagnosed with<br />

the support of telecardiology technologies applied to public emergency health<br />

care number "118" (Italy).<br />

Methods: 27,841 patients from all over Apulia (southern Italy, 4 millions inhabitants)<br />

who referred to public emergency health care number "118" underwent<br />

ECG evaluation according to a previously fixed inclusion protocol with a ECG<br />

recorder device. Data recorded were transmitted with a mobile telephone support<br />

to a telecardiology "hub" active 24-hours in a day with a cardiologist (ECG device<br />

did not allow 118 crew members to read ECG). Rate prevalence of AF, age and<br />

symptoms complained by patients were reported and analyzed.<br />

Results: AF was diagnosed in 11.68% of patients who underwent ECG examination.<br />

Typical palpitations were complained by only 14.08% of patients with AF. This<br />

rate significantly decreased with age (80 years 9.62%; 26.50% in patients 70 years, p


358 Gender matters / Ambulatory blood pressure measurement<br />

P2183 Oxidative stress and disturbed glutathione redox<br />

status in females with metabolic syndrome<br />

M. Atalay 1 ,J.Lietava2 ,V.Husarova2 , M. Caprnda2 , P. Blazicek3 ,<br />

G.J. Fodor4 . 1Physiology of University of Kuopio, Institute<br />

of Biomedicine, Kuopio, Finland; 2Comenius University, 2-nd<br />

Department of Internal Medicine, Bratislava, Slovak Republic; 3Military Hospital,<br />

Department of Biochemistry, Bratislava, Slovak Republic; 4University of Ottawa<br />

<strong>Heart</strong> Institute, Ottawa, Canada<br />

Introduction: Metabolic syndrome (MS) is associated with increased level of oxidative<br />

stress, while the antioxidant defences of the syndrome were less studied.<br />

Glutathione is a central antioxidant involved with the redox regulation and the ratio<br />

of the oxidized glutathione (GSSG) to reduced glutathione (GSH) is a sensitive<br />

marker of oxidative stress. We hypothesized that females with MS have increased<br />

level of glutatione oxidative ratio in addition to the increased other oxidative stress<br />

markers.<br />

Material and methods: Study group was consisted of 104 non-smoking females<br />

aged 61.8±9.42 yrs with MS defined according to IDF 2005 criteria (MS+) and of<br />

40 controls aged 54.8±16.37 yrs enrolled into SLOV-FIN- Glutathione study. We<br />

analysed parameters of oxidative stress and antioxidant defences, including total<br />

homocysteine (THCY), glutathione oxidation ratio, ultrasensitive C-reactive proteine<br />

(uCRP), GSSG, oxidised LDL cholesterol (oLDL), protein carbonyls (PC),<br />

Shiff-base substances (SBS), uric acid and total antioxidant status (TAS).<br />

Results: MS+ females had high glutathione oxidation ratio (GSSG/GSH)<br />

(p


P2187 The relationships of ambulatory arterial stiffness<br />

index with pulse wave velocity in hypertensives:<br />

focus on the superiority of nighttime haemodynamics<br />

C. Thomopoulos, C. Tsioufis, D. Chatzis, E. Andrikou, V. Tzamou,<br />

T. Makris, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic,<br />

University of Athens, Hippokration Hospital, Athens, Greece<br />

Purpose: To evaluate the role of ambulatory arterial stiffness index (AASI) on<br />

aortic pulse wave velocity (PWV) levels in hypertensives.<br />

Methods: We studied 264 consecutive untreated hypertensives (aged 48±6<br />

years, 176 males, 133 smokers, and office BP 149/98mmHg). Subjects underwent<br />

ambulatory BP monitoring and echocardiography, while carotid – femoral<br />

PWV was measured by an automatic device (Complior SP) and accordingly<br />

were divided into two groups (those with high and low PWV levels, cut-off point<br />

7.6 m/sec). From 24h ambulatory BP monitoring, daytime and nighttime AASI<br />

(24hAASI, dAASI, nAASI) were estimated. Metabolic profile and glomerular filtration<br />

rate (GFR) by using the MDRD formula were estimated.<br />

Results: Hypertensives with high PWV (n=136) with respect to those with low<br />

(n=128) had similar body mass index, smoking habits and heart rate (29.8±3<br />

vs. 29.2±3 kg/m2 , 52% vs. 50%, 76±6 vs.77±8 bpm, respectively p=NS for all).<br />

The former group with respect to the latter demonstrated higher total cholesterol<br />

and LDL levels (222±39 vs. 212±35, p=0.046 and 154±32 vs. 39 mg/dl,<br />

p=0.035) while glucose, triglycerides, HDL and GFR did not differ between the<br />

groups (p=NS, for all). Left ventricle mass index, 24h systolic and diastolic BP<br />

and 24h pulse pressure were higher in hypertensives with high PWV compared<br />

to those with low (109±25 vs. 99±23 gr/m2 , 141±9 vs.137±6 mmHg, 87±7 vs.<br />

84±6.5 mmHg and 54±6 vs.52±7mmHg, respectively, p


360 Ambulatory blood pressure measurement<br />

P2191 Masked hypertension is associated with non-dipper<br />

or riser circadian pattern and impaired renal function<br />

in the elderly with hypertension: Analysis of a<br />

1202-patient database<br />

F. Uchida, K. Harada, R. Kuramachi, Y. Yui, T. Ishikawa, Y. Saitou,<br />

H. Maki, Y. Tsubokou, K. Takeda, I. Kuwajima. Tokyo Metropolitan Geriatric<br />

Hospital, Division of Cardiology, Tokyo, Japan<br />

Purpose: Masked hypertension (MHT), which is characterized with normal officemeasured<br />

blood pressure (BP) and elevated 24-hour ambulatory BP monitoring<br />

(ABPM) or home BP, has poor cardiovascular prognosis in treated hypertensives.<br />

Nocturnal BP was shown to convey additional risk information about heart failure.<br />

To study whether MHT is associated with nocturnal hypertension (HT) or not.<br />

Methods: ABPM was performed in 1202 elderly Japanese patients with treated<br />

HT (74.8±0.2 yrs, men 43%) between 2005 and 2007. Abnormal dipping patterns<br />

were diagnosed when the nocturnal systolic BP fall was less than 10% (nondipper),<br />

or less than 0% (riser). The BP recording at the beginning of ABPM was<br />

used for office BP.<br />

Results: Ten percent of patients showed increased values on ABPM with normal<br />

office BP (MHT, n=118), while 19% showed elevated office BP with normal values<br />

on ABPM (white-coat HT, WCHT, n=223), and 28% showed both elevated<br />

office BP and increased values on ABPM (resistant HT, RHT, n=340). Office<br />

systolic BPs were 130±7mmHg (MHT), 152±10 mmHg (WCHT), and 160±15<br />

mmHg (RHT), all of which were significantly higher than 120±13 mmHg of wellcontrolled<br />

HT (NT, n=521). Values on ABPM were 142±6mmHg (MHT), 125±7<br />

mmHg (WCHT), 151±13 mmHg (RHT), and 117±11mmHg (NT), respectively.<br />

The non-dipper or riser circadian patterns were present in 88% of MHT, as compared<br />

with 79% (WCHT), 74% (RHT), and 78% (NT). Moreover, riser patterns<br />

were present in 46% of MHT, as compared with 15% (WCHT), 31% (RHT), and<br />

31% (NT). Serum creatinine levels in MHT and RHT were higher than those in NT<br />

(1.05±0.58 mg/dl and 1.07±0.83 mg/dl vs. 0.90±0.40 mg/dl, p


tension (WCHT) to vascular damage is not yet fully clarified, while urinary albumin<br />

excretion is an established index of atherosclerosis progression beyond<br />

the renal glomerulus. In the present study, we examined the interrelationships of<br />

MHT, WCHT and sustained hypertension (SHT) with urinary albumin excretion<br />

expressed as the albumin to creatinine ratio (ACR).<br />

Methods: 335 consecutive untreated non-diabetic subjects who referred to<br />

our clinic for 24-h ambulatory blood pressure (BP) monitoring, were classified<br />

as subjects with sustained normal BP (office BP


362 On the rescue: circulating stem cells<br />

P2199 The abundance of adipose tissue-derived progenitor<br />

cells in the adipose tissue is affected by age and<br />

blood glucose levels<br />

R. Madonna 1 , C. Cellini 1 , F.V. Renna 1 , L. Rinaldi 1 , R. Ippedico 1 ,<br />

R. Cotellese 1 ,N.Picardi 1 ,R.DeCaterina 2 . 1 G. D’Annunzio<br />

University, Chair of Cardiology, Chieti, Italy; 2 G. D’annunzio University - Chieti,<br />

University Cardiology Division, Chieti, Italy<br />

Adipose tissue-derived stromal cells (ADSCs) are being recognized as a source<br />

of stem cells potentially useful for cardiovascular repair, most likely by differentiating<br />

into vascular cells or by secreting angiogenic cytokines. The influence of<br />

cardiovascular risk factors on ADSC levels and their viability in elderly patients<br />

are currently unknown. We analyzed the abundance and angiogenic activity of<br />

adipose tissue-derived progenitor cells in patients most likely to benefit from this<br />

novel source of stem cells, i.e., elderly patients with cardiovascular risk factors.<br />

Methods: 40 subjects (age 67.9±11.7 years) with variable degrees of cardiovascular<br />

risk, underwent abdominal surgery for intercurrent diseases. Visceral<br />

adipose tissue (3±1 g visceral fat/patient) was processed by collagenase type<br />

I to obtain ADSCs from the stromal-vascular fraction, and immediately used for<br />

analyses, without further amplification in vitro or cell selection. The number of<br />

total ADSCs in primary cultures after digestion was automatically quantified by<br />

a Multisizer Coulter Counter. Progenitor cells (PCs) within ADSCs were quantified<br />

by flow cytometry as %CD45-/CD34+/CD133+ cells of total ADSCs. Matrigel<br />

angiogenesis assay was used to analyze the ability of ADSC to form tubes or<br />

networks.<br />

Increasing age (r = - 0.48, p


in the postero- and midseptal region. Interestingly, much larger MLC2a-positive<br />

APs were additionally found in the right and left lateral free wall regions. Periostin<br />

staining in the annulus fibrosis was however locally interrupted at locations where<br />

these broad lateral MLC2a-positive APs crossed the isolating annulus fibrosis of<br />

EPDC-inhibited hearts.<br />

Conclusion: Periostin expression on the developing annulus fibrosis seems to<br />

indicate AV-junctional myocardium fate. Small septal periostin-positive APs in<br />

the wildtype heart remain only temporarily functionally active, while broad lateral<br />

periostin-negative APs in EPDC-inhibited hearts persist and might provide a<br />

pathological substrate for postnatally persistent APs.<br />

P2203 The status of circulating endothelial progenitor cells<br />

in patients with documented coronary endothelial<br />

dysfunction<br />

B.A. Boilson, T.J. Kiernan, A. Lerman, R.D. Simari. Mayo Clinic,<br />

Interventional Cardiology, Rochester, United States of America<br />

Endothelial dysfunction is an early manifestation of vascular disease and a<br />

marker of atherosclerotic risk burden. There is growing evidence that bone<br />

marrow-derived hematopoietic stem cells may have a diagnostic and reparative<br />

role in vascular disease and may be a source of endothelial progenitors. Recent<br />

studies have shown depleted numbers of these cells both in established vascular<br />

disease and in patients with increased burden of cardiovascular risk. We hypothesized<br />

that hematopoietic stem cell numbers in circulating blood would be altered<br />

in the setting of coronary endothelial dysfunction (CED) in the absence of overt<br />

coronary disease.<br />

Methods: Fifty consecutive patients having undergone diagnostic coronary angiography<br />

for evaluation of chest pain and without significant coronary disease<br />

were enrolled. Presence of coronary endothelial dysfunction was determined by<br />

response to intracoronary acetylcholine. Five ml of whole blood was obtained<br />

from each patient at the time of cardiac catheterization and analyzed by flow cytometry<br />

for CD34 and CD133 using ISHAGE criteria. A group of twelve patients<br />

had 50ml of whole blood drawn at the time of cardiac catheterization and buffy<br />

coat was extracted using density gradient centrifugation. This was subjected to<br />

flow cytometric analysis for CD34 and CD133 and plated on fibronectin coated<br />

wells for colony forming units (CFUs) assay analysis at 7 days.<br />

Results: Thirty-one patients were determined to have CED as assessed by intracoronary<br />

acetylcholine challenge testing. Decreased numbers of CD34+ (whole<br />

blood, 10±1 vs 17±3 cells/100μL; buffy coat, 40±7 vs 81±11 cells/100μL,<br />

p


364 On the rescue: circulating stem cells<br />

Methods and Results: Mononuclear cells (MNC) were isolated from human<br />

blood by Ficoll gradient and were cultured over 4 days using endothelial cell selection<br />

medium. The resulting EPCs were incubated with angII (10-6 M and 10-7<br />

M), which led to a significant reduction of DiI-Ac-LDL/lectin double-positive cells<br />

compared to control (fluorescence microscopy, cell count). This effect could be<br />

inhibited by co-stimulation with an AT1 receptor antagonist, but not with an AT2<br />

receptor antagonist. AngII had no effect on cell proliferation (BrdU-FACS analysis),<br />

but increased apoptosis (histone DNA assay), enhanced intracellular reactive<br />

oxygen species formation (DCF fluorescence), reduced migratory capacity (modified<br />

Boyden chamber), and impaired colony forming unit formation (CFU assay)<br />

in cultured EPCs. Treatment of wild-type mice with angII (0.7 mg/kg/d) for 12d by<br />

osmotic minipumps led to decreased numbers of sca1/flk1-positive EPCs in peripheral<br />

blood and reduced the number, migratory capacity, and CFU formation of<br />

spleen-derived Dil-Ac-LDL/lectin double-positive EPCs, which was accompanied<br />

by a diminished reendothelialization and increased neointima formation after focal<br />

carotid injury. These angII effects were completely abolished in AT1a-/- mice. Salvage<br />

of reendothelialization by intravenous application of spleen-derived MNCs<br />

into angII-treated wild-type mice was more pronounced with AT1a-/- cells than<br />

with wild-type cells.<br />

Conclusions: Angiotensin II causes a reduction of EPC counts and impairs the<br />

functional capacity of these cells in vitro and in vivo. These findings indicate a<br />

relationship between the activation of the renin-angiotensin system and reduced<br />

number and function of circulating EPCs, which may play an important role in<br />

impaired endothelial regeneration and atherogenesis.<br />

P2208 Cyclosporin A suppresses proliferative capacity of<br />

endothelial progenitor cells: involvement of nitric<br />

oxide synthase inhibition<br />

L. Yang, X.-C. Yang, J.-K. Yang, F.-F. Yi, Q. Fan, X.-L. Liu, Y.-G. Ge.<br />

Beijing, China, People’s Republic of<br />

Background: The calcineurin inhibitor cyclosporin A (CsA) is a potent immunosuppressive<br />

agent that has formed the pharmacologic cornerstone of solid organ<br />

transplantation. Vascular injury has generally been considered a common-ground<br />

factor of CsA-induced organ damage. Endothelial toxicity is a feature of CsAinduced<br />

vascular injury. Vascular endothelial progenitor cells (EPCs) are the precursors<br />

of mature endothelial cells, and contribute to postnatal neovasculorization<br />

and re-endothelialization. Endothelial nitric oxide synthase (eNOS) is an important<br />

regulator of EPCs. Thus, we hypothesized that the vasculopathy induced<br />

by CsA may be partly due to its harmful effect on EPCs in which eNOS is involved.<br />

Purpose: To investigate the effects of CsA on proliferative capacity and<br />

eNOS/nitric oxide (NO) in cultured human EPCs from peripheral blood.<br />

Methods: EPCs were obtained from cultured mononuclear cells isolated from<br />

peripheral blood of healthy adults, and stimulated with CsA (10 μg/ml) in the<br />

presence or absence of recombinant human vascular endothelial growth factor<br />

165 (VEGF; 50 ng/ml). Cells’ proliferation and apoptosis were determined by<br />

the Cell Counting Kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferasemediated<br />

dUTP nick end labeling (TUNEL) staining respectively. eNOS was assayed<br />

by reverse transcription-polymerase chain reaction (RT-PCR) analysis. NO<br />

generation was detected by Griess method. To determine the effects of CsA at<br />

the different concentrations on EPCs’ proliferation, some cells were treated with<br />

CsA in a series of final concentrations (0, 10, 100, 1000, and 10000 ng/ml) for 48<br />

h, and cells’ proliferation was detected by CCK-8 assay.<br />

Results: CsA significantly inhibited EPCs’ proliferation at the concentrations from<br />

100 ng/ml to 10000 ng/ml, and the effect was dose dependent. While at the concentrations<br />

of 10 ng/ml, CsA failed to prevent EPCs’ proliferation obviously. VEGF<br />

(50 ng/ml) markedly promoted EPCs’ proliferation, eNOS gene expression, and<br />

NO generation production, which were completely abrogated by pre-treatment<br />

with CsA (10 μg/ml). In the presence or absence of VEGF (50 ng/ml), cells stimulated<br />

with CsA (10 μg/ml) resulted in a decrease of numbers by both ways of<br />

preventing proliferation and promoting apoptosis, eNOS mRNA and NO generation<br />

productions were potently decreased in CsA-treated samples.<br />

Conclusions: CsA significantly inhibits proliferative capacity, prevents eNOS<br />

gene expression, and decreases NO productions in cultured human peripheral<br />

blood EPCs.<br />

P2209 Impaired in-vivo re-endothelialization capacity,<br />

accelerated senescence of endothelial progenitor<br />

cells (EPCs) and endothelial dysfunction in patients<br />

with pre-hypertension<br />

G. Giannotti 1 , M. Mueller2 , C. Doerries3 ,T.Horvath2 ,<br />

S.A. Sorrentino2 , N. Steenken2 , C. Manes3 , M. Marzilli1 ,H.Drexler2 ,<br />

U. Landmesser3 . 1University Hospital of Pisa, Department of Cardiology,<br />

Pisa, Italy; 2Hannover Medical School, Department of Cardiology, Hannover,<br />

Germany; 3University of Zurich, Cardiovascular Center, Zurich, Switzerland<br />

Purpose: Prehypertension, a precursor of stage 1 hypertension, is associated<br />

with increased cardiovascular risk. Endothelial dysfunction has been suggested<br />

to contribute to development of hypertension; however, no data on endothelial<br />

function and functional capacity of EPCs are available in subjects with prehypertension<br />

(systolic blood pressure of 120-139 mmHg). We therefore examined<br />

endothelium-dependent vasodilation, in vivo re-endothelialization capacity and<br />

senescence markers of EPCs in subjects with prehypertension.<br />

Methods: Endothelium-dependent, flow-mediated vasodilation (FDD) of the radial<br />

artery, a highly sensitive measure of endothelial function, was assessed using<br />

high-resolution ultrasound. In vivo re-endothelialization capacity of EPCs was<br />

determined after transplantation of 5 x 105 EPCs into nude mice using a carotid<br />

endothelial injury model, and re-endothelialized area (REA) was assessed after<br />

3 days. EPC senescence was detected by acidic beta-galactosidase staining and<br />

telomere length analysis. Healthy subjects (n=16), prehypertensive (n=16) and<br />

hypertensive subjects (n=20) were matched for age, sex and body mass index.<br />

All participants had no hypercholesterolemia, no diabetes, no known cardiovascular<br />

disease, were non-smokers and did not take any medication.<br />

Results: Endothelium-dependent vasodilation was impaired in prehypertensive<br />

subjects (FDD: 9.0±1.9% vs. 11.4±2.9%; p


elevation myocardial infarction (AMI). However the safety of stem cell transplantation<br />

in patients with severe left ventricular dysfunction after AMI has not been<br />

evaluated.<br />

Methods: The study population consisted of patients who suffered AMI, were<br />

treated with percutaneous coronary angioplasty and stenting and had left ventricular<br />

ejection fraction less than 40% 5 to 10 days after AMI. Peripheral blood stem<br />

cells (PBSCs) were mobilized by G-CSF 10 μg/kg body weight for 5 days and<br />

delivered to infarcted myocardium via intracoronary infusion.<br />

Results: Eleven consecutive patients 54±12 years old with an ejection fraction<br />

of 36±7.8% were treated. Four of those patients were survivors of post MI<br />

cardiogenic shock. G-CSF stimulation led to sustained mobilization of mononuclear<br />

cells, with a 5-fold increase (from 10314±2871/mm 3 at baseline to<br />

50762±15723/mm 3 on day 5; P=0.001). PBSCs transplantation was performed<br />

16±2 days after AMI. An average of 3.1±1.3x109 nucleated cells were infuced<br />

containing 9.8±2.5x106CD34+ cells. Adverse events related to infusion occurred<br />

in 3 patients (27%). One patient with a LVEF of 25% developed temporary occlussion<br />

of the left anterior descending coronary artery (LAD) during the transplantation<br />

procedure which resolved after approximately 30 minutes and a second<br />

patient with a LVEF of 23% developed hemodynamic collapse in every LAD occlusion<br />

with rapid hemodynamic restoration after balloon deflation. A third patient<br />

suffered periprocedural MI diagnosed by troponin elevation.<br />

Conclusion: Intracoronary infusion of PBSCs should be performed with great<br />

caution in patients with significant left ventricular dysfunction after AMI<br />

P2212 Cardiomyogenic differentiation potential of<br />

mesenchymal stem cells declines with increase in<br />

age: rebuilding the heart with old or new bricks?<br />

D.A. Pijnappels, M.J. Schalij, A.A. Ramkisoensing, J. Van Tuyn,<br />

H.A. Farias, C.L. Gomez, A.A.F. De Vries, D.L. Ypey, A. Van Der<br />

Laarse, D.E. Atsma. Leiden University Medical Center, Cardiology Department,<br />

Leiden, Netherlands<br />

Background: In cardiac cell therapy, often autologous stem cells from adult patients<br />

are used as therapeutic agent. However, the correlation between the cardiomyogenic<br />

differentiation potential of stem cells and the host’s age is not studied<br />

in much detail. Therefore we assessed, in an in-vitro model, the capacity of<br />

both neonatal and adult rat mesenchymal stem cells (MSCs) to differentiate into<br />

cardiac cells.<br />

Materials and Methods: Bone-marrow derived MSCs of 2-day old neonatal rats<br />

(nr) and 10-weeks old adult rats (ar) were studied for their surface-maker profile<br />

by flow cytometry. To assess cardiomyogenic differentiation, either 50x10 3<br />

eGFP-labeled nrMSCs or arMSCs were co-cultured with 1.5x10 6 nr ventricular<br />

cardiomyocytes (CMCs) for 10 days on coated glass coverslips. Cardiomyogenic<br />

differentiation of MSCs was assessed both at day 3 and 10 of co-culture by a<br />

combination of immunocytochemical analysis for cardiac protein expression, and<br />

whole-cell patch clamp experiments to study action potential characteristics after<br />

pharmacological gap junctional uncoupling.<br />

Results: Flow cytometric analysis of nrMSCs and arMSCs showed expression<br />

of traditional MSC surface-markers with only minor differences in expression levels.<br />

After 3 days of co-culture with nrCMCs, 34±5% and 30±6% of the nrM-<br />

SCs showed positive diffuse staining for sarcomeric alpha-actinin and cardiac<br />

troponin-I, respectively, while only less than 10% of the arMSCs stained positive.<br />

Interestingly, 10 days after co-culture, positive staining for sarcomeric alphaactinin<br />

and cardiac troponin-I in nrMSCs increased to 60±4% and 63±6%, respectively,<br />

but now including 17±5% (n=65) of positive staining in typical sarcomeric<br />

cross-striation (without signs of cell fusion). In contrast, only 20% (n=75) of<br />

the arMSCs showed positive diffuse staining for both cardiac markers at day 10,<br />

without cross-striation. Importantly, at day 10 of co-culture, nrMSC-derived CMCs<br />

(16%, n=9) were found to be beating independently from surrounding nrCMCs in<br />

the presence of the gap junction uncoupler 2-APB, while showing action potential<br />

characteristics (maximal diastolic potential: -63±4 mV) comparable to native<br />

nrCMCs (n=10). However, arMSCs were non-beating and showed only maximal<br />

diastolic potentials of -16±6 mV.<br />

Conclusion: Neonatal rat (nr) mesenchymal stem cells (MSCs) are able<br />

to undergo functional cardiomyogenic differentiation upon co-culture with nrcardiomyocytes,<br />

in contrast to adult rat MSCs. Therapeutic efficiency of autologous<br />

cell therapy using adult MSCs, aiming at cardiac regeneration, might therefore<br />

be seriously limited.<br />

P2213 Administration of intracoronary bone marrow<br />

mononuclear cells on chronic myocardial infarction<br />

improves diastolic function<br />

Kang Yao1 , R.C. Huang2 , Juying Qian1 ,JieCui1 , Lei Ge1 ,<br />

Yanlin Li1 , Feng Zhang1 , Aijun Sun1 ,Y.Z.Zou1 , Junbo Ge1 .<br />

1Zhongshan Hospital, Fudan University, Cardiology, Shanghai, China, People’s<br />

Republic of; 2First Hospital, Dalian Medical University, Cardiology Department,<br />

Dalian, China, People’s Republic of<br />

Background: Regeneration of the myocardium and improved ventricular function<br />

have been demonstrated in patients with acute myocardial infarction (MI) treated<br />

by intracoronary delivery of autologous bone marrow mononuclear cells (BMC)<br />

a few days after successful myocardial reperfusion by percutaneous coronary<br />

On the rescue: circulating stem cells 365<br />

intervention (PCI); however, the effects of intracoronary cell infusion in chronic MI<br />

patients are still unknown.<br />

Aims: The purpose of the present study was to investigate whether intracoronary<br />

infusion of BMC into the infarct-related artery in patients with healed MI could<br />

lead to improvement in left ventricular (LV) function.<br />

Methods: Among 47 patients with stable ischemic heart disease due to a previous<br />

MI (13±8 months previously), 24 were randomized to intracoronary infusion<br />

of BMC (BMC group) and 23 to a saline infusion (CON group) into the target vessel<br />

after successful PCI within 12 hours after chest pain occurred. LV systolic and<br />

diastolic function, infarct size, and myocardial perfusion defect were assessed<br />

with the use of echocardiography, magnetic resonance imaging (MRI), or 201Tl<br />

single-photon-emission computed tomography (SPECT) at baseline and repeated<br />

at the 6 month follow-up examination.<br />

Results: BMC treatment did not result in a significant increase in LV ejection fraction<br />

in any of the groups by any of the methods used, and the apparent tendency<br />

of an improvement was not statistically different between the two groups. The two<br />

groups also did not differ significantly in changes of LV end-diastolic and systolic<br />

volume, infarct size, or myocardial perfusion. However, there was an overall effect<br />

of BMC transfer compared with the control group with respect to E/A (P


366 On the rescue: circulating stem cells / Tracking and homing<br />

derived mononuclear cell (BMDMNC) implantation on improving 6-month left ventricular<br />

(LV) function and reducing LV remodelling in a mini-pig model of acute<br />

anterior myocardial infarction (AAMI).<br />

Methods: The AAMI was developed by ligation of middle left anterior descending<br />

artery. The BMDMNCs were acquired using bone marrow aspiration from iliac<br />

crest of mini-pig. These cells were then isolated by Ficoll-paque solution and<br />

cultured for 1 week before implantation into infarcted area (IA). Eighteen male<br />

mini-pigs (weight 16-18 kilograms) were equally divided into group 1 (AAMI plus<br />

saline injection in IA), group 2 (AAMI plus 3.0 x 107 BMDMNC transplantation<br />

into the IA), and group 3 (normal control). Autologous BMDMNCs were promptly<br />

implanted into IA following induction of AAMI. The two-dimensional (2-D) echocardiography<br />

was performed before induction of AAMI and on days 7, 30, 90, and<br />

180.<br />

Results: The 2-D echocardiography on 90th and 180th day demonstrated the<br />

LV end diastolic and LV end systolic dimensions were higher, whereas LV ejection<br />

fraction (LVEF) was lower in group 1 than in groups 2 and 3 (all p <<br />

0.01). Six-month LV angiogram identified that LVEF was lower in group 1 than<br />

in groups 2 and 3 (all p < 0.01). In IA and peri-IA, the mRNA expressions of<br />

endothelial nitric oxide synthase, Bcl-2, interleukin-8 and peroximase proliferatoractivated<br />

receptor-γ coactivator (PGC)-1α were lower, whereas caspase-3, Bax<br />

and endothelin-1 were higher in group 1 than in groups 2 and 3 (all p < 0.01).<br />

Additionally, the apoptotic body was higher, whereas the number of small vessels<br />

was significantly lower in group 1 than in groups 2 and 3 (all p < 0.005).<br />

Conclusion: Autologous BMDMNC transplantation improves LV function and reduces<br />

LV remodelling via eliciting molecular-cellular mechanisms.<br />

P2216 Comparison of early and late combined<br />

(intramyocardial and intracoronary) application of<br />

autologous bone marrow stem cells after myocardial<br />

infarction<br />

M. Gyoengyoesi, I. Lang, M. Dettke, G. Beran, S. Graf, H. Sochor,<br />

N. Nyolczas, A. Kaider, G. Maurer, D. Glogar on behalf of MYSTAR<br />

Study investigators. Medical University of Vienna, Internal Medicine II, Dept. of<br />

Cardiology, Vienna, Austria<br />

Purpose: The MYSTAR multicenter randomized study compares the results of<br />

early (E) and late (L) combined (intracoronary+intramyocardial) injections of large<br />

number of unselected autologous bone marrow (BM)-derived mononuclear cells<br />

(MNCs) in 60 patients with a recent first acute myocardial infarction (AMI) with a<br />

reopened infarct-related artery (IRA).<br />

Methods: Patients with a left ventricular (LV) ejection fraction (EF)


assigned to receive either unselected BMCs (n=137) transplant or saline (n=134)<br />

within 3 hours after successful PCI to the distal vessel of the infarct-related artery<br />

through micro-catheter.<br />

Results: All patients were followed up within 12 months. Intracoronary BMCs<br />

application did not incur cardiovascular events, including ventricular arrhythmias<br />

or syncope, occurred during 12-month follow-up. By quantitative LV angiography<br />

at six months, LV ejection fraction (LVEF) significantly increased (p


368 Tracking and homing / Development from primitive to adult progenitor cells<br />

areas. The unipolar voltage of the ischemic area has decreased from 44.1±18%<br />

to 24,2±17.2%. The LLS maps have shown the decrease of akinetic and hypokinetic<br />

areas that resulted in normal contraction of these areas. The percentage<br />

of hypokinetic and akinetic areas has decreased from 39.2±17% to 29,2±15%.<br />

Furthermore, the defect myo-cardial perfusion has decreased from 52.4±17% to<br />

27,1±15% based on SPECT data. The mean LVEF was 35.9±4% at follow up<br />

compared with 29,5±4% at baseline. The CCS and NYHA functional class has<br />

decreased from 2.9 to 1.5 and 3.4 to 2.1 respectively at follow up.<br />

Conclusions: Endocardial stem cells implantation with Noga system in patients<br />

with ischemic heart failure, ejection fraction less then 35%, III-IV NYHA and CCS<br />

angina functional class has showed to be a safe procedure and may improve left<br />

ventricular function and clinical status.<br />

P2224 PET imaging of peripheral stem cell homing after<br />

intracoronary transfer in patients following MI in<br />

acute and chronic conditions<br />

C. Dedobbeleer, D. Blocklet, M. Toungouz, M. Lambermont,<br />

P. Unger, J.-P. Degaute, S. Goldman, G. Berkenboom. Hopital<br />

Erasme, Cardiology, Brussels, Belgium<br />

Purpose: Transcoronary transplantation of progenitor cells seems to be a promising<br />

therapeutical approach of ischaemic cardiomyopathy. As the timing of the<br />

transplantation remains controversial, we aimed to compare the homing of these<br />

cells in acute and chronic conditions and also to assess the feasibility of a peripheral<br />

approach for CD34+ isolation (rather than bone marrow harvesting).<br />

Methods: 12 patients (range age: 41 to 71 years) with a history of reperfused anterior<br />

myocardial infarction underwent intracoronary infusion of purified CD34+<br />

cells 9±3 days (n=6, group A) or 20±5 months (n=6, group B). At baseline,<br />

the ejection fraction was lower in group B than in group A: 41±7% vs 56±7%<br />

(P


was injected. Left ventricular function was determined with a 9.4T animal MRI six<br />

weeks after surgery.<br />

Results: Proliferation was significantly increased when cells were cultured with<br />

conditioned medium of the other cell type, pointing at a paracrine mutual stimulation.<br />

Left ventricular function was preserved after transplantation of EPDCs,<br />

CMPCs, or a combination of CMPCs and EPDCs when compared to vehicle injection<br />

(p


370 Development from primitive to adult progenitor cells / Imaging in coronary heart disease: cardiovascular magnetic resonance<br />

CPC) is lacking, and no efficient, reproducible method exists to isolate CPC from<br />

human hearts.<br />

Objective: To determine which zone within the hearts of patients with ischemic<br />

and non-ischemic heart disease contains larger reservoir of hCPCs with regenerative<br />

capacity.<br />

Methods and Results: We developed an efficient and reproducible method to<br />

isolate hCPCs from the myocardium of patients with ischemic and non-ischemic<br />

heart disease, heart failure and diabetes. Following patients’ consent, tissue samples<br />

were donated during all kinds of open heart surgery and percutaneous RV<br />

septum biopsies. Isolated cells created typical clones, possessed self-renewal capacity<br />

and expressed stem cell markers including c-kit (22%), Isl-1 (7%), progenitor<br />

cell markers such as GATA 4 (60%), cardiac α-actin (60%). In the culture there<br />

are 70%) for the hematopoietic and endothelial marker CD34,<br />

the endothelial marker CD31, the endothelial and mesenchymal stem cell (MSC)<br />

marker CD105, as well as for CD29 and CD49b. Using the primary explant technique,<br />

outgrowth of spindle-shaped cells from the myocardial samples was apparent<br />

at 5-7 days after seeding. Outgrowing cells were highly enriched in ALDHhigh<br />

cells (61±11%; n=24). At 3-6 weeks, spherical cell clusters ("cardiospheres")<br />

were obtained. Cells derived from cardiospheres were expanded by serial passages<br />

from P1 to P5 and characterized by FACS analysis. They showed positive<br />

(>95%) for the MSC markers CD13, CD44 and CD105, as well as for CD29<br />

and CD49b, but negative for lymphoid (CD3), myeloid (CD11b), leukocyte (CD45)<br />

markers, CD117 (c-kit), CD135 and CD150. They contained significant subsets<br />

of CD90, CD31, CD38, CD49a, CD49d, CD71 and CD106-positive cells. Overall,<br />

cells expressing the stem cell marker CD133 were rare but, occasionally, cardiospheres<br />

contained up to 80% of CD133-positive cells. In conclusion, human<br />

myocardium contains ALDH-high cells that can be passaged (>P20) and form<br />

cardiospheres that predominantly consist of MSCs, stromal progenitors and, to a<br />

lesser extent, endothelial progenitors. These findings indicate that high ALDH activity<br />

is a functional marker of adult human cardiac-resident progenitor cells which<br />

can be highly enriched by the primary explant technique.<br />

P2234 Endovascular gingival fibroblast cell therapy reduced<br />

the size of aneurysms in a rabbit model of<br />

elastase-induced carotid injury<br />

E. Durand1 , N. Reynald1 , L. Couty1 , B. Fournier1 ,C.Brasselet1 ,<br />

M. Lemitre 1 , B. Coulomb1 , B. Gogly1 , A. Lafont2 . 1University Paris Descartes, INSERM U849, Paris, France; 2Hopital Europeen Georges<br />

Pompidou, Service De Cardiologie, Paris Cedex 15, France<br />

Background: Aortic aneurisms are associated with excessive enlargement remodeling,<br />

medial elastin degradation and overexpression of MMP-9. We recently<br />

reported that gingival fibroblast prevent medial elastin degradation in vitro and in<br />

an ex-vivo model via overexpression of TIMP-1. We therefore aimed to evaluate<br />

in vivo cell therapy using endovascular gingival fibroblasts in a model of arterial<br />

aneurism.<br />

Methods and Results: Elastase from porcine pancreas (4U/artery) was incubated<br />

during 15 minutes in rabbit carotid arteries (n = 18). Four to 6 weeks later,<br />

carotid arteries were seeded endoluminally at the site of aneurism with either<br />

rabbit gingival fibroblasts (n=7), or culture medium only which served as control<br />

(n=11). Vessel diameter and elastin density were assessed 4 weeks after cell<br />

therapy. Carotid diameter was similar before cell therapy in both group (3.39±0.54<br />

mm vs 3.10±0.37 mm, p=0.30). In contrast, carotid diameters were significantly<br />

decreased in aneurismal arteries seeded with rabbit gingival fibroblast as compared<br />

to control aneurismal arteries (2.59±0.64 mm vs 3.60±0.52, p=0.003).<br />

Moreover, elastin density was significantly higher in the media after endovascular<br />

gingival fibroblast than in controls (40.79±4.70% vs 17.48±8.22%, p=0.001)<br />

Conclusions: Endovascular gingival fibroblast cell therapy restored elastin integrity<br />

and reduced the size of aneurysms in a rabbit model.<br />

IMAGING IN CORONARY HEART DISEASE:<br />

CARDIOVASCULAR MAGNETIC RESONANCE<br />

P2235 Prognostic value of late gadolinium enhancement by<br />

CMR in predicting major adverse events in patients<br />

with or suspected coronary artery disease with<br />

different resting systolic function<br />

A.K.Y. Chan, W.W.M. Lam, Y.Y. Lam, Q. Zhang, W.W.M. Chan,<br />

J.Y.S. Chan, C.M. Yu. The Chinese University of Hong Kong, Hong Kong, Hong<br />

Kong SAR, People’s Republic of China<br />

Background: Clinical utility of myocardial infarct/scar detection by contrast enhanced<br />

cardiac magnetic resonance imaging (CMR) is well validated after myocardial<br />

infarction. The prognostic value of late gadolinium enhancement (LGE)<br />

on major adverse cardiovascular events (MACE) in stable CAD patients with preserved<br />

or depressed left ventricular systolic function is not known.<br />

Methods: Gadolinium-enhanced CMR were performed in 269 consecutive patients<br />

(mean age 62.2±11.1 years) referred for evaluation of systolic function and<br />

detection of infarct/scar by late gadolinium enhancement (LGE). Depending on<br />

left ventricular ejection fraction (LVEF), patients were classified into 2 groups: relative<br />

preserved systolic function with LVEF ≥ 40%; depressed systolic function<br />

with LVEF


of MACE in patients with LGE and depressed systolic function with LVEF


372 Imaging in coronary heart disease: cardiovascular magnetic resonance<br />

Results: At baseline, 329/640 segments were dysfunctional, by displaying


P2243 Blood oxygenation level-dependent magnetic<br />

resonance imaging in patients with coronary artery<br />

disease: a validation study against positron emission<br />

tomography<br />

T.D. Karamitsos 1 , A. Recio-Mayoral2 ,J.R.Arnold1 , L. Leccisotti 2 ,<br />

R.K. Howells1 , M.D. Robson1 , O.E. Rimoldi2 ,P.G.Camici2 , S. Neubauer1 ,<br />

J.B. Selvanayagam1 . 1Oxford Centre for Clinical Magnetic Resonance,<br />

Cardiovascular Medicine, Oxford, United Kingdom; 2Imperial College,<br />

Hammersmith Hospital, MRC Clinical Sciences Centre, London, United Kingdom<br />

Purpose: Elevated deoxyhaemoglobin seen downstream a territory subtended by<br />

a stenotic coronary artery can be assessed by blood oxygenation level-dependent<br />

(BOLD) magnetic resonance imaging (MRI). Previous animal studies have used<br />

a T2-prepared steady-state free-precession (SSFP) sequence to determine the<br />

BOLD signal in the myocardium. We sought to apply this method at 3 Tesla (T)<br />

in patients with documented coronary artery disease (CAD) and compared it to<br />

perfusion measurements by positron emission tomography (PET).<br />

Methods: 13 patients (mean age 62±8 years, 10 men) with angiographically documented<br />

CAD (at least 1 stenosis of > 70% diameter at quantitative coronary<br />

angiography-QCA) underwent 3T BOLD-MRI and PET imaging. For BOLD-MRI<br />

a single midventricular slice was acquired every 30 seconds at rest and during<br />

adenosine stress (140 μg/kg/min). A set of 6 images was acquired at rest and<br />

at peak stress. Using PET imaging with oxygen-15 labelled water, myocardial<br />

blood flow (MBF) was measured at baseline and during hyperaemia following i.v.<br />

adenosine. The BOLD short-axis view was divided into 6 segments, according<br />

to the midventricular segments of the 17-AHA segment model and mean signal<br />

intensities (SI) at rest and stress were calculated using QMass (Medis) software.<br />

SI values were corrected for differences in T1-weighting owing to heart<br />

rate changes at stress and rest. PET images were analysed with MATLAB software<br />

(the MathWorks Inc.) and registered with the BOLD short-axis image using<br />

anatomical landmarks.<br />

Results: Rest MBF in territories (n=34) subtended >70% stenoses (STE;<br />

1.02±0.35 ml/min/g) did not differ from MBF in remote myocardium (REM; n=44)<br />

subtended by non-diseased arteries (0.98±0.32 ml/min/g; p=0.6). By contrast, hyperaemic<br />

MBF in STE was significantly lower than in REM (2.2±1.0 vs 2.9±0.8<br />

ml/min/g; p=0.002). Similarly, BOLD-SI change was 1.9±10% in STE compared<br />

with 7.6±9% in REM (p=0.001). Taking QCA as the gold standard, cut-off values<br />

for stress MBF (≤ 2.45ml/min/g) and BOLD SI change (≤ 3.59%) were determined<br />

in order to define ischaemic myocardial segments. BOLD-MRI and PET<br />

agreed with respect to the presence or absence of ischaemia in 11 of the 13 patients<br />

(85%). With regards to per segment analysis, taking PET as the gold standard<br />

and by applying the determined cut-off values for stress MBF and BOLD<br />

SI, BOLD MRI had good sensitivity (76%) but moderate specificity (62%) for the<br />

identification of ischaemia.<br />

Conclusions: T2-prepared SSFP 3T BOLD imaging is feasible in the clinical setting<br />

and has good agreement with PET perfusion measurements for the detection<br />

of myocardial ischaemia.<br />

P2244 Evaluation of coronary artery disease; coronary<br />

stenosis on MSCT versus myocardial perfusion on<br />

MRI<br />

J.M. Van Werkhoven1 , J.D. Schuijf1 ,J.W.Jukema1 ,J.Schreur2 ,<br />

M. Heijenbrok2 ,E.E.VanDerWall1 ,J.J.Bax1 . 1Leiden University<br />

Medical Center, Cardiology, Leiden, Netherlands; 2Medical Center<br />

Haaglanden, Cardiology, Den Haag, Netherlands<br />

Purpose: Non-invasive computed tomography coronary angiography (CTA) can<br />

accurately assess the presence of coronary artery disease (CAD). Because of<br />

the high negative predictive value it may be particularly effective to rule out CAD.<br />

In patients with abnormal CTA, optimal treatment strategy may remain uncertain<br />

as no information on the hemodynamic effect is obtained. The purpose of this<br />

study was to assess the combined use of CTA and myocardial perfusion imaging<br />

with magnetic resonance imaging (MRI).<br />

Methods: In this prospective study, 55 patients (62% male, average age 57±9<br />

years, pre-test likelihood low to intermediate 62%) underwent 64-slice CTA and<br />

1.5 Tesla MRI within 40 days. CAD (normal 50%) was determined on CTA and first pass perfusion during<br />

adenosine stress was assessed on MRI.<br />

Results: CTA was normal in 15 (27%), 30-50% in 24 (44%) and >50% in 16<br />

(29%) patients. MRI revealed a perfusion defect in 21 (38%) patients, and was<br />

Figure 1<br />

Imaging in coronary heart disease: cardiovascular magnetic resonance 373<br />

normal in 34 (62%). Figure 1 shows the MRI results for the individual CTA cateogies.<br />

In patients with an abnormal perfusion on MRI, CTA was normal in only 1<br />

(5%) patient and showed non-significant and significant CAD in respectively 9<br />

(43%) and 11 (52%) patients. Conversely, in patients with normal perfusion on<br />

MRI, normal CTA was observed in 14 (41%). Non-significant and significant CAD<br />

was noted in 15 (44%) and 5 (15%) patients respectively.<br />

Conclusion: Although the prevalence of abnormal perfusion increases with the<br />

degree of stenosis, a substantial proportion of patients with significant CAD on<br />

CTA have normal perfusion on MRI. Conversely, underlying CAD is present in the<br />

majority of patients with a normal MRI perfusion study. The combination of both<br />

techniques may allow more refined characterization of CAD.<br />

P2245 Contractile reserve by dobutamine cardiac magnetic<br />

resonance imaging of dysfunctional myocardial<br />

segments corresponds well with improvement in<br />

quantitative wall thickening after revascularization<br />

S.W.M. Kirschbaum, K. Gruszczynska, D.J. Duncker, A. Rossi,<br />

G.P. Krestin, P.W. Serruys, P.J. Feyter, R.J. Van Geuns. Erasmus Medical Center,<br />

Cardiology Dept, Rotterdam, Netherlands<br />

Purpose: We investigated the relation between transmural extent of infarction,<br />

contractile reserve and improvement after revascularization in chronic dysfunctional<br />

myocardial segments.<br />

Methods: MRI was performed in 40 patients before recanalisation of a chronic total<br />

coronary artery occlusion and at 6 months follow-up (FU) this was compared<br />

to 21 patients without revascularization. Segmental wall thickening (SWT) was<br />

quantified at rest and with low dose dobutamine (5 and 10 microgram/kg/min)<br />

(LDD). Contractile reserve and the transmural extent of infarction (TEI) were related<br />

to SWT at follow-up.<br />

Results: Mean SWT of all dysfunctional CTO perfused segments increased during<br />

LDD with 15 percentage points 16±19% to 31±34% (p


374 Imaging in coronary heart disease: cardiovascular magnetic resonance<br />

Patients with abnormal MDCT (defined as CT calcium score >0 and/or coronary<br />

artery stenosis >50%) all underwent conventional invasive coronary angiography.<br />

Significant CAD was defined as >70% stenosis on invasive coronary<br />

angiography, or 50-70% stenosis with additional fractional flow reserve<br />

measurement


P2250 Prognostic value of revascularization-related<br />

irreversible myocardial injury<br />

K. Rahimi, A.P. Banning, A.S.H. Cheng, T.J. Pegg, T.D. Karamitsos,<br />

S. Darby, D. Taggart, S. Neubauer, J.B. Selvanayagam. Oxford,<br />

United Kingdom<br />

Background: Myocardial revascularization, either by coronary artery bypass<br />

grafting (CABG) or by percutaneous coronary intervention (PCI), improves outcomes<br />

in patients with coronary artery disease. However, these procedures may<br />

themselves cause irreversible myocardial injury, and their prognostic impact is uncertain.<br />

Delayed enhancement cardiovascular magnetic resonance imaging (DE-<br />

CMR) has been shown to reliably identify areas of irreversible myocardial injury.<br />

Objectives: To evaluate the impact of procedural myocardial injury as measured<br />

by DE-CMR on medium-term prognosis following myocardial revascularization.<br />

Methods: A prospective observational study in a tertiary hospital setting of 152<br />

CABG or PCI patients with clinical follow up of median 2.9 years. The primary<br />

endpoint was defined as death, non-fatal myocardial infarction (MI), ventricular<br />

arrhythmia (VA), or unstable angina or heart failure requiring hospitalization.<br />

Results: 27 patients (18%) reached the primary endpoint. 49 patients (32%) had<br />

evidence of new procedure-related myocardial hyperenhancement (HE) with a<br />

median mass of 5.0g (interquartile range 2.7-9.8). After adjustment for age and<br />

sex, these patients had a 3.1-fold (95% confidence interval 1.4, 6.8; p=0.004)<br />

higher risk of adverse outcome than patients without new HE. Neither periprocedural<br />

cardiac troponin levels nor quantitative measures of left ventriclular function<br />

showed any significant independent association with the primary endpoint after<br />

adjustment for new HE, nor did they alter the independent association of new HE<br />

with the primary endpoint. Exclusion of cases due to hospitalization for angina or<br />

heart failure yielded a similar association between new HE and the outcome.<br />

Conclusion: Myocardial injury during PCI or CABG, identified by DE-CMR, is a<br />

more powerful prognostic marker of adverse clinical outcome than widely-used<br />

biochemical and functional measures of myocardial injury. Particularly in low risk<br />

patients, the competing risk of new myocardial damage caused by the intervention<br />

may well outweigh the benefit of salvaged myocardium.<br />

P2251 Microvascular obstruction over time as a predictor for<br />

left ventricular remodeling<br />

J.F. Rodriguez Palomares1 ,J.T.Ortiz2 , D.C. Lee3 ,E.Wu3 .<br />

1 2 Barcelona, Spain; Hospital Clinic, Cardiology, Barcelona, Spain;<br />

3Northwestern Memorial Hospital, Cardiology, Chicago, United<br />

States of America<br />

Introduction: Microvascular obstruction (MO) can be evaluated using contrastenhanced<br />

CMR and is identified as areas of hypoperfusion in the infarct zone<br />

within 3 minutes. However, a similar phenomenon can be seen on delayed viability<br />

images 10 minutes after contrast injection following acute myocardial infarction<br />

(AMI). Due to its shorter scanning time, the inversion-recovery single-shot true<br />

fast imaging with steady-state precession (ss-IR) allows analysis of any dynamic<br />

changes in infarct and "no-reflow" sizes over time after contrast administration.<br />

Purpose: The aim of this study is to analyze dynamic changes of MO at different<br />

times after contrast administration and the size of hypoperfusion that best<br />

correlates with ventricular remodeling in patients following AMI.<br />

Methods: Subjects were evaluated using CMR within the first week (n= 60), 3<br />

months (n=47) and one year (n= 25) after a ST-segment elevation MI percutaneously<br />

revascularized. Cine CMR was performed to measure left ventricular<br />

function. Additionally, as a gold-standard, segmented inversion-recovery (seg-IR)<br />

were acquired 10 min after the administration of contrast, and ss-IR images were<br />

acquired sequentially at 1, 3, 5, 7, 10, 15, 20, and 25 min after bolus contrast<br />

administration to measure microvascular obstruction. Inversion times were set to<br />

properly null normal myocardium at each time point. All images were blinded,<br />

randomized, and measured for hypo- and hyper-enhancement volumes.<br />

Results: There was a significant reduction of hypo-enhancement volumes over<br />

time (p


376 Imaging in coronary heart disease: cardiovascular magnetic resonance / Contrast echocardiography<br />

-0.39; p= 0.014). Both T2-LGE (r = -0.52; p=0.002) and LGE alone (r = 0.41; p=<br />

0.018) correlated with delta EDV. T2-LGE correlated with delta-ESV (r= -0.39, p=<br />

0.026) but LGE alone did not (p= 0.43). The relation between T2-LGE, delta EDV<br />

and delta-ESV remained significant after correcting for the inter-study duration,<br />

time to reperfusion, ejection fraction and LGE extent.<br />

Conclusion: We propose a myocardial salvage index based on the difference<br />

between T2-weighted abnormality and late gadolinium enhancement. This novel<br />

CMR-based parameter may have the potential to serve as a surrogate end-point<br />

in studies assessing the efficacy of infarct reperfusion strategies.<br />

CONTRAST ECHOCARDIOGRAPHY<br />

P2254 Prognostic significance of perfusion abnormalities<br />

identified by myocardial contrast echocardiography in<br />

diabetics with no significant coronary lesions<br />

C. Aggeli, G. Giannopoulos, G. Roussakis, E. Christoforatou,<br />

G. Marinos, C. Toli, C. Kokkinakis, A. Michaelides, C. Pitsavos,<br />

C. Stefanadis. 1st Dept. of Cardiology, University of Athens, Athens, Greece<br />

Aim: To assess the prognostic significance of myocardial perfusion abnormalities<br />

detected by the combination of dobutamine stress echocardiography (DSE) and<br />

myocardial contrast echocardiography (MCE) in patients with diabetes mellitus,<br />

who were angiographically shown to have coronary arteries free of significant<br />

stenoses.<br />

Methods: 60 (45 men, 68±7 years old) diabetics, who were submitted to coronary<br />

angiography and DSE/MCE within an one-month period without any intervening<br />

clinical events, were retrospectively selected from the database of our<br />

laboratory. Elligible patients were those with type 2 diabetes who were found on<br />

angiography to be free of significant coronary artery stenoses (≥50% reduction<br />

in luminal diameter). The DSE protocol consisted in four 3-minute stages of IV<br />

dobutamine infusion (10-40 μg/kg/min) with atropine as needed to achieve 90%<br />

of age-predicted maximal heart rate. An echo-contrast agent was infused at rest<br />

and at peak stress to better evaluate wall motion, as well as to assess myocardial<br />

perfusion. The patients were followed for two years. The composite endpoint was<br />

an acute coronary event or hospitalization for heart failure or death of cardiac<br />

causes.<br />

Results: 18 patients (30%) were found to demonstrate perfusion abnormalities at<br />

peak stress on DSE/MCE in at least two adjacent myocardial segments (MCE+<br />

subgroup), while the rest 42 (70%) had normal DSE/MCE studies (MCE- subgroup).<br />

The two subgroups did not differ significantly as far as age, gender and<br />

prevalence of hypertension, dyslipidemia and smoking habit were concerned. The<br />

two-year event rate in the MCE+ subgroup was 22.2%(4/18), versus only 4.8%<br />

(2/42) in the MCE- subgroup (p=0.025). In the multivariate binary logistic regression<br />

analysis the result of MCE remained a significant predictor of the composite<br />

endpoint (p=0.045).<br />

Conclusion: This is a report on the potential prognostic significance of perfusion<br />

abnormalities detected by stress-contrast echocardiography in diabetic patients<br />

with "normal" coronary arteries. The observed difference in the event rate could<br />

be linked to microcirculation abnormalities (giving rise to perfusion abnormalities<br />

on MCE) or to non-obstructive coronary artery wall lesions (as demonstrated to<br />

exist by past intravascular ultrasound [IVUS] studies in patients with normal coronary<br />

"luminograms"), which may cause impaired coronary flow reserve and, thus,<br />

perfusion abnormalities at stress. It should be noted that, given the small number<br />

of events and the retrospective nature of the study, these interesting findings need<br />

to be confirmed prospectively in larger series of subjects.<br />

P2255 Unification of the planes of the right ventricle<br />

obtained by contrast echocardiography and<br />

computed tomography<br />

A. Laucevicius 1 , D. Zakarkaite1 ,S.Aidietiene2 , M. Mataciunas1 ,<br />

A.E. Tamosiunas1 . 1Vilnius University Santariskiu Hospital, Centre<br />

of Cardiology and Angiology, Vilnius, Lithuania; 2Vilnius University Medical<br />

Faculty, Clinic of <strong>Heart</strong> Diseases, Vilnius, Lithuania<br />

Purpose: The aim of our study was to explore methodological aspects of right<br />

ventricle (RV) assessment from multiple echocardiographic (Echo) planes for better<br />

visualization using contrast enhancement and to explore the correspondence<br />

of areas obtained by Echo with those obtained by multislice computer tomography<br />

(CT).<br />

Methods: Conventional parasternal long and short axis views at a different level,<br />

the apical four-chamber view as well as multiple subcostal views of the RV were<br />

obtained in 54 patients (12 women). All the patients underwent Echo examination<br />

without, and then, with contrast enhancement using iE33 (Philips) ultrasound<br />

machine. For the enhancement of the right heart cavities, echocontrast was administered<br />

by: 1) the injection of 10 ml agitated saline solution mixed with small<br />

amount of diluted blood and applying ultrasound oscillations with the mechanical<br />

index (MI) between 0.13 and 1.2; 2) the injection of commercially available<br />

echocontrast Optison (GE Healthcare) and applying ultrasound oscillations with<br />

MI = 0.21.<br />

In 10 patients areas of RV planes on subcostal and parasternal Echo views were<br />

compared with the corresponding areas obtained on CT.<br />

Results: The comparison of Echo and CT data enabled us to separate three<br />

non-parallel (perpendicular) planes of the RV on Echo. The comparison of the<br />

areas of the RV on these Echo planes with the areas of corresponding CT slices<br />

revealed close correlation between both methods (r = 0.88, p = 0.028). When<br />

using echocontrast enhancement with agitated saline solution we were able to<br />

enhance more close to the probe wall contour, the distal contour was obscured<br />

by gas in bubbles. The optimal contrasting of the RV cavity was obtained when<br />

using ultrasound vibrations with MI 0.9-1.1. Standard use of Optison produced<br />

quick rise of echogeneity of RV myocardium and non-homogenous distribution of<br />

echocontrast in the RV cavity. Better results of RV enhancement were obtained<br />

when Optison was combined with agitated saline solution after echocontrast fills<br />

the left ventricle cavity.<br />

Conclusions: 1) RV assessment from three non-parallel (perpendicular) planes<br />

of the RV on Echo can be used for mathematical reconstruction of the RV cavity.<br />

2) The close correlation between both methods was found when comparing the<br />

areas of the RV from Echo planes with the areas of corresponding CT slices.<br />

3) Combination of Optison enhanced by agitated saline solution can be one of the<br />

solutions for optimal echocontrast enhancement of RV endocardial borders.<br />

P2256 Marked decline in clinical use of ultrasound contrast<br />

agents following black box warning: observations<br />

from the clinic<br />

Y.M. Smyth, R.S. Gabriel, E. Mayer Sabik, A.L. Klein, R. Grimm,<br />

J.D. Thomas, V. Menon. Cleveland Clinic, Cardiovascular Imaging,<br />

Cleveland, United States of America<br />

Purpose: The utility of contrast echocardiography is well established. Recent adverse<br />

events have led regulatory agencies in the USA to issue a warning on the<br />

utilization of perflutren containing contrast agents (Definity; BMS and Optison;<br />

GE, USA). We sought to evaluate the impact of this on contrast utilization at our<br />

institution<br />

Methods: Over a 4 week period all transthoracic (TTE) and stress echocardiograms<br />

(SE) in a quaternary referral center and 3 outpatient facilities were studied.<br />

For each echocardiogram, the sonographer indicated whether contrast would<br />

have been given prior to the FDA warning. We analyzed current rates of utilization,<br />

contraindications to utilization and monitored for adverse events as dictated<br />

by the package insert. Actual usage was compared to data from previous years.<br />

Results: Questionnaires on 1381 studies were included, 72% TTE (10% bedside)<br />

and 28% SE. Contrast was indicated in 8.3% of studies, more frequently<br />

for SE (13.4% vs 6.3% TTE, p


needed to achieve 90% of age-predicted maximal heart rate (APMHR). An echocontrast<br />

agent was infused at rest and at peak stress in order to better evaluate<br />

wall motion, as well as to assess myocardial perfusion. All patients remained<br />

under surveillance for at least 30 minutes after the completion of the test. Adverse<br />

events were recorded during the test and for the 24 hours following it. The<br />

diagnostic accuracy of DSE/MCE was assessed on the basis of CAG findings<br />

(stenoses of ≥50% were considered as clinically significant).<br />

Results: As far as adverse events were concerned, no deaths or life-threatening<br />

events were encountered. One patient (0.95%) exhibited an excessive vasovagal<br />

reaction, which responded immediately to atropine administration and placement<br />

in the recumbent position. The most common adverse effects were mild-tomoderate<br />

in severity: xerostomia (N=11, 10.5%), headache (N=4, 3.8%), tremor<br />

(N=2, 1.9%), backpain (N=3, 2.9%), dizziness (N=4, 3.8%) and mild allergic reactions,<br />

consisting in pruritic skin rash (N=2, 1.9%), readily responsive to antihistamines.<br />

Urinary retention lasting for a few hours after the test was observed<br />

in 4 (3.8%) patients (all were men who received atropine to achieve APMHR).<br />

Onset of atrial fibrillation was observed in 2 patients (1.9%), both of whom spontaneously<br />

reverted to sinus rhythm in the first 24 hours after the test. No sustained<br />

supraventricular or ventricular arrhythmias were observed. 71.4% (N=75)<br />

of the patients were found to have significant stenoses on CAG. The sensitivity<br />

of DSE/MCE was 90.7% and its specificity was 80%. Of the 74 patients found<br />

positive for ischemia on DSE/MCE, 68 had significant stenoses on CAG (positive<br />

predictive value 91.9%), while the negative predictive value was 77.4%. The<br />

overall accuracy was 87.6%.<br />

Conclusion: DSE/MCE is a safe and accurate diagnostic technique for the assessment<br />

of coronary artery disease in octogenarians unsuitable for exercise<br />

stress testing.<br />

P2258 Feasibility and safety of contrast-enhanced real-time<br />

3D echocardiography within 24 hours after acute<br />

myocardial infarction<br />

G. Nucifora, N. Ajmone Marsan, H. Siebelink, J.M. Van Werkhoven,<br />

J.D. Schuijf, M.J. Schalij, E.R. Holman, J.J. Bax. Leiden University<br />

Medical Center, Department of Cardiology, Leiden, Netherlands<br />

Objectives: Contrast-enhanced (CE) echocardiography has been demonstrated<br />

to be useful in optimizing endocardial border delineation both for 2D and realtime<br />

3D echocardiography (RT3DE). However, no specific data exist regarding<br />

feasibility, efficacy and safety of CE RT3DE for the evaluation of left ventricular<br />

(LV) function among patients with acute myocardial infarction (AMI). In the present<br />

study we report our experience regarding the use of CE RT3DE performed the<br />

first day after AMI.<br />

Methods: 110 consecutive patients (57±11 years; 76% male) admitted to the<br />

coronary care unit because of ST-elevation AMI were included in the study.<br />

RT3DE with and without contrast was performed within 24 hours from patients’<br />

admission to evaluate LV volumes and ejection fraction (EF). Perflutren was used<br />

as contrast agent. Adequacy of endocardial border visualization was graded for<br />

each of the 16 cardiac segments as follows: 0= border invisible; 1= border visualized<br />

only partially throughout the cardiac cycle and/or incomplete segment length,<br />

and 2= complete visualization of the border. The 3D data sets were analyzed offline<br />

and LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF were<br />

measured using a dedicated analysis software.<br />

Results: During non-CE RT3DE, from the total number of 1760 LV segments,<br />

the endocardial border was invisible in 185 (10%) and visualized only partially in<br />

392 (22%). A complete visualization of the border was possible in 1183 (67%)<br />

segments. During CE RT3DE, adequate-to-full LV opacification was seen in 94%<br />

of patients and a complete visualization of the border was possible in 1493 (85%)<br />

segments (p


378 Contrast echocardiography<br />

mogeneities of the myocardial mechanical properties. The fibers are wound in a<br />

spiral structure around the cavity, generating the rotation of the left ventricle (LV)<br />

during contraction and relaxation. LV rotation tends to equalize the sarcomere<br />

shortening between the myocardial layers. The purpose of this study was to develop<br />

a method of measuring the transmural changes of LV rotation, torsion and<br />

circumferential strain in normal subjects, in order to establish the normal behavior.<br />

Methods:The method is based on B-mode ultrasound cines that underwent post<br />

processing utilizing 2D-Strain program (2DS) of speckle tracking imaging and a<br />

novel signal processing method of 3 dimensional wavelet de-noising (2DS-W).<br />

This new method enabled high temporal and spatial resolution measurements of<br />

the myocardial velocities, so that the circumferential strain and the myocardial rotation<br />

were evaluated during a full heart cycle for 3 myocardial layers. The study<br />

included two stages: validation process of the algorithm utilizing tissue mimicking<br />

phantoms, and a clinical stage. At the clinical stage, three levels of short-axis<br />

ultrasound echo cines (Apical, Papillary muscle and Mitral valve levels) were obtained<br />

from 36 normal subjects in order to measure the circumferential strain and<br />

the myocardial rotation.<br />

Results: The average error of rotation in respect to the real value, as obtained<br />

during the analysis of a software implemented phantom, was 7.5%, 2.9% and<br />

3.4% for the inner, middle and outer layers, respectively. The average error of circumferential<br />

strain in respect to the real value was 3%, 5% and 7% for the inner,<br />

middle and outer layers, respectively. The clinical results show a significant transmural<br />

difference in the myocardial rotation, torsion and circumferential strain. The<br />

rotation is larger for the endocardium (apex 8.7±3.7deg, base -4.9±3.6 deg) and<br />

decreases towards the epicardium (apex 5.1±2.8 deg, base -2.8±2.5 deg), while<br />

the apex and base rotate in counter directions. Similarly, the circumferential strain<br />

is larger at the endocardium (apex -32.7±7.8%, papillary muscles -27.9±5.7%,<br />

base -24.4±6.5%) than at the epicardium (apex -16.3±4.5%, papillary muscles<br />

-14.0±4.1%, base -13.8±4.1%).<br />

Conclusion: 2 dimensional echocardiography contains sufficient information to<br />

allow measurements of LV transmural inhomogeneities of the rotation, torsion<br />

and circumferential strain, providing a simple, affordable and commonly available<br />

diagnostic modality.<br />

P2262 Early end diastolic wall thickness changes after<br />

reperfusion in acute myocardial infarction predict late<br />

infarct transmurality as assessed by cardiac magnetic<br />

resonance<br />

M. Chaparro Munoz, A. Recio, E. Merli, A. Fischer, N. Bunce,<br />

G.R. Sutherland. London, United Kingdom<br />

Purpose: Complete reperfusion of acute infarcted segments results in an immediate<br />

increase in end-diastolic wall thickness (EDWT), which correlates with<br />

reactive hyperemia and extra cellular edema. We sought to determine whether<br />

the magnitude in EDWT after successful reperfusion for acute myocardial infarction<br />

(MI) correlates with transmural necrosis at follow up, as assessed by delayed<br />

enhancement imaging.<br />

Methods: We assessed EDWT and wall motion abnormalities in 26 consecutive<br />

patients with a first acute MI by standard M Mode and 2D echocardiogram performed<br />

within first 12 hours after successful primary angioplasty. After 3 months of<br />

follow up, a repeat echocardiogram was carried out to assess changes in EDWT<br />

and contractile function and magnetic resonance imaging (MRI) was performed to<br />

evaluate location and size of the infarct zone. Necrosis was judged as transmural<br />

when delayed enhancement after gadolinium contrast was extended >50%.<br />

Results: 416 segments were analysed. Compared with remote myocardium,<br />

dysfunctional segments in the infarct territory (n=144) had an increased EDWT<br />

(11±1.9 versus 9.4±1.1 mm, p


presence/absence of VIVC assessed under standard conditions by TDE compared<br />

to CMR using post-contrast saturation (delayed enhancement-DE).<br />

Patient group and methods: In total, 57 consecutive patients with an ischemic<br />

cardiomyopathy (LVEF 33.5±5%) were included in study. All of them were during<br />

09/04-12/07 examined by echocardiography, myocardial gated SPECT and cardiac<br />

MR. A total of 689 LV segments were analyzed with a complete data acquisition<br />

(76% of the total number of segments). Viability of myocardium in individual<br />

segments was evaluated on 3 levels of DE/wall thickness on MR cut-off ratio (25,<br />

50, 75%) and in 3 subgroups according to the extent of DE: 0-24% (MR1), 25-<br />

74% (MR2) a >75% (MR3). Wall thickness (mm) and extent of DE in individual<br />

segments and perfusion SPECT rest score (Q rest) were also evaluated.<br />

Results: 1. Using χ-square test a significantly lower occurrence of VIVC=1 was<br />

found in the MR3 subgroup in comparison with MR1 and MR2 respectively (p =<br />

0.0001 for MR1 vs. MR3 comparison; p = 0.003 for MR2 vs. MR3).<br />

2. Cohen’s kappa coefficient was used for assessment of agreement rate of VIVC<br />

presence/absence and viability on MR (MR1: κ = 0.089, MR2: κ = 0.116, MR3: κ =<br />

0.118). The low values of κ indicate a very poor agreement rate. Statistically significant<br />

correlations of VIVC and MR parameters were as follows: wall thickness<br />

(r=0.262, p0,05) on<br />

the first day but significantly lower in control group after follow-up (0,07 vs. 0,25;<br />

p75%.<br />

The risk of persistent contractility defect after 3 months was related to the grade<br />

of perfusion impairment. For G1, G2 and G3 the risk of persistent akinesis was<br />

higher then in G4 - (OR 7,2; CI 85-97%), (OR 5,7; CI 83-95%) and (OR 1,9;<br />

82-96%) respectively.<br />

The short-term risk of postinfarctional aneurysm development was higher in G1<br />

(OR 4,0; CI 87-94%) segments then G4 and was related to the capacity of nonperfused<br />

myocardium.<br />

3D PE early identifies STEMI patients at risk of persistent contractility disturbances<br />

and aneurysm development regardless of restored TIMI 3.<br />

P2267 The relationship between inflammation biomarkers<br />

and myocardial perfusion assessed by contrast<br />

echocardiography and outcome in patients with<br />

end-stage renal disease<br />

A. Tomaszuk-Kazberuk, B. Sobkowicz, J. Malyszko, T. Hryszko,<br />

J.S. Malyszko, M. Mysliwiec, M. Kalinowski, E. Skibinska, R. Sawicki, W.J. Musial.<br />

Medical University, Cardiology, Bialystok, Poland<br />

Background: Cardiovascular risk stratification in patients with end-stage renal<br />

disease (ESRD) is of great importance as coronary artery disease (CAD) is the<br />

main cause of death in this population. Markers of inflammation predict adverse<br />

outcome in patients with CAD and are also associated with all all-cause mortality<br />

in ESRD patients.<br />

Aim: To evaluate the relationship between C-reactive protein (CRP) and myocardial<br />

perfusion defined by myocardial contrast echocardiography (MCE) and their<br />

impact on clinical outcome in patients with ESRD.<br />

Contrast echocardiography 379<br />

Material and methods: We studied 58 consecutive patients with ESRD (21<br />

women, mean age 59±14 years) on regular hemodialysis. Real-time MCE was<br />

performed using Optison contrast agent. Perfusion assessment was qualitative.<br />

The criterion for MCE was defined as homogenous enhancement in 50% of<br />

wall thickness in each segment. Demographic, clinical and laboratory parameters<br />

(serum C-reactive protein (CRP) levels, full blood count and iron metabolism<br />

parameters such as iron level, total iron blood capacity (TIBC) and ferritine) were<br />

analyzed. Composite clinical endpoint (CCE) included cardiac death, cardiac arrest,<br />

myocardial infarction, myocardial revascularization, hospitalization for cardiac<br />

cause, stroke over 6-month FU. The patients were divided into 2 groups<br />

according to the presence or absence of CCE.<br />

Results: 20 (34%) patients out of 58 experienced CCE. The patients with CCE<br />

were older (65±10 vs. 57±14 years, p=0,016), men in prevalence (p=0,014), DM<br />

in prevalence (56 vs. 18% p=0,007) as well as lower EF (45±12 vs. 58±7%,<br />

p=0,0001) in comparison with those without CCE. 18 out of 20 patients (90%)<br />

who experienced CCE demonstrated perfusion defect on MCE. Out of biochemical<br />

variables CRP levels as well as TIBC were significantly elevated in patients<br />

with CCE. In logistic regression analysis perfusion defects on MCE (p=0,002) and<br />

elevated CRP (p=0,009) were independent predictors of CCE during FU. Moreover<br />

we found the relationship between perfusion defects on MCE and elevated<br />

CRP level (p=0,037). The lower level of iron and higher reticulocytes count were<br />

also associated with perfusion defects on MCE (p=0,022 and p=0,013, respectively).<br />

The level of ferritine was not different between groups.<br />

Conclusions: 1. In patients with ESRD both perfusion defects on MCE and elevated<br />

CRP levels are associated with unfavorable clinical outcome. 2. Risk stratification<br />

in ESRD patients could be extended by an assessment of inflammatory<br />

markers, such as CRP and functional iron deficiency (as a sign of chronic inflammation)<br />

in relation with myocardial perfusion evaluation by MCE.<br />

P2268 Integrated analysis of cardiac tissue structure and<br />

function allows improved identification of reversible<br />

myocardial dysfunction<br />

R. Hoffmann, A. Lenzen, F. Schmitz, H. Kuehl, N. Kraemer,<br />

K. Stempel, G. Krombach, M. Kelm, M. Becker. University Aachen,<br />

Medical Clinic 1, Aachen, Germany<br />

Objective: Myocardial deformation imaging and contrast-enhanced cardiac magnetic<br />

resonance imaging (ceMRI) have been used to define myocardial viability in<br />

ischemic left ventricular dysfunction. This study evaluated the incremental predictive<br />

value of an integrated analysis of function and tissue structure for functional<br />

improvement after revascularization therapy.<br />

Methods: In 59 patients with ischemic left ventricular dysfunction, myocardial viability<br />

was defined by pixel-tracking-derived myocardial deformation imaging and<br />

ceMRI to predict recovery of function at 9±2 months follow-up after revascularization.<br />

For each left ventricular segment in a 16-segment model peak systolic<br />

radial strain was determined from parasternal 2D echocardiographic views using<br />

an automatic frame-by-frame tracking system of natural acoustic echocardiographic<br />

markers (EchoPAC, GE Ultrasound), and extent of hyperenhancement<br />

using ceMRI. 5 categories were generated for each parameter, allowing subsequent<br />

combination. The predictive power for segmental improvement in function<br />

was determined for each of the modalities as well as the combination of both.<br />

Results: From 512 dysfunctional segments at baseline, 251 segments (49%)<br />

demonstrated functional recovery. The accuracy to predict functional recovery<br />

was AUC= 0.846 for peak systolic radial strain, and AUC= 0.834 for extent of<br />

hyperenhancement. A combination of both parameters improved the predictive<br />

accuracy compared to hyperenhancement alone, AUC=0.861, p


380 Contrast echocardiography / Telemonitoring in heart failure<br />

tory of myocardial infarction, mean age 60±12 years), on regular dialysis were included.<br />

Elective coronary angiography was done for the evaluation of CAD symptoms.<br />

Coronary artery stenosis > 75% was defined as significant. TFC for the<br />

three main coronary vessels were calculated. For LAD the corrected TIMI frame<br />

count (CTFC) was applied. Measurements were done with the frame counter on<br />

the HORIZON Cardiology cineviewer.<br />

Results: In 19 pts (48,7%) out of 39 significant epicardial coronary artery disease<br />

was found. 9 of 19 (47%) had single-vessel disease, 10 (53%) multivessel.<br />

11 patients had LAD stenosis, one of them chronic total occlusion (CTO). 13 patients<br />

had Cx stenosis and 9 RCA stenosis (3 of them CTO). In the whole study<br />

group the mean corrected TFC for the LAD was 36,9±19, for the Cx 42,2±25 and<br />

for the RCA 40,0±26 frames. Distribution of the TFC for the three main coronary<br />

arteries reflected prevalence for higher TFC values (slower flow). For the three<br />

main coronary vessels there were no statistically significant differences between<br />

the mean TFC values according to the presence or absence of the severe coronary<br />

artery stenoses on angiography (LAD: 31,9±14 vs 36,9±18; Cx: 38,5±18<br />

vs 44,0±29; RCA: 28,4±13 vs 32,7±21 respectively).<br />

Conclusions: Our results demonstrate for the first time the reduction in velocity<br />

of the blood flow in the coronary arteries in the entire group of ESRD patients<br />

regardless the presence of the significant epicardial coronary artery obstruction.<br />

This finding may reflect microvascular injury in ESRD patients.<br />

P2270 The value of contrast enhancement in quantification<br />

of left ventricular function by realtime 3D<br />

echocradiography<br />

N. Hashemi1 , A. Manouras2 ,R.Winter2 . 1Danderyd Hospital,<br />

Kardiology, Stockholm, Sweden; 2Karolinska Hospital,Huddinge,<br />

Stockholm, Sweden<br />

Left ventricular (LV) volumes and ejection fraction (EF) are strong predictors<br />

of morbidity and mortality in patients with cardiac disease, and important in<br />

therapy guidance. Contrast-enhanced imaging has been proven valuable for<br />

2D-echocardiography. We aimed to study whether contrast enhancement also<br />

improves the accuracy and reproducibility of real time3D echocardiography<br />

(RT3DE).<br />

Methods: 27 consecutive patients referred for echocardiographic examination on<br />

clinical grounds were evaluated by RT3DE echocardiography and image acquisition<br />

before and after contrast enhancement (Sonovue ® , 0.5-0.7 ml/min i.v.). Image<br />

analysis was performed blinded off-line by two independent observers using<br />

(GE EchoPAC) with TomTec 4D LV analysis V2.0. Endocardial borders were<br />

manually traced in a simultaneous apical triplane projection in end-diastole and<br />

end-systole, as automatically deteced by the software.<br />

Results: Interobserver correlation was high and further improved for assessment<br />

of EF when contrast enhancement employed (r2=0.95, SE±2.4) vs (r2=0.86,<br />

SE±3.9) but remained the same for EDV (r2=0.98, SE±2.5) vs (r2=0.98, SE±3.3)<br />

and ESV (r2=0.98, SE±1.4) vs (r2=0.98, SE±1.5). Intraobserver variability was<br />

consistently lower When contrast enhancement was employed (coefficient of variation:<br />

EF 8.9% vs 12.1, ESV 9.4% vs 12.6%, EDV 18.6% vs 19.4%). The analysis<br />

time was the same for both methods (4.5±1 minvs4.1±1 min).<br />

Interobserver regression analysis.<br />

Conclusions: Contrast-enhanced RT3DE improves the accuracy and reproducibility<br />

of the LV function asseeement by improving interobserver correlation<br />

and reducing variability of the results. Contrast-enhanced RT3DE should be considered<br />

when serial accurate estimation of EF is necessary. Quantification of LVvolumes<br />

and EF by RT3DE is rapid and not timeconsuming.<br />

TELEMONITORING IN HEART FAILURE<br />

2339 Intra-thoracic impedance for the assessment of heart<br />

failure hospitalization risk<br />

M. Lunati 1 ,M.Santini2 , M. Landolina3 ,M.Sassara4 , G. Perego5 ,<br />

A. Vado6 , L. Padeletti 7 ,R.Massa8 , S. Marchesini 9 , A. Varbaro10 .<br />

1 2 3 Niguarda, Milano, Italy; San Filippo Neri, Roma, Italy; Policlinico S.<br />

Matteo, Pavia, Italy; 4Osp. Belcolle, Viterbo, Italy; 5Auxologico S. Luca, Milano,<br />

Italy; 6S. Croce e Carle, Cuneo, Italy; 7Careggi, Firenze, Italy; 8Molinette S.<br />

Giovanni Battista, Torino, Italy; 9Medtronic Italia, Sesto S.Giovanni (Mi), Italy;<br />

10Medtronic Italy, Clinical & new Business, Sesto San Giovanni, Italy<br />

Purpose: Some implantable CRT-D devices can provide useful patient diagnostic<br />

information, including an index of pulmonary fluid accumulation based on intrathoracic<br />

impedance monitoring. We studied the association between these information<br />

and heart failure (HF) hospitalization.<br />

Methods: Clinical and device data of 558 HF patients (pts) indicated for CRT-D<br />

therapy, averaging 326±216 days of follow-up, were collected from 34 centers.<br />

Device-recorded fluid index threshold crossing event (TCE), patient activity, night<br />

heart rate (NHR) and heart rate variability (HRV) were compared within pts with<br />

vs. without HF hospitalization.<br />

Results: Kaplan Meier analysis indicated that pts with more TCEs were significantly<br />

more likely to be hospitalized (figure). Multivariate analysis showed<br />

that TCE resulted in a 36% increased risk of HF hospitalization (OR=1.356,<br />

95%CI=1.081-1.700, p=0.008). TCE net duration, the number of days with low<br />

activity or with low HRV were also significantly associated with hospitalization<br />

(respectively OR=1.009 95%CI=1.001-1.018, p=0.037; OR=1.006 95%CI=1.000-<br />

1.011, p=0.032; OR=1.004 95%CI=1.000-1.007, p=0.047). Pts hospitalized for<br />

HF had significantly higher rates of TCE (2.99 vs 1.41, p


2341 Telemonitoring in an elderly, urban, multi-ethnic<br />

population: results of a UK multi-centre randomised<br />

controlled trial. The Home <strong>Heart</strong> Failure (HOME-HF)<br />

study<br />

O.A. Dar 1 ,J.Riley2 , C. Chapman3 ,S.Dubrey4 ,S.Rosen5 ,S.Morris6 ,<br />

M.R. Cowie1 . 1Imperial College London, Dept. of Clinical Cardiology,<br />

London, United Kingdom; 2Royal Brompton Hospital NHS trust, Post-graduate<br />

Education for Nurses, London, United Kingdom; 3West Middlesex Hospital<br />

NHS trust, London, United Kingdom; 4Hillingdon Hospital NHS trust, London,<br />

United Kingdom; 5Ealing Hospital NHS trust, London, United Kingdom; 6Health Economic Research Group, Brunel Uni, London, United Kingdom<br />

Background:Telemonitoring (TM) is increasingly used to manage heart failure<br />

(HF) in the USA. Evidence for its impact within Europe is limited. HOME-HF, a<br />

multi-centre randomised controlled trial, compared TM with usual care (UC) in<br />

HF patients discharged from 3 hospitals in London, UK.<br />

Methods: HF patients were randomised at discharge to home TM of symptoms<br />

& signs (dyspnoea, weight, oxygen saturation, blood pressure & heart rate) or<br />

UC for 6 months. TM data were reviewed daily by a HF nurse who responded to<br />

change from preset limits with advice on diuretic & lifestyle therapy, or arranged<br />

clinic or primary care review.<br />

Results: 182 patients (40% of all eligible) were randomised: 120 (66%) male,<br />

mean age 71 (SD ±12), 49 (27%) non-White. Medication at randomisation:<br />

ACEi/ARB (89%), beta-blocker (56%), aldosterone antagonist (41%), and diuretic<br />

(93%). 95% of TM patients were monitored >90% of the time. There were 89 hospital<br />

readmissions (TM: 49 & UC: 40), with no difference in the number of days<br />

alive and out-of-hospital between groups (Median [IQR] TM: 178(90-180); UC:<br />

180(165-180) p=0.29). Time to first event (readmision or death) was slightly earlier<br />

in the TM group (p=0.08). There were a greater proportion of unplanned HF<br />

admissions in the UC group [UC:15/16 (94%) versus TM: 8/21(38%), p=0.001].<br />

UC patients made more outpatient visits (733) than TM (622). Quality of life scores<br />

were similar in both groups during follow-up.<br />

Conclusion: Introduction of TM into a well treated, elderly, multi-ethnic, urban<br />

HF population resulted in a similar outcome to UC, but with fewer outpatient visits<br />

and unscheduled HF re-admissions. TM is acceptable to elderly HF patients, with<br />

high adherence rates in a <strong>European</strong> urban population.<br />

2342 Correlation between Intra-thoracic impedance<br />

monitoring and standard clinical assessment in<br />

detecting acute decompensation in patients with<br />

chronic heart failure<br />

G. Zanotto1 ,R.Ometto2 , C. Bonanno2 , M. Maines3 , G. Vergara3 ,<br />

G. Lonardi4 , W. Rauhe5 , C. Perrone6 , T. De Santo7 , C. Vassanelli 1 .<br />

1 2 Borgo Trento Hospital, Cardiologia, Verona, Italy; S. Bortolo, Cardiologia,<br />

Vicenza, Italy; 3S. Maria del Carmine, Cardiologia, Rovereto, Italy; 4Mater Salutis, Cardiologia, Legnago, Italy; 5S. Maurizio, Cardiologia, Bolzano, Italy;<br />

6 7 ULSS 5, Cardiologia, Arzignano, Italy; Medtronic Italia, Cardiologia, Roma,<br />

Italy<br />

Purpose: During ambulatory follow-up an increase of NT-proBNP plasma levels<br />

and abnormalities in diastolic filling pattern at echo Doppler are commonly considered<br />

clinical markers of acute decompensation in chronic heart failure (CHF)<br />

pts. Recent ICDs are able to daily monitor intra-thoracic impedance and to alert<br />

patients (pts) when its value acutely decreases, potentially indicating heart failure<br />

deterioration. We evaluated the correlation between these standard clinical<br />

markers and intra-thoracic impedance.<br />

Methods: 6 Italian centers collected device and clinical data of 111 CHF pts<br />

(85% male, aged 68±10 years, LVEF=26±5%) implanted with a biventricular ICD,<br />

equipped with impedance monitoring and alert system. During regular follow-ups<br />

and in case of CHF decompensation or device alerts, intra-thoracic impedance,<br />

NT-proBNP plasma levels, echo Doppler trans-mitral flow indices and clinical status<br />

-quantified through an <strong>Heart</strong> Failure Score (HFS)- were reported. A linear<br />

mixed model for repeated measurements was used to assess the relationship<br />

among all parameters.<br />

Results: Over a mean follow-up of 12.4±3.6 months, 955 visits were performed,<br />

186 because of device alert. Clinical evidence of CHF deterioration were found<br />

by a clinician, blinded to impedance data, in 131 cases and an increment in diuretic<br />

dosage followed (true positive). After the alert visit, only 11 hospitalizations<br />

were reported. Follow-ups without alert and with absence of clinical deterioration<br />

(true negative) were 727, so the negative predictive value was about<br />

94%. The rate of unexplained alert was 0.47 per patient/year. Intra-thoracic<br />

impedance was significantly correlated with standard assessment: NT-proBNP<br />

(p


382 Telemonitoring in heart failure / <strong>Heart</strong> failure with preserved systolic function: mechanisms and outcomes<br />

Conclusions: The chest x-ray was used in this study to verify the ability of surface<br />

thoracic impedance monitoring to predict AHF at the preclinical stage. It<br />

confirmed that the new method of LI measurement is of sufficient sensitivity to<br />

detect evolving AHF in its pre-clinical stage in patients with AMI. There seems to<br />

be ample time at this stage to initiate therapy in an attempt to prevent AHF.<br />

HEART FAILURE WITH PRESERVED SYSTOLIC<br />

FUNCTION: MECHANISMS AND OUTCOMES<br />

2345 Diastolic versus systolic left ventricular dysfunction as<br />

independent predictors for unfavourable postoperative<br />

evolution in patients undergoing coronary artery<br />

bypass grafting<br />

L. Iliuta, H. Moldovan, D. Filipescu, B. Radulescu, C. Macarie. Institute<br />

of cardiovasc.diseases C.C.Iliescu, Cardiac Surgery I, Bucharest, Romania<br />

Purpose: 1. Assessement of the immediate prognostic implications of the type of<br />

the LV diastolic filling pattern (LVDFP) compared with LV systolic performance in<br />

patients undergoing CABG 2. Defining the echographic parameters which can be<br />

independent predictors for immediate and long term prognosis in these patients<br />

and their value for calculation of a preoperative risk score.<br />

Material: Prospective study on 512 patients undergoing CABG, divided in 4 subgroups:<br />

Group A – 328pts with normal LV systolic function with 2 subgroups (A1:<br />

219pts with nonrestrictive LVDFP and A2: 109pts with restrictive LVDFP); Group<br />

B – 184pts with LV systolic dysfunction (LVEF


<strong>Heart</strong> failure with preserved systolic function / Electrical and morphological cardiac adaptation in athletes 383<br />

had delayed relaxation, 11 (7%) were pseudonormal and 1 (0.6%) was restrictive.<br />

At 1 year, 50% were unchanged, 26% had progressed and 24% improved; see<br />

Table for correlates of deterioration. Change in Em was independently correlated<br />

with age (p


384 Electrical and morphological cardiac adaptation in athletes<br />

ercise ECG was able to reveal cardiac anomalies in 1,227 athletes that reported<br />

a normal pattern at resting ECG. At the end of the pre-participation screening,<br />

a total of 196 (0.6%) athletes were considered to be ineligible for competitive<br />

sports. Among the 159 athletes disqualified at the end of the screening for cardiac<br />

causes, a large proportion (n=126, 79.2%) reported significant abnormalities<br />

only at the exercise testing. A logistic regression analysis showed that age > 30<br />

years was the major significant predictor of disqualification for cardiac cause at<br />

the exercise testing.<br />

Conclusions: Pre-participation screening program including resting and exercise<br />

ECGs seems to represent an effective preventive measure for identifying high-risk<br />

young and middle-aged athletes.<br />

2369 Abnormal electrocardiographic patterns in elite<br />

athletes: the Greek experience<br />

A. Anastasakis, A. Vouliotis, E. Sevdalis, C. Kotsiopoulou, K. Ritsatos,<br />

N. Protonotarios, C. Stefanadis. Hippokration Hospital, A’ Dpt of<br />

Cardiology, A Dpt of Cardiology, University of Athens, Athens, Greece<br />

Objectives: There is a wide clinical perception that routine implementation of 12<br />

lead electrocardiogram (ECG) will convey a large proportion (40%) of abnormal<br />

findings requiring additional testing to resolve the ambiquity of cardiovascular diagnosis<br />

and raising substantially the cost of screening. In this study, we tried to<br />

evaluate ECG abnormalities in a population of elite athletes.<br />

Methods: We studied the prevalence of ECG abnormalities in 460 highly trained<br />

athletes (275 males) from a broad variety of sports activities, aged 12-38 (mean<br />

age 22,2 years), all of them members of the Greek Olympic Team. All ECG patterns<br />

were evaluated according to <strong>European</strong> Society of Cardiology adopted criteria.<br />

Results: The most frequent abnormalities were sinus bradycardia (29,13%),<br />

left ventricular hypertrophy (28,40%) and early repolarization pattern (24,13%).<br />

These ECG abnormalities plus incomplete RBBB (3,92%), sinus arrhythmia<br />

(4,14%) and first degree AV block (0,44%), are regarded as part of the spectrum<br />

of benign changes of athlete’s heart. In 57 athletes, ECG patterns were<br />

considered suspect for cardiovascular disease. Distinct ECG abnormalities included<br />

QTc interval > 460ms (1,09%), pre-excitation pattern (1,09%), left axis<br />

deviation/left anterior hemiblock (1,09%), right axis deviation/left posterior hemiblock<br />

(1,52%), right atrial enlargement (0,22%), left atrial enlargement (1,74%)<br />

and supraventricular ectopic beats (0,22%). In addition, we identified ST-segment<br />

and T-wave repolarization abnormalities in 32 athletes (6,96%) and ventricular<br />

ectopic beats (0,65%). T-wave inversion in right precordial leads (V1 – V3) was<br />

present in 5 athletes (1,09%), while 6 more athletes showed T-wave inversion only<br />

in leads V1-V2 (1,30%). Sixteen ECGs (3,48%) accomplished voltage criteria for<br />

LVH and showed repolarization abnormalities as well. With regard to type of sport<br />

discipline, long distance running, football and weight lifting had the largest proportion<br />

of distinctly abnormal ECG patterns, while all individuals engaged in rowing,<br />

sailing and wrestling had normal ECGs. The prevalence of distinctly abnormal<br />

ECGs was almost the same in males and females (12,36% vs 12,43%).<br />

Conclusion: The results show that abnormal ECG patterns, suggestive for further<br />

evaluation, were found in a minority of elite athletes (57 athletes, 12,39%<br />

of the overall study population). ECG changes, suspicious for underlying cardiac<br />

disease, such as inverted T waves in right precordial leads (2,39%), LVH with<br />

repolarization abnormalities (3,48%) or QTc interval > 460ms (1,09%) do not<br />

exceed 7% of the overall study population.<br />

2370 Supraventricular tachycardias in elite athletes:<br />

diagnosis, treatment and long term outcome<br />

C. Berndt, A. Dorszewski, U. Wetzel, J. Vogt, K.P. Mellwig,<br />

D. Horstkotte. <strong>Heart</strong> Center of Northrhine Westphalia, Cardiology, Bad<br />

Oeynhausen, Germany<br />

Introduction: Diagnosis and treatment of tachyarrhythmias of unknown origin in<br />

elite athletes are very important for prognosis, their physical activity and further<br />

professionel carrier. In our study we characterize symptomatic supraventricular<br />

tachyarrhythmias of top ahtletes, their treatment, outcome and long term follow<br />

up.<br />

Methods: Out of 292 elite athletes (age: range: 17.9±38.9, mean: 25.3±4.42<br />

yrs.) 11 athletes, 9 male and 2 female, age: 25.7±12.9 years, presented with a<br />

history of recurrent highly symptomatic tachyarrhythmias occuring during or after<br />

maximum physical exercise. In all patients (pts.) but one tachycardias led to<br />

termination of active participation and consecutively exchange during the competition.<br />

All pts. underwent electrophysiological study according to a standardized<br />

protocol.<br />

Results: Structural heart disease was ruled out via non invasive testings in all pts.<br />

The electrophysiological study revealed slow-fast AV-nodal reentrant tachycardia<br />

in 10 pts., cycle length of 277.8±26.4 ms. After modulation of the slow pathway<br />

of the AV-node via radiofrequency catheter ablation in typical location there<br />

were no AV-nodal reentrant tachycardias inducible, even not during medical testing<br />

with orciprenaline, mean procedure time 53.7±19.4 min., mean fluoroscopy<br />

time 5.1±2.3 min. 3–4 days after curative radiofrequency catheter ablation the<br />

pts. could start full physical training again. One patient had a WPW-syndrome and<br />

underwent successful ablation of a left posterior accessory pathway. The overall<br />

procedure time for the accessory pathway was 83 min., fluoroscopy duration 19.2<br />

min. In this case the full physical training was started 8 days after ablation due<br />

to the arterial access. During a mean follow up of 9.8±6.5 months all pts. were<br />

free of symptoms. No mild or severe complications occurred. The follow up was<br />

without any rhythm disturbances or complications. All top athletes could continue<br />

their professional carrier.<br />

Conclusion: In elite athletes supraventricular tachycardias occur which are limiting<br />

for their physical activity and may be devestating for their further professionel<br />

sportive carrier. Electrophysiologic study is necessary for classification, diagnosis<br />

and curative therapy of the tachycardias. The slow pathway modulation is a safe<br />

and effective treatment for AV nodal reentrant tachycardia and as well the ablation<br />

of accessory pathways. All top athletes were able to start full physical training 4,<br />

respectively 8 days after the ablation procedure, and continued their carrier with<br />

just minor interruption due to short hospitalization.<br />

2371 Myocardial function and biomarkers in elderly male<br />

amateur marathon runners<br />

F. Knebel1 ,I.Schimke2 , S. Schroeckh2 ,S.Schattke2 , S. Eddicks 2 ,<br />

A. Grohmann2 ,S.Grubitz2 ,J.Schmidt2 , G. Baumann2 , A.C. Borges2 .<br />

1 2 Berlin, Germany; Charite, Berlin, Germany<br />

Background: There is an increasing number of elderly participants in marathons.<br />

Age-related changes in myocardial function after prolonged exercise in the elderly,<br />

who carry an increased cardiovascular risk, have not yet been studied. There is<br />

evidence of myocardial dysfunction after running a marathon in younger runners<br />

and controversy about the extent of myocardial damage. The focus of this study<br />

is to examine Tissue Doppler Echocardiography and myocardial biomarkers before,<br />

immediately after and two weeks after a marathon in elderly male amateur<br />

runners.<br />

Methods and Results: 78 runners of the 2006 Berlin Marathon were included<br />

(28 elderly> 60 years, range 60-72, mean 63±3 years and 50 younger controls;<br />

range 22-59, mean: 53±14 years. They were examined before, immediately and<br />

two weeks after the race by echocardiography including Tissue Doppler Imaging<br />

(TDI) and blood tests. 42 (53.8%) of all runners had increases in TnT and/or<br />

NT-proBNP after the race. There was no correlation of NT-proBNP and TnT increase<br />

(p=0.16). The increases in biomarkers were not correlated to age, training<br />

level, running time or renal function. Immediately after the marathon, there was<br />

an age-independent increase in fractional shortening (39.9±7.6 vs. 46.8±9.2,<br />

p


the most dilated, LA mostly influences PR duration, whereas in strength-trained<br />

athletes, only RR duration acts on PR duration. Some specificities are shown<br />

when sports are classified according to Mitchell’s classification: the highest the<br />

dynamic (volume overload) component is, the highest the LVEDD, IVSWT, and<br />

V’O2max are; the more the static (pressure overload) component is, the highest<br />

LA and V’O2max are (Chi2>1.96; p


386 How about a healthy lifestyle? / Stable angina: risk markers and potential treatments<br />

creased to 10. Only VO2 max remained statistically significantly higher compared<br />

to baseline values (+5.6%, p


Conclusion: In patients with stable angina pectoris despite standard doses of<br />

beta-blockers, the addition of ivabradine further improves exercise capacity. The<br />

combination of ivabradine and beta-blockers is well tolerated.<br />

2381 How good is angiography in selecting stenoses to be<br />

revascularised?<br />

M. Hamilos1 , P. Tonino2 , N. Piljs2 , H. Samady3 , W.F. Fearon4 ,<br />

V. Klauss5 , E. Barbato1 , J. Bartunek1 , W. Wijns1 ,B.DeBruyne1 .<br />

1 2 3 Aalst, Belgium; Einthoven, Netherlands; Atlanta, United States of<br />

America; 4Stanford, United States of America; 5Munich, Germany<br />

Purpose: Angiography is notoriously inappropriate to gauge stenosis severity.<br />

Nevertheless, the vast majority of decisions about the need for revascularisation<br />

are based on visual estimation of coronary angiography. The goal of the<br />

present analysis is to compare quantitative coronary angiography to pressurederived<br />

fractional flow reserve (FFR) in a large patient’s population.<br />

Methods: In 2413 lesions (2225 patients) that were all considered for percutaneous<br />

coronary intervention (PCI), FFR was obtained and off-line QCA was performed.<br />

Patients were part of 2 large randomized studies (FAME and DEFER)<br />

and 2 large registries (‘FFR post stent registry and ‘Aalst FFR registry’).<br />

Results: A significant relationship was found between FFR and both diameter<br />

stenosis (r =-0.54, p


388 Stable angina: risk markers and potential treatments / Diabetes and myocardial infarction: not all sugar<br />

Methods: 4298 patients with a diagnosis of myocardial infarction (MI) or angina<br />

pectoris (AP) were included in the CLARICOR trial and randomized to clarithromycin<br />

500 mg/day versus placebo for two weeks. Patients were categorized<br />

according to serum YKL-40 at entry: Group I under 50% percentile:


2388 Magnitude of glycaemia variation: a new risk tool in<br />

acute coronary syndromes?<br />

S. Monteiro, N. Antonio, R. Teixeira, C. Lourenco, R. Batista, E. Jorge,<br />

P. Monteiro, L. Goncalves, M. Freitas, L. Providencia. Coimbra,<br />

Portugal<br />

Introduction: Hyperglycaemia in acute coronary syndrome (ACS) patients is associated<br />

with an increased risk of death and in-hospital complications. However,<br />

little is known about the prognostic value of the magnitude of glycaemia variations<br />

(MGV) during an ACS.<br />

Aim: To evaluate the relationship between the MGV during hospitalization and<br />

in-hospital and long-term prognosis.<br />

Population and methods: 1210 consecutive patients admitted to a coronary<br />

care unit for ACS, between May 2004 and July 2007. Our population was divided<br />

in diabetics (n=386) and non-diabetics (n=824). Each of these subpopulations<br />

was divided according to MGV: Q1 7.8 mmol/l, 2% had a FG > 7 mmol/l and a PPG < 7.8<br />

mmol/l, and finally 5% had a FG >7 mmol/l and a PPG > 7.8 mmol/l.<br />

Third day FG and PPG were significantly correlated with 6-months death combined<br />

to in-hospital heart failure (c statistic: 0.64±0.05, p = 0.003 and 0.65±0.05,<br />

p = 0.002, respectively). After adjustment for the GRACE (Global Registry of<br />

Acute Coronary Events) risk score and the echocardiographic left ventricular fractional<br />

ejection, both PPG and FG, separately, at day 3, remained strong predictors<br />

of outcomes (OR [95%IC]; 1.70 [1.14-2.54], p = 0.010 and 1.27 [1.07-1.51], p =<br />

0.005, respectively).<br />

Conclusion: Our results show that third day FG or PPG are independent predictors<br />

of outcomes in non-diabetic patients. As regards of the recent data of<br />

DIGAMI II, further studies are needed, in around 50% of patients, after acute<br />

coronary syndrome, to optimize glycemic control in these specific groups.<br />

Diabetes and myocardial infarction: not all sugar / Challenges in valvular heart disease 389<br />

2390 Insulin treatment in patients with type 2 diabetes<br />

mellitus affects the expression of inflammatory<br />

cytokines and subsequently modifies thrombotic<br />

mechanisms in patients with coronary atherosclerosis<br />

C. Antoniades, D. Tousoulis, K. Marinou, K. Toutouzas, S. Brili,<br />

N. Papageorgiou, C. Tsioufis, G. Siasos, G. Latsios, C. Stefanadis. Hippokration<br />

Hospital, Athens, Greece<br />

Introduction: Type 2 diabetes mellitus (T2DM) is characterised by endothelial<br />

dysfunction, increased thrombogenicity and abnormal inflammatory response.<br />

Aim: We examined the impact of insulin dependence/exogenous insulin administration<br />

on thrombotic/inflammatory status and endothelial function in patients with<br />

T2DM and coronary artery disease (CAD).<br />

Methods: Fifty-five patients with T2DM+CAD (26 insulin-treated (INS) and 29<br />

under oral biguanide+sulphonylurea (TABL)) were recruited. Endothelial function<br />

was assessed by gauge-strain plethysmography. Levels of interleukin-6 (IL-6), tumor<br />

necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule (sVCAM-<br />

1), monocytes chemoattractant protein 1 (MCP-1), von Willebrand factor (vWF),<br />

tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-<br />

1), protein C (PrtC) and protein 2 (prtS) were determined by enzyme linked immunosorbent<br />

assay.<br />

Results: There were no significant differences in endothelium-dependent dilation<br />

(EDD) between the study groups (61.1±4.8% vs 66.2±6.0% respectively,<br />

p=NS), while EDD was correlated with fasting glucose levels in both INS (r=-<br />

0.776, p=0.0001) and TABL (r=-0.702, p=0.0001). However, patients in INS group<br />

had significantly higher levels of IL-6, TNF-a and sVCAM-1 (6.9±0.57 pg/ml,<br />

3.87±0.43pg/ml and 596±43.4ng/ml respectively) compared to patients in TABL<br />

(4.67±0.5 pg/ml, 2.76±0.28pg/ml and 475±26 ng/ml respectively, p


390 Challenges in valvular heart disease<br />

2429 Left ventricular contractile function and aortic valve<br />

stenosis. Is exercise Doppler echocardiography a<br />

relevant tool for asymptomatic patients?<br />

E. Donal, A. Bellouin, R. Gervais, C. De Place, F. Carre, P.H. Mabo,<br />

J.C. Daubert. Rennes, France<br />

Aim: Patients with asymptomatic severe aortic stenosis (AS) and abnormal<br />

hemodynamic responses to exercise testing are at increased risk of cardiac<br />

events. This study assesses left ventricular myocardial function by rest and exercise<br />

Doppler echocardiography in a cohort of asymptomatic patients with AS.<br />

Methods and results: 66 patients (68 years old) with asymptomatic AS underwent<br />

quantitative Doppler echocardiographic measurements at rest and exercise<br />

(standardized bycicle exercise stress test). Of these patients, 39 had an abnormal<br />

response to exercise (positive exercise stress test according to guidelines). Theses<br />

patients had a significantly worse ‘exercise global longitudinal strain’ (-14±4<br />

versus -17±4%, p 20 ml. In the<br />

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patients with RV > 30 ml this correlation was stronger (r=0.97, p=0.005) and additionally<br />

there was a correlation between the RV and posterior mitral leaflet angle<br />

(r=0.90, p =0.037), between tenting area and posterior mitral leaflet angle (r=0.90,<br />

p=0.04), between tenting area and anterior mitral leaflet angle (r=0.82, p=0.08).<br />

Conclusions: Anterior and posterior mitral leaflet angle value may be helpful in<br />

the evaluation of the severity of IMR and mitral apparatus deformation.<br />

2433 Real-time 3 dimensional echocardiography is useful in<br />

the assessment of tricuspid valve dimensions in<br />

patients with right heart dilatation<br />

S. Khan, R. Duehmke, J. Boyd, K. Parker, R.A. Rusk. Papworth<br />

Hospital, Cardiology, Cambridge, United Kingdom<br />

Background: Real-time 3 dimensional echocardiography (RT3DE) is useful in<br />

the assessment of tricuspid annular dimension in normal hearts but little is known<br />

about its role in patients with right heart dilatation.<br />

Methods: 10 consecutive patients (mean age 62 years, 7 males) with right heart<br />

dilatation secondary to mitral valve disease or pulmonary hypertension underwent<br />

2D and 3D transthoracic echocardiographic assessment with an IE33 ultrasound<br />

machine (Philips Ultrasound, Bothell, USA). All datasets were acquired from an<br />

apical window. Tricuspid annulus dimensions were measured off-line by two independent<br />

observers, blinded to the clinical details. Major and minor axes were<br />

obtained from 3D datasets and a single major axis from the 2D dataset.<br />

Results: Measurements could be made in all patients. There was good agreement<br />

between the average of major and minor axes obtained by RT3DE and<br />

the major 2D measurement (3D dimensions 43.5 (5.5)mm vs 42 (5.1)mm by 2D,<br />

r=0.8). However, the maximum diameter measured by RT3DE was greater than<br />

that measured by 2D with a mean difference of 4.8 (5.4)mm, p


392 Newer prognostic approaches in heart failure<br />

Methods: A cohort of 992 consecutive ambulatory CHF patients was prospectively<br />

followed for a median of 44 months, and multivariate Cox models were<br />

developed to predict cardiac mortality (primary end-point, n=213), as well as allcause<br />

mortality (n=267), pump-failure death (n=123) and sudden death (n=90).<br />

Results: The four final models included several combinations of the same 10<br />

independent predictors: Prior atherosclerotic vascular event, indexed left atrial<br />

size >26 mm/m 2 , ejection fraction ≤35%, atrial fibrillation, left bundle branch<br />

block or intraventricular conduction delay, non-sustained ventricular tachycardia<br />

and frequent ventricular premature beats, estimated glomerular filtration<br />

rate 1000ng/L and<br />

Troponin-positive. Model performance was excellent, with a correlation between<br />

predicted and actual survival by deciles of 0.99, and a ROC area under the curve<br />

of 0.80 (95% CI, 0.77-0.83) for both total and cardiac mortality models, 0.79 (0.76-<br />

0.83) for pump-failure death model, and 0.75 (0.70-0.89) for sudden death model.<br />

Risk scores for each type of mortality<br />

All-cause Cardiac Pump Failure Sudden Death<br />

Prior AVE 3 3 8<br />

Indexed LA size>26 mm/m2 8 9 9 11<br />

Ejection fraction≤35% 5 5 5<br />

Atrial Fibrillation 3<br />

LBBB or IVCD 7<br />

NSVT & frequent VPBs 3 4 7<br />

eGFR1.000 ng/L 7 7 10 7<br />

Troponin-Positive<br />

High Risk patient if score > 20.<br />

4 5 7<br />

Conclusions: It is possible to predict mortality in CHF patients, using a simple<br />

score including a limited number of predictors, so that it could be easily used in<br />

clinical practice. None of these predictors require invasive or expensive procedures<br />

to be determined, and all of them are objective variables. Use of this model<br />

identifies a small subgroup of high-risk patients that should be managed closely<br />

by specialized heart failure units.<br />

2489 Clinical determinants and prognostic importance of<br />

glycosylated haemoglobin (Hgb A1c) in chronic heart<br />

failure<br />

P. Rozentryt 1 ,J.Nowak1 ,M.Greif1 , S. Von Haehling2 ,L.Polonski1 ,<br />

S.D. Anker 2 . 1Silesian Centre for <strong>Heart</strong> Diseases, Iii Department of<br />

Cardiology, Zabrze, Poland; 2Campus Charite, Applied Cachexia Research,<br />

Berlin, Germany<br />

Purpose: Abnormalities in glucose metabolism are frequent in chronic heart failure<br />

(CHF). The prognostic importance of glycosylated haemoglobin (Hb A1c) is<br />

well known in diabetes. In CHF glucose-related protein damage may be dependent<br />

on factors linked to heart failure itself, i.e. inflammation or oxydative stress.<br />

We examined important clinical and laboratory as well as body composition measures<br />

and their relationship to Hb A1c. We assessed prognosticators by Cox proportional<br />

hazard analysis.<br />

Material & Methods: Using the turbidimetric method we measured Hb A1c level<br />

in 369 patients with CHF (308 male; 61 female; age 54±13 years; NYHA: I/II/III/IV<br />

40, 136, 146, 43; ischaemic: 66%; diabetes 23%). All patients underwent routine<br />

laboratory and functional assessment combined with body composition analysis<br />

by DEXA. Patients were optimally treated with beta-blockers, ACE-I/ARB, diuretics<br />

and spironolactone, if appropriate. All patients were followed for a median of<br />

589 days. During follow-up, 42 (11%) of patients died.<br />

Results: In this population, the median Hb A1c was 6.2% (range 4.7 to 12.9%).<br />

There was stepwise increase of Hb A1c according to NYHA class (I: 6.3±1.0%, II:<br />

6.3±1.0%, III: 6.6±1.1%, IV: 6.8±1.7%, ANOVA p


BIOMARKERS: NEW KIDS ON THE BLOCK<br />

2492 Matrix-metalloproteinase-2 predicts mortality and heart<br />

failure following myocardial infarction<br />

K. Ng, O. Dhillon, D. Kelly, S.Q. Khan, P.A. Quinn, I.B. Squire,<br />

J.E.Davies,L.L.Ng.University of Leicester, Cardiovascular Sciences,<br />

Leicester, United Kingdom<br />

Objectives: Matrix metalloproteinases (MMPs) are implicated in adverse ventricular<br />

remodelling after acute myocardial infarction (AMI) but whether they independently<br />

complement NTproBNP in determining prognosis is not established.<br />

We compared MMP-2,-3 and -9 to N-terminal pro-B type natriuretic peptide (NTproBNP),<br />

a marker of death and heart failure post acute myocardial infarction<br />

(AMI).<br />

Methods: We studied 1046 patients with AMI (45.7% STEMI, 71.3% male, median<br />

age 67 years). MMP-2, 3 and 9 was measured on discharge plasma samples.<br />

NTproBNP and MMP levels were determined using non-competitive immunoassays.<br />

Patients were followed-up for the combined endpoint of death or<br />

heart failure (median 478, range 1-1059 days).<br />

Results: MMP-3 was higher in males; MMP-2 and MMP-9 had no gender differences.<br />

MMP-3 correlated better with eGFR (r=-0.212, P


394 Biomarkers: new kids on the block / Stroke and the heart<br />

2496 Presence of microalbuminuria in patients with acute<br />

coronary syndrome identifies a high risk group for<br />

new-onset heart failure<br />

J.M. Garcia Acuna, E. Gonzalez Babarro, M. Gutierrez Feijoo,<br />

A. Lopez Lago, L. Grigorian Samahian, J. Fernandez Villanueva,<br />

M. Alvarez Barredo, E. Abu Assi, J.R. Gonzalez Juanatey. University Clinic<br />

Hospital, Cardiology, Santiago, Spain<br />

Microalbuminuria (MA) is a powerful predictor of cardiovascular disease. In several<br />

studies was observed a particular relationship between MA and heart failure<br />

(HF) but this association was not described in patients with Acute Coronary Syndrome<br />

(ACS).<br />

Patients and Methods: MA presence (defined as albumin excretion 30-300<br />

mg/24 hours) was studied in 24 hours urine test of 478 consecutively hospitalized<br />

patients with SCA. At hospital admission were obtained blood samples to determined<br />

leukocyte count, hemoglobin and hematocrit levels and serum troponin-I,<br />

total cholesterol, HDL-cholesterol, LDL-cholesterol, fibrinogen, high sensitive C<br />

reactive protein (US-CRP), gGlucose and glycosilated hemoglobin (HbA1) levels.<br />

Left ventricular function was determined in all cases by echocardiography and a<br />

coronariography study performed in 95% of patients. We planned a prospective<br />

follow-up of cohort with a maximum of 4 years.<br />

Results: 191 patients showed MA (40%). This subgroup of patients was older<br />

(p=0.001), higher prevalence of hypertension (p=0.001), diabetes (p=0.0001),<br />

prior stroke cases (p=0.04), Peripheral Arteriophaty (p=0.0001) and cchronic<br />

renal failure (p=0.0001). In the MA group 37% presented Killip >I stage<br />

(p=0.0001), worse ejection fraction (51% versus 46%, p=0.001), worse renal function<br />

(p=0.001) and higher glucose blood levels (p=0.0001). During hospital stay<br />

the patients with MA presented higher mortality rate (9% versus 4%; p=0.004),<br />

more cases of HF (46% versus 19%; p=0.0001), atrial fibrillation (25% versus<br />

12%; p=0.004) and stroke (4% versus 1%, p=0.02). During the 4 years of followup,<br />

mortality rate was 19% (p=0.0001). In the multivariate analysis MA was identified<br />

as an independent risk factor of HF (OR: 1.99; IC 95% 1.19-3.33; p=0.009).<br />

Conclusions: MA identifies a subgroup of patients with ACS with a short a longterm<br />

very high cardiovascular risk with a strong relationship with new-onset HF.<br />

2497 Growth differentiation factor-15 (GDF-15) predicts<br />

mortality and morbidity after cardiac resynchronisation<br />

therapy<br />

P.W.X. Foley 1 , S. Chalil1 ,K.Ng2 ,N.Irwin3 , S. Ramachandra3 ,<br />

A. Proudler3 , H. El-Gendi1 , M.P. Frenneaux4 ,L.Ng2 ,F.Leyva1 .<br />

1University of Birmingham, Good Hope Hospital, Cardiology, <strong>Heart</strong> of England<br />

NHS Trust, Sutton Coldfield, United Kingdom; 2University of Leicester, Leicester,<br />

United Kingdom; 3Good Hope Hospital, Sutton Coldfield, United Kingdom;<br />

4University of Birmingham, Cardiovascular Medicine, Birmingham, United<br />

Kingdom<br />

Background: Growth differentiation factor-15 (GDF-15), a transforming growth<br />

factor-β-related cytokine which is upregulated in cardiomyocytes via multiple<br />

stress pathways, predicts mortality in patients with heart failure. We explored<br />

whether GDF-15 predicts mortality and morbidity in patients with moderate-tosevere<br />

heart failure (HF) undergoing cardiac resynchronisation therapy (CRT).<br />

Methods and results: GDF-15 was measured (immunoluminometric assay)<br />

before and days after implantation in 122 patients with HF and sinus rhythm<br />

(age 68±11 yrs [mean ± SD], LVEF 25.1±11.0%, NYHA class III or IV, QRS<br />

153.7±29.2 ms) undergoing CRT and followed up for a maximum of 5 years for<br />

events. In Kaplan-Meier survival analyses, a GDF-15 ≥2720 ng/L predicted the<br />

composite endpoints of death or unplanned hospitalization for major cardiovascular<br />

events (MCE) and cardiovascular death or unplanned hospitalization for HF<br />

(both p


the importance of calling the emergency medical services (EMS), as well as a<br />

bookmark and a sticker with the EMS telephone number. We fitted a lognormal<br />

survival regression model with frailty terms shared by inhabitants of the same zip<br />

code area.<br />

Results: A total of 75,720 inhabitants received the intervention. Between 2004<br />

and 2005, 741 patients were admitted with stroke from the control areas (n=24)<br />

and 647 from the intervention areas (n=24). A prehospital time ≤ 2(≤ 3) hours<br />

was achieved by 22% (28%) of patients in the control group compared to 26%<br />

(34%) in the intervention group. In the lognormal model, time to hospital was<br />

significantly reduced in the intervention group in women (acceleration factor 0.75;<br />

95% 0.58; 0.96) while we found no effect in men.<br />

Conclusions: The population-based intervention was effective in reducing prehospital<br />

delays in women but not in men. Future research needs to focus on the<br />

transferability of the intervention to other settings and its sustainability as well as<br />

on gender-specific interventions.<br />

2500 Perioperative stroke in non-cardiac surgery; the impact<br />

of prophylactic beta-blocker therapy<br />

S.E. Hoeks1 , O. Schouten1 , M. Dunkelgrun1 , F. Van Lier1 ,<br />

A.E. Durazzo2 , A.N. Neskovich3 , J.B. Froehlich 4 ,J.J.Bax5 ,<br />

E. Boersma1 , D. Poldermans1 . 1Erasmus MC, Rotterdam,<br />

Netherlands; 2Sao Paulo, Brazil; 3Belgrade, Serbia; 4Michigan, United States of<br />

America; 5Leiden University Medical Center, Leiden, Netherlands<br />

Background: Beta-blockers are widely used to improve postoperative cardiac<br />

outcome in patients with coronary artery disease scheduled for non-cardiac<br />

surgery. The recently published POISE (PeriOperative ISchemic Evaluation) trial<br />

using metoprolol controlled release (CR) therapy confirmed their beneficial effects<br />

for myocardial infarction and cardiovascular death. However, metoprolol CR<br />

was associated with an increased overall mortality rate. This was particularly due<br />

to ischemic strokes 41/4174; 1.0% vs 19/4177; 0.5% (odds ratio (OR) 2.2, 95%<br />

CI 1.3-3.7) that might be related to over treatment of beta blockers, resulting in<br />

perioperative hypotension. In the POISE trial metoprolol CR, up to 400 mg, was<br />

administered in four doses starting 2 to 4 hours prior to surgery. This dose is<br />

100% of the maximal recommended therapeutic daily dose (MRTD). In contrast,<br />

in the DECREASE (Dutch Echo Cardiographic Risk Evaluation Applying Stress<br />

Echo) trials the average dose of bisoprolol was 2.5 mg once daily; 12.5% of the<br />

MRTD and started at least 30 days prior to surgery.<br />

Aim: To assess the incidence and risk factors associated with perioperative stroke<br />

in the DECREASE trials.<br />

Methods: All 3889 patients of the DECREASE trials were evaluated for bisoprolol<br />

dose as percentage of MRTD. The MRTD of bisoprolol at the start of the trial<br />

and during surgery was 12.5% and 16.5% respectively. All cardiac risk factors<br />

and medication use were noted. The incidence of stroke, diagnosed on clinical<br />

symptoms and CT scan, within 30 days after surgery is reported.<br />

Results: The incidence of perioperative stroke in the DECREASE trials was<br />

18/3889 (0.46%) compared to 41/4174 (0.98%) in the POISE trial, p=0.006.<br />

Among beta-blocker users, the incidence was 0.5% in the DECREASE trials and<br />

1.0% in the POISE study. In the DECREASE trials all strokes had an ischemic<br />

origin. A history of stroke was associated with perioperative stroke: OR 5.4, 95%<br />

CI 1.9-15.2. Statins and anti-coagulants were not associated with perioperative<br />

stroke; OR 0.9; 95% CI 0.3-2.5 and OR 1.1, 95% CI 0.3-3.9. Importantly, no association<br />

with bisoprolol therapy was assessed, OR 1.5, 95% CI 0.5-4.3.<br />

Conclusion: In the DECREASE trials using low dose bisoprolol regimen starting<br />

at least 30 days prior to surgery, no association was observed between betablocker<br />

use and perioperative stroke, in contrast to high-dose metoprolol CR therapy<br />

in the POISE study.<br />

2501 Cardiovascular risk profile, costs and incidence of<br />

events in patients with stroke in a population attended<br />

in primary care<br />

J. Fernandez De Bobadilla1 ,A.Sicras2 ,R.Navarro2 , D. Ezpeleta3 ,<br />

C. Alvarez 1 , C. Sanchez4 ,J.Soto1 . 1Pfizer, Outcomes Research,<br />

Madrid, Spain; 2Badalona Servicios Asistenciales, Barcelona, Spain; 3Hospital General Universitario Gregorio Maran, Neurology, Madrid, Spain; 4Euroclin Institute, Outcomes Research, Madrid, Spain<br />

Objective: To assess the prevalence of stroke, and the differences between patients<br />

with and without previous stroke, in terms of mortality and cardiovascular<br />

events in Spain.<br />

Methods: Patients aged>30 years, attending to primary care centres in Spain<br />

during 2006 were evaluated. Variables assessed: prevalence of stroke, cardiovascular<br />

risk factors, morbidity budget, costs, family history of cardiovascular heart<br />

disease, incidence of cardiovascular events and death. The population with and<br />

without previous stroke was compared using student’s t test and chi square distribution.<br />

Results: Of the 57,026 patients, 54.8% were female. Prevalence of hypertension<br />

was 26.5%; diabetes 11.1%; dyslipidemia 27.6%, obesity 11.3%, smoking<br />

20.1% and excessive alcohol consumption 2.1%. The prevalence of CVD different<br />

to stroke was 1.4% for angina; 3.4% myocardial infarction and 2.5% peripheral<br />

arteriopathy. Profiles of patients with vs without previous stroke: Age 72.5<br />

(with stroke) and 53.5 (without stroke), females 41.8% vs 55.4%, morbidity bud-<br />

Stroke and the heart 395<br />

get: 3.2% vs 2.53%, number of CVRF 3.4 vs 1.2, angina 5.07 vs 1.22, previous<br />

myocardial infarction 16.17 vs 2.76, annual mortality 4.2 vs 1.2, cardiovascular<br />

events: 19.7 vs 1.8. Total costs were � 2,590 for patients with stroke and � 985.3<br />

in patients without stroke.<br />

Conclusions: The annual incidence of cardiovascular events or death in patients<br />

with stroke in Spain is 20%. The average cost of a patient with antecedents of<br />

stroke is 2590� , 60% more than patients without previous stroke. It would be<br />

advisable to use all therapeutics resources supported by scientific evidence in<br />

the secondary prevention of this population<br />

2502 Percutaneous Left Atrial Appendage Transcatheter<br />

Occlusion (PLAATO) for stroke prevention in atrial<br />

fibrillation: 2-years outcome<br />

J.-W. Park 1 ,U.Gerk1 , B. Leithauser2 , M. Vrsansky1 , F. Jung3 .<br />

1Hoyerswerda Hospital, Cardiology/Angiology, Hoyerswerda,<br />

Germany; 2Clinic For Angiology, Hannover, Germany; 3Berlin-Brdbg Center for<br />

Regenerative Therapy, Charite, Campus Virchow-Klinikum, Berlin, Germany<br />

Purpose: In > 90% of patients with atrial fibrillation (AF), stroke is due to thrombotic<br />

embolisation from the left atrial appendage (LAA). Transcatheter occlusion<br />

with PLAATO, a self-expanding, membrane-covered spherical nitinol cage, is feasible<br />

and an alternative to anticoagulation therapy.<br />

Methods: Single-centre prospective registry study for verification of stroke risk<br />

reduction in patients with AF 2 years after PLAATO.<br />

Results: 73 patients with AF (permanent 65, paroxysmal 8) in whom anticoagulation<br />

therapy was contraindicated or rejected underwent transcatheter LAA occlusion<br />

with PLAATO. LAA angiography revealed residual thrombi in 7 patients<br />

(10%), which have not been detected with prior transesophageal echocardiography<br />

(TEE). One patient died periprocedural due to implant embolization and one<br />

patient underwent open heart surgery because of implant instability. The remaining<br />

71 patients were followed for 24 months. In 52 patients a stable anchoring<br />

of the PLAATO device without migration or dislocation could be documented by<br />

TEE. No thrombotic deposition was found on the LA luminal surface of the device.<br />

Statistically, in our patient cohort 7 strokes would have been expected without any<br />

treatment within 24 months. In fact no stroke was reportet. Ten out of 71 patients<br />

died during follow up, 6 in our hospital, 4 at home. None of them died from stroke.<br />

Conclusions: 97% of AF patients could be successfully treated with PLAATO. After<br />

mechanical LAA occlusion, the 2-years risk of stroke in AF patients is markedly<br />

reduced. Therefore, this therapeutical concept is a clear alternative for patients<br />

with AF and contraindications for oral anticoagulation.<br />

2503 Predictors of ischaemic stroke during acute phase of<br />

ST Elevation Myocardial Infarction (STEMI)<br />

S. Pernencar on behalf of Portuguese Society of Cardiology Acute<br />

Coronary Syndromes Investigators. Leiria, Portugal<br />

Aim: Identify the independent predictors and other complications associated<br />

with stroke during hospitalization for an acute Myocardial Infarction (MI).<br />

Methods: Multicentric and retrospective analysis of a database with 17165 patients<br />

(pts) admitted since 2002 for acute MI and had 6-month follow-up data. Pts<br />

were then subdivided in two groups:<br />

Group A – 17015 pts with acute MI and without stroke during the hospitalization<br />

Group B – 150 pts with acute MI complicated with stroke<br />

Results: Female gender was more prevalent in group B 44% vs 30% (p=0.001).<br />

Pts in Group B had a higher risk profile, with increased prevalence of others CV<br />

risk factors, such as Diabetes (33% vs 23%, p=0.002) and previous stroke (17%<br />

vs 7%, p


396 Sudden death, devices and public awareness<br />

SUDDEN DEATH, DEVICES AND PUBLIC AWARENESS<br />

2526 Long-term mortality in MADIT II patients with<br />

implantable cardioverter defibrillators<br />

I. Cygankiewicz1 , W. Zareba1 , I. Goldenberg1 , J. Gillespi2 ,H.Klein1 ,<br />

S. Mc Nitt 1 , M.L. Andrews 1 ,J.W.Hall1 ,A.J.Moss1on behalf of MADIT<br />

II Investigators. 1University of Rochester Medical Center, Rochester<br />

Ny, United States of America; 2University of Buffalo, Rochester Ny, United States<br />

of America<br />

Objectives: Data on long-term follow-up and factors influencing mortality among<br />

ICD recipients are limited. Therefore, the aim of the study was to evaluate the<br />

survival rate during long term follow up and the predictive value of various risk<br />

markers in MADIT II patients.<br />

Methods: Study involved patients from MADIT II trial randomized to ICD treatment.<br />

Data regarding long-term mortality was retrieved from the National Death<br />

Registry. Several clinical, biochemical and ECG variables were tested in multivariate<br />

Cox model for predicting long term mortality.<br />

Results: Studied population consisted of 655 patients (547M) mean age 64±10<br />

yrs. During a mean of 63 months 294 deaths occurred. According to Kaplan Meier<br />

curves 6-year probability of death was 40%. Compared with surviving patients<br />

those who died were significantly older, had lower LVEF, more frequently presented<br />

diabetes, renal dysfunction, higher NYHA class and non-sinus rhythm.<br />

Multivariate analysis identified age>65 yrs (HR=1.48,p=0.002), NYHA class 3-4<br />

(HR=1.78,p


Sudden death, devices and public awareness / Bone marrow progenitors: filling the bench to bedside gap 397<br />

Results: In all, 863 cases of OHCA were included during the intervention. Another<br />

657 OHCA fulfilled the inclusion criteria and were used as historical controls<br />

during 2004. Baseline characteristics and demographic data did not differ<br />

between the two groups. Among dual dispatches, fire department arrived first<br />

on scene and initiated treatment in 36% of cases. EMS arrived before the fire<br />

department in 50% and simultaneously in 14%. The median time from call to arrival<br />

of first responder decreased from 7.5 to 7.1 minutes during the intervention<br />

(p=0.004). The proportion of patients in shockable rhythm did not change after the<br />

introduction of the program. The proportion of patients alive 1 month after OHCA<br />

rose from 4.4% during the historical control to 6.8% (unadjusted OR: 1.6; 95% C.I:<br />

1.0-2.5) after the introduction of the project (adjusted OR: 1.6; 95% C.I: 0.9-2.9).<br />

The difference in 1-month survival was particularly marked among patients with<br />

witnessed cardiac arrests with a rise from 5.7% to 9.7% (adjusted OR: 2.0; 95%<br />

C.I: 1.1-3.7). Survival after OHCA in the rest of Sweden (Stockholm excluded)<br />

changed from 8.3% to 6.6% during the corresponding time period (p=0.052). In<br />

all, only three OHCA occurred at public venues equipped with AEDs; none of<br />

these patients survived to hospital.<br />

Conclusion: An introduction of a fire department led early defibrillation program<br />

in Stockholm has led to shortened response times and to improved survival for patients<br />

with witnessed OHCA. The increase in survival is mainly believed to be associated<br />

with shortened time intervals (to arrival and defibrillation) and improved<br />

CPR (due to more persons treating the patient with ongoing cardiac arrest).<br />

2530 Gender differences in clinical manifestations of<br />

Brugada syndrome<br />

B. Benito1 ,A.Sarkozy2 , L. Mont1 , S. Henkens2 , P. Berne1 ,<br />

A. Berruezo1 , D. Tamborero1 , R. Brugada3 , P. Brugada2 , J. Brugada1 .<br />

1Hospital Clinic of Barcelona, Cardiology, The Thorax Institute,<br />

Barcelona, Spain; 2UZ Brussel, VUB Brussels, <strong>Heart</strong> Rhythm Management<br />

Centre, Brussels, Belgium; 3Montreal <strong>Heart</strong> Institute, Cardiovascular Genetics<br />

Center, Montreal, Canada<br />

Background: Brugada syndrome is an autosomal dominant disease with a male<br />

predominance. No specific data are available, however, concerning gender differences<br />

on the clinical manifestations, phenotype and their role in prognosis.<br />

Methods: Patients were recruited and followed prospectively. A spontaneous<br />

or induced (after sodim-blocker administration) coved-type ECG pattern (type-<br />

1) was required in all patients. Baseline clinical characteristics, ECG parameters<br />

after sodium blockers and events (sudden death [SD] or documented ventricular<br />

fibrillation [VF]) in follow-up were recorded for all patients.<br />

Results: Among 384 patients, 272 (70.8%) were male and 112 (29.2%) female.<br />

At inclusion, males had suffered previously more frequently of syncope (18%) or<br />

aborted SD (6%) than females (14% and 1% respectively, p=0.04). Males also<br />

had higher rates of spontaneous type-1 ECG (47% vs 23%, p=0.0001) and inducibility<br />

of VF during electrophysiological study (32% vs 12%, p=0.0001). The<br />

amount of spontaneous ST-segment elevation was also higher in males (3.5±1.8<br />

mm vs 2.5±0.7 mm, p=0.0001). However, conduction parameters and corrected<br />

QT interval significantly increased more in females in response to sodium blockers.<br />

During a mean follow-up of 58±48 months, SD or documented VF occurred<br />

in 31 males (11.6%) and 3 females (2.8%) (p=0.003) (figure).<br />

Conclusions: Males with Brugada syndrome present with a higher risk clinical<br />

profile than females: at diagnosis, they have had more symptoms, including<br />

aborted SD, have more abnormalities on the spontaneous ECG and have more<br />

frequently inducible VF. Males have a worse prognosis as evidenced by a higher<br />

rate of SD or aborted SD during follow-up.<br />

2531 Comparison between percutaneous extraction of<br />

implantable cardioverter defibrillator leads and<br />

pacemaker leads<br />

D. Klug 1 , C. Marquie2 , F. Brigadeau2 , L. Guedon2 , C. Kouakam2 ,<br />

D. Lacroix 2 ,S.Kacet2 . 1Hopital Cardiologique, CHRU Lille, Service de<br />

Cardiologie A, Lille Cedex 9, France; 2Lille, France<br />

The indications for implantable cardioverter defibrillator (ICD) are increasing. For<br />

some complication the ICDs’ leads have to be extracted. We have compared<br />

our experience in percutaneous extraction of pacemaker (PM) leads and ICD<br />

leads.<br />

Population: Between January 1998 and <strong>September</strong> 2007 1081 leads in 611 patients<br />

with 81 ICD leads in 81 patients (13%) have been percutaneously extracted.<br />

In 2006 and 2007, ICD leads represent 24% of our extraction procedures.<br />

Results: Leads characteristics and results of extraction are summarized in table<br />

1. ICD leads were single-coils leads in 58%. Failure of ICD leads extraction occurred<br />

in 2 relative young leads (11 and 56 months) and 1 old leads (13 years)<br />

in comparison age of PM leads with failure was 105±53 months. Coils were responsible<br />

of the failure in the 3 cases including a distal coils clung on the tricuspid<br />

valve in a young boy. Laser sheath and femoral extraction were required in 45 and<br />

14% of ICD leads extractions.<br />

PM ICD p<br />

Age of leads 75±62 M 31±37 M


398 Bone marrow progenitors: filling the bench to bedside gap<br />

Methods and Results: Adherent platelets express substantial amounts of SDF-1<br />

and recruit CD34+ cells in vitro and in vivo. A monoclonal antibody to SDF-1 or<br />

to its counter receptor CXCR4 inhibits stem cell adhesion on adherent platelets<br />

under high arterial shear in vitro and after carotid ligation in mice, as determined<br />

by intravital fluorescence microscopy. Platelets adherent on human arterial<br />

endothelial cells enhance the adhesion of CD34+ cells on endothelium under<br />

flow conditions, a process which is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion<br />

in mice, anti-SDF-1 and anti-CXCR4, but not isotype control<br />

antibodies, abolish the recruitment of CD34+ cells in microcirculation. Moreover,<br />

platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation<br />

of CD34+ cells into endothelial progenitor cells, as verified by colony<br />

forming assays in vitro. When CD34+ cells were cultivated to form colony forming<br />

units, they exhibit similar endothelial surface markers such as CD146, CD144,<br />

or CD31 compared to primary endothelial cell cultures cultivated from human arteries.<br />

PCR-analysis showed that CD34+ cell-derived endothelial progenitor cells<br />

exhibit positive signals for eNOS, Tie-2, and VEGFR-2 similar to those signals<br />

obtained from arterial endothelial cells.<br />

Conclusions: These findings imply that platelet-derived SDF-1 regulates adhesion<br />

of stem cells in vitro and in vivo and promotes differentiation of CD34+ cells<br />

to endothelial progenitor cells. Since tissue regeneration depends on progenitor<br />

cell recruitment to peripheral vasculature and their subsequent differentiation,<br />

platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.<br />

2534 Bone marrow-derived cells are not involved in<br />

reendothelialized endothelium as endothelial cells in<br />

simple endothelial denudation models in mice<br />

M. Tsuzuki. Nagoya University, Department of Cardiology, Nagoya,<br />

Japan<br />

Purpose: It has been shown that bone marrow (BM)-derived cells are involved<br />

in repaired endothelium as endothelialcells in the murine arterial injury models<br />

which produce neointima. However, it has not been shown in simple endothelial<br />

denudation models.<br />

Methods: Male wild-type and green fluorescent protein (GFP)-transgenic<br />

C57BL/6J mice were used. For qualitative studies, at least 4 mice aged 8 to<br />

12 weeks were operated. For BM-transplantation model, recipient wild-type and<br />

donor GFP transgenic mice aged 6-week were used. The recipient mice were irradiated<br />

(10 Gy) and infused GFP-positive donor BM cells (3×1,000,000 cells). BMtransplanted<br />

mice were operated at least 4 weeks after transplantation. A newly<br />

established model of 0.35-mm guide wire-induced endothelial denudation, which<br />

formed no neointima at 14 days after operation, of common carotid artery (CCA<br />

model) and a conventional femoral endothelial denudation model using 0.25-mm<br />

guide wire (FA model) were performed.<br />

Results: In terms of the CCA model, although endothelial detachment in carotid<br />

bifurcation was found, these lesions had continuity with the detachment/neointima<br />

in ligated external carotid artery (ECA). Endothelial detachments were also found<br />

in ECAs of sham-operated mice. At 7 days after operation, the common carotid<br />

arteries (CCAs) were reendothelialized from the aortic arch and the carotid bifurcation<br />

but not completely by Evans Blue extravasation. Scanning electron<br />

microscopy revealed that unendothelialized area was covered with platelets. In<br />

terms of BM transplanted animals, there was no GFP positive endothelial cell in<br />

denuded CCA by whole mount CD31 immunohistochemical staining at 7 or 28<br />

days after operation. On the other hand, GFP positive "dendritic" cells were recruited<br />

in repaired endothelial layer. These GFP positive cells were also seen in<br />

endothelial layer of uninjured side of carotid bifurcation. These "dendritic" cells<br />

were assumed to be vascular dendritic cells and/or pericytes because of morphological<br />

features. In terms of the FA model, neointima formation was observed at 28<br />

days after operation. However, no GFP positive endothelial cells were observed<br />

in neointimal area by whole mount CD31 staining at 7 or 28 days after operation<br />

otherwise "dendritic" cells were seen at the endothelium and in the neointima.<br />

Conclusions: These results suggest that BM-derived cells may not be involved in<br />

reendothelialization as endothelial cells in simple denudation models of endothelium.<br />

2535 Mobilization of bone marrow-derived Oct-4+SSEA-4+<br />

very small embryonic-like cells in patients with acute<br />

myocardial infarction<br />

W. Wojakowski1 ,M.Kucia2 , E. Zuba-Surma2 , E. Paczkowska3 ,<br />

J. Ciosek1 ,M.Kazmierski1 ,A.Ochala1 , B. Machalinski3 ,<br />

M.Z. Ratajczak2 , M. Tendera1 . 1Medical University of Silesia, III Division of<br />

Cardiology, Katowice, Poland; 2University of Louisville, Stem Cell Institute,<br />

Louisville, United States of America; 3Pomeranian Medical University, General<br />

Pathology, Szczecin, Poland<br />

Acute myocardial infarction (MI) induces mobilization of bone marrow stem cells.<br />

Recently rare population of small non-hematopoietic lin-CD133+CD45-CXCR4+<br />

(very small embryonic-like stem cells, VSEL), expressing markers of embryonic<br />

pluripotent stem cells (PSC) was identified in murine bone marrow and human<br />

umbilical cord blood.<br />

Aim: Aim of the study was to assess the mobilization of VSEL in patients with<br />

AMI, isolate VSEL from peripheral blood and measure expression of PSC, cardiac<br />

and endothelial markers.<br />

Methods: 31pts with acute MI and 30 healthy subjects (CTRL) were enrolled.<br />

Blood (20 mL) was sampled on admission, after 24 hours and 5 days, erythrocytes<br />

were lysed and CD34+CXCR4+lin-CD133+CD45- cells were isolated using<br />

live cell sorting system (FACSAria). Plasma levels of SDF-1, HGF, VEGF, G-CSF<br />

were measured.<br />

Results: In healthy subjects number of circulating VSEL is very low (1,1±0,2<br />

cells/μL). In acute MI VSELs were mobilized early (2,77±0,8 cells/μL; p


Bone marrow progenitors: filling the bench to bedside gap / Magnetic navigation for arrhythmia ablation 399<br />

aggregates between platelets and stem cells. Patients with ACS (n=51) showed a<br />

significantly increased number of CD34+ cells (P


400 Magnetic navigation for arrhythmia ablation / Preventing complications in atrial fibrillation ablation<br />

MNS offers further advantages for ablation of the slow pathway since physician’s<br />

radiation exposure is virtually zero with a fairly low radiation exposure to the patient.<br />

2562 Magnetic remote radiofrequency ablation in wpw<br />

patients with left accessory pathways<br />

A. Ardashev, E. Zhelyakov, A. Shavarov, M. Rybachenko, A. Konev.<br />

Burdenko Head clinical hospital, Interventional Cardiology Dept.,<br />

Moscow, Russian Federation<br />

Purpose: to access feasibility of retrograde aortic approach for radiofrequency<br />

catheter ablation (RFA) of left accessory pathways (APs) using NIOBE magnetic<br />

navigation system.<br />

Methods and Results: Study was conducted on 22 consecutive patients (8<br />

women, 34.3±12.5 years of age) with the apparent (17 pts) and concealed leftsided<br />

APs which were verified during electrophysiology study (left lateral APs<br />

in 18 cases, left anterior-lateral in 4 cases). Magnetic 4-mm tip, catheter Helios<br />

was passed through aortic valve and advanced to the target positions (atrial (18<br />

cases) and ventricular (4 cases) insertion sites of AP) guided by using the X-ray<br />

examination and magnetic NIOBE system.<br />

Three step maneuver used for catheter advancement through aortic valve. First<br />

step - catheter was advanced to aortic valve into aortic root using motor drive.<br />

Second step - tip of catheter was positioned near right coronary artery ostium using<br />

uniform magnetic field. Third step – catheter was passed through aortic valve<br />

guided by catheter advancer system (Cardiodrive) while curved by itself. These<br />

maneuvers were successful in all cases (22 pts). RFA was performed (50° C,<br />

maximum 50 W, mean duration 20±7 s) in all cases. There were no complication<br />

associated with catheter advancement through aortic valve and RFA.<br />

Conclusion: Retrograde aortic approach using NIOBE magnetic navigation system<br />

is safe and feasible technique for advancement of mapping catheter towards<br />

either left atrium or left ventricle.<br />

2563 New insights in AVNRT ablation: lower incidence of<br />

junctional rhythm with magnetic navigation compared<br />

to conventional ablation<br />

P. Ricard, D.G. Latcu, N. Zarqane, K. Yaici, C. Turchina, J.P. Rinaldi,<br />

N. Saoudi. Centre Hospitalier Princesse Grace, Cardiology, Monaco,<br />

Monaco<br />

Introduction: The occurrence of accelerated junctional rhythm during radiofrequency<br />

ablation of the slow pathway in patients with atrioventricular nodal re-entry<br />

tachycardia (AVNRT) is frequent. The aim of the present study was to compare<br />

the occurrence of junctional rhythm during magnetic remote catheter ablation to<br />

the conventional manual ablation (CMA) of slow-fast AVNRT.<br />

Methods: Twenty-six patients (Male: 7; age: 51±15) who underwent slow pathway<br />

ablation with a magnetic navigation system (MNS) (Niobe, Stereostaxis)<br />

were compared to a control group of 11 patients (Male: 3; age: 53±16) treated<br />

with CMA. Ablations were performed in both groups with 4-mm non-irrigated tip<br />

catheters. Radiofrequency energy was applied with settings of 30 W and 60°C for<br />

all patients.<br />

Results: Acute success, defined as the absence of inducible AVNRT and no more<br />

than one echo beat, was obtained in all patients. In the MNS group, 3 patients had<br />

no junctional beat (JB) at all and 7 patients had ≤ 10 JB. In contrast, in the CMA<br />

group no patient had ≤ 10 JB. The mean number of JB in the MNS group was<br />

66±94 (0-410) versus 200±243 (43-914) in the CMA group (p=0.019). Duration<br />

of radiofrequency application was not statistically different among groups. In the<br />

MNS group 1 patient had a first degree atrio-ventricular block. No other complication<br />

occurred.<br />

Conclusions: MNS ablation of AVNRT is effective and is associated with less JB<br />

than CMA. Since MNS has been shown to provide lower catheter pressure compared<br />

to CMA, we may suppose that this feature explain our finding. Therefore JB<br />

may not be considered as a mandatory indicator for successful AVNRT ablation<br />

with MNS.<br />

PREVENTING COMPLICATIONS IN ATRIAL FIBRILLATION<br />

ABLATION<br />

2564 Role of intraesophageal temperature monitoring to<br />

prevent esophageal injury during AF catheter ablation<br />

T. Gaspar, C. Piorkowski, C. Staab, A. Bollmann, A. Arya, D. Husser,<br />

M. Esato, S. Kircher, P. Sommer, G. Hindricks. <strong>Heart</strong> Center Universitiy<br />

Leipzig, Electrophysiology, Leipzig, Germany<br />

Background: The relationship between the posterior left atrium and the esophagus<br />

is a potential hazard for left atrial PV ablation. Esophageal perforation is<br />

a life threatening complication. The current prospective study collected new insights<br />

into clinical effects of radiofrequency ablation on esophageal temperature<br />

using a newly designed intraesophageal temperature probe containing multiple<br />

temperature sensors.<br />

Methods: 20 consecutive patients received a circumferential PV ablation using<br />

irrigated tip ablation within the NavX system. Complete PV isolation with bidirectional<br />

block was the procedural endpoint. Throughout the procedure a catheter<br />

with three circular temperature sensors was placed in the esophagus of the sedated<br />

patient. This catheter was visualized on NavX. In case of temperature increases<br />

above 40°C ablation was discontinued until esophageal temperature had<br />

returned to baseline. Postinterventional gastroscopy was performed to assess for<br />

acute alterations of esophageal mucosa.<br />

Results: Visualization of the temperature probe on NavX provided a reliable analysis<br />

of esophageal course and contact. In 75% of the patients ablation energy and<br />

irrigation flow rate had to be reduced due to esophageal temperature increases.<br />

Still 40% of the patients showed temperature increases above 40°C with an energy<br />

setting of 20W and 20ml/h. In 25% of the patients continuous and transmural<br />

ablation at the posterior left atrium was not possible, and PV isolation had to be<br />

performed on a more distal level within the PV antrum. During postinterventional<br />

gastroscopy none of the patients showed alteration of the esophageal mucosa<br />

with respect to ulceration or erythema.<br />

Conclusion: A temperature probe containing multiple temperature sensors covering<br />

most of the lenght of the posterior left atrium shows surprising intraesophageal<br />

temperature increases even with low RF energy settings. Intraesophageal<br />

temperature response during posterior left atrial ablation shows a large<br />

interindividual variability. Simultaneous visualization of the temperature probe on<br />

NavX combines anatomical information about dangerous ablation target sites with<br />

functional information about actual esophageal heating, in order to individually adjust<br />

ablation energy. With an intraesophageal temperature threshold of 40°C no<br />

damage to the esophageal mucosa could be observed during gastroscopy.<br />

2565 Using delayed-enhancement MRI to detect esophageal<br />

tissue damage following radiofrequency ablation for<br />

atrial fibrillation<br />

T. Badger1 , R.S. Oakes1 ,E.Fish1 , N. Segerson1 ,M.Daccarett1 ,<br />

N. Akoum1 , E. Kholmovski2 , E.V. Dibella2 , R.S. Macleod3 ,<br />

N.F. Marrouche1 . 1AF Program, University of Utah, Cardiology, Salt Lake City,<br />

United States of America; 2Utah Center for Advanced Radiology Research,<br />

Radiology, Salt Lake City, United States of America; 3Scientific Computing<br />

Institute (SCI), Utah, Biomedical Engineering, Salt Lake City, United States of<br />

America<br />

Objectives: Atrioesophageal (AE) fistula is a severe complication of radiofrequency<br />

(RF) ablation in the treatment of atrial fibrillation (AF). Currently, little is<br />

known in regards to how mediastinal structures posterior to the left atrium respond<br />

following ablation. We report the discovery of esophageal tissue damage<br />

three months following RF ablation using delayed-enhancement cardiovascular<br />

MRI (DE-MRI).<br />

Methods: Patients who presented for Pulmonary Vein Antrum Isolation received<br />

a DE-MRI at 3 months follow up. 3D segmentations of the left atrium (LA) and<br />

esophagus were performed with application of a color look-up table (CLUT) to<br />

illuminate tissue with delayed washout kinetics of the contrast agent, gadolinium.<br />

Qualitative assessment was performed to analyze the presence of esophageal<br />

enhancement in regions of close proximity to the LA, as well as quantitative assessment<br />

to analyze esophageal wall thickening.<br />

Results: Of 103 patients who received a DE-MRI at 3 months follow up, 3 (2.9%)<br />

showed hyper-enhancement in the esophagus. All 3 patients showed increased<br />

enhancement in the anterior wall of the esophagus with an average 216% anterior<br />

wall thickening in comparison to the posterior wall. In three dimensional models,<br />

increased esophageal enhancement (red) indicating tissue injury was seen in<br />

regions that shared a common surface with the posterior wall of the LA. All 3<br />

patients were asymptomatic.<br />

Esophagus panel.<br />

Conclusions: Esophageal tissue damage from RF ablation can be detected by<br />

DE-MRI 3 months post-procedure. More research is needed to categorize the<br />

extent and clinical implications of this tissue damage and to detect whether these<br />

patients are high risk for AE fistula in repeat ablation.<br />

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2566 Esophageal capsule endoscopy in consecutive<br />

patients: a new tool to assess esophageal damage<br />

following atrial fibrillation ablation<br />

L. Di Biase 1 ,S.Poe 2 , L.C. Saenz 3 ,M.Vacca 3 ,A.Siu 2 , J. Santisi 2 ,<br />

M. Dodig 2 ,R.Schweikert 2 ,W.Saliba 2 , A. Natale 4 . 1 Cleveland<br />

Clinic/University of Foggia, Cardiovascular Medicine, Cleveland/Foggia, United<br />

States of America; 2 Cleveland, United States of America; 3 Bogota, Colombia;<br />

4 Stanford University, Palo Alto, United States of America<br />

Introduction: Left atrioesophageal fistula is a rare but devastating complication<br />

that can occur following catheter ablation of atrial fibrillation. Little information is<br />

known on the esophageal injury following the procedure and its correlation with<br />

symptoms.<br />

Methods: Consecutive patients undergoing AF ablation for symptomatic atrial<br />

fibrillation refractory to AAD have been enrolled in this study. All patients underwent<br />

esophageal temperature monitoring during the procedure. Radiofrequency<br />

energy was discontinued when the luminal temperature increased. After ablation<br />

all patients had capsule endoscopy (Pillcam Eso) to assess the presence for endoluminal<br />

tissue damage of the esophagus.<br />

Results: 107 consecutive patients (79 males) with a mean age of 60+10.4, mean<br />

LA dimension of 4.2 cm + 0.5 and mean EF 49.6 + 7.1 have been enrolled in this<br />

study (63 paroxysmal and 44 non paroxysmal).<br />

Of the patient 27% reported chest discomfort post ablation. Symptoms during<br />

ablation were non specific and not correlated with the positive findings. We identified<br />

10 positive findings located in distal esophagus at the level of the ablation<br />

catheter as linear erosion with clean base and 3 positive findings described as<br />

mid esophageal ulceration with or without trace of blood, not at the level of the<br />

ablation catheter.<br />

Of the patient with positive findings only one (1) had chest disconfort after ablation.<br />

The Max Esophageal temp was 39.4+ 0.5 C; the time to baseline temperature<br />

Recovery was 17+ 2.4 sec and the time to peak Temperature was 20+ 8 sec.<br />

No complication occurred during and after the administration of the pill cam.<br />

Conclusion: The use of capsule endoscopy is a safe and efficacy tool to identify<br />

patients with esophageal damage. Importantly the positive findings were not<br />

associated with post procedural symptoms. Further studies are required to better<br />

understand whether patients with positive findings following ablation, require<br />

a different follow-up and additional treatment.<br />

2567 Pulmonary vein stenting for the treatment of acquired<br />

severe PV stenosis<br />

T. Neumann, T. Dill, M. Kuniss, G. Conradi, J. Sperzel, S. Zaltsberg,<br />

A. Berkowitsch, C. Hamm, H. Pitschner. Kerckhoff <strong>Heart</strong> Center,<br />

Cardiology, Bad Nauheim, Germany<br />

Purpose: The preferred therapy for symptomatic pulmonary veins stenosis (PVS)<br />

is pulmonary vein (PV) angioplasty, but this treatment modality is followed by<br />

restenosis in 44 to 70%. Whether there is additional long-term benefit from PVS<br />

stenting is uncertain. The aim of this study was the evaluation of the long-term<br />

success after PV stenting of severe stenosis.<br />

Method: Ten patients with 13 PVS (≥ 70% stenosis) were prospectively evaluated.<br />

PV stenting was performed (diameter 10mm, length 25mm). Magnetic resonance<br />

imaging, lung perfusion scans and multislice CT-scans were performed<br />

before, directly after and every further 12 months. Primary endpoint of the study<br />

was the occurrence of restenosis after PV stenting.<br />

Results: After a median follow-up of 47.7 (IQR’s 25/75 47.2-48.5) months, the primary<br />

endpoint were achieved in 3 out of 13 pulmonary veins (23% of the treated<br />

PVs). We observed one instent restenosis two years after PV stenting. The patient<br />

had dyspnea that arised some weeks before. After an additional balloon<br />

angioplasty the instent restenosis was resolved. In two asymptomatic patients we<br />

observed an occlusion of the PV stent one year after stenting. Normalization of<br />

lung perfusion was noted 4 years after PV stenting versus directly after stenting<br />

in all patients without instent restenosis (n=7).<br />

Conclusion: PVS stenting seems to be superior to balloon angioplasty and effective<br />

at least over a period of 4 years in treating acquired PVS after pulmonary vein<br />

stenosis. Late instent restenosis after PVS stenting can occur. The normalization<br />

of the initially disturbed lung perfusion scan is possible and remains stable, even<br />

4 years after successful PVS stenting.<br />

2568 How close are the atrial arteries to the pulmonary<br />

veins? A potential cooling effect with implications for<br />

catheter ablation of patients with atrial fibrillation<br />

J.A. Cabrera1 , V. Climent2 , B. Fuertes3 , M. Murillo4 , E. Gonzalez5 ,<br />

Y. Ho 6 , M. Vanegas5 , D. Sanchez-Quintana7 . 1Hospital Quiron Madrid,<br />

Cardiology, Madrid, Spain; 2University of Extremadura, Faculty of Medicine,<br />

Badajoz, Spain; 3Hospital Quiron Madrid, Cardiology, Madrid (Pozuelo), Spain;<br />

4 5 University of Extremadura, Faculty of Medicine, Badajoz, Spain; Hospital<br />

Quiron Madrid, Cardiology, Madrid (Pozuelo), Spain; 6Royal Brompton Hospital,<br />

Cardiology, London, United Kingdom; 7University of Extremadura, Faculty of<br />

Medicine, Badajoz, Spain<br />

Introduction: Luminal blood flow of the atrial arteries may produce intramural<br />

cooling reducing the effectiveness of ablative energy to create transmural lesions<br />

Preventing complications in atrial fibrillation ablation 401<br />

around the orifices of the pulmonary veins (PVs) in atrial fibrillation. The presence<br />

of coronary arteries with a close anatomic relation to the PVs and their junctions<br />

with the left atrium has not been previously described.<br />

Methods: In 32 structurally normal human hearts (24 m, 46±18 y) we examined<br />

by disecction techniques and histological sections the arterial vascularization<br />

around the PVs orifices. We measured the external diameters of the arteries<br />

and its distances to the endocardial surface of the left atrium at the veno-atrial<br />

junction.<br />

Results: Histological sections did not revealed significant arteries in close proximity<br />

to the orifices of the right-PVs. On the left veno-atrial junction we observed<br />

in 27 specimens (67%) an arterial branch termed lef intermediate atrial artery<br />

that originated from the left circumflex next to the inferior border of the left atrial<br />

appendage (LAA). This artery ran on the epicardial aspect of the left lateral wall<br />

of the left atrium, over the left lateral ridge between the orifices of the LAA and<br />

left-PVs. The mean external diameter of the left intermediate artery was 1.1±0.3<br />

mm (range 0.5 to 1.6 mm) and ist distance to the endocardial surface of the left<br />

veno-atrial junction ranged between 1.8 to 3.7 mm (2.5±0.5 mm). In most specimens<br />

(62%) the artery ran on the venous side of the ridge closer to the orifice of<br />

the left-PVs than to the appendage.<br />

Conclusions: During ablation around de orifices of the PVs, ablationists should<br />

be mindful of the potentially cooling effect of the left intermediate artery close<br />

to endocardial aspect of the left-PVs, which may protect the surrounding atrial<br />

muscle<br />

2569 Ablation of extra pulmonary atrial foci around or inside<br />

the orifice of the left atrial appendage. The anatomic<br />

risk of induce left phrenic nerve injury<br />

J.A. Cabrera1 ,V.Climent2 , B. Fuertes3 , M. Murillo2 , E. Gonzalez4 ,<br />

Y. Ho 5 , M. Vanegas3 , D. Sanchez -Quintana6 . 1Hospital Quiron<br />

Madrid, Cardiology, Madrid, Spain; 2University of Extremadura, Faculty of<br />

Medicine, Badajoz, Spain; 3Hospital Quiron Madrid, Cardiology, Madrid, Spain;<br />

4 5 Hospital Quiron Madrid, Cardiology, Madrid, Spain; Royal Brompton Hospital,<br />

Cardiology, London, United Kingdom; 6University of Extremadura, Faculty of<br />

Medicine, Badajoz, Spain<br />

Introduction: The risk of induce left phrenic nerve (LPN) injury is a recognized<br />

complication during ablation of atrial fibrillation when creating transmural lesions<br />

inside or around the orifice of the left atrial appendage (LAA). Detailed information<br />

of the anatomic relations between the LPN and the LAA may be useful to perform<br />

the ablation techniques more safely.<br />

Methods: Twenty human cadavers (12 male, 8 female; mean age 70±9 years<br />

old) without obvious signs of thoracic pathology or prior surgery were carefully<br />

dissected. We examined by gross inspection and histological sections the course<br />

of the LPN in relation with the LAA and its distance to the mouth of the left appendage.<br />

Results: The LPN, branch of the cervical plexus runs along the left brachiocephalic<br />

vein. It continues closely applied over the aortic arch, pulmonary trunk<br />

and left atrial appendage and descends in front of the root of the left lung embedded<br />

between the fibrous pericardium and the mediastinal pleura to the diaphragm.<br />

When the LPN course was related to the anterior aspect of the LAA<br />

(5 specimens, 25%) the nerve passed adjacent to its mouth. The mean minimal<br />

distance between the neck of the LAA and the left phrenic nerve was 8.3±3.5 mm<br />

with a range of 2.5 to 14.5 mm<br />

Course of the left phrenic nerve<br />

Conclusions: During ablation of extra-pulmonary atrial foci, ablating tools resulting<br />

in deeper lesions may reach the left phrenic nerve which is in close relation to<br />

the orifice of the left atrial appendage increasing the risk of induce left diaphraghm<br />

paralysis.<br />

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402 Safety is the new efficacy<br />

POSTER SESSION 4<br />

MODERATED POSTERS 1<br />

SAFETY IS THE NEW EFFICACY<br />

P2587 Risk factors for gastroduodenal ulcer during<br />

treatment with acetylsalicylic acid for cardiovascular<br />

risk management<br />

A. Lanas1 , N. Yeomans2 , O. Junghard3 , L.-E. Svedberg3 on behalf<br />

of ASTERIX Investigators. 1University Hospital Lozano Blesa,<br />

Gastroenterology, Zaragoza, Spain; 2University of Western Sydney, School of<br />

Medicine, Sydney, Australia; 3AstraZeneca R&D, Molndal, Sweden<br />

Purpose: Treatment with low-dose acetylsalicylic acid (ASA) is the cornerstone<br />

of cardiovascular (CV) risk management. However, long-term administration of<br />

low-dose ASA is associated with an increased risk of adverse gastrointestinal<br />

events, including peptic ulcers. We have previously reported the efficacy of acidsuppressive<br />

therapy with esomeprazole (ESO) for reducing the risk of such events<br />

in patients (pts) receiving low-dose ASA for CV risk management. We report here<br />

a descriptive analysis of possible risk factors among pts who developed gastroduodenal<br />

ulcers as part of this study.<br />

Methods: ASTERIX was a randomised, double-blind study that enrolled pts aged<br />

≥60 yrs, without baseline gastroduodenal ulcer at endoscopy, who were receiving<br />

continuous low-dose ASA (75-325mg) for CV risk management. Pts were<br />

randomised to ESO 20mg once daily or placebo for 26 wks. The primary study<br />

end point was the development of endoscopic gastroduodenal ulcers among the<br />

intention-to-treat population (ESO, 493 pts; placebo, 498 pts).<br />

Results: A total of 35 pts (placebo, 27; ESO, 8) developed gastroduodenal ulcers<br />

during the study (gastric ulcers, 25 pts [placebo, 19, ESO, 6]; duodenal ulcers, 10<br />

pts [placebo, 8; ESO, 2]). For both treatment groups combined, H. pylori was a<br />

significant risk factor for duodenal ulcer while on low-dose ASA (odds ratio 4.96;<br />

95% confidence interval [CI]: 1.39, 17.76; p=0.014). However, H. pylori was not<br />

a significant risk factor for gastric ulcer while on low-dose ASA (odds ratio 0.87;<br />

95% CI: 0.32, 2.36; p=0.98). Although asymptomatic ulcers often develop in pts<br />

taking NSAIDs, those who developed gastroduodenal ulcers on low-dose ASA<br />

did have almost double the mean antacid consumption (statistically significant in<br />

the placebo group, p=0.005), perhaps reflecting ulcer-related symptoms in some.<br />

The risk of ulcers was almost three times higher at ASA doses >100 mg/d (odds<br />

ratio 2.7; 95% CI: 1.37, 5.32; p=0.0055). There was a trend towards ulcers being<br />

more likely to develop in women (odds ratio 1.81; 95% CI: 0.92, 3.59; p=0.12).<br />

There was no significant effect of age in this study, although all pts were ≥60 yrs<br />

as an entry requirement.<br />

Conclusion: H. pylori is a significant risk factor for developing a duodenal (but<br />

not gastric) ulcer in patients aged ≥60 yrs receiving low-dose ASA for CV risk<br />

management. Aspirin dose also contributes, and female sex may contribute, to<br />

increased risk of gastroduodenal ulcers in these patients.<br />

P2588 Angiotensin-converting enzyme inhibitors and<br />

changes in serum creatinine levels after coronary<br />

angiography and angioplasty<br />

A. Abbate, F. Shaikh, Q. Cheema, A. Nusca, G.W. Vetrovec.<br />

Richmond, United States of America<br />

Background: Contrast-induced nephropathy (CIN) is a dreaded consequence<br />

of cardiac catheterization and an important cause of morbidity and mortality in<br />

hospitalized patients. There have been relatively few and small studies examining<br />

the association between the use of angiotensin-converting enzyme (ACE)inhibitors<br />

and their subsequent effects on the risks of developing contrast-induced<br />

nephropathy. The results of these studies have been mixed. In current practice<br />

and ACE-inhibitors are often held prior to IV dye. The aim of this study is to determine<br />

the effects of ACE-inhibitors on changes in serum creatinine values and<br />

incidence of CIN after coronary angiography/angioplasty.<br />

Methods: A cohort of 600 consecutive patients at high risk of developing CIN because<br />

of baseline impairment in renal function (eGFR100 pg/mL were randomized to<br />

3 months’ double-blind treatment with placebo or aliskiren (150 mg once daily)<br />

added to standard therapy (ACE-I or angiotensin receptor blocker [ARB] and beta<br />

blocker [BB]).<br />

Results: Of the 302 patients enrolled in the study, 106 (35.1%) had diabetes.<br />

Mean age of patients with diabetes was 67.9 years, 20.8% were female, 36.8%<br />

were obese (BMI ≥30 kg/m 2 ) and 36.7% had estimated glomerular filtration rate<br />

(eGFR) 14.28 mmol/L 4 (7.0) 6 (12.2) 0.508 9 (9.1) 9 (9.5) >0.999<br />

Creatinine >176.8 μmol/L 6 (10.5) 3 (6.1) 0.500 5 (5.1) 5 (5.3) >0.999<br />

Potassium 0.999<br />

Potassium >5.5 mmol/L 5 (8.8) 2 (4.1) 0.447 8 (8.1) 10 (10.5) 0.626<br />

Potassium ≥6.0 mmol/L 1 (1.8) 1 (2.0) >0.999 2 (2.0) 5 (5.3) 0.272<br />

Data are number (%) of patients with clinically significant laboratory abnormalities at any time<br />

during the study.BUN, blood urea nitrogen.<br />

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(7.0%) patients receiving aliskiren versus 3/49 (6.1%) patients receiving placebo.<br />

In the aliskiren group, symptomatic hypotension, renal dysfunction and hyperkalemia<br />

occurred in 4, 1 and 5 patients respectively, versus 1, 1 and 1 patients<br />

in the placebo group. The table shows the incidence of predefined laboratory abnormalities.<br />

Conclusion: In ALOFT, addition of aliskiren to optimized medical therapy in patients<br />

with chronic stable HF and diabetes was generally well tolerated.<br />

P2592 Risk assessment of cardiovascular ischemic events<br />

in patients with type 2 diabetes Mellitus receiving<br />

Pioglitazone and Concomitant treatment with nitrates,<br />

ACE/ARBs, or insulin<br />

R.S. Spanheimer 1 , B.C. Charbonnel2 , A.P. Perez1 , S.K. Kupfer1 ,<br />

E.E. Erdmann3 on behalf of PROactive study investigators. 1Deerfield, United<br />

States of America; 2Nantes Cedex, France; 3Koln, Germany<br />

Patients with advanced type 2 diabetes (T2D) are frequently treated with insulin<br />

due to beta cell failure, as well as multiple cardiovascular (CV) agents due<br />

to ischemic complications. PROactive (PROspective pioglitAzone Clinical Trial<br />

In macroVascular Events) was a randomized, double-blind, placebo-controlled<br />

prospective trial that evaluated mortality and CV morbidity in 5238 high-risk<br />

patients with T2D and macrovascular disease. Target HbA1c was 6.5% per<br />

International Diabetes Federation Guidelines. Patients in PROactive were assigned<br />

to pioglitazone (PIO) or placebo in addition to their baseline glucoselowering<br />

and CV medications, including insulin (33.0%), nitrates (39.3%), and<br />

angiotensin-converting enzyme inhibitor (ACE-I)/angiotensin-receptor blockers<br />

(ARBs) (69.7%). Because concomitant use of these medications was associated<br />

with higher CV ischemic risk in another thiazolidinedione (TZD), we evaluated the<br />

effect of PIO on a composite endpoint of all-cause death, nonfatal myocardial infarction<br />

(MI), or stroke in the subgroups of patients using nitrates, ACE-I/ARBs, or<br />

insulin at baseline. Composite CV endpoint risk for PIO treatment was similar regardless<br />

of baseline use of nitrates, ACE-I/ARBs, or insulin (Graph). Additionally,<br />

the interaction between each subgroup and treatment was not significant. Median<br />

HbA1c at final visit was 6.9% in the PIO group and 7.5% in placebo.<br />

The results of this post hoc analysis from the PROactive study did not reveal<br />

an increased risk of all-cause death, MI, or stroke in patients receiving nitrates,<br />

ACE-I/ARBs, or insulin in patients treated with PIO. Rather, patients with these<br />

baseline medications realized the same trend of benefit with PIO as did patients<br />

without these baseline medications.<br />

P2593 The genetic A842G/C50T polymorphism of the<br />

cyclooxygenase-1 gene and the risk of thrombotic<br />

events during aspirin therapy<br />

N. Clappers1 , M.G.A. Van Oijen2 , S. Sundaresan2 , M.A. Brouwer2 ,<br />

R.H.M. Te Morsche2 , W. Keuper2 , W.H.M. Peters2 , J.P.H. Drenth2 ,<br />

F.W.A. Verheugt2 . 1Radboud University Nijmegen Medical Centre, Cardiology<br />

Dept., Nijmegen, Netherlands; 2Radboud University Medical Centre, Gastro<br />

enterology, Nijmegen, Netherlands<br />

Background: Aspirin reduces the risk of thrombotic events by inhibiting platelet<br />

cyclooxygenase-1 (COX-1), consequently reducing thromboxane A2 formation<br />

and platelet aggregation. The C50T genetic polymorphism of COX-1 is associated<br />

with an impaired inhibition of both thromboxane production and platelet aggregation<br />

by aspirin. We studied whether this polymorphism is associated with a<br />

higher risk of clinical thrombotic events in patients using aspirin.<br />

Methods: Patients admitted to our Coronary Care Unit for various indications<br />

and who were prescribed low dose (80-100 mg) aspirin were genotyped for the<br />

COX-1 C50T polymorphism and followed over time. We compared clinical outcomes<br />

between patients with the common genotype and the variant genotype.<br />

The primary endpoint was the composite of myocardial infarction, stroke, or cardiovascular<br />

mortality. Univariate and multivariate hazard ratios were calculated<br />

with Cox regression analysis.<br />

Results: Between April 2002 and January 2004 we included 578 patients in the<br />

total cohort, and 502 of these were treated with aspirin. For 496 patients genotyping<br />

and clinical follow-up was available. The common genotype was present in<br />

86.7%, the variant in 13.3% (12.5% heterozygous, 0.8% homozygous). Baseline<br />

variables were well balanced, except patients with the most common genotype<br />

more frequently already used aspirin prior to the index admission. The median<br />

Safety is the new efficacy / Measuring platelet function: do we need it? 403<br />

(IQR) follow up was 2.5 (1.9-3.2) years, and 98 patients (19.7%) had a primary<br />

endpoint. The unadjusted hazard ratio (HR, 95% CI) for the primary endpoint for<br />

patients with the variant versus most common genotype was 1.07 (0.62-1.85),<br />

P=0.8. The multivariate adjusted HR was 0.86 (0.49-1.50), P=0.6. Independent<br />

predictors of the primary outcome were increasing age, increasing serum creatinine<br />

and diabetes mellitus. With respect to the secondary outcomes, myocardial<br />

infarction occurred in 9.6% of the patients, stroke in 1.6%, cardiovascular death in<br />

12.0%. The rates of these events were not significantly different between patients<br />

with the variant and with the common genotype.<br />

Conclusion: In laboratory studies the genetic C50T polymorphism of COX-1 is<br />

related to an impaired inhibition of thromboxane production and platelet aggregation<br />

by aspirin. However, in this cohort of patients using aspirin for secondary<br />

prevention the polymorphism was not associated with a higher risk of clinical<br />

thrombotic events.<br />

P2594 Laropiprant reduces niacin-induced flushing at<br />

initiation of therapy in Asian patients with<br />

dyslipidemia<br />

D. Kush 1 ,H.S.Kim2 ,D.Hu3 , R. Kirchoff1 , E. Chen1 ,W.Sirah1 ,<br />

C. Mccrary Sisk1 , J.F. Paolini1 . 1Merck Research Laboratories,<br />

New Jersey, United States of America; 2Seoul National University<br />

Hospital, Seoul, Korea, Republic of; 3Peking University, Beijing, China, People’s<br />

Republic of<br />

Purpose: Niacin is underutilized due to prostaglandin D2 (PGD2)-mediated flushing.<br />

Laropiprant, a selective PGD2 receptor (DP1) antagonist, reduces flushing<br />

associated with extended release (ER) niacin. This Phase III randomized, doubleblind,<br />

study compared the acute flushing symptoms with a combination tablet of<br />

ER niacin/laropiprant vs. an ER niacin without laropiprant over one week in lipid<br />

clinic patients in Asia.<br />

Methods: Following a 1-week placebo run-in period, 332 dyslipidemic patients<br />

from China, Korea and Singapore were randomized to ER niacin/laropiprant 1<br />

g/20 mg (designated ERN/LRPT 1 g), Niaspan 1 g (NSP) or placebo (PBO) in<br />

a 2:2:1 ratio for 1 week. Effects of ERN/LRPT vs. NSP on patient-reported flushing<br />

severity were assessed using the validated Global Flushing Severity Score<br />

(GFSS; none/mild [0-3], moderate [4-6], severe [7-9], extreme [10]), captured in a<br />

daily electronic diary.<br />

Results: Compared with NSP, patients treated with ERN/LRPT experienced significantly<br />

less flushing (p


404 Measuring platelet function: do we need it?<br />

aggregometry with thromboxane-specific indexes and point-of-care tests in order<br />

to evaluate the agreement between these platelet function tests.<br />

Methods: Patients with stable coronary artery disease (n=45) were compared<br />

with healthy subjects (n=21) treated with non-enteric coated aspirin 75 mg once<br />

daily for 11 days. Although patients were already treated with aspirin, a run-in<br />

phase was performed. In healthy subjects blood samples were drawn both prior<br />

to and during aspirin treatment. Compliance was optimized by interviews and pill<br />

counting at each visit. Optical platelet aggregometry a.m. Born (OPA) and 3 pointof-care<br />

tests (Multiplate, PFA-100 and VerifyNow) were performed in duplicate<br />

on 4 consecutive days one hour after aspirin ingestion. OPA was induced with<br />

adenosine diphosphat (ADP) 5.0 and 10.0 μM and arachidonic acid (AA) 0.5, 1.0<br />

and 1.5 mM. Additionally, urinary 11-dehydro-TXB2 and serum thromboxane (TX)<br />

B2 were measured during aspirin treatment and at baseline in healthy subjects.<br />

Results: Coefficients of variation (3-46%) and day-to-day variability (3-33%) differed<br />

markedly between tests and was lowest for VerifyNow. The prevalence<br />

of aspirin non-responsiveness was 9% (OPA, 1.0 mM AA), 3% (PFA-100, collagen/epinephrine<br />

cartridge), 0% (Multiplate, 0.75 mM AA) and 0% (VerifyNow,<br />

AA cartridge). The agreement between tests was very low (Kappa ≤ 0.21 for all<br />

comparisons with OPA). Aspirin inhibited serum TXB2 more than 99% in healthy<br />

subjects (median 1.1 ng/mL, interquartile range 0.8;1.9). In patients, mean serum<br />

TXB2 was suppressed to a similar extent (0.9 ng/mL, 0.7;1.5) confirming 100%<br />

compliance as also indicated by interviews and pill-counting. No differences in<br />

urine (p=0.96) or serum (p=0.27) thromboxane metabolites were observed between<br />

aspirin responders and non-responders defined by OPA.<br />

Conclusions: The prevalence of aspirin non-responsiveness was highly assaydependent,<br />

and the agreement between tests was low. Aspirin responsiveness<br />

was high when assessed by thromboxane-specific assays in compliant patients.<br />

However, despite very low levels of thromboxane metabolites in urine and serum,<br />

some patients were "resistant" according to one point-of-care test and optical<br />

platelet aggregometry.<br />

P2597 Assessment of the platelet inhibitory effects of<br />

clopidogrel and prasugrel by the VerifyNow P2Y12<br />

point-of-care device in comparison with LTA and<br />

VASP-phosphorylation in aspirin treated CAD patients<br />

C. Varenhorst1 ,S.James1 ,D.Erlinge2 , O.O. Braun2 ,K.J.Winters3 ,<br />

J.T. Brandt3 , J.A. Jakubowski3 , A. Sugidachi4 , L. Wallentin1 , A. Siegbahn5 .<br />

1Uppsala Clinical Research Center, Dept Internal Medicine, Cardiology, Uppsala,<br />

Sweden; 2Dept of Cardiology, Lund, Sweden; 3Lilly Research Laboratories,<br />

Indianapolis, United States of America; 4Daiichi Sankyo Co., Ltd, Tokyo, Japan;<br />

5Coagulation Laboratory, Dept Medical Sciences, Uppsala, Sweden<br />

Purpose: Prasugrel, a new P2Y12 antagonist, has been reported to achieve<br />

greater inhibition of platelet aggregation (IPA) than clopidogrel. We compared<br />

platelet function by light transmission aggregometry (LTA), whole blood flow<br />

cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP)phosphorylation<br />

and the point-of-care assay VerifyNow P2Y12 (VN-P2Y12).<br />

Studies were performed in aspirin-treated patients with stable coronary artery<br />

disease (CAD) during administration of the thienopyridines prasugrel and clopidogrel.<br />

Methods: After a run-in on 75 mg aspirin, 110 subjects were randomized to double<br />

blind treatment with clopidogrel (n=55) 600 mg LD followed by 75 mg o.d.<br />

(once daily) maintenance dose (MD) for 28 days or prasugrel (n=55) 60 mg LD<br />

followed by 10 mg o.d. MD for 28 days. Platelet aggregation using 20 μMADPwas<br />

measured by LTA (IPA, %), VASP, platelet reactivity index (PRI,%) and VN-P2Y12<br />

device reported percent inhibition at pre-dose, 2 and 24h post-LD and repeated<br />

pre-dose at days 14 and 29. The relationship between the three methods was<br />

evaluated with Pearson’s correlation.<br />

Results: The correlation between % inhibition (VN-P2Y12) vs. % IPA (LTA) was<br />

0.76 (Figure) and % inhibition (VN-P2Y12) vs. % PRI (VASP) was -0.84 (both<br />

p


P2600 Final aggregation response is a more sensitive<br />

marker of the effects of P2Y12 receptor antagonists<br />

than maximal aggregation response<br />

R.F. Storey 1 , C.P. Cannon 2 , R.A. Harrington 3 , P.M. Sandset 4 ,<br />

S. Heptinstall 5 ,M.Wickens 6 ,G.Peters 7 ,H.Emanuelsson 8 ,<br />

S. Husted 9 . 1 University of Sheffield, Department of Cardiology, Sheffield,<br />

United Kingdom; 2 Brigham and Women’s Hospital, Cardiovascular Division,<br />

Boston, United States of America; 3 Duke Clinical Research Institute,<br />

Medicine/Cardiovascular, Durham, United States of America; 4 Ullevaal<br />

University Hospital, Department of Haematology, Oslo, Norway; 5 University of<br />

Nottingham, Cardiovascular Medicine Department, Nottingham, United Kingdom;<br />

6 AstraZeneca, Research & Development, Charnwood, United Kingdom;<br />

7 AstraZeneca, Research & Development, Wilmington, United States of America;<br />

8 AstraZeneca, Research & Development, Molndal, Sweden; 9 Aarhus University<br />

Hospital, Department of Medicine and Cardiology, Aarhus, Denmark<br />

Background: P2Y12 amplifies and sustains the platelet aggregation (PA) response<br />

to ADP, which is initiated by P2Y1. Clopidogrel (CLOP) and AZD6140,<br />

the first reversible oral P2Y12 antagonist, block P2Y12 and inhibit PA. Measuring<br />

maximal or final PA responses to ADP can assess these effects. To assess<br />

the relationship between these measures, we analysed pooled PA data from the<br />

DISPERSE and DISPERSE2 clinical trials.<br />

Methods: Effects of CLOP (75 mg once daily) and AZD6140 (50-200 mg twice<br />

daily, 400 mg once daily) in patients with stable atherosclerotic disease (DIS-<br />

PERSE, n=200) and non-ST elevation acute coronary syndromes (DISPERSE2<br />

substudy, n=45) were assessed using optical aggregometry and ADP 20 μM. Inhibition<br />

of PA (IPA) was measured at multiple time points after drug treatment<br />

using maximal (max IPA) and final PA response (final IPA). Correlation (Spearman<br />

R) and agreement (Bland-Altman, average vs difference) were analysed by<br />

study and treatment (GraphPad Prism).<br />

Results: All analyses showed good correlation between max IPA and final IPA<br />

(R=0.65-0.93). Correlation was greatest for CLOP in DISPERSE (R=0.93) and<br />

lowest for AZD6140 400 mg once daily in DISPERSE (R=0.65). Agreement fell<br />

with increasing IPA and was poorest for regimens that achieved highest IPA, as<br />

high final IPA was associated with highly variable and lower max IPA (figure).<br />

Conclusion: There is good correlation between max and final IPA for assessing<br />

P2Y12 inhibition. However, max IPA may be limited (in view of a P2Y1-mediated,<br />

P2Y12-independent component) so that agreement between both measures is<br />

poor at high levels of P2Y12 inhibition. This analysis suggests that final IPA is a<br />

more sensitive measure of P2Y12 inhibition than max IPA.<br />

P2601 Optimal pretreatment timing for 600mg clopidogrel<br />

before planned percutaneous coronary intervention<br />

for maximal antiplatelet effectivity<br />

Z. Motovska1 ,P.Widimsky1 ,R.Petr1 ,D.Bilkova1 ,I.Marinov2 ,<br />

S. Simek 3 ,P.Kala4on behalf of the PRAGUE 8 study investigators.<br />

1Third Medical Faculty Charles University, 3rd Internal-Cardiology Clinic, Prague,<br />

Czech Republic; 2The Institute of Hematology and Blood Transf., Prague, Czech<br />

Republic; 3First Medical Faculty Charles University, Prague, Czech Republic;<br />

4Masaryk University & University Hospital, Brno, Czech Republic<br />

Background: The optimal dose and timing of pretreatment to achieve maximum<br />

benefit with clopidogrel during PCI remains controversial. The optimal timing for<br />

600mg clopidogrel before planned PCI in patients with stable coronary artery<br />

disease (CAD) has never been tested in a randomized trial.<br />

Methods: The laboratory substudy of the PRAGUE-8 study was performed. The<br />

PRAGUE-8 study compared two 600mg clopidogrel regimens on the outcomes of<br />

patients undergoing elective coronary angiography (CAG)±ad-hoc PCI:the routine<br />

clopidogrel >6h before CAG (group A) vs. the selective clopidogrel only for<br />

PCI patients in the catheterization laboratory, after the CAG and just prior to PCI<br />

(group B). In group A, the mean duration between clopidogrel administration and<br />

procedure was 21±5h. In a laboratory substudy, the time course of platelet inhibition<br />

was investigated in 105 group A patients. Flow cytometric analysis of the<br />

VASP phosphorylation state was done and Platelet Reactivity Index (PRI) was<br />

calculated before and 12, 28, 36, 60, 84 and 108h after clopidogrel use.<br />

Results: The highest pre-clopidogrel PRI was seen in association with diabetes.<br />

The maximal inhibition of platelet activation was achieved by 28h after drug (PRI<br />

mean 36±23%), and 2/3 of patients had PRI value


406 Measuring platelet function: do we need it? / Atrial fibrillation<br />

the three loading regimens. The rates of suboptimal response (IRPA


Results: Female patients (27.7%) were markedly 11 years older than males.<br />

They had a lower prevalence of prior MI and prior coronary interventions. Despite<br />

the older age no differences in the degree of coronary artery disease were<br />

observed. Adjunctive medical treatment including GPIIb/IIIa blocker was similar<br />

in women and men. Hospital mortality was significantly higher in women as in<br />

men. After correction for age and co-morbidity, no differences in hospital mortality<br />

of primary PCI remained between women and men in clinical practice (OR 1.37,<br />

95% CI 0.91-1.91).<br />

Conclusion: Women undergoing primary PCI in Europe were one decade older<br />

than men. Adjunctive medical treatment did not differ between women and men in<br />

the setting of primary PCI. After adjustment for the marked age difference, female<br />

gender did not impact on hospital outcome of primary PCI.<br />

P2609 Ablation of left atrial flutter guided first postpacing<br />

interval electroanatomical mapping<br />

A. Perez, J.L. Merino, R. Peinado, O. Quintero, A. Viana,<br />

J.A. Carbonell, J.L. Lopez-Sendon. Hospital Universitario La Paz,<br />

Madrid, Spain<br />

Catheter ablation is the therapy of choice for well defined supraventricular arrhythmias.<br />

However, the success rate is significantly lower in more complex arrhythmia<br />

substrates, such as left atrial flutter (LAF), despite the use of voltage and<br />

activation electroanatomical mapping. The first postpacing interval (FPI) is an established<br />

mapping method to determine if an endocardial site is in the reentrant<br />

circuit. However, this mapping method has never been implemented on a virtual<br />

anatomical map of a 3D electrophysiology navigation system.<br />

Methods: 21 consecutive patients who underwent ablation attempt of 34 LAFs<br />

were included in the study. Following anatomical reconstruction with a 3D<br />

non-fluoroscopic mapping system (Ensite-NavX), entrainment mapping was attempted<br />

from at least 10 different sites of the left atrium. Entrainment was attempted<br />

by pacing with a cycle length 10-20 ms shorter than the flutter cycle<br />

length (FCL). Differences between the FPI and the FCL (FPI-FCL) at each site<br />

were marked on the anatomical map as "artificial" activation values, where 0 ms<br />

FPI-FCL difference was coded as -300 ms activation time, 10 ms FPI-FCL difference<br />

as -250 ms activation time, and so on with 50 ms activation time increments<br />

for each 10 ms FPI-FCL increment. Once the reentrant circuit was defined on the<br />

FPI map (an area of 0 to 10 ms FPI-FCL difference, which was coded in white<br />

color) ablation was attempted by radiofrequency application at the slow conduction<br />

area or along the narrowest isthmus of conduction of the circuit.<br />

Results: Frequent conversion into different LAFs or atrial fibrillation at entrainment<br />

attempt precluded FPI electroanatomical mapping in 3 patients. A FPI map<br />

was obtained in 31 LAFs in 18 patients and showed the reentrant circuits in<br />

the following positions: 16 perimitral (with different dispositions), 5 in the roof,<br />

6 septal, 1 in the posterior wall, 3 pulmonary vein related. The perimitral circuits<br />

were located all around the mitral valve orifice except in the lateral and superior<br />

part in some patients. Radiofrequency application successfully ablated 25<br />

out of 29 LAFs (86%). Fifteen LAF were ablated by focal radiofrequency application.<br />

Conclusions: First postpacing interval mapping can be implemented on the<br />

anatomical map of 3D electrophysiology navigation systems. These maps provide<br />

precise information about the location and size of the LAF circuits, which<br />

may increase the success rate of the ablation procedure.<br />

P2610 The natural history of asymptomatic ventricular<br />

preexcitation in children. A long-term<br />

electrophysiologic-based follow-up study for risk<br />

stratification<br />

V. Santinelli, A. Radinovic, G. Paglino, G. Vicedomini, C. Pappone.<br />

San Raffaele University Hospital, Electrophysiology And Cardiac<br />

Pacing, Milan, Italy<br />

Purpose: Sudden death can be the first clinical manifestation in children with ventricular<br />

preexcitation, but no risk stratification has been defined to identify subjects<br />

at risk.<br />

Methods: Between 1997 and 2007 we prospectively collected data from 184<br />

children (66% males; median age, 10 years; range 8-12) incidentally found with<br />

asymptomatic ventricular preexcitation on the ECG, who were referred for electrophysiologic<br />

evaluation and risk stratification. Children were followed as outpatients<br />

taking no medications. Primary end point of the study was the occurrence<br />

of life-threatening events and potential predictors.<br />

Results: Over a median follow-up of 20 months after electrophysiologic testing<br />

(min-max, 8-60), 51 children had the first arrhythmic event, which was lifethreatening<br />

in 19 of them (mean age, 10 years; range, 10-14) while the remaining<br />

133 children during a median follow-up of 57 months (min-max, 32-90) did not<br />

experience arrhythmic events, remaining asymptomatic. Life-threatening events<br />

produced an aborted sudden death (3 patients), syncope (3 patients), uncommon<br />

symptoms (8 patients) or no symptoms at all (5 patients). Children who became<br />

symptomatic were successfully ablated. Inducibility (p=0.012), short anterograde<br />

refractory period of accessory pathways (p=0.017) and multiple pathways<br />

(p=0.021) predicted life-threatening events. By combining these 3 risk factors,<br />

children were stratified into low, moderate, and high-risk groups.<br />

Conclusions: This study has important clinical implications in terms of early iden-<br />

Atrial fibrillation 407<br />

tification of high-risk asymptomatic children with ventricular preexcitation. Subjects<br />

with short anterograde effective refractory period of the accessory pathway,<br />

multiple pathways and inducibility are the best candidates for prophylactic ablation,<br />

being at higher risk.<br />

P2611 Image-integration of intraprocedural rotational<br />

angiography based 3D-reconstructions into<br />

electroanatomical mapping: Accuracy of a novel<br />

modality in atrial fibrillation ablation<br />

G. Noelker1 , S. Asbach2 , K.J. Gutleben1 , H. Marschang1 ,<br />

A.M. Sinha1 ,G.Ritscher1 ,M.Schmidt1 , H. Rittger1 , N.F. Marrouche3 ,<br />

J. Brachmann1 . 1Coburg, Germany; 2Freiburg, Germany; 3Salt Lake City, United<br />

States of America<br />

Purpose: Integration of preprocedural imaging into electroanatomical mapping<br />

has been widely adopted in atrial-fibrillation procedures. Three-dimensional reconstructions<br />

of left atrial (LA) and pulmonary vein (PV)-anatomy are currently<br />

prepared by electroanatomical mapping (EAM) systems themselves as part of<br />

the procedure. However, intraprocedural imaging has been shown to be accurate<br />

in comparison to preprocedural multislice computed tomography and may be<br />

superior in terms of actuality. Furthermore, workflow-improvements can possibly<br />

be made by intraprocedural imaging and direct integration of pre-reconstructed<br />

anatomy.<br />

Patients and Methods: 17 patients (12 male, mean age 62±8) presenting for<br />

ablation of atrial fibrillation (9 paroxysmal, 8 persistent) underwent intraprocedural<br />

DynaCT Cardiac. Reconstructed LA and PV-anatomy was directly importet into<br />

CARTOMerge. 128±77 mapping points were taken and a comparison of EAM<br />

and DynaCT Cardiac was performed by statistical analysis of distances between<br />

the 2 modalities.<br />

Results: Direct image integration of prereconstructed 3D-anatomy was feasible<br />

in all patients. The procedure time was 158±25 minutes including 11±3 minutes<br />

for DynaCT Cardiac registration and segmentation. No acute complications<br />

occured. Deviation of mapping points to intraprocedural DynaCT Cardiac 3Dreconstructions<br />

was 2.2±0.5 mm (2.10±0.46 mm in patients suffering from paroxysmal<br />

atrial fibrillation (AF) vs. 2.34±0.40 mm persistent AF, n.s.)<br />

Conclusions: Direct image-integration of 3D-reconstructions of both LA and PV<br />

into EAM was feasible and not time-consuming. The work-flow seemed to be<br />

improved by skipping preprocedural imaging. Intraprocedural DynaCT Cardiac is<br />

highly accurate in comparison to EAM.<br />

P2612 Ablation of electrogram guided substrate for<br />

persistent atrial fibrillation is not enough<br />

H. Estner, J. Wu, T. Reents, B. Zrenner, G. Hessling, I. Deisenhofer.<br />

German <strong>Heart</strong> Center Munich, Cardiology, Munich, Germany<br />

Background: Ablation of complex fractionated atrial electrograms<br />

(CFAE) is a new approach for the treatment of atrial fibrillation (AF). The purpose<br />

of the present study was to assess the efficacy of pulmonary vein isolation<br />

(PVI) additive to the CFAEs ablation in patients with chronic AF.<br />

Methods: This study included 77 consecutive patients with chronic AF who underwent<br />

radiofrequency ablation of CFAEs as a sole ablation procedure (CFAE<br />

group, n=23 patients) or a combined approach of CFAE ablation plus PVI (CFAE<br />

plus PVI group, n=54 patients). Procedures were guided by three-dimensional<br />

mapping systems. After the procedure, AF recurrences were evaluated with 7–<br />

day Holter recordings at 1, 3 and 6 months and every 6 months thereafter. Treatment<br />

failure was defined as ≥1 AF episode lasting >30 seconds on Holter recordings<br />

during follow-up.<br />

Results: After a mean follow-up time of 13±10 months 2 of 23 patients (9%) undergoing<br />

CFAE ablation and 22 of 54 patients (41%) patients undergoing CFAE<br />

ablation plus PVI in the absence of antiarrhythmic drug therapy (P=0.008) remained<br />

in sinus rhythm after a single ablation procedure and in the absence of<br />

antiarrhythmic drugs. After undergoing repeat ablation procedures, at the end of<br />

follow-up sinus rhythm was present without antiarrhythmic drugs in 39/54 patients<br />

(72%) undergoing CFAE plus PVI vs 5/23 patients (22%; P


408 Atrial fibrillation<br />

practice. Up to date, the impact of this new technique in the clinical outcome of<br />

atrial fibrillation (AF) ablation has not been clearly demonstrated.<br />

Methods: Procedural and clinical outcome of 549 pts who underwent a first<br />

catheter ablation for paroxysmal AF between January 2005 and April 2007 were<br />

collected from 13 Italian Centers. Three type of procedure were included, all<br />

aimed to obtain pulmonary veins (PVs) isolation documented by circular mapping<br />

catheter: segmental ostial PVs isolation (LASSO, 239 pts); circumferential antral<br />

PVs isolation guided by electoanatomical mapping (CARTO, 95 pts); and circumferential<br />

antral PVs isolation guided by electoanatomical mapping integrated with<br />

MR/CT image of the left atrium (MERGE, 215 pts).<br />

Results: Procedure duration resulted significantly shorter (p


with atrial fibrillation (AF) undergoing radiofrequency catheter ablation (RFCA),<br />

using real-time three-dimensional echocardiography (RT3DE).<br />

Methods: A total of 57 patients referred for RFCA were studied. Paroxysmal AF<br />

was present in 43 patients (75%), while 14 patients had persistent AF. After a<br />

mean follow-up of 7.9±2.7 months, patients were divided into 2 groups: successful<br />

RFCA (SR group) and recurrence of AF (AF group). RT3DE was performed<br />

before, within 3 days and 3 months after RFCA to assess LA volumes (maximum,<br />

minimum and preA) and function (passive, active and reservoir).<br />

Results: A total of 38 patients (67%) had a successful RFCA (SR group). No<br />

differences in baseline characteristics were found between SR and AF groups<br />

except for higher percentage of persistent AF (42 vs. 11%, p


410 Atrial fibrillation<br />

Results: Ninety-two PVAI patients had OSA and CAF. Patient demographics are<br />

given in table 1. There was no significant difference in baseline characteristics.<br />

Twelve patients were lost due to inadequate follow up data. The success rate in<br />

Group 1 (treated) was 53.1% versus 39.5% in Group 2 (untreated) p=0.02.<br />

Conclusion: Our results show that there was a trend suggesting that AF recurrence<br />

is less in OSA treated patients; however, further more extensive and larger<br />

randomized studies are necessary to determine whether this trend is indeed due<br />

to the treatment effect.<br />

P2621 Multi-electrode ablation with duty-cycled low power<br />

bipolar/uniplolar RF energy for chronic AF<br />

L.V.A. Boersma1 , C. Scharf2 ,W.Davies3 , P. Kanagaratnam3 ,<br />

V. Paul4 ,E.Rowland4 ,A.Grace5 ,S.Fyn5 ,H.Oral6 , F. Morady6 .<br />

1 2 St.Antonius Hospital, Cardiology, Nieuwegein, Netherlands; Klinik<br />

im Park, Cardiology, Zurich, Switzerland; 3St.Mary’s Hospital, Cardiology,<br />

London, United Kingdom; 4St.George’s, Cardiology, London, United Kingdom;<br />

5 6 Papworth Hospital, Cardiology, Cambridge, United Kingdom; University of<br />

Michigan, Cardiology, Ann Arbor, United States of America<br />

Background: Widespread adaptation of radiofrequency catheter ablation (RFCA)<br />

of chronic atrial fibrillation (CAF) has been limited by long procedure times and<br />

low efficacy. This study was designed to evaluate the safety and efficacy of multielectrode<br />

catheters delivering low power duty-cycled radiofrequency energy for<br />

RFCA of CAF.<br />

Methods: Fifty-three patients (51 male, 57±6 years) with documented CAF were<br />

enrolled in a multi-center <strong>European</strong> study. Inclusion criteria included a failed<br />

class I or III AAD and a DCCV. Three anatomically specific catheters (PVAC,<br />

MASC, and MAAC, Ablation Frontiers Inc, Carlsbad CA) were used to isolate<br />

the pulmonary veins (PVI) and eliminate complex fractionated atrial electrograms<br />

(CFAEs) on the septum and left atrial wall. Bipolar/unipolar alternating radiofrequency<br />

energy (GENius, Ablation Frontiers Inc, Carlsbad CA) was delivered simultaneously<br />

through operator selected electrodes at ratios of 1:1, 2:1, or 4:1, depending<br />

on location and the desired lesion depth. All ablations were 60 seconds<br />

with a maximum power limit of 10 W/electrode to produce a target temperature of<br />

60°C at each electrode pair. An early additional procedure (which reset the follow<br />

up period) was allowed for patients if sinus rhythm was not maintained after 2<br />

months. Anti-arrhythmic drugs were discontinued at 3 months. The chronic efficacy<br />

endpoint was measured as an 80% reduction in AF burden, assessed with<br />

a continuous 7-day Holter recording at 6 months post procedure.<br />

Results: Fifty of 53 patients (94%) had documented successful PVI, with CFAE<br />

ablation at the septum, LA roof, posterior wall, and mitral valve annulus, with<br />

SR post procedure. Once trans septal puncture was complete procedure time<br />

was 145±44 minutes, with fluoroscopy time of 49±21 min. Current follow up<br />

is 172±58 days with a 6 month Holter recording completed in 47 patients. No<br />

AF was present in 36 of 47 patients, while 2 additional patients had PAF for<br />

less than 10% of the 7-day Holter recording. The current cumulative efficacy for<br />

CAF at 6 months is 81%, with 34 of 38 patients off all AADs after 4 months.<br />

The two-procedure rate was 51%. Five of the 8 efficacy failures did not receive<br />

a retreatment procedure. Serious complications included 1 transient neurologic<br />

event, 1 cardiac tamponade secondary to the transseptal puncture and 2 groin<br />

hematomas.<br />

Conclusions: Multi-electrode catheters in conjunction with low power duty-cycled<br />

bipolar-unipolar RF energy may allow safe and efficient procedures for RFCA of<br />

CAF, with a current efficacy at 6 months of 81%.<br />

P2622 Relationship between catheter forces, lesion<br />

charactheristics, popping, and char formation:<br />

experience with robotic navigation system<br />

L. Di Biase1 ,J.Cummings2 ,W.Saliba2 ,C.Barrett2 , R. Schwiekert 2 ,<br />

A. Natale3 . 1Cleveland Clinic/University of Foggia, Cardiovascular<br />

Medicine, Cleveland/Foggia, United States of America; 2Cleveland, United<br />

States of America; 3University of Stanford, Palo Alto, United States of America<br />

Introduction: Popping, char and perforation are complications that can occur<br />

following catheter ablation.<br />

We measured the amount of grams applied to the endocardium with a robotic<br />

system. We evaluated the relationship between lesion formation, pressure, and<br />

such complications using different catheter pressure and power settings.<br />

Methods: Using a robotic navigation system, lesions were placed in the LA atrium<br />

at 6 settings (Table 1), using a constant duration (40 sec) and flow rate with an<br />

open irrigated catheter (OIC).<br />

Necropsy was then performed.<br />

Results: Lesions using 30 W were more likely to be transmural at higher (>40 gr)<br />

than lower (40gr of pressure demonstrated "popping" and crater formation as compared to<br />

lesions with 20-30gr of pressure (41.7% vs 16.7%, p40 50% 33.4% 16.7%<br />

Group 6 45 >40 100% 0% 66.7%<br />

Conclusions: Using OIC at lower power settings (< 35 Watts) and at<br />

lower/medium pressure, lesions were more likely have a relatively spared endocardial<br />

surface. Higher catheter pressure at higher power (>45 watss) were likely<br />

to result in a transmural lesion. However, this also appears to be related to char,<br />

crater formation and "popping". Moderate pressures (20-30g) were associated<br />

with transmurality with lower incidence of complications.<br />

P2623 Safety and efficacy of paediatric outpatient<br />

radiofrequency catheter ablations<br />

M. Tomaske, R. Candinas, M. Weiss, U. Bauersfeld. University<br />

Children’s Hospital, Paediatric Cardiology, Zurich, Switzerland<br />

Purpose: Radiofrequency catheter ablations (RFA) are frequently<br />

performed as treatment for supraventricular tachycardia in children older than 4<br />

years of age. Aim of this study was to evaluate safety and efficacy of paediatric<br />

outpatient RFA.<br />

Patients and Methods: Between 06/2002 and 03/2007, 201 RFA were prospectively<br />

analyzed. Exclusion criteria for outpatient procedures were complex RFA<br />

in congenital heart disease, arterial access or distance to home more than 1<br />

hour. All RFA were performed under general anaesthesia. In case of transseptal<br />

puncture, patients received a single-shot dose heparin. All patients underwent<br />

postprocedural echocardiography and electrocardiogram and were discharged<br />

within 6 hours after conclusion of RFA. To identify potential complications after<br />

discharge, parental follow-up phone calls the day after outpatient RFA procedure<br />

were performed.<br />

Results: A total of 65/ 201 (32%) patients aged 13.6±3.8 years qualified for outpatient<br />

RFA. Accessory pathway ablations (n=33) and atrioventricular node modifications<br />

(n=28) were the most common RFA. A transseptal approach was performed<br />

in 24 RFA. Median procedure time was 1.5 hours (range: 1.1 – 4.3), with<br />

a median fluoroscopy time of 10 minutes (range: 5 - 86). RFA was successful in<br />

63/65 (97%) patients. Postprocedural echocardiography with special attention for<br />

intracardiac thrombi, pleural effusion and inflow patterns from systemic veins or<br />

the coronary sinus were normal in all patients. Anaesthetic adverse events, predominantly<br />

post-interventional nausea and vomiting, were observed in 9 (10%)<br />

patients. Hospital discharge within 6 hours after conclusion of RFA was practicable<br />

in all but one patient due to ongoing nausea. Follow-up phone calls did not<br />

reveal further complications. Recurrence of tachycardia after RFA was observed<br />

in 4 of 65 (6%) patients.<br />

Conclusions: Outpatient RFA are feasible and safe in selected paediatric patients.<br />

No RFA related complication was observed. Anaesthetic adverse events<br />

were nausea and vomiting due to general anaesthesia. Success rate and recurrence<br />

rate of tachycardia was favourable after outpatient RFA.<br />

P2624 Feasibility and safety of radiofrequency catheter<br />

ablation in outpatients<br />

E. Marijon1 ,M.Zimmermann2 ,M.Schmutz2 ,S.Boveda1 ,<br />

H. Burri2 , N. Combes1 , J.P. Albenque1 . 1Pasteur Clinic, Cardiology<br />

Department, Toulouse, France; 2Tour-Meyrin Hospital, Cardiology<br />

Department, Geneva, Switzerland<br />

Purpose: Radiofrequency catheter ablation is now the treatment of choice of<br />

most of arrhythmias. Standard clinical practice has been to keep patients in the<br />

hospital for 2 or 3 days after the procedure. We sought to assess safety, feasibility<br />

and short-term outcome of routine radiofrequency catheter ablation (RCA) on an<br />

outpatient basis with discharge from the hospital on the same day.<br />

Methods: The study population comprised 1270 consecutive patients (760 men,<br />

510 women, mean age 57±17 years) who underwent RCA of the slow pathway<br />

for treatment of AV nodal reentrant tachycardia (426), cavotricuspide isthmus for<br />

atrial common flutter (585), atrial tachycardia (73) and accessory pathways (186)<br />

in two different volume activity centers. All patients were hospitalized in the morning,<br />

underwent RCA after venous (1189) or arterial (81) femoral assess, and were<br />

discharged 4 to 8 hours later after systematic clinical exam, ECG and echocardiography<br />

after transeptal approach (28). Patients were scheduled for a one-month<br />

follow-up, and hospitalization and complication rates were prospectively collected.<br />

Results: During the one-month follow-up, no death occurred and the hospitalization<br />

rate was 0.6%: 6 patients had significant local complications (4 hematoma, 2<br />

arterio-venous fistula), requiring surgical repair within one week after the procedure<br />

in 4 cases, and 2 patients developed symptomatic delayed pulmonary embolisms.<br />

No symptomatic pericardial effusion was reported. In intention to treat,<br />

92% of the overall planed outpatients (1380) were really discharged the same<br />

day. Moreover, we observed no significant association between complication rate<br />

and volume center activity (p=0.37).<br />

Conclusions: In view of these findings, RCA for routine arrhythmias appears to<br />

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e feasible and safe. This approach is highly appreciated by patients and should<br />

have important consequences in terms of cost-saving considerations.<br />

P2625 Impact of anatomical factors on cryoballoon<br />

pulmonary vein isolation<br />

C. Herrera Siklody, M. Allgeier, J. Allgeier, R. Weber, P. Fluegel,<br />

C. Restle, D. Kalusche, T. Arentz. Herz-Zentrum Bad Krozingen,<br />

Rhythmologie, Bad Krozingen, Germany<br />

Introduction: Electrical isolation of the pulmonary veins (PV) is the cornerstone<br />

of atrial fibrillation catheter ablation. Balloon-mounted cryoablation devices have<br />

been recently introduced as an alternative to radiofrequency catheters. We aimed<br />

to assess the impact of anatomical factors on feasibility of PV isolation using such<br />

devices.<br />

Methods: We included 18 consecutive patients (88,9% Males, 56±9 years old)<br />

who underwent PV isolation. A CT scan was performed before the procedure,and<br />

3-D models of the left atrium were reconstructed and analyzed. PV antrum was<br />

considered to be oval when the longest diameter was at least twice the shortest<br />

one. Through a single transeptal puncture a cryoballoon (Cryocath, 4x23 mm,<br />

14x28 mm) was advanced into the antrum of every PV and frozen twice over<br />

5 minutes. In patients with a common left pulmonary ostium (CO), the 2 main<br />

branches were consecutively isolated. Electrical isolation was then checked with<br />

a multipolar circular catheter and additional focal cryoablations were performed<br />

when needed (Cryocath).<br />

Results: Two patients (13,3%) presented with a a left CO and another 3 with 1<br />

or 2 supplementary right-sided veins. PV isolation was achieved with the balloon<br />

in 63 of the 72 targeted veins (87,5%). Oval-shaped PV (8/72, 11,1%) could be<br />

primarily isolated in 62,5% of the attempts, whereas round-shaped ones were<br />

isolated in 90,6% of the cases (p=0,023). The mean diameter of primarily isolated<br />

PV was slightly larger than the one of the not isolated ones (19,1±3,0 mm vs<br />

17,0±2,2 mm,p=0,05). The following PV could not be isolated: 5 right lower, 3 left<br />

lower and 1 left upper. Superior PV were more often successfully isolated than<br />

theinferior ones (p=0,013). After 2,7±1,1 focal applications, all 72 targeted PV<br />

could be successfully isolated at the end of the procedure.<br />

Conclusions: Despite complex anatomical substract (CO, supplementary PV),<br />

PV isolation could be safely performed with the combined use of a cryoballoon<br />

and punctual cryoablation applications in all patients. The shape and size of the<br />

PV antrum were predictive factors in the primary achievement of electrical isolation<br />

withthe balloon, and should be taken into account in the design of new<br />

devices.<br />

P2626 Cost-effectiveness of radiofrequency ablation for<br />

supraventricular tachycardia: results of healthcare<br />

database of an Italian region<br />

G. Barbato1 ,E.Berti2 ,V.Carinci1 ,S.Mall2 , G. Di Tanna2 ,<br />

F. Pergolini1 , G. Di Pasquale1 . 1Maggiore Hospital, Cardiology,<br />

Bologna, Italy; 2Agenzia Sanitaria Emilia Romagna, Bologna, Italy<br />

Background: Although Radiofrequency ablation (RFA), is considered the firstline<br />

treatment for symptomatic supraventricular tachycardia (PSVT), there are few<br />

study regarding procedure cost-effectiveness versus medical treatment. We compared<br />

the two different strategies evaluating the regional healthcare administrative<br />

database.<br />

Methods: The study population was drawn from the administrative healthcare<br />

database of the region Emilia-Romagna (Italy). Including criteria were: admission<br />

to one of the hospital of the region for PSVT in 2004. and at least 2 access<br />

for PSVT to the public health service in the past 12 month. Then we follow this<br />

cohort of patients, recording every events or hospitalization, during the following<br />

12 months.<br />

Results: In the 2004 736 pts had an access to our regional facilities for PSVT. Of<br />

these 179 pts presented inclusion criteria. 74 have been discharged on medical<br />

therapy (group A), 105 underwent to RFA (group B). In the following 12 months<br />

67/74 (90%) pts of group A presented at least 1 clinical events (hospitalization<br />

or medical visit). In the group B 42/102 pts (41%) had no clinical events, 56/102<br />

had 1 clinical visit (55%), 4/102 one complication (2 one more hospitalization, 1<br />

pace.maker implantation, 1 other complication). The initial cost for pts, in group<br />

A was 1724.6 euro, in group B 6717.2 euro. In the cost analysis, considering for<br />

group A similar annual rate of events, and for group B no more events related to<br />

procedure, the RFA cost is recouped in 3 years.<br />

Conclusion: On the clinical setting of real-life regional healthcare administrative<br />

database the RFA treatment of pts highly symptomatic for PSVT is cost-effective.<br />

Compared to medical therapy, the initial cost is recouped in 3 years, after then<br />

there is a progressive cost reduction.<br />

P2627 Catheter ablation of atrial fibrillation as first line<br />

therapy? Experience from daily practice<br />

H. Tanner, L. Roten, J. Seiler, N. Schwick, J. Fuhrer, E. Delacretaz.<br />

University Hospital of Bern, Cardiology, Bern, Switzerland<br />

Purpose: Catheter ablation of atrial fibrillation (AF) is generally considered<br />

in patients (pts) with symptomatic AF refractory to class I and III antiar-<br />

Atrial fibrillation 411<br />

rhythmic drug (AAD). However, catheter ablation of AF as first line therapy is an<br />

alternative for selected pts.<br />

Methods: We studied all pts undergoing catheter ablation for symptomatic AF between<br />

2002 and 2007. Pts without AAD pre-treatment (Group 1) were compared<br />

to all others (Group 2). Moreover, reasons for choosing this treatment strategy<br />

were analysed.<br />

Results: From the 284 pts included, 43 (15%, Group 1) underwent AF catheter<br />

ablation as first line therapy, and 241 pts (85%, Group 2) had at least one preceding<br />

AAD trial. In pts with catheter ablation as first line therapy, the main reason<br />

for this strategy was pt’s preference, driven by the fear of AAD side effects, n=32<br />

(74%), accepting the risks of catheter ablation. Almost half of these pts (44%) had<br />

a physically very active lifestyle (i.e. endurance sports). In 11 pts (26%) catheter<br />

ablation as first line therapy was chosen because of medical considerations, i.e.<br />

prolonged sinus pauses on termination of AF. AF duration prior to ablation was<br />

shorter in group 1, but other clinical, procedural, and follow-up data did not differ<br />

significantly (table).<br />

Patient characteristics and outcome<br />

Group 1 (n=43) Group 2 (n=241) P value<br />

Age, years, mean±SD 59±11 58±10 ns<br />

Gender, male, n (%) 35 (81) 189 (78) ns<br />

AF duration, months, mean±SD 45±45 80±86 0.009<br />

Persistent AF, n (%) 13 (30) 80 (33) ns<br />

Structural heart disease, n (%) 22 (51) 104 (44) ns<br />

LVEF,%,mean±SD 60±8 50±10 ns<br />

LA, mm, mean±SD 44±6 45±7 ns<br />

Major complications, n (%)<br />

Success rate (n=164, with serial 7-day-ECG<br />

2 (5) 10 (4) ns<br />

follow-up), % 76 71 ns<br />

Conclusions: Catheter ablation as first line therapy of AF is feasible. The main<br />

reason for first line catheter ablation of AF was pt’s preference because of fear of<br />

drug side effects with respect to their very active lifestyle and to a lesser extent<br />

by medical reasons. Success rates and complications did not differ between first<br />

and second line catheter ablation for AF.<br />

P2628 Pulmonary vein isolation for atrial fibrillation in<br />

patients with brady-tachy type sick sinus syndrome<br />

K. Ishikawa, H. Hirayama, Y. Yoshida, M. Nanasato, Y. Tatematsu,<br />

N. Inoue, Y. Aoyama, T. Hashimoto, T. Yamamoto, N. Kanemura.<br />

Nagoya Daini Red Cross Hospital, Cardiology Dept., Nagoya, Japan<br />

Background: Sick sinus syndrome is commonly associated with tachyarrhythmias<br />

and bradyarrhythmias that often are symptomatic and an indication for pacemaker<br />

implantation. The aim of this study was to assess the effect of pulmonary<br />

vein isolation in patients with sick sinus syndrome and atrial fibrillation (AF).<br />

Methods and Results: Forty three consecutive patients diagnosed as sick sinus<br />

syndrome with AF underwent pulmonary vein isolation between December 2001<br />

and July 2007. Sick sinus syndrome was defined as a prolonged sinus pause<br />

(≥3 seconds) found in any electro cardiography or sinus bradycardia (≤40bpm)<br />

with dizziness or fatigue. Four patients were implanted pacemaker previously to<br />

ablation. Patients had AF for average of 4.3±4.8 years. Their mean age was<br />

64.6±10 years old, left atrium diameter was 37.4±6mm and had ejection fractions<br />

of 60.7±9%. AF reccurred in 13 patients (30%) during the follow up period<br />

(1.5±1.9 years). Eight underwent second pulmonary vein isolation and 5 had successful<br />

result. The overall long-term success rate was 81.4%. Pacemakers were<br />

implanted in seven patients after the procedure (18% of no previous pacemakers).<br />

Conclusion: Cure of AF by pulmonary vein isolation helped resolve the clinical<br />

manifestations of sick sinus syndrome. It may be an alternative therapy to pacemaker<br />

implantation for patients with brady-tachy type sick sinus syndrome.<br />

P2629 Three-dimensional image integration based on gated<br />

vs. non-gated cardiac computed tomography to<br />

assist ablation of atrial fibrillation: evaluation of<br />

integration accuracy and patient radiation dose<br />

J. Ector, S. De Buck, W. Huybrechts, D. Nuyens, S. Dymarkowski,<br />

J. Bogaert, F. Maes, H. Heidbuchel. University Hospital Gasthuisberg, Cardiology,<br />

Leuven, Belgium<br />

Background: We developed methods for real-time biplane integration of threedimensional<br />

(3D) left atrial models with fluoroscopic images to assist catheter<br />

ablation of atrial fibrillation (AF). This approach allows quantitative assessment of<br />

3D image integration accuracy by direct comparison with combined angiographic<br />

images of the four pulmonary veins (PVs).<br />

Methods: Sixty patients underwent AF ablation under biplane fluoroscopic guidance<br />

after selective angiography of the 4 pulmonary veins. CT-based 3D models<br />

were integrated in the fluoroscopic framework using a landmark-based registration<br />

approach. Integration accuracy was quantitatively assessed and compared<br />

for 3D models based on ECG-gated (n=31) vs. non-gated (n=29) 64-slice cardiac<br />

CT. Effective patient radiation dose from cardiac CT was calculated based on the<br />

CT dose-length product and conversion factor for chest examinations.<br />

In 30 of the 60 patients (3D+ group), the integrated 3D model was used for realtime<br />

3D-augmented fluoroscopic catheter navigation and the effects on proce-<br />

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412 Atrial fibrillation<br />

dural parameters and patient radiation dose (as calculated from per-procedural<br />

dose-area product levels) were evaluated.<br />

Results: Low PV alignment errors in the entire patient group (n=60) indicated<br />

accurate 3D-fluoroscopy integration in both planes based on the landmark-based<br />

registration approach (median[IQR] total alignment error: RAO 2 [0.5-5] mm vs.<br />

LAO 2[0-4] mm, p=0.06).<br />

The effects of ECG-gating and respiratory phase during CT-acquisition on integration<br />

accuracy were small and clinically irrelevant. Only the alignment error in<br />

the RAO-plane showed a borderline significant reduction for ECG- gated vs. nongated<br />

CT-acquisitions (2[0-4] mm vs. 2[2-6] mm, p=0.05). ECG-gated CT however<br />

resulted in a very important increase in patient radiation dose vs. non-gated CT<br />

(17.3±5.2 mSv vs. 4.4±3 mSv,p


coagulant therapy (P=0.038; OR=2.424, 95% CI= 1.048 – 5.606) was a predictor<br />

of venous obstruction.<br />

Conclusion: Warfarin prophylaxis reduced the frequency of venous thrombosis<br />

after transvenous devices implantation in high risk patients.<br />

P2634 Impact of RVOT pacing on time course of<br />

inter-ventricular and intra-ventricular dyssynchrony.<br />

A six months follow up<br />

S.K. Dwivedi, A. Makhija, S. Mukerjee, R. Sethi, A. Puri, V.S. Narain,<br />

V.K. Puri, R.K. Saran. KG’s Medical University., Cardiology, Lucknow,<br />

India<br />

Objective: Right ventricular apical (RVA) permanent pacemaker implantation<br />

(PPI) produces abnormal pattern of ventricular depolarization with adverse functional<br />

and structural changes in the left ventricle (LV). Right ventricle outflow tract<br />

(RVOT) as an alternative site for PPI is under investigation. Aim of present study<br />

was to prospectively evaluate the impact of RVOT pacing on LV electromechanical<br />

dyssynchrony using tissue Doppler imaging (TDI) over a follow up of 6 months<br />

in patients with normal LV functions undergoing VVI pacing.<br />

Methods: Seventy four consecutive patients (age 63.6±10.1 years, 65.3% males)<br />

with symptomatic bradycardia were randomized to RVOT pacing (n=37) or<br />

RVA pacing (n=37). Inter-ventricular dyssynchrony (Inter VD) was defined as<br />

time difference between aortic and pulmonary pre-ejection time intervals. Intraventricular<br />

dyssynchrony (Intra VD) was defined as time difference between the<br />

shortest and the longest LV wall electromechanical delays among basal septum,<br />

lateral, anterior and inferior segments on pulsed TDI. Baseline parameters were<br />

taken on RVA pacing in both groups.<br />

Results: RVOT pacing resulted in significantly narrower QRS complex as compared<br />

to RVA pacing (133.3±14.1 vs. 142.8±17.0 msec, p=0.013). Both Inter<br />

VD and intra VD were significantly lesser on RVOT pacing as compared to RVA<br />

pacing (-13.7±0.8 msec, p= 0.004 and -16.7±0.5 msec, p=0.001 respectively) at<br />

6 months follow up. Fall in ejection fraction (EF) was lesser in RVOT pacing as<br />

compared to RVA pacing (-1.4±0.4% vs. -3.4±0.4%, p=0.06). Fall in EF >10%<br />

occurred in four and one patients on RVOT pacing and RVA pacing respectively.<br />

Echocardiographic parameters on follow up<br />

Basal 1 Month 6 Month RVOT<br />

RVOT RVA RVOT RVA RVOT RVA<br />

EF% 56.6±3.8 57.9±4.6 55.4±3.9 54.6±4.9 55.3±3.9 54.2±5.5<br />

Inter VD (msec) 50.9±12.6 49.4±13.0 36.6±10x 50.3±9.9 36.9±7.8x 50.4±12.2<br />

Intra VD (msec) 65.3±24.5 68.5±13.7 48.2±9.5x 69.1±13.3 48.2±10.8x xp value65 ms) and dobutamine stress echo (up to 40 mcg/kg/min,<br />

with presence of CR defined as a wall motion score index, WMSI, increase >0.20)<br />

with core lab reading. "Responders" were identified by clinical (survivors, with<br />

NYHA class improvement ≥1 grade) and/or echocardiographic (LV end-systolic<br />

volume, ESV, decrease ≥15% at 6-months follow-up) criteria.<br />

Results: In the follow-up, 28 (51%) patients were responders to CRT. At individual<br />

patient analysis, CR was more often associated with a favourable outcome<br />

whereas DYS criteria were equally present in the 2 groups: see figure. Changes<br />

in ESV from baseline to 6 months post-CRT were correlated with pre-CRT reststress<br />

changes in ESV (r=.439; p=.003) and in WMSI (r=-.458; p=.001) but not<br />

with baseline DYS values. At multivariate analysis, CR (OR= 6.2, 95% CI= 1.4-<br />

27.6) and ischemic etiology (OR= 0.20, 95% CI= 0.05-0.73) were the best predictors<br />

of clinical and echo response to CRT, regardless of DYS.<br />

Conclusions: Patients with CR during stress echo show a favourable clinical<br />

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414 Cardiac resynchronization therapy: miscellaneous<br />

and reverse LV remodelling response to CRT. This finding shifts the focus from<br />

electrical (DYS) to the myocardial substrate of functional response to CRT: no<br />

muscle, no party!<br />

P2638 Is right ventricular lead positioning important for<br />

cardiac resynchronization therapy?<br />

D. Manolatos, A.M. Sideris, M. Efremidis, S. Xidonas, G. Gavrielatos,<br />

L.K. Pappas, D. Bramos, V. Derveni, D. Kardara, F. Kardaras.<br />

Athens, Greece<br />

Objective: The optimal left ventricular (LV) pacing site for cardiac resynchronization<br />

therapy (CRT) has been investigated, but less is known about the optimal site<br />

in the right ventricle (RV).<br />

Methods: This study compared the acute haemodynamic response to biventricular<br />

pacing (BiV) at two different RV stimulation sites: RV outflow tract (OUT)<br />

and RV apex (APEX) in 15 patients with heart failure and ventricular conduction<br />

delay. Pacing catheters were placed in the high right atrium, lateral wall of the<br />

left ventricle (LV), right ventricular apex (APEX) and right ventricular outflow tract<br />

(OUT). A continuous cardiac output thermodilution catheter was placed in the pulmonary<br />

artery. Patients were studied during: 1) atrio-BiV pacing from APEX and<br />

LV (APEX+LV) 2) atrio-BiV pacing from OUT and LV (OUT+LV) 3) AAI mode (used<br />

as reference). Haemodynamic changes and QRS duration (QRS) with atrio-BiV<br />

pacing, were assessed relative to the AAI pacing data. Pacing was performed at<br />

100 beats/min with an AV delay of 150ms. During each pacing mode the ECG and<br />

haemodynamic parameters [cardiac index (CI), pulse pressure (PP), pulmonary<br />

artery diastolic pressure (PADP)] were recorded. A repeated measures one-way<br />

analysis of variance was used to determine differences in haemodynamics among<br />

the different pacing modalities. Post hoc paired comparisons were made using<br />

Tukey’s HSD test with p set at 0.05.<br />

Results: Haemodynamic measurements and QRS were not significantly<br />

changed during atrio-BiV pacing from OUT+LV when compared to the atrio-BiV<br />

pacing from APEX+LV. Both atrio-BiV pacing modes had a favorable effect on<br />

haemodynamics and QRS compared to AAI pacing (Table 1).<br />

Table 1. The impact of RV pacing site on haemodynamic parameters and QRS during BiV pacing<br />

AAI OUT+LV APEX+LV P value<br />

QRS (ms) 154.93 132.00 128.27


ison between responders and nonresponders (independent T- and Fisher exact<br />

test); defining a ESV decrease of ≥ 15% and being alive without transplant as a<br />

responder.<br />

Results: Overall, CRT induced an immediate increase in dP/dt max during implantation<br />

(721±177 to 932±215 mmHg/s, p


416 Syncope and cardiac pacing: miscellaneous<br />

Methods: The database of the obligatory external quality control program in the<br />

federal state of Hessen was analysed, which includes all stationary primary pacemaker<br />

implantations. Data completeness is > 95%.<br />

Results: In the federal state of Hessen 17.826 patients underwent pacemaker<br />

implantation in 72 hospitals from 2003 to 2006. Of these, 9405 (52.8%) have<br />

been male and 8421 have been female (47.2%).<br />

The data for both genders are shown in table 1 (t-test for continuous variables,<br />

χ 2 -test for nominal scaled variables).<br />

Conclusion: In this large scale cohort, female patients with a primary pacemaker<br />

implant were significantly older, had fewer AV-blocks and more Sick Sinus Syndrome,<br />

compared to men. They received more single chamber devices and had<br />

more operative complications. Atrial pacing thresholds were higher and P-wave<br />

amplitudes were lower in women. Ventricular and procedural parameters showed<br />

no significant difference between both genders.<br />

P2646 Deleterious effect of right ventricle apical dual<br />

chamber pacing on left ventricle diastolic function in<br />

patients with preserved ejection fraction<br />

F. Fang, J.Y.S. Chan, Q. Zhang, J.W.H. Fung, G.W.K. Yip,<br />

W.W.M. Chan, A.K.Y. Chan, C.M. Yu. The Chinese University of<br />

Hong Kong, Hong Kong, Hong Kong SAR, People’s Republic of China<br />

Background: Little is known about the effect of right ventricle apical (RVA) pacing<br />

on LV diastolic function or diastolic dyssynchrony, and whether such impact is<br />

different between patients with and without pre-existing LV diastolic dysfunction<br />

(DD).<br />

Methods: 99 patients with sick sinus syndrome (68±11yrs, 29male) who had<br />

ejection fraction>50% and implanted with permanent pacemakers were examined<br />

by echocardiography with tissue Doppler imaging (TDI) (iE33, Philips) during<br />

ventricular sensing and pacing modes in a random order. LV diastolic function<br />

was assessed by Doppler parameters, mitral annulus early diastolic velocity (E’),<br />

transmitral early diastolic velocity to E’ ratio (E/E’), while diastolic dyssynchrony<br />

was assessed by the standard deviation of time to peak myocardial early diastolic<br />

velocity in 12 LV segments (Te-SD).<br />

Results: During ventricular pacing, LV diastolic function was deteriorated mainly<br />

in those with pre-existing DD with prolongation of deceleration time of E wave, reduction<br />

of E’and increased E/E’and Te-SD (Table). In those with normal diastolic<br />

function, only a mild reduction in E’was observed while E/E’remain unchanged.<br />

There were 12 patients shifted towards more severe patterns of diastolic dysfunction<br />

while 47 patients had E’reduced by≥10%. These changes occurred mainly<br />

in those with pre-existing DD (57% vs 31%, p=0.038). The change in Te-SD was<br />

only weakly correlated with the change in E’(r=0.21, p=0.045). By multivariate<br />

analysis, pre-existing DD was the only independent predictor for reduction of<br />

E’(OR=2.672, p=0.043).<br />

Parameters Without pre-existing DD (n=38) With pre-existing DD (n=61)<br />

V sense V pace P value V sense V pace P value<br />

Deceleration time of E wave,<br />

ms 210±39 231±51 0.018 223±60 240±53 0.028<br />

E’, cm/s 8.0±1.9 7.6±2.0 0.034 6.3±1.9* 5.5±1.5*


Table 1. Systolic, diastolic and dyssynchrony parameters for different AV-intervals<br />

AV-default AV optimal p-value<br />

Stroke volume [ml] 71±18 77±19 0,003<br />

Cardiac index [l/min/m 2 ] 2,58±0,66 2,74±0,78 0,03<br />

Stroke work [mmHg/ml] 5931±1891 6867±2133 0,00004<br />

+dp/dtmax [mmHg/s] 1308±389 1319±377 n.s.<br />

-dp/dtmax [mmHg/s] -1297±233 -1350±331 n.s.<br />

tau [ms] 38±10 38±8 n.s.<br />

Peak filling rate [ml/s] 778±423 832±450 n.s.<br />

Systolic dyssynchrony [%] 17,7±7,0 19,4±7,1 0,01<br />

Global cycle efficiency [%] 62±10 72±29 0,04<br />

chanic efficiency as suggested by the decreased systolic dyssynchrony and the<br />

improved global cycle efficiency.<br />

P2650 Is warfarin pause or bridging therapy necessary for<br />

pacemaker implantation?<br />

H. Lahtela1 , J. Koistinen1 , P. Korkeila1 , P. Karjalainen2 ,A.Ylitalo2 ,<br />

J. Airaksinen1 . 1Turku University Hospital, Department of Internal<br />

Medicine, Turku, Finland; 2Satakunta Central Hospital, Department<br />

of Cardiology, Pori, Finland<br />

Purpose: There are no established guidelines regarding interruption of warfarin<br />

anticoagulant therapy prior to implantation of cardiac pacemakers, but it is a common<br />

consensus to postpone pacemaker implantation to reach INR levels < 1.5-<br />

1.8 and use bridging therapy in patients with high risk of thromboembolism. The<br />

purpose of this prospective multicentre study (FinPAC) is to compare bleeding and<br />

thromboembolic complications of pacemaker implantation during uninterrupted<br />

and interrupted oral anticoagulant treatment. We report interim results from 2<br />

centres.<br />

Methods: A total of 61 patients (mean age 73 years, 34 men) with long-term<br />

warfarin treatment have been randomized to either a interrupted (≥2 days) or<br />

continuous warfarin therapy before implantation. Patients on aspirin (N=33) are<br />

recruited as a control group. Bridging therapy was not allowed.<br />

Results: The periprocedural INR levels were higher without a warfarin pause<br />

(2.28 vs 1.92, p 50 mmHg. Based on<br />

the ability to give a clear history of the accidental fall, patients with femoral fracture<br />

were categorized in two groups: group A included patients who were able to<br />

Syncope and cardiac pacing: miscellaneous 417<br />

fully describe the index event, while group B included subjects with unexplained<br />

falls.<br />

Results: Eighteen patients (35.3%) who presented with hip fracture had a positive<br />

response to carotid sinus massage; six out of 33 (18.2%) patients in group<br />

A and 12 out of 18 (66.7%) patients in group B (p < 0.001). Nine controls<br />

(17.6%) also demonstrated CSH. Patients in group B were older (A: 75.5±8.5<br />

vs B: 80.1±5.9, p = 0.029) and were more likely to have a history of unexplained<br />

falls or syncope in the past (A: 0% vs B: 66.7%, p < 0.0001) than individuals in<br />

group A. When compared with the control group, CSH was still more common in<br />

group B (B: 66.7% vs control: 17.6%, p < 0.0001) but not in group A (A: 18.2%<br />

vs control: 17.6%, p = 1.000).<br />

Conclusions: The prevalence of CSH is increased in elderly patients presenting<br />

with femoral fractures, only in those who present with unexplained fall and report<br />

a history of syncope or unexplained falls in the past. Early identification and treatment<br />

of these patients could possibly prevent the occurrence of femoral fractures<br />

later in their lives.<br />

P2652 Efficacy of an outpatient clinic for high risk syncope<br />

discharged from emergency department<br />

N. Romero Rodriguez1 , G. Baron-Esquivias2 , S. Gomez-Moreno1 ,<br />

F. Errazquin Saez De Tejada1 , A. Pedrote1 , A. Martinez-Martinez1 .<br />

1Virgen del Rocio University Hospital, Cardiology, Sevilla, Spain;<br />

2Virgen del Rocio University Hospital, Cardiology, Seville, Spain<br />

Purpose: Those patients presenting syncope with certain cardiovascular risk<br />

profile (age>65 years, abnormal electrocardiogram, syncope without prodromes<br />

and/or cardiovascular disease in clinical history) are associated with a higher mortality<br />

rate, even though they might be discharged from emergency departments.<br />

In order to optimize the correct diagnosis and follow up of these patients we evaluated<br />

the usefulness of a monographic out-hospital syncope unit.<br />

Methods: those patients discharged from the emergency department that fulfilled<br />

this clinical profile were studied in our unit in less than 72 hours and, following<br />

<strong>European</strong>s syncope guidelines, we analyzed the diagnostic value of each test<br />

once a definite origin of the syncope was established, with a follow up of more<br />

than two years.<br />

Results: A total of 107 consecutive patients were evaluated, out of which we finally<br />

included 82 that fulfilled high risk syncope criteria. We did an echocardiography<br />

to every patient together with completing an ambulatory monitoring. A total of<br />

23 tilt table tests were done, 4 electrophysiological studies developed and 2 Reveals<br />

implanted. A final diagnosis was achieved in 92,7% of them: 50% neurally<br />

mediated, 22% orthostatic, 12,2% arritmogenic, 6,1% neurological, 1,2% cardiac<br />

y 1,2% psychiatric. The overall mortality rate included 9 patients (11%), due to<br />

vascular causes in 5 cases (4 cerebravascular accidents and 1 acute myocardial<br />

infarction), oncologic in 3 and traumatologic in 1. Diagnosis cost was 573� per<br />

patient.<br />

Conclusions: The existence of a syncope unit improves the attention of those<br />

high risk patients, improving the overall management following <strong>European</strong> syncope<br />

guidelines and significantly increasing the final percentage of patients in which a<br />

final diagnose is achieved with a low final economic cost and risk.<br />

P2653 Is tilt training also an efficacious therapy in older<br />

patients with neurally mediated syncope?<br />

T. Reybrouck, H. Heidbuchel, R. Willems, H. Ector. Gasthuisberg<br />

University Hospital, Department Cardiovascular Rehabilitation,<br />

Leuven, Belgium<br />

Background: Falls with loss of consciousness are frequently observed in older<br />

patients. In many cases the cause of loss of consciousness is a neurally mediated<br />

syncope (NMS). In younger patients tilt training has shown to be a successful first<br />

line therapy. The aim of this study is to analyse whether older patients can also<br />

successfully be treated with tilt training therapy.<br />

Methods: 73 patients above 65 years of age (mean age 73.6±5.1 years, median<br />

72.7) with recurrent neurally mediated syncope were admitted to the hospital for a<br />

program of tilt training. The patients underwent a diagnostic tilt test without pharmacological<br />

provocation, according to the Westminster protocol (60° inclination).<br />

The patients were tilted daily until syncope or maximally 45 min (= normal value).<br />

This patient group was compared to a group of 250 young patients with neurally<br />

mediated syncope (< 35 years, mean age: 19.5 ± median 17.5 years) who also<br />

underwent tilt training therapy. After discharge from the hospital the patients were<br />

instructed to continue tilt training at home for 1 or 2 periods of 30 min per day.<br />

The results show that tilt training is also effective in older patients with NMS. A<br />

negative tilt test could be obtained in all patients. However the time to achieve a<br />

first negative tilt test is slightly longer in older patients compared to younger ones.<br />

All patients became syncope-free during daily life.<br />

Results tilt training (N° = number)<br />

Group N Duration diagnostic tilt test (min) N° first negative tilt test<br />

> 65 years 73 25.7±13.9 3.4±1.3<br />

< 35 years 250 21.4±13.8 2.9±1.3<br />

P = 0.019 P = 0.028<br />

Conclusion: Older patients with NMS can be treated successfully with tilt training<br />

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418 Syncope and cardiac pacing: miscellaneous<br />

therapy. A major advantage of this therapy is the lack of side effects as many<br />

elderly patients have comorbidities and are already taking multiple drugs.<br />

P2654 Reactive vasodilation and the clinical expression of<br />

vasovagal syncope<br />

P. Flevari, K. Fountoulaki, D. Leftheriotis, C. Komborozos, J. Lekakis,<br />

D. Kremastinos. Athens, Greece<br />

Purpose: In an attempt to elucidate the role of vasodilative mechanisms<br />

in VVS, we assessed, in supine patients with VVS, i) peripheral basal flow<br />

and post-ischaemic vasodilative responses, ii) their relation with the syndrome’ s<br />

severity.<br />

Methods: Thirty-four patients were studied, mean aged (±1 SE) 44±4 years, 16<br />

male, with recurrent VVS and a recent, positive head-up tilt test. Seventeen age<br />

and sex-matched healthy subjects served as controls. Venous occlusion plethysmography<br />

was used to assess forearm blood flow (FBF) i) at rest, ii) during reactive<br />

hyperaemia. Hyperaemic FBF corresponded to the mean value of the first 4<br />

measurements observed after arterial occlusion release. FBF was expressed in<br />

ml/100 ml/min. The duration of hyperaemia was the time (sec) at which FBF returned<br />

to 50% of its maximal increase relative to baseline flow. The clinical severity<br />

of the syndrome, as assessed by the total number of syncopal and presyncopal<br />

episodes, was related to the intensity and duration of the vasodilative reflex.<br />

Results: No significant differences were observed between patients and controls<br />

in baseline FBF (3.9±0.3 vs 4.6±1.1, p: NS) or in hyperaemic FBF (8.2±0.7 vs<br />

8.8±1.3, p: NS). The duration of reactive hyperaemia was longer in patients compared<br />

to normal subjects (22.3±4.1 sec vs 14.2±2.6 sec respectively, p


Syncope and cardiac pacing: miscellaneous / Understanding determinants of hemodynamics and ventricular function 419<br />

tion is less clear. This study examines the effect of CRT on diastolic function using<br />

load-independent tissue Doppler measures of diastolic function. As a mitral annular<br />

relaxation velocity (EM)>3 and LV end diastolic filling pressure (LVEDP)<br />

(E/EM)3 and E/Em


420 Understanding determinants of hemodynamics and ventricular function<br />

pairment is related to the severity of HT. These abnormalities were reversed after<br />

L-thyroxine therapy.<br />

P2663 Torsion and rotation rate of left ventricle are related to<br />

cardiac function in experimental canine<br />

W. Wu 1 , H.A.O. Wang2 . 1Cardiovascular Institute and Fuwai<br />

Hospital, Department of Echocardiography, Beijing, China, People’s<br />

Republic of; 2Cardiovascular Institute and Fuwai Hospital, Beijing,<br />

China, People’s Republic of<br />

[Objective] To evaluate the correlation between torsion, rotation rate and cardiac<br />

function in health mongrel dogs. [Methods] Left ventricle (LV) ejection fraction<br />

(EF) by modified Simpson’s method and mitral inflow measurements included<br />

peak early (E), peak late (A) velocities, E/A ratio and other diastolic indices were<br />

measured in 10 health mongrel dogs (range1-2 yr, 22.55±2.78kg weight, 5 females).<br />

Mean rotation, rotational rate were measured at basal, papillary and apex<br />

levels of LV using the two dimensional speckle tracking imaging (STI). Dogs underwent<br />

cardiac catheterization for LV end-diastolic pressure (LVEDP) and the<br />

peak rates of LV pressure decline (–dp/dtmax) using a6Frpigtailcatheter.The<br />

correlations were analyzed between torsion, rotation rate and LVEF, LVEDP, –<br />

dp/dtmax. [Results] 152 of 180 segments were analyzed by 2D-STI successfully.<br />

In normal canine, basal rotation was clockwise (negative) during systole, but apical<br />

rotation was consistently counterclockwise (positive). The difference on Time<br />

to peak rotation and rotation rate among the three short axis views was not significant<br />

but there was the sequential shortening from basal loop to apical loop.<br />

Torsion was correlated well with LVEF (R=0.941, P=0.005). –dp/dtmax inversely<br />

was correlated with the ratio of early and late peak rotation rate (PRRe/PRRa)<br />

(R=-0.805, P=0.05). There were close relations between LVEDP and the indices<br />

of PRRe and PRRa (P=0.018 vs. 0.033). But there was no significant difference<br />

between. –dp/dtmax, LVEDP and torsion. [Conclusions] Torsion is a novel index<br />

to assess LV systolic function; PRRe and PRRe/PRRa have potential to become<br />

a clinical tool for quantifying LV diastolic function.<br />

P2664 Low cardiac output in young adults with chronic<br />

fatigue syndrome and small heart<br />

K. Miwa1 ,M.Fujita2 . 1Nanto Home and Regional Medical Center,<br />

Department of Internal Medicine, Nanto, Japan; 2Kyoto University<br />

Graduate School of Medicine, Human Health Sciences, Kyoto,<br />

Japan<br />

Purpose: "Small heart syndrome", previously referred to so-called "neurocirculatory<br />

asthenia" in young adults associated with a small heart shadow on the chest<br />

roentgenogram, is characterized by weakness or fatigue even after mild exertion,<br />

palpitation, dyspnea and fainting, many of which resemble symptoms in patients<br />

with chronic fatigue syndrome (CFS). We sought to determine the significance of<br />

"small heart syndrome" in the pathogenesis of CFS.<br />

Methods: The study population comprised 42 patients with CFS younger than 40<br />

years of age. Cardiac function was evaluated echocardiographically.<br />

Results: "Small heart" (Cardiothoracic ratio ≤42%) was noted in 26 (62%) of<br />

CFS. Echocardiographic examination revealed significantly smaller mean values<br />

of both the left ventricular (LV) end-diastolic and end-systolic dimensions, stroke<br />

volume indexes and cardiac indexes in CFS patients with "small heart" than in<br />

those without it and also in 20 control subjects. Thus, CFS with "small heart" had<br />

an actually small LV chamber and poor cardiac performance. During a long followup<br />

period of 10 CFS patients with "small heart", all above-mentioned echocardiographic<br />

parameters improved significantly during the remission phase as compared<br />

with exacerbation phase (Table).<br />

Comparison of Echocardiographic Findings<br />

Exacerbatioin Remission p value<br />

<strong>Heart</strong> rate (beats/min) 71±9 63±60.014 LV end-diastolic dimension (mm) 37.7±3.6 42.8±2.5


their downstream effector, myosin heavy chain, are involved in the pathogenesis<br />

of diabetic cardiomyopathy.<br />

P2667 Acute increase in left ventricular filling pressure<br />

leads to hyperventilation in heart failure patients with<br />

central but not obstructive sleep apnoea<br />

O. Oldenburg, T. Bitter, C. Piper, C. Langer, M. Wiemer, D. Horstkotte.<br />

<strong>Heart</strong> Center NRW, Ruhr University Bochum, Department of<br />

Cardiology, Bad Oeynhausen, Germany<br />

Purpose: The pathohysiology of Cheyne-Stokes-respiration (CSR) in congestive<br />

heart failure (CHF) is not fully understood. It is supposed that an increase in<br />

pulmonary capillary Wedge pressure (PCWP) leads to stimulation of pulmonary<br />

J-receptors and consecutive hyperventilation and fall in arterial pCO2 below the<br />

apnoea threshold. The present study investigates the influence of an acute increase<br />

in PCWP in CHF pts with central (CSR) and obstructive sleep apnoea<br />

(OSA).<br />

Methods: Simultaneous left and right heart catheterisation were performed in 17<br />

pts with sleep disordered breathing (SDB) and symptomatic compensated CHF<br />

(NYHA ≥ II, LVEF ≤ 40%). PCWP and arterial pCO were measured under standardised<br />

settings at baseline and after left ventricular angio- and/or aortography<br />

to acutely increase intravascular volume. CSR and OSA were determined by cardiorespiratory<br />

polygraphy in the night before heart catheterisation. Central CO2 –<br />

receptor sensitivity was verified by testing the hypercapnic – hyperoxic – ventilatory<br />

response (HCVR) according to Read.<br />

Results: CSR was diagnosed in 11 pts (apnoea-hypopnoea-index [AHI]<br />

29.4±19/h; age 59±11 years; LVEF 31.6±7%) and OSA (AHI 12.7±5.6/h; 67±8<br />

years; LVEF 31.7±5%) in 6 pts. HCVR was significantly higher in pts with CSR<br />

(6.70±6.9 l/min/mmHg) than in OSA pts (2.1±0.6 l/min/mmHg; p < 0.05). PCWP<br />

were elevated at baseline and increased significantly after angiography in both<br />

groups (CSR: 20.6±6.1 mmHg to 23.8±7.6 mmHg; OSA 27.7±5.6 to 31.2±5.4<br />

mmHg; both p


422 Understanding determinants of hemodynamics and ventricular function<br />

P2671 Non-invasive determination of cardiac output by<br />

CW-Doppler ultrasound - comparison with cardiac<br />

magnetic resonance tomography<br />

J. Saur, T. Papavassiliu, S. Fluechter, F. Trinkmann, J. Weissmann,<br />

M. Borggrefe, J.J. Kaden. University Hospital Mannheim, 1st<br />

Department of Medicine, Mannheim, Germany<br />

Objective: Cardiac output (CO) is an important parameter in the diagnosis and<br />

therapy of cardiac diseases. The current standard methods for the determination<br />

of CO, however, are either invasive (e.g. right heart catheterization, PiCCO) or<br />

technically expendable and expensive (cardiac magnetic resonance tomography,<br />

CMR). The traditional non-invasive methods of determining CO by rebreathing of<br />

carbon dioxide or bio impedance cardiography are easily carried out but suffer<br />

from methodical inaccuracies. Therefore the aim of the prospective study at hand<br />

was to evaluate a new method for determining the CO based on CW-Doppler<br />

ultrasound (CWD).<br />

Methods: The CO of 32 consecutive patients scheduled to undergo CMR was<br />

determined in reclining position. The measurements were either performed immediately<br />

before or after the CMR examination using CWD (USCOM, USCOM LTD,<br />

Sydney Australia). The data determined by CMR for cardiac output and stroke<br />

volume (SV) served as reference values which were compared to the arithmetic<br />

mean of two serial CWD measurements. The statistic comparison of the methods<br />

was drawn by means of Bland-Altman analysis.<br />

Results: The patient collective consisted of 20 men (aged 17-80 years, median<br />

51 years) and 12 women (aged 27-78 years, median 64 years). In 29 out of 32<br />

consecutive patients during the investigation period CO and SV could be determined<br />

by CWD, in 3 patients (9%) no acceptable ultrasonic signal could be obtained.<br />

The cardiac output determined by CMR was 5.2±1.1 l/min (mean ± SD,<br />

minimum 3.0 l/min, maximum 7.5 l/min) and 4.7±1.1 l/min (minimum 2.8 l/min,<br />

maximum 8.0 l/min) by CWD. Bland-Altman analysis revealed a good correspondence<br />

of the two methods with a mean bias of 0.5±1.0 l/min for the determination<br />

of CO and 6.9±16 ml for the SV, respectively. CWD showed a good repeatability<br />

with a mean bias of 0.1±0.5 l/min for CO and 0.3±7.7 for SV.<br />

Conclusion: CW-Doppler ultrasound allows reliable non-invasive measurements<br />

of cardiac output and stroke volume with good repeatability. The future importance<br />

of the method for diagnosing and treating cardiac diseases remains to be<br />

assessed in further investigations.<br />

P2672 Increased left ventricular dimensions and lower<br />

ejection fraction are associated with enhanced<br />

cardiac function in patients with growth hormone<br />

deficiency<br />

D. Barker, R. Moisey, N. Lewis, S. Orme, L.B. Tan. Leeds General<br />

Infirmary, Leeds, United Kingdom<br />

Objectives: Echocardiographic left ventricular ejection fraction (EF) and cardiac<br />

dimensions are used to represent cardiac function - low EF or a dilated left ventricle<br />

suggest poor function. Some studies have shown cardiac dimensions and<br />

mass to be lower in patients with growth hormone deficiency (GHD) compared<br />

to controls. The aim of this study was to assess the relationship between directly<br />

measured cardiac function and cardiac dimensions/EF.<br />

Methods: Eighteen patients with severe GHD awaiting growth hormone therapy<br />

(mean age 46 years, range 25-64 years) underwent transthoracic echocardiogram.<br />

Left ventricular (LV) dimensions, volumes and EF were measured using<br />

Simpson’s method. LV mass was calculated and corrected for body surface area<br />

(LV mass index, LVMi). To evaluate cardiac pump function directly, patients also<br />

underwent maximal cardiopulmonary exercise testing with non-invasive assessment<br />

of cardiac output (CO) using the CO2-rebreathing method. Cardiac power<br />

output (CPO) was calculated from peak CO multiplied by mean arterial pressure.<br />

Results: All measurements were within normal reference ranges with none of<br />

the patients showing significant LV systolic or diastolic dysfunction. Peak exercise<br />

CPO positively correlated with LV systolic (r = 0.61, p < 0.01) and diastolic (r =<br />

0.74, p < 0.01) dimensions, LV end-systolic volume (r = 0.82, P = 0.001) and<br />

LVMi (r = 0.69, P = 0.003). There was a negative correlation between peak CPO<br />

and EF (r = -0.68, P < 0.01).<br />

Conclusions: We found that in patients with significant GHD, greater LV dimensions,<br />

volumes or LVMi were paradoxically associated with enhanced cardiac<br />

function. We also found that patients with lower EF had better cardiac function.<br />

These findings contradict the usual belief that higher EF and lower cardiac dimensions<br />

are better.<br />

P2673 Left ventricular geometry after septal anterior<br />

ventricular exclusion and Dor operation among<br />

patients with ischemic cardiomyopathy<br />

Y. Takahara, K. Mogi, M. Hatakeyama, A. Dou. Funabashi Municipal<br />

Medical Center, Cardiovascular Surgery, Funabashi, Japan<br />

Purpose: To demonstrate left ventricular (LV) geometry after endoventricular reconstruction<br />

using septal anterior ventricular exclusion (SAVE) and endoventricular<br />

circular patch plasty (Dor operation) among patients with ischemic cardiomyopathy.<br />

Methods: Twenty-one patients (LVEF < 35%) with preoperative LVDd more than<br />

60 mm or diastolic LV sphericity index (DSI; transversal length/longitudinal length)<br />

more than 60% underwent endoventricular reconstruction. Eleven patients underwent<br />

SAVE and 10 patients underwent Dor operation. The mean age was<br />

65.1±10.5 years old in the SAVE group, and 63.3±9.4 years old in the Dor group.<br />

There were no significant differences in the preoperative characteristics concerning<br />

hypertension, diabetes, hyperlipidemia, and chronic renal failure between the<br />

groups. LV geometry of the two procedures was studied by transthoracic echocardiogram<br />

comparatively.<br />

Result: Preoperative LVEF was 22.8±6.9% (SAVE) vs. 27.4±4.7% (Dor, p<br />

= 0.095), LVDd was 56.2±4.8mm vs. 60.2±4.5mm (p = 0.081), LVDs was<br />

45.2±6.4mm vs. 49.2±4.8mm (p = 0.123), DSI was 56.7±7.2% vs. 59.1±8.1%<br />

(p = 0.497), SSI (systolic LV sphericity index) was 51.0±5.4% vs. 54.8±7.8% (p =<br />

0.206), and the mean grade of mitral regurgitation was 1.45±1.29 vs. 1.90±1.73<br />

(p = 0.509). There was no hospital mortality. In the postoperative evaluation within<br />

3 months after the operation, significant difference in LVDd, LVDS and DSI were<br />

found between the two procedures (table).<br />

Postoperative echocardiogram<br />

SAVE Dor p<br />

LVEF (%) 35.7±5.9 32.2±4.6 0.336<br />

LVDd (mm) 52.8±5.1 59.6±7.1 0.012*<br />

LVDs (mm) 42.6±5.7 50.4±6.8 0.010*<br />

DSI (%) 52.7±8.0 61.2±9.4 0.037*<br />

SSI (%) 48.9±12.8 56.2±10.4 0.172<br />

*Significant difference between both procedures.<br />

Conclusion: Endoventricular reconstruction surgery results in satisfactory outcomes.<br />

Postoperative LVDd, LVDs and DSI were more improved in SAVE procedure<br />

than Dor operation.<br />

P2674 Impact of glycemic control on the short and midterm<br />

outcome in type II diabetic patients undergoing<br />

elective coronary bypass surgery<br />

M.J. Santos1 ,D.Lowenstein1 , H. Sanabria 1 ,F.Robles1 ,<br />

M. Rodriguez Acuna1 , R. Boughen1 , A. Arnedo1 , R.R. Favaloro1 ,<br />

A. Ciccale Smit1 , E. Gabe2 . 1Buenos Aires, Argentina; 2Icycc Favaloro<br />

Foundation, Cardiology Dept., Buenos Aires, Argentina<br />

Background: Patients (pt) with diabetes mellitus (DM) have increased rates of<br />

complications after coronary surgery (CABG).<br />

Purpose: We examined the association between glycaemia control determined<br />

by preprocedural haemoglobin A1c (A1c) on the short and midterm outcome in<br />

type II diabetic pt undergoing elective CABG.<br />

Methods: A total of 80 consecutive diabetic pt were prospectively enrolled from<br />

March 2006 to <strong>September</strong> 2007. Fifty four nondiabetic pt who underwent elective<br />

CABG during the same period were randomly selected as the control group.<br />

Optimal glycemic control was defined as A1c ≤ 7%, and suboptimal control was<br />

defined as A1c > 7%. We defined major complications as: death sepsis, mediastinitis,<br />

perioperative myocardial infarction, cardiac failure, stroke and renal dysfunction<br />

requiring dialysis.<br />

Results: DM pt more often had peripheral vascular disease (22.5 vs. 5.6%, p<br />

0.008), and impaired Left Ventricular function (15 vs. 1.9%, p 0.01) than pt without<br />

DM. There were no important differences in clinical, angiographic characteristics,<br />

and risk scores (Parsonett and Euroscore) between DM pt with A1c > 7% and <<br />

7%. The mean values of A1c in DM pt with A1c > 7% and < 7% were significantly<br />

different (8.6% vs. 6.1%, p 0.0001). There were 32 pt (40%) with A1c < 7%, and<br />

48 (60%) with A1c > 7%. Diabetic pt with optimal glycemic control had a rate of<br />

in-hospital complications, similar to that of non diabetic pt (3.1% vs 13%, p = NS).<br />

Diabetic pt with A1c > 7% had a significantly higher rate of postoperative complications<br />

than those with A1c < 7% (29.2% vs. 3.1%, p = 0,003). In a multiple<br />

logistic regression analysis, A1c > 7% was found to be a significant independent<br />

predictor of in-hospital complications (odds ratio 1.8, 95% CI 1.12 to 2.8; p<br />

= 0,01).The mean follow up was 12 months (1-20), 66 pt were followed (3 deaths<br />

in-hospital, and 1 pt lost). Although pt with optimal glycemic control had fewer<br />

complications than pt with A1c > 7, we did not find statistically significant differences<br />

(7% vs 23%, Long Rank test p= 0.08)Postoperative length of stay (LOS)<br />

ranged from 4 to 165 days; the median postoperative LOS was 7 days. Patients<br />

with A1c > 7% had a significantly higher postoperative LOS than those with A1c<br />

< 7% (Mann-Whitney U Test. 6 vs. 8 days, mean rank 32 vs 46, p = 0.008)<br />

Conclusions: In diabetic pt undergoing elective CABG, optimal glycemic control<br />

(A1c < 7%) is associated with a lower rate of immediate postoperative complications,<br />

similar to non diabetic pt. These data suggest that aggressive treatment<br />

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Understanding determinants of hemodynamics and ventricular function / Novel insight in heart failure biology and genetics 423<br />

of DM to achieve A1c < 7% is beneficial in improving the clinical outcome after<br />

CABG.<br />

NOVEL INSIGHT IN HEART FAILURE BIOLOGY AND<br />

GENETICS<br />

P2675 Prevalence of chymase and angiotensin converting<br />

enzyme gene polymorphisms and relation to clinical<br />

findings in patients with heart failure<br />

R. Amir1 ,O.Amir2 ,H.Paz2 ,R.Mor1 ,R.Wolff2 ,M.Sagiv1 ,<br />

N. Yaniv2 , R. Ammar2 , M. Sagiv1 ,B.S.Lewis2 . 1Zinman College<br />

of Sports Sciences, Genetics and Molecular Biology, Netanya, Israel; 2Lin and<br />

Lady Davis Carmel Medical Centers, <strong>Heart</strong> Center, Haifa, Israel<br />

Background: Angiotensin II, which plays a crucial role in the myocardial remodeling<br />

process of heart failure (HF), is generated via the angiotensin-converting<br />

enzyme (ACE) and chymase (CMA) pathways. We investigated the associations<br />

of ACE and CMA1 polymorphisms in patients with systolic HF and the correlation<br />

with clinical status and left ventricular (LV) function.<br />

Methods: We genotyped 191 patients with HF and systolic LV dysfunction (LV<br />

ejection fraction


424 Novel insight in heart failure biology and genetics<br />

mentation and by flow cytometry using Propidium Iodide. Nonapoptotic cell death<br />

was detected by Cytotoxicity Detection Kit. EPCs (CD133/CD34) and c-kit positive<br />

cells were quantified using a cytometer.<br />

Results: Our data showed that TNF-α concentration was significantly higher in<br />

serum sample from severe and mild patients compared to controls (6.09±1.06,<br />

3.57±0.62 vs 1.22±0.83, P


the abundance of profibrotic CCN2 protein was significantly increased in hyperglycaemic<br />

animals (1±0.47 1.67±0.28 respectively p


426 Novel insight in heart failure biology and genetics<br />

signal application and was associated with an increase of LV peak dP/dt. Application<br />

of CCM signals in-vitro for as little as 10 sec increased P-PLB in isolated<br />

cardiomyocytes at both S-16 and T-17.<br />

In-Vivo Studies<br />

Time 0 min 1 min 5 min 10 min<br />

P-PLB at S-16/CSQ 0.23 0.47 0.46 0.56<br />

P-PLB at T-17/CSQ 0.23 0.54 0.55 0.57<br />

LV dP/dt (mmHg/sec)<br />

In-Vitro Studies<br />

1270 1640 1590 1490<br />

Time 0 sec 10 sec 20 sec 30 sec<br />

P-PLB at S-16/CSQ 0.35 0.85 0.96 1.04<br />

P-PLB at T-17/CSQ 0.76 0.96 0.99 1.16<br />

Conclusions: CCM signals rapidly increase P-PLB in-vitro and in-vivo. The exact<br />

mechanism remains unknown. The increase in P-PLB observed in this series of<br />

studies can explain the rapid increase in LV contractility observed with initiation<br />

of therapeutic CCM signal delivery.<br />

P2687 Toll-like receptor is involved in cardiac dysfunction in<br />

angiotensin II-induced hypertension<br />

S.M. Matsuda1 , S.U. Umemoto1 , H.Y. Yoshino1 , S.I. Itoh2 ,<br />

H.A. Aoki3 ,K.Y.Yoshimura3 , T.M. Murata4 , M.M. Matsuzaki1 .<br />

1Yamaguchi University Hospital, Department of Medicine and<br />

Clinical Science, Ube, Japan; 2Yamaguchi University Hopital, Department of<br />

Medicine and Clinical Science, Ube, Japan; 3Yamaguchi University School,<br />

Department of Molecular Cardiovascular Biolog, Ube, Japan; 4Yamaguchi University, Science Research Center, Ube, Japan<br />

Toll-like receptor 4 (TLR4) is associated with innate immunity, and recent evidence<br />

has suggested that TLR4 is expressed in cardiac myocytes and may play<br />

an important role in cardiac hypertrophy and the development of heart failure.<br />

We investigated the role of TLR4 in cardiac hypertrophy and function following<br />

angiotensin II (Ang II) or norepinephrine (NE)-induced pressure overload in mice<br />

in vivo.<br />

TLR4-knocked out mice (C.C3H-Tlr4 (lps-d), n=8∼10), and wild-type (WT) genetic<br />

background mice (BALB/c, n = 8-10) were randomized into two groups of<br />

4-5 rats each and implanted osmotic minipumps of Angiotensin II (AT II) or Norepinephrine<br />

(NE) for 2 weeks. Left ventricular end-diastolic dimension (LVEDd), LV<br />

end-systolic dimension (LVESd), fractional shortening (%FS), the ejection fraction<br />

(EF) and interventricular septum (IVS) as well as LV posterior wall dimension<br />

(LVPWd) calculated by the Teichholtz method were assessed by averaging<br />

three cardiac cycles based on transthoracic echocardiography using a ultrasound<br />

equipped with a 15-MHz probe under light anesthesia with sevoflurane.<br />

In each heart, we evaluated the wall-to-lumen ratio and the perivascular fibrosis<br />

in the heart by analyzing Masson Trichrome-stained sections using a computerassissted<br />

image analysis system.<br />

Both Ang II and NE induced a significant increase in systolic blood pressures<br />

among the four groups (p


parison with IL-8 as well as the existance of correlation among PMN locomotory<br />

response and clinical or hemodynamic parameter of cardiac function.<br />

Seventy-one CHF patients with LVEF


428 Perspectives in diastology<br />

NT-proBNP levels in COPD patients.<br />

Conclusion: Severity of COPD is associated with elevated NT-proBNP levels in<br />

vascular surgery patients with a preserved LVEF.<br />

P2695 Increased Serca2a/PLN ratio can rescue ventricular<br />

diastolic dysfunction which caused by deletion of<br />

Tbx5<br />

Y. Zhu 1 ,A.Gramolini2 , J. Takeuchi2 ,Y.Zhou2 , D. Maclennan2 ,<br />

B. Bruneau2 . 1Xi’an, China, People’s Republic of; 2University of<br />

Toronto, Toronto, Canada<br />

Objective: To investigate the mechanisms involved in increased Serca2a activity<br />

to rescue left ventricular diastolic dysfunction which caused by deletion of Tbx5.<br />

Method and results: First, we have generated Tbx5del/+ and ventricular specific<br />

deletion Tbx5LDN/+; Nkx2.5-Cre (Tbx5V-del/+) mice. In these mice, cardiac function<br />

was impaired and the E/A ratio was decreased and isovolumic relaxation time<br />

was prolonged, suggesting a direct role for Tbx5 in regulating LV diastolic function<br />

by down-regulation of Serca2a expression. The decay of Ca2+ transients<br />

was slower in Tbx5V-del/+ myocytes as indicated by an increased time for 50%<br />

relaxation compared to control myocytes (12.5±0.5 vs. 9.5±0.42 msec, P


and EF (-0.5%) which significantly differed from those of controls: SV (+19%,<br />

p


430 Perspectives in diastology<br />

P2703 Structural and functional determinants of left atrial<br />

volume in essential hypertension<br />

E. Taxiarchou, C. Tsioufis, D. Chatzis, M. Selima, A. Kasiakogias,<br />

D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic,<br />

University of Athens, Hippokration Hospital, Athens, Greece<br />

Purpose: Hypertension-induced cardiac adaptations like left ventricular (LV) hypertrophy,<br />

diastolic dysfunction and left atrial (LA) enlargement have been described<br />

in a large number of studies. The aim of our study was to investigate<br />

the interrelationship between LV structural alterations and diastolic dysfunction<br />

indexes and LA size in essential hypertensive subjects.<br />

Methods: We studied 339 consecutive subjects (aged 52±10 years) with untreated<br />

newly diagnosed stage I-II essential hypertension [office BP =152/98<br />

mmHg]. All the participants underwent echocardiography and 24-hour ambulatory<br />

BP monitoring. LA volume and LV mass were indexed for body surface area<br />

to estimate LA volume index (LAVI) and LV mass index (LVMI). Furthermore, LV<br />

diastolic function was estimated by means of TDI echocardiography, averaging<br />

diastolic mitral annular peak velocities (Em, Am, Em/Am ratio) from four separate<br />

LV sites. The study population was divided into those with increased LAVI<br />

(>26ml/m2 , n=117) and those without increased LAVI ≤26ml/m2 , n=222).<br />

Results: Subjects with increased LAVI compared to those without increased LAVI<br />

had significantly increased 24-h pulse pressure (54.1±9.7 vs 50.8±8.0 mmHg,<br />

p=0.001), while there was not difference regarding age, body mass index, 24-h<br />

systolic and diastolic BP and metabolic profile. Moreover, subjects with increased<br />

LAVI compared to those without increased LAVI had significantly increased left<br />

ventricular mass index (112±28 vs 101±26 gr/m2 , p=0.001) while they did not<br />

differ in relative wall thickness (0.44±0.07 vs 0.43±0.08, p=NS), and greater<br />

E/Em (9.8±3.1 vs 8.9±2.3, p


of effects on systemic BP and cardiac hypertrophy. Increased collagen deposition<br />

and gene expression may explain these changes in LV diastolic function. Rho<br />

kinase may in part be involved in the pathogenic LV remodeling leading to diastolic<br />

dysfunction.<br />

P2707 Obesity as an independent risk predictor of mild to<br />

moderate diastolic dysfunction<br />

A. De Guzman1 , E. Demerre2 . 1St Luke’s Medical Center, <strong>Heart</strong><br />

Institute, Quezon City, Philippines; 2St. Lukes Medical Center, <strong>Heart</strong><br />

Institute, Quezon City, Philippines<br />

Background: Diastolic dysfunction is prevalent among obese individuals hence,<br />

is associated with increased cardiovascular morbidity and mortality risk. As to how<br />

severe in terms of diastolic dysfunction and which among the diastolic function<br />

indices is affected as the level of body mass index remains unclear and elusive.<br />

Objective: To determine correlation and the degree of risk in developing diastolic<br />

dysfunction based on the different diastolic function indices and grades of obesity<br />

in terms of body mass index (BMI)<br />

Methods: 2711 Filipinos were retrospectively reviewed with different grades of<br />

obesity. Multiple linear regression analysis were done with sub-analysis among<br />

subjects with "isolated" obesity.<br />

Results: After adjustment of clinical risk factors, the risk was doubled (Adjusted<br />

OR- 2.02, CI: 0.99 – 4.1, p-value 0.05) among overweight patients as compared<br />

to the normal population. There was a 4-fold increased (Adjusted OR - 4.00, CI:<br />

1.94 – 8.21, p-value


432 Pericardial and myocardial disease<br />

PERICARDIAL AND MYOCARDIAL DISEASE<br />

P2711 Diagnostic value of tumor markers in the pericardial<br />

fluid for the diagnosis of malignant pericardial<br />

effusions<br />

K. Karatolios1 , S. Pankuweit 2 ,N.Timmesfeld3 , A. Richter2 ,<br />

B. Maisch2 . 1University hospital of Marburg, Cardiology, Marburg,<br />

Germany; 2University Hospital of Marburg and Giessen, Cardiology, Marburg,<br />

Germany; 3University of Marburg, Medical Biometry and Epidemiology, Marburg,<br />

Germany<br />

Background: The diagnosis of malignant pericardial effusion is often a vexing<br />

problem, since pericardial fluid cytology findings are positive in only 50-70% of<br />

cases. The assessment of tumor markers in the pericardial fluid may help to establish<br />

the diagnosis of malignant pericardial effusion, but their precise diagnostic<br />

role in differentiating malignant from benign pericardial effusions remains unclear.<br />

The aim of this study was to estimate the value of the assessment of tumor markers<br />

in the pericardial fluid for the recognition of malignant pericardial effusion.<br />

Methods and Patients: We analyzed 88 patients, who underwent pericardiocentesis<br />

and pericardial biopsy with subsequent pericardial fluid and tissue analysis<br />

by cytology, biochemistry, and molecular biology during 1999-2007. The examined<br />

patients’ population consisted of 22 patients with confirmed malignant pericardial<br />

effusion and 66 patients with benign pericardial effusion. Pericardial fluid<br />

samples were assayed for carcinoembryonic antigen (CEA), alpha-fetoprotein<br />

(AFP), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous<br />

cell carcinoma antigen (SCC) and neuronspecific enolase (NSE).<br />

Results: The median value of all tumor markers, except for AFP, was statistically<br />

significantly higher in the malignant group than in the benign group (Table).<br />

Malignant PE Benign PE Significance<br />

CA 72-4 7,5 kU/l


Conclusion: Compared to previously published data, our survey shows a decrease<br />

of some historical causes of cardiac tamponade such as tuberculosis,<br />

myxoedema or uraemia. The leading cause is currently malignant diseases which<br />

carries a very poor prognosis.<br />

P2715 Tricuspid flow velocity paradox in evolving cardiac<br />

tamponade<br />

E. Siniorakis1 , K. Sfakianakis1 , D. Barlagiannis1 , A. Samaras1 ,<br />

S. Pamouki1 ,E.Tsika1 ,I.Zarreas1 ,D.Mytas2 ,K.Karidis1 ,<br />

N. Exadaktylos 1 . 1Sotiria Chest Diseases Hospital, Cardiology,<br />

Athens, Greece; 2Athens, Greece<br />

Introduction: In severe pericardial effusions (PE), Doppler tricuspid recording of<br />

inflow E velocity presents large respiratory fluctuations. We sought to examine if<br />

progression from the subclinical to the overt form of tamponade in these patients<br />

(pts) is accompanied by any modifications of the aforementioned respiratory pattern.<br />

Methods: Eighty seven pts (M=52, F=35, age = 68±12 yrs) with newly diagnosed<br />

lung cancer and secondary large PE, not in clinical tamponade, were addressed<br />

to us for haemodynamic evaluation. By Doppler echocardiography, E velocities<br />

across the tricuspid valve (EI=inspiratory E, EE=expiratory E) and their respiratory<br />

fluctuations (�E) were measured at baseline and weekly afterwards, for a total of<br />

20 days. 23 pts (group A) evolving to tamponade, had their last assessment just<br />

before surgical drainage. The other pts (group B) remained clinically stable during<br />

the follow-up period. Initial E values (E1) were compared to the final ones (E2) by<br />

t-test.<br />

Results: E and �E remained unchanged in group B, during the follow up period.<br />

Contrarily, group A presented a dramatic decline of E and �E values, progressing<br />

to the final stage (Table 1).<br />

Table 1. Tricuspid flow velocities on the two groups<br />

Parameter Group A Group B p<br />

EI1 (cm/s) 55.4±9.5 51.7±8.8 NS<br />

EE1 (cm/s) 36.1±9.2 33.3±7.6 NS<br />

�E1 (%) 51.3±10.0 48.1±8.3 NS<br />

EI2 (cm/s) 31.6±4.4** 53.2±7.1


434 Pericardial and myocardial disease<br />

sive studies in myotonic dystrophy (MD) with electrocardiographic data of these<br />

patients and to evaluate the nature of arrhythmias during the follow-up. Patients<br />

with MD were reported as at high risk of complete atrioventricular (AV) block or<br />

ventricular arrhythmias development.<br />

Methods: 102 patients, 54 women, 48 men, mean age 45±14 years, with MD<br />

were enrolled; one had sustained ventricular tachycardia (VT), 2 had syncope<br />

and other patients were asymptomatic; 2 men had history of myocardial infarction<br />

(MI). Surface ECG, measurement of left ventricular ejection fraction (EF) at<br />

echocardiography, 24 hour Holter monitoring and study of heart rate variability<br />

(HRV), signal-averaged ECG (SAECG) and electrophysiological study (EPS) (n=<br />

42) were performed.<br />

Results: ECG and Holter monitoring were normal in 59 and 69 patients. HRV was<br />

normal in all patients. Late potentials were present in 18 patients and were not<br />

correlated with spontaneous or induced VT. EF was normal in all, but 3 patients<br />

(60±10%). HV interval was prolonged in 0 of 12 patients with normal ECG, 5 of<br />

9 patients with first d AV block older than 40 years, 7 of 9 patients with hemiblock<br />

(HB), 4 of 7 patients with bundle branch block (BBB) and 3 of 5 patients with<br />

atrial fibrillation (AF). Paroxysmal AF or flutter was noted at ECG in 7 patients,<br />

non sustained AF at Holter ECG in 12 patients and AF was induced in 15 of 42<br />

patients (36%). Non sustained VT was noted at Holter ECG in 2 patients and was<br />

induced in 5 of 42 patients (12%). Sick sinus syndrome was noted in 4 patients<br />

at Holter ECG and in 6 of 42 patients at EPS. During the follow-up (4±4 years),<br />

one patient with MI died suddenly. 8 patients developed chronic AF; 1 of them<br />

was resuscitated from cardiac arrest and 1 died from heart failure; 4 patients died<br />

from respiratory failure and heart failure; 4 patients developed permanent atrial<br />

flutter, requiring ablation. Pace-maker was implanted in 22 patients.<br />

Conclusions: HV interval was normal in patients with normal ECG and those with<br />

first degree AV block younger than 40 years. HV interval was prolonged in half of<br />

patients with HB or BBB independently on the age. Ventricular tachyarrhythmias<br />

were rare and related to associated ischemic cardiomyopathy. The most frequent<br />

arrhythmia during the follow-up was atrial flutter or fibrillation which can induce<br />

dilated cardiomyopathy with a risk of sudden death.<br />

P2720 The prevalence of effusive constrictive physiology<br />

and cardiac tamponade in patients with suspected<br />

tuberculous pericardial effusion<br />

M. Ntsekhe, F. Syed, B. Mayosi, J. Russel, O.E. Usim on behalf<br />

of IMPI study group. Groote Schuur Hospital, Cardiology Dept.,<br />

Observatory, South Africa<br />

Purpose: Effusive constrictive pericarditis occurs when pericardial fluid and visceral<br />

conscriction coexist to cause pericardial tamponade and constrictive physiology.<br />

The hall mark of the syndrome is the finding of persistantly elevated right<br />

atrial pressures despite the normalization of intra-pericardial pressures following<br />

pericardiocentesis. Effusive constrictive pericarditis is thought to be a precursor<br />

to constrictive pericarditis. Because of the difficulty in establishing a definitive diagnosis,<br />

the prevalence of the syndrome in tuberculous pericardial effusions is<br />

unknown. Some have speculated that due to the inflammatory, exudative nature<br />

of tuberculous effusions, effusive constrictive pericarditis may be very common<br />

but under recognized.<br />

Objectives: 1)To determine the prevalence of effusive constrictive pericarditis<br />

in patients with large effusions suspected to be tuberculous in aetiolgy. 2) To<br />

determine the prevalence of cardiac tamponade in patients with large effusions<br />

suspected to be TB in aetiolgy. 3) To determine the frequency of effusive constrictive<br />

pericarditis in those with cardiac tamponade prior to evacuation of the<br />

pericardium.<br />

Methods: Consecutive patients with large effusions suspected to be TB in origin<br />

were enrolled. Right atrial and intra-pericardial pressures were obtained before<br />

and after pericardiocentesis. Effusive constrictive pericarditis was defined as failure<br />

of the right atrial pressure to fall by 50% or to a new level of ≤10mmHg after<br />

the intra-pericardial pressure was lowered to near 0 mmHg. Tamponade was<br />

defined as measured intrapericardial pressures that exceeded the upper limit of<br />

normal right atrial pressure (12mmHg).<br />

Results: 69 patients underwent pericardiocentesis. 55 had intra-pericardial and<br />

right atrial pressure measurements that were of acceptable quality for analysis.<br />

36.5% (20/55) met the haemodynamic criteria for effusive constrictive pericarditis.<br />

51% (28/55) had cardiac tamponade at presentation. Of the patients with cardiac<br />

tamponade, 60.1% (17/28) had evidence of effusive constrictive disease after<br />

evacuation of the pericardium. This compared with only 9% (1/11) of the patients<br />

without features of cardiac tamponade.<br />

Conclusion: In this first and largest study of its kind in the world, effusive constrictive<br />

pericarditis occured in 37% of patients with a suspected tuberculous pericardial<br />

effusion. Approximately half of patients with suspected tuberculous pericardial<br />

effusion have hemodynamic evidence of cardiac tamponade at presentation<br />

and the majority of those patients with tamponade have hemodynamic evidence<br />

of co-existing visceral constriction.<br />

P2721 The utility of enalapril treatement in<br />

anthracyclines-induced cardiac injury in children with<br />

malignancies- preliminary study<br />

C. Mandric 1 , A.G. Dimitriu 1 ,I.Miron 1 ,L.Dimitriu 2 . 1 University<br />

of Medicine and Pharmacy, Pediatric Cardiology, Iasi, Romania;<br />

2 MEDEX Medical Center, Iasi, Romania<br />

Background: Treatement with angiotensin converting enzyme (ACE) inhibitors<br />

in children with malignancies who received high doses of anthracyclines have<br />

been shown useful in order to reduce manifestations of anthracyclines-induced<br />

cardiotoxicity.<br />

Purpose: Study of effects of enalapril treatment on anthracyclines-induced<br />

echocardiographic change in children with malignancies.<br />

Methods: We performed, a prospective clinical study comparing enalapril to<br />

placebo treatement in 30 survivors of pediatric cancer (aged beetwen 6 -14 years)<br />

from the Department of Pediatric Hemato-Oncology from "Saint Mary" Children<br />

Hospital Iasi, treated with certain therapeutical protocols for hematological malignancies,<br />

who included anthracyclines- doxorubicin or adriamicin; all of this patients<br />

had at least one cardiac abnormality identified at any time after anthracyclines<br />

exposure; those chidren were devided in two groups: group A - 10 children<br />

treated enalapril (dose range beetwen 0.2-0.5 mg/kgc/d); it was performed<br />

regular echocardiographic examinations during enalapril therapy, mean age at<br />

cancer diagnosis - 6 years, mean median follow-up since the start of enalapril, 16<br />

month; group B placebo - 20 children treated with similar doses of anthracyclines,<br />

without enalapril treatment, after completion of doxorubicin therapy. Cardiological<br />

evaluation was performed at baseline and at 3, 6, 12, 16 month after initiation of<br />

enalapril/placebo therapy.<br />

Results: Over the 16 month of enalapril therapy, there was progressive improvement<br />

in left ventricular (LV) dimension end-systolic and end-diastolic, fractional<br />

shortening, LV mass, LV per cent posterior wall thickening, interventricular per<br />

cent septal thickening, Tei index, comparative with evolution of the same ecocardiographic<br />

parameters of the controller group, who was constant or it worsened<br />

in course of follow-up<br />

Conclusions: Enalapril treatment improved anthracyclines-induced ecocardiographic<br />

changes in patient included in study, justifing precocious introduction of<br />

enalapril in children with cardiotoxocity anthracyclines induced.<br />

P2722 Myocardial contractility disorders caused by<br />

pericardial inflammatory diseases influence or not left<br />

ventricular haemodynamics and performance?<br />

I.S. Benedek 1 ,T.Hintea 2 ,M.Chitu 2 , C. Matei 2 ,A.Sarbu 2 .<br />

1 University Emergency Hospital Targu-Mures, Cardiology Clinic,<br />

Targu-Mures, Romania; 2 University Emergency Hospital Targu Mures,<br />

Cardiology, Targu-Mures, Romania<br />

In pericarditis, extension of inflammatory process from the pericardium to myocardium<br />

could lead to alteration of wall motion, involving segments located in<br />

contact with the diseased pericardial layer. This study use Computerized 3D<br />

echocardiography (C3DE) for evaluation of myocardial motion disorder associated<br />

with pericarditis.<br />

Materials and methods: 15 pts with chronic pericarditis, in whom 2D echo<br />

showed presence of thick pericardium (4.2±0.5 mm) and pericardial fluid<br />

(5.6±3,2 mm), located at the lateral (7 pts - 46.66%), inferior (5 pts - 33.33%) and<br />

apical segments (3 pts-20%). C3DE was performed with Philips 7.500 and QLab<br />

software. Volumetric curve of each myocardial segment during cardiac cycle and<br />

polar map of time delay from onset till the maximum contraction were obtained.<br />

Intracavitar haemodynamics was evaluated using Doppler flow mapping at 3 levels<br />

(basal, median and apical) along 3 longitudinal axes, and flow decelerations<br />

were calculated.<br />

Results: Contractility disorder (CD) was defined as a flat type of the volumetric<br />

curve, with the difference between the maximum and minimum volume less than<br />

3.5 ml, and a spot on the time delay polar map located at the same segment,<br />

representing a delay in contraction augmentation more than 50 msec. LVEF calculated<br />

by C3DE was normal in all cases (avg. 53.4±4.2%). CD was revealed by<br />

C3DE located at the level of lateral segment in 6 cases (40%), inferior in 5 pts<br />

(33.33%), apical in 3 pts (20%) and lateroapical in 1 patient (6,66%), in accordance<br />

with the location of the pericardial inflammation (p=0.001). Time difference<br />

between maximum and minimum volume during contraction was 375 msec in<br />

segments with CD compared with 323 in the rest of the segments (p=0.002). Delay<br />

in contraction augmentation was 57 msec in segments with CD compared with<br />

normal contracting segments. When performed, coronarography showed normal<br />

coronary arteries. Doppler flow mapping showed no perturbance of intracavitary<br />

flow (gradual decrease of flow velocity from basis to apex uniformly distributed on<br />

the longitudinal axis – 0.12 msec in the basal half and 0.13 msec in the apical half<br />

– p=0.002).<br />

Conclusions: Extension of the inflammatory process from the pericardium to<br />

the myocardial layer could influence myocardial contractility, which was identified<br />

in this study using C3DE, based on objective evaluation and quantification<br />

of contractility parameters. However, these did not influence LV performanced<br />

expressed by LVEF or the intracavitary flow hemodynamics. Further studies are<br />

required to elucidate the impact of inflammatory process on LV performance.<br />

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P2723 Differential virus-associated TRBV dominance in<br />

murine and human acute myocarditis<br />

M. Noutsias1 , M. Rohde1 ,A.Block1 , K. Blunert 1 ,M.Hummel1 ,<br />

D. Lassner2 , U. Kuehl1 ,S.Rutschow1 , H.P. Schultheiss1 ,H.D.Volk3 .<br />

1Charite - Campus Benjamin Franklin, Department of Cardiology &<br />

Pneumonology, Berlin, Germany; 2IKDT,Berlin,Germany; 3Charite - Campus<br />

Mitte, Institute of Medical Immunology, Berlin, Germany<br />

Background: Acute myocarditis can be induced by various cardiotropic viruses,<br />

among others Coxsackievirus (CBV), human herpes virus type 6 (HHV6) and<br />

Parvovirus B19 (B19V). Viral proteins lead to clonal expansions of particular Tcells,<br />

thereby inducing specific dominances of the T-cell receptor Vbeta (TRBVs).<br />

Methods and Results: Using a preamplified real-time RT-PCR system for murine<br />

and human TRBV expression, myocardial tissues from SWR mice and human<br />

EMBs were investigated. In the murine SWR model of CBV induced myocarditis,<br />

a highly significantly increased TRBV4 expression was observed compared<br />

to controls at the time of maximum infiltration at d7 (p


436 Pericardial and myocardial disease<br />

tentials (LP) and in patients without bundle branch block, we used the combination<br />

of any 2 of the 3 parameters, filtered QRS duration > 120 ms, low amplitude signal<br />

duration (LAS) > 40 ms and root mean square voltage of the last 40 ms of<br />

QRS(RMS40)< 20μv.<br />

Results: Surface ECG was normal in 29 patients and remained normal in 20 of<br />

them. First d AV block (n= 5) or bundle branch block were present in 18 patients<br />

and were stable at second study in 14 patients. In other patients AV conduction<br />

disturbance or atrial arrhythmia were noted at second ECG. Holter was normal<br />

in 40 patients and remained normal in 34 of them; 6 developed sinus pauses.<br />

In 7 patients with abnormal Holter ECG, only one with nonsustained (NS) atrial<br />

fibrillation (AF) developed permanent AF. Mean QRS duration did not change significantly<br />

(102±19 vs 105.5±19 ms); RMS 40 decreased significantly from 29±16<br />

μv to20±16 μv(p


Methods: During 2007, 10 patients (46±12 years, 7 males) were referred to our<br />

centre for unexplained new-onset AHF with persistent LV systolic dysfunction (EF<br />

29±9%). EMB specimens were studied by using light and electron microscopy,<br />

immunohistochemical and polymerase chain reaction techniques. All but one patient<br />

with the presence of cardiotropic pathogen or inflammatory infiltrate in EMB<br />

specimens were then specifically treated with antibiotics or antiviral agents or<br />

with combined immunosuppressive therapy (Tx +, n=5); remaining 5 patients (Tx<br />

-) were treated only by conventional AHF therapy.<br />

Results: Cardiotropic (viral or bacterial) pathogen was found in EMB specimens<br />

in 5 patients (50%), isolated inflammatory infiltrate was present in 1 patient (10%).<br />

At admission, there were no differences regarding LV ejection fraction, LV diameters<br />

and NYHA class between Tx + and Tx – patients. After 3 months of follow-up,<br />

the LV ejection fraction and LV end-systolic diameter considerably improved only<br />

in Tx + patients (30±8 vs.45±12%, 59±5 vs.46±8mm, p=0.05). In all but one<br />

Tx + patient the improvement in NYHA class was noted; in contrast only 2 Txsubjects<br />

functionally improved and 2 Tx – patients have had to undergo heart<br />

transplantation.<br />

Conclusions: Inflammatory cardiomyopathy was present in half of the patients<br />

with unexplained new-onset AHF and persistent LV systolic dysfunction. Specific<br />

treatment of these patients was associated with better LV functional improvement<br />

and clinical outcome compared to conventionally treated subjects. Performing<br />

EMB thus has a definite role in the management of the patients with unexplained<br />

new-onset AHF.<br />

P2732 Loss of TIR-domain-containing adaptor protein<br />

inducing IFN-beta (TRIF) leads to interferon beta<br />

dependent exacerbation of viral myocarditis in mice<br />

A. Riad 1 , M. Becher 2 ,O.Lettau 2 , D. Lassner 2 , S. Bereswill 2 ,<br />

M.M. Heimesaat 2 , D. Westermann 2 , H.P. Schultheiss 2 ,<br />

C. Tschope 2 . 1 Charite Berlin, Cardiology Dept., Berlin, Germany; 2 Charite<br />

Universitaetsmedizin Berlin, Cardiology, Berlin, Germany<br />

Introduction: Viral myocarditis leads to intense cardiac inflammation. TIRdomain-containing<br />

adaptor protein inducing IFN-β (TRIF) mediates intracellular<br />

signalling of Toll-like receptor 3 and 4 leading among others to the activation of<br />

interferon (IFN) beta. In the present study we investigated the role of TRIF in<br />

coxsackievirus B3 (CVB3)-induced myocarditis in mice.<br />

Materials and methods: TRIF knock out mice (TRIF-/-) and wildtype (WT) mice<br />

were infected with CVB3 (Nancy strain 5*105 PFU, i. p.). In a mortality study, WT<br />

(n=20), TRIF-/- (n=11) and IFN beta treated (10 MIU/kg, i.p.) TRIF-/- mice were<br />

obtained during 60 days post CVB3 infection. In a further study, left ventricular tissue<br />

was prepared for molecularbiological and immunohistological analyses seven<br />

days after CVB3 infection.<br />

Results: Sixty days after CVB3 infection 100% of TRIF-/-, but none of WT mice<br />

died (P


438 Pericardial and myocardial disease<br />

spectively, p=0.0001), ischemic heart failure (54%;16%,12% vs 1%;2%;1% respectively,<br />

p=0.0001) or normal subjects (54%;16%,12% vs 5%;0%;2.5% respectively,<br />

p=0.0001). Univariate predictors of death/transplantation were: young age,<br />

longer symptom duration, giant cell myocarditis, NYHA II-IV, presentation with<br />

left ventricular (LV) dysfunction, clinical signs/symptoms of heart failure, multiple<br />

echocardiographic and hemodynamic indexes of LV and right ventricular dysfunction<br />

and AECA. Independent negative predictors by Cox regression were higher<br />

mean right atrial pressure (RR 1.3, p=0.02), lower LV ejection fraction (RR 1.03,<br />

p=0.038) and AECA (RR 5.8, p=0.01). AECA was the only independent predictor<br />

for death/transplantation after correction for hemodynamic variables (p=0.02, RR<br />

6.5, 95% CI 1.7-25, p=0.007).<br />

Conclusion: The finding of AECA provides an independent negative serological<br />

predictor in biopsy-proven myocarditis and suggests that immune-mediated<br />

cardiac endothelial dysfunction may have a key role in disease progression.<br />

P2736 Paradox role of the matrix metalloproteinase 2 in<br />

inflammatory cardiomyopathy<br />

D. Westermann, O. Lettau, K. Savvatis, S. Bereswill,<br />

M.M. Heimesaat, C. Tschoepe. University Hospital Benjamin<br />

Franklin, Cardiology Dept., Berlin, Germany<br />

Background: Increased activity of matrix metalloproteinases (MMPs) disturb the<br />

integrity of the cardiac extracellular matrix in different cardiomyopathies and it was<br />

shown that increased MMP levels in cardiac failure are delirious for cardiac function<br />

after myocardial infarction or pressure overload cardiomyopathy. Therefore,<br />

inhibition of MMPs is generally supposed to be beneficial. Nevertheless, MMP-2<br />

(a gelatinases) can also degrade inflammatory cytokines as well as other proteins<br />

and therefore might have anti-inflammatory properties, but whether that is<br />

relevant in vivo is unknown. To further investigate the potential role of MMP-2<br />

in inflammatory cardiomyopathies, we used a viral induced myocarditis model,<br />

which is characterized by invading inflammatory cells and cytokines, and investigated<br />

the effect of gene deletion of MMP-2 after viral myocarditis on cardiac<br />

inflammation and cardiac function utilizing knock out mice.<br />

Methods: 80 MMP-2 knockout mice and their wildtypes littermates were used in<br />

the current study. 40 were infected with coxsackievirus B3 (CVB3) to induced<br />

acute murine myocarditis. We investigated the LV function of all mice after 7<br />

days using pressure volume measurements by conductance catheter in vivo and<br />

measured mortality. Furthermore, myocardial inflammation was analyzed by immunohistochemical<br />

detection of inflammatory cells and by measuring the protein<br />

and mRNA abundance of inflammatory cytokines. Furthermore, cardiac apoptosis<br />

was analyzed by TUNEL staining and by measuring the protein content of bax<br />

and bcl-2 and caspase 3. Moreover, the viralload was analyzed.<br />

Results: Interestingly, MMP-2 gene deletion aggravated cardiac function after<br />

CVB3 myocarditis compared to their CVB3 wildtype littermates. This was accompanied<br />

by increased cardiac inflammation with highly increased numbers of inflammatory<br />

cells (+450%) as well as highly increased abundance of pro inflammatory<br />

cardiac cytokines in the cardiac tissue. Furthermore, we measured increased<br />

apoptosis (+250%) in the cardiac tissue in both knock out mice strains<br />

as well as an increased viral load (+350%) in MMP knock out mice. Additionally,<br />

we observed high mortality in MMP-2 knock mice (survival rate 10%) compared<br />

to wildtypes (95%) after CVB3 induced myocarditis.<br />

Conclusion: During acute viral myocarditis, gene deletion of MMP-2 aggravates<br />

cardiac injury. These data suggest that MMP-2 has beneficial effects in viral induced<br />

cardiomyopathy and might be necessary for virus control in myocarditis,<br />

which is in contrast to their delirious role in non viral induced cardiomyopathies.<br />

P2737 Intermediate dose of pentaglobin eradicates<br />

inflammation in parvo B19 and adenovirus positive<br />

myocarditis<br />

B. Maisch, H. Haake, S. Schlotmann, R. Funck, A. Richter,<br />

S. Pankuweit. Philipps-University, Department of Internal Medicine<br />

- Cardiology, Marburg, Germany<br />

Background and purpose: Treatment of viral myocarditis is a matter of controvery<br />

and discussion.<br />

Patients: 152 consecutive patients with myocarditis according to the quantitative<br />

World <strong>Heart</strong> Federation Criteria (>14 infiltrating cells/mm2 by endomyocardial<br />

biopsy (EMB)) were analysed for cardiotropic agents. In 90 pts parvoviruses<br />

B19 (59,5%) and in 36 pts adenoviruses (23,8%) were assessed by PCR as<br />

causative viral pathogens. All virus positive patients were treated with 10 g/day<br />

Pentaglobin an i. v., enriched IgG, IgA and IgM preparation, at day 1 and 3. After<br />

six months all patients were reevalutated clinically, 73 patients (48%) in addition<br />

by EMB.<br />

Methods: We compared the following parameters before and after therapy:<br />

left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter<br />

(LVEDD), shortening fraction (SF) by transthoracic echocardiography and LVEF<br />

or the left ventricular end-diastolic volume index (LVEDVI) using angiography. For<br />

exercise capacity we evaluated exercise ECG by treadmill test and clinical parameters<br />

according to the NYHA classification, before and after therapy.<br />

Results: After Pentaglobin therapy, all patients demonstrated a significant clinical<br />

improvement of the NYHA class, of exercise capacity and of LVEF (from 54,4 to<br />

60,0%, p


cardiomyocyte apoptosis was highest on day 5 (0.16±0.01% vs. 0.03±0.01% in<br />

controls, p


440 Pericardial and myocardial disease<br />

P2744 Late onset valvular and myocardial dysfunction in<br />

Hodgkin lymphoma survivors<br />

T. Wethal1 , M. Lund2 , S.D. Fossa1 , J. Kjekshus1 , T. Edvardsen1 ,<br />

A.H. Pripp2 ,H.Holte2 , A. Fossa2 . 1University of Oslo, Department<br />

of Cardiology., Oslo, Norway; 2Rikshospitalet University Hospital,<br />

Department of Respiratory Medicine, Oslo, Norway<br />

Background: Hodgkin’s lymphoma survivors (HLS) have an elevated risk for cardiovascular<br />

diseases that appear several years after radiotherapy. HLS have frequently<br />

reported valvular dysfunction and many have received anthracyclines,<br />

which increase the risk for cardiomyopathy. Little is known about the progression<br />

of valvular dysfunction in HLS and whether anthracyclines negatively affect myocardial<br />

function beyond 10 years after treatment.<br />

Methods: A longitudinal follow-up study was performed with 47 patients diagnosed<br />

with Hodgkin’s lymphoma. Echocardiography was performed in 1993 and<br />

again in this study between 2005 and 2007, approximately 9 and 22 years after<br />

initial mediastinal radiotherapy. Twenty-seven (57%) of the patients had received<br />

treatment with anthracyclines.<br />

Results: The second echocardiograph indicated 38% of the patients had mild<br />

to severe aortic stenosis not previously reported. Of those without and with mild<br />

valvular regurgitation in 1993, 39% developed moderate regurgitation in the aortic<br />

and/or the mitral valve. Of 24 patients with moderate valvular regurgitation in<br />

1993, 33% progressed to severe valvular regurgitation or developed moderate<br />

to severe valvular regurgitation in a valve unaffected in 1993. Multiple linear regression<br />

analyses demonstrated that use of anthracyclines significantly predicted<br />

deterioration in left ventricular function (left ventricular end systolic diameter, B =<br />

0,089 (95% CI: 0,006 – 0,172), p = 0,036; interventricular septum, B = - 0,161<br />

(95% CI: - 0,297 - - 0,025), p = 0,021; left ventricular posterior wall, B = - 0,178<br />

(95% CI: - 0,325 - - 0,031), p = 0,019; and left ventricular end diastolic diameter,<br />

B = 0,051 (95% CI: - 0,001 – 0,102), p = 0,053).<br />

Discussion: Severe progression of valvular disease was found in four out of ten<br />

HLS ∼22 years after radiotherapy despite normal echocardiographic findings after<br />

9 years. Treatment with anthracyclines markedly aggravated left ventricular<br />

function at 22 years compared to 9 years after treatment, and compared to those<br />

that received mediastinal radiotherapy alone or with adjuvant chemotherapy other<br />

than anthracyclines.<br />

P2745 NS1 specific type-1 and cytotoxic effector T-cells with<br />

TRBV11 dominance in a patient with parvovirus B19<br />

associated inflammatory cardiomyopathy<br />

M. Noutsias 1 ,M.Streitz 2 , R. Volkmer-Engert 2 , M. Rohde 1 ,<br />

G. Brestrich 2 , K. Klippert 2 ,K.Kotsch 2 , U. Kuehl 1 ,H.D.Volk 2 ,<br />

F. Kern 2 . 1 Charite - Campus Benjamin Franklin, Department of Cardiology &<br />

Pneumonology, Berlin, Germany; 2 Charite - Campus Mitte, Institute of Medical<br />

Immunology, Berlin, Germany<br />

Background: Parvovirus B19 (B19V) is the most commonly detected virus in<br />

endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy<br />

(DCMi). Despite the importance of T-cells in antiviral defense, little is known about<br />

the role of B19V specific T-cells in this entity.<br />

Methods & Results: Using B19V proteom-spanning peptide pools, strong CD8+<br />

T-cell responses (intracellular IFNg secretion) were elicited to the 10-amico-acid<br />

peptides SALK (19.7% of all CD8+ cells) and QSAL (10%) in a DCMi patient<br />

with an exceptionally high myocardial B19V viral load (115,091 viral copies/μg<br />

nucleic acids) and B19V viremia in the initial presentation. Additionally, two further<br />

peptides were identified: GLCP (0.53%) and LLHT (0.03%). Real-time RT-PCR of<br />

SALK- and GLCP-reactive T-cells enriched by an IFNg secretion assay revealed<br />

an over proportional T-cell receptor Vbeta (TRBV) 11 expression. Furthermore,<br />

dominant expression of type-1 (IFNg, IL2, IL27 and T-bet) and of cytotoxic T-cell<br />

markers (CTL: Perforin and Granzyme B) were found, whereas gene expression<br />

indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low.<br />

Conclusions: Our results show that B19V Ag-specific effector T-cells are involved<br />

in B19V associated DCMi. In particular, a dominant role of TRBV11 and<br />

type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested.<br />

This novel B19V proteom-spanning peptide pool based approach will lend<br />

itself very well to the in depth study of this phenomenon.<br />

P2746 Molecular pathogenesis of acute rheumatic fever and<br />

rheumatic heart disease<br />

B. Maisch1 , T.G. Loof2 , G.S. Chhatwal2 ,A.Grover3 , V. Ruppert 1 ,<br />

S. Pankuweit 1 . 1University Hospital Giessen and Marburg, Internal<br />

Medicine - Cardiology, Marburg, Germany; 2Helmholtz Center<br />

for Infection Research, Infection Immunology Research Group and Depar,<br />

Braunschweig, Germany; 3Post Graduate Institute of Medical Education,<br />

Department of Cardiology, Chandigarh, India<br />

Acute rheumatic fever (ARF) is an autoreactive disease secondary to a group A<br />

streptococcal infection involving the heart, joints, skin and brain. During an infection<br />

activated antigen presenting cells present the bacterial antigen to helper T<br />

cells, which subsequently activate B cells and induce the production of antibodies<br />

against the cell wall of Streptococcus. These antibodies also react against the<br />

myocardium, producing the symptoms of rheumatic heart disease. The cell wall of<br />

group A streptococcus pyogenes is composed of branched polymers containing<br />

"M proteins" which are highly antigenic and may crossreact with cardiac myosin.<br />

Here we focus on heart specific antibodies in sera from patients with rheumatic<br />

fever.<br />

Methods: Sera from 9 patients with acute rheumatic fever, 17 patients with<br />

chronic/rheumatic heart disease (CHD/RHD) and 17 controls from individuals<br />

without heart disease were probed in one- and two-dimensional Western blots<br />

for reactivity against heart tissue antigens, respectively.<br />

Results: Antibodies against fragments of the myosin heavy chain were demonstrated<br />

in 77% of sera of patients with ARF, in 35% of sera of patients with<br />

CHD/RHD but not in control sera. Antibodies directed against proteins with a<br />

molecular weight of 50kd, 45kd,37 kd and to a much lesser extend of 40kd were<br />

directed against a lysate of cardiac tissue (Fig. 1). Antibodies against 55 kd, 50kd,<br />

45kd proteins from a lysate of streptococcus M-protein were not found in controls<br />

but in 44 - 77% of patients with ARF and in about 12 - 25% of cases in CHD/RHD<br />

(Fig. 2).<br />

Figure 1 and Figure 2<br />

Conclusion: Sequence analysis of the above characterized proteins will possibly<br />

identify additional myocardial antigens involved in the secondary immunopathogenesis<br />

of ARF and CHD/RHD.<br />

P2747 Use of N-terminal pro-B-type natriuretic peptide to<br />

predict mortality and treatment failure in patients with<br />

community-acquired pneumonia<br />

M. Noveanu, T. Breidthardt, M. Potocki, T. Reichlin, M. Christ-Crain,<br />

D. Stolz, K. Laule, M. Tamm, B. Mueller, C. Mueller. University<br />

Hospital Basel, Department of Internal Medicine, Basel, Switzerland<br />

Puropse: Community-acquired pneumonia (CAP) is the most common infectious<br />

disease addressed by clinicians and an important cause of mortality and morbidity<br />

worldwide. Risk stratification in CAP is still complex and time-consuming.<br />

We hypothesized that cardiac stress may determine outcome also in non-cardiac<br />

disease such as CAP.<br />

Methods: N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP), a marker of<br />

cardiac stress and inflammation marker (C-reactive protein- CRP, white blood cell<br />

count- WBC, procalcitonin- PCT) as well as the pneumonia severity index (PSI)<br />

were determined in 302 consecutive patients presenting to the emergency department<br />

with CAP. The accuracy of these parameters to predict death was evaluated<br />

as the primary endpoint. Prediction of treatment failure was considered the<br />

secondary endpoint.<br />

Results: NT-proBNP levels were significantly higher in non-survivors compared<br />

to survivors (median 3926 [IQR 790-15500] vs. 643 [170-3436] pg/ml, p


higher for NT-proBNP (area under the curve (AUC) 0.744; 95% confidence interval<br />

CI 0.648-0.840) compared to the PSI (AUC 0.706; 95%CI 0.622-0.791), PCT<br />

(AUC 0.688; 95%CI 0.600-0.755) or CRP (AUC 0.596; 95%CI 0.487-0.705). The<br />

accuracy of NT-proBNP (AUC 0.690; 95%CI 0.607-0.772) to predict treatment failure<br />

was also superior compared to PCT (AUC 0.662; 95% CI 0.589-0.735) and<br />

CRP (AUC 0.590; 95%CI 0.508-0.671), but inferior to PSI (0.739; 95%CI 0.666-<br />

0.812).<br />

Conclusions: In patients with CAP, NT-pro BNP is a more powerful predictor of<br />

death and treatment failure than the routinely determined marker of inflammation<br />

PCT, CRP or WBC. Regarding the prediction of death, NT-proBNP in fact seems<br />

superior to the current gold-standard PSI. Cardiac stress seems to determine<br />

outcome in non-cardiac disease such as CAP.<br />

P2748 Long term cardiac remodelling in chronic Chagas’<br />

heart disease<br />

P.R. Benchimol Barbosa1 , G.S. Duque2 , J. Barbosa-Filho3 . 1Rio de<br />

Janeiro Fire Dept., UERJ, USF (USA), Cardiology, Rio De Janeiro,<br />

Brazil; 2State University of Rio de Janeiro, Cardiology, Rio De<br />

Janeiro, Brazil; 3Gama Filho University, Rio De Janeiro, Brazil<br />

Introduction and Objectives: Cardiac remodeling impacts adverse outcome and<br />

has not been fully investigated in Chagas’ disease. Clinical, echocardiographic<br />

and electrocardiographic variables were assessed in long term longitudinal study<br />

of subjects with chronic Chagas’ disease for adverse outcomes, defined as new<br />

onset atrial fibrillation episode lasting >24h (AF), nonfatal embolic stroke and<br />

cardiac death.<br />

Methods and Results: Fifty adult outpatients (34 to 74 years old, 31 females)<br />

staged according to Los Andes Classification I, II and III and complaining of palpitations<br />

were enrolled. During a follow-up of (mean±SD) 84.2±39.0 months, nine<br />

subjects developed AF (incidence: 3.3±1.0%/year), five had nonfatal embolic<br />

stroke (incidence: 1.3±1.0%/year), and nine died (mortality rate: 2.3±0.8%/year),<br />

five suddenly. The rate of both left ventricular (LV) mass increase and LV ejection<br />

fraction reduction in subjects who experienced adverse outcomes (respectively,<br />

16.4±20.0 g/year and -8.6±7.6%/year) was significantly higher than in those<br />

who did not (respectively, -8.2±8.4 g/year; p = 0.03; and -3.0±2.5%/year; p =<br />

0.04, Fig 1). In a stepwise multivariate Cox proportional-hazard regression model,<br />

Los Andes Class III (HR=20.8; 95%CI [2.7–158.8], p=0.003) and new onset AF:<br />

HR=4.2; 95% CI [1.1–15.7]) were independent predictors for adverse outcomes.<br />

Frequency domain analysis of signal averaged ECG was a significant predictor<br />

for cardiac death (HR: 5.4; 95%CI [1.4-20.5]; p=0.01).<br />

Long term cardiac remodeling.<br />

Conclusion: Los Andes Class III and new onset atrial fibrillation are independent<br />

long-term predictors for adverse outcomes in chronic Chagas’ disease. The rate<br />

of LVM enlargement and LV systolic function deterioration impacts survival, and<br />

myocardial electrical transients underlie death mechanism in this population.<br />

P2749 Exercise training improved myocardial response to<br />

isoproterenol stimulation in rats fed with a<br />

high-fat-diet induced heart triacylglycerols<br />

accumulation<br />

C. Lajoie1 ,J.M.Lavoie2 , M.C. Aubin3 , R. Clement3 , H. Gosselin3 ,<br />

A. Calderone3 . 1UQTR, Kinesiologie, Trois-Rivieres, Canada;<br />

2 3 Montreal University, Kinesiology, Montreal, Canada; Montreal <strong>Heart</strong> Institute,<br />

Pharmacology, Montreal, Canada<br />

Excessive accumulation of fat within the cardiomyocytes is nefarious for the heart.<br />

The purpose of the present study was to assess the effect of an exercise training<br />

program conducted concurrently with a high-fat (HF)-diet regimen on the effect<br />

of a β adrenergic agonist stimulation on myocardial performance. Two groups of<br />

rats were fed either a standard (SD) or a High fat (HF) diet (42% kcal) for 8 wk<br />

and were additionally assigned either to a sedentary (Sed) or a treadmill-trained<br />

group (HF-Sed; n=9 SD-Sed; n=11 HF-TR; n=10 and SD-TR; n=8). Training (5<br />

days/wk) was initiated at the same time as the HF diet and was progressively increased;<br />

reaching 60 min at 26 m/min, 10% grade, for the last 4 wk. <strong>Heart</strong> weight<br />

of HF-Sed rats (0,95g) was significantly higher as compared to SD-Sed rats<br />

(0,88g). HW/BW was significantly lower in HF-Sed (2,8mg/g) as compared to SD-<br />

Sed (3,1mg/g). Exercise training normalized HW/BW in HF-diet rats. At the end<br />

of the 8-wk period, HF-Sed rats exhibited 85% higher heart triacylglycerol con-<br />

Pericardial and myocardial disease / Unstable angina 441<br />

centration than SD-Sed rats (means ± sd: 8,5±0,9 vs 4,6±0,5 mg/g; p


442 Unstable angina<br />

Results: The incidence at 30 days of the primary endpoint was 60 percent in<br />

the group assigned to immediate PCI and 39 percent in the group assigned to<br />

deferred PCI. (Relative risk 1.5, 95 percent, CI 1.09-2.15; p=0.004). There were<br />

no deaths in both groups. Myocardial infarction was significantly more frequent in<br />

the group assigned to immediate PCI (60 percent vs 37 percent, relative risk 1.6,<br />

CI 1.12-2.28, p=0.005). Unplanned revascularization was similar in both groups.<br />

The observed difference was preserved over a 6 month follow up period. (Figure<br />

1, logrank p=0.008)<br />

Fig 1. primary composite EP at 6 months.<br />

Conclusions: The results showed no benefit associated with routine immediate<br />

intervention in non-refractory intermediate to high risk NSTE-ACS patients. Immediate<br />

PCI was associated with an increased rate of MI as compared to a 24-48<br />

hours deferred strategy.<br />

P2752 Aspirin use is associated with reduction in 15 year<br />

mortality in patients presenting with acute ischemic<br />

chest pain- The olmsted county chest pain study<br />

V. Mathew 1 , R. Lennon1 , A. Aneja2 ,S.Bansilal2 ,H.Wiste1 ,<br />

G. Reeder1 , M.E. Farkouh2 on behalf of Olmsted County Acute<br />

Chest Pain Study Group. 1Mayo Clinic, Cardiology, Rochester, United States of<br />

America; 2Mount Sinai School of Medicine, Cardiology, New York, United States<br />

of America<br />

Purpose: The long-term mortality benefit of aspirin (ASA) in a population-based<br />

cohort with definite unstable angina (UA) has not been well documented.<br />

Methods: We retrospectively identified all residents of Olmsted County (OC),<br />

Minnesota presenting to local emergency departments with acute chest pain from<br />

Jan 1985 through Dec 1992. Medical records were obtained from the Rochester<br />

Epidemiology Project, the OC Health Care Utilization and Expenditures Database<br />

and reviewed by a nurse abstractor. Follow-up mortality data for a median duration<br />

of 16.7 years was obtained through State of Minnesota Electronic Death<br />

Certificates and Death Tapes, OC Electronic Death Certificates, and Mayo Clinic<br />

records. Aspirin therapy had emerged as standard of care during this time period.<br />

Patients were stratified by ASA use at discharge, in hospital, both, and none. Cox<br />

models were used to estimate the adjusted association between ASA use and<br />

deaths.<br />

Results: 1628 (23.9%) patients were identified with definite UA. Mean age of<br />

cohort was 66y, and 60% were men. Aspirin was given both in hospital and at<br />

discharge in 41%, only in hospital in 12%, only on discharge in 5%, and none at<br />

all in 42%. There were 986 deaths over over the median follow-up of 16.7 years.<br />

Survival rates are shown in the Kaplan Meier figure. Risk factor adjusted data<br />

showed that ASA use was associated with a lower mortality rate when given both<br />

in hospital and at discharge, HR 0.75 (95% CI 0.67, 0.84), in-hospital only HR<br />

Aspirin use and long-term mortality.<br />

0.83 (95% CI 0.71, 0.99) and discharge only HR 0.77 (95% CI 0.61, 0.96) when<br />

compared with no ASA at all.<br />

Conclusions: Any ASA use for UA in a population-based cohort is associated<br />

with a reduction in long term mortality. This unique community database confirms<br />

our practice of routine aspirin use to reduce mortality.<br />

P2753 The impact of optimal medical therapy and<br />

revascularization on outcome of patients with chronic<br />

kidney disease and on dialysis who presented with<br />

acute coronary syndrome<br />

L. Bonello1 , A. Delabriolle1 ,P.Roy1 , D. Steinberg1 ,Z.Xue1 ,<br />

R. Torgusson1 ,L.Satler1 ,A.Pichard1 , J. Lindsay 1 , R. Waksman2 . 1Washington hospital center, internal medicine, cardiology, Washington, United States of<br />

America; 2Washington Hospital Center, Cardiovascular Research Institute,<br />

Washington, United States of America<br />

Objectives: We aimed to investigate the prognosis of acute coronary syndrome<br />

(ACS) in chronic kidney disease (CKD) patients with and without dialysis compared<br />

to patients without CKD when receiving optimal contemporary medical<br />

therapy and percutaneous coronary intervention (PCI).<br />

Background: Coronary artery disease (CAD) is the main cause of death in patients<br />

with CKD. The poor prognosis associated with ACS in these patients has<br />

been related to therapeutic nihilism.<br />

Methods: The study included 2357 ACS patients who had PCI. According to their<br />

creatinine level and medical history, they were divided into 3 groups: dialysis = 73;<br />

CKD = 293; and control = 1991. Rates of cardiovascular events were recorded<br />

over a 1-year follow-up period.<br />

Results: Patients in all groups received similar contemporary medical therapy for<br />

ACS and PCI. On admission, CKD patients and patients under dialysis more often<br />

presented with cardiogenic shock (p = 0.05 and 0.02, respectively). A graded increase<br />

in the rate of major adverse cardiovascular events at 1 year was observed<br />

with decreasing renal function (control 13% vs CKD 22.9% vs dialysis 45.2%; p<br />


or higher) in 85 patients (4.2%). Median TnT rise was 0.09ng/ml (range 0.01-<br />

5.62). Patients were split into 3 age groups as shown in table 1. Median troponin<br />

requests per year 410 (range 247-457).<br />

Of the patients with a detectable troponin only 61 (29%) were admitted to hospital<br />

within 7 days of the sample collection. At both 30 days and one year the<br />

Kaplan Meier survival function shows a statistically significant difference (log<br />

rank test 0.1ng/ml.<br />

Table 1<br />

Age (yrs) Number Detectable TnT TnT>0.1 Admitted within 1 week of TnT>0.1<br />

(TnT>0.01ng/ml) (ng/ml) (ng/ml)<br />

75 518 117 (22.6%) 35 (6.8%) 7 (20%)<br />

Conclusions: Patients suspected of having an ACS should be admitted for risk<br />

assessment and treatment. When admission to hospital is inappropriate due to<br />

significant co-morbidity, measurement of TnT will add little to the management of<br />

the patient. We recommend that serum troponin should not be measured within<br />

primary care.<br />

P2755 Efficacy of coronary revascularization in patients with<br />

acute chest pain managed in chest pain unit<br />

P. Merlos Diaz 1 , J. Sanchis Fores 1 ,V.BodiPeris 1 , J. Nunez Villota 1 ,<br />

L. Mainar Latorre 1 ,R.Robles 1 , E. Santas 1 ,A.Cortell 1 ,X.Bosch 2 ,<br />

A. Llacer 1 . 1 Hospital Clinic Universitari, Cardiologia, Valencia,<br />

Spain; 2 Hospital Clinic, Cardiologia, Barcelona, Spain<br />

Purpose: Chest pain unit protocols involve exhaustive evaluation prompting<br />

revascularizations. Our aim was to investigate the safe discharge of patients<br />

deemed at low risk and the prognostic impact of revascularization of patients<br />

deemed at high risk.<br />

Methods: The study population consisted of 1088 patients presenting at the<br />

emergency department with chest pain without ischemia in the electrocardiogram<br />

or troponin elevation. They were managed by a chest pain unit protocol including<br />

early exercise testing. Three groups were distinguished: Group I, patients discharged<br />

after exercise testing (n=424); Group II, unstable angina ruled out after<br />

in-hospital evaluation (n=208); and Group III, unstable angina confirmed or not<br />

ruled out (n=456). In Group III, 183 patients were revascularized at the index<br />

episode. The end point was one-year death or myocardial infarction. Adjustments<br />

were made for patient characteristics and a propensity score for revascularization<br />

(C-statistic=0.83).<br />

Results: Groups I and II showed the lowest end point rate compared with Group<br />

III (Group I: n=7, 1.7%; Group II: n=1, 0.5%; Group III: n=62, 13.6%; p=0.0001). In<br />

Group III, despite the worse baseline risk profile of non-revascularized patients,<br />

revascularization did not improve outcome (HR=1.4, 95% CI 0.7 to 2.5, p=.4)<br />

although decreased post-discharge revascularization (HR=0.3, 95% CI 0.1 to 0.7,<br />

p=0.008). After excluding non-fatal periprocedural infarctions, revascularization at<br />

the index episode reduced the end point (3.8% vs 10.7%, p=0.007).<br />

Conclusions: Chest pain unit protocols are associated with safe discharge. Early<br />

revascularizations, however, do not improve one-year outcome in terms of death<br />

or myocardial infarction mainly because periprocedural events neutralize any potential<br />

benefit.<br />

P2756 CD34+ cells in patients with non-ST elevation acute<br />

coronary syndrome<br />

M.M. Ruda, O.N. Vyborov, T.I. Arefieva, Y.A. Karpov, Y.V. Parfyonova.<br />

Russian Cardiology Research Center, Moscow, Russian Federation<br />

Purpose: Circulating progenitor cells (CPCs) play an important role in endothelial<br />

repair and in angiogenesis. We studied whether CPCs number is associated with<br />

severity of coronary artery disease (CAD) and presence or absence of myocardial<br />

damage, and how CPCs number changes in the early period after non-ST<br />

elevation acute coronary syndrome (ACS).<br />

Methods: CD34+ cells number was measured in peripheral blood of 77 patients<br />

(40-69 years old, mean age 56) by flow-cytometry: in 27 patients with ACS (16<br />

– cardiac troponin-negative (cTn–) and 11 cTn-positive (cTn+)) within 24h after<br />

onset of symptoms; 32 patients with stable angina pectoris (SAP) and 18 subjects<br />

without CAD – control group (CG). Besides, in 18 patients with ACS we<br />

counted the number of CD34+ cells on the 11th day (the 2nd point) after onset of<br />

symptoms as well as in 24h (the 1st point).<br />

Results: All patients with CAD had reduced numbers of CD34+ cells as compared<br />

to CG: decreased by 39.3% in ACS group (p=0.002) and showed the same<br />

tendency (by 18.5%) in SAP group (p=0,076). Furthermore, in patients with ACS<br />

CPCs number was reduced by 20.8% vs. patients with SAP (p=0.032). cTn– ACS<br />

patients had reduced number of CPCs in comparison with CG (p=0.028) and had<br />

no significant difference from SAP group (p=0.251). Most interestingly, cTn+ patients<br />

had further reduced number of CPCs than cTn– patients (by 29%, p=0.041)<br />

Unstable angina 443<br />

(than SAP, p=0.009 and CG, p=0.002). By the 11th day CD34+ cells number in<br />

ACS group had noticeably increased in comparison with the 1st day (p=0.078)<br />

and had almost reached the values of SAP patients (p=0.443), while was still<br />

significantly reduced compared to CG (p=0.043).<br />

Conclusions: In peripheral blood of CAD patients CPCs numbers are reduced.<br />

The association of CPCs number with CAD severity is shown by its progressive<br />

reduction for patients with the following conditions: SAP, ACS cTn– and ACS<br />

cTn+. We suggest that above endothelial damage, myocardial damage plays the<br />

leading role in CPCs number reduction. The CPCs number in ACS patients has<br />

a tendency to recover from the 1st to the 11th day.<br />

P2757 Quality indicators in management of acute coronary<br />

syndromes in Europe. Results from Euro <strong>Heart</strong><br />

Survey- ACS registry<br />

F. Schiele1 , M. Tubaro2 ,K.Fox3 ,J.P.Bassand4 ,A.Gitt5 . 1Pole Coeur-Poumons, Department of Cardiology, Besancon, France;<br />

2 3 4 Cardiology, Roma, Italy; Cardiology, Edinburgh, United Kingdom; Cardiology,<br />

Besancon, France; 5Cardiology, Ludwigshafen, Germany<br />

Rationale: Based on guidelines, quality indicators (QI) can be defined. The rate<br />

of use of these indicators, in STEMI and NSTE-ACS patients and their impact on<br />

clinical outcome needs to be documented.<br />

Methods: QI were defined for STEMI and NSTE-ACS by expert consensus for<br />

assessment at admission, in-hospital treatment, time delays, treatment at discharge<br />

and for patients with ACS and heart failure. These QI were applied to<br />

6485 patients (2830 STEMI and 3655 NSTE-ACS) included in the Euro <strong>Heart</strong><br />

Survey-ACS Registry. The rate of use and the impact of these<br />

QI was tested on in-hospital survival and expressed as odds ratio.<br />

Results: Definitions and rate of use in STEMI and NSTE-ACS are displayed on<br />

the table. The lowest rates of use were observed for clopidogrel in-hospital and at<br />

discharge, ACE inhibitors or ARB and, in patients with heart failure, betablockers<br />

and aldosterone antagonists. Excepted for patients with acute heart failure, QI<br />

were significantly more often used in STEMI than in NSTE-ACS patients. All QI<br />

related to in-hospital management were univariate predictors of in-hospital survival.<br />

Table 1<br />

Quality indicators Total STEMI NSTEACS OR (95% CI) on survival<br />

6485 2830 3655<br />

Troponin assessment < 48 h 85.1 84.1 85.8 1.82 (1.40-2.37)<br />

Assessment of LV function<br />

In hospital medication<br />

93.0 92.9 93.1 3.61 (2.64-4.94)<br />

Aspirin 96.4 97.2 95.7 3.15 (2.13-4.66)<br />

Clopidogrel 76.4 83.5 70.9 2.23 (1.77-2.80)<br />

ACEI or ARB 82.4 84.3 80.8 4.72 (3.77-5.92)<br />

Anticoagulation<br />

Time delays (median)<br />

96.9 98.9 95.4 0.93 (0.56-1.90)<br />

Time from symptoms to admission 3:15 2:55 3:45 ns<br />

Delay from admission to PCI<br />

Discharge medication<br />

9:30 1:00 42:30 ns<br />

Aspirin 93.3 95.6 91.5<br />

Clopidogrel 66.5 77.7 58.2<br />

Aspirin + clopidogrel 63.6 75.6 54.8<br />

ACEI or ARB 80.3 84.8 77.0<br />

Statins 83.4 89.0 79.3<br />

LVEF < 0.40 or heart failure n=365 n=153 n=182<br />

Betablockers 83.1 85.6 80.6<br />

ACEI or ARB 87.8 91.3 84.4<br />

Aldosterone antagonists 40.4 43.1 37.8<br />

In-hospital mortality 5.1 7.9 3.0<br />

Conclusions: QI, as defined for the EHS-ACS, provide important information on<br />

the degree of application of guidelines-recommended treatment and are related<br />

with survival.<br />

P2758 High-risk markers do not guide treatment strategies<br />

of elderly acute coronary syndrome patients: real-life<br />

data from the Contacts-registry<br />

J. Lumme 1 , K.E.J. Airaksinen 2 , J. Hartikainen 3 ,I.Tierala 4 ,<br />

S. Vikman 5 on behalf of Contacs Study Group. 1 Oulu University<br />

Hospital, Oulu, Finland; 2 Turku University Hospital, Turku, Finland; 3 Kuopio<br />

University Hospital, Kuopio, Finland; 4 Helsinki University Hospital, Helsinki,<br />

Finland; 5 Tampere University Hospital, Tampere, Finland<br />

Purpose: We analyzed factors in the physicians’ decision-making leading to conservative<br />

treatment strategy in acute coronary syndrome (ACS).<br />

Methods: A nationwide, multicenter prospective registry on conservatively<br />

treated ACS patients (n=967) in 49 centers representing the whole health care<br />

system from primary care to tertiary hospitals.<br />

Results: Median age of the patients was 78 years and 49% of them were women.<br />

Coronary angiography was performed in 35% of the patients during the index<br />

hospitalisation. After adjustment for age and gender, angiography was performed<br />

less often in patients with diabetes (29% vs. 38%, p=0.023), polyvascular disease<br />

(16% vs. 38%, p


444 Unstable angina / Reperfusion<br />

of the patients (33%), estimated high risk/benefit ratio (14%) and in 25% of the patients<br />

angiography was considered "unnecessary". Patients referred to coronary<br />

angiography were more often treated with ESC guideline-based medication: aspirin<br />

95% vs. 88%, p=0.0026), clopidogrel (56% vs. 33%, p


teria as a final Thrombolysis In Myocardial Infarction (TIMI) flow ≤ 2 or final TIMI<br />

flow 3 with a myocardial blush grade (MBG) < 2. Electrocardiographic definition<br />

of no-reflow included the lack of ST segment resolution (defined as a reduction<br />


446 Reperfusion / Prognosis in ST-elevation myocardial infarction<br />

gression analysis using this cut-point. Other variables like age, symptoms-needle<br />

time, previous AMI and AMI localisation were included in the model.<br />

Results: During the study period, 80 patients admitted with STEMI were treated<br />

with tenecteplase. The treatment failure rate was 29%. Using plot points from<br />

ROC curve (area under the curve=0,76, p75 years 38.4% 17.5% 16.7%


cantly correlated to in-hospital death. There was a significant interaction between<br />

hemoglobin levels and leukocytosis (p


448 Prognosis in ST-elevation myocardial infarction<br />

Conclusion: Major bleeding complications in ACS are independently associated<br />

with a 2-fold increased hospital mortality in clinical practice in Europe.<br />

P2774 The ratio of contrast load to Glomerular Filtration<br />

Rate (GFR) as a predictor for renal dysfunction and<br />

subsequent mortality following emergent PCI for<br />

STEMI<br />

R. Kornowski, H. Vaknin Assa, T. Bental, I. Ben Dor, D. Brosh,<br />

E. Lev, S. Fuchs, A. Assali. Rabin Medical Center, Petach Tikva,<br />

Israel<br />

Background: The ratio of contrast load utilized during PCI to baseline glomerular<br />

filtration rate (GFR) has been proposed as a surrogate marker for the development<br />

of contrast induced nephropathy post elective PCI. We sought to use<br />

the ratio in order to predict the renal and cardiac prognosis among patients with<br />

STEMI who were treated using primary PCI.<br />

Methods: Data from consecutive patients who underwent PCI for STEMI at our<br />

hospital were imputed into a dedicated clinical database. We compared the clinical<br />

outcome (death, re-MI, TVR, MACE) at 6 month in patients distinguished by<br />

the ratio of contrast load utilized during PCI to baseline GFR prior to PCI.<br />

Results: Results of 871 consecutive (non-shock) patients with STEMI are summarized<br />

in the table:<br />

Contrast Volume/GFR Ratio 0.14-1.5 (N=290) 1.5-2.35 (N=290) >2.35 (N=290)<br />

Age (years) 62±10 63±12 63±11<br />

Males (%) + 83 86 76<br />

Diabetes Mellitus (%) 24 23 28<br />

Anterior MI (%) + 37 46 56<br />

Multivessel Disease (%) + 46 56 70<br />

Killip>1(%) + 11 10 22<br />

Successful PCI (%) 98 98 92<br />

Multivessel PCI (%) + 2.4 8.6 13.8<br />

EF


nosis in patients with myocardial infarction (MI). In this context, left atrial volume<br />

index (LAVI) was shown to be an independant and powerful predictor of mortality<br />

after MI. The aim of this study was to evaluate the prognostic value of LAVI in<br />

patients presenting with first anterior MI, and treated by modern clinical practice.<br />

Methods: This prospective study included 255 patients with inaugural anterior<br />

MI. Clinical and echocardiographic data were collected at baseline. LAVI was<br />

determined in a blinded analysis at a core echocardiographic laboratory. Patients<br />

with LAVI 32 mL/m 2 . The endpoint was a composite of all-cause mortality or<br />

hospitalization for heart failure.<br />

Results: Acute reperfusion was attempted in 210 patients (82%). At discharge,<br />

94% of patients received a beta-blocker, 96% an angiotensin-converting enzyme<br />

inhibitor or angiotensin II receptor blocker. Fifty-one (20%) patients had a LAVI<br />

>32 mL/m 2 . During a median follow-up of 1229 days, 40 patients (16%) died or<br />

were hospitalized for heart failure. LAVI was a significant predictor of all-cause<br />

mortality or hospitalization for heart failure (p=0.001). The Kaplan-Meier survival<br />

curves according to baseline LAVI are shown in the figure below. However LAVI<br />

did not prove to be an independent predictor by multivariate Cox analysis (hazard<br />

ratio 1.41, 95%CI 0.67-2.96, p=0.36).<br />

Kaplan-Meier curves according to LAVI.<br />

Conclusions: Increased LAVI is a powerful, but non independant, predictor of<br />

clinical outcome in term of death or hospitalization for heart failure, after first anterior<br />

MI in patients treated according to modern practice.<br />

P2779 Does the time of primary cardiac arrest in relation to<br />

PCI affect the outcome?<br />

F.M. Szymanski, M. Grabowski, G. Karpinski, A. Hrynkiewicz,<br />

K.J. Filipiak, G. Opolski. Medical University of Warsaw, First<br />

Cardiology Department, Warsaw, Poland<br />

Purpose: No data are available for the prognostic value of primary cardiac arrest<br />

(CA) due to ventricular fibrillation before, during, and after primary percutaneous<br />

coronary intervention (PCI) in patients with acute ST-segment elevation acute<br />

myocardial infarction (AMI) treated with primary angioplasty. We sought to determine<br />

differences in prognosis between patients with primary CA before, during,<br />

and after PCI.<br />

Methods: Among 448 patients with first ST-segment elevation AMI, we selected<br />

34 (7.6%) with primary CA due to ventricular fibrillation (VF) and 6 (1.3%) with<br />

secondary CA. The patients with primary CA were categorized into the groups<br />

according to the time of the first episode of primary CA, either before [12 (35.3%)],<br />

during [18 (52.9%)], and after [4 (11.8%)] PCI procedure. The 30-days all cause<br />

mortality rate was analyzed.<br />

Results: Short-term mortality increased: patients without CA 7.1% (29/408), patients<br />

with primary CA 35.3% (12/34), patients with secondary CA 50% (3/6); P<br />

value for trend < 0.0001. When the patients were categorized into the groups<br />

according to the time of the first episode of primary CA, the mortality also increased:<br />

8.3% (1/12) for patients with primary CA before PCI, 44.4% (8/18) for<br />

patients with primary CA during PCI, 75% (3/4) for patients with primary CA after<br />

PCI procedure; P value for trend = 0.007.<br />

Conclusions: The patients with primary CA have the same poor prognosis as<br />

the patients with secondary CA. The prognosis make worse according to the time<br />

of the episode of primary CA. It might be reasonable to isolate subgroups of STsegment<br />

elevation AMI patients treated with PCI with primary CA according to<br />

time of primary CA which can help to better stratify the risk of these patients.<br />

P2780 Multicenter randomized trial of facilitated<br />

percutaneous coronary interventions with<br />

minimal-dose tenecteplase in patients with acute<br />

myocardial infarction. The ATHENS PCI trial<br />

E.P. Tsagalou1 , I. Kanakakis1 ,N.Agrios1 , M. Anastasiou-Nana1 ,<br />

F. Katsaros1 , A. Masdrakis1 , S. Sarafoglou1 , B. Tzoumerle 2 , S. Rokas1 ,<br />

J. Nanas1 . 1University of Athens, Athens, Greece; 2Pamakaristos Hospital,<br />

Athens, Greece<br />

Background: Facilitated percutaneous coronary intervention (PCI) preceded by<br />

administration of glycoprotein IIb/IIIa inhibitors, full-dose thrombolytics, or both,<br />

is associated with no benefit or a higher incidence of adverse events than PCI<br />

Prognosis in ST-elevation myocardial infarction 449<br />

alone. We hypothesized that minimal-dose tenecteplase might result in early infarct<br />

related artery (IRA) patency, without causing the adverse events of full-dose<br />

thrombolytics.<br />

Purpose: To examine the safety and efficacy of minimal-dose tenecteplase, administered<br />

before PCI to restore Thrombolysis In Myocardial Infarction (TIMI)<br />

grade 2 or 3 blood flow in the IRA, in patients with ST elevation myocardial infarction<br />

(STEMI) scheduled to undergo PCI with a shortest anticipated delay of<br />

30 min.<br />

Methods: Patients with STEMI < 6 h in duration were randomly assigned to PCI<br />

preceded by 10 mg of tenecteplase (facilitated PCI group, n=137) versus standard<br />

PCI (control group, n=135). All patients received aspirin and unfractionated<br />

heparin (70 IU/kg bolus) at time of randomization. Both groups received IIb/IIIa<br />

inhibitors in the catheterization laboratory and for at least 20 h after PCI.<br />

Results: The median door-to-balloon time was 122 min (91-175) in the facilitated<br />

PCI versus 120 min (89-175) in the control group. IRA patency on arrival in the<br />

catheterization laboratory was 60,5% in the facilitated PCI (24.3% TIMI-2, 36.2%<br />

TIMI-3), versus 37% in the control (7.4% TIMI-2, 29.6% TIMI-3) group (P=0.004).<br />

Conclusions: Facilitation with minimal-dose tenecteplase, in patients presenting<br />

with STEMI, was associated with a high IRA patency rate before PCI.<br />

P2781 Prognostic relevance of TIMI flow and Nt-proBNP<br />

concentrations in ST-elevation myocardial infarction:<br />

a substudy of ASSENT IV-PCI<br />

R. Jarai 1 , K.-B. Bogaerts 2 , W.-D. Droogne2 , J.-E. Ezekowitz3 ,<br />

P.-S. Sinnaeve 2 , K.-H. Huber4 , C.-G. Granger5 , A.-R. Ross6 ,<br />

P.-A. Armstrong3 ,F.-W.VanDeWerf2on behalf of ASSENT-4-PCI. 1Wilhelminen Hospital, 3rd Department of Medicine/Cardiology, Vienna, Austria; 2Leuven, Belgium; 3Edmonton, Canada; 4Vienna, Austria; 5Durham, United States of<br />

America; 6Washington D.C., United States of America<br />

Background: We investigated the prognostic significance of Nt-proBNP in addition<br />

to TIMI flow determined prior to coronary intervention in STEMI patients from<br />

ASSENT IV-PCI.<br />

Methods: Plasma Nt-proBNP was available in 1,037 STEMI patients when<br />

pts were randomized to primaryPCI) or to full-dose tenecteplase prior to PCI<br />

(fPCI).The study endpoint was the composite of death, cardiogenic shock or congestive<br />

heart failure at 90 days. The Chi-square (Chi2) Automatic Interaction Detectors<br />

algorithm (CHAID) of classification-tree analysis comprised our statistical<br />

calculations.<br />

Results: Failure of fibrinolytic therapy to achieve TIMI-3 flow prior to PCI (n=296)<br />

was associated with a significantly higher 90-day event rate (22.0%) compared to<br />

pts with successful fibrinolysis (n=228; 12.7%; p=0.006) or primary PCI (TIMI-3<br />

flow n=66: 13.6% p=0.13; TIMI 0-2 flow n=425: 12.0%: p694 pg/ml (>80th percentile) had highest<br />

risk for 90-day events in both treatment arms (pPCI: 30.1%, and fPCI: 36.3%;<br />

p=0.4) irrespective of TIMI-flow grade before PCI (Figure). The lowest 90-day<br />

event rate was observed in patients with a TIMI-3 flow before PCI pre-treated<br />

with fibrinolysis and Nt-proBNP levels ≤694pg/m. However, in fibrinolytic nonresponders<br />

(TIMI 0-2 flow) event rates were significantly higher than in all other<br />

groups.<br />

Conclusion: Clinical outcome of pts with high baseline plasma concentrations of<br />

Nt-proBNP was poor irrespective of TIMI-flow before PCI or the assigned treatment.<br />

By contrast in pts with low Nt-proBNP levels outcome appeared modulated<br />

by prePCI TIMI flow when pre-treated with fibrinolysis.<br />

P2782 Baseline concentrations of the interleukin receptor<br />

family member ST2 add independent prognostic<br />

information to risk scores in STEMI patients treated<br />

with PCI<br />

M. Grabowski1 , F.M. Szymanski1 ,J.Januzzi2 ,A.H.B.Wu3 ,<br />

A. Hrynkiewicz 1 , K.J. Filipiak1 ,G.Opolski1 . 1Medical University<br />

of Warsaw, 1st Department of Cardiology, Warsaw, Poland; 2Massachusetts General Hospital, Department of Cardiology, Boston, United States of America;<br />

3University of California, Department of Laboratory Medicine, San Francisco,<br />

United States of America<br />

Aim: To evaluate hypothesis that baseline serum levels of novel Interleukin-1<br />

receptor family member (ST2) add prognostic information to widely-accepted risk<br />

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450 Prognosis in ST-elevation myocardial infarction<br />

scores in unselected ST-elevation acute myocardial infarction (STEMI) patients<br />

treated with primary angioplasty (PCI).<br />

Methods: SIMPLE, TIMI, GRACE and ZWOLLE risk scores were calculated, and<br />

ST2 baseline levels were obtained in 68 consecutive patients. 1-year follow-up for<br />

all-cause mortality was performed.<br />

Results: There was moderate correlation between baseline ST2 levels and SIM-<br />

PLE (r=0.28; p=0.02), TIMI (r=0.32; p=0.008), GRACE (r=0.4; p=0.0007) and<br />

ZWOLLE (r=0.37; p=0.002) risk scores. The area under the receiver operating<br />

characteristic curve for ST2 to predict death – 0.804 (p=0.003) was comparable<br />

to risk scores: SIMPLE – 0.763, TIMI – 0.669, GRACE – 0.827, ZWOLLE - 0,637;<br />

p for difference vs. ST2, respectively: p=0.75; 0.24; 0.83; 0.12. When patients<br />

were divided into subgroups by low and high values of ST2 and risk scores (quartile<br />

1-3 and 4 for ST2 and each risk score) there was an increase in mortality with<br />

high compared to low ST2 levels in both low and high risk groups by risk scores<br />

(figure). After incorporation of ST2 to models consisting of each risk score (quantitative),<br />

consistent improvement of each C-statistic was noted, with an increase<br />

for SIMPLE to 0.786, TIMI to 0.711, GRACE to 0.84 and ZWOLLE to 0.808.<br />

1-year all-cause mortality<br />

Conclusions: Serum ST2 levels obtained on admission in STEMI patients<br />

treated with PCI add significant prognostic information to widely accepted risk<br />

stratification models, suggesting an important clinical role for this marker.<br />

P2783 Plasma concentration of sphingosine-1-phosphate<br />

and related sphingoid bases after the myocardial<br />

infarction in humans<br />

M. Knapp1 , M. Baranowski2 , D. Czarnowski2 ,A.Lisowska2 ,<br />

W.J. Musial 2 , J. Gorski2 . 1Medical University in Bialystok, Dept.<br />

of Cardiology, Bialystok, Poland; 2Medical University, Physiology Department,<br />

Baialystok, Poland<br />

The major bioactive sphingolipids are: ceramide, sphingosine-1-phosphate (S1P),<br />

sphingosine, sphinganine-1 phosphate (SH1P), sphinganine and ceramide-1phosphate.<br />

S1P has recently attracted much attention as an important factor protecting<br />

the heart against ischemia-reperfusion injury. Increased generation of S1P<br />

was shown to mediate the ischemic preconditioning in the perfused murine heart.<br />

The aim of this study was to evaluate whether concentration of S1P in the plasma<br />

is affected by the myocardial infarction in man.<br />

Material and method: The study comprised two groups of males: 21 healthy<br />

controls (mean age 66.7±6.3) with no specific complains (and no treatment) and<br />

21 patients with STEMI (diagnosed according to the ESC guidelines) treated by<br />

primary PCI (mean age 63.3±8.2). In the control group the blood was taken after<br />

an overnight fast. In the group of patients the blood was taken twice: on admission<br />

to the intensive care unit and at the fifth day of hospitalization. Patients received<br />

aspirin, clopidogrel and unfractionated heparin before the first blood sample was<br />

taken. The concentration of S1P, SH1P, free sphingosine, free sphinganine and<br />

ceramide in the plasma was determined simultaneously by means of high pressure<br />

liquid chromatography. All data are presented as means ±SD. Statistical<br />

comparisons were made by using one-way ANOVA followed by Newman-Keuls<br />

post-hoc test. P


lesion classification, stent type used, stent/lesion length, number of stents used<br />

did not show significant impact on mortality. We developed a prediction scoring<br />

system for outcome (MACE and death) using the significant clinical predictors.<br />

Conclusion: Age, female gender, diabetes, renal impairment, anemia, hypotension<br />

and development of cardiogenic shock, CIN, large rise in CK and lowered<br />

LVEF are clinical predictors of mortality in patients with STEMI post PPCI. A scoring<br />

system can be used to predict the clinical outcomes in these patients.<br />

P2786 Obstructive sleep apnea impairs the myocardial<br />

tissue perfusion in patients with acute myocardial<br />

infarction<br />

H. Nakashima1 ,S.Izumida2 , K. Amenomori 1 , Y. Honda1 ,<br />

S. Suzuki1 . 1Nagasaki Citizens Hospital, Department of Cardiology,<br />

Nagasaki, Japan; 2Nagasaki Citizens Hospital, Cardiology, Nagasaki, Japan<br />

Aims: Vascular endothelial dysfunction is noted in patients with obstructive sleep<br />

apnea (OSA). This study was designed to examine our hypothesis that OSA may<br />

impair the coronary microcirculation in patients with acute myocardial infarction<br />

(AMI).<br />

Methods: This study included 100 consecutive patients with a first AMI who<br />

underwent primary percutaneous coronary intervention (PCI). After reperfusion,<br />

coronary flow velocity at baseline and maximal hyperemia was measured using<br />

by Doppler guidewire. The sum of ST-segment elevation was measured at 30 min<br />

after PCI and compared with that on admission. Tissue perfusion grade was evaluated<br />

by coronary flow velocity reserve (CFVR), the presence of early systolic<br />

reversal flow (SRF), and ST-resolution. All patients underwent polysomnography<br />

and OSA was defined as AHI ≥ 15 events/h, of which more than 50% were obstructive.<br />

Results: Forty-six patients showed OSA. CFVR was comparable between the<br />

two patient groups (1.66±0.57 vs. 1.63±0.47, p=0.840). The incidence of SRF<br />

was significantly higher in OSA patients than in control patients (24% vs.<br />

7%, p=0.021). Patients with OSA showed a significantly lower ST-resolution<br />

(0.17±0.63 vs. 0.48±0.55, p=0.016). Significantly fewer OSA patients showed<br />

ST resolution ≥ 0.50 (37% vs. 61%, p=0.016). Multiple logistic regression analysis<br />

showed that OSA was independent negative predictor for ST resolution ≥<br />

0.50 (p=0.047).<br />

Conclusions: The novel finding in this study is that OSA may impair the tissue<br />

perfusion after primary PCI.<br />

P2787 Efficacy of a 24-hour primary percutaneous coronary<br />

intervention service on outcome in patients with<br />

STEMI in clinical practice<br />

T. Bauer1 , R. Hoffmann2 , C. Juenger3 , R. Zahn1 , O. Koeth1 ,<br />

T. Heer1 ,A.Gitt1 , K. Bestehorn4 , J. Senges3 ,U.Zeymer1on behalf<br />

of ACOS study group. 1Herzzentrum Ludwigshafen, Cardiology Department,<br />

Ludwigshafen, Germany; 2Universitaetsklinik Aachen, Cardiology Department,<br />

Aachen, Germany; 3Institut fuer Herzinfarktforschung, Ludwigshafen, Germany;<br />

4MSD, Munich, Germany<br />

Objectives: Little is known about the influence of a 24-hour, 7-day primary percutaneous<br />

coronary intervention (PCI) service on clinival events in patients with<br />

ST elevation myocardial infarction (STEMI). So far, randomised trials or data from<br />

observational studies are missing. Therefore we sought to investigate the impact<br />

of a 24-hour primary PCI service on in-hospital outcome in patients with STEMI<br />

in clinical practice.<br />

Methods: We analyzed data of consecutive patients with STEMI prospectively<br />

enrolled in the German Acute Coronary Syndromes registry between July 2000<br />

and November 2002 who were admitted to hospitals with catheter laboratory.<br />

Results: Overall 6350 patients were divided into two groups: 2779 (43.8%) were<br />

treated in hospitals with and 3571 (56.2%) without a 24-hour on-call cardiac<br />

catheter laboratory. 83.0% of the patients at facilities with and only 69.9% of the<br />

patients at facilities without 24-hour PCI service received early reperfusion therapy<br />

(p


452 Prognosis in ST-elevation myocardial infarction<br />

Methods: A total of consecutive 304 PPCI patients were prospectively enrolled;<br />

of these, 58 (19.1%) were elderly (≥75 years). Epicardial perfusion was evaluated<br />

by thrombolysis in myocardial infarction (TIMI) flow grade and corrected<br />

TIMI frame count (CTFC), and myocardial perfusion was evaluated by the TIMI<br />

myocardial perfusion grade (TMPG) and myocardial blush grade (MBG).<br />

Results: Compared to younger patients, elderly patients presented with a significantly<br />

higher adverse clinical and angiographic profiles. Despite a similar rate of<br />

procedural success (94.8% vs. 96.7%; P = NS), and a comparable epicardial perfusion<br />

before (TIMI flow grade 3: 8.6% vs. 6.5%, CTFC: 85.5±34.3 vs. 90.2±22.9;<br />

P = NS) and after PPCI (TIMI flow grade 3: 89.7% vs.91.1%, CTFC: 30.7±22.5<br />

vs. 28.3±26.0; P = NS), the rate of successful myocardial perfusion was markedly<br />

lower in the elderly than younger patients (TMPG ≥ 2 grade: 63.8% vs. 79.7%, P<br />

= 0.010; MBG ≥ 2 grade: 67.2% vs. 80.9%, P = 0.023; respectively). Multivariate<br />

analysis showed that advanced age (≥75 years) was the independent predictor<br />

of failure to achieve TMPG grade≥2 (OR 1.72, 95% CI 1.22-2.71, P = 0.016) or<br />

MBG grade≥2 (OR 1.56, 95% CI 1.10-2.24, P = 0.035). The incidence of 30day<br />

major adverse cardiac events (MACE) in elderly patients was 2.8-fold higher<br />

than in younger patients (P=0.001). In the whole population, multivariate analysis<br />

found that both advanced age (age≥ 75 years: OR 2.81, 95% CI 1.20-6.66,<br />

P = 0.011) and unsuccessful myocardial perfusion (TMPG≤1 grade: OR 2.34,<br />

95% CI 1.10-5.62, P = 0.040) were independently associated with 30-day MACE.<br />

In elderly patients, multivariate analysis identified unsuccessful myocardial perfusion<br />

(TMPG≤1 grade: OR 8.95, 95% CI 2.67-29.1, P = 0.003) as the the most<br />

important determinant of 30-day MACE.<br />

Conclusions: Impaired myocardial perfusion and not epicardial perfusion is associated<br />

with the worsened outcomes in elderly patients undergoing PPCI. To<br />

further improve the outcome of elderly patients with STEMI, efforts should be<br />

aimed at improving myocardial perfusion, beyond epicardial recanalization.<br />

P2791 Contrast induced nephropaty after primary or rescue<br />

PCI: prevalence and prognostic impact<br />

A. Perkan, F. Giannini, A. De Monte, B. D’agata, M. Merlo,<br />

G. Vitrella, S. Rakar, E. Della Grazia, A. Salvi, G. Sinagra on behalf<br />

of Primary/Rescue PCI Registry of Trieste. Ospedali Riuniti and<br />

University, Cardiovascular Department, Trieste, Italy<br />

Purpose: Contrast induced nephropathy (CIN) is a possible complication of coronary<br />

diagnostic and interventional procedures. Recent studies evaluated ST elevation<br />

myocardial infarction (STEMI) patients treated with percutaneous coronary<br />

intervention (PCI) as a group at high risk of CIN. Nevertheless the real prevalence<br />

and prognostic impact of CIN in STEMI patients is still unclear. The aim of<br />

this study was to assess prevalence, clinical predictors and outcome of CIN after<br />

primary or rescue PCI for STEMI patients.<br />

Methods: Three hundred and eighty one STEMI patients (73% men, mean age<br />

65±12 yrs; iodixanol was used in 72% of pts., 194±79 cc/procedure), underwent<br />

primary and rescue PCI from December 2003 to June 2007. We measured serum<br />

creatinine levels at baseline and in the following (2 and 3-7) days. CIN was defined<br />

as an absolute increase in creatinine >0,5 mg/dl after PCI in the absence of other<br />

causes of renal failure.<br />

Results: CIN occurred in 25 patients (6,6%). Patients developing CIN were older,<br />

had a higher incidence of diabetes mellitus and lower left ventricular ejection fraction.<br />

An estimated glomerular filtration rate (eGFR)


Prognosis in ST-elevation myocardial infarction / Percutaneous coronary intervention; longterm outcome 453<br />

P2794 Relation of Nt-proBNP and time to treatment to<br />

outcome of patients with ST-elevation myocardial<br />

infarction: an ASSENT IV-PCI substudy<br />

R. Jarai 1 , K.-B. Bogaerts 2 , W.-D. Droogne 2 , J.-E. Ezekowitz 3 ,<br />

P.-S. Sinnaeve 2 , K.-H. Huber 4 , C.-G. Granger 5 , A.-R. Ross 6 ,<br />

P.-A. Armstrong 3 ,F.-W.VanDeWerf 2 on behalf of ASSENT-4-PCI. 1 Wilhelminen<br />

Hospital, 3rd Department of Medicine/Cardiology, Vienna, Austria; 2 Leuven,<br />

Belgium; 3 Edmonton, Canada; 4 Vienna, Austria; 5 Durham, United States of<br />

America; 6 Washington D.C., United States of America<br />

Background: Survival of ST-elevation myocardial infarction (STEMI) pts depends<br />

on time between symptom onset and coronary reperfusion. In the present substudy<br />

from ASSENT-IV PCI pts were randomly assigned to primary PCI (pPCI)<br />

or fibrinolytic-facilitated PCI (fPCI), and we investigated, whether elevated NtproBNP<br />

in the acute phase of STEMI relates to time to reperfusion and independently<br />

predicts outcome irrespective of time.<br />

Methods: Plasma Nt-proBNP was available in 1,037 STEMI patients when<br />

pts were randomized to primaryPCI) or to full-dose tenecteplase prior to PCI<br />

(fPCI).The study endpoint was the composite of death, cardiogenic shock or congestive<br />

heart failure at 90 days. The Chi-square (Chi2) Automatic Interaction Detectors<br />

algorithm (CHAID) of classification-tree analysis comprised our statistical<br />

calculations.<br />

Results: Nt-proBNP concentrations and time-to-treatment showed a weak but<br />

significant linear correlation (r=0.22; p


454 Percutaneous coronary intervention; longterm outcome<br />

of stents was 5.4±2 per patient with a mean stent length of 132±47 mm. Patients<br />

were 64±10 years old (male; 89%), hypertension 68%, hyperlipidaemia 63%,<br />

diabetes 29%, family history 47%, smoker 19%. Patients had unstable angina<br />

27%, prior PCI 31%, prior CABG 19%, prior MI 46% and a mean ejection fraction<br />

53%. There were 4 (0.9%) definite ST; 1 acute (0.2%), 2 sub-acute (0.5%), 1 late<br />

(0.2%) and 0 very late.<br />

Conclusions: This study demonstrates an acceptable occurrence of MI, death<br />

and repeat revascularization in this cohort of complex patients with an incidence<br />

of definite ST similar to real world use in less complex patients.<br />

P2798 Cardiac outcome 8 years after stent implantation<br />

versus off-pump bypass surgery<br />

J.J. Regieli 1 , H.M. Nathoe2 , P.R. Stella2 , E.W.L. Jansen2 ,D.Van<br />

Dijk2 , J.C. Fanggiday 2 , F.D. Eefting3 , D.E. Grobbee2 ,P.P.T.De<br />

Jaegere4 , P.A. Doevendans2 on behalf of OCTOPUS study group.<br />

1University Medical Center Utrecht, <strong>Heart</strong>-Lung Institute, Dept of Cardiology,<br />

Utrecht, Netherlands; 2UMC Utrecht, Cardiology, Utrecht, Netherlands; 3St Antoinius Hospital, Cardiology, Nieuwegein, Netherlands; 4Erasmus MC,<br />

Cardiology, Rotterdam, Netherlands<br />

Purpose: To compare the long-term clinical effects of a stenting strategy versus<br />

off-pump bypass surgery.<br />

Methods: In the OCTOSTENT study, 280 patients at relatively low risk and in<br />

need of coronary revascularization were randomized. Long-term follow-up data<br />

were obtained by patient interviews and subsequent retrieval of hospital records.<br />

Results: Patients included had a mean age of 60 years, were predominantly<br />

(70%) males with stable angina (70%), one vessel disease (70%) and normal LVfunction<br />

(90%). The surgery group experienced 10% all-cause mortality, and the<br />

stenting group 7% (p=0.43). Stroke, myocardial infarction (MI) or all cause mortality<br />

were equally experienced in both groups (14% vs 13% respectively, p=0.80)<br />

whereas the need of coronary re-interventions was significantly (p=0.03) higher<br />

in patients initially treated with a bare-metal stent (16 vs 27%). The figure displays<br />

plotted Relative Risks representing effect of surgery versus stenting on the<br />

various outcomes.<br />

Effect of surgery versus stenting.<br />

Conclusion: In low risk CAD patients, off-pump surgical revascularization offers<br />

no significant long-term benefit on hard outcomes as compared to bare metal<br />

stenting. However, re-interventions are significantly more frequent after stenting.<br />

A strategy of stent-implantation can therefore safely be recommended as the first<br />

choice coronary revascularization procedure in selected patients.<br />

P2799 Risk factors and clinical outcomes for contrast<br />

induced nephropathy post percutaneous coronary<br />

intervention in patients with impaired baseline renal<br />

function<br />

E. Chong, Liang Shen, K.K. Poh, C.T. Hong, H.Y. Ong, H.C. Tan.<br />

National University Hospital, The <strong>Heart</strong> Institute, Singapore,<br />

Singapore<br />

Purpose: Baseline renal impairment is a recognized risk factor for developing<br />

contrast nephropathy (CIN) post percutaneous coronary intervention (PCI). We<br />

examine other risk predictors for CIN in patients with impaired baseline renal<br />

function who are already receiving prophylactic treatment.<br />

Methods: A cohort of 770 patients with impaired renal function (estimated<br />

glomerular filtration rate (GFR) < 60ml/min/1.73m 2 ) who received prophylactic<br />

saline hydration and oral N-acetylcysteine treatment undergoing PCI between<br />

May 2001 to March 2007 were recruited. We examine the incidence of CIN in<br />

this cohort and aim to identify clinical risk predictors.<br />

Results: The mean age of the cohort was 65±18 years, 28.6% were older than<br />

70, 65.8% was men, 45.9% was diabetics, 77% was hypertensive, 27.1% had<br />

acute coronary syndrome. CIN occurred in 11.4% of the patients. Clinical predictors<br />

for CIN were age (OR 1.59, 95% CI 1.0-2.52, p=0.049); anemia with<br />

hemoglobin < 11mg/dl (OR 2.26, 95% CI 1.41 – 3.61, p=0.001); post procedural<br />

creatinine kinase rise (OR 1.12, 95% CI 1.07 – 1.16 for every 500 u/l increase,<br />

p


P2802 In-hospital and long-term mortality after emergency<br />

and elective PCI of unprotected left main stem<br />

stenosis with provisional side-branch stenting<br />

strategy. The Krakow experience<br />

J. Legutko 1 ,D.Dykla1 ,M.Suska1 ,L.Rzeszutko1 ,R.Singh2 ,<br />

W. Gutkowski3 ,B.Guzik1 , A. Machnik1 , L. Bryniarski1 , D. Dudek1 . 1Jagiellonian University, Institute of Cardiology, Cracov, Poland; 2Nottingham University<br />

Hospitals, Trent Cardiac Centre, Nottingham, United Kingdom; 3Swietokrzyskie Cardiology Centre, Kielce, Poland<br />

Background: Unprotected left main stem stenosis (UPLMS) is class IA indication<br />

for surgical revascularization. However, there is increasing evidence, that stenting<br />

of UPLMS is safe and feasible. The aim of the study was to evaluate in-hospital<br />

and long-term mortality after emergency and elective UPLMS stenting.<br />

Methods: Data was collected for 246 consecutive patients who underwent UP-<br />

LMS PCI with provisional side-branch stenting strategy. Of these, 170 pts presented<br />

with stable angina (SA), 36 pts with unstable angina (UA), 16 pts with non<br />

ST-elevation myocardial infarction (NSTEMI) and 24 pts with ST-elevation myocardial<br />

infarction (STEMI). Majority of the lesions involved distal bifurcation of the left<br />

main (72%). Stents were implanted in all patients (Drug Eluting Stents: 61%, Bare<br />

Metal Stents: 39%). One stent was used for 97% of pts. In-hospital and long-term<br />

mortality was assessed.<br />

Results: Mean time of follow-up was 26,7 months. In-hospital and long-terrm<br />

mortality is shown in table. Moreover, patients with acute coronary syndromes<br />

(STEMI, NSTEMI, UA) in-hospital mortality was significantly higher in patients<br />

presenting with cardiogenic shock (23% vs. 2%, shock vs. non-shock respectively,<br />

p


456 Percutaneous coronary intervention; longterm outcome<br />

Conclusions: In comparison to BMS, DES were associated with similar longterm<br />

safety (mortality and myocardial infarction) and maintained their efficacy in<br />

reducing repeat revascularisation and MACE.<br />

P2806 Long-term clinical outcome with<br />

titanium-nitride-oxide-coated stents, paclitaxel eluting<br />

stents and bare-metal stents for coronary<br />

revascularization in an unselected population<br />

P.P. Karjalainen1 , A.-P. Annala1 ,A.Ylitalo1 , K.E.J. Airaksinen2 .<br />

1 2 Satakunta Central Hospital, Dept. of Cardiology, Pori, Finland; Turku University<br />

Hospital, Dept. of Internal Medicine, Turku, Finland<br />

Purpose: The main purpose of this study was to compare long-term clinical outcome<br />

of titanium-nitride-oxide-coated bio-active stents (BAS), paclitaxel eluting<br />

stents (PES) and bare-metal stents (BMS) in routine clinical practice.<br />

Methods: Between May 2003 and November 2004 all patients undergoing percutaneous<br />

coronary intervention (PCI) were eligible in this study. The primary end<br />

point of the study was major adverse cardiac events (MACE) at 3 years including<br />

myocardial infarction (MI), cardiac death and target vessel revascularization<br />

(TVR).<br />

Results: A total of 589 patients were included in this analyses of which 201 received<br />

BAS, 204 PES and 184 BMS. Complete follow-up datasets were available<br />

in 100% of patients. After 3 years of follow-up, the rate of MACE was 13.9% for<br />

BAS, 23.5% for PES and 31.5% for BMS (Table). A higher rate of MI was observed<br />

in the PES group (19.1%) compared with BAS (7.5%) group. The rate of<br />

TVR was 8.5% for BAS, 11.3% for PES and 14.1% for BMS. Stent thrombosis<br />

(ST) occurred in 15 patients in the PES (7.4%) group and in 5 patients in the<br />

BMS (2.7%) group. There was no ST in the BAS group.<br />

Outcome events at 3 years<br />

BAS (n=201) PES (n=204) BMS (n=184) P<br />

Myocardial infarction, % 7.5 19.1 14.7 0.002*<br />

Cardiac death, % 1.0 3.4 6.0 0.02 †<br />

Target vessel revascularization, % 8.5 11.3 14.1 NS<br />

Target lesion revascularization, % 5.5 9.3 12.0 NS<br />

MACE, % 13.9 23.5 31.5 < 0.001 †<br />

Stent thrombosis, % 0 7.4 2.7 < 0.001*, 0.03 ‡<br />

All cause death, % 5.5 6.4 8.7 NS<br />

* BAS versus PES; † BAS versus BMS; ‡ BMS versus PES.<br />

Conclusions: After 3 years follow-up, BAS resulted in better long-term clinical<br />

outcome compared with PES or BMS. The incidence of ST tended to be highest<br />

in the PES group.<br />

P2807 High on-treatment platelet reactivity as a risk factor<br />

for clinical events beyond the duration of treatment<br />

with clopidogrel<br />

D. Trenk1 , W. Hochholzer 2 ,C.M.Valina1 ,C.Stratz1 ,H.-<br />

P. Bestehorn1 , H.J. Buettner1 , F.-J. Neumann1 . 1Herz-Zentrum Bad Krozingen, Abt. fuer Klinische Pharmakologie, Bad Krozingen, Germany;<br />

2Universitaetsspital Basel, Internal Medicine, Basel, Switzerland<br />

Background: The EXCELSIOR study demonstrated the impact of residual<br />

platelet aggregation after loading with clopidogrel 600 mg in patients undergoing<br />

elective percutaneous coronary intervention (PCI) with stent placement. Patients<br />

with an attenuated antiplatelet response before discharge at day 1 after<br />

PCI carried a 3-fold increased risk for the 12-months incidence of the composite<br />

endpoint death and myocardial infarction (MI). We investigated if the impact of<br />

high on-treatment platelet reactivity extended beyond the duration of clopidogrel<br />

administration.<br />

Methods: This secondary analysis of the EXCELSIOR-study comprised 765 patients<br />

undergoing coronary stent implantation after loading with 600 mg of clopidogrel.<br />

After PCI, all patients received aspirin (≥100 mg per day), lifelong, and<br />

clopidogrel (75 mg per day) for 30 days after placement of bare-metal stents or<br />

for 6 months after placement of at least one drug-eluting stent. We analyzed the<br />

impact of residual platelet aggregation (RPA) using the cut-point obtained in EX-<br />

CELSIOR (≤14% vs. >14% using ADP 5 μmol/L) on the incidence of death and<br />

MI (primary endpoint) after discontinuation of clopidogrel during a follow-up period<br />

of 12 months after PCI.<br />

Results: We found a significant difference in the incidence of the primary endpoint<br />

after discontinuation of clopidogrel between the strata defined by RPA (4.1%<br />

in patients with RPA >14% and 1.6% in patients with RPA ≤14%; p=0.039). Considering<br />

the period after discontinuation of clopidogrel in the subset with at least<br />

one drug-eluting stent, the incidence of the primary end point differed significantly<br />

(4.3% vs. 0.5%; p=0.018 by log-rank test) between the two strata defined by predischarge<br />

RPA. Among patients who received a bare-metal stent, the difference<br />

in 1-year outcome between the two strata with respect to the primary end point<br />

was substantially smaller (4.1% for RPA >14% versus 2.4% for RPA ≤14%) with<br />

a non-significant hazard ratio for the stratum with RPA >14% of 1.75 (95% CI,<br />

0.6-5.1; p=0.30).<br />

Conclusions: The impact of high on-treatment platelet reactivity extended beyond<br />

the duration of clopidogrel administration. Even after discontinuation of clopidogrel,<br />

the difference in the incidence of death and myocardial infarction was par-<br />

ticularly prominent in patients having received a drug-eluting stent. Our findings<br />

may suggest that robust platelet inhibition during dual antiplatelet therapy may<br />

reduce cardiac complications that occur late after discontinuation of clopidogrel.<br />

P2808 Immediate and long-term outcome of DES<br />

implantation for the treatment of long (>30 mm)<br />

chronic total coronary artery occlusions<br />

V. Tzifos 1 ,A.Gatsis1 , J. Kalpogiannakis2 , H. Mantzouratos2 ,<br />

G. Daveli 1 ,X.Trika1 , A. Eleutheriou1 , P. Papavasilopoulos1 ,<br />

S. Stamatelopoulos1 , G. Theodorakis1 . 1Henry Dunant Hospital, Intervantional<br />

Cardiology, Athens, Greece; 2Thriasion Hospital, Interventional Cardiology,<br />

Athens, Greece<br />

Objective: The long term angiographic patency and the angiographic variables<br />

associated with long term success of coronary artery stenting for chronic (> 6<br />

months) coronary artery occlusion in very long lesions (>30 mm) was associated<br />

with poor prognosis in the bare metal stent era. Aim of the present study was<br />

to evaluate the early results and outcome following the treatment of very long<br />

chronic totally occluded coronary arteries with drug eluting stent implantation.<br />

Methods and Results: In the last 3 years, we treated 178 chronic occlusions;<br />

42 of these (23.6%) being > 30 mm long. Angiographic success with coronary<br />

stenting was obtained in 36 (85.7%) lesions. The number of stents implanted per<br />

patient was 2.1±1.1. A total of 66 drug eluting stents were used. More precisely<br />

38 Cypher, 15 Taxus, 9 Endeavor and 4 Infinnium stents. Mean stent diameter<br />

was 3.2±0.6mm and mean stent length was 44±12 mm. Among the successfully<br />

treated lesions, vessel location was RCA in 18 (50%) patients, LAD in 14 (38.9%)<br />

and Cx in 4 (11%). There were two minor perforations during the procedure without<br />

clinical incidence. At the follow-up period (16±3.2 months), 31 patients remained<br />

asymptomatic (86.1%). Clinical follow up was obtained for all patients.<br />

One patient died of non cardiac cause and 4 had recurrence of angina. Follow-up<br />

angiography nine months after the procedure was obtained in 26 (72%) patients.<br />

Significant restenosis (> 50%) was observed in 5 (19%) patients. Reocclusion<br />

was noted in 1 (3.8%) patient. A significant correlation was noted between the incidence<br />

of restenosis and the MLD < 2.75 mm post procedure (R=0.68) and the<br />

total length of stents used (R=0.76) during the initial percutaneous intervention.<br />

Conclusions: Although recanalization of long (> 30 mm) chronically occluded<br />

coronary arteries is technically feasible, the 9 month restenosis rate remains still<br />

high despite the use of drug eluting stents. High TLR rate was associated with<br />

the total stent length and with a post procedure MLD < 2.75 mm.<br />

P2809 Impact of atherosclerotic disease progression on<br />

repeat revascularization in diabetic patients in the<br />

drug-eluting stent era<br />

P. Tousek1 ,A.Pavei2 ,G.Martin2 , J. Oreglia2 ,B.Farah2 , J. Fajadet2 .<br />

1 2 Prague, Czech Republic; Toulouse, France<br />

Background: Percutaneous coronary interventions (PCI) in patients with diabetes<br />

mellitus (DM) with use of either bare-metal stent (BMS) or drug-eluting<br />

stents (DES) are associated with elevated rates of repeat revascularization (RR).<br />

However, impact of restenosis or atherosclerosis progression on RR in the DES<br />

era is not well known.<br />

Aim: To determinate if RR in diabetic patients treated with prior DES, is the result<br />

of DES restenosis or due to native progression of atherosclerotic disease in the<br />

coronary vasculature.<br />

Methods and Results: We followed 364 consecutive diabetic patients (264 men,<br />

age 68±8.8 years) treated between April 2005 and <strong>September</strong> 2006 with at least<br />

one DES. Out of these 292 patients (80%) had multivessel coronary disease,<br />

148 patients (41%) had previous coronary revascularization and 109 patients<br />

(30%) had insulin-dependent DM. Only DES stents were implanted in 318 (87%)<br />

of the patients, combination of DES and BMS implantation was performed in<br />

30 (8%) patients and DES implantation with additional balloon angioplasty was<br />

performed in 16 (4%) patients. During the follow-up (range 12-28 months, mean<br />

18±8 months) there were 39 repeat revascularizations (38 PCI, 1 CABG). In 20<br />

patients repeat revascularization was performed for restenosis (18 after DES implantation,<br />

1 after BMS implantation and 1 after balloon angioplasty), out of which<br />

in 3 patients treatment was also required for disease progression. In 19 patients<br />

PCI was performed for symptomatic atherosclerotic disease progression without<br />

restenosis. Thus disease progression contributed to 52% of repeat revascularization<br />

procedures. Furthermore, in 5 of 6 patients (83%) admitted for myocardial<br />

infarction, culprit lesion was caused by atherosclerotic disease progression.<br />

Conclusion: Atherosclerotic disease progression was more than 50% the cause<br />

of repeat revascularization in diabetics patients treated previously with DES and<br />

was the main cause of readmission for myocardial infarction. Major adverse clinical<br />

events in trials with long term follow-up in diabetic patients can thus be influenced<br />

by native disease progression and not by DES failure and therefore should<br />

be interpreted with caution.<br />

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P2810 Long-term clinical results following percutaneous<br />

coronary intervention to the left main stem with bare<br />

metal and drug-eluting stents<br />

Y. Onuma, N. Kukreja, J. Daemen, E. Meliga, P.H. Van Twisk,<br />

N. Piazza, R. Van Domburg, P.W. Serruys. Thorax center, Erasmus<br />

MC, Interventional Cardiology, Rotterdam, Netherlands<br />

Objectives: Long-term clinical outcomes after drug-eluting stent (DES) implantation<br />

for unprotected left main coronary artery disease (ULMCA) in comparison<br />

with bare metal stent (BMS) have not been yet fully investigated. This study<br />

evaluated the long-term (3-year) clinical outcome of patients treated by percutaneous<br />

coronary intervention (PCI) with DES implantation for ULMCA compared<br />

with BMS.<br />

Methods: Between January 1, 2000 and December 31, 2005, 251 consecutive<br />

patients with ULMCA were treated with either BMS (n=84; January, 2000 to April,<br />

2002) or DES (n=167; SES used from April 2000 to February 2003, PES from<br />

March 2003 to December 2005). Annual follow-up on the occurrence of death<br />

(obtained from municipal civil registries) and clinical events were collected. Cox<br />

multivariate regression analysis was performed to account for differences in demographics,<br />

clinical and angiographic variables.<br />

Results: Clinical follow-up was available for 98.4% of patients for a mean of<br />

1020±720 days. At 3 years, all-cause mortality was comparable between BMS<br />

and DES groups (34.5% vs. 26.3%, adjusted hazard ratio [HR] 0.79[95%CI: 0.48-<br />

1.31]) with comparable target lesion revascularisation (TLR) rate (11.9% vs. 7.8%,<br />

adjusted HR 0.81 [95%CI: 0.33-1.97]). The major adverse cardiac event (MACE:<br />

death, myocardial infarction or target vessel revascularisation) rates were 47.6%<br />

in BMS group and 39.5% in DES group (adjusted HR 0.73 [95% CI: 0.48-1.10).<br />

Definite stent thrombosis rates were 1.2% in both groups. In elective cases, DES<br />

group demonstrated lower all-cause mortality (21.9% vs. 15.7%, adjusted HR<br />

0.60 [95% CI: 0.22-1.61]) with lower TLR rate (25% vs 8.6%, adjusted HR 0.11<br />

[0.03-0.40]). MACE rate was significantly lower in DES group (43.7% vs. 27.1%,<br />

adjusted HR 0.43 [95%CI; 0.22-0.87]). There were no cases of definite stent<br />

thrombosis.<br />

Conclusions: Overall, long-term MACE and repeat revascularisation rates at 3<br />

years were high after PCI for the ULMCA with no significant difference between<br />

BMS and DES groups. In elective cases, DES was associated with improved<br />

long-term outcomes.<br />

P2812 Long-term safety and efficacy of sirolimus- versus<br />

paclitaxel-eluting stent implantation for acute<br />

ST-elevation myocardial infarction: 3-year follow-up of<br />

PROSIT trial<br />

H.S. Kim1 , J.H. Lee2 ,J.H.Park2 , Y.J. Choi1 ,G.Y.Cho1 , J.O. Jeong2 ,<br />

I.W. Seong2 ,K.S.Rhee3 ,J.K.Ko3on behalf of PROSIT trial. 1Hallym University<br />

Sacred <strong>Heart</strong> Hospital, Cardiology, Anyang-Si, Korea, Republic of; 2Chungnam National University Hospital, Cardiology, Daejeon, Korea, Republic of; 3Chonbuk National University Hospital, Cardiology, Jeonju, Korea, Republic of<br />

Purpose: This study compared long-term safety and efficacy of sirolimus- (SES)<br />

versus paclitaxel-eluting stent (PES) implantation for the treatment of acute STelevation<br />

myocardial infarction (STEMI).<br />

Methods: A total of 308 consecutive patients were randomly treated with SES<br />

(n=154) or PES (n=154) in the setting of primary percutaneous coronary intervention<br />

for acute STEMI at three cardiac centers. Thirty-day and long-term (35±10<br />

months) clinical outcomes were assessed. Primary endpoint was incidence of<br />

stent thrombosis and major adverse cardiac events (MACE) including all cause<br />

mortality, myocardial infarction (MI), and ischemia-driven target lesion revascularization<br />

(TLR). We applied a classification of stent thrombosis set by the Academic<br />

Research Consortium (ARC).<br />

Results: The both group had similar clinical and angiographic characteristics. At<br />

30 days, the rate of all cause mortality (2.6% for SES and 5.2% for PES, p=0.25)<br />

and MI (0% for SES and 1.3% for PES, p=0.50) were similar in both groups.<br />

Angiographic in-segment restenosis rate was significantly lower in SES over PES<br />

at 6-month (5.9% vs. 14.8%, p=0.03). During the 3-year follow-up, no significant<br />

differences were seen between two groups in terms of death (6.5% for SES and<br />

10.4% for PES, p=0.219), MI (2.6% vs. 3.9%, p=0.750), TLR (5.2% vs. 8.4%,<br />

p=0.258) and MACE (12.3% vs. 18.8%, p=0.116). Overall cumulative incidence<br />

of stent thrombosis by any ARC criteria was gradually increased; 0.6% at 30<br />

days, 0.6% at 1 year, 1.6% at 2 years, and 2.6% at 3 years. Late stent thrombosis<br />

(> 1 month) occurred in 1.9% for both SES and PES. The incidence of stent<br />

thrombosis was also similar in both groups during the 3-year follow-up (1.9% for<br />

SES versus 3.2% for PES, p=0.723).<br />

Conclusions: SES significantly outperformed PES in preventing angiographic<br />

restenosis in STEMI patients treated with primary angioplasty. However, longterm<br />

safety and efficacy evaluated by incidence of stent thrombosis and MACE<br />

were not different between two groups during the 3-year follow-up.<br />

Percutaneous coronary intervention; longterm outcome 457<br />

P2813 Percutaneous intervention or bypass grafting as<br />

primary revascularization in patients with acute<br />

coronary syndrome: insights from a prospective<br />

cohort study<br />

W. Hochholzer 1 , H.J. Buettner2 , D. Trenk2 , T. Breidthardt1 ,<br />

K. Laule1 ,M.Christ1 , F.-J. Neumann2 , C.H. Mueller1 . 1University Hospital Basel, Department of Internal Medicine, Basel, Switzerland;<br />

2Herz-Zentrum, Bad Krozingen, Germany<br />

Purpose: New <strong>European</strong> Society of Cardiology/American College of Cardiology<br />

(ESC/ACC) guidelines classify patients with acute coronary syndrome (ACS) and<br />

elevated cardiac troponin levels as non-ST segment elevation myocardial infarction<br />

(NSTEMI) who would have been classified as unstable angina (UA) by older<br />

WHO definition. The optimal revascularization strategy in these patients is poorly<br />

defined.<br />

Methods: This prospective cohort study included 1,024 consecutive patients<br />

with ACS classified into UA, NSTEMI according to the WHO definition ("WHO<br />

NSTEMI"), and NSTEMI additionally identified by the novel ESC/ACC definition<br />

("additional NSTEMI"). All patients underwent coronary angiography within 24<br />

hours and were treated with immediate percutaneous coronary intervention (PCI)<br />

or early coronary artery bypass grafting (CABG). The primary endpoint was allcause<br />

mortality during follow-up of 36 months.<br />

Results: Death occurred in 67 patients. There was a significant interaction between<br />

"additional NSTEMI" group and revascularization strategy regarding longterm<br />

mortality (interaction p


458 Percutaneous coronary intervention; longterm outcome<br />

P2815 Four-year follow-up patients with ST-segment<br />

elevation acute myocardial infarction treated with<br />

Sirolimus-eluting stent and Paclitaxel-eluting stent:<br />

Multicenter registry in Asia<br />

S. Nakamura1 ,J.H.Bae2 , Y.H. Cahyadi3 , W. Udayachalerm 4 ,<br />

D. Tresukosol5 , S. Tansuphaswadikul6 . 1New Tokyo Hospital, Department<br />

of Cardiology, Chiba, Japan; 2Konyang University Hospital, Daejeon, Korea,<br />

Republic of; 3Husada Hospital, Jakarta, Indonesia; 4King Chulalongkorn<br />

Memorial Hospital, Bangkok, Thailand; 5Her Majesty’s Cardiac Center Siriraj<br />

Hospital, Bangkok, Thailand; 6Chest Disease Institute, Bangkok, Thailand<br />

Background: Previous clinical study utilizing Sirolimus-eluting stent (SES) and<br />

Paclitaxel-eluting stent (PES) in simple coronary lesions demonstrated an impressive<br />

reduction in intimal hyperplasia and restenosis. However, clinical efficacy of<br />

SES and PES in treating patients with ST-segment elevation myocardial infarction<br />

(STEMI) has not been validated.<br />

Methods: We assessed baseline clinical and angiographic characteristics, inhospital<br />

and 12, 24 and 36-month major adverse cardiac events (MACE) in 1,838<br />

consecutive STEMI patients who received on SES, PES or bare metal stents<br />

(BMS) without cardiogenic shock undergoing emergent PCI.<br />

Results: The baseline clinical characteristics between 3 groups were similar. See<br />

table for the clinical results.<br />

BMS SES PES p<br />

Number of patients 388 843 607 –<br />

In-hospital Clinical success (%) 98.5 98.8 99.0 NS<br />

Death (%) 1.0 0.8 1.0 NS<br />

Stent thrombosis (%) 0.5 0 0 NS<br />

30 days to 12 mo Death (%) 0.5 0.2 0.3 NS<br />

Angiographic restenosis (%) 16.0 3.8* 4.9* 0.01<br />

Repeat PCI (%) 10.8 3.0* 4.9* 0.01<br />

Stent thrombosis (%) 0 0.2 0.3 NS<br />

30 days to 36 mo Death (%) 0.8 0.8 0.5 NS<br />

Angiographic restenosis (%) 17.5 5.3* 5.9* 0.01<br />

Repeat PCI (%) 11.9 3.8* 5.9* 0.01<br />

Stent thrombosis (%) 0 1.2 0.3 NS<br />

30 days to 48 mo Death (%) 1.0 1.1 0.2 NS<br />

Angiographic restenosis (%) 17.8 5.3* 6.1* 0.01<br />

Repeat PCI (%) 11.9 4.0* 6.1* 0.01<br />

Stent thrombosis (%) 0 1.2 0.2 NS<br />

Conclusion: Implantation of SES and PES in STEMI patients is not associated<br />

with any risk of adverse in-hospital events, and reduced the need for repeat PCI<br />

at follow-up.<br />

P2816 Long-term outcome of coronary bifurcations after<br />

implantation of two drug-eluting stents: is the late<br />

and very late stent thrombosis a real risk?<br />

A. Ielasi1 ,A.Latib1 , G. Bassanelli 1 , C. Godino1 ,J.Cosgrave2 ,<br />

R.T. Gerber2 , A. Chieffo 1 , F. Airoldi1 , M. Montorfano1 , A. Colombo2 .<br />

1 2 San Raffaele Scientific Institute, Interventional Cardiology, Milan, Italy; EMO<br />

Centro Cuore Columbus, Interventional Cardiology, Milan, Italy<br />

Objectives: Drug-eluting stent (DES) implantation in coronary bifurcations has<br />

been identified as a possible risk factor for stent thrombosis (ST). In particular,<br />

there are concerns that implanting two stents in a bifurcation may pose a high<br />

thrombogenic risk. In view of these concerns and lack of convincing data, we<br />

performed this study to examine the long-term safety of implanting two DES in a<br />

bifurcation.<br />

Methods: Retrospective cohort analysis of consecutive non-left main bifurcations<br />

treated with two DES between April 2002 and December 2005 at two centres. ST<br />

was defined according to the Academic Research Consortium definitions.<br />

Results: We identified 315 patients with 331 bifurcation lesions treated with two<br />

sirolimus-eluting stents (SES) in 227 (68.6%), 2 paclitaxel-eluting stents (PES) in<br />

101 (30.5%), and a mixture of SES and PES in 3 (0.9%) bifurcation lesions. Of<br />

these 315 patients, 76 (24.1%) were diabetic and 82 (26%) had unstable angina<br />

at presentation. The site of the treated bifurcation was the left anterior descending<br />

artery (LAD)/diagonal (Diag) in 225 (68%), left circumflex/obtuse marginal in<br />

82 (24.8%), and the right coronary artery in 24 (7.3%). Majority of bifurcations<br />

(71.7%) were stented using the crush technique. During a median follow-up of<br />

968 days (IQR 621-1400), 3 (0.9%) patients had a definite ST: 1 acute, 1 subacute<br />

(4 days), and 1 very late ST (962 days). All 3 patients with definite ST<br />

presented with an acute MI and the patient with acute ST died from the event.<br />

Five (1.5%) patients were adjudicated as having a probable ST due to a MI in the<br />

territory of the stented bifurcation (1 subacute, 2 late and 2 very late ST) and all<br />

of these patients survived from the event. In the 8 patients with definite/probable<br />

ST, 4 occurred while on dual antiplatelet therapy, 5 patients were diabetic, and<br />

all ST involved the LAD/Diag bifurcation. Only diabetes was an independent predictor<br />

of ST (OR=4.68; 95% CI 1.05 – 20.08; p=0.04). At follow-up, a total of 17<br />

(5.4%) patients had died; 13 (4.1%) of cardiac death. Angiographic follow-up was<br />

performed in 245 (77.8%) patients, restenosis occurred in 67 (20.2%) lesions. MI<br />

occurred in 15 (4.8%) and target-lesion revascularisation in 56 (17.8%) patients<br />

during the follow-up period.<br />

Conclusions: Implantation of 2 DES in a coronary bifurcation appears safe with a<br />

1.6% incidence of definite or probable late and very late ST at a median follow-up<br />

of almost 3 years.<br />

P2817 Long term mortality after bare metal stent<br />

implantation: a 12-year single centre experience with<br />

1561 patients<br />

C. Cernigliaro1 , M. Sansa2 , A.S. Bongo2 , E. Novelli3 . 1Interventional Cardiology Clinica S.Gaudenzio, Interventional Cardiology, Novara,<br />

Italy; 2Cardiologia Ospedaliera, Ospedale Maggiore, Novara, Italy; 3Dpt of<br />

Biostatistics, Clinica San Gaudenzio, Novara, Italy<br />

Objectives: the assessment of the long term mortality (up to 12 years), after bare<br />

metal stent (BMS) coronary artery stenting.<br />

Methods: between 1995 and 2003, 1561 patients 63±10.7 years of age, 1235<br />

(79.1%) males, 774 (49.6%) with a family history of ischemic heart disease, 588<br />

(37.7%) current smokers, 824 (52.8%) hypertensive, 178 (11.4%) type 2 diabetic,<br />

109 (7.0%) type 1 diabetic, 763 (48.9%) dyslipidemic, underwent a first stent implantation<br />

(2160 stents, 47 different types of BMS, 1.3 stents per patient). Indication<br />

for percutaneous coronary intervention (PCI) was: stable angina in 460<br />

(29.5%) patients, unstable angina in 478 (30.6%) patients and acute myocardial<br />

infarction in 623 (39.9%) patients. Ejection fraction was 52.0±9.1%. Death certificate<br />

records of study population were obtained from the Regional Mortality Registry<br />

for the years 1995 – 2007, with a mean follow-up period of 7.8±1.8 years<br />

(range, 4.2 – 12.4 years). Fifty-seven (3.7%) patients were lost at follow-up.<br />

Results: coronary angiography, performed 6 months after stent implantation in<br />

1342 (86%) patients, demonstrated restenosis in 349 (26%) patients. Cumulative<br />

death rate during follow-up was 174 (11.6%) patients, causes of death were<br />

cardiac in 84 (5.6%) patients. Cumulative survival rates at 4, 8, 12 years were<br />

95.1%, 87.9% and 83.8% respectively. Survival from cardiac death at 4, 8, 12<br />

years was 97.5%, 94.1% and 92.3% respectively. Cox proportional hazard regression<br />

showed that advanced age (HR 1.06, 95% CI 1.04–1.08, p


Percutaneous coronary intervention; longterm outcome / Bring issues in percutaneous cardiovascular interventions 459<br />

P2819 Mid- to long-term survival in patients with left<br />

ventricular dysfunction undergoing sirolimus- or<br />

paclitaxel- eluting stent implantation<br />

A. Abbate 1 , N. Nusca 2 , D. Appleton 1 ,A.Varma 1 , M.J. Lipinski 3 ,<br />

E. Goudreau 1 ,M.J.Cowley 1 ,G.W.Vetrovec 1 . 1 Richmond, United<br />

States of America; 2 Rome, Italy; 3 Charlottesville, United States of America<br />

Introduction: Drug eluting stents (DES) reduce the rate of in-stent restenosis and<br />

target-vessel revascularization (TVR) without a net effect on mortality or acute<br />

myocardial infarction (AMI) when compared to bare metal stents (BMS). Recent<br />

data has shown a potential increase in mortality associated with DES possibly<br />

due to late stent thrombosis (LST). Left ventricular (LV) dysfunction is considered<br />

a risk factor for LST. Aim of the current study was to assess mid- to long-term<br />

survival rates in high risk patients with LV systolic dysfunction undergoing drugeluting<br />

stent implantation.<br />

Methods and Results: Patients with an ejection fraction < 45% undergoing PCI<br />

between April 2003 and December 2005 who had at least one sirolimus- or<br />

paclitaxel-eluting stent placed were selected for screening. As historical control<br />

patients treated with bare-metal stents prior to the introduction of DES between<br />

May 1996 and March 1999 were studied. Mortality rates were retrieved from the<br />

Social Security database. One hundred twenty three patients who received at<br />

least one DES were selected for inclusion in the study, and compared with 113<br />

historical control patients treated with BMS. Survival at 1-, 2- and 3-year follow<br />

up was 95%, 90% and 86% for patient who received a DES, respectively (see<br />

Figure).<br />

Conclusion: The favorable survival data with DES in patients with left ventricular<br />

dysfunction is reassuring and within the limitations of a retrospective analysis<br />

suggests added benefit of DES (vs BMS) in a higher risk cohort such as those<br />

with LV dysfunction, without showing any signal of late mortality hazard.<br />

P2820 Completeness of revascularization and 3 year event<br />

free survival in the ARTS II trial<br />

B.J. Rensing1 ,P.W.Serruys2 ,M.Morice3 ,B.DeBruyne4 ,<br />

A. Colombo5 ,C.Macaya6 , G. Richardt7 , J. Fajadet8 ,C.Hamm9 ,<br />

K. Wittebol2 on behalf of ARTSII investigators. 1St. Antonius<br />

Hospital, cardiology, Nieuwegein, Netherlands; 2Rotterdam, Netherlands;<br />

3 4 5 6 7 Massy, France; Aalst, Belgium; Milan, Italy; Madrid, Spain; Bad Segeberg,<br />

Germany; 8Toulouse, France; 9Bad Nauheim, Germany<br />

Background: Incomplete revascularization (IR) is a known predictor of outcome<br />

after multivessel (MV) PCI and CABG. Drug eluting stents (DES) might improve<br />

outcome after MV stenting. We conducted a sub analysis of the ARTS2 trial in<br />

which MV disease patients were treated with DES.<br />

Methods: Completeness of revascularisation was assessed by an independent<br />

corelab. The primary end-point was 1 year MACCE free survival (Death, MI, CVA,<br />

revascularization). All events were centrally assessed. The ARTS1 (randomized<br />

MV non-DES PCI vs CABG) surgical arm was used as control.<br />

Results: Of 607 enrolled patients 588 angiograms were available for review. 360<br />

pts had complete revascularization (CR), 228 were incompletely revascularized<br />

(IR).<br />

Outcome (%)<br />

Arts2 30 day Arts 2 1yr Arts2 3yr Arts1 CABG 3 yr<br />

cr ir cr ir cr ir cr ir<br />

n=360 n=228 n=360 n=228 n=360 n=228 n=477 n=90<br />

death 0 0 0,6 1,8 2,5 3,9 4,2 5,6<br />

MI 0,3 1,3 1,4 1,8 3,3 3,9 4,2 7,8<br />

Revasc 0,6 3,9 6,7 9,6 11,9 17,1 4,8 7,8<br />

Death/MI/stroke 0,3 1,8* 2,2 4,8 8,1 8,8 10,3 12,2<br />

MACCE free 99 95* 92 87* 83 78** 86 82<br />

MI = myocardial infarction, MACCE = major adverse cardiac and cerebrovascular events,<br />

*p


460 Bring issues in percutaneous cardiovascular interventions<br />

ger scoring system. Five variables selected from the initial multivariate model<br />

were weighted proportionally to their respective odds ratio for stent thrombosis<br />

(thienopyridines discontinuation [6 points], baseline left ventricular ejection fraction<br />

< 50% [4 points], bifurcation lesion [3 points], angioplasty in the setting of<br />

acute coronary syndromes [3 points], left anterior descending as target vessel [2<br />

points]. Three strata of risk were defined (low risk, 0 to 4; intermediate risk, 5 to<br />

8; high risk ≥ 9) with excellent prognostic accuracy for early, late and very late<br />

thrombosis (c statistic = 0.75, 0.72 and 0.74, respectively) in the derivation set.<br />

Conclusions: The DERIVATION score can stratify patients with very low and<br />

high stent thrombosis rates and it can be used as a simple clinical tool for the<br />

identification of a sizable cohort in whom close monitoring and aggressive therapy<br />

may be beneficial.<br />

P2824 Clinical events after clopidogrel discontinuation in<br />

patients treated with titanium-nitride-oxide-coated<br />

stents, paclitaxel eluting stents or bare-metal stents<br />

P.P. Karjalainen1 , A.-P. Annala1 ,A.Ylitalo1 , K.E.J. Airaksinen2 .<br />

1Satakunta Central Hospital, Dept. of Cardiology, Pori, Finland;<br />

2Turku University Hospital, Turku, Finland<br />

Purpose: The purpose of this study was to evaluate clinical events and stent<br />

thrombosis (ST) after clopidogrel discontinuation in patients treated with titaniumnitride-oxide-coated<br />

bio-active stents (BAS), paclitaxel eluting stents (PES) and<br />

bare-metal stents (BMS).<br />

Methods: Between May 2003 and November 2004 all patients undergoing percutaneous<br />

coronary intervention (PCI) were eligible in this single centre study.<br />

The primary end point of the study was major adverse cardiac events (MACE)<br />

including myocardial infarction (MI), cardiac death and target lesion revascularization<br />

(TLR). All patients who where MACE free at the time of the clopidogrel<br />

discontinuation were followed for an additional 12 months after the clopidogrel<br />

withdrawal.<br />

Results: A consecutive series of 589 nonselected patients underwent PCI during<br />

the study period and 519 of them remained MACE free at the time of clopidogrel<br />

discontinuation (BAS 184, PES 183, BMS 152). Complete follow-up datasets<br />

were available in all patients. During 12 months follow-up, the incidence of MACE<br />

was comparable in the 3 groups, but MI and ST were more common in PES group<br />

(Table). There was no ST observed in the BAS group.<br />

Outcome events during 12 months FU<br />

BAS (n=184) PES (n=183) BMS (n=152) P<br />

Myocardial infarction, % 2.2 8.2 2.0 0.01*, 0.01 †<br />

Cardiac death, % 0 1.6 2.0 NS<br />

Target lesion revascularization, % 1.1 4.9 3.9 NS<br />

MACE, % 3.8 9.3 7.9 NS<br />

Stent thrombosis, % 0 3.8 0.7 0.009*<br />

All cause death, %<br />

* BAS versus PES;<br />

1.6 2.7 2.6 NS<br />

† BMS versus PES.<br />

Conclusions: After the clopidogrel discontinuation, we observed an increased<br />

incidence in MI and ST with the use of PES.<br />

P2825 Comparison between on-label versus off-label use<br />

and results for drug-eluting coronary stents in clinical<br />

practice<br />

R. Zahn 1 , C. Nienaber 2 ,K.Kuck 3 , S. Schneider 1 , J. Senges 1 on<br />

behalf of DES.DE Registry. 1 Ludwigshafen, Germany; 2 Rostock,<br />

Germany; 3 Hamburg, Germany<br />

Background: In clinical practice drug-eluting stents (DES) are often used for "offlabel"<br />

indications. This might be associated with highr complication rates compared<br />

to "on-label" use of DES.<br />

Methods: We analysed data from the prospective German DES.DE registry.<br />

Results: Between <strong>September</strong> 2005 and Oktober 2006 5315 patients were treated<br />

with DES. In 2170 patients (40,8%) DES were used for "on-label" indications (1<br />

lesion, native arteries, de novo stenosis, lesion length


vessels (DES 16.7%, BMS 6.7%, p=0.06), with no significant difference between<br />

DES and BMS for ST (DES 10.2%, BMS 6.7%, p=0.4).<br />

Conclusions: Thus, after a 3 year follow-up, DES are overall as safe as BMS for<br />

acute stenting in STEMI. However, there seems to be a particular benefit of DES<br />

in STEMI-PCI in patients with small/bypass graft infarct vessels, but not in large<br />

native infarct vessels. If these findings are confirmed in larger randomized data<br />

sets, they may directly impact on DES use in STEMI.<br />

P2828 Angiographic predictors of improvement in left<br />

ventricular regional function after delayed primary<br />

percutaneous coronary intervention<br />

A.M.M. Mahrous, M. Abdelghany, S. Ghareeb, S. Eltobgi. Cairo,<br />

Egypt<br />

Background: There are few data concerning the association between angiographic<br />

parameters and short-term recovery of left ventricular (LV) regional asynergy<br />

after primary percutaneous coronary intervention (PCI)<br />

Objective: To define angiographic predictors of recovery of LV regional function<br />

after primary PCI in patients with acute STEMI.<br />

Methods: Thirty-five consecutive patients with acute STEMI who presented 6<br />

hours after onset of chest pain and scheduled for primary PCI were submitted<br />

for assessment of thrombus scoring system, thrombolysis in myocardial infarction<br />

(TIMI) flow grade, corrected TIMI frame count (cTFC), tissue myocardial perfusion<br />

grading (TMP) and myocardial dye intensity before and after successful PCI. The<br />

X-sizer thrombectomy catheter systems were used in 10pts. The left ventricular<br />

global wall motion index (GWMI) was determined by echocardiography before and<br />

6 months after intervention. Improved regional left ventricular function at follow-up<br />

was defined as GWMI reduction > 0.3.<br />

Gray scale calculation & coloured blush.<br />

The two groups were similar in terms of clinical and pre-interventional angiographic<br />

characteristics. On multivariate analysis, improvement of TMP grade<br />

(0.30±0.73 at baseline Vs 2.20±0.95 after PCI, p=0.007) & use of a thrombectomy<br />

device (p=0.02) were the only independent predictors of 6-months improvement<br />

of GWMI (r2=0.64). GWMI at Fu showed significant correlation with reduction<br />

of the thrombus score (4.40±0.88 at baseline Vs 0.15±0.48 after PCI,<br />

r2=0.42,p=0.012) and with enhanced myocardial dye intensity (5.86±5.95 Vs<br />

10.55±4.72Pixel, r2=-0.65, p 13. During a mean follow-up of 28.0±14.5 months MACE occurred in<br />

26 patients (12.5%): cardiac death in 9 patients (4.3%) and TLR in 17 patients<br />

(8.2%). The cumulative MACE-free survival was 89.0%, 87.4% and 85.4% at 1,<br />

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462 Bring issues in percutaneous cardiovascular interventions<br />

2, and 3 years, respectively. ST occurred in 3 patients (1.4%): one case was definite<br />

and the other two cases were probable/possible ST. There were no cases<br />

of very late ST. Angiographic follow-up was performed in 79.3% of patients. Binary<br />

restenosis occurred in 13 patients (8.3%). In 11 (7.0%) patients restenosis<br />

occurred in the distal LMCA; these were in-stent involving only the ostium of the<br />

LCX in 10 patients (91%) and the ostium of both LAD and LCX artery in 1 patient<br />

(9%). The others 2 patients had ostial LMCA lesion and restenosis occurred in<br />

the proximal segment adjacent to the stent. An Euroscore >6 was the only independent<br />

predictor of MACE [hazard ratio (HR) 2.24, 95% confidence interval<br />

(CI) 1.05-4.77, p= 0.04]. There was a trend toward an increased risk of MACE<br />

associated with distal ULMCA (HR 2.14, 95% CI 0.87-5.29, p= 0.10).<br />

Conclusions: Our study showed DES implantation in ULMCA to be feasible, safe<br />

and effective at long-term. Randomized trials comparing percutaneous versus<br />

surgical revascularization are warranted to better define the treatment of choice<br />

for ULMCA disease.<br />

P2832 Comparison of the cost-effectiveness of<br />

serolimus-eluting versus bare-metal stents in relation<br />

to patient coronary artery disease status<br />

S.N. Willich, D. Mcbride, S. Roll, T. Reinhold, B. Brueggenjuergen.<br />

Charite University Medical Center Berlin, Institute for Social<br />

Medicine, Epidemiology, Berlin, Germany<br />

Objective: To evaluate the cost-effectiveness of serolimus-eluting stents (SES)<br />

to bare-metal stents (BMS) in patients with single-vessel coronary artery disease<br />

(SVD) compared with patients with multi-vessel disease (MVD).<br />

Methods: In the prospective GERSHWIN study (German Stent Health Outcome<br />

and Economics Within Normal Practice) in 35 hospitals in Germany, patients<br />

with coronary artery disease (CAD) undergoing percutaneous coronary intervention<br />

(PCI) were electively treated with SES or BMS (sequential control design).<br />

Standardized questionnaires completed by patients and physicians through 18<br />

months following PCI documented major adverse coronary events (MACE), including<br />

death, myocardial infarction, coronary artery bypass surgery and re-PCI<br />

in target vessel, as well as disease-related direct and indirect costs.<br />

Results: From April 2003 until June 2005, 658 patients were treated with SES<br />

(87% male, mean age 63±9) und 294 patients with BMS (79% male, mean age<br />

64±10). SVD was documented in 34% BMS patients and 29% SES patients. After<br />

18 months, 4% of SES vs 16% of BMS patients with SVD had suffered MACE (p<br />

adjusted


patients receiving a DES and the rate of CV events notably high at almost 5%. A<br />

thorough assessment of the patients’ likelihood of needing a surgical procedure<br />

within 2 years of DES placement should be undertaken and the risk of placing a<br />

bare metal stent versus a DES carefully evaluated.<br />

P2836 Longterm outcomes of Drug-Eluting Stents (DES):<br />

comparision with Bare-Metal Stents (BMS)<br />

Y.-S. Choi1 , K.-B. Seung2 , W.-S. Chung2 ,J.-H.Park2 ,S.-S.Oh2 ,<br />

C.-S. Park 2 ,Y.-S.Oh2 , H.-J. Youn2 ,H.-Y.Kim2 ,P.-J.Kim2 . 1St. Mary’s Hospital, Seoul, Korea, Republic of; 2The Catholic University<br />

of Korea, Internal Medicine, Seoul, Korea, Republic of<br />

Backgrounds: There were no questions about the superiority of DES over BMS<br />

in terms of reducing angiographic restenosis. However, the long-term safety of<br />

DES is far less certain. The aim of this study was to compare the longterm outcomes<br />

of DES and BMS in real world.<br />

Methods: Total 2313 patients [BMS: DES=759 (32.8%): 155 4(67.2%), mean age<br />

DES=62±10 vs BMS=61±10 years, (male %) DES vs BMS=64.6% vs 70.3%]<br />

were enrolled and they were registered to The Catholic University Percutaneous<br />

Coronary Intervention Registry from January 2004 to March 2006. We included<br />

the patients only if the follow up duration was at least 12 months. The primary<br />

objective was all cause mortality and secondary objectives were cardiac mortality<br />

and stent thrombosis. The presence or abscence of such events were investigated<br />

by telephone interview and database from National Health Insurance. Stent<br />

thrombosis was determined based on the definition of the Academic Research<br />

Consortium (ARC).<br />

Results: 1. Mean follow up duration of BMS and DES was 41.9±13.9 month<br />

and 25±8.6 month respectively (p


464 Bring issues in percutaneous cardiovascular interventions<br />

Methods: to test this hypothesis we studied 2429 consecutive pts, 1331 with<br />

acute coronary syndromes, and 1098 with stable angina undergoing PCI in a<br />

multicenter study in Italy. In all pts CRP levels were determined at admission;<br />

troponin I (cTNI) and CK-MB were assessed before and after PCI. End-point of<br />

the study was total mortality at two years follow-up.<br />

Results: after two years 102 pts died. At univariate analysis baseline CRP, creatinine,<br />

ejection fraction and diabetes and post-PCI CK-MB and cTNI elevation were<br />

all significant determinant of prognosis. However, at multivariate survival analysis<br />

CRP > 3 mg/L was an independent determinant (with creatinine, ejection fraction<br />

and diabetes) of future events (CRP OR= 1.81, p


Results: The two groups had similar risk factors for atherosclerosis. The �PTX3<br />

was larger in the DES group than in the BMS group (0.10±0.05 vs. -0.01±0.06<br />

ng/ml, p18mm in length) group (n=18) than in the short group (≤18mm, n=13)<br />

(0.14±0.09 vs. 0.02±0.10 ng/ml, p


466 Bring issues in percutaneous cardiovascular interventions / Cardiovascular effects of diabetes mellitus<br />

Health Survey (SF-36) in patients treated with SES (n=585), BMS (n=483) or<br />

CABG (n=492).<br />

Results: The corresponding participating rates varied from 100% at baseline to<br />

93% at 36 months. Both stenting and CABG resulted in significant improvement<br />

of HRQL and anginal status. There was a trend towards better HRQL after CABG<br />

than BMS beyond 6 months. Already from the first month up to three years, SES<br />

patients had, on average, 10% significant better HRQL than BMS patients on<br />

all HRQL subscales (p


among their non-DM counterparts (HR 1.00, 95%CI 0.86-1.17; zeta score 0.041;<br />

p=0.967).<br />

Conclusion: The present report based on patients with coronary artery disease<br />

is the first to demonstrate that the prognostic capability of resting heart rate is<br />

equally important in patients with and without diabetes.<br />

P2853 Neopterin predicts the risk for fatal ischemic heart<br />

disease in type 2 diabetes mellitus: results from the<br />

HUNT study<br />

I. Vengen1 ,A.C.Dale2 ,R.Wiseth1 , K. Midthjell1 , V. Videm2 .<br />

1 2 NTNU, Laboratory Medicine, Trondheim, Norway; St. Olav’s<br />

Hospital, Cardiology, Trondheim, Norway<br />

Purpose: Neopterin is produced by activated monocytes. Activation of the<br />

monocyte-macrophage system may contribute to plaque instability in subjects<br />

with coronary artery disease. Neopterin has therefore emerged as a novel predictor<br />

of coronary events. Hs-CRP, a marker of low-grade inflammation, has traditionally<br />

been used in prediction of risk for fatal ischemic heart disease (IHD).<br />

However, the predictive value of hs-CRP has been disputed. The aim of this study<br />

was to investigate the predictive value of neopterin and hs-CRP on long-term risk<br />

for fatal IHD in patients with recently diagnosed diabetes, compared to a matched<br />

group of non-diabetic subjects.<br />

Methods: 200 patients with newly detected diabetes and a matched control<br />

group without diabetes were selected from HUNT1, a large population study conducted<br />

in Norway in 1984–86. Blood was drawn at baseline and frozen serum<br />

was stored. The diabetic patients were followed for ten years with annual HbA1cmeasurements.<br />

Fatal IHD was registered until 2004. Neopterin and hs-CRP concentrations<br />

were divided into tertiles, and Cox regression analysis with correction<br />

for age, gender, hypertension, body mass index, previous cardiovascular disease,<br />

total cholesterol and HbA1c was used to estimate hazard ratios (HR) for fatal IHD.<br />

Results: At baseline hs-CRP was significantly increased in the diabetic compared<br />

to the control group (p < 0.0005). Baseline neopterin concentrations did not<br />

significantly differ between the groups (p = 0.65). Neither hs-CRP nor neopterin<br />

emerged as significant predictors of fatal IHD in the control group. In the diabetes<br />

group neopterin was an independent predictor of fatal IHD (HR 2.7, 95% CI 1.2<br />

– 6.3) whereas hs-CRP did not significantly predict fatal IHD (HR 2.2, 95% CI<br />

0.9-5.3).<br />

Conclusions: Neopterin is a novel and robust predictor of fatal IHD in diabetic<br />

patients. In the present study of newly diagnosed diabetic subjects neopterin was<br />

a better predictor of fatal IHD than was hs-CRP. This could be caused by neopterin<br />

being a more plaque-specific marker, whereas hs-CRP reflects non-specific lowgrade<br />

inflammation common both for atherosclerosis and diabetes.<br />

P2854 In-hospital mortality in diabetic and non-diabetic<br />

patients with AMI: a time trend analysis based on the<br />

Chilean National Acute Myocardial Infarction Register,<br />

2001-2006<br />

C. Nazzal1 , R. Corbalan2 , P. Campos3 ,J.Bartolucci4 ,G.Cavada1 ,<br />

J.C. Prieto 5 , F. Lanas6 on behalf of GEMI Group. 1School of Public Health,<br />

Universidad de Chile, Epidemiology Dept., Santiago, Chile; 2Catholic University<br />

Hospital, Santiago, Chile; 3Hospital de Urgencias, Santiago, Chile; 4Universidad de Los Andes, Santiago, Chile; 5Universidad de Chile, Santiago, Chile;<br />

6Universidad de la Frontera, Temuco, Chile<br />

Diabetics with acute myocardial infarction (AMI) are known to have higher mortality<br />

rates than nondiabetics.Therefore we evaluate in-hospital mortality trends<br />

and in-hospital treatment in patients with AMI, diabetics and non-diabetics, of the<br />

Chilean Register of Myocardial Infarction (GEMI).<br />

Methods: 8219 diabetics and non diabetics patients with AMI, admitted in 15<br />

hospitals from the GEMI Group between 2001 and 2006 were analyzed. Demographic<br />

characteristics, in hospital treatment and in hospital mortality were<br />

compared between the two groups. We conducted logistic regresión analyses,<br />

adjusted by age and gender and expressed results as OR and 95% CI.<br />

Results: 25.8% of patients had diabetes, being significantly older (65 vs 62 years,<br />

p


468 Cardiovascular effects of diabetes mellitus<br />

(AMI) has been demonstrated as a strong predictor of short- and long-term<br />

mortality. It has been also recognized that DM is associated with increased rate of<br />

post-infarctional heart failure. Progressive heart failure after acute myocardial infarction<br />

in non-diabetic patients is related mainly with left ventricular (LV) remodeling,<br />

which is a complex process influenced by multiple factors including microvascular<br />

reperfusion. However only few and conflicting data relating the effects of<br />

DM on post-infarctional LV remodeling are available, especially in patients treated<br />

with primary coronary intervention (PCI). The link between LV remodeling and<br />

impaired microvascular reperfusion has been observed in several studies. DM is<br />

associated with abnormal endothelial function, increased inflammatory response,<br />

increased platelets’ and leukocytes’ plugging and seems to be important factor<br />

deteriorating microvascular reperfusion in acute phase of myocardial infarction.<br />

Aim: The aim of our study was to evaluate the relations between diabetes mellitus,<br />

myocardial reperfusion and left ventricular remodeling in patients with acute<br />

myocardial infarction.<br />

Methods: The study population consisted of 189 patients with first anterior AMI<br />

successfully treated with PCI. LV remodeling was defined as an increase in enddiastolic<br />

volume ≥20%, based on repeated measurements in individual patients.<br />

The study population was divided into 2 groups according to the presence n=36<br />

(19%) (DM group) or absence n=153 (81%) (NDM group) of DM.<br />

Results: The impaired myocardial reperfusion measured as myocardial blush<br />

grade 0-1 was observed not significantly more often in DM group (44.4% vs<br />

37.9%, p=0.47). ST-segment resolution >50% was observed in 49.7% of patients<br />

in NDM group and in 19.4% of DM group, p=0.001. LV remodelling was not significantly<br />

more often in DM group (33.3% vs 21.6%, p=0.19). The symptoms of HF<br />

developed in 55.2% of patients with DM and in 27.1% of NDM group (p=0.006).<br />

Diastolic HF was noticed significantly more often in DM group (36,1% vs 18.3%,<br />

p=0.02). Logistic regression analyses revealed impaired myocardial reperfusion<br />

(OR 2.76; p=0,006), basic EDV (OR 0.98; p=0.001) as independent predictors of<br />

LV remodelling.<br />

Conclusion: In patients with myocardial infarction DM was associated with development<br />

of diastolic HF, but not LV remodelling. Impaired myocardial reperfusion<br />

and basic EDV lead to a higher percentage of LV remodelling in AMI patients.<br />

P2857 Prognostic role of the glucometabolic status<br />

assessed in a metabolically stable phase after a first<br />

acute myocardial infarction<br />

I. Janszky1 , J.H. Hallqvist2 , R. Ljung2 , N. Hammar2 . 1Karolinska Institute, Public Health Sciences, Stockholm, Sweden; 2Stockholm, Sweden<br />

Context: The prognostic role of the glucometabolic status evaluated at a metabolically<br />

stable phase after an AMI is not known. Objective: To examine fasting glucose<br />

and insulin levels in patients surviving 3 months after a first AMI in relation<br />

to long-term prognosis. Design, Settings and Patients: A total of 1167 consecutive<br />

patients between 45-70 years with a first non-fatal AMI underwent a standardized<br />

clinical examination and were followed for a mean of 8 years. Impaired<br />

fasting glucose (IFG) was defined as fasting glucose between 5.6-7mmol/L, and a<br />

level ≥7 mmol/L as newly detected diabetes. Patients with a fasting glucose level<br />


tigated the long-term consequences of diabetes on the heart in a prospective<br />

population-based study.<br />

Methods: The population-based MONICA/KORA-Augsburg cohort study provided<br />

anthropometric, biochemical and echocardiographic data for 1005 individuals<br />

examined during a baseline survey in 1994/95 and a follow-up investigation<br />

ten years later. We defined three groups of individuals: who were persistently,<br />

at both examinations, non diabetics (nonDM, i. e.; defined as no history of diabetes<br />

and not using medications for glycemic control at both examinations; n =<br />

811), who were persistently diabetic (PDM, i. e., defined as disease known to the<br />

patient as reported by standard questionnaire or the use of antiglycemic medications<br />

or insulin or non-fasting glucose blood levels ≥200mg/dl; n = 34) and who<br />

presented incident diabetes at follow-up (incDM; n = 19). We evaluated prospectively<br />

the impact of diabetes on the 10-year changes in left ventricular (LV) mass<br />

indexed to height 2.7 (in g/m 2.7 ), left ventricular end-diastolic diameter (LVEDD in<br />

mm), wall thickness (WT = septal + posterior wall thickness in mm), relative wall<br />

thickness (RWT, WT in mm divided by in mm), left atrial diameter (LA in mm) and<br />

the ratio of early diastolic peak transmitral flow and early diastolic peak myocardial<br />

relaxation velocities (E/EM) using linear regression models adjusting for age<br />

and sex and other relevant confounders including systolic blood pressure.<br />

Results: For the relative changes over the ten years period, there was a positive<br />

trend across the three groups for LV mass2.7 (p=0.011), LVEDD (p=0.002) and<br />

LA (p=0.020). Specifically, compared the mean difference with the nonDM group,<br />

the PDM group, had a bigger relative increase of 12.6% (95% confidence interval:<br />

4.20% to 20.9%, p=0.003) in the LV mass2.7, 6.0% (2.70% to 9.30%, p


470 Cardiovascular effects of diabetes mellitus<br />

P2864 Implications of diabetes mellitus for temporal<br />

changes in arterial stiffness. The MONICA/KORA<br />

augsburg cohort study<br />

M.R.P. Markus 1 ,J.Stritzke 1 , S. Duderstadt 1 ,W.Lieb 1 , A. Luchner 2 ,<br />

A. Doering 3 , H. Schunkert 1 , H.-W. Hense 4 on behalf of The<br />

MONICA/KORA Augsburg Cohort Study.. 1 Luebeck, Germany; 2 Regensburg,<br />

Germany; 3 Neuherberg, Germany; 4 Muenster, Germany<br />

Background: Several studies suggest that diabetes mellitus is one of the most<br />

important risk factors for the increase in arterial stiffness which is associated with<br />

cardiovascular events. However, details of the mechanisms of this process are still<br />

unclear. We investigated the impact of diabetes on aorta stiffness in a prospective<br />

population-based study.<br />

Methods: The population-based MONICA/KORA-Augsburg cohort study provided<br />

anthropometric, biochemical and echocardiographic data for 1005 individuals<br />

examined during a baseline survey in 1994/95 and a follow-up investigation<br />

ten years later. In the follow-up study, pulse wave analysis was also realized. We<br />

defined two groups of individuals: persistent non-diabetics (nonDM, no history of<br />

diabetes and not using medications for glycemic control at both examinations;<br />

n = 839) and diabetics at follow-up who either were persistent diabetics at both<br />

examinations or incident diabetic at follow-up (DM, by patient history or use of<br />

antiglycemic medications or insulin, or having non-fasting glucose blood levels<br />

≥200mg/dl; n = 56). We evaluated, by cross sectionally analysing the follow-up<br />

examination, the association of incident plus persistent diabetes with peripheral<br />

and central measures of blood pressure (pulse wave analysis). We adjusted for<br />

sex, age, body fat, height 2.7 and the use of antihypertensive medication.<br />

Results: At the follow-up observation, the peripheral SBP, after adjustment, was<br />

not statistically different between the two groups. Compared to the non-DM group,<br />

the DM group had a higher outgoing pressure wave height (29.1 mmHg [95% Cl:<br />

27.3 to 31.0] vs. 26.8 mmHg [26.4 to 27.3], p=0.019), a lower sub-endocardial<br />

viability index (166.1% [161.1 to 171.1] versus 172.2%[171.0 to 173.5], p=0.021)<br />

and a reduced time to peak of reflected wave (212.3 ms [208.9 to 215.6] vs. 216.0<br />

ms [215.1 to 216.8], p=0.036).<br />

Conclusions: Subjects with prevalent and incident diabetes showed significantly<br />

raised indicators of central aortic stiffness despite similar peripheral blood pressures.<br />

This observation may indicate that diabetes independently contributes to<br />

the alterations of central vascular properties.<br />

P2865 Diabetes is associated with increased extracoronary<br />

atherosclerotic burden in young patients with<br />

coronary artery disease<br />

A.A.M. Farrag, N. Abdel Razek, G. Yousef, A. Zaki. Cairo University,<br />

Cardiology, Cairo, Egypt<br />

Background: Diabetes mellitus is one of several known risk factors to develop<br />

coronary artery disease (CAD) especially in young age. Coronary atherosclerosis<br />

is continued to be one of the major causes for morbidity and mortality worldwide.<br />

In this study we test the hypothesis that diabetes is associated not only with<br />

increased coronary atherosclerotic burden but also extracoronary calcific burden<br />

as well.<br />

Methodology: We studied 111 patients below age 65; scheduled for coronary angiography<br />

(CA) because of presence/suspected coronary artery disease (CAD).<br />

Transthoracic echocardiography was done to assess for the presence of aortic<br />

sclerosis and/or mitral annular calcification. Calcium score in the coronary arteries<br />

(CCS), aortic valve (AVC), mitral annulus (MAC), aortic arch (AAC) and descending<br />

aorta (DAC) were measured by multidetector computed tomography (4detector<br />

system, GE, with a dedicated software for calcium measurement, Smart<br />

Score). We consider the presence of ≥50% diameter stenosis (by quantitative<br />

CA) of any major epicardial vessel to be an obstructive plaque (OP). Patients<br />

were classified into a diabetic group (n= 59) and a non-diabetic group (n= 52).<br />

Data for calcium score was expressed as median.<br />

Results: Echocardiography revealed that 61% of diabetic group had aortic sclerosis<br />

and 30.5% had mitral annular calcification compared to 36.5% and 9.6%<br />

in non-diabetic group with p= 0.01 and 0.007 respectively. CA revealed that diabetics<br />

have a higher prevalence of OP 3.34±2.6 vs. 1.9±1.6, p= 0.005. Diabetic<br />

group had significantly higher levels of CCS, AVC, MAC, AAC and DAC as compared<br />

to non-diabetic group (table).<br />

Clacium score by computed tomography<br />

Variable Diabetics Non-diabetics p value<br />

CCS 133 (0-1571) 90 (0-624)


culogenesis. Reduction of VPC and EPC among BK sensitive cells in diabetic<br />

patients suggests an imbalance among the spectrum of cells recruited by kinins.<br />

P2868 Postprandial hyperglycemia is an important<br />

determinant of platelet activation in early type 2<br />

diabetes mellitus. Evidence from biochemical<br />

measurements and pharmacological intervention with<br />

acarbose<br />

F. Santilli1 ,G.Formoso1 , P. Sbraccia2 ,M.Averna3 ,R.Miccoli4 ,<br />

N. Pulizzi4 , A. Consoli 1 , R. Lauro2 , C. Patrono5 ,G.Davi’ 1 . 1G. d’Annunzio<br />

University Foundation, Center of Excellence on Aging, Chieti, Italy; 2University of Rome Tor Vergata, Department of Internal Medicine, Rome, Italy; 3University of Palermo, Department of Internal Medicine, Palermo, Italy; 4University of Pisa,<br />

Department of Endocrinology and Metabolism, Pisa, Italy; 5Catholic University<br />

School of Medicine, Department of Pharmacology, Rome, Italy<br />

Purpose: Chronic hyperglycemia is a major determinant of in vivo platelet activation<br />

in diabetes mellitus (DM). Acarbose, an α-glucosidase inhibitor, is associated<br />

with a significant reduction in the risk of cardiovascular events in patients with<br />

impaired glucose tolerance. We performed a randomized, double-blind, placebocontrolled,<br />

multicenter study evaluating the effects of acarbose on platelet activation<br />

and its potential determinants in newly-diagnosed type 2 diabetic patients.<br />

Methods: Forty-eight subjects (26 M, 22 F, aged 61±8 yr), with early type 2<br />

DM (baseline HbA1c


472 Cardiovascular effects of diabetes mellitus<br />

Plaque area (PA) was calculated as VA-LA. Percentage plaque area (%PA) was<br />

calculated as PA/VA.<br />

Results: VA in DM, AGT, and NTG group was 14.8±4.1 mm 2 , 16.0±4.1 mm 2 , and<br />

14.9±4.5 mm 2 respectively group (p=ns). LA was 7.3±3.0mm 2 ,8.2±2.2mm 2 ,<br />

and 9.3±3.3mm 2 respectively. LA of DM group was significantly smaller than<br />

that in AGT and NGT group (p


y echo-tracking technique calibrated for blood pressure (Aloka Alpha10). A local<br />

CCA wave speed (WS) was derived by the water hammer equation. Carotidfemoral<br />

pulse wave velocity (PWV, Complior) was measured as an index of aortic<br />

stiffness.<br />

Results: DM1 subjects had, compared to C, higher (p


474 Diabetes mellitus, predictors and drugs<br />

P2881 Insulin sensitizers decrease adverse events in<br />

diabetic patients with heart failure<br />

J. Luu, C. Gans, P. Mesgarzadeh, T. Stamos, J. Kao. University of<br />

Illinois-Chicago, Medicine, Chicago, United States of America<br />

Background: The mortality rate among patients with heart failure<br />

(HF) is 4-8 times greater than that of the general population. HF patients with<br />

diabetes have even worse outcomes; diabetes increases the mortality risk by<br />

11-25%. Myocardial contractility and filling are depressed in the insulin-resistant<br />

state, but use of insulin sensitizers has historically been precluded in HF patients.<br />

Whether insulin sensitizers can mitigate these adverse cardiovascular effects,<br />

and whether these contraindications are warranted, remain unclear.<br />

Methods: Patients with both diabetes and HF followed in outpatient cardiology<br />

clinic at a single institution from 2000-2007 (n=119) were grouped by diabetic<br />

regimen: insulin-sensitizers (metformin +/- thiazolidinediones [TZD], n = 56) vs.<br />

non-sensitizers (insulin +/- sulfonylureas, n = 63). The sensitizer group consisted<br />

of 36 metformin-only, 2 TZD-only, and 18 metformin + TZD patients. The primary<br />

endpoint was admission for HF exacerbation.<br />

Results: Fewer insulin-sensitizer (IS) patients had HF exacerbations compared<br />

to non-sensitizer (NS) patients, and Kaplan-Meier curves showed longer<br />

exacerbation-free time at 5 years (P < 0.0001). IS patients had fewer total number<br />

of HF exacerbations (0.65 vs. 2.6, P= 0.0035). At baseline, IS patients were<br />

heavier and had lower creatinine levels (1.02 vs. 1.29, P = 0.001); all demographics<br />

were otherwise similar.<br />

Time to <strong>Heart</strong> Failure Exacerbation<br />

Conclusions: Insulin sensitization improves outcomes in diabetic patients with<br />

HF. Patients have longer times to HF exacerbation and fewer total exacerbations.<br />

Use of insulin sensitizers in HF patients, however, remains controversial.<br />

Our study adds to the body of data that suggests increased benefit, and not risk,<br />

of insulin sensitization in this population.<br />

P2882 Chronic phosphodiesterase 5 inhibition improves<br />

endothelial function in men with type-2 diabetes<br />

C. Vitale 1 ,A.Aversa 2 , M. Volterrani 1 , A. Fabbri 3 , G. Spera 2 ,<br />

M. Fini 1 , G.M.C. Rosano 1 . 1 IRCCS San Raffaele Hospital, Medical<br />

Sciences, Roma, Italy; 2 University La Sapienza, Medical Sciences,<br />

Roma, Italy; 3 University Tor Vergata, Medical Sciences, Roma, Italy<br />

Objective: Diabetic patients have a reduced endothelial response to<br />

phosphodiesterase-5 inhibitors. Aim of this study was to evaluate the effects of<br />

daily Sildenafil (SIL) on endothelial function in patients with type-2 diabetes mellitus<br />

(DM2).<br />

Methods: In a double-blind, placebo-controlled parallel design, 20 patients without<br />

erectile dysfunction randomly received a loading dose of SIL (100 mg) for 3<br />

days followed by either SIL-25 mg three times a day (tds) for 4 weeks or SIL-25<br />

mg tds for four days followed by placebo tds for 3 weeks. Brachial artery flow<br />

mediated dilatation (FMD) with high-resolution Doppler ultrasound and reactivehyperemia<br />

peripheral arterial tonometry by Endopath, were measured, respectively.<br />

Also, variations of bioumoral markers of endothelial function were assessed.<br />

Results: After one week, flow mediated dilatation (FMD) improved significantly<br />

(>50% compared with baseline) in patients allocated to both SIL arms (62% and<br />

64%, respectively). In patients allocated to chronic SIL, progressive increase in<br />

percentage of patients with FMD improvement was noted (78%, 86%, 94% at 2,<br />

3 and 4 weeks respectively) while a progressive decrease in the placebo group<br />

occurred (45%, 18%, 6% at 2, 3 and 4 weeks respectively). At the end of the<br />

study a significant improvement in FMD compared with baseline was noted after<br />

chronic SIL (FMD from 6.8±0.5 to 12.5±0.7%, p=0.01 vs. baseline). A decrease<br />

in endothelin-1 levels and an increase in nitrite/nitrate levels were found after<br />

chronic SIL; significant changes from baseline in CRP, IL-6, ICAM and VCAM<br />

levels were also found.<br />

Conclusions: in DM2 patients, daily SIL administration improves endothelial<br />

function and reduces markers of vascular inflammation. Thus, diabetes-induced<br />

impairment of endothelial function and erectile dysfunction may be improved by<br />

prolonged phosphodiesterase-5 inhibition.<br />

P2883 Effect of allopurinol therapy on endothelial function<br />

in patient with diabetes mellitus<br />

N. Kalay1 , M. Tasdemir 1 ,I.Murat1 , I. Ozdogru 2 , A. Dogan2 ,<br />

M.T. Inanc2 ,M.G.Kaya3 . 1Sorgun State Hospital, Cardiology<br />

Department, Yozgat, Turkey; 2Erciyes University, Cardiology,<br />

Kayseri, Turkey; 3Cardiology, Kayseri, Turkey<br />

Introduction: Endothelial dysfunction and atherosclerosis are common well<br />

known problem in diabetes mellitus (DM). Uric aside is an associated factor with<br />

endothelial function (EF) and atherosclerosis even if physiological range. It was<br />

demonstrated that xanthine oxidase inhibition with allopurinol decreases oxidative<br />

stress and improves EF. We investigated effect of high dose and long term<br />

allopurinol therapy on EF in diabetic patients without hypertension.<br />

Method: This study is a randomized, single-blind, and placebo-controlled trial.<br />

Patients with DM were randomized as treatment and control groups. The patient<br />

group consisted of 34 patients and the control group consisted of 32 patients.<br />

To the patient group, daily oral 900 mg allopurinol was started after randomization<br />

and maintained for 12 weeks. Carotis intima-media-thickness (IMT), brachial<br />

artery flow-mediated-dilatation (FMD), and arterial-waveform patterns were measured<br />

at baseline and after the allopurinol therapy.<br />

Results: There was significant correlation between FMD and IMT (r=0.446,<br />

p=0.03). The baseline FMD level was 6.9 in patients and 6.6 in control group<br />

(p=0.8). After allopurinol therapy, FMD significantly increased in the patient group<br />

but no significant change was observed in the control group (Figure). Carotis-<br />

IMT thickness after allopurinol therapy was significantly lower in the patient group<br />

(respectively 73.7±16.4 vs. 66.9±14.7, p=0.01) however it was similar in control<br />

group (respectively 72.4±16.3 vs. 70.5±15.4, p=0.09). There was no significant<br />

change in arterial-waveform pattern in groups.<br />

Figure 1<br />

Conclusion:In diabetic patients, long term and high dose allopurinol has favorable<br />

effect on EF. Further studies are necessary to confirm the clinical significance<br />

of long term and high dose allopurinol therapy.<br />

P2884 Effects of diabetes on the prevalence of aspirin<br />

resistance during low dose aspirin therapyy<br />

P.A. Gurbel, K.P. Bliden, J. Dichiara, T.A. Suarez, S. Yadev,<br />

S. Chaganti, M.J. Antonino, O. Bailon, U.S. Tantry. Sinai Center for<br />

Thrombosis Research, Center For Thrombosis Research, Baltimore,<br />

United States of America<br />

Background: Controversy exists regarding the relation of diabetes and other demographic<br />

variables on the prevalence of aspirin resistance (AR).<br />

Methods: AR was measured after 81 mg aspirin for four weeks in 120 patients<br />

(diabetes = 23) with coronary artery disease by COX-1 specific assays (arachidonic<br />

acid (AA)-induced light transmittance aggregation (AGG), AA-induced AGG<br />

by thrombelastography (TEG), VerifyNow, urinary thromboxane levels) and COX-<br />

1 nonspecific assays (ADP-and collagen-induced AGG and PFA-100).<br />

Results: In the total group a low prevalence of AR (


P2885 Statins are effective in reducing coronary atheroma<br />

progression in diabetic patients. A serial, volumetric,<br />

intravascular ultrasound study<br />

F. Alfonso Manterola, L. Hernando, A. Suarez, V. Lennie,<br />

M.L. Capote, P. Jimenez, R. Hernandez-Antolin, G. Aleong,<br />

J. Escaned, C. Macaya. San Carlos University Hospital, Cardiovascular Institute,<br />

Madrid, Spain<br />

Objective: The value of statins to prevent coronary atheroma progression is a<br />

subject of major interest. However, the effects of statin therapy in selected high<br />

risk subgroups of patients (Pts), including diabetics (D), remains to be established.<br />

We sought to assess the value of conventional statin treatment on coronary<br />

artery disease progression in D Pts.<br />

Methods: 199 consecutive Pts (Mean age 65±10 years, 45 [22%] female) undergoing<br />

serial intravascular ultrasound (IVUS) studies were analyzed: 109 Pts<br />

(55%) were D and 90 (45%) non-D. According to routine clinical practice 167 Pts<br />

(84%) received statin therapy (89% D and 77% non-D). A validated system for<br />

IVUS analysis was used for volumetric analysis. Baseline characteristics, coronary<br />

atheroma burden, and disease progression at follow-up (median 366 days)<br />

was compared according to a)statin therapy and b) D status. Study end-point was<br />

IVUS-detected percent change in atheroma volume.<br />

Results: Pts with conventional statin treatment had an adverse cardiovascular<br />

risk profile, including diabetes, hyperlipidemia and previous coronary interventions.<br />

At last follow-up, total cholesterol (172±26.8 mg/dL vs 189±22.2 mg/dL)<br />

and LDL cholesterol (98.3±26.6 mg/dL vs 117.3±22.5 mg/dL), were significantly<br />

reduced in the treatment group. Baseline percent atheroma volume (PAV) was<br />

similar in patients with and without statin therapy (44.7±10% vs 47.9±11%,<br />

p=0.12) and in D as compared with non-D (44.9±9.9% vs 45.6±10.8%, p=0.61).<br />

In non-D Pts, change in PAV was similar in patients with and without statin therapy<br />

(p=0.99). However, as illustrated in the Figure, change in PAV was significantly reduced<br />

by statin therapy in D Pts (p=0.007).<br />

�PAV according to therapy and D status.<br />

Conclusions: Statin therapy appears to be particularly effective to reduce disease<br />

progression in D Pts.<br />

P2886 Impact of antidiabetic therapy on infarction size and<br />

viability in diabetic patients with ST segment<br />

elevation myocardial infarction<br />

M. Rayan 1 , M. Ghareeb2 ,M.Fahmy2 ,A.Mosa2 . 1Ain Shams<br />

University„ Cardiology Departement, Cairo, Egypt; 2Ain shams<br />

University, Cardiology, Cairo, Egypt<br />

The prevalence of type II diabetes mellitus is rapidly increasing, and cardiovascular<br />

disease is already present at the time of diagnosis. The diabetic patient has<br />

an unfavourable prognosis following acute coronary events.<br />

Aim: To investigate the effect of anti-diabetic therapy on infarction size and viability<br />

in diabetic patients with ST segment elevation myocardial infarction.<br />

Patients and methods: The study enrolled one hundred diabetic patients receiving<br />

either oral anti-diabetic therapy or insulin as a study group and twenty<br />

non-diabetic patients as a control group. All of the subjects survived their first<br />

documented myocardial infarction. All the patients underwent rest Trimetazidine<br />

99mTc Sestamibi SPECT for the estimation of their infarction size and evaluation<br />

of myocardial viability.<br />

Results: The mean age was 55.2 years ±6.6. Males comprised 81.67% of the<br />

sample size. The infarction size was significantly larger in the diabetic group<br />

(n=100) as compared to control group (n=20), (47.5±13.95% vs. 38.75±15.19%,<br />

P


476 Diabetes mellitus, predictors and drugs<br />

P2889 Medical therapy in heart failure patients with diabetes<br />

- supply shortage in women and HFNEF patients<br />

R. Wachter1 , F. Edelmann2 , H.D. Duengen3 , A. Kockskaemper4 ,<br />

S. Stoerk 5 , C. Lueers2 , G. Gelbrich 6 ,B.Pieske4on behalf<br />

of German <strong>Heart</strong> Failure Network. 1University of Goettingen,<br />

Cardiology and Pneumology, Goettingen, Germany; 2University of Goettingen,<br />

Cardiology and Pneumology, Goettingen, Germany; 3University Charite<br />

Campus Virchow Klinikum, Cardiology, Berlin, Germany; 4Medical University<br />

Graz, Cardiology, Graz, Austria; 5Medical University Wuerzburg, Cardiology,<br />

Wuerzburg, Germany; 6University of Leipzig, Center for Clinical Trials, Leipzig,<br />

Germany<br />

Background: Diabetes (DM) is a common comorbidity in patients with heart failure<br />

and DM itself is one of the leading predictors of mortality in heart failure<br />

patients (e.g. in the CHARM trial). We therefore analysed pharmacotherapy of<br />

patients with heart failure and DM according to current ESC guidelines which recommend<br />

ACE/AT1-inhibitor therapy, betablockers, diuretics and aldosteron antagonists.<br />

We spotlighted on therapy in women and on patients with heart failure and<br />

preserved ejection fraction (HFNEF).<br />

Methods: 3442 patients with heart failure from the German <strong>Heart</strong> Failure Network<br />

trial were included (mean age 63.8±13.6 years, 32.7% women). 2429 patients<br />

had systolic heart failure (SHF, ejection fraction below 50%), 1013 patients had<br />

HFNEF (ejection fraction ≥ 50%). 31.3% of patients in the SHF group and 25.1%<br />

of patients in the HFNEF group suffered also from DM (p < 0.001).<br />

Results: Diabetics with HFNEF received an ACE/AT1-inhibitor therapy less often<br />

than patients with SHF (75.8% vs. 90.2%, p < 0.001). Also betablockers (59.1%<br />

vs. 85.8%, p


Conclusions: The patient-centred health programme presented here is suitable<br />

for reducing car-diovascular risk in a sustained fashion.<br />

P2893 The role of gamma-glutamyltransferase as a predictor<br />

of incident diabetes in a cohort of 98,059 men and<br />

women<br />

H. Ulmer1 , C. Kelleher2 , L.J. Brant3 ,H.Concin4 ,G.Diem4 ,<br />

A. Strasak5 , M. Lechleitner6 , E. Ruttmann5 on behalf of VHM&PP.<br />

1Innsbruck Medical University, Department of Medical Statistics, Innsbruck,<br />

Austria; 2Dublin, Ireland; 3Baltimore, United States of America; 4Bregenz, Austria; 5Innsbruck, Austria; 6Zirl, Austria<br />

Purpose: Recent studies have demonstrated an association of serum gammaglutamyltransferase<br />

(GGT) with risk factors for cardiovascular disease, diabetes,<br />

incident morbidity and mortality from heart disease and stroke. Additionally, it was<br />

hypothesized that GGT mediates the relation of overweight with type 2 diabetes<br />

and that overweight itself may not be a sufficient risk factor.<br />

Methods: We assessed whether GGT is an independent predictor for incident diabetes<br />

and whether there is an interaction of GGT with body-mass index (BMI) in<br />

98,059 participants of the Vorarlberg Health Monitoring & Promotion Programme.<br />

Participants (mean age 42 years) had fasting glucose levels < 100mg/dl at baseline<br />

and were longitudinally followed for up to 16.5 years (1989-2005). Fasting<br />

glucose greater than 125 mg/dl (7 mmol/l and higher) was defined as criteria for<br />

a hyperglycaemic condition indicating diabetes. Sex-stratified Cox proportionalhazards<br />

models, adjusted for age, BMI, cholesterol, triglycerides, blood pressure<br />

and smoking, were performed to calculate hazard ratios (HR) and 95% confidence<br />

intervals per quintiles of GGT.<br />

Results: There were 4,675 participants (4.8%) with diabetes during follow-up.<br />

Compared to the lowest GGT quintile, adjusted HR were 1.33 (1.19-1.49) for the<br />

fourth quintile, and 1.68 (1.51-1.87) for the highest quintile. Regarding age, there<br />

was a significant interaction (p=0.015) revealing higher risk of elevated GGT in<br />

older participants. In participants over 65 years and older, HR for diabetes in the<br />

highest quintile of GGT was 2.28 (1.67-3.13). BMI was the strongest risk factor<br />

for diabetes revealing a 1.1 fold increase of risk per index unit. There was no<br />

significant interaction of body-mass index with GGT and other risk factors. The<br />

association of triglycerides with diabetes was strong and even more pronounced<br />

in females and older individuals. Interaction of triglycerides with sex (p=0.001)<br />

and age (p


478 Diabetes mellitus, predictors and drugs<br />

of diabetes14±12 years, HbA1c 7.7±5.4%,NT-proBNP 240±414pg/ml, NYHAclass<br />

I/II/III/IV 86/11/3/0%, proteinuria 24.2%, blood pressure 141±23mmHg, history<br />

of a cardiac disease 17.3%). 30 patients reached the defined endpoint.<br />

In a Cox regression analysis, NT-proBNP was the most potent single predictor<br />

for the defined endpoint, (Exp (B) 1.001p


P2900 Should left ventricular hypertrophy diagnosed by<br />

echocardiography be incorporated into<br />

cardiovascular risk assessment among patients with<br />

type2diabetes?<br />

K.K. Poppe, G.A. Whalley, J. Somaratne, W. Bagg, S. Wells,<br />

R. Jackson, R.N. Doughty. University of Auckland, Medicine,<br />

Auckland, New Zealand<br />

Purpose: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular<br />

disease (CVD). New Zealand Guidelines (NZG) recommend that CVD<br />

risk should be estimated using a modified Framingham equation that incorporates<br />

multiple clinical and laboratory variables. NZG risk assessment does not<br />

include ECG-defined left ventricular hypertrophy (LVH) as it is rare in the general<br />

population. We aimed to assess the prevalence of LVH in patients with T2DM at<br />

mild-moderate CVD risk.<br />

Method: We prospectively studied 360 primary care patients with T2DM without<br />

known clinical CVD. Patients underwent clinical assessment, HbA1c, cholesterol<br />

and echocardiography. Absolute 5-year CVD risk was calculated using the NZG<br />

equation. LV mass was measured (American Society of Echocardiography (ASE)<br />

guidelines) and indexed to body surface area (LVMi): LVH was defined by both<br />

ASE (women≤95g/m2 ,men≤110g/m2 ) and <strong>European</strong> Society of Hypertension<br />

(ESH; women≤110g/m2 ,men≤125g/m2 ) cut-offs.<br />

Results: Mean age 57±11yrs, BP 135/82mmHg, cholesterol 4.8mmol/L, HbA1c<br />

7.6%, diabetes duration 8yrs, LVMi 107ml/m2 . Prevalence of LVH was: ASE 50%;<br />

ESH/ESC 32%. Average NZG 5yr risk was 15.6%: 49% (n=179) were classified<br />

as having mild-moderate (5-15%) risk, of whom 65 (36%) met ASE and 37 (21%)<br />

met ESH LVH criteria (figure).<br />

Conclusion: In these community-based patients with T2DM, half were classified<br />

as having mild-moderate CVD risk, among whom at least 20% had LVH (even<br />

with more conservative LVH criteria). LVH, a significant CVD risk factor, is not<br />

accounted for in current risk assessment of patients with T2DM. Data on the<br />

independent predictive power of LVH diagnosed by echocardiography is required<br />

to determine whether community echo screening for LVH among patients with<br />

T2DM will impact on improved risk prediction and management.<br />

P2901 Hypertensive response during stress test is<br />

associated with impaired glucose regulation in<br />

subjects without hypertension: introducing an<br />

integrated cardio-metabolic clinical tool<br />

M.V. Papavasileiou, C. Thomopoulos, G. Aggelidis, S.M. Karas.<br />

Sismanoglion Hospital, Cardiology, Athens, Greece<br />

Objectives: Subjects suffering from insulin resistance have increased risk for<br />

future cardiovascular disease including hypertension, while normotensives with<br />

exaggerated BP response (EXBPR) compared to those with non-EXBPR during<br />

stress test are more likely to develop hypertension. We investigated the association<br />

between impaired glucose regulation and EXBPR in non hypertensives<br />

undergoing stress test.<br />

Methods: 142 consecutive non hypertensives (aged 46±6 years, 67% males,<br />

34% smokers, office BP 121±6/77±3mmHg) underwent 24h BP monitoring,<br />

echocardiographic study and treadmill stress test according to the Bruce protocol.<br />

Sex and age adjusted criterion for systolic BP at the second stage of exercise<br />

(ex-SBP2) was used to define EXBPR classifying the total population in two subgroups.<br />

Fasting blood samples were obtained for fasting glucose (FG), fasting<br />

insulin (FI), and lipid profile determination. An index of insulin resistance (HOMA)<br />

was estimated, while a standardized oral glucose tolerance test was performed<br />

and glucose levels at 120 minutes (G120) were recorded.<br />

Results: EXBPR occurred in 28.16% of subjects (n=40, aged 48.8±4.9 years,<br />

67% males) while non EXBPR occurred in 71.84% of subjects (n=102, aged<br />

45.01±6.28 years, 65% males) (p


480 Autonomic nervous system in hypertension<br />

AUTONOMIC NERVOUS SYSTEM IN<br />

HYPERTENSION<br />

P2904 Influence of head-up tilt test provocation on<br />

autonomic nervous system in patients suffered from<br />

idiopathic epilepsy during interictal period<br />

T. Zapolski1 , J. Przegalinski1 , A. Wysokinski1 , W. Brzozowski1 ,<br />

A. Tomaszewski1 ,M.Prasal1 ,M.Tynecka2 . 1Department of<br />

Cardiology, Medical University, Chair and Department of Cardiology, Lublin,<br />

Poland; 2Department of Neurology, Medical University, Lublin, Poland<br />

Aim: The neurohormonal disturbances, particularly abnormalities in catecholamines<br />

production and uptake, play an important role in pathophysiology of<br />

epilepsy. The aim of our study was interictal activity of autonomic nervous system<br />

in patients with idiopathic epilepsy.<br />

Material and Methods: Study group consisted with 21 patients (12 men and 9<br />

women, 21 - 72 mean 44,4±11,3 years old), with idiopathic epilepsy. Standard<br />

12-lead EKG and 24-hours EKG monitoring by Holter’s method were performed.<br />

During Holter EKG the following parameters were analyzed: maximal, minimal,<br />

mean heart rate and time domain HRV indices (SDNN, SDANN, SDNN Index,<br />

rMSSD, pNN50). After first 2 hours of Holter EKG the head-up tilt test due to<br />

Westminster’s protocol was performed. Half an hour before tilt test and half an<br />

hour after standard 12-lead EKG was recorded to assess QT length (mean calculated<br />

from 12 leads), QT dispersion index (QTI) due to pattern: QTI = (QT standard<br />

deviation QT: mean QT) x 100. Additionally half an hour before tilt test and<br />

half an hour after 0,5 ml of blood sample was taken to measurement of serum<br />

catecholamines level. Catecholamines concentration was assessed using High<br />

Performance Liquid Chromatography (HPLC).<br />

Results: Rhythm disturbances were found in 6 patients. QTI decreased significantly<br />

after tilt test (3,8±0,87 vs 3,1±0,8). Patients with decreased minimal heart<br />

rate had lower values of QTI. After tilt test all catecholamines level markedly decreased:<br />

noradrenaline (460,1±78,4 vs 392,2±70,7), adrenaline (60,8±10,6 vs<br />

57,15±10,5) and dopamine (35,12±11,9 vs 33,52±11,78). Moreover significant<br />

correlation between noradrenaline concentration and rMSSD as well as pN50<br />

were demonstrated. Patients with higher adrenaline concentration characterized<br />

QT elongation.<br />

Conclusions: In patients with idiopathic epilepsy during head-up tilt test decrease<br />

of noradrenaline, adrenaline, dopamine as well as QT dispersion index<br />

were observed. QT elongation correlated with higher adrenaline concentration<br />

could be a cause of cardiac rhythm disturbances in these patients. Patient with<br />

idiopathic epilepsy require periodic cardiological evaluation including standard 12lead<br />

EKG, Holter’s EKG monitoring and head-up tilt test due to often coexisting<br />

both cardiac rhythm and consciousness disturbances. Those test allow to differentiate<br />

epilepsy ictus form neurocardiogenic syncope.<br />

P2905 Alpha 2b adrenergic receptor deletion polymorphism<br />

is associated with alterations in cardiac autonomic<br />

modulation in obese children<br />

D.M. Prado1 , A.G. Silva1 , M.M. Ribeiro1 , E.S.T. Frazzatto1 ,<br />

M.S. Brasileiro2 , A. Halpern1 , I.C. Trombetta2 ,C.E.Negrao2 ,<br />

S.M.F. Villares1 . 1EndocrinologyHCFMUSP, Endocrinology, Sao Paulo, Brazil;<br />

2InCorHCFMUSP, Sao Paulo, Brazil<br />

α2B-Adrenergic receptor (α2B-AR) polymorphism has been associated with obesity<br />

and alterations in vagal and sympathetic cardiac modulation. Unknown is<br />

whether these associations begin in the childhood. We tested the hypothesis that<br />

obese children carrying α2B-AR deletion polymorphism would have alterations in<br />

the cardiac autonomic modulation.<br />

Methods: A total of 106 obese children were studied (45 M/ 61 F; BMI=30.3<br />

+0.4 kg/m 2 ). From these children, 57 (53.7%) were homozygous for the long form<br />

(Glu12/Glu12), 43 (40.5%) were heterozygous (Glu12/Glu9) and 6 (5.7%) were<br />

homozygous for the short form (Glu9/Glu9). The sympathovagal balance was assessed<br />

by power spectral analysis of heart rate variability at the rest condition.<br />

The genotypes were determined by polymerase chain reaction (PCR) with electrophoresis.<br />

Results: There were no differences in physical characteristics (body weight, BMI,<br />

lean body mass and fat body mass) and metabolic profile (fasting plasma glucose,<br />

fasting plasma insulin, serum total cholesterol, serum triglycerides and leptin)<br />

(P>0.05) among the genotypes. <strong>Heart</strong> rate was similar among genotypes.<br />

However, low frequency (nu) values were significantly higher in children with<br />

Glu9/Glu9 genotype when compared with Glu12/Glu12 and Glu12/Glu9 genotypes<br />

(73.1 +0.9 vs 45.8 +0.5 and 46.5 + 0.5, respectively, P


P2908 Telmisartan up-regulates the expression of<br />

angiotensin-converting enzyme 2 in human umbilical<br />

vein endothelial cells<br />

L. Wang. The First affiliated Hospital, Cardiology Department,<br />

Guangzhou, China, People’s Republic of<br />

Purpose: To determine the effect of telmisartan on the protein and gene expression<br />

of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein<br />

endothelial cells (HUVECs).<br />

Method: HUVECs were treated with various final concentrations of telmisartan<br />

(10-7,10-6 and 10-5mol.L-1) for 24 h. In a time-control experiment, HUVECs were<br />

treated with telmisartan at the final concentration of 10-6mol.L-1 for 6, 12 and 24<br />

h, respectively. In an another protocol, HUVECs were treated with PD123 319(10-<br />

6mol.L-1) separately or combined with same final concentration of telmisartan for<br />

12h, respectively. Changes in both protein and gene expression of ACE2 were<br />

detected by Western blot analysis and RT-PCR technique, respectively.<br />

Results: Telmisartan caused a concentration- and time-dependent increase in<br />

both protein and gene expression of ACE2 (p0.05).<br />

Conclusion: Telmisartan up-regulates the protein and gene expression of ACE2<br />

in a concentration and time dependent manner in HUVECs. This effect may be<br />

mediated via its specific pathway.<br />

P2909 Effects of chronic electrical baroreceptor stimulation<br />

on the sympathovagal balance in patients with<br />

drug-resistant arterial hypertension<br />

K. Wustmann1 ,J.P.Kucera2 , I. Scheffers 3 , Y. Allemann1 ,<br />

J. Schmidli1 ,E.Delacretaz1on behalf of DEBuT-HT trial. 1University Hospital Bern, Cardiology, Bern, Switzerland; 2University of Bern, Physiology,<br />

Bern, Switzerland; 3University Hospital Maastricht, Cardiology, Maastricht,<br />

Netherlands<br />

Objectives: In patients (pts) with drug-resistant hypertension, electrical stimulation<br />

of the carotid baroreflex (ESCB) is a new device-based therapy that produces<br />

a dose-dependent reduction in blood pressure (BP). The aim of the study was<br />

to investigate the effects of chronic ESCB on the sympathovagal balance using<br />

analysis of heart rate variability (HRV) and heart rate turbulence (HRT).<br />

Methods: 13 pts with drug-resistant hypertension were prospectively included in<br />

this substudy of the DEBuT-HT trial. 24-hour ECG were recorded for HRV and<br />

HRT analyses 1 month after implantation with the stimulator turned off and after<br />

3 months of individually optimized electrical therapy. For HRT analysis, the initial<br />

acceleration (turbulence onset) of sinus rhythm following a postextrasystolic<br />

pause and the subsequent slowing (turbulence slope) were analysed after either<br />

premature atrial or ventricular beats.<br />

Results: Chronic ESCB decreased office BP and heart rate (table). HRV timedomain<br />

and frequency-domain parameters assessed using an autoregressive<br />

model (not shown) and fast Fourier transformation (FFT) were significantly<br />

changed during ESCB, indicating a decreased sympathetic activity and an increased<br />

vagal outflow. Furthermore, HRT analysis (conducted in a subset of patients)<br />

suggested an increased vagal tone.<br />

Stimulator off Stimulator on p-value<br />

Systolic BP, mmHg 194±33 158±23 0.002<br />

Diastolic BP, mmHg 121±21 102±14 0.006<br />

Mean heart rate, bpm 82±11 77±10 0.02<br />

NN50* 1554 4139 0.005<br />

RMSSD 19±7 26±30.002 SDNN Index 39±10 48±13 0.004<br />

FFT HF Normalized 88±21 88±17 0.48<br />

FFT LF Normalized 73±9 70±8 0.01<br />

FFT Ratio LF/HF* 2.7 2.3 0.002<br />

Data are given as mean±SD except *: median; HF, LF, high and low frequency.<br />

Conclusion: Chronic ESCB lowers BP in pts with drug-resistant systemic hypertension<br />

by sustained inhibition of sympathetic activity and by increased vagal<br />

outflow. Whether the modulation of sympathovagal balance has favorable cardiovascular<br />

effects beyond BP control should be investigated with further studies.<br />

P2910 Association of aortic pressures with fasting plasma<br />

glucose in patients with and without impaired fasting<br />

glucose<br />

S. Cay, S. Ozturk, F. Biyikoglu, S. Korkmaz. Yuksek Ihtisas Hospital,<br />

Department of Cardiology, Ankara, Turkey<br />

Background: Diabetes mellitus and also impaired fasting glucose are associated<br />

with future cardiovascular disorders. Aortic pulse and fractional pulse pres-<br />

Autonomic nervous system in hypertension 481<br />

sures are strong and independent indicators of the risk of coronary heart disease.<br />

These conditions have been reported to be associated with endothelial dysfunction.<br />

In the present study aortic pulse and fractional pulse pressures of patients<br />

with and without impaired fasting glucose were evaluated.<br />

Methods: Fifty patients with IFG with a mean age of 56.8±12.2 years and 47 patients<br />

with NFG with a mean age of 53.1±11.2 years were included in the study.<br />

All subjects had angiographically proven normal coronary arteries without coronary<br />

slow flow. Aortic systolic and diastolic blood pressures were measured invasively.<br />

Mean, pulse and fractional pulse pressures (aortic pulse pressure/mean<br />

pressure) were calculated.<br />

Results: All parameters measured were significantly higher in IFG group than in<br />

the control (NFG) group (133±21 mmHg and 117±12 mmHg, p


482 Autonomic nervous system in hypertension / Hypertension: regional and ethnic profiles<br />

Chemoreceptor deactivation in response to the administration of 100% oxygen<br />

induced a reduction in MSNA that was significantly more important in CHF+CHR<br />

group than in control (MSNA decreased by 7,7±3,9% versus -0.76±2.4%; p=<br />

0,005). This led to a slight but significant decrease in systolic blood pressure.<br />

Conclusion: CRF exert tonic activation of excitatory chemoreflex afferents and<br />

thus contributes to increased efferent sympathetic activity to muscle circulation<br />

and to blood pressure control in patients with CHF. These findings may have<br />

important implications for understanding mechanisms underlying the link between<br />

CRF and CHF as the bad prognosis of this morbid association (i.e. increased<br />

mortality or sudden death due to sympathetic overactivity.).<br />

P2913 Symmetric dimethylarginine is an independent<br />

predictor of intradialytic hypotension<br />

A.A. Mangoni1 ,C.L.Hewitson1 , R.J. Woodman1 , M.J. Whiting1 ,<br />

B. Mcateer-Carr1 , J.A. Barbara2 . 1Flinders University, Dept. Clinical<br />

Pharmacology, Adelaide, Australia; 2Flinders Medical Centre,<br />

Nephrology, Adelaide, Australia<br />

Objectives: The plasma concentrations of the methylated forms of the amino acid<br />

L-arginine NG-monomethyl L-arginine (L-NMMA), asymmetric dimethylarginine<br />

(ADMA), and symmetric dimethylarginine (SDMA) 1) are elevated in patients with<br />

end-stage renal disease (ESRD) and 2) significantly decrease during haemodialysis<br />

(HD). We sought to determine whether these abnormalities play a role in<br />

the occurrence of intradialytic hypotension (IDH) through effects on endothelial<br />

function and arterial tone.<br />

Methods: Systolic blood pressure (SBP), L-arginine, L-NMMA, ADMA, and<br />

SDMA were measured at the beginning (pre-HD) and within the last hour of HD<br />

(end-HD) in 52 consecutive HD patients (age 64.4±13.4 years, mean±SD). IDH<br />

was defined as a SBP reduction of > 20 mmHg end-HD vs. pre-HD.<br />

Results: Fourteen patients demonstrated IDH. The mean reduction in SBP during<br />

HD in this group was -35±13 mmHg compared to an increase of +2±12<br />

mmHg amongst the 38 patients without IDH (no-IDH). Baseline demographic,<br />

clinical, and biochemical parameters did not differ between the IDH and no-<br />

IDH groups. However, the IDH group had higher pre-HD SBP (155±17 vs.<br />

132±14 mmHg, p


important sex-based differences in clinical presentation and the development of<br />

advanced forms of heart disease. Primary and secondary prevention programs<br />

will need to be adjusted accordingly to meet the potentially different needs of<br />

men and women in this community.<br />

P2917 High blood pressure in the Australian population:<br />

results of a national blood pressure screening day<br />

M. Carrington, S. Stewart, G. Jennings, G. Lee. Baker <strong>Heart</strong><br />

Research Institute, Preventative Cardiology, Melbourne, Australia<br />

Purpose: There are few large-scale population studies in Australia<br />

(and other high income countries) that report the underlying prevalence of hypertension<br />

and other preventable cardiovascular (CV) risk factors: particularly on a<br />

region-by-region basis.<br />

Methods: We established 100 surveillance sites in all States and Territories of<br />

Australia on a single Saturday in high "people traffic areas". Sites were distributed<br />

per 250,000 people in major cities and for each population centre sized > 20,000<br />

people. Registered nurses used a standardised protocol to measure resting blood<br />

pressure (BP) using an A&D digital BP monitor, waist and hip circumference and<br />

body mass index. Self-reported CV risk factors, medical history, and BP treatment<br />

and awareness were also documented.<br />

Results: Overall, data were available for 13,825 participants from 99 sites (1 in<br />

1000 adult Australians) with a mean age of 48±16 years (range 18 to 96 years).<br />

A total of 58% were aged ≥ 45 years and 45% were male. Mean systolic and<br />

diastolic BP was 132±18 and 80±12 mmHg, respectively. Overall, systolic and<br />

diastolic BP was higher than 140 mmHg and 90 mmHg, respectively for 30%<br />

(38% in men and 23% in women) and 18% (22% in men and 15% in women) of<br />

participants. In total, 42% of men and 27% of women had resting BP indicative<br />

of underlying hypertension. Men recruited from rural centres (n = 1,376) compared<br />

to metropolitan centres (n = 4,783) had higher systolic (139±17 vs. 136±17<br />

mmHg) and diastolic BP (83±12 vs. 81±12 mmHg), with 48 vs. 41% found to be<br />

hypertensive (p


484 Hypertension: regional and ethnic profiles<br />

HCTZ, N and T/HCTZ, but better response was in A allele carriers of AGTR1 under<br />

N and T/HCTZ administration. AGTR1 CC-carriers require initially combined<br />

and more "aggressive" therapy for adequate hypotensive efficacy.<br />

P2921 Genetic polymorphism on angiotensin receptor type 2<br />

(A1675G) increases cardiovascular risk in<br />

hypertensive individuals: effects on pro-atherogenic<br />

inflammatory mechanisms<br />

N. Koumallos, D. Tousoulis, C. Antoniades, A.S. Antonopoulos,<br />

D. Mentzikof, C. Vasiliadou, C. Vlachopoulos, E. Stefanadi, C. Tentolouris,<br />

C. Stefanadis. Hippokration Hospital, 1st Cardiology Department, Athens,<br />

Greece<br />

Evidence suggest that there is a balance between angiotensin II effects on<br />

proatherogenic constitutive type 1, and antiatherogenic inducible type 2 (AT2R)<br />

receptors. The AT2R gene is located in chromosome X, and the biological effect<br />

of a newly described polymorphism (A1675G) in this gene is unclear.<br />

Aim: We examined the impact of A1675G polymorphism on AT2R, on the risk<br />

for coronary atherosclerosis, and its effect on the expression of proatherogenic<br />

inflammatory molecules.<br />

Methods: The study population consisted of 437 males: 155 with coronary artery<br />

disease (111 with hypertension) and 282 healthy age-matched controls (121 with<br />

hypertension). The presence of A1675G polymorphism on AT2R gene (located in<br />

chromosome X) was determined by PCR. Serum levels of C-reactive protein and<br />

fibrinogen was measured in all the participants.<br />

Results: The frequency of the A allele was similar among healthy individuals<br />

(41.8% 118/282) and CAD patients (47.7%, 74/155, p=NS). However, presence<br />

of the A allele was more frequent in hypertensives with CAD (55%, 59/107) than<br />

in hypertensives without CAD (35.8%, 43/120, p


Hypertension: regional and ethnic profiles / The endothelium: at the heart of vascular biology (bench) 485<br />

P2925 Upgrading the role of uric acid in essential<br />

hypertension: cross-sectional relationships with<br />

subclinical inflammation, asymmetric<br />

dimethylarginine and arterial stiffening<br />

C. Tsioufis, K. Dimitriadis, E. Taxiarchou, D. Tsiachris, A. Miliou,<br />

D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of<br />

Athens, Hippokration Hospital, Athens, Greece<br />

Purpose: Elevated uric acid (UA) levels are associated with enhanced cardiovascular<br />

risk, while low-grade inflammation, arterial stiffening and increased asymmetric<br />

dimethylarginine (ADMA) levels contribute to atherosclerosis progression.<br />

In this study, we investigated the relationships between serum UA levels, highsensitivity<br />

C-reactive protein (hs-CRP), ADMA and arterial stiffness in essential<br />

hypertensives.<br />

Methods: In our population of 185 newly diagnosed untreated non-diabetic patients<br />

with stage I to II essential hypertension [120 men, aged 49 years, office<br />

blood pressure (BP)=152/97 mmHg], the distribution of UA was split by the median<br />

(5.1 mg/dl) and accordingly subjects were classified into those with high<br />

and low values. In all participants, arterial stiffness was evaluated on the basis<br />

of carotid to femoral pulse wave velocity (PWV), by means of a computerized<br />

method (Complior SP) and venous blood sampling was performed to estimate<br />

metabolic profile, hs-CRP and ADMA levels.<br />

Results: Patients with high UA (n=91) compared to those with low UA (n=94)<br />

exhibited higher 24-h systolic BP (139±8 vs 131±11 mmHg, p


486 The endothelium: at the heart of vascular biology (bench)<br />

Nicotine alone does not reproduce the effects seen with SS tobacco smoke suggesting<br />

that other chemical components of tobacco smoke are responsible for the<br />

acute endothelial toxicity of passive smoking.<br />

P2929 Nrf2-dependent upregulation of antioxidative<br />

enzymes – a novel pathway of proteasome<br />

inhibitor-mediated cytoprotection in cardiovascular<br />

cells<br />

H. Dreger, K. Westphal, N. Wilck, G. Baumann, V. Stangl, K. Stangl,<br />

S. Meiners. Charite - Universitaetsmedizin Berlin, Med. Klinik M. S.<br />

Kardiologie Und Angiologie, Berlin, Germany<br />

Purpose: Increased levels of reactive oxygen species cause oxidative stress and<br />

severely damage lipids, proteins, and DNA. We have previously shown that low<br />

dose and non-toxic proteasome inhibition induces a protective antioxidative gene<br />

pattern in endothelial cells. This is associated with a marked protection against<br />

oxidative stress. Here, we elucidate the causal relationship and detailed mechanisms<br />

of proteasome inhibitor-mediated upregulation of antioxidative enzymes<br />

and cytoprotection.<br />

Methods and Results: Non-toxic proteasome inhibition uniformly upregulated<br />

mRNA expression of two key antioxidative enzymes – superoxide dismutase<br />

1 (SOD1) and heme oxygenase 1 (HO-1) – in several human endothelial and<br />

vascular smooth muscle cell types. Inhibition of RNA polymerase II activity by<br />

pretreatment of with alpha-amanitin completely abolished proteasome inhibitormediated<br />

mRNA induction indicating transcriptional activation of these enzymes<br />

in response to proteasome inhibition. Comprehensive deletion and mutation analyses<br />

of the SOD1 promoter revealed that transcriptional upregulation can be<br />

largely confined to an antioxidative response element (ARE), which is not only<br />

essential but also sufficient for transcriptional activation of SOD1. Cotransfection<br />

studies and bandshift analysis confirmed that transcriptional regulation of HO-1<br />

depends on binding of the antioxidative transcription factor Nrf2 to the highly conserved<br />

ARE site in the HO-1 promoter. Western blot analysis revealed that Nrf2<br />

is partly stabilized upon proteasome inhibition. In order to prove the essential role<br />

of Nrf2 for the mediation of the cytoprotective effects of proteasome inhibition in<br />

the vessel, we are currently studying Nrf2-dependent protection against oxidative<br />

stress in Nrf2-knock out mice.<br />

Conclusion: Our data suggest that low and non-toxic proteasome inhibition<br />

protects cardiovascular cells by Nrf2-mediated upregulation of antioxidative enzymes.<br />

P2930 Exposure to cold induces activation of NF-KB in<br />

endothelial cells<br />

E.M. Awad, B.R.B. Binder on behalf of Binder. Centre of<br />

Biomolecular Medicine and Pharmacol, Vascular Biology and<br />

Thrombosis Research, Vienna, Austria<br />

Organs for transplantation are generally stored in the cold for better preservation<br />

of organ function. However, following transplantation and re-perfusion, endothelial<br />

cells in the transplanted organs often appear activated with adherent leukocytes<br />

and micro-thrombi. In this study, we analyzed whether storage in the cold itself<br />

might be responsible for endothelial cell activation. Pre-exposure of human umbilical<br />

vein endothelial cells (HUVECs) to temperatures below 37°C resulted upon<br />

re-warming in increased secretion of plasminogen activator inhibitor-1 (PAI-1). Already<br />

after 20 minutes cold pre-exposure of HUVECs to 8°C, PAI-1 mRNA and<br />

antigen increased upon re-warming. Pre-exposure to 8°C also induced expression<br />

of tissue factor and adhesion molecules indicating a pro-thrombotic, antifibrinolytic<br />

and pro-adhesive state of cold pre-exposed endothelial cells. When<br />

we analyzed NFκB activation as potentially causing endothelial cell activation, we<br />

found that upon re-warming to 37°C of HUVECs pre-exposed for 30 minutes to<br />

8°C IκB was degraded and NF-κB was transiently translocated to the nucleus.<br />

For further evidence that these changes were due to NF-κB activation the BAY<br />

inhibitor (an NF-κB-specific inhibitor) could significantly inhibit PAI-1, E-selectin<br />

and ICAM-1 mRNAs expression after 30 minutes cold exposure and rewarming<br />

at 37°C for 2 and 4 hours. From these data, we conclude that cold exposure itself<br />

leads upon re-warming to activation of NF-κB in endothelial cells and in turn endothelial<br />

cell activation. This might explain the adverse outcome in some cases<br />

of transplantation of cold preserved organs.<br />

P2931 In-vivo activation of myocardial AT2 receptor<br />

expression by endogenous NO and pentaerythrithol<br />

tetranitrate<br />

T.V. Dao, S. Schaaf, T. Suvorava, G. Kojda. Heinrich-Heine-<br />

University, Institute for Pharmacology, Duesseldorf, Germany<br />

Purpose: There are many vascular signaling interactions between the vascular<br />

endothelial NO system and the renin-angiotensin-system. We hypothesized that<br />

endothelial NO might impact on the expression of angiotensin (AT) type 1 (AT-1)<br />

and type 2 (AT-2) receptors.<br />

Methods: We generated mice with an endothelial-specific overexpression of endothelial<br />

NO-synthase (eNOS) using the Tie-2 promotor and backcrossed these<br />

mice to the C57BL/6 background. Two of these lines were characterized by<br />

eNOS-western analyses and blood pressure measurements in comparison to<br />

trangene negative littermates. In addition, C57Bl/6 mice were fed with either 6,<br />

60 or 300 mg pentaerythrithol tetranitrate (PETN)/kg body weight/day for 4 weeks<br />

and characterized as well.<br />

Results: Analysis of line 1 of trangenic eNOS mice (1-eNOS++) showed a<br />

2.3±0.15 fold higher aortic expression of eNOS and a reduction of blood pressure<br />

to 109.6±2.0 mmHg (P


whether the selective mineralocorticoid receptor antagonist eplerenone improves<br />

vascular dysfunction and reduces platelet activation in diabetic rats.<br />

Methods and results: Male Wistar-rats were injected with streptozotocin (STZ,<br />

50 mg/kg body weight i.v.) to induce diabetes. Treatment with eplerenone (100<br />

mg/kg/day) or placebo was initiated 2 weeks after injection of STZ and continued<br />

for another 2 weeks. Thereafter, platelet activation was assessed in freshly<br />

obtained whole blood; vascular function was analysed using isolated aortic segments<br />

in organ bath chambers. Endothelium-dependent, NO-mediated vasorelaxation<br />

induced by acetylcholine was significantly attenuated in diabetic rats<br />

(EC50 in nmol/l: control 19.0±3.7, STZ-Placebo 170.0±44.4, STZ-eplerenone<br />

25.2±2.9; maximum relaxation in % of precontraction: control 95.4±2.8, STZplacebo<br />

82.3±2.6, STZ-eplerenone 99.1±0.4) and was normalized by treatment<br />

with eplerenone.<br />

Treatment with the selective mineralocorticoid receptor antagonist eplerenone<br />

significantly reduced fibrinogen-binding on activated GPIIb/IIIa (mean fluorescence:<br />

control 161.0±6.9, STZ-placebo 207.8±15.9, STZ-eplerenone<br />

173.1±6.0).<br />

Conclusions: We demonstrate that eplerenone improves endothelial dysfunction<br />

and NO bioavailability in diabetic rats. In parallel, in vivo platelet activation<br />

was significantly reduced by treatment with eplerenone. These effects might be a<br />

new potential therapeutic approach for mineralocorticoid receptor antagonism as<br />

treatment of vascular dysfunction in diabetes.<br />

P2934 Aortic stiffness and flow-mediated dilatation in<br />

normotensive offspring of parents with history of<br />

hypertension. Non-invasive indicators of<br />

atherosclerosis<br />

H. Evrengul, H. Tanriverdi, D. Dursunoglu, I.D. Kilic, H.A. Kaftan,<br />

M. Kilic. Pamukkale University, Cardiology, Denizli, Turkey<br />

Objectives: Although hypertension has been shown to be one of the most important<br />

predictors of atherosclerosis, there is not enough data about the presence<br />

of subclinical atherosclerosis in normotensive subjects with parental history<br />

of hypertension. Accordingly, the current study was designated to evaluate flowmediated<br />

dilatation (FMD) and aortic stiffness those are early signs of atherosclerosis<br />

aortic in young subjects with parental history of hypertension.<br />

Material and methods: One hundred two healthy, non-obese subjects (ages 18–<br />

22 years) were included in this study and divided into two groups. Group I included<br />

the 48 offspring of hypertensive parents (ages 20 years, 18 men) and<br />

group II as controls the 54 offspring of normotensive parents (ages 19 years,<br />

22 men). In all subjects endothelium-dependent/-independent vasodilatation of<br />

the brachial artery and aortic elastic parameters were investigated using highresolution<br />

Doppler echocardiography.<br />

Results: The demographic data of the subjects with and without parental history<br />

of hypertension were not significantly different. Offspring of hypertensive parents<br />

had higher systolic blood pressure and pulse pressure than the controls. Normotensive<br />

offspring of parents with history of hypertension demonstrated that<br />

higher values of aortic stiffness (7.1±1.88 vs. 6.42±1.56, respectively) but lower<br />

distensibility (9.47±1.33 vs. 11.8±3.36 cm 2 /dyn/10 6 ) and FMD (4.57±1.3 vs.<br />

6.34±0.83%, p = 0.0001, respectively) than offspring of normotensive parents.<br />

Conclusion: We observed blunted endothelium-dependent dilatation and aortic<br />

stiffness in normotensive offspring of hypertensive parents compared with normotensive<br />

offspring of normotensive parents. This is evident in the absence of<br />

overt hypertension and other diseases, suggesting that parental history of hypertension<br />

a risk of subclinical atherosclerosis and it may contribute to the progression<br />

to hypertension and overt atherosclerosis in later life.<br />

P2936 Sirolimus-induced vascular dysfunction - Detection of<br />

mitochondrial and NADPH oxidase-dependent<br />

superoxide production and decreased vascular NO<br />

formation<br />

A. Jabs, S. Goebel, P. Wenzel, A.L. Kleschyov, M. Hortmann,<br />

M. Oelze, A. Daiber, T. Muenzel. University of Mainz, II. Dept. of Medicine -<br />

Cardiology, Mainz, Germany<br />

Objectives: In view of coronary endothelial dysfunction and impaired reendothelialization<br />

observed following sirolimus-eluting stent implantation, we<br />

sought to analyze mechanisms that could mediate vascular dysfunction induced<br />

by sirolimus.<br />

Methods: To mimic the continuous sirolimus exposure of a stented vessel, Wistar<br />

rats (n=34 in total) underwent drug-infusion (5mg/kg/d) or infusion of vehicle<br />

(DMSO) with a subcutaneous osmotic pump for 7 days.<br />

Results: A marked degree of endothelial dysfunction as well as vascular desensitization<br />

to the endothelium-independent vasodilator nitroglycerin was observed in<br />

aortae from sirolimus-treated animals. Also, sirolimus stimulated intense transmural<br />

superoxide formation as detected by dihydroethidine fluorescence. A marked<br />

stimulation of p67phox/rac1 NADPH oxidase subunit expression as well as increased<br />

rac1 membrane association was found, indicating vascular NADPH oxidase<br />

dependent superoxide production. In addition, rat heart mitochondria in the<br />

sirolimus group showed increased superoxide release, as measured by L012enhanced<br />

chemiluminescence. This effect was partially reversed by mitochondrial<br />

pre-incubation with the mPTP blocker cyclosporine A, the KATP channel inhibitor<br />

The endothelium: at the heart of vascular biology (bench) 487<br />

glibenclamide, and the complex I inhibitor rotenone. As a consequence, electron<br />

paramagnetic resonance showed a 40% reduction in vascular NO bioavailability,<br />

which was further supported by decreased serum-nitrite levels.<br />

Conclusions: In an animal model of sirolimus-induced vascular dysfunction, we<br />

found continuous sirolimus exposure to cause impaired endothelium-dependent<br />

and -independent vascular relaxation, reduced vascular NO formation, and increased<br />

transmural superoxide production. Superoxide was generated by increased<br />

NADPH oxidase expression and membrane association as well as stimulation<br />

of mitochondrial release via the mitochondrial permeability transition pore.<br />

P2937 The effect of pravastatin on microvascular constrictor<br />

responses and the role of nitric oxide (NO)<br />

N. Ghaffari, J.A. Kennedy, J.F. Beltrame. The University of Adelaide,<br />

TQEH, Medicine/Cardiology TQEH, Adelaide, Australia<br />

Purpose: Statin therapy ameliorates vasomotor dysfunction which<br />

arises from an imbalance between vasoconstrictor and vasodilator substances.<br />

Pleiotropic effects of statin therapy include increases NO bioavailability, but<br />

whether such effects extend to the microvasculature is less clear. Accordingly,<br />

this study investigated the effect of pravastatin on rat micro-vascular constrictor<br />

responses and the mechanisms responsible.<br />

Methods: Rat mesenteric arterial rings (250-500mm diameter, n=6/treatment)<br />

were placed in a Mulvany wire myograph and endothelial integrity assessed with<br />

acetylcholine. Concentration-response curves to phenylepherine (PE), thromboxane<br />

analogue (U46619), and endothelin-1 (Et-1) were determined before and after<br />

60min preincubation with a therapeutically-equivalent pravastatin concentration<br />

(112nM). Constrictor responses were expressed as % of depolarizing potassium<br />

responses. To assess the contribution of the endothelium-derived NO in<br />

mediating effects of pravastatin, the experiments were repeated after preincubation<br />

with the NO synthase inhibitor, L-NAME (300μM), and after denuding the<br />

endothelium. ET-1 experiments were repeated with the ETB receptor antagonist<br />

(BQ788; 3μM) to assess the potential influence of concurrent ETB mediated NO<br />

release. Data were expressed as mean ± SEM and analyzed by paired t-test.<br />

Results: In endothelium-intact vessels, pre-treatment with pravastatin reduced<br />

the maximal constrictor response to PE (Baseline = 122±4%, Pravastatin =<br />

90±6%, p = 0.0001) and U46619 (Baseline = 109±5%, Pravastatin = 85±4%,<br />

p = 0.003), but had no effect on ET-1 responses (Baseline= 111±5%, Pravastatin<br />

= 111±5%, p = 0.98). Both endothelial denudation and NOS inhibition abolished<br />

pravastatin effect on PE and U46619 constrictor responses, confirming a central<br />

role of endothelium-derived NO. ET-B receptor blockade unmasked an inhibitory<br />

effect of pravastatin response in Et-1 constricted vessels (Baseline = 117±7%,<br />

Pravastatin = 90±7%, p = 0.0005).<br />

Conclusions: Pravastatin increases NO bioavailability in microvessels thereby<br />

inhibiting constrictor responses. In Et-1 constrictor responses this is masked by<br />

ET-B receptor-mediated NO release.<br />

P2938 Effects of calcium channel blocker and angiotensin2<br />

receptor blocker on endothelial function in porcine<br />

drug eluting stent model<br />

N. Kubota, T. Kasai, T. Iesaki, K. Miyauchi, H. Daida. Juntendo<br />

University School of Medicine, Cardiolody, Tokyo, Japan<br />

Background:Drug-eluting stent (DES) implantation may be related to endothelial<br />

dysfunction and inflammatory reaction. Several drugs such as calcium channel<br />

blocker (CCB) and angiotensinII receptor blocker (ARB) improve endothelial dysfunction<br />

and inhibit inflammatory reaction. However, co-administration effects of<br />

CCB and ARB on endothelial function and improving inflammation reaction after<br />

vascular injury remained unknown.<br />

We investigated whether (1) CCB or ARB could recovery endothelial dysfunction<br />

and inhibit inflammatory reaction after DES and (2) recovery form endothelial<br />

dysfunction and inflammation was accelerated by co-administration of CCB and<br />

ARB in porcine coronary artery.<br />

Methods: Twenty four pigs were randomized to four groups: control, combination<br />

with CCB and ARB, only CCB or ARB group. Drug administration was started<br />

one week before stenting and continued for 4 weeks. Sirolimus eluting stent<br />

was implanted at mid-portion of the left anterior descending (LAD). After euthanasia,<br />

edge of stent site was dissected and, the vessels were contracted,<br />

and then, endothelium-dependent relaxation, elicited by increasing the cumulative<br />

concentration of bradykinin, was examined. Relaxation was expressed as<br />

percent change of steady-state level of contraction. The degree of inflammation<br />

was determined by immunohistological examination. Inflammatory cell infiltration<br />

in the stent site was evaluated with scanning electron microscopy (SEM).<br />

Results:At 4 weeks after stent implantation, there were no significant differences<br />

in blood pressure among four groups. In the control group, the endotheliummediated<br />

vasodilatation of the edge was significantly impaired as compared with<br />

the intact site (78% versus 90.5%, P


488 The endothelium: at the heart of vascular biology (bench)<br />

in the both treated group. In combination with CCB, ARB had a synergic effect on<br />

inflammatory cells infiltration by 70%.<br />

Conclusion:Endothelial dysfunction and prolonged inflammatory reaction after<br />

DES implantation was observed in the porcine coronary artery. However, recover<br />

of endothelial function and suppression of inflammation was enhanced by coadministration<br />

of CCB and ARB.<br />

P2939 Effects of vardenafil, a selective<br />

phophodiesterase-5-inhibitor on endothelial<br />

dysfunction induced by reactive oxidant hypochlorite<br />

R. Arif1 , T. Radovits2 , T. Boemicke 1 ,M.Karck1 , G. Szabo1 .<br />

1University of Heidelberg, Department of Cardiac Surgery,<br />

Heidelberg, Germany; 2Semmelweis University, Budapest, Hungary<br />

Background: Reactive oxygen species, such as myeloperoxidase-derived<br />

hypochlorite (OCl-) induce oxidative stress and DNA injury leading to dysfunction<br />

of the endothelium in the cardiovascular system. It has been recently proposed,<br />

that elevated intracellular cGMP levels may contribute to an effective cytoprotection<br />

against oxidative stress. In this study we investigated the effects of vardenafil,<br />

an inhibitor of the cGMP-degrading enzyme phosphodiesterase-5 (PDE5) on endothelial<br />

dysfunction induced by hypochlorite.<br />

Methods: In organ bath experiments for isometric tension we investigated<br />

the phenylephrine-induced contraction and endothelium-dependent and –<br />

independent vasorelaxation of isolated aortic rings of rats by using cumulative<br />

concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP). Endothelial<br />

injury was induced by exposing the rings to hypochlorite (100, 200 and<br />

400μM). In the treatment groups, rats were pretreated with 30 or 300μg/kg vardenafil<br />

iv. 10 minutes before removal of the aorta. Histochemical analysis was<br />

performed to detect oxidant-induced changes in the aortic wall.<br />

Results: Exposure to hypochlorite resulted in a dose-dependent impairment of<br />

endothelium-dependent vasorelaxation of aortic rings (maximal relaxation to ACh:<br />

86.21±1.57% control vs. 75.39±2.89% 100μM OCl- vs. 66.57±3.14% 200μM<br />

OCl- vs. 54.99±4.05% 400μM OCl-,p


THE ENDOTHELIUM: AT THE HEART OF VASCULAR<br />

BIOLOGY (BEDSIDE)<br />

P2943 Temporal variation of flow mediated dilation in type 2<br />

diabetes. The benefit of serial measurements<br />

M. Misiorna-Boehme1 , E. Soendergaard2 ,K.Egstrup1 . 1Funen Hospital Svendborg, Department of Medical Research, Svendborg,<br />

Denmark; 2Skejby Hospital, Department of Cardiology, Aarhus,<br />

Denmark<br />

Purpose: To investigate the temporal variation of flow mediated dilation (FMD)<br />

assessed within an interval of 50 to 90 s postocclusion in the population of type<br />

2 diabetes subjects with no documented atherosclerotic disease and näive to<br />

HMG-CoA reductase inhibitors. Furthermore, to examine the difference between<br />

the FMD estimated at the fixed time point of 60 s postocclusion and the FMD<br />

yield by serial measurements. Also to assess time to the maximal vasodilatory<br />

response. Additionally, univariate and multiple linear regression analyses were<br />

carried out to determine potential predictors of FMD.<br />

Methods: One hundred and eighty six ultrasonographic studies on the vasoreactivity<br />

of the brachial artery ad modum Celemajer were performed.<br />

Arterial diameter was measured at end diastole from the anterior to the posterior<br />

lumen-intima interface at fixed distance from anatomical markers using electronic<br />

callipers. Three measurements along a wall segment were performed. FMD was<br />

defined as a percent change in arterial diameter after end occlusion. The arterial<br />

diameter was determined prior to and 50, 60, 70, 80 and 90 s after cuff deflation.<br />

The maximal dilation (peak FMD) was computed from the maximal artery diameter<br />

postocclusion. FMD at separate time points was calculated from the corresponding<br />

mean arterial diameter. The cumulative response to hyperemia within<br />

50-90 s postocclusion, area under the curve (AUC, %·s) were assessed. Time to<br />

peak was defined as the shortest time interval from cuff deflation to the detection<br />

of the maximal dilation.<br />

Results: Peak FMD of 1.7% (±1.96) was significantly higher (p


490 The endothelium: at the heart of vascular biology (bedside)<br />

P2947 Effects of atorvastatin 10 mg versus 40 mg in eight<br />

months follow-up pulse wave velocity and clinical<br />

events in patients with acute myocardial infarction<br />

S.J. Hong, W.J. Shim, S.M. Park, J.S. Park, J.I. Choi, S.Y. Lim,<br />

D.S. Lim. Korea University Anam Hospital, Cardiology Department,<br />

Seoul, Korea, Republic of<br />

Purpose: Pulse wave velocity (PWV) had been used as an index of atherosclerosis<br />

and arterial compliance, and many data indicate that statins decrease the progression<br />

of atherosclerosis. We compared the effects of atorvastatin 10 mg versus<br />

40 mg in follow-up clinical events and in restoring PWV during the 8 months<br />

follow-up in patients with acute myocardial infarction.<br />

Methods: Carotid-femoral PWV was measured by using a commercially available<br />

device (PP-1000) in 102 consecutive patients with acute myocardial infarction<br />

5 days after the successful primary coronary intervention with sirolimus-eluting<br />

stents. Stented patients were randomly assigned to either atorvastatin 10 mg<br />

(ATOR10, n=52) or atorvastatin 40 mg (ATOR40, n=50). All patients received aspirin<br />

and clopidogrel. Clinical events such as death, myocardial infarction, and<br />

target lesion revascularization (TLR) were compared during the 8-month followup.<br />

Results: PWV decreased significantly in both groups during the 8 months followup<br />

(7.9±2.5 at baseline vs. 7.3±2.8 m/s at follow-up in the ATOR10, p


P2951 Reproducibility of endothelial function and arterial<br />

stiffness assessed using finger peripheral arterial<br />

tonometry<br />

Y. Reisner, R. Lusky, Y. Shay-El, R. Schnall, S. Herscovici. Itamar<br />

Medical Ltd., Caesarea, Israel<br />

Purpose: Endothelial function and arterial stiffness are recognized markers of<br />

subclinical atherosclerosis. One of the possible limitations for the clinical utilization<br />

of these markers is an excessive inter-measurement variability. The purpose<br />

of this study was to assess the reproducibility of endothelial function and arterial<br />

stiffness indices assessed using finger peripheral arterial tonometry (PAT).<br />

Methods: 113 adult volunteers (40 females), mean age 40.4±12.6, underwent<br />

concurrent vascular function testing of PAT reactive hyperemia and arterial stiffness<br />

on the mornings of 2 consecutive days under similar controlled conditions.<br />

Endothelial function, expressed by the reactive hyperemia response, was assessed<br />

by calculating the ratio of post-occlusion to baseline PAT amplitude. The<br />

score is further compensated for systemic changes using simultaneous recording<br />

from the un-occluded contra-lateral finger. Augmentation index was calculated<br />

from the mean PAT waveform of the baseline period.<br />

Results: Mean values of the log transformed reactive hyperemia index (F_RHI)<br />

were 0.56±0.38 and 0.54±0.37 for days 1 and 2 respectively (p = 0.53) and augmentation<br />

indices (AIs) were 5.7±14.9 and 5.8±16.0 respectively (p = 0.82). Intra<br />

class correlations (ICC’s) for the day-to-day comparison were 0.56 (p


492 The endothelium: at the heart of vascular biology (bedside)<br />

P2955 Chronic treatment with clopidogrel does not improve<br />

endothelial dysfunction in patients with stable<br />

coronary artery disease<br />

A. Warnholtz, M.A. Ostad, E. Nick, V. Paixao-Gatinho, S.E. Ostad,<br />

T. Munzel. Johannes Gutenberg-University, Mainz, Germany<br />

Purpose: Clinical studies have demonstrated beneficial effects for clopidogrel in<br />

patients with atherothrombotic disease. Recently we have demonstrated a dosedependent<br />

improvement of endothelial dysfunction after administration of a single<br />

loading dose of clopidogrel in patients with coronary artery disease (CAD). We<br />

hypothesized that chronic therapy with clopidogrel will improve endothelial dysfunction<br />

in patients with CAD.<br />

Methods: We have conducted a double-blind, randomized, monocentric clinical<br />

trial. One hundred and twenty patients with CAD were randomized to one of the<br />

following treatment arms: Clopidogrel (C) 75mg q.d., acetylsalicylic acid (ASA)<br />

100mg q.d. or a combination of ASA and C. Endothelial function was assessed<br />

by measurement of flow-mediated dilation (FMD) of the brachial artery before<br />

and after 28 days of treatment. Endothelial-independent nitroglycerin-mediated<br />

dilation was measured in order to evaluate vascular dilatory capacity. The effect<br />

of clopidogrel was monitored in-vitro by ADP-induced platelet aggregation in<br />

platelet rich plasma. Effects of treatment on platelet superoxide production were<br />

measured in-vitro by lucigenin enhanced chemiluminescence in washed platelets.<br />

Statistical analysis was performed in the intention-to-treat population.<br />

Results: Treatment groups were comparable regarding age, gender, cardiovascular<br />

risk factor distribution and concomitant medication. Neither of the<br />

three treatments caused a significant effect on FMD (C: +0.23±0.48%; C+ASS<br />

+0.5±0.47%; ASS +0.83±0.56%. p=n.s.), NMD, or platelet superoxide production.<br />

Clopidogrel alone and in combination with ASA significantly inhibited ADPinduced<br />

platelet aggregation as expected.<br />

Conclusion: In contrast to the results of our previous trial that demonstrated significant<br />

improvement of FMD upon a single dose of 300mg and 600mg clopidogrel,<br />

this trial failed to demonstrate a sustained beneficial effect of clopidogrel on<br />

endothelial dysfunction in patients with CAD. In-vitro studies have demonstrated<br />

the expression of the ADP P2Y12 receptor on endothelial cells. One possible<br />

explantation for our unexpected finding in this trial could include the underdosing<br />

of clopidogrel if a receptor-dependent effect was the underlying mechanism<br />

seen upon 300mg and 600mg single dose. Counteracting mechanisms may have<br />

compensated the effect after 28 days of treatment.<br />

P2956 Energy restricted weight loss alone improves conduit<br />

and resistance artery endothelial function in<br />

overweight and obese adults: relation to abdominal<br />

visceral fat, nitric oxide bioavailability and age<br />

G.L. Pierce, S.B. Beske, B.L. Lawson, K.L. Southall, F.J. Benay,<br />

A.J. Donato, D.R. Seals. University of Colorado, Integrative Physiology, Boulder,<br />

United States of America<br />

Purpose: Obesity is associated with vascular endothelial dysfunction, as indicated<br />

by impaired endothelium-dependent dilation (EDD). Presently there is no<br />

direct evidence that energy restricted weight loss alone improves conduit or resistance<br />

artery EDD, the mechanisms involved, or if improvements differ with patient<br />

age.<br />

Methods: 40 overweight or obese (body mass index ≥25


P2959 Brachial flow-mediated dilation is associated with<br />

long-term cardiovascular events in healthy subjects<br />

M. Shechter1 ,A.Issachar1 , I. Marai1 , N. Koren-Morag2 , Y. Shahar1 ,<br />

A. Shechter1 , M.S. Feinberg1 . 1Chaim Sheba Medical Center, The<br />

<strong>Heart</strong> Institute, Tel Hashomer, Israel; 2Tel Aviv University, Sackler<br />

Faculty of Medicine, Tel Aviv, Israel<br />

Background: Endothelial dysfunction is considered an important prognostic factor<br />

in atherosclerosis. The aim of this study was to find out the long-term association<br />

of peripheral vascular endothelial function and clinical outcome in healthy<br />

subjects with no apparent coronary artery disease (CAD).<br />

Methods and Results: We prospectively assessed flow-mediated dilation (FMD)<br />

in 435 consecutive healthy subjects: 281 (65%) men, mean age 54±12 years. Following<br />

overnight fasting FMD and endothelium-independent nitroglycerin (NTG)mediated<br />

vasodilatation were assessed using high resolution (15 MHz) linear array<br />

ultrasound. Subjects were divided into 2 groups: below (n=221) and above<br />

(n=214) the median FMD of 10.7. The 2 groups were comparable in regard to<br />

CAD risk factors, lipoproteins, fasting glucose, C-reactive protein, and concomitant<br />

medications, with a mean clinical follow-up of 32±2 months. Composite cardiovascular<br />

endpoints (all-cause mortality, non-fatal myocardial infarction, hospitalization<br />

for heart failure or angina pectoris, stroke, coronary artery bypass grafting<br />

and percutaneus coronary interventions) were significantly more common in<br />

subjects with FMD below rather than above the median of 10.7% (11.8% vs 4.7%,<br />

p=0.007, respectively). Univariate analysis demonstrated that the median FMD<br />

significantly predicted cardiovascular events [odds ratio (OR) of 2.78 and 95% CI<br />

(1.35 to 5.71) (p=0.003)]. After multivariate analysis that included conventional<br />

CAD risk factors, median FMD was the best independent predictor of long-term<br />

cardiovascular adverse events [OR of 2.70 and 95% CI (1.16 to 6.32) (p=0.011)]<br />

(Figure).<br />

Conclusions: Brachial artery median FMD independently predicts long-term adverse<br />

cardiovascular events in healthy subjects in addition to traditional risk factor<br />

assessment.<br />

P2960 Effects of early statin treatment on endothelial<br />

function in patients with acute myocardial infarction:<br />

randomized study<br />

V. Giga, M. Ostojic, D. Lepojevic, S. Komnenovic, B. Beleslin,<br />

S. Stojkovic, A. Djordjevic-Dikic, J. Stepanovic, M. Nedeljkovic,<br />

Z. Vasiljevic. Institute for Cardiovascular Diseases, Belgrade, Serbia<br />

Background: It has been shown that statin treatment improves endothelial function<br />

in many cardiovascular conditions. However, it remains unclear wheter the<br />

beneficial effects of statin treatment on endothelial function in patients with acute<br />

myocardial infarction (AMI) are dependent of statin dosage.<br />

The aim of our study was to assess the effects of different statin doses on endothelial<br />

function as assessed by flow mediated vasodilatation of brachial artery<br />

(FMD), in patients with myocardial infarction.<br />

Methods: Ninty patients with acute myocardial infarction were randomized, within<br />

24-72h from hospitalization, in three groups according to the statin dose used-<br />

Group I-commonly used statin dose in CCU, Group II-atorvastatin 40mg, Group III<br />

atorvastatin 80mg. Endothelial function was assessed by FMD of brachial artery<br />

prior to randomization, on day 7, and on day 30 after the randomization, as well<br />

The endothelium: at the heart of vascular biology (bedside) 493<br />

as lipid fractions-total cholesterol (Chol), LDL-cholesterol (LDL), HDL-cholesterol<br />

(HDL) and triglycerides (TG).<br />

Results: There was no difference in clinical characteristics (age, peak-creatinine<br />

kinase, prevalence of smoking and diabetes, p=NS for all), baseline FMD<br />

(2.69±4.32 (group I) vs 4.39±4.76 (group II) vs. 3.39±5.22 (group III), p=NS<br />

for all) and lipid fractions (Chol 6.4±2.1 (I) vs. 5.8±1.3 (II) vs. 5.7±1.1 (III);<br />

LDL 4.3±1.7 (I) vs. 3.8±1.1 (II) vs. 3.7±0.9 (III), HDL 0.98±0.32 (group I)<br />

vs. 0.87±0.24 (group II) vs. 0.93±0.35 (group III); TG 1.23±0.46 (group I) vs.<br />

1.27±0.57 (group II) vs. 1.34±0.53 (group III) p=NS for all comparisons), between<br />

the groups prior to randomization. Overall, statin treatment improved FMD after<br />

7 days (3.18±4.74-baseline vs. 5.21±4.30-day 7 p


494 The endothelium: at the heart of vascular biology (bedside) / Cardiovascular magnetic resonance<br />

Methods: PB samples from patients with AMI were studied by flow cytometry<br />

within 12 hours (n=30), at 6±1 days (n=23) and 30±2 days (n=15) of the event<br />

index. Aditionally, 6 PB samples from healthy subjects were included. Clinical variables<br />

were recorded: gender, age, type of AMI, start-up time of revascularization,<br />

size of infarct (defined by CPK levels) and left ventricular systolic function.<br />

Results: 30 patients have been included and until now 15 patients have completed<br />

the study. 25 patients (83.3%) were males. The mean age were 64.0±2.4<br />

years. In patients suffering AMI the majority of cells detected, among cellular population<br />

expressing CD146 protein, displayed immunophenotypic characteristics of<br />

T lymphocytes (CD146+, CD3+, CD45++) (p


P2966 Detection of late enhancement in cardiac MRI is a<br />

predictor for the occurrence of ventricular<br />

tachycardias in patients with dilated cardiomyopathy<br />

K. Kouraki 1 ,B.Mark 1 , T. Kleemann 1 , B. Cornelius 2 , A. Kilkowski 1 ,<br />

T. Becker 1 ,G.Layer 2 ,K.Seidl 1 ,R.Zahn 1 . 1 Herzzentrum<br />

Ludwigshafen, Kardiologie, Ludwigshafen, Germany; 2 Klinikum Ludwigshafen,<br />

Radiologie, Ludwigshafen, Germany<br />

Objectives: Previous studies have shown that detection of late enhancement<br />

(LE) in patients with dilated cardiomyopathy (DCM) is associated with a worse<br />

prognosis as well as with increased inducibility of ventricular tachycardias. Aim of<br />

this study was to assess whether the presence of LE in DCM is associated with<br />

an increased occurrence of ventricular arrhythmia episodes in patients receiving<br />

an implantable cardioverter defibrillator (ICD).<br />

Methods: Between 06/2003 and 12/2007, 30 consecutive patients with DCM and<br />

an ejection fraction below 40% underwent coronary angiography and cardiac MRI<br />

before receiving an ICD. Ventricular arrythmia was defined as episodes of ventricular<br />

tachycardia (VT) or ventricular fibrillation (VF) which were terminated by<br />

antitachycardia pacing or appropriate ICD-shock. Average follow-up time was 18<br />

months.<br />

Results: LE was seen in 13 patients (43%), the pattern was in 7 cases longitudinal<br />

midwall in the intraventricular septum and in 4 cases patchy diffuse midwall<br />

or transmural. Among those patients, 7 (54%) had VT/VF episodes, whereas in<br />

the control group without LE only 5 patients (18%) had VT/VF episodes (p


496 Cardiovascular magnetic resonance: insights into comprehensive management programme<br />

P2970 Immunohistological basis of late gadolinium<br />

enhancement phenomenon in tako tsubo<br />

cardiomyopathy by cardiac MRI<br />

A. Rolf 1 ,H.Nef 1 , H. Moellmann 1 ,S.Kostin 2 ,S.Voss 2 , G. Conradi 1 ,<br />

J. Rixe 1 ,A.Elsaesser 1 ,C.Hamm 1 , T. Dill 1 . 1 Kerckhoff <strong>Heart</strong><br />

Center, Cardiology/Cardiac Imaging, Bad Nauheim, Germany; 2 Max Planck Inst.<br />

of <strong>Heart</strong> and Lung Research, Bad Nauheim, Germany<br />

Objective: The absence of Late Gadolinium Enhancement (LGE) in patients with<br />

Tako Tsubo Cardiomyopathy (TTC) has been a widely accepted paradigm. Recently<br />

several authors reported single cases of LGE, the reason for this phenomenon<br />

yet unknown. LGE can be attributed to one or more of the following<br />

tissue conditions: edema, necrosis or fibrosis. As published previously we found<br />

transient interstitial fibrosis in myocardial biopsies of TTC patients. We therefore<br />

sought to determine, if the LGE phenomenon in TTC is based on a transient increase<br />

in extracellular fibroid matrix.<br />

Methods: The diagnosis of TTC was based on apical ballooning with hyper contractile<br />

basal segments after rule out of CHD on X-ray coronary angiograms.<br />

Written informed consent was obtained from all patients to undergo biopsy. Viral<br />

myocarditis was ruled out by PCR. We performed collagen-1 staining on the<br />

myocardial biopsies and computed the mean percentage areas of collagen per<br />

field of view. Creatininkinase levels were compared as markers of necrosis. Patients<br />

underwent cardiac MRI (CMR). Late Enhancement was documented on inversion<br />

recovery Fast Gradient Echo Sequences (FLASH, Siemens) and graded<br />

as present or absent. Edema was calculated as mean percentage area of the<br />

myocardium on Turbo Spin Echo Sequences in two long axis orientations. Mann-<br />

Whitney-U-Test were used to compare group differences. Absolute values are<br />

given ± SD. P- values equal or less than 0.05 were considered significant.<br />

Results: Complete data were available for 8 patients, two of which were LGE positive.<br />

There was no significant difference in CK values or edema between groups<br />

(CK: LGE pos. 115.5±48.8 U/L vs. LGE neg. 138.6±41.3 U/l p = 0.7; edema:<br />

LGE pos. 18.7±0.2% vs. LGE neg. 21.3±15.8% p = 0.56). The extracellular matrix<br />

however, as represented by collagen-1 staining, was significantly increased in<br />

LGE positive Patients (LGE pos. 12±4.8% vs. LGE neg. 4.6±1.8% p = 0.046).<br />

Conclusion: The present data suggest that LGE in patients with TTC is caused<br />

by transient increase of extracellular fibroid matrix, contradicting the paradigm,<br />

that LGE rules out TTC. A limitation of the study is the small sample size due<br />

to the low frequency of the disease. Therefore further studies with larger patient<br />

cohorts are warranted to corroborate these findings.<br />

P2971 Cardiovascular magnetic resonance monitors<br />

reversible and irreversible myocardial injuries in<br />

myocarditis and predicts long term LV-remodeling:<br />

Insights from a comprehensive approach<br />

H. Abdel-Aty, A. Zagrosek, P. Boye, R. Wassmuth, D. Messroghli,<br />

W. Utz, A. Rudolf, S. Bohl, R. Dietz, J. Schulz-Menger. Franz-Volhard-<br />

Klinik,Charite Campus Buch, Kardiologie, Universitatsmedizin Berlin, Berlin,<br />

Germany<br />

Purpose: Myocarditis is associated with a wide-range of myocardial tissue injuries<br />

and may lead to long-term left ventricular (LV) remodeling. We sought to<br />

assess the value of CMR to monitor patients over the course of myocarditis and<br />

to explore if myocardial tissue injury assessed by cardiovascular magnetic resonance<br />

(CMR) could predict LV-remodeling.<br />

Methods: We studied 36 patients (31 males, 51±16 y) hospitalized with myocarditis<br />

during the acute phase and 18±10 months thereafter. CMR was performed<br />

on two 1.5T scanners and included the following sequences: steady<br />

state free precession, T2-weighted, early (global relative enhancement, gRE) and<br />

late T1-weighted after gadolinium-DTPA injection (late gadolinium enhancement,<br />

LGE). The primary end-point was 10% or more increase in end-diastolic volume<br />

at follow-up (delta-EDV).<br />

Results: In the acute phase, T2 ratio was elevated in 86%, relative enhancement<br />

in 80% and LGE was present in 63%. There was a significant correlation<br />

between T2 ratio and troponin folds (beta = 0.53; p= 0.005). At follow-up<br />

both T2 ratio (1.9±0.2 vs. 2.4±0.5; p


tissue as an enhanced area. On the other hand, transient inflammatory changes<br />

following thermal injury from radiofrequency ablation and development of scar<br />

tissue would allow a direct comparison of electrophysiologic results and permit<br />

correlation with clinical outcomes.<br />

Methods: Fifty-six patients underwent radiofrequency ablation of the cavotricuspid<br />

isthmus (CTI) for isthmus-dependent atrial flutter (AFL; 12 females,<br />

59±12 years). All patients were performed right atrial conventional angiography<br />

to determine the CTI length and the CTI morphology. During CTI ablation, bipolar<br />

electrograms were recorded along the ablation line during proximal coronary<br />

sinus pacing, and measured an interval of double potential (DP) to determine<br />

complete isthmus block. MRI was performed before, 1 day after, and 1 month after<br />

CTI ablation. The change of CTI wall thickness and the prevalence of delayed<br />

enhancement at the CTI after ablation were analyzed.<br />

Results: The mean CTI length was 44±10 mm. The 30 patients (46%) showed<br />

concave characteristics, and pouch-like recesses were seen in 16 patients (29%).<br />

Complete isthmus block was obtained all 56 patients, and the mean DP intervals<br />

were 102±20 ms. One day after CTI ablation, the contrast-enhanced MRI<br />

revealed delayed enhancement at the CTI in 46 patients (82%), and relative to<br />

baseline CTI wall thickness was significantly increased (1.6±0.1 mm vs. 2.3±0.2<br />

mm, p< 0.0001). In contrast, one month after CTI ablation, those edematous<br />

changes had disappeared, and the CTI wall thickness was not significantly different<br />

from baseline. The delayed enhancement at the CTI was clearly found in<br />

48 patients (86%). No correlation was observed between the prevalence of scar<br />

tissue after CTI ablation and the CTI morphology.<br />

Conclusions: MRI is useful to assess the creation of endocardial edema and<br />

scar tissue resulting from CTI ablation. These results may correlate with anatomical<br />

isthmus block after CTI ablation in a large portion of patients with isthmusdependent<br />

AFL.<br />

P2975 Magnetic resonance imaging identifies myocardial<br />

injury in the course of ablation procedures for atrial<br />

fibrillation<br />

A.M. Sinha1 , C. Mahnkopf1 , G. Ritscher1 , R. Oakes2 , T. Badger2 ,<br />

M. Schmidt1 , H. Marschang1 , E.V.R. Dibella3 , N.F. Marrouche2 ,<br />

J. Brachmann1 . 1Klinikum Coburg, Ii. Medizinische Klinik, Coburg, Germany;<br />

2University of Utah Medical School, Salt Lake City, United States of America;<br />

3Utah Center for Advanced Imaging Research, Salt Lake City, United States of<br />

America<br />

Purpose: Pulmonary vein antrum isolation (PVAI) is regarded as an effective<br />

therapy in patients with atrial fibrillation (AF). Extension and location of ablation<br />

lesions often remain unclear during the procedure. We report a new approach on<br />

visualization of myocardial injury using magnet resonance imaging (MRI) during<br />

PVAI procedure.<br />

Methods: Patients who underwent PVAI, received MRI before and at the terminal<br />

phase of PVAI. Delayed enhancement (DE-MRI) sequences were applied, and<br />

maximum intensity projections (MIP) obtained. Myocardial injury size was then<br />

measured on manually segmented 3D images by a computer algorithm using<br />

dynamic thresholding.<br />

Results: 30 patients received PVAI from December 2007 to February <strong>2008</strong>. In a<br />

subset of 10 patients, MRI was performed before and during the procedure. Using<br />

DE-MRI, the average lesion to healthy myocardium ratio was 7.56±1.27% during<br />

PVAI. The figure shows an example of MIP of a DE-MRI scan in 2D (A,D) and<br />

MRI in PVAI patients.<br />

Cardiovascular magnetic resonance: insights into comprehensive management programme 497<br />

3D (C,D) segmentation in a anterior view pre (A,C), and during PVAI procedure<br />

(B,D). Myocardial injury is identifiable as white tissue around PV single ostia (D,<br />

full arrows) and common trunk (D, dashed arrows).<br />

Conclusion: Using MRI is feasible in the course of ablation procedures. In PVAI<br />

patients, DE-MRI allowed identification of location and extension of myocardial<br />

injury. Therefore, this new MRI approach might improve ablation techniques, and<br />

thus long-term success of PVAI.<br />

P2976 Insufficiency in diagnosis and treatment of cardiac<br />

diseases in patients with muscular dystrophy with<br />

conventional evaluation methods: a novel approach<br />

using cardiovascular magnetic resonance imaging<br />

A. Yilmaz1 , H.J. Gdynia2 , H. Baccouche1 , H. Mahrholdt1 ,<br />

A.D. Sperfeld2 , A.C. Ludolph2 , U. Sechtem1 . 1Stuttgart, Germany; 2Ulm, Germany<br />

Purpose: Muscular dystrophy type Becker-Kiener (BMD) represents an X-linked<br />

genetic disease due to dystrophin gene mutations. Apart from skeletal myopathy,<br />

cardiac muscle involvement with the development of dilated cardiomyopathy<br />

(DCM) has been described in BMD patients previously, mainly based on echocardiographic<br />

and nuclear imaging studies. The course of the disease can potentially<br />

be alleviated by timely onset of adequate medication. However, both echocardiography<br />

and nuclear imaging have well known method-inherited limitations. Therefore,<br />

cardiovascular magnetic resonance imaging (CMR) represents a promising<br />

non-invasive tool for comprehensive cardiac evaluation of patients with muscular<br />

dystrophy.<br />

Methods: In a prospective two-center-study, 14 male patients with BMD (mean<br />

age 36.4±14.7; range 11 to 56 years) underwent comprehensive neurological<br />

and cardiac evaluation. Cardiological work-up comprised echocardiography and<br />

CMR (1.5-T). A 16-segment model was applied for evaluation of regional wall<br />

motion abnormalities (rWMA) and quantification of a global systolic wall motion<br />

score index (GWMS). The CMR study included late gadolinium enhancement<br />

(LGE) imaging with quantification of myocardial fibrosis.<br />

Results: Within this study, pathologic echocardiographic results (defined as left<br />

ventricular ejection fraction (LVEF) < 55% and/or rWMA) were found in 8 of 14<br />

(57.1%) patients with all of them demonstrating reduced LVEF and rWMA (mean<br />

GWMS 0.27±0.34). By contrast, CMR revealed pathological findings (defined as<br />

LVEF < 60% and/or rWMA and/or presence of LGE) in 12 of 14 (85.7%) patients<br />

(p = 0.040 compared to echocardiography) with 10 (71.4%) of them having<br />

reduced LVEF (p = 0.16) and 9 (64.3%) demonstrating rWMA (mean GWMS<br />

0.30±0.34; p = 0.43). Importantly, myocardial fibrosis was present in 11 of 14<br />

(78,6%) patients as assessed by LGE imaging with a mean myocardial fibrosis<br />

extent of 11.7±10.0% (range 0 to 31.0%). Correlation analyses revealed a substantial<br />

association between increased myocardial fibrosis and decreased LVEF<br />

(r 2 = 0.46; p = 0.008). Nine patients (64.3%) were actually in need of medical<br />

therapy based on clinical symptoms and CMR results. However, only 4 patients<br />

(28.6%) were already taking heart failure medication (p = 0.019).<br />

Conclusions: Cardiac involvement in patients with BMD is underdiagnosed by<br />

echocardiographic methods resulting in undertreatment of occult heart failure. For<br />

a sensitive diagnosis of cardiac involvement in patients with BMD, comprehensive<br />

CMR studies including LGE imaging are required.<br />

P2977 Left ventricular trabeculae: quantification in different<br />

cardiac diseases with cardiac magnetic resonance<br />

C. Fernandez-Gofin Loban1 , J. Zamorano1 , M. Pachon Iglesias2 ,<br />

C. Corros1 ,L.PerezDeIsla1 , J. Ferreiros1 ,A.Bustos1 ,<br />

B. Cabeza1 , G. Pizarro1 ,C.Macaya1 . 1Hospital Clinico San Carlos,<br />

Cardiovascular Imaging Unit, Madrid, Spain; 2Hospital Virgen de la Salud,<br />

Cardiology, Toledo, Spain<br />

Background: Left ventricle trabeculae are frequently seen in different cardiac diseases<br />

Differential diagnosis with non compaction cardiomyopathy is often difficult.<br />

Cardiac magnetic resonance (CMR) accurately identify left ventricular trabeculations<br />

but normal reference values in different cardiac conditions are not known.<br />

Objective: To calculate with CMR, left ventricle trabecuale mass (LVTM) and<br />

LVTM percentage (LVTM%) in different heart diseases, evaluating its posible<br />

diffrent distribution between groups.<br />

Methods: 59 patients were enrolled: 13(22.0%) controls; 17(28.8%) ischemic<br />

cardiomyopathy; 15(25.4%) idiopathic cardiomyopathy, 7(11.9%), valvular heart<br />

disease and 7(11.9%) hyperthrophyc cardiomyopathy. Cine-MR images (General<br />

Electrics 1.5T.Signa) were acquired with steady-state free precession sequence<br />

(FIESTA) covering left ventricle in a short axis view from base to apex (slice thickness<br />

8 mm, gap 2 mm). LVTM was calculated as the difference between LVM<br />

excluding trabecuale from the blood cavity and left ventricle mass including trabeculae<br />

as part of the blood cavity. LVTM% was then calculated as the percentage<br />

of the whole left ventricle mass excluding trabeculae form the blood cavity.<br />

All analysis were performed using GE Resport Card work Station.<br />

Results: 59 patients (mean age 47.60±22.03; male 62.7%) were included. Main<br />

results are shown in Figure 1.<br />

Conclusions: CMR can accurately determine LVTM and LVTM percentage.<br />

LVTM and LVTM percentage varies among different cardiac conditions being<br />

more prevalent in patients with dilated and ischemic cardiomyopathy. Calculation<br />

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498 Cardiovascular magnetic resonance / New developments in time Doppler imaging<br />

Figure 1. Main results.<br />

and distribution of LVTM and LVTM% with CMR may help in diferencial diagnosis<br />

between non compaction cardiomyopathy and other cardiac diseases.<br />

P2978 Useful of cardiac magnetic resonance in detecting<br />

myocardial features in patients with chest pain and<br />

normal coronary arteries: clinical applications<br />

M. Perazzolo Marra1 , L. Cacciavillani1 , F. Corbetti 2 ,A.Marzari1 ,<br />

A.B. Ramondo1 ,R.Turri1 , S. Iliceto1 . 1Dpt of Cardio, Thoracic and<br />

Vascular Sciences, Padua, Italy; 2Service of Radiology, Padua, Italy<br />

Background: In clinical practice more and more patients presenting symptoms<br />

typical of ischemia accompanied by ECG changes and biomarkers classic for<br />

miocardial infarction (MI) reveal none coronary stenosis. However, coronary angiography<br />

is not a perfect tool and coronary lesion could have missed or understimated.<br />

Cardiac Magnetic Resonance (CMR) is an accurate noninvasive tool<br />

for detecting MI and other causes of myocardial damage.Aim: To evaluate clinical<br />

characteristics in a population presenting with chest pain, enzymatic and ECG<br />

features suggesting acute coronary syndrome (ACS) or myocarditis and to compare<br />

final clinical diagnosis with CMR findings.<br />

Methods: We studied consecutive patients hospitalized in our Cardiologic Intensive<br />

Care from October 2006 to Jannuary <strong>2008</strong> for chest pain, suspected ACS<br />

or myocarditis and normal coronary angiography. All patients undewent coronary<br />

angiography and MRI. CMR was performed with 1.0-T scanner and images were<br />

acquired using a steady-state free-precession sequences,T2-weighted images<br />

for edema evaluation and contrast-enhanced sequences. For each group we analyzed<br />

clinical characteristics, ECG and angiographic findings.<br />

Results: We evaluated 49 patients (mean age 50±17 years;22 female); mean<br />

peak increase of troponin I was 7,6±7 ug/L, mean ejection fraction was 59±16%.<br />

Initial diagnosis was ACS without ST segment elevation (NSTE) in 25 (51%) patients,<br />

ACS with ST segment elevation (STE) in 9 (18%), suspected myocarditis<br />

in 15 (31%). All the patients showed normal coronary arteries on angiography.<br />

Final diagnosis was MI with normal coronary arteries in 15 (31%) patients (only<br />

one patient showed coronary vasomotion), myocarditis in 30 (61%), tako-tsubo<br />

cardiomyopathy in 4 (8%). CMR showed isolated regional wall motion abnormalities<br />

without delayed enhancement (DE) in 2 (4%) patients, and subendocardial<br />

DE, suggesting AMI with normal coronary arteries, in 5 (10%). T2-weighted sequences<br />

and distribution of DE concluded for myocarditis in 31 (64%) patients. In<br />

7 patients (14%) cine, T2-weight and DE sequences CMR suggested tako-tsubo<br />

cardiomyopathy. Negative CMR was found in 4 (8%) patients.<br />

Conclusion: Our experience confirms that in patients presenting symptoms typical<br />

of ischemia with ECG changes and enzymatic increasing classic for MI, but<br />

normal coronary arteries, CMR images is also helpful. CMR patterns can identify<br />

patients with myocarditis allowing a noninvasive follow-up, also in patients with<br />

DE showing subendocardial necrosis suggests a more invasive study of coronary<br />

arteries called as normal.<br />

P2979 Evaluation of marfan syndrome by cardiovascular<br />

magnetic resonance<br />

F. Alpendurada, R. Mohiaddin. Royal Brompton Hospital, CMR Unit,<br />

London, United Kingdom<br />

Introduction: Marfan syndrome (MS) is a rare connective tissue disease<br />

caused by mutations of the fibrillin-1 gene. Cardiovascular Magnetic Resonance<br />

(CMR) plays an important role in identifying and evaluating cardiovascular<br />

manifestations in this population, which is the major source of morbidity and mortality.<br />

CMR was used in this study to assess the prevalence of cardiovascular<br />

manifestations in a Marfan population.<br />

Methods: The study population consisted of 120 consecutive Marfan patients referred<br />

to our centre between January 2003 and June 2007 including 77 males<br />

(64.2%) and 43 females (35.8%), mean age 34.9 years. 33 patients (27.5%) had<br />

history of previous aortic or cardiac surgery. We evaluated thoracic aortic dimensions<br />

and assessed for structural abnormalities of the aorta, aortic arch branches,<br />

and main pulmonary artery. Left ventricular (LV) volumes and mass, and aortic<br />

(AV) and mitral valves (MV) anatomy and function were also evaluated. Assessment<br />

of chest wall deformities was also performed.<br />

Results: The aortic root was dilated in 69 patients (57.5%), the ascending aorta<br />

was dilated in 23 patients (19.2%), the aortic arch was dilated in 19 patients<br />

(15.8%), and the descending aorta was dilated in 18 patients (15.0%). The arch<br />

vessels were dilated in 9 patients (7.5%), and the abdominal aorta was involved in<br />

9 patients (7.5%). The main pulmonary artery was dilated in 16 patients (13.3%).<br />

Aortic dissection was noted in 9 patients, and intramural haematomas were seen<br />

in 2 patients.<br />

There was native aortic regurgitation in 50 patients (49.5%), which was moderate<br />

or severe in 14 patients (13.9%). 43 patients (37.1%) met criteria for MV prolapse.<br />

Mitral regurgitation was identified in 22 patients (19.0%), which was moderate or<br />

severe in 8 patients (6.9%).<br />

LV indexed end-diastolic and end-systolic volumes were increased in 50 (43.1%)<br />

and 48 (41.4%) patients, respectively. LV ejection fraction was decreased in 31<br />

patients (26.7%), and mass index was increased in 32 patients (27.6%).<br />

Fifty three patients (44.2%) had pectus carinatum and 13 patients (10.8%) had<br />

pectus excavatum. Scoliosis was present in half of the patients, being moderate<br />

or severe in 32 patients (26.7%).<br />

Conclusions: This study shows a high prevalence of aortic complications in this<br />

group of patients. Valvular involvement, increased LV volumes and decreased<br />

ejection fraction were frequent findings, warranting regular follow-up in this population.<br />

The prevalence of chest wall deformities highlights the importance of CMR<br />

in assessing the cardiovascular system of these patients in whom echocardiography<br />

is likely to be difficult.<br />

P2980 Characterization of myocardium using in vivo<br />

late-gadolinium enhancement high-resolution<br />

myocardial T1 mapping in mice on a 11,75 magnet<br />

S.S. Bun, F. Kober, J. Kalifa, A. Jacquier, P.J. Cozzone, M. Bernard.<br />

CRMBM, Cardiology Department, Marseille, France<br />

Background: Late-gadolinium enhancement magnetic resonance imaging (LGE)<br />

is an accurate method to assess myocardial fibrosis. T1 relaxation time in normal<br />

mouse myocardium before and after contrast agent is of importance for optimizing<br />

LGE acquisitions. However, at high field strength, T1 of myocardium was reported<br />

quantitatively only without contrast agent, under slice-selective inversion<br />

conditions [1], and no blood T1 values were reported.<br />

Purpose: To establish the normal range and reproducibility of myocardial and<br />

blood T1 as assessed with high-resolution global-inversion myocardial T1mapping<br />

in mice with and without contrast agent at 11.75T.<br />

Methods: Look-Locker Inversion-Recovery GE T1 mapping (resolution 195x390<br />

μm 2 , slice thickness 1.5mm, imaging time 15min [2]) was performed in eight<br />

12-week old C57Bl/6J mice under isoflurane anesthesia using a 11.75T vertical<br />

scanner. The measurements were performed before and 20 min after intravenous<br />

injection of gadolinium-DTPA (0.30 mmol/kg). Blood T1 was measured using a<br />

homogeneous spin-inversion over the entire animal was produced.<br />

Results: Baseline mean ± SD myocardial T1 was 1.95±0.16s, and was reduced<br />

to 1.01±0.15s, 20min after injection of gadolinium. Baseline mean blood T1 was<br />

1.73±0.24s, and decreased to 0.52±0.20s.<br />

T1 maps pre (a) and post (b) Gd<br />

Conclusion: High-resolution myocardial T1-maps were obtained. Myocardial and<br />

blood T1 values pre- and post-contrast were calculated at 11.75T. As a result of<br />

global spin inversion and myocardial perfusion, T1 values were higher than those<br />

previously reported. Quantitative T1 assessment might enable direct quantification<br />

of myocardial fibrosis in cardiomyopathies.<br />

[1] Schneider JE et al. J Magn Reson Imaging. 2003 Dec;18(6):691-701.<br />

[2] Kober F et al. Magn Reson Med. 2005 Mar;53(3):601-6.<br />

NEW DEVELOPMENTS IN TIME DOPPLER IMAGING<br />

P2981 The contribution of Tissue Doppler Imaging (TDI) in<br />

early diagnosis of myocardial dysfunction induced by<br />

the use of cardiotoxic drugs<br />

H. Michalopoulou, P. Stamatis, A. Bakhal, J. Vaitsis, D. Stamatis.<br />

Metaxa Hospital, Cardiology Department, Athens, Greece<br />

Purpose: Treatment with anthracyclines in breast cancer while associated with a<br />

high response contains the risk of cardiotoxicity. The early diagnosis of myocar-<br />

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dial dysfunction is critical for the prognosis of these patients. The present study<br />

evaluated the systolic and diastolic function of the left ventricle in asymptomatic<br />

women with breast cancer who received anthracyclines.<br />

Methods: 66 consecutive women (53±12 years old) suffering from breast cancer<br />

[group A] and 49 healthy volunteers [group B] were studied. The individuals of<br />

the study did not manifest symptomatology related to cardiac disease. They underwent<br />

echocardiographic study (standard and TDI) prior to chemotherapy and<br />

6 months later. The ejection fraction (EF) was evaluated, as well as the systolic<br />

(Sm), early diastolic (Dm) and late-diastolic (Am) myocardial velocities on the longitudinal<br />

axis.<br />

Results: No differences were observed at the systolic performance of the left<br />

ventricle with the use of standard echocardiography (EF: 63.8±3.7% in group A<br />

vs 64.2±2.6% in group B p=NS).<br />

Nevertheless, with TDI an impaired systolic and diastolic function of the left<br />

ventricle was shown in women who received anthracyclines in comparison to<br />

healthy women. Sm:3.92±0.7 in group A vs 4.62±0.9 in group B (p=0.001),<br />

Em:4.82±1.3 in group A vs 5.73±1.4 in group B (p=0.001), Am:5.34±1.2 in group<br />

Avs4.23±0.8 in group B (p=0.001).<br />

Conclusion: Patients who have received treatment with anthracyclines, even<br />

though asymptomatic and with seemingly normal systolic performance with the<br />

use of standard echocardiography, display an impaired function of the left ventricle.<br />

Tissue Doppler echocardiography can help in early diagnosis and consequently<br />

in the timely treatment of myocardial dysfunction.<br />

P2982 The utility of tissue Doppler imaging in predicting<br />

early left ventricular dysfunction in a murine model of<br />

anthracycline-induced cardiomyopathy<br />

C. Hans, A. Sharma, R. Ahmadie, T. Fang, P.K. Singal, D. Jassal. St.<br />

Boniface General Hospital, Winnipeg, Canada<br />

Background: Trastuzumab, an antagonist to the HER-2 receptor, significantly decreases<br />

the rates of breast cancer recurrence and mortality. Despite this benefit,<br />

Trastuzumab (T) and Doxorobucin (Dox) is associated with a 10-15% incidence<br />

of cardiotoxicity and its early detection may improve patient management. Liposomal<br />

encapsulation of Dox (Myocet) is associated with minimal cardiotoxicity; its<br />

effects in combination with T remain unknown.<br />

Objective:To determine whether Myocet+T would be less cardiotoxic as compared<br />

to Dox+T using Tissue Doppler imaging and conventional echocardiography.<br />

Methods: Wild-type C57Bl/6 mice (n=50) received one of the following; i) Dox<br />

(20 mg/kg); ii) Myocet (10 mg/kg); ii) T (20 mg/kg); iv) Dox+T; or v) Myocet+T.<br />

TDI-derived peak endocardial systolic velocity (Vendo), strain rate (SR), and LV<br />

ejection fraction (EF) were measured serially for five days. On day 5, the heart<br />

and liver were removed for histological and biochemical analysis.<br />

Results: Mice treated with Myocet+T was associated with minimal cardiotoxicity<br />

in comparison to Dox alone or Dox+T. Progressive LV dilatation and LV systolic<br />

dysfunction by day 4 of treatment with Dox+Trast was observed, as compared to<br />

preserved LVEF in the remaining groups. TDI parameters decreased within 24<br />

hours in the Dox alone or Dox+T groups and predicted early mortality. There was<br />

a significant increase in apoptosis (Bax/Bcl ratio) in the Dox+T group as compared<br />

to the other groups. The survival rate was only 20% at day 5 of the experiment in<br />

Dox+T, whereas 100% of mice receiving T, Myocet or Myocet + T survived the 5<br />

days.<br />

Conclusion: TDI can detect LV dysfunction prior to alterations in conventional<br />

echo indices and predicts early mortality in mice receiving Dox+T as compared<br />

to Myocet+T in an acute model of chemotherapy induced cardiotoxicity.<br />

P2983 Global strain is superior to mitral annulus<br />

displacement to quantify myocardial infarct mass in<br />

chronic ischemic heart disease<br />

O. Gjesdal, T. Vartdal, T. Helle-Valle, K. Lunde, E. Hopp, H.-J. Smith,<br />

H. Ihlen, T. Edvardsen. Rikshospitalet University Hospital, Dept. of<br />

Cardiology, Oslo, Norway<br />

Purpose: Global longitudinal strain (GS) and mitral annulus displacement (MD)<br />

are markers of longitudinal LV function. We compared the two method’s ability to<br />

quantify LV function in patients with myocardial infarct.<br />

Methods: LV infarct mass was measured by late enhancement MRI in 61 patients<br />

9±5 months after a first myocardial infarction (MI). Longitudinal strain was<br />

assessed in 16 LV segments by speckle tracking echocardiography and mitral annulus<br />

displacement in 6 segments by tissue Doppler imaging. GS and MD were<br />

calculated by averaging the segmental values, and were then compared to LV<br />

infarct mass by regression analysis and tested for ability to separate small (0-30<br />

g), medium (30-50 g) and large (≥50 g) MI.<br />

Results: GS and MD correlated well with infarct mass (Figure). Myocardial func-<br />

Mean values<br />

Small (0-30g) Medium (30-50g) Large (>50g)<br />

Infarct Mass (g) 13±10 41±5 † 74±20*<br />

GS (%) -17±2 -15±2 † -10±3*<br />

MD (mm) 11±1 10±1 8±2*<br />

Mean values ± SD by infarct mass. *p≤0.05 vs medium, † p≤0.05 vs small myocardial infarct.<br />

Correlation plots.<br />

New developments in time Doppler imaging 499<br />

tion was progressively lower in patients with larger infarcts as assessed by both<br />

methods. Both indices separated large from medium sized MI (*p


500 New developments in time Doppler imaging<br />

morphological distinct segments (the basal smooth muscle and the apical trabecular)<br />

and longitudinal deformation was measured for both. This deformation data<br />

were compared to normal values (from 37 controls) and to 4 pts with both severe<br />

LV hypertrophy and pronounced global RV enlargement and systolic dysfunction<br />

detected by angiography and TTE.<br />

Results: All 35 pts had normal RV diameters and function reported by standard<br />

TTE. In all pts severe LV hypertrophy was present (septal wall 22±5 mm). In contrast<br />

to controls (S: basal – 43±11%, apical - 41±11%; peak SR: basal –2,9±1<br />

1/s, apical –2,6±0,9 1/s), the regional systolic deformation values (S: basal –<br />

27±7%, apical -26±9%; peak SR: basal -2±0,5 1/s, apical – 2±0,6 1/s) were significantly<br />

reduced. In the 4 pts with unequivocal RV dysfunction by conventional<br />

methods deformation was even further reduced (S: basal -12%, apical -6%). In a<br />

subset of HCM pts (n = 6) both regional deformation values were >1,5 SD below<br />

the control (S: basal -20±3%, apical -20±5%) values, despite conventional TTE<br />

being normal. In 3 pts basal deformation parameters were > 1,5 as apical; 2 of<br />

these showing apical hypertrophy.<br />

Conclusion: Regional RV deformation analysis is feasible in pts with HCM and<br />

shows pronounced regional impaired systolic deformation, despite conventional<br />

methods (TTE, angiogram) failed to detect these changes. S and SR is a useful<br />

non invasive tool to detect subtle changes in RV/LV function. Additional use of this<br />

methods especially regarding RV involvement and function might help to distinguish<br />

HCM clinically from other cardiac disorders with LV hypertrophy mimicking<br />

its clinical features (i.e. hypertensive heart disease, cardiac storage disease) with<br />

consequences for prognosis and therapy.<br />

P2986 Tissue Doppler echocardiography in persons with<br />

hypertension, diabetes or ischemic heart disease<br />

R. Mogelvang 1 , P. Sogaard 1 , S.A. Pedersen 1 ,N.T.Olsen 1 ,<br />

P. Schnohr 2 , J.S. Jensen 1 . 1 Cardiology, Gentofte, Denmark;<br />

2 Epidemiological Research Unit, Bispebjerg, Denmark<br />

Purpose: Echocardiographic tissue Doppler imaging (TDI) has proven useful in<br />

the hospital setting in various cardiac diseases, but the diagnostic significance<br />

in evaluating cardiac function in the general population is unknown. This study<br />

was performed to evaluate the potential role of tissue Doppler imaging in the<br />

characterization of myocardial function in the general population.<br />

Methods: Within a large, community-based population study, cardiac function<br />

was evaluated in 1,036 men and women both by conventional echocardiography<br />

and by color TDI. An abnormal conventional echocardiographic examination was<br />

defined as hypertrophy, dilatation, low ejection fraction (15 mmHg (Sensitivity 90%,<br />

specificity 80%, positive predictive value 90%) Sensitivity, specificity and positive<br />

predictive value of peak E wave velocity >1 m/s suggesting severe MR were found<br />

to be different in pts with normal (>50%) and low (


for testing the load dependence. The latter was evaluated on a series of 33 patients<br />

daily imaged during ECLS output variations. 22 of them tolerated acute<br />

decrease to 33 or 10% of the initial support (70 load conditions). The haemodynamic<br />

status was assessed with the mean invasive arterial pressure (MAP),<br />

Aortic Doppler VTI, Mitral Doppler E wave (Em), and Ejection Fraction (EF). The<br />

lateral and septal wall motion were assessed using 2DSRI: systolic peak velocity<br />

(Sv), strain (S), strain rate (SR) and early diastolic velocity (Ev). Moreover, systolic<br />

and early diastolic (E’) Tissue Doppler velocities were studied at the mitral<br />

annulus level.<br />

Results: The load manipulation induced by the decrease of the ECLS output<br />

were documented by the significant changes (p≪0.01) of MAP, aortic VTI,<br />

EM and EF: decrease of Em (-25cm s -1 ) and Em/E’ (+2), increase of MAP<br />

(+16mmHg), VTI (+3cm) and EF (+4%). The load dependence of 2DSRI parameters<br />

is shown on Table 1. Similarly, the TD velocities are modified by load<br />

variations (p≪0.01) even if these variations are low (-0.3cm s -1 ).<br />

Table 1. The load dependence of 2DSRI<br />

ECLS output (L min-1 ) SV (cm s-1 ) EV (cm s-1 ) S (cm s-1 ) Systolic SR (%) Diastolic SR (%)<br />

Maximum (3.8 + 1.0) 1.18 + 0.85 1.33 + 0.95 4.06 + 4.80 0.43 + 0.33 0.41 + 0.35<br />

Minimum (0.9 + 0.5) 1.79 + 0.77 1.90 + 1.16 6.71 + 6.00 0.58 + 0.42 0.58 + 0.37<br />

p 0.001 0.004 0.001 0.03 0.01<br />

Conclusion: 2DSRI parameters demonstrate a clear load dependence during<br />

acute manipulations associated with ECLS<br />

P2990 Asymmetrical longitudinal left atrial myocardial<br />

systolic velocities: speckle tracking<br />

echocardiography<br />

Sweden<br />

M.(J.R.) Henein 1 , P. Lindqvist 1 , M. Henein 2 . 1 <strong>Heart</strong> Centre, Umea<br />

University Hospital, Cardiology, Umea, Sweden; 2 <strong>Heart</strong> Centre,<br />

Umea and Canterbury University, Cardiology, Umea And London,<br />

Background: Left ventricular velocities vary according to their location in the cavity<br />

with the basal segments, adjacent to the mitral ring, having the highest velocities<br />

with respect to the apical ones. HYOPTHESIS: Since atrial myocardial fibres<br />

are predominantly longitudinal and insert around the circumference of the mitral<br />

ring we hypothesis that their segmental velocities may follow the pattern of their<br />

opponents in the left ventricle.<br />

Methods: We studied 40 normal subjects (age 59±15 years, 19 females) with no<br />

symptoms, signs or history of cardiovascular disease using conventional Doppler<br />

echocardiography and 2D strain technique. Global atrial function was assessed<br />

from left ventricular atrial filling component. Regional left atrial longitudinal function<br />

was studied by 2D strain from the lateral and septal atrial walls at the annular,<br />

mid-cavity and rear levels.<br />

Results: The highest atrial systolic velocities were at the mitral annular level<br />

which fell progressively at the segments away from the mitral annulus; Lateral wall<br />

5.1±1.9 cm/s vs 3.0±1.5cm/svs1.17±1.3 cm/s (P


502 New developments in time Doppler imaging<br />

free of any known cardiovascular disease based on a thorough history, physical<br />

examination and a normal electrocardiogram. Regional longitudinal function was<br />

analysed in an 18-segment model of the left ventricle by extracting peak systolic<br />

strain rate (SRsys) and maximal systolic strain (Ssys) using dedicated software.<br />

Regression coefficients were calculated for SRsys and Ssys in each wall and age.<br />

Results: In contrast with the inferoseptal wall, peak SRsys and Ssys in the anterolateral<br />

wall correlated significantly with age: regression lines: InfSep Ssys =<br />

-0.24 + 0.0003*X vs. AntLat Ssys = -0.25 + 0.0015*X (figure).<br />

Conclusions: Aging does not equally affect all myocardial walls and segments.<br />

The anterolateral wall and apical segments are significantly influenced by aging<br />

while inferoseptal and inferior walls and basal segments are less affected. Differences<br />

in regional wall stress might account for these findings. This can explain<br />

conflicting data in current literature.<br />

P2994 Usefulness of longitudinal myocardial deformation<br />

analysis by two-dimensional echocardiography for<br />

the non invasive diagnosis of cardiac allograft<br />

vasculopathy in heart transplant patients<br />

V. Sanchez Sanchez1 , J.F. Delgado2 , A. Fontenla2 , A. Gonzalez2 ,<br />

F. Lombera2 , S. Fernandez2 , J. Garcia-Tejada2 ,A.Forteza2 , C. Saenz De La<br />

Calzada2 . 1Madrid, Spain; 2Hospital Doce de Octubre, Cardiology, Madrid,<br />

Spain<br />

Cardiac allograft vasculopathy (CAV) is the most frequent complication after heart<br />

transplantation. Up to 58% of heart transplantation (HTx) recipients present significant<br />

intimal thickening in IVUS 1 year later. However, coronary angiography<br />

is still the gold standard for the diagnosis of cardiac CAV for which alternative<br />

non-invasive diagnostic approaches are currently investigated. Two dimensional<br />

strain (2D S) offers a technique for quantifying transmural gradient of function<br />

across ischemic segments.<br />

Aim: To analyse usefulness of 2D S analysis to identify CAV in segments with<br />

normal contractility at rest.<br />

Methods: 48 consecutive HTx recipients with normal contractility at rest (mean<br />

age 55±18 years, 41 men, time post-HTx 86±62 months) scheduled for echocardiography<br />

evaluation were included in the study. 16 presented CAV in angiography<br />

and/or IVUS: 13 severe CAV and 3 moderate CAV. Longitudinal global 2D<br />

S and strain rate (SR) were measured in 4, 2 and 3 chambers views. Sensitivity<br />

(S), specificity (Sp) and area under the ROC curve (AUC) were analyzed for each<br />

parameter<br />

Results: Mean EF was 71±7%. HTx recipients with angiographic CAV showed<br />

significantly lower longitudinal global S than those without CAV (-13.77±6%<br />

vs -16.42±3%, p 0.001). No significant differences were found in SR values<br />

(0.98±0.3 s -1 vs -1.06±0.3 s -1 , p = NS). The most sensitive parameter to identify<br />

CAV by two dimensional strain was global longitudinal S (77%) but with low<br />

specificity (59%): AUC 0, 65 using a cutoff value of -16.85%. If we analyse the<br />

potential usefulness to identify severe CAV, S and SR were significantly lower in<br />

CAV segments: S -13.77±6% vs -16.42±3%, p


diastolic velocity (-12.3±4.9 vs -15.8±5.4 cm/s, p

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