Monday, 1 September 2008 - European Heart Journal

298 Perspectives in heart failure treatment
P1945 Intravenous mildronate improves flow-mediated
vasodilatory response in stable chronic heart failure:
double-blind placebo-controlled crossover study
L. Voronkov, I. Shkurat, O. Lutsak. Institute of Cardiology, Heart
Failure, Kiev, Ukraine
Background: Taking to account recently established independent role of endothelial
dysfunction (ED) in chronic heart failure (CHF) progression and mortality,
normalization of ED may be considered as an important therapeutic goal in
CHF. Mildronate (trimethylhydrazinium propionate dihydrate) is a new, now clinically
tested in stable angina, partial fatty acids oxidation inhibitor with concomitant
experimentally established potent endothelium-mediated vasorelaxation properties.
Objective: To evaluate the ability of mildronate to modulate flow-mediated vasodilatory
response (FMVR) in stable CHF.
Method: 30 pts with stable CHF (NYHA II-III, left ventricular EF ≤ 40%) at
chronic (≥ 2 months) ACE-inhibitor/β-blocker/diuretic therapy were examined. All
pts signed informed consent for the participation in trial. A. brachialis diameter
was detected ultrasonographically at Sonoline Omnia system before (D1) and
after (D2) standard forearm cuff test (200 mm Hg during 5 min). FMVR was calculated
by formula: (D2 – D1)/D1 x 100%. Forearm cuff test also was performed
in 30 healthy age-matched controls. Placebo protocol (PP) was represented by
initial FMVR test (A), 30 min recovery period (B), 100 ml saline (0,85% NaCl)
infusion during 30 min (C), repeated FMVR test 30 min after end of infusion (D).
Points A, B and D of active drug protocol (ADP) were similar to PP; C point was
represented by mildronate 1000 mg infusion in 100 ml of saline during 30 min.
The interval between PP and ADP was 48 hours, at that in one group (15 pts) PP
was performed first and in other group (15 pts) – the ADP first. Neither pts nor
FMVR performer knew about presence/absence of active drug in infused solution.
Groups FMVR, % p A vs B
Baseline (A) After infusion (B)
CHF placebo protocol (I) 9,6±0,7 10,4±0,8 NS
CHF active drug protocol (II) 8,3±0,8 14,4±0,9 < 0,001
Controls 11,1±0,8 –
pIvsII NS < 0,001
p I vs controls < 0,01 –
p II vs contols < 0,001 –
Conclusion: Intravenous mildronate dramatically improves impaired FMVR in
conventionally treated stable CHF patients.
P1946 Influence of regeneration of heart muscle by
intracoronary autologous bone marrow cell
transplantation on the BNP levels in patients with
chronic ischemic heart disease
R. Turan, M. Brehm, M. Koestering, S. Steiner, T. Zeus, T. Bartsch,
S. Yokus, C.M. Schannwell, B.E. Strauer. Heinrich Heine University Duesseldorf,
Cardiology, Pneumology And Angiology, Duesseldorf, Germany
Introduction: We recently demonstrated in patients with chronic myocardial infarction
by intracoronary transplantation of autologous bone marrow mononuclear
cells (BMCs) after 3 months follow-up that the infarct size was reduced by 30%,
whereas the global LV ejection fraction increased by 15% and regional infarct wall
movement velocity by 57%. (The IACT Study)
We analyzed the influence of regeneration of human infarcted heart muscle by
intracoronary cell therapy after 3 months follow up on the BNP levels in PB
Methods and Results: Peripheral blood levels of BNP were measured by BNPassay
in 40 patients with chronic ischemic heart disease pre intracoronary cell
therapy as well as 3 months after intracoronary cell therapy. We showed in patients
with chronic myocardial infarction by intracoronary transplantation of autologous
bone marrow cells (BMC) after 3 months follow up a significant reduced
of infarct size and increase of global LV-ejection fraction as well as infarct wall
movement velocity. Clinically we observed significant improvement in NYHA classification
3 months after intracoronary stem cell therapy as compared to before
(p=0.002). Furthermore we found a significant decrease of the BNP levels in peripheral
blood 3 months after intracoronary stem cell therapy as compared to
before (p=0.002)
Conclusion: Selective intracoronary transplantation of autologous bone marrow
mononuclear cells reduces infarct size and improves LV-Function. In Addition
this intracoronary cell transplantation improves clinical symptoms in patients with
chronic ischemic heart disease
P1947 Clinical effects and safety profile of initial
monotherapy with bisoprolol versus enalapril in
elderly patients with heart failure
D. Dobre 1 , D.J. Van Veldhuisen 1 , M.A. Goulder 2 ,H.Krum 3 ,
R. Willenheimer 4 . 1 University Medical Centre Groningen, Clinical
Pharmacology, Groningen, Netherlands; 2 Nottingham Clinical Research Limited,
Nottingham, United Kingdom; 3 Monash University/Alfred Hospital, Melbourne,
Australia; 4 Heart Health Group and Lund University, Cardiology, Malmo, Sweden
Purpose: To assess the clinical effects and safety profile of initial monotherapy
with either bisoprolol or enalapril in elderly patients with heart failure (HF).
Methods: In CIBIS III, 1010 patients with mild to moderate HF, age ≥ 65 years
and left ventricular ejection fraction ≤ 35% were randomized to monotherapy with
bisoprolol or enalapril for 6 months. We evaluated the effect on the combined endpoint
of all-cause mortality or hospitalization, each individual end-point, causes of
death, signs and symptoms of HF, and safety profile. The primary end point of allcause
mortality or hospitalization, and mortality and hospitalizations separately,
were analyzed by Cox proportional hazards model with treatment as the only
independent variable.
Results: Bisoprolol had a similar effect as enalapril regarding the combined endpoint
of all-cause mortality or hospitalization (hazard ratio [HR] 1.02; 95% confidence
interval [CI] 0.78 to 1.33, p=0.90). Slightly fewer patients died on bisoprolol
than on enalapril (23 vs. 32, p=0.24) which was related to the number of sudden
deaths (8 vs. 16; p=0.11). On the other hand, more cases of worsening HF requiring
hospitalization or occurring while in hospital were observed in the bisoprolol
group (HR 1.67; 95% CI 1.04 to 2.70, P=0.03). The two groups were similar with
regard to treatment cessations (7% vs. 10%, p=0.11) and early introduction of the
second drug (8% vs. 7%, p=0.81).
Conclusions: Bisoprolol and enalapril had a similar effect on the combined endpoint
of mortality or hospitalization during 6 months monotherapy. Although a
trend to fewer deaths was observed with bisoprolol, this was offset by more HF
hospitalizations.
P1948 Antithrombotic drugs in patients with chronic heart
failure
M. Lainscak1 , L. Hodoscek-Majc2 , S. Von Haehling3 , W. Doehner3 ,
S.D. Anker 3 . 1University Clinic of Respiratory Diseases, Division
of Cardiology, Golnik, Slovenia; 2General Hospital Murska Sobota,
Department of Internal Medicine, Murska Sobota, Slovenia; 3Charite Campus
Virchow-Klinikum, Division of Applied Cachexia Research, Berlin, Germany
Background: Limited data supports the use of antithrombotic drugs (antiplatelets
and anticoagulants) in patients with chronic heart failure (CHF). According to recent
CHF guidelines, only patients with concomitant atrial fibrillation (AF) could be
treated, whereas AF guidelines suggest risk stratification (e.g. CHADS2 score).
Our aim was to investigate the prevalence and predictors of antithrombotic drugs
prescription in patients with CHF and their prognostic impact.
Methods: In our population based survey, we screened all discharges and deaths
from our community hospital (population 125.000) from 2001 to 2003. We identified
638 patients (73±10 years, 48% men, 74% NYHA class III) who were discharged
alive and had diagnosis of CHF according to ICD 10. Medical charts and
ECG recordings were reviewed in detail, and vital status was obtained from a
Central Population Registry.
Results: AF was present in 330 (52%) patients with CHF, who were older (74±10
vs 72±11 years, p=0.021), had lower eGFR (50±18 vs 53±21 mL/min, p=0.044)
and total cholesterol (4.6±1.6 vs 5.0±1.5 mmol/L, p=0.002) and higher uric acid
(434±145 vs 406±132 mmol/L, p=0.020). At discharge, patients with AF were
prescribed with more optimal treatment: ACE inhibitors (83% vs 75%, p=0.019,
OR 1.60, 95% CI 1.08-2.35), beta-blockers (31% vs 20%, p=0.003, OR 1.71,
95% CI 1.21-2.50), and spironolactone (49% vs 37%, p=0.003, OR 1.63, 95%
CI 1.19-2.24). Overall, antithrombotic drugs and warfarin were prescribed in 430
(67%) and 197 (31%) patients, respectively. CHADS2 score was ≥2 in 85% of
patients with AF. Patients with AF were more likely to receive antithrombotics
(n=274 [83%], OR 4.77, 95% CI 3.31-6.86) and warfarin (n=168 [51%], OR 9.98,
95% CI 6.43-15.48). AF was not associated with higher disk of death (HR 1.13,
95% CI 0.93-1.37). Kaplan-Meier and univariate Cox proportional hazard analysis
showed that use of warfarin (log rank test p=0.0008, HR 0.62, 95%CI 0.47-0.81)
but not of antiplatelet drugs (log rank test, p=0.34, HR 1.16, 95%CI 0.85-1.59)
was associated with reduced mortality in patients with AF. In a Cox proportional
hazard model, adjusted for age, gender, eGFR, total cholesterol, uric acid, and
treatment with ACE inhibitors, beta blockers, and spironolactone, the finding for
warfarin was borderline: HR 0.74, 95% CI 0.53-1.05.
Conclusions: In large unselected cohort of patients with CHF from a community
hospital, AF was very prevalent but it was not predictive of mortality. According to
CHADS2 score, warfarin was underprescribed. Warfarin but not antiplatelet drugs
were associated with better outcome in patients with AF.
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