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THE EGYPTIAN SOCIETY OF CARDIOLOGY
BOARD OF DIRECTORS
2010
Dr. M. Khairy Abdel Dayem
Dr. Abdel Fattah Ferer
Dr. Mokhtar Gomaa
Dr. Wagdy Galal
Dr. Mahmoud Hassanein
PRESIDENT
Dr. Mohamed Sobhy
VICE PRESIDENT
Dr. Sherif El-Tobgy
SECRETARY GENERAL
Dr. Mohamed Awad Taher
TREASURER
Dr. Adel El-Atreby
Ass. Secretary
Dr. Hesham Aboul Einein
MEMBERS
Dr. Sherif Mokhtar
Dr. Ahmed Nassar
Dr. Aly Ramzy
Dr. Ashraf Reda
Dr. Osama Sanad
EDITOR OF THE EGYPTIAN HEART JOURNAL

Osama Abd El-Aziz
Khairy Abd El-Dayem
Alia Abd El-Fattah
Samir Abd El-Kader
Wafaei Abou El-Einein
Gamal Abou El-Nasr
Sayed Akl
Omar Awad
Mohamed Taher Awad
Wagdy Ayad
Amal Ayoub
Helmy Bakr
Tarek El-Badawy
Reda El-Eisawy
Mohamed El-Gawady
EGYPTIAN ADVISORY BOARD
Ayman Abou El-Magd
Ramzy Hamed El-Mawardy
Galal El-Said
Ezz El-Deen El-Sawy
Hamdy El-Sayed
Sherif El-Tobgy
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Wagdy Galal
Ramez Gendy
Mokhtar Gomaa
Magdy Gomaa
Ebtihag Hamdy
Mahmoud Hasanien
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Mohamed Mohsen Ibrahim
II
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Fathy Maklady
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The Egyptian Heart Journal will be pleased to consider for publication articles by members of the
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IV

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VI

General Cardiology:
Myocardial Depression in Sepsis Syndrome Prognostic Value of Toll-Like Receptor 4
Ahmed Mowafy, Gamal Hamed, Sanaa Abd El Shafee
Cardiac Affection after Subarachnoid Hemorrhage, Correlation with Severity and Etiology
Rania El Hoseiny, Ahmed Battah, Mohamed Ashraf
Endothelial Dysfunction and Insulin Resistance in Normoglycemic Offsprings of Patients with
Type 2 Diabetes Mellitus
Eman S Mohammad, Yasser Kamel, Hannan Taha, Essam Saad, Yasser Makram
Comparative Study between Tissue Doppler Imaging and Radionuclide Scintigraphy in
Evaluation of Right Ventricular Function in Patients with Chronic Obstructive Pulmonary
Disease
Sherine Elgangihi, Randa Aly, Sally Salah, Amr Elhadidy
Metabolic Syndrome and its Impact on Vascular Damage Extent
Ayman Sadek, Magdy Nouh Ain, Hany Fouad Hanaa, Ramzy Hamed El-Mawardy
Cardiovascular Risk Factors in Patients with End Stage Renal Failure on Regular Hemodialysis
Yaser AA El-Hendy, Mohamed Abdou
Hypertension:
White Coat Hypertension and Target Organ Damage
Hamza Kabil, Metwally El-Emary, Ahmed Abdel-Moneim, Abdel-Rahman Samra
Microalbuminuria and Subclinical Cardiac Structural Changes Relation to Isolated Systolic
Hypertension in Elderly Patients
Hamza Kabil, El-Metwally El-Shahawy, Amr Afifi, Hsassan Galal, Ashraf Talaat
Urinary Albumin Excretion is Associated with Arterial Stiffness in Hypertensive Adults
Mohammed A Abdel Wahab, Mohamed M Saad, Amr S Amin, Khalid A Baraka, Nasser M Taha
Early Vascular Changes Preceding Morphological Cardiac Changes in Hypertensive Patients
Mohammed A Abdel Wahab
Metabolic Syndrome as A Predictor of Non Dipping Hypertension
Islam Mohamed Mahdy El-Helaly, Mohamed Ayman Saleh, Ayman Sadek, Ahmed Onsy
Echocardiography:
THE EGYPTIAN HEART JOURNAL
(EHJ)
Volume 62 • Number 1 •
March 2010
TABLE OF CONTENTS
Quantitative Power Doppler Technique of Myocardial Contrast Echocardiography: For the
Detection of Segmental Myocardial Perfusion Profile
Youssef FM Nosir, Ashraf A Ali, Ali A Abd-Elmagid, Mamdouh Altahan, Mansour Mostafa,
Abdelmaksoud S Ahmed, Ayman Kholief, Hassan Chamsi Pasha, Ezz El-Ssawy
The Carotid-Femoral Arterial Index and the Severity of Coronary Atherosclerosis
Mahmoud Soliman, Hesham Hasan, Tamer Gazy, Walaa Fareed, Ashraf Reda, Said Shalaby
Page
1
7
19
25
39
53
63
69
77
83
89
103
111

Value of Contrast Echocardiography for the Diagnosis of Hepatopulmonary Syndrome in
Patients with Chronic Liver Disease Due to Hepatitis C Virus
Amal S Bakir, Ghada El-Shahed
Cardiac Output Measurement by a New Transesophageal Doppler Probe in Circulatory Shock
Nashwa Abed, Mohamed Afify
Interventional:
Comparison between Double Intravenous Bolus, Intracoronary Bolus, and Conventional
Intravenous Bolus Dose of Tirofiban in Patients with Acute Anterior Myocardial Infarction
Treated by Primary Coronary Intervention
Ahmed Ibrahim Nassar, Nagwa Nagi El-Mahallawy, Bassem Wadei Habib, Adel Gamal Hassanin,
Iman Esmat, Haytham Galal
Safety and Feasibility of Transradial Versus Transfemoral Approach for Diagnostic Coronary
Angiography During Early Phase of the Learning Curve
Mahmoud M Sabbah, Mohamed A Oraby, Gamela M Nasr, Ahmed A El Hawary
Correlation between Clinical Presentation, ECG and Echocardio-Graphic Findings and Those
of Angiography in Patients Undergoing Coronary Angiography
Fathi A Maklady, Hanan M Kamal, Azza Z El-Eraky, Omar M Saleh
Measurement of Fractional Flow Reserve (FFR) for Guiding Percutaneous Coronary Intervention
in Clinical Practice
Hussein Shaalan
Coronary Heart Disease:
Angiographic Coronary Artery Disease in Women with Chest Pain and History of Anxiety
Disorders
Khaled E Darahim, Mona I Awaad
Depression Post Acute Coronary Syndromes: Incidence and Predictors
Mona I Awaad, Khaled E Darahim
Coronary Ectasia: Risk Markers and Risk Factors
Mahmoud A Soliman, Hosam M El Ezzawy
Valvular Heart Disease:
Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index as a New Technique for
Assessment of Mitral Stenosis Severity: Comparison with Planimetry and PHT Methods
Hany Younan
Laboratory:
(B)
Thrombin-Activatable Fibrinolysis Inhibitor Thr325Ile Polymorphism as a Risk Factor of
Myocardial Infarction in Egyptians
Hanan M Kamal, Amal S Ahmed, Manal S Fawzy, Faten A Mohamed, Amani A Elbaz
Page
117
125
135
141
147
155
165
173
181
187
197

Egypt Heart J 62 (1): 1-5, March 2010
Myocardial Depression in Sepsis Syndrome Prognostic Value of
Toll-Like Receptor 4
AHMED MOWAFY, MD; GAMAL HAMED, MD; SANAA ABD EL SHAFEE, MD
Background: Myocardial dysfunction frequently accompanies severe sepsis and septic shock. Whereas myocardial depression
was previously considered a preterminal event, it is now clear that cardiac dysfunction as evidenced by biventricular dilatation
and reduced ejection fraction is present in most patients with severe sepsis and septic shock. Myocardial depression exists
despite a fluid resuscitation-dependent hyperdynamic state that typically persists in septic shock patients until death or recovery.
Cardiac function usually recovers within 7–10 days in survivors. Myocardial dysfunction appears to be due to circulating
depressant factors (e.g. tumor necrosis factor alpha and IL-1ß). It was hypothesized that the Toll-like receptor 4 (TLR4) mediates
myocardial dysfunction in sepsis through activation of cytokine production by monocytes/macrophages and through an increase
in NO and TNF production by the myocytes themselves.
Objective: To study the relationship between the Toll-like receptor 4 concentrations and myocardial dysfunction, clinical
course and outcome of septic patients.
Methods: A total of 20 septic patients were enrolled into the study. Excluded from our study were the patients known to
have cardiac problems and those on immunosuppressive therapy. All included patients were subjected to the measurements of
TLR4. Blood samples were withdrawn at day 1 of ICU admission. Our end points were length of ICU stay, Need for organ
supportive measures (Inotropic/Vasopressor support and/or Mechanical ventilation) and final outcome for all patients until ICU
discharge or demise or up to a total of 28 days.
Results: Toll-like receptor-4 concentrations were elevated in patients who were admitted to the ICU with septic criteria.
TLR-4 concentrations were higher in patients who needed Inotropic/Vasopressor support during their ICU stay than those who
did not require it (p value = 0.015). TLR-4 concentrations were higher in patients who developed impaired ventricular function
during their ICU stay than those with preserved systolic cardiac function (p value = 0.006) and were significantly higher in
patients who died in the ICU than those who survived (p value = 0.024).
Conclusion: Estimation of Toll-like receptor-4 level may be a potentially useful prognostic test for the evaluation of septic
patients when admitted to the ICU and for the prediction of their adverse outcomes (e.g. impaired ventricular function,
haemodynamic compromise with need for inotropic/vasopressor support and mortality).
Key Words: Toll-like receptor-4 – Myocardial depression – Septic shock.
Introduction
Despite continuing advances in intensive care
medicine, Sepsis represents a significant health
problem. Severe sepsis and septic shock present
high incidence of morbidity and mortality and are
The Department of Critical Care, Cairo University.
Manuscript received 11 Nov., 2009; revised 15 Dec., 2009;
accepted 16 Dec., 2009.
Address for Correspondence: Dr. Ahmed Mowafy, Critical
Care Med. Department, Cairo University.
1
considered among the most important causes of
death in the intensive care units [1]. The overall
mortality is approximately 30%, rising to 50% or
more in patient with septic shock, despite recent
progress in understanding its pathophysiology and
improvements in supportive intensive care [2].
Multiple organ systems are compromised during
sepsis with several underlying mechanisms have
been proposed. Myocardial dysfunction, a central
component in the complex pathophysiology of
sepsis, contributes to the high mortality associated
with this disorder. Cardiac dysfunction starts during

Myocardial Depression in Sepsis Syndrome Prognostic Value
the first 24 hours of the development of sepsis,
and it is reversible in survivors within 7 to 10 days
[3].
Sepsis develops when the initial immune response
to an infection becomes amplified and then
dysregulated [4]. The pathogenesis of sepsis involves
a complex interaction between host and
infecting microorganism, including bacterial recognition,
cell activation, transmigration, phagocytosis
and killing of the pathogens. Bacterial recognition
and cellular activation are mainly driven by
the interaction of the pathogens associated molecular
pattern (PAMPs) and pattern recognition receptors
(PRRs), among them the Toll-like receptor
[5].
Toll-like receptors (TLRs) are a class of single
membrane-spanning non-catalytic receptors that
recognize structurally conserved molecules derived
from microbes once they have breached physical
barriers such as the skin or intestinal tract mucosa,
and activate immune cell responses. They play a
key role in the innate immune system. This discovery
fills an essential gap in our understanding of
the molecular events that follow microbial infection
and the initial host defense to invasive pathogens.
The TLRs are the critical pattern recognition molecules
that alert the host to the presence of a
microbial pathogen [6]. They receive their name
from their similarity to the protein coded by the
Toll gene identified in Drosophila in 1985 by
Christiane Nüsslein-Volhard [6].
The presence of cardiovascular dysfunction in
sepsis is associated with significantly increased
mortality rate of 70% to 90% compared with 20%
in septic patients without cardiovascular impairment
[7]. Numerous studies support the hypothesis that
endogenous mediators like tumour necrosis factor
(TNF)-α, interleukin (IL)-1ß, as well as nitric
oxide (NO) mediate myocardial dysfunction during
septic shock [8]. Furthermore, cardiac myocytes
themselves synthesize significant amounts of TNF
after LPS administration. Thus, cardiac synthesis
of proinflammatory mediators seems to play a
major role in the pathogenesis of LPS-induced
myocardial dysfunction. However, little is known
about the cell types and the relevant signalling
pathways that are involved in mediating myocardial
dysfunction during gram-negative sepsis [9].
In our study we tried to correlate the level of
TLR4 with the prognosis of septic patients.
2
Patients and Methods
Out of 85 patients, with septic criteria, admitted
to critical care department of Cairo University,
twenty patients were eligible to this study. Inclusion
criteria were age ≥17 yrs, with clinical signs of
sepsis syndrome. Sepsis was assessed according
to American Colleague Of Chest Physicians/Society
of Critical Care Medicine (ACCP/SCCM) criteria
to have the following; clinically suspected infection
with two or more of the following: temp > than
38oC or less than 36oC, HR> 95/min, RR >20/min
or PaCo2 12.000/mm 3 or

Ahmed Mowafy, et al
Patients were divided according to the etiology of
sepsis into three groups medical, surgical or post
traumatic patients, and according to the severity
of sepsis into patients with severe sepsis or septic
shock.
Table 1: Demographic data of all patients.
Parameter Range
Age (years)
Sex
Admitting diagnosis
Medical cases
Surgical cases
Trauma
Severity of sepsis
Severe sepsis
Septic shock
22-74
Male (%) Female (%)
13 (65%) 7 (35%)
No. of patients (%)
8 (40%)
7 (35%)
5 (25%)
10 (50%)
10 (50%)
Mean age
± SD
45±17.21
M:F ratio
1.85
The level of TLR-4 and its correlation to the
clinical status of the patients were thoroughly
studied. TLR-4 value did not differ significantly
between patients with severe sepsis and others
with septic shock (8.04 mg/100 mg blood vs. 11.56
ug/100 uL blood respectively; p value: 0.906) Table
(2).
Table 2: TLR-4 in patients with severe sepsis versus septic
shock.
Group No.
Severe sepsis
Septic shock
10
10
Mean TLR-4
±SD
8.04±5.95
11.56±5.75
p value
0.906
TLR4 level showed great variation in patient
with heamodynamic compromise. Patients who
needed vasopressor support showed higher levels
of TLR4 than other stable patients (Table 3).
Patients who needed mechanical ventilation showed
higher levels of TLR4 than other patients (Table
3).
Table 3: TLR-4 value in relation to vasopressor support and
need for MV.
Mechanical
ventilation (MV):
No
Yes
Inotropic/vasopressor
support:
Yes
No
No.
2
18
No.
16
4
Mean TLR-4±SD
7.28±6.47
13.45±3.04
Mean TLR-4±SD
10.39±6.1
2.43±1.56
p value
0.136
p value
0.015
3
There was remarkable difference in the level
TLR4 in patients with myocardial dysfunction.
Echocardiography was done on day 1 of the study
& followed up weekly. Patients who showed early
signs of myocardial dysfunction & reduction in
ejection fraction had higher level of TLR4 than
other stable patients (Table 4).
Table 4: TLR-4 value and Echocardiographic findings.
Reduction in EF% No. Mean TLR-4±SD p value
Yes
No
9
11
12.8±4.9
5.4±5.5
0.006
The overall mortality of all patients was very
high. Fourteen out of twenty patients with severe
sepsis and septic shock died during hospital stay.
However, the mean TLR4 level was significantly
lower in patients who survived Table (5).
Table 5: TLR4 level and relation to mortality.
TLR4 level
no of pls
Survivors Non survivors p value
6 (30%)
2.5
Discussion
14 (70%)
10.6
0.02
Sepsis and septic shock have been recognized
as an increasingly serious clinical problem, accounting
for substantial morbidity and mortality.
The past four decades have seen the age-adjusted
mortality of sepsis increase from 0.5 to 7 per
100,000 episodes despite major advances in the
understanding of its pathophysiology [10]. The
incidence of severe sepsis in the United States
today is estimated at 750,000 cases per year, resulting
in 215,000 deaths annually [11]. The majority
of these sepsis patients die of refractory hypotension
and cardiovascular collapse.
Myocardial dysfunction frequently accompanies
severe sepsis and septic shock. Whereas myocardial
depression was previously considered a preterminal
event, it is now clear that cardiac dysfunction as
evidenced by biventricular dilatation and reduced
ejection fraction is present in most patients with
severe sepsis and septic shock. Cardiac function
usually recovers within 7-10 days in survivors.
Myocardial dysfunction does not appear to be due
to myocardial hypoperfusion but due to circulating
depressant factors, including the cytokines tumor
necrosis factor alpha and IL-1ß. At a cellular level,

Myocardial Depression in Sepsis Syndrome Prognostic Value
reduced myocardial contractility seems to be induced
by both nitric oxide-dependent and nitric
oxide-independent mechanisms.
Kumar et al. [12] were the first to report that
the myocardial depressant activity of human serum
from patients with septic shock could be eliminated
by the immunoprecipitation of TNF-α and IL-1ß.
Giroir et al. [13] reported that myocardial TNF-α
mRNA expression increased after lipopolysaccharide
(LPS) administration. Kapadia et al. [14] subsequently
demonstrated that cardiac myocytes
themselves produce significant amounts of TNFα
after endotoxemia. These findings suggested that
the compartmentalized production of TNF-α and
other cytokines might play an important role in
the pathogenesis of LPS-induced myocardial depression
in vivo. Supporting this hypothesis is the
finding that the administration of TNF binding
proteins preserves myocardial function in endotoxemic
rats [15]. To date, however, the signaling
pathways that lead to the expression of these proinflammatory
mediators in the heart during gramnegative
sepsis remain undefined.
A recent advance in unraveling the early events
in LPS signaling has been the identification of
Toll-like receptors (TLRs). Toll is a transmembrane
receptor in Drosophila species that is involved in
dorsal-ventral patterning in the embryo and in the
induction of an antifungal response in the adult
fly [16].
It was hypothesized that the Toll-like receptor
4 (TLR-4) mediates myocardial dysfunction in
sepsis through activation of cytokine production
by monocytes/macrophages and through an increase
in NO and TNF production by the myocytes themselves
[17].
In our study we tried to correlate the relationship
between level of TLR4 in serum of septic patients
with their prognosis. The level of TLR4 was thoroughly
studied in relation to the hospital course
of the patients, their need for vasopressor support,
mechanical ventilation, myocardial dysfunction
and their final outcome.
There was clear evidence that patients with
septic shock had higher levels of TLR4 than patients
with severe sepsis. TLR-4 concentrations were
significantly higher in patients who needed inotropic/vasopressor
support during their ICU stay.
The TLR-4 levels were also significantly higher
in patients with impaired left ventricular function.
4
Finally, the TLR-4 concentrations were also significantly
higher in patients who died in the ICU
than those who survived.
The results reported here provide compelling
evidence for the presence of a direct relationship
between TLR4 level with morbidity and mortality
of septic patients. The level of TLR-4 was higher
in heamodynamically unstable patients who needed
vasopressor support or mechanical ventilation.
Higher level of TLR-4 was usually related with
adverse events.
Although the above discussion focused attention
on the potential deleterious effects of TLR-4 in
the heart, there may be questionable beneficial
effect. Although the potential salutary effects of
the TLR-4 pathway in the heart remain largely
unknown, it has been suggested recently that TLR-
4, and perhaps other TLRs, may contribute to the
activation of an innate immune response in injured
cardiac tissue [18,19]. Given the observation that
TLR-4 is tightly coupled to TNF-kB activation
and proinflammatory cytokine expression in the
heart, and that both TNF-kB and proinflammatory
cytokines (physiologic levels) are cytoprotective
in the heart [18,20,21], it will be important in future
studies not only to delineate the full spectrum of
TLRs and ligands in the heart, but also to elucidate
the adaptive and maladaptive signaling pathways
that are downstream from TLR-mediated signaling
in the adult heart.
Concluding remarks:
Patients with severe sepsis and septic shock
represent real challenge in the ICU setting. Despite
major advances in the diagnostic tools and therapeutic
options, these entity of patient still represent
a high mortality percentage. The human immune
system is well endowed with potent detection and
alarm systems to respond to the ever present threat
of microbial pathogens. The recent discovery of
the TLR family now permits a detailed evaluation
of the molecular pathogenesis of sepsis. The availability
of human and microbial functional genomics
should allow us to more fully understand the complex
interactions that exist between host and pathogen
in septic patients in the future. The above
findings indicate that the Toll-Like Receptor-4
may be a potentially useful prognostic test for the
evaluation of septic patients when admitted to the
ICU and for the prediction of their adverse outcomes
(e.g. impaired ventricular function, haemodynamic
compromise with need for inotropic/
vasopressor support and mortality). Higher level

Ahmed Mowafy, et al
of TLR4 is usually related to poor prognosis of
septic patients.
References
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3- Parker MM, Shelhamer JH. Bacharach SL, et al: Profound
but reversible myocardial depression in patients with
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4- Alberti C, Brun-Buisson C, Burchardi H, Martin C,
Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno
R, Boulmé R, Lepage E, et al: Epidemiology of sepsis
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121.
5- Medzhitov R, Janeway C Jr: Innate immunity. N Engl J
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6- Hansson GK, Edfeldt K: "Toll to be paid at the gateway
to the vessel wall". Arterioscler. Thromb. Vasc. Biol.
2005; 25 (6): 1085–7. doi:10.1161/01.ATV.0000168894.
43759.47. PMID 15923538.
7- Parrillo JE, Suffrendini AF, Danner RL, Cunnion: Septic
shock in human advances in understanding of pathogenesis,
cardiovascular dysfunction and therapy 1990.
8- Knaus WA, Draper EA, Wagner DP, et al: "APACHE II:
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9- Horton JW, Maass D, White J, Sanders: Nitric oxide
modulation of TNF-alpha induced cardiac contractility
dysfunction in concentration dependent Am J Physical
Heart Cir 2000.
10- Center for Diseases Control and Prevention: National
Center or Health Statistics: mortality patterns – United
States, 1990. Monthly Vital Stat Rep 1993, 41: 5.
11- Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G,
Carcillo J, Pinsky MR: Epidemiology of severe sepsis in
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the United States: analysis of incidence, outcome and
associated costs of care. Crit Care Med 2001; 29: 1303-
1310.
12- Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo JE.
Tumor necrosis factor α and interleukin 1ß are responsible
for in vitro myocardial cell depression induced by human
septic shock serum. J Exp Med 1996; 183: 949-58.
13- Giroir BP, Johnson JH, Brown T, Allen GL, Beutler B:
The tissue distribution of tumor necrosis factor biosynthesis
during endotoxemia. J Clin Invest 1992; 90: 693-
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14- Kapadia S, Lee J, Torre-Amione G, Birdsall HH, Ma TS,
Mann DL: Tumor necrosis factor-α gene and protein
expression in adult feline myocardium after endotoxin
administration. J Clin Invest 1995; 96: 1042-52.
15- Meng X, Ao L, Meldrum DR, et al: TNF-α and myocardial
depression in endotoxemic rats: temporal discordance of
an obligatory relationship. Am J Physiol 1998; 275: R502-
8.
16- Kopp EB, Medzhitov R. The toll-receptor family and
control of innate immunity. Curr Opin Immunol 1999;
11: 13-8.
17- Francis SE, Holden H, Holt CM, Duff GW: Interleukin-
1 in myocardium and coronary arteries of patients with
dilated cardiomyopathy. J Moll Cell Cardiol 1998; 30,
215-243.
18- Medzhitov RC, Janeway CA: Innate immunity: the virtues
of a nonclonal system of recognition. Cell 1997; 91: 295-
8.
19- Frantz S, Kobzik L, Kim YD, et al: Toll4 (TLR4) expression
in cardiac myocytes in normal and failing myocardium.
J Clin Invest 1999; 104: 271-80.
20- Xuan YT, Tang XL, Banerjee S, et al: Nuclear factor
kappaÅ]B plays an essential role in the late phase of
ischemic preconditioning in conscious rabbits. Circ Res
1999; 84: 1095-109.
21- Kurrelmeyer K, Michael L, Baumgarten G, et al: Endogenous
myocardial tumor necrosis factor protects the adult
cardiac myocyte against ischemicÅ]induced apoptosis in
a murine model of acute myocardial infarction. Proc Natl
Acad Sci USA 2000; 97: 5456-61.

Egypt Heart J 62 (1): 7-17, March 2010
Cardiac Affection after Subarachnoid Hemorrhage, Correlation with
Severity and Etiology
RANIA EL HOSEINY, MD; AHMED BATTAH, MD; MOHAMED ASHRAF, MD
Introduction: Cardiac injury and dysfunction after subarachnoid hemorrhage (SAH) is a well-recognized phenomenon,
ECG changes, arrhythmias, serum elevations of cardiac enzymes and left ventricular (LV) systolic dysfunction have been
described in SAH patients. In recent years, considerable investigative interest has been directed at evaluation of frequency of
this cardiac injury, clinical implications, predictors and outcome, Despite the large body of evidence testifying the development
of myocardial injury in SAH, the true incidence in this population remains unknown.
Methodology: Thirty patients with acute subarachnoid hemorrhage were included in the study, of whome twenty patients
had aneurysmal SAH (12 women, 8 men, with mean age 47.55±12.356 years) and ten patients had traumatic SAH (4 women,
6 men, with mean age 42.10±14.75 years), patients with evidence of epidural, subdural or intracerebral hemorrhage, history
of cardiac disease, renal impairement and systemic sepsis were excluded from the study, All patients were subjected to detailed
medical history taken from the patient or a family member, daily clinical assessment of neurological status (graded according
to Hess and Hunt score) and cardiac status, daily ECG, biochemical measurement of cardiac troponin I every other day for 7
days using IMMULITE test (reference range for upper limit of normal 1ng/ml) and transthoracic echocardiographic examination
on admission (day 1) of the patient and follow-up after one week (day 7) for assessment of both global and regional systolic
functions of the left ventricle, it was reported as abnormal if there was evidence of regional wall motion abnormality RWMA
or EF

Cardiac Affection after Subarachnoid Hemorrhage
Conclusions: Different types and frequencies of ECG changes were found in patients with SAH, most frequently were
repolarization abnormalities, independent of previous history of ischemic heart disease.
Elevated cardiac troponin I and Left ventricular systolic dysfunction both global and regional were frequently observed
after SAH, aneurysmal exhibit more severe affection than traumatic.
ECG abnormalities, elevated cardiac troponin I and left ventricular dysfunction were associated with more severe neurological
injury.
Key Words: ECG – Echocardiography – Cardiac troponin I – Subarachnoid hemorrhage.
Introduction
Subarachnoid hemorrhage (SAH) is a major
clinical problem worldwide, it has a wide variety
of neurological and extraneurological complications,
of which the most frequent were cardiovascular
complications [1,2].
The association between central nervous system
disease and cardiac affection is well known and
has been described in intracerebral hemorrhage,
intracranial tumors, meningitis, and stroke [3].
However, this association is particularly strong in
SAH, after which electrocardiogram (ECG) changes
[4] arrhythmias, left ventricular (LV) dysfunction,
and elevation of the creatine phosphokinase (CPK)-
MB fraction and cardiac troponin I (cTnI) have
been reported, of which, the most common is the
ECG changes.
The pathophysiology of cardiac affection after
SAH in humans remains unknown and controversial,
although data from animal models indicates
that catecholamine-mediated injury is the most
likely cause of cardiac injury after SAH.
Cardiac affection after SAH negatively influences
mortality and, more specifically, the sequelae
of heart failure affect outcome after SAH, as hypotension
is the main cause of secondary brain
injury, therefore, early identification and monitoring
of cardiac dysfunction is a critical issue [5].
Aim of the work:
• To evaluate cardiac affection in patients with
subarachnoid hemorrhage.
• To correlate cardiac affection with the neurological
status in these patients.
Methods
The present study was carried out on 30 patients
diagnosed to have acute subarachnoid hemorrhage
8
(confirmed by CT brain) and admitted within 24
hours to Kasr El-Aini Hospital, Cairo University
in the period between December 2008 to June
2009, with the calendar day of SAH onset was
referred to as day 1.
Our patients were divided into two groups:
• Group 1: Patients diagnosed to have aneurysmal
SAH [20 patients] (with aneurysm identified with
cerebral angiography).
• Group 2: Patients diagnosed to have traumatic
SAH [10 patients].
Exclusion criteria:
1- Patients with evidence of epidural, subdural or
intracerebral hemorrhage.
2- History of cardiac disease:
• Coronary artery disease.
• Impairement of left ventricular systolic function.
3- Renal impairement defined as serum creatinine
level more than 1.5mg/dl that causes a non
specific elevation of the troponin.
4- Systemic sepsis that also causes a non specific
elevation of the troponin.
All patients were subjected to:
Detailed medical history taken from the patient
or a family member including: Age, sex, history
of smoking, history of diabetes mellitus, history
of hypertension, history of neurological troubles
and history of cardiac diseases.
Daily clinical assessment of:
a- Neurological status (graded according to Hess
and Hunt score) [6].
b- Cardiac status for evidence of cardiac dysfunction
and/or arrhythmias.

Rania El Hoseiny, et al
Daily ECG:
Twelve lead ECG with consistent chest leads
positioning performed daily for 7 days.
ECG was considered abnormal if the following
detected:
• ST-T wave changes:
º ST segment elevated or depressed greater than
0.1mV in limb leads or 0.2mV in precordial
leads.
º T wave inversion, flattening or peaking, T wave
was considered peaked if its amplitude exceeded
0.5mV in any limb lead or 1.5mV in any
precordial lead [11].
• QTc interval prolongation (>460msec) measured
with modified Bazett’s formula [QTc=QT+
0.00175 (ventricular rate-60)] [12,13].
• Arrhythmias.
Biochemical measurement:
Cardiac troponin I was measured every other
day for 7 days using IMMULITE test, an immune
assay method quantitatively measure cardiac troponin
I in ng/ml (reference range for upper limit of
normal 1ng/ml).
Transthoracic echocardiographic examination:
All patients were subjected to transthoracic
echocardiographic examination done upon admission
(day 1) of the patient and follow-up done after
one week (day 7).
The study was conducted using an ATL HDI
5000 colored echocardiographic machine using a
transducer 3.5MHz.
Both global and regional systolic functions of
the left ventricle were assessed. Echocardiogram
was reported as abnormal if there was evidence of
regional wall motion abnormality RWMA or EF

Cardiac Affection after Subarachnoid Hemorrhage
Correlation between hypertension and cardiac
function: There was no statistically significant
difference between both groups (hypertensive and
non hypertensive) as regard:
1- The frequency of abnormal ECG changes both
on day 1 (p value=0.471) and on day 7 (p value=
0.32).
2- The frequency of elevated cardiac troponin I
both on day 1 (p value=0.6) and day 7 (p value=
0.556).
3- The frequency of LV systolic dysfunction both
on day 1 (p value=0.448) and day 7 (p value=
0.464).
Frequency and distribution of cardiac abnormalities
in the aneurysmal SAH group:
Out of twenty patients included in this group,
fifteen patients (75%) had cardiac abnormalities,
their distribution was as follow:
a- Patients with ECG changes:
All the fifteen patients had ECG changes, distributed
as follow:
1- ST-T wave changes were detected in thirteen
patients since day 1, by day 7, these ST-T wave
changes were completely reversed in four patients
and showed partial reversibility in six
patients.
2- Long QTc was detected in three patients, that
normalized in two of them by day 7.
3- Arrhythmias were detected in six patients, of
whom, four had sinus tachycardia, one patient
had sinus bradycardia and three patients had
atrial premature beats (two of them had sinus
tachycardia), by day 5, three patients out of the
four patients with sinus tachycardia exhibited
slowing which of this tachycardia was persistent
in the fourth patient till day 7, all the patients
with atrial extrasystoles, showed complete recovery
by day 7 and the patient with sinus
bradycardia showed persistence of this rhythm
till day 7.
b- Patients with elevated cTnI:
Six patients were detected to have elevated
cardiac troponin (cTnI), of whom, three patients
had cTnI normalized on day 7.
c- Patients with echocardiographic abnormalities:
There were two patients who had a low ejection
fraction (EF=42% & 44%) on day 1, that improved
on day 7 (EF =63% & 54% respectively).
10
Three patients were detected to have regional
wall motion abnormalities on day 1, then these
changes completely disappeared in two patients
and partially disappeared in one patient on day 7.
Table 1: Distribution of cardiac abnormalities in the aneurysmal
SAH group.
ECG changes
ST-T wave changes
Long QTc interval
Arrhythmias:
Sinus tachycardia
Sinus bradycardia
Atrial extrasystoles
Positive cardiac
troponin I
Low EF
RWMAs
Number
of affected
patients
13
3
6
4
1
3
6
2
3
Complete
reversibility
on day 7
4
2
3
–
3
3
2
2
Partial
reversibility
on day 7
Frequency and distribution of cardiac abnormalities
in the traumatic SAH group:
a- Patients with ECG changes:
Out of ten patients included in this group, only
three had cardiac abnormalities represented by ST-
T wave changes associated with sinus tachycardia,
by day 7, two patients showed partial reversibility
of these changes and it was persistent in the third
patient.
There was no evidence of elevated cTnI nor
echocardiographic abnormalities in any of the
Patients included in this group.
Table 2: Distribution of cardiac abnormalities in the traumatic
SAH group.
ECG changes
ST-T wave changes
associated with sinus
tachycardia
Positive cardiac
troponin I
Low EF & RWMAs
Number
of affected
patients
3
0
0
Complete
reversibility
on day 7
–
–
–
6
–
–
–
–
–
–
1
Partial
reversibility
on day 7
2
–
–

Rania El Hoseiny, et al
Correlation between neurological status and
cardiac function in aneurysmal SAH group:
a- Correlation between neurological status and
ECG analysis:
In the present study, we evaluated the neurological
status of the studied patients by Hess &
Hunt scoring system and divided them into:
Twelve patients exhibited mild affection (Hess
& Hunt score 1&2) while severe affection (Hess
& Hunt score 3-5) was exhibited by 8 patients.
There was a statistically significant higher
frequency of abnormal ECG on day 1 in those
patients with severe aneurysmal SAH (H&H score
3-5) when compared to those with mild aneurysmal
SAH (H&H score 1&2) (100% vs 58.3%) (p value=0.035),
Fig. (1). On day 7 there was no statistically
significant difference between both groups
(75% versus 41.7%, p value=0.142).
100
90
80
70
60
50
40
30
20
10
0
p value: 0.035
58.3
100
Mild aneurysmal SAH Severe aneurysmal SAH
Figure 1: Abnormal ECG in day 1.
b- Correlation between neurological status and
cardiac troponin I measurement:
Out of twelve patients included in the mild
aneurysmal SAH group, none showed positive
cardiac troponin I on day 1 (0%), while six (out
of eight patients) included in the severe aneurysmal
SAH group (75%) had positive cardiac troponin I
(p value=0.001) Fig. (2).
80
70
60
50
40
30
20
10
0
p value: 0.001
0
Mild aneurysmal SAH Severe aneurysmal SAH
Figure 2: Frequency of positive troponin in day 1.
75
11
Similarly, we found a statistically significant
higher frequency of positive cardiac troponin I in
day 7 in those patients with severe aneurysmal
SAH (37.5%) when compared to cases with mild
aneurysmal SAH (0%) (p value=0.021) Fig. (3).
40
35
30
25
20
15
10
5
0
p value: 0.021
0
Mild aneurysmal
SAH
37.5
Severe aneurysmal
SAH
Figure 3: Frequency of positive troponin in day 7.
c- Correlation between neurological status and
echocardigraphic findings:
In the present work there was a statistically
significant higher incidence of systolic dysfunction
(global & regional) in the cases with severe aneurysmal
SAH (37.5%) when compared to cases with
mild aneurysmal SAH (0%) (p value=0.021) in
day 1, with no statistically significant difference
between both subgroups in day 7 (p value=0.4)
Fig. (4).
40
35
30
25
20
15
10
5
p value: 0.021
0
37.5
0
Mild aneurysmal Severe aneurysmal
SAH
SAH
Figure 4: Frequency of systolic dysfunction in day 1.

Cardiac Affection after Subarachnoid Hemorrhage
Table 3: Correlation between neurological status and cardiac
function in aneurysmal SAH group on day 1.
Frequency of ECG changes
Frequency of positive
cardiac troponin I
Frequency of echocardiographic
findings
Mild
affection
subgroup
58.3%
0%
0%
Severe
affection
subgroup
100%
75%
37.5%
p
value
0.035
0.001
0.021
Table 4: Correlation between neurological status and cardiac
function in aneurysmal SAH group on day 7.
Frequency of ECG changes
Frequency of positive
cardiac troponin I
Frequency of echocardiographic
findings
Mild
affection
subgroup
41.7%
0%
0%
Severe
affection
subgroup
75%
37.5%
12.5%
p
value
0.14
0.021
0.4
Comparison between aneurysmal and traumatic
SAH groups as regards:
a- Neurological status (assessed by Hess & Hunt
score):
We found a statistically significant higher frequency
of poor neurological status in the traumatic
SAH group when compared to the aneurysmal
SAH group On day 1 and day 7 (p value 0.002 &
0.001 respectively).
b- Electrocardiographic abnormalities:
In the current study, there was a statistically
significant higher incidence of ECG abnormalities
in the aneurysmal SAH group (75%) when compared
to the traumatic SAH group (30%) on day
1 (p value=0.045), yet, we did not find any statistically
significant difference between both groups
as regard the incidence of ECG abnormalities on
day 7 (p value=0.24).
c- Cardiac troponin I (cTnI):
On day 1, there was a statistically significant
higher frequency of positive cardiac troponin I in
the aneurysmal SAH group (30%) compared to
traumatic SAH group (0%) (p value=0.05), yet, on
day 7 there was no statistically significant difference
between both groups [aneurysmal (15%) versus
traumatic (0%)] (p value=0.246).
12
d- Global and regional left ventricular systolic
function:
There was no statistically significant difference
between both groups as regard the frequency of
LV systolic dysfunction both on day 1 and day 7,
(p value=0.281 & 0.714 respectively).
Table 5: Comparison between aneurysmal and traumatic SAH
groups on day 1.
Variable
Frequency of poor
neurological status
Frequency of ECG changes
Frequency of positive cTnI
Frequency of LV systolic
dysfunction
Aneurysmal
SAH
40%
75%
30%
15%
Traumatic
SAH
100%
30%
0%
0%
p
value
0.004
0.045
0.05
0.28
Table 6: Comparison between aneurysmal and traumatic SAH
groups on day 7.
Variable
Frequency of poor
neurological status
Frequency of ECG changes
Frequency of positive CTAI
Frequency of LV systolic
dysfunction
Aneurysmal
SAH
80%
55%
15%
5%
Discussion
Traumatic
SAH
100%
37.5%
0%
0%
p
value
0.001
0.24
0.24
0.71
Primary findings of the study compared with
published literature revealed:
1- Regarding the frequency of abnormal ECG
findings in patients with aneurysmal subarachnoid
hemorrhage:
We detected abnormal ECG findings in 15 out
of 20 patients (representing 75%), this frequency
is consistent with most of the published data, the
distribution of these findings was as follow: ST-
T wave changes were detected in thirteen patients
since day 1, long QTc was detected in three patients
and arrhythmias detected in six patients, of whom,
four patients had sinus tachycardia, one patient
had sinus bradycardia and three patients had atrial
premature beats.
Penka, et al, in 2005; detected abnormal ECG
findings in 45 out of 56 patients with aneurysmal

Rania El Hoseiny, et al
SAH which represent 80.4%, out of the later 43.1%
(n=22 cases) showed repolarization changes, 21.6%
(n=11 cases) showed conductive disturbances,
19.6% (n=10 cases) showed LVH, 15.6% (n=8
cases) heart rhythm disturbances [7].
Parekh, et al, in 2000; reported ECG changes
in 23 out of 39 patients with aneurysmal SAH
representing 59% with ST-T wave changes was
detected in 17 patients, long QTc in six patients
and supraventricular arrhythmias in four patients
[14].
Naidech, et al, in 2005; detected abnormal ECG
findings in 174 out of 253 patients with aneurysmal
SAH which represent 69% [10].
Sugimoto, et al, in 2008; observed abnormal
ECG findings-in the form of pathological Q wave,
ST segment deviation, T wave inversion and QT
prolongation-in 29 out of 47 patients with aneurysmal
SAH which represent 62% [15].
Sakr, et al, in 2004; reported ECG changes in
106 out of 159 patients with aneurysmal SAH
representing 66.7% [17].
Contrary to our results were the data published
by Frontera, et al, in 2008; studied the frequency
of cardiac arrhythmias after SAH in 580 patients
and they detected a variety of arrhythmias in 4.3%
(n=25) of these patients, Atrial fibrillation and
atrial flutter were the most common arrhythmias
(19 patients). This frequency (4.3%) is much lower
than detected in our study, as we detected arrhythmias
in 30% (n=6 out of 20) of the patients but
this can be related to the marked discrepancy in
samples size [16].
2- Regarding the frequency of abnormal ECG
findings in patients with traumatic subarachnoid
hemorrhage:
We detected abnormal ECG findings in 3 out
of 10 patients (representing 30%) represented by
ST-T wave changes associated with sinus tachycardia
detected in all of them.
Review of literature revealed that electrocardiographic
abnormalities after head injury have
so far been scarcely reported, no studies to date
has been conducted evaluating cardiac complications
in traumatic SAH patients, most previous
studies have dealt with ECG changes and other
cardiac consequences of aneurysmal subarachnoid
hemorrhage (SAH) [18].
13
Wittebole X, et al and Hemant, et al, published
two case reports showed different patterns of ECG
changes after closed head injury.
Wittebole X, et al, in 2005 described different
patterns of ECG changes-sinus tachycardia, a pattern
of subepicardial injury with elevated ST segment
in leads I, II, aVL, aVF, V5, V6 and a terminal
T-wave negativity with prolonged QT interval and
numerous self-terminating salvos of polymorphous
ventricular tachycardia-in a 32 year old man admitted
after a head trauma with a brain CT scan
was normal, by 16 th day, the ECG only showed
residual T-wave inversion in the inferior leads,
four months later, the 12-lead ECG was normalized
[19].
Hemant, et al, 2008 reported ECG repolarization
abnormalities (ST segment elevation in the inferolateral
leads) and sinus tachycardia in a 31-year
old male patient with head injury, within 48 hours,
this patient was subjected to coronary angiography
on the 9 th day that revealed normal coronaries [20].
3- Regarding the frequency of elevated cardiac
troponin I in patients with aneurysmal subarachnoid
hemorrhage:
In our study, 30% (n=6 cases) of patients had
evidence of elevated cardiac troponin I, a result
that is consistent with the published data.
Similar to our results, Sommargren, et al, in
2002; detected elevated cTnI in 21 out of 100
patients (21%) included in their study [21].
Parekh, et al, in 2000; studied the incidence of
myocardial injury in aneurysmal SAH using cTnI
assay daily for 7 days, 39 patients were included
in the study, of whom, 8 patients (representing
20%) detected to have elevated cTnI [14].
Tung, et al, in 2004; studied the neurocardiogenic
injury after aneurysmal SAH in 223 patients,
all of them subjected to serial cTnI measurement
on days 1, 3 and 6 after enrollement in the study,
elevated cTnI was detected in 45 patients (representing
20%) which is matched with our results
[22].
Ramappa, et al, in 2007, reported frequency of
elevated cTnI 37% in their retrospective study on
incidence of elevated cTnI in patients with aneurysmal
SAH, the study was conducted on 83 patients,
of whom, 31 patients had elevated cTnI [24].

Cardiac Affection after Subarachnoid Hemorrhage
Hravnak, et al, in 2009, conducted a prospective
longitudinal study on 204 patients diagnosed to
have aneurysmal SAH, elevated cTnI was detected
in 65 patients (representing 31%) which is very
close to our results [8].
Naidech and colleagues in 2005; studied cTnI
elevation in aneurysmal SAH and its relation to
cardiovascular morbidity and outcome after the
hemorrhage, 253 patients were included in the
study, cTnI was measured in all patients on admission
then serial measurements were conducted for
patients with elevated cTnI level on the first day,
out of the 253 patients only 172 (representing 68%)
detected to have elevated cTnI which is much
higher than our results [10] also Tanabe, et al, in
2008, studied frequency of cTnI elevation in patients
with aneurysmal SAH, the study was conducted
on 103 patients, elevated cTnI was reported
in 54 patients (representing 52%) which is also
higher than our results, this may be explained by
marked discrepancy in samples size (253&103
versus 20 patients) [23].
4- Regarding the frequency of elevated cardiac
troponin I in patients with traumatic subarachnoid
hemorrhage:
In our study there was no evidence of elevated
cardiac troponin I in patients with traumatic subarachnoid
hemorrhage.
Review of literature revealed that no studies to
date has been conducted on evaluation of cardiac
troponin I in traumatic SAH patients, only one
study conducted by Salim, et al, in 2008 evaluated
cardiac troponin I elevation in patients with traumatic
brain injury, they reported this elevation in
125 out of 420 patients (representing 29.8%) [25].
5- Regarding the prevelance of left ventricular
systolic dysfunction, in patients with aneurysmal
SAH:
In our study, 15% (n=3 out of 20) of patients
had evidence of left ventricular systolic dysfunction,
all of them had regional wall motion abnormalitiesthat
were reversible on follow up on day 7, compeletely
in 10% of patients and partially in 5% -
and two patients had low ejection fraction (

Rania El Hoseiny, et al
Review of literature revealed studies conducted
only on evaluation of cardiac dysfunction due to
traumatic brain injury.
Bahloul, et al, in 2006, studied cardiac dysfunction
due to traumatic brain injury in 202 patients,
only two patients (representing about 1%) reported
to have global hypokinesia with a decrease in
LVEF to 0.40 that completely recovered during
follow-up 7 days after the initial study [28].
Wittebole, et al, in 2005, described-in the previously
mentioned case report-hypokinesia of the
inferior wall of the left ventricle that normalized
on day 6 after the trauma [19].
7- Regarding the correlation between neurological
status and ECG analysis:
In the present study we found a statistically
significant higher frequency of abnormal ECG in
day 1 in those patients with severe aneurysmal
SAH (100%) when compared to those with mild
aneurysmal SAH (58.3%) [p value=0.035], then
there was a tendency toward higher frequency of
abnormal ECG in day 7 in those patients with
severe SAH as compared to those with mild SAH,
yet this tendency lacked any statistical significance
(75% versus 41.7%, p value=0.142).
Similarly, Zaroff, et al, in 1999, who studied
ECG abnormalities in aneurysmal SAH and their
correlation with neurological status (assessed with
Hess & Hunt score), their study was conducted on
58 patients and they concluded that ECG abnormalities
are associated with more severe neurological
injury [9].
Contrary to our results the data published by
Penka, et al, in 2005, who studied the correlation
between ECG abnormalities in aneurysmal SAH
patients and the degree of neurological impairment
(assessed with Hess & Hunt score),they concluded
higher frequency of ECG changes (88.89%) in
patients with lower grades of neurological impairement
(patients with Hess & Hunt score 1&2)
(p

Cardiac Affection after Subarachnoid Hemorrhage
the incidence of systolic dysfunction (global &
regional) in day 7 [p value=0.4].
Similarly, Mayer, et al, in 1999, who studied
left ventricular performance and its correlatin with
neurological status in 72 patients with aneurysmal
SAH, stated that RWMAs are more common in
patients with poor neurological grades (p=0.002)
[26].
Kothavale, et al, in 2006, reported high prevelance
of RWMAs in patients with high Hess &
Hunt grades (3-5) (p=0.046) in the study conducted
on three hundred patients with aneurysmal SAH,
which goes in line with our results [27].
Conclusions
• Different types and frequencies of ECG changes
were found in patients with SAH, most frequent
were repolarization abnormalities, this supports
the hypothesis that neurogenic form of myocardial
injury develops during and/or following SAH,
more support comes from the observed elevation
of cardiac troponin I and left ventricular systolic
dysfunction.
• The incidence of cardiac injury was positively
correlated with the severity of SAH.
• All these findings were much less evident in the
traumatic SAH compared with the aneurysmal
SAH.
• Cardiac injury and dysfunction following SAH
is a potentially reversible phenomenon.
References
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3- Kantor HL, Krishnan SC: Cardiac problems in patients
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7- Penka A Atanassova, Maria P: Abnormal ECG patterns
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8- Hravnak M, Crago EA, Frangiskakis JM, et al: Elevated
Cardiac Troponin I and Relationship to Persistence of
Electrocardiographic and Echocardiographic Abnormalities
After Aneurysmal Subarachnoid Hemorrhage. Stroke
Nov. 2009.
9- Zaroff JG, Rordorf GA, Newell JB, et al: Cardiac outcome
in patients with subarachnoid hemorrhage and electrocardiographic
abnormalities. Neurosurgery 1999; 44: 34-39.
10- Naidech AM, Kurt T: Cardiac troponin elevation, cardiovascular
morbidity, and outcome after subarachnoid
hemorrhage. Circulaion 2005; 112 (18): 2851-6.
11- Macfarlane PW, Lawrie TDV: Comprehensive Electrocardiology.
Vol III. New York: Pergamon Press 1989; 1459.
12- Macfarlane PW, Lawrie TDV: The normal electrocardiogram
and vectorcardiogram. In: Macfarlane PW, Lawrie
TDV, eds. Comprehensive Electrocardiology. Vol I. New
York: Pergamon Press 1989; 451-452.
13- Hodges M, Salemo D, Erlien D, et al: Bazett’s QT correction
reviewed. Evidence that a linear QT correction for
heart is better. J Am Coll Cardiol 1983; 1: 69.
14- Nilesh Parekh, Bala Venkatesh: Cardiac troponin I predicts
myocardial dysfunction in aneurysmal subarachnoid
hemorrhage, J Am Coll Cardiol 2000; 36: 1328-1335.
15- Sugimoto K, Watanabe E, Yamada A, et al: Prognostic
implications of left ventricular wall motion abnormalities
associated with subarachnoid hemorrhage. Int Heart J Jan
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after Subarachnoid Hemorrhage: Risk Factors and Impact
on Outcome.Cerebrovasc Dis Jun 2008; 26 (1): 71-78.
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changes to neurological outcome in patients with aneurysmal
subarachnoid hemorrhage, Int J Cardiol 2004; 96
(3): 369-73.
18- Sakr YL, Ghosn I, Vincent JL, et al: Cardiac manifestations
after subarachnoid hemorrhage: A systematic review of
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changes after head trauma, Journal of Electrocardiology
2005; 38: 77-81.
20- Hemant Bhagat, Rajiv Narang1, Deepak Sharma, et al:
ST elevation - An indication of reversible neurogenic
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Annals of Cardiac Anaesthesia Jul-Dec 2009; Vol. 12: 2.
21- Sommargren CE, Zaroff JG, Banki N, et al: Electrocardiographic
repolarization abnormalities in subarachnoid
hemorrhage, J Electrocardiol 2002; 257-62.
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after subarachnoid hemorrhage. Stroke 2004; 35 (2): 548-
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elevation in cardiac troponin I to clinical severity, cardiac
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Egypt Heart J 62 (1): 19-24, March 2010
Endothelial Dysfunction and Insulin Resistance in Normoglycemic
Offsprings of Patients with Type 2 Diabetes Mellitus
EMAN S MOHAMMAD, MD*; YASSER KAMEL, MD; HANNAN TAHA, MD**;
ESSAM SAAD, MD; YASSER MAKRAM, MD***
Background: Endothelial dysfunction and insulin resistance are among the earliest detectable abnormalities in people at
risk for atherosclerosis. Similar genetic and environmental factors may contribute independently to both atherosclerosis and
type 2 diabetes mellitus. Whether family history for diabetes predispose to alteration in vascular function through an unknown
''genetic susceptibility'' or through higher prevalence of insulin resistance has not yet been fully investigated.
Objectives: To investigate endothelial function in normotensive normoglycemic offspring of diabetic subjects and to explore
its relationship with the insulin resistance.
Patients and Methods: We compared normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) (n=36)
with matched healthy control subjects without family history of diabetes (n=21). Flow-mediated dilation (FMD) and nitroglycerinmediated
dilation (GTN-MD) were assessed in brachial artery by colored Duplex ultrasound to evaluate endothelium-dependent
and independent vascular function. Homeostasis model assessment (HOMA) was performed to calculate insulin resistance.
Results: FMD% was lower in NOPD than in control (7.31±2.73 Vs. 10.45±3.15, p

Endothelial Dysfunction & Insulin Resistance in Normoglycemic Offsprings
particularly in skeletal muscle [10]. Insulin stimulates
bulk flow as an endothelium-dependent vasodilator
via nitric oxide production [11]. Impaired
endothelial function in type 2 diabetics is documented
by reduced effect of endothelial-dependent
vasodilators such as acetylcholine (ACH) [12].
Insulin resistance is defined as a state of reduced
responsiveness to normal circulating levels of
insulin. This condition is a feature of various
disorders, such as type 2 diabetes, is also implicated
in impaired glucose tolerance (IGT) or impaired
fasting glucose (IFG), both considered as ''prediabetes''
by the Expert Committee on the Diagnosis
and Classification of Diabetes Mellitus, as well as
in obesity, hypertension, dyslipidaemia [13], the
possibility of existence of earlier in life metabolic
effect in genetically predisposed persons as offspring
of type 2 diabetics was thought as another
face of the coin.
Whether family history for diabetes predispose
to alteration in vascular function through an unknown
''genetic susceptibility'' or through higher
prevalence of insulin resistance has not yet been
fully investigated. The aim of the present study
was to investigate endothelial function in normotensive
normoglycemic offspring of diabetic subjects
and to explore its relationship with the insulin
resistance.
Patients and Methods
The study population consisted of 57 subjects:
NOPD group: 36 healthy subjects, with one or
both parents having type 2 diabetes mellitus.
Control group: 21 healthy normotensive normoglycemic
subjects with no family history of
type 2 diabetes mellitus.
Exclusion criteria: Tobacco smoking, history
or clinical evidence of cardiac diseases or systemic
diseases, obesity [body mass index (BMI) ≥30kg/
m 2 and/or Waist-to-hip ratio (WHR) >0.9m in
males and >0.85m in females], hypertension, diabetes,
or dyslipidemia. All women were premenopausal
and their investigations were undertaken
during the first week of their menstrual cycles.
None of them were taking oral contraceptives.
Anthropometric, metabolic characteristics and
laboratory measurements:
Height, weight and waist circumference were
determined for all participants. BMI was determined
as body weight (kg)/height (m) 2. Total and
20
HDL cholesterol, triglycerides and routine chemistry
were measured by standard laboratory techniques.
Oral glucose tolerance test (OGTT):
A standard OGTT was done after an overnight
10- to 12-h fast. Blood samples were obtained
before and 2h after 75g of glucose administration.
Homeostasis model assessment (HOMA):
Serum insulin was determined by an electrochemiluminescense
assay. Insulin resistance [14]
was calculated as follows:
HOMA-IR=fasting glucose (mmol/L) x insulin (mIu/mL)
––––––––––––––––––––––––––––––––––––––––––––––––
22.5
Endothelial function:
Endothelial function was measured 1h before
the OGTT was started. All studies were performed
in the morning in a quiet room. Brachial artery
reactivity was measured by colored Doppler ultrasound,
using a 7.5MHz linear array transducer
ultrasound system. The mean right brachial artery
antero-posterior diameter was measured 3-5cm
above the elbow, between media and adventitia
from 4 cycles synchronized with the end-diastole
at the R wave peaks [15]. The ECG was monitored
continuously throughout the study.
• A basic scan of the brachial artery diameter and
flow was taken.
• 2 nd scan was taken after applying a pneumatic
tourniquet of 250-300mmHg. (Using mercurial
sphygmomanometer) for about 5 minutes. The
scan was taken to measure brachial artery diameter,
60 seconds after releasing the tourniquet
measuring the maximum FMD (index of endothelium-dependent
vasodilation).
• 3 rd scan was taken after 15 minutes of rest to
allow recovery of the artery after FMD and considered
the basic scan of GTN-MD reading.
• 4 th scan was taken 4 minutes after administration
of 400mg of GTN spray sublingually to assess
non-endothelium dependent dilation. GTN serves
as an exogenous source of Nitric Oxide (NO),
bypassing the need for endogenous endothelial
NO production.
o FMD percentage was calculated by the following
equation:
2 nd scan – 1 st scan
FMD% = ––––––––––––––––– x 100
1 st scan

Eman S Mohammad, et al
o GTN-MD percentage was calculated by the
following equation:
4 th scan – 3 rd scan
GTN – MD% = ––––––––––––––––– x 100
3 rd scan
o Dilatation ratio was calculated by the following
equation:
FMD%
DilRatio = –––––––––––––
GTN – MD%
Results
The study included 57 subjects; 36 NOPD and
21 controls. Table (1) shows the demographic and
Table 1: Demographic and metabolic data for NOPD and
controls.
Gender:
Male
Female
Age
BMI
WHR:
Male
Female
Fasting Insulin
Fasting Glucose
HOMA-IR
NOPD (n=36) Controls (n=21)
Number
10
26
Mean
25.83
23.98
0.84
0.78
9.478
5.02
2.11
%
27.8
72.2
SD
6.38
2.95
0.08
0.07
2.63
0.59
0.63
Number
6
15
Mean
25.33
22.89
0.79
0.82
8.68
4.76
1.65
%
28.6
71.4
SD
6.28
2.71
0.05
0.03
2.15
0.67
0.615
p value
0.759
p value
0.762
0.160
0.057
0.06
0.222
0.194
0.013
Abbreviations:
BMI : Body mass index.
WHR: Waist to hip ratio.
HOMA-IR: Homeostasis model assessment-Insulin resistance.
25
20
15
10
5
0
p=0.24
GTN% FMD%

Endothelial Dysfunction & Insulin Resistance in Normoglycemic Offsprings
2.5
2
1.5
1
0.5
0
HOMA-IR
HOMA-IR
p=0.013
Control NOPD
Figure 3: HOMA-IR in NOPD and Controls.
Discussion
The present study showed that: (a) normotensive
normoglycemic offsprings of type 2 diabetic subjects
present insulin resistance and early endothelial
dysfunction, as they had impaired FMD, while the
direct vasodilator capacity induced by GTN was
not impaired. (b) FMD was impaired more in
offsprings of diabetics with more insulin resistance.
Our findings are in agreement with Caballero
et al [16] who showed decreased FMD and decreased
microvascular reactivity in first degree
relatives of type 2 diabetic subjects as compared
to controls.
Balletshofer et al [17] found impaired FMD in
normoglycemic offspring of diabetic parents, but
this was significant only in insulin resistant normoglycemic
offspring of diabetic parents compared
to controls. There was no significant difference in
GTN-MD between all the studied groups. Of note,
that study included only 10 control subjects to
compare with 53 subjects with diabetic parents
and smokers were not excluded from study. This
may attenuate the difference between offspring of
diabetic parents and controls as regard FMD.
Furthermore, Chen et al [18], McSorley et al
[19] and Iellamo et al [20] found a significantly
reduced forearm vasodilation, indicating endothelial
dysfunction in normoglycemic first degree relatives
of type 2 diabetic subjects. However, McSorley et
al [19] did not find significant difference in HOMA-
IR, an index of insulin resistance, between NOPD
and controls, nonetheless, several findings from
that study suggested the presence of hyperinsulinemic
state in the NOPD group. These include higher
22
values of HbA1c and higher values for blood glucose
120 minutes after OGTT concomitant with
higher insulin levels, reflecting a relative hyperinsulinemic
state. In addition, the area under glucose
curve (AUCs) for glucose and insulin during OGTT
were inversely correlated with FMD.
Goldfine et al [21] found that FMD was reduced
in normoglycemic offsprings of type 2 diabetic
subjects (even the most insulin-sensitive), with no
difference in GTN-MD. This significant attenuation
of endothelial dysfunction even in insulin sensitive
offsprings could be due to enriched familiar difference
in that study as both parents were diabetic.
Moreover, the studied subjects had non significantly
higher BMI compared to our subjects (23.98±2.95
Vs 22.89±2.71).
Tesauro et al [22] found that normoglycemic
offsprings of type 2 diabetic subjects were more
insulin resistant on average than the control group,
and had significantly lower both FMD and GTN-
MD compared with the control group. They suggested
that in addition to decreased insulin sensitivity;
otherwise healthy subjects with a family
history of type 2 diabetes mellitus have impairment
in vascular responsiveness to NO that may be
endothelium dependent and/or independent.
In concordance of our results, Amudha et al
[23] found that NOPD had significantly impaired
FMD and higher HOMA-IR, reflecting endothelial
dysfunction and insulin resistance.
Frequent presence of vascular pathology at the
time of diagnosis of diabetes suggests importance
for identification of prediabetic persons with diminished
endothelial function and early atherosclerotic
disease and family history of diabetes is a
recognized risk for development of diabetes [21].
In normoglycemic offspring of patients with
type 2 diabetes mellitus, significant endothelial
dysfunction and insulin resistance are detectable
even in the absence of frank diabetes. This suggests
that genetic factors contributing to insulin resistance
and diabetes may also influence development of
cardiovascular diseases including atherosclerosis
and coronary heart disease that are related to endothelial
dysfunction [22].
From data of our study and other studies, we
can speculate that NOPD present a blunted endothelial
function in relation to a primary inherited
genetic susceptibility yet to be identified, or in
relation to the metabolic alteration detectable even

Eman S Mohammad, et al
in normotensive and normoglycemic subjects.
Certainly, the blunted endothelial function observed
in NOPD subjects may also be related to glycemic
burden, even in the nondiabetic range, given that
hyperglycemia has been shown to decrease NO
bioavailability through activation of PKC (protein
kinase C) via diacylglycerol, increased hexosamine
pathway flux, increased advanced glycation end
product formation, increased oxidative stress and
increased polyol pathway flux [24,25]. It has been
found that fasting hyperglycemia diminishes microvascular
hyperemia and inversely correlates
with endothelial dependant vasodilataion [26].
Indeed, our NOPD subjects had still normal but
already higher glycemia as compared to controls.
In addition, reciprocal relationships between
insulin resistance and endothelial dysfunction may
be secondary to impaired activation of endothelial
signalling pathways in the context of inherited
insulin resistance [27]. It has been found that genetic
mutations of insulin receptor genes and alteration
of insulin signal transduction could contribute to
the impairment of insulin secretory profile and
insulin resistance [28].
Thus the endothelial dysfunction and insulin
resistance we found are inherited conditions, transmitted
from the diabetic parents in whom endothelial
dysfunction and insulin resistance were previously
proved [29,30].
Conclusions
We demonstrate that nondiabetic offspring of
diabetic parents have impaired endothelial dependant
vasodilatation as well as insulin resistance.
These data suggest bioavailability of nitric oxide
is lower in offspring of diabetic subjects and may
contribute to cardiovascular risk in advance of
development of overt diabetes. Modest hyperglycemia,
even within the normative range and insulin
resistance may contribute to attenuated endothelial
function. Finally, as endothelial dysfunction is
present in nondiabetic offspring of diabetic parents,
strong family history of type 2 diabetes mellitus
could be considered an additional cardiac risk
factor.
These results may have important implications
for identifying populations that can derive substantial
benefits from early lifestyle interventions
including diet and exercise that are known to
improve endothelial function, increase insulin
sensitivity and lower circulating markers of inflammation.
23
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Egypt Heart J 62 (1): 25-37, March 2010
Comparative Study between Tissue Doppler Imaging and Radionuclide
Scintigraphy in Evaluation of Right Ventricular Function in Patients
with Chronic Obstructive Pulmonary Disease
SHERINE ELGANGIHI, MD; RANDA ALY, MD; SALLY SALAH; AMR ELHADIDY, MD*
Background: Cor-pulmonale complicates 2-6/1000 of patients with chronic obstructive pulmonary disease (COPD). The
early diagnosis of RV dysfunction 2 nd ry to pulmonary hypertension can reduce morbidity and mortality.
Purpose: The objective of our study is to assess the usefulness of tissue Doppler imaging (TDI) in evaluation of RV function
in patients with COPD in comparison of first pass radionuclide angiography (FPRNA) which is the gold standard method.
Another aim is to determine the relationship between lateral tricuspid annulus TDI parameters and PASP as estimated by
continuous wave Doppler in patients with COPD.
Methods: Thirty patients with COPD diagnosed by history, clinical examination, CXR, laboratory findings (ABG, CBC),
12-lead ECG, TDI (to measure MPI, Sm, SmVTI, Em/Am), FPRNA (to measure RV EF).
Results: Based on the nuclear study (FPRNA) our 30 pts divided to 17pts (56.7%) with RVEF >45% (55.2±1.4) and 13
pts (43.3%) with RVEF

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
ventricular after load and eventually lead to clinical
syndrome of right heart failure with systemic
congestion [3].
Two dimensional echocardiography is not feasible
in assessment of right ventricular (RV) function.
In addition two dimensional echocardiography
doesn't provide homodynamic information about
right ventricular filling pressures, which can be
derived from Doppler echocardiography studies
[4].
Tissue Doppler imaging TDI is an extension of
conventional Doppler flow echocardiography &
has been proven to be useful & feasible clinical
tool for assessing systolic & diastolic function
since its introduction in early 1990s [5,6]. Also, it
recently has emerged as a new method useful for
predicting right atrial pressure and evaluation of
right ventricular systolic and diastolic function
[7,8,9].
Radionuclide ventriculography (RNV) is considered
the gold standard for estimating the right
ventricular ejection fraction (RVEF). Abnormal
RV function in patients with COPD has been demonstrated
by both first-pass & gated blood pool
scanning [10].
Aim of the work:
to assess the usefulness of tissue Doppler imaging
TDI in evaluation of RV function in patients
with chronic obstructive pulmonary disease in
comparison to first pass radionuclide angiography
FPRNA which is the gold standard method.
To describe the gastric mucosal morphologic
abnormalities occurring in the septic settings, and
whether or not, these findings correlate with the
clinical course, prognosis and mortality of septic
patients.
Patients and Methods
Patients: We prospectively enrolled Thirty
patients (25 males, 5 females mean age 60.8±10.5
yrs) were included in the study, admitted to Critical
care department, Cairo university hospitals; from
July 2007 to March 2009.
Inclusion criteria: Any patient presented with
COPD diagnosed by history, physical examination,
laboratory analysis and imaging.
Exclusion criteria: Rt. Ventricular infarction,
Cardiomyopathies, Rheumatic heart diseases, Pri-
26
mary Pulmonary hypertension, Congenital heart
disease, Pregnancy, Paced heart and Pulmonary
embolism.
Evaluation of Patients: All included patients were
subjected to the following:
1- Full clinical evaluation: Including history
tacking including smoking index, physical examination
and standard 12-leads electrocardiogram.
2- Laboratory investigations: Including Arterial
blood gases, Complete blood count (CBC) and
Other routine labs.
Laboratory results indicative for the diagnosis of
COPD:
• Secondary polycyathemia due to chronic hypoxemia.
• Hematocrite of more than 52% in males and more
than 47% in female indicates disease.
• ABG on admission: Chronic hypoxia, hypercapnia
& high level of HCO 3 as a compensatory.
• PCO 2 >45mmHg.
• Hypoxia PaO 2 27mg/dl.
3- Imaging studies:
a- Chest radiograph: PA X-ray reveal signs of
hyperinflation, including a flattening of the
diaphragm, increased retrosternal air space, and
a long narrow heart shadow. Hyperlucency of
the lungs are signs of emphysema.
b- Echocardiographic examination: All patients
underwent echocardiographic examination, including
the routine transthoracic and tissue
Doppler study. Each patient was examined in
the left lateral decubitus position according to
the recommendations of the American Society
of Echocardiography. The study was conducted
using an ATL HDI 5000 colored echocardiographic
machine with TDI software incorporated
in the device using a 3.5MHz. transducer.
i- Routine echocardiographic study including
LVEDD, VESD, EF and right ventricular
dimensions to exclude cardiac myopathies
and to give an idea about right ventricular
size.
ii- Tissue Doppler study: Tissue Doppler Imaging
(TDI) was done in the pulsed modality
from the apical 4 chamber view placing the

Sherine Elgangihi, et al
sample volume of the Doppler cursor at the
lateral tricuspid annulus to determine the
following parameters (in a pt. with HR 70
bpm):
Isovolumic contraction time (IVCT): Measured
in (msec) by Pulsed-Doppler from the end of A
wave to the beginning of systolic wave (N: 50ms).
Isovolumic relaxation time (IVRT): Measured
in (msec) by Pulsed-Doppler from the end of systolic
wave to the beginning of E wave (N: 60ms).
Ejection time (ET): Measured in (msec) by
Pulsed-Doppler as the period of aortic or pulmonary
valve opening or the time of peak myocardial
systolic velocity (N: 250ms).
Myocardial performance index (MPI): Calculated
by the following equation:
IVRT + IVCT
MPI = –––––––––––––– (N: 0.39)
ET
Peak myocardial systolic velocity (Sm): Measured
in Cm/s by drawing a perpendicular line
from the summit of the wave to the baseline (N:
12-17cm/s).
Velocity time integral (Sm VTI): It is area measured
under the Doppler velocity envelope for
systolic wave measured by tissue Doppler (N
>2.7cm).
Early diastolic wave (E): Corresponding rapid
filling phase, measured in Cm/s by drawing a
perpendicular line from baseline to summit of
wave.
Late diastolic wave (Am): Corresponding to
atrial contraction, measured in Cm/s by drawing
a perpendicular line from baseline to summit of
wave.
iii- Nuclear imaging: Myocardial nuclear imaging
was done following stabilization of the
patient's medical condition.
First pass radionuclide angiography (FPR-
NA): First pass technique was used to assess the
RV ejection fraction by injecting 25-30mCi Tc-
99m Sestamibi intravenously. Intravenous access
should be obtained using a large-bore indwelling
polyethylene catheter, either a 18-or 20-gauge
catheter in an external jugular vein or a 14- or 16-
27
gauge in a medial antecubital vein. The catheter
should be connected to a saline-loaded 30 to 35ml
syringe using tubing that has a 3 to 5ml capacity
and a three-way stopcock. The tracer is then loaded
into the tubing and subsequently forced through
this system using maximal hand pressure on the
syringe after starting the acquisition. The images
are acquired in anterior view, (the acquisition
duration should be set for at least 30 seconds in
order to allow for complete transition through the
central circulation then processed and analyzed
using the frame method for RV, which creates a
representative ventricular volumes cycles by summing
frames of several (usually 2 or 4 for RV)
cardiac cycles, aligned by matching their ED to
get the RV by semi-automated method.
The statistics:
• Data were collected on special format, verified
and then coded when needed prior to analysis.
• All continuous data were expressed as mean ±
SD, categorical data were expressed as frequency
in tables.
• Chi-square test and kappa for assessing agreement
between two methods in categorical data.
• Tools to assess the accuracy of diagnostic test
have been calculated.
• Sensitivity, specificity, positive and negative
predictive values together with Odds ratio.
º Sensitivity = [True positive -– false negative]/
True positive.
º Specificity = [True negative – false positive]
/ True negative.
º Positive predictive value = [True positive –
false positive] / True positive.
º Negative predictive value = [True negative –
false negative] / True negative.
• p value

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
Patients with COPD who have Rt ventricular impairment
could be detected by the following:
1- Pulsed wave tissue Doppler echocardiography
at lateral tricuspid annulus that showed the
following parameters:
• Peak myocardial systolic velocity (Sm)

Sherine Elgangihi, et al
Out of our 30 pts, Sm ≥12Cm/s and MPI

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
%
100
90
80
70
60
50
40
30
20
10
0
11.1 61.9
88.9 38.1
RVD Normal RVD Dilated
TDI Normal RV function
TDI impaired RV function
Figure 4: Shows the relation between (conventional echocardiograph)
& TDI ± in assessment of RV function.
A significant agreement between two methods
RV diameter by measured by conventional echo
TDI) in assessment of Rt ventricular function where
sensitivity=62%, specificity=89%, +ve PV=92.9,
–ve PV=50% & p value=0.011. But there is no
correlation between conventional echocardiograph
& FPRNA in assessment of Rt ventricular function
where p value 0.127.
Table 6: Shows a comparison between TDI & clinical data
in assessment of Rt ventricular functions.
Normal RV function
Impaired Rt
ventricular function
Total
%
100
80
60
40
20
0
TDI
–ve signs
cor-pulmonale
Signs of Cor-pulmonale
No.
14
1
15
–ve +ve
6.7
93.3
Normal RV function
Impaired RV function
+ve signs
cor-pulmonale
86.7
13.3
Figure 5: Shows the relation between TDI & clinical data in
evaluation of RV function.
%
93.3
6.7
100
No.
2
13
15
%
13.3
86.7
100
p value

Sherine Elgangihi, et al
VI- The comparison between Rt ventricular systolic
function (RVEF) detected by FPRNA &
Rt ventricular dysfunction detected clinically
(cor-palmonale):
Our study group show 15 pt (50%) have no
manifestation of cor-pulmonale & from which 13
pt (86.7%) with normal Rt ventricular systolic
function (RVEF >45%) detected by FPRNA & two
Pts (13.3%) have Rt ventricular dysfunction by
FPRNA.
Also there are 15 pts (50%) presented with
manifestation of cor-pulmonale clinically from
which only 11 pts (73.3%) have Rt ventricular
impairment (RVEF 45%).
There is a significant correlation between Rt
ventricular function evaluated clinically & by
FPRNA where p value is 0.01.
VII- Correlation between PASP detect by continuous
wave Doppler & lateral annulus velocities
of tricuspid valve in patients with COPD:
All patients of our study (30 pts) had elevated
PASP as detected by pulsed wave Doppler echocardiography.
Data of lateral annulus velocities of
tricuspid valve are shown in Table (8).
Relationship between PASP and tricuspid lateral
annulus systolic velocities are shown in Figs.
(9,10,11).
There were a significant negative correlation
between PASP and Sm, SmVTI & Em/Am.
Where: r=–0.61 p

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
Figure 12: Tissue Doppler imaging = Sm 12.8 cm/s, IVRT = 33 ms, IVCT = 54 ms, MPI = 0.4,(EJ = 220), SmVTI = 2.2 cm,
Em/Am = 0.8 (pt. No. 20).
Figure 13: Tissue Doppler imaging = Sm 11.7 cm/s, IVCT = 75 ms, IVRT = 93 ms, ET = 177 ms, MPI = 0.9, SmVTI = 1.7,
Em/Am = 0.3 (pt. No. 26).
Discussion
Evaluation of ventricular performance is often
of paramount importance in ICU. Accurate and
timely assessment of systolic ventricular function
should be an integral part of medical management
of the hemodynamically unstable critically ill
patients [11].
Right ventricular dysfunction is common, and
its role in critically ill pts is underestimated [12].
Additionally in the critical care setting, the RV
function is also altered by increasing RV after load
including high levels of positive end-expiratory
pressure or increased pulmonary vascular resistance
[13].
For early diagnosis, electrocardiography and
two dimensional echocardiography [159,160] are
used. However, it is difficult to assess both RV
anatomy and function with reliable conventional
echocardiographic examination because of its complex
structure.
32
Tissue Doppler imaging (TDI) has been evolved
as a new technique that enables myocardial velocities
to be detected and makes the quantitative
assessment of the systolic and diastolic movements
of myocardial walls possible [16,17]. TDI has been
considered to be a technique that leads to assessment
of the RV function [18]. As determined from
the position of the RV tricuspid annulus by TDI,
myocardial velocities and the myocardial performance
index (MPI), which are new parameters in
assessing left ventricular function [19], can also
give information about RV function.
Despite RV function is less often measured than
LV function it has been shown to hold clinical
diagnostic and prognostic importance in many
disorders [20-24]. Owing to its accuracy, First Pass
Radionuclear Angiography has become a non invasive
standard reference for RVEF, and has often
been performed in concern with other measurements
of RV function as a calibration method
[25,26].

Sherine Elgangihi, et al
Pulmonary artery pressure (PAP) is an important
hemodynamic parameter that is used in the follow
up of various cardiac & pulmonary disorder. It's
the primary cause of right ventricular systolic and
diastolic dysfunction and thus failure in COPD
patients [27].
In various studies the PASP could be determined
by echocardiography in less than half of patients
with COPD mostly due to absence of adequate TR
velocity [28-31].
Tissue Doppler imaging (TDI) is an extension
of conventional Doppler flow echocardiography
and has been established new method useful for
predicting right atrial pressure, evaluation of right
ventricular systolic and diastolic function also
detecting the effect of PASP on the lateral tricuspid
annulus velocities [7-9].
The objective of present study is to assess the
usefulness of tissue Doppler imaging in evaluation
of RV function in patients with COPD in comparison
with FPRNA which is the gold standard method,
also to determine the relationship between
lateral tricuspid annulus velocities detected by TDI
& PASP as estimated by continuous wave Doppler
in patients with COPD.
Previous studies using pulsed tissue Doppler
in healthy adults have established normal reference
values for adults at the level of the RV free wall
and at the lateral tricuspid annulus and concluded
that a peak systolic annular velocity

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
motion indices and PASP where there's a –ve correlation
between PASP and Sm, SmVTI. (PASP
Vs Sm r=–0.61, p value

Sherine Elgangihi, et al
& lateral tricuspid annulus velocity where PASP
vs Sm=–0.61, p

Comparative Study between Tissue Doppler Imaging & Radionuclide Scintigraphy
19- (Copyright © 2009 Radiological Society of North America,
Inc. (RSNA).
20- Wencker D, Borer JS, Hochreiter C, et al: Preoperative
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Cardiology 2000; 93: 37.
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right ven-tricular ejection fraction predicts exercise capacity
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22- Hochreiter C, Niles N, Devereux RB, et al: Mitral regurgitation:
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23- Sciurba FC, Rogers RM, Keenan RJ, et al: Improvement
in pul-monary function and elastic recoil after lungreduction
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1996; 334: 1095.
24- Bartlett MI, Seaton D, McEwan L, et al: Determination
of right ventricular ejection fraction from reprojected
gated pool SPECT. Comaprison with first-pass ventriuclargraphy.
Eur J Nucl Med 2001; 28-608.
25- Caplin JL, Flatman WD, Dymond DS: Effects of projection
background correction method upon calculation of right
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26- Johnson LL, Lawson MA, Blackwell GG, et al: Optimizing
the method to calculate right ventricular ejection fraction
from first-pass data acquired with a multicrystal camera.
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27- Rich S, McLaughlin VV: Pulmonary hypertension. In:
Zipes DP, Libby P, Bonow RO, Braunwald E (eds) Braunwald's
Heart Disease. Elsevier Saunders, Philadelphia,
PP 1807-1842.
28- Arcasoy SM, Christie JD, Ferrari VA, et al: Echocardiographic
assessment of pulmonary hypertension in patietns
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29- Tramarin R, Torbicki A, Marchandise B, Laaban JP,
Morpurgo M: Doppler echocardigoraphic evaluation of
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Egypt Heart J 62 (1): 39-52, March 2010
Metabolic Syndrome and its Impact on Vascular Damage Extent
AYMAN SADEK, MD; MAGDY NOUH AIN, MD; HANY FOUAD HANAA, MD;
RAMZY HAMED EL-MAWARDY, MD
Background: Metabolic syndrome is associated with increased risk of cardiovascular diseases in patients without a
cardiovascular history, there is nearly 3 fold increase cardiovascular related mortality compared to subjects without metabolic
syndrome.
Aim of the Work: Was to investigate the relation between metabolic syndrome and extent of vascular damage.
Methods and Results: We conducted a prospective observational study of 50 patients with history of coronary artery disease,
history of stroke TIA or Peripheral arterial disease between January 2005 and March 2006 at Ain Shams University hospitals,
Egypt. Patients having criteria of metabolic syndrome were identified. Echocardiography, carotid and femoral duplex, detection
of microalbuminuria were done for the study population The study population was divided into three groups: Group I included
12 patients with 3 metabolic risk factors, group II included 17 patients with 4 metabolic risk factors and group III included 21
patients with 5 metabolic risk factors. Comparison between the study groups as regard intima media thickness (IMT) of the
carotid and femoral arteries revealed that right carotid IMT was 0.97mm ±0.17, 1.13mm ±0.14 and 1.18mm ±0.17 in group I,II
and III respectively (p=0.002). Left carotid IMT was 0.97mm ±.19, 1.12mm ±0.12 and 1.19mm ±0.19 in group I,II and III
respectively [p=0.003 right femoral IMT was 0.98 mm ±0.23, 1.11mm ± 0.18 and 1.09 mm ±0.20 in group I,II and III respectively
(p=078)] left femoral IMT was 0.90mm ±.23, 1.10mm ±0.09 and 1.08 mm ±0.15 in group I,II and III respectively (p=0.003).
Comparison between the study groups as regard presence of carotid or femoral plaques revealed that presence of carotid plaque
was positive in 0.0 patient (0%) of group I and 5 patients (29.4%) of group II and 12 patient (57.1%) of group III (p=0.023).
Presence of femoral plaque was positive in 3 patients (25%) of group I and 4 patients (23.5%) of group II and 8 patient (38.1%)
of group III (p=0.56). Microalbuminuria was positive in 1 patient (8.3%) in group I, 4 patients (23.5%) of group II and 11
patients (52.4%) of group III (p=0.022). When comparing between the study groups as regard number of vascular beds affected
in each group (coronary, cerebral and peripheral vascular beds), we found that group I 10 patients (40%) was having one vascular
bed affected, 2 patients (8.7%) having two vascular beds affected and 0.0 patient (0%) having three vascular beds affected, in
group II we found that 10 patients 40% was having one vascular beds affected 7 patients (30.4%) having two vascular beds
affected and 0.0 (0%) patient having three vascular beds affected. In group III we found that 5 patients (20%) was having one
vascular beds affected 14 patients (60.5%) having two vascular beds affected and 2 (100%) patients having three vascular beds
affected. Right femoral IMT was 1.06±0.19mm when one vascular bed affected, 1.13±0.22mm when two vascular beds affected
and 1.12±0.17mm when three vascular beds affected (p=0.59). Left femoral IMT was 0.9±0.22mm when one vascular bed
affected, 1.09±0.22mm when two vascular beds affected and 1.09±0.15mm when three vascular beds affected (p=0.003)
Comparison between the presence of positive microalbuminuria and number of vascular beds affected revealed that it was
positive in 2 patients (8.0%) when one vascular bed affected, 12 patients (52.2%) when two vascular beds affected and 2 patients
(100%) when three vascular beds affected (p=0.001).
Conclusions: Metabolic syndrome is constellation of risk factors for atherosclerosis and increase in traits of metabolic
syndrome is associated with increase in extent of vascular damage. The increase in traits of metabolic syndrome is associated
with increase in carotid and femoral IMT and presence of microalbuminuria. The presence of thickened carotid and femoral
IMT and presence of microalbuminuria is associated with increase in extent of vascular damage.
Key Words: Metabolic syndrome – Vascular damage.
Faculty of Medicine, Ain Shams University.
Manuscript received 10 Sep., 2009; revised 20 Oct., 2009;
accepted 21 Oct., 2009.
Address for Correspondence: Dr. Ayman Sadek, Faculty of
Medicine, Ain Shams University.
39

Metabolic Syndrome & its Impact on Vascular Damage Extent
Introduction
The metabolic syndrome is a constellation of
interrelated risk factors of metabolic origin (metabolic
risk factors) that appear to directly promote
the development of atherosclerotic cardiovascular
disease (ASCVD). According to Adult Treatment
Panel III (ATP III) the metabolic syndrome is
diagnosed when three or more metabolic abnormalities
(impaired glucose metabolism, elevated
blood pressure, hypertriglyceridemia, low HDL
cholesterol and central obesity) cluster in the same
person [1].
This syndrome confers an increased risk for
the development of diabetes mellitus and for cardiovascular
morbidity and mortality [2-4].
According to different investigators the increase
of thickness of intima media complex is said to be
the earliest morphological alteration in pathogenesis
of arteriosclerosis. Reitzschel and Associates
(2001), were interested in the multivariate relation
between most of cardiovascular risk factors and
the carotid and femoral IMT. All the traditional
risk factors were assessed for all candidates and
cardiovascular risk was calculated using Framingham
equation, which was directly related to CIMT
and FIMT. Both the CIMT and FIMT were intercorrelated
but the CIMT is easier and more suitable
for risk stratification in low risk population [5].
The appearance of trace amounts of albumin
(microalbuminuria, 30 to 300mg/d) and larger
amounts (frank proteinuria, ≥1g/d) are associated
with an increased risk for renal failure, heart disease,
stroke and cardiovascular mortality [6,7].
Miettinen et al., (1996) found an association between
amount of urinary protein excretion and risk
of stroke and lower extremity amputation in a
cohort of subjects that was independent of diabetes
status and traditional risk factors [8].
The syndrome is diagnosed when three or more
metabolic abnormalities cluster in the same person:
Impaired glucose metabolism (Fasting blood
glucose >110mg/dl).
Elevated blood pressure (≥130mmHg systolic
or ≥85mmHg diastolic).
Hypertriglyceridemia (serum triglycerides
>150mg/dl).
Low HDL-cholesterol (88cm in women) [1].
This syndrome confers an increased risk for
the development of diabetes mellitus and for cardiovascular
morbidity and mortality [2].
From several epidemiological studies it became
clear that measurement of carotid intima media
thickness (IMT) can be applied as a marker for
generalized atherosclerosis and as an indicator of
cardiovascular risk [9].
Similarly albuminuria and decreased ankle
brachial pressure index (ABPI) are markers of
atherosclerosis and indicators of increased cardiovascular
risk [10].
The presence of the metabolic syndrome at
baseline increased the risk for development of
diabetes mellitus almost 2-fold in American Indians
and in Finnish men roughly 4-fold increase was
shown [11].
In a study by Lakka et al, men with metabolic
syndrome had a nearly 3-fold increase in cardiovascular
related mortality compared to subjects
without the metabolic syndrome [12].
In addition, the risk for coronary heart disease
and stroke tripled in metabolic syndrome subjects
with a 10% increase in cardiovascular mortality
during 6.9 years of follow-up [13].
Aim of work:
The aim of this study is to investigate whether
the metabolic syndrome is related to the extent of
vascular damage in patients with various manifestations
of vascular disease.
Patients and Methods
Patient selection:
This study was conducted on 50 patients, in
the period between July, 2005 and February, 2006
who were referred to the cardiology, neurology,
internal medicine and vascular departments in Ain
Shams University Hospital. Patients who were
newly presented with a manifest atherosclerotic
disease (coronary heart disease, stroke, peripheral
arterial disease):
Patients with coronary heart disease were patients
with recent onset coronary heart disease
whom were primarily referred for Coronary angiography,
those with stroke had a TIA or cerebral
infarction, those with PAD were symptomatic and

Ayman Sadek, et al
had documented obstruction of distal arteries of
the leg (Peripheral angiography or lower limb
arterial duplex).
The following patients were be excluded from the
whole study:
Previous neck or femoral irradiation, Previous
neck or femoral surgery, or any neck or lower limb
deformity interfering with carotid or femoral ultrasonography
respectively.
Methods:
Every patient was subjected to the following:
Proper history taking and examination:
Full history for the presence of cardiovascular
risk factors:
Smoking, Hypertension, Diabetes mellitus,
Dyslipidemia, Family history of ischemic heart
disease, Symptoms suggestive of coronary artery
diseases Peripheral vascular disease Cerebrovascular
strokes or transient ischemic attacks:
Complete general and local clinical examination
with stress on the following points:
Weight: Measured in kilograms.
Height: Measured in meters.
Body mass index = Weight in kilograms/(height
in meters) 2
Table 1: Criteria for clinical diagnosis of metabolic syndrome.
Measure
(any 3 of 5 constitute
diagnosis of metabolic
syndrome)
Elevated waist circumference*
Elevated triglycerides
Reduced HDL-C
Elevated blood pressure
Elevated fasting glucose
Categorical
Cutpoints
≥102 cm (≥40 inches) in
men ≥88 cm (≥35 inches)
in women
≥150 mg/dL (1.7
mmol/L)Or On drug
treatment for elevated
triglycerides
≤40 mg/dL (1.03 mmol/L)
in men≤50 mg/dL (1.3
mmol/L) in women
≥130 mm Hg systolic blood
pressure or ≥85 mm Hg
diastolic blood pressure
or On antihypertensive
drug treatment in a patient
with a history of
hypertension
≥100 mg/dL or On drug
treatment for elevated
glucose
41
Pulse: Radial, brachial with stress on pulse
pressure and dorsalis pedis arteries were examined
for rate, rhythm, volume, special character and
equality of pulsations.
Morning urine sample to measure microalbuminuria:
Using HemoCue Urine albumin operator
manuals instrument.
1- We open the package and carefully remove the
cuvette then we fill the cuvette by contact with
the urine sample (a urine drop on a hydrophilic
surface i.e a plastic film).
2- Open the lid and push the filled cuvette into the
cuvette holder.
3- Measuring should begin within 30 seconds after
the cuvette has been filled with urine.
4- Within 90 seconds the result will be displayed
in mg/dl.
12 lead surface ECG:
Echocardiography:
Echocardiography was done for measurement
of (LVEDD), (LVEDD, (EF), (LVPWT) and
(IVST).
And assessment of RSWMA.
Carotid and femoral arterial duplex:
All patients underwent ultrasonography of the
right and left carotid and femoral arteries where
the following measured:
1- Carotid intima-media thickness (IMT):
The characteristic B-scan pattern of the arterial
walls shows two parallel echogenic lines separated
by a relatively hypoechoic space "the double line
pattern". This pattern is found in the posterior wall
of the common carotid arteries; the inner line is
generally more regular, smooth and thin than the
outer one and represents the lumen intima interface.
The outer one is produced by the collagen containing
upper layer of tunica adventitia, close to the
media-adventitia interface.
The intima-media thickness (IMT) is measured
from the leading edge of the inner line to the
leading edge of the outer one [14].
An ultrasonographically determined increase
in IMT may be regarded as an indicator of generalized
atherosclerosis [15].
We measured the carotid IMT bilaterally by Bmode
ultrasonography (7-8MHz linear array, gen-

Metabolic Syndrome & its Impact on Vascular Damage Extent
eral electric vivid 5) in a linear segment of 10-
12mm length of common carotid artery. The carotid
IMT is measured as the distance between the bloodintima
and media-adventitia interfaces as previously
described by Pignoli et al. (1986)(16). In healthy
adults, IMT ranges from 0.25 to 1.5mm and values
>1.0mm are often regarded as abnormal [17].
2- Carotid plaques:
A plaque was defined as a localized intimal
thickening

Ayman Sadek, et al
with mean age of 51.2±9.21 years. There was no
significance difference between the three subgroups
as regard age and sex distribution (p>0.05). These
data are presented in Table (2).
I- Description and comparison between the
study groups:
1- Age and sex:
Fig. (1) demonstrates age and gender distribution
among the study.
14
12
10
8
6
4
2
0
Males
Females
Group I Group II Group III
Figure 1: Sex distribution in the three studied groups.
2- Risk factors:
Every patient was asked about risk factors of
atherosclerosis and special habits of medical importance
and it was found that 25% of group I,
41.7% among group II and 32% among group III
were smokers or ex-smokers, whereas, positive
family history of IHD, CVA or peripheral vascular
disease was found to be 8.3% among group I, 5.9%
among group II and 23% among group III. Past
history of HTN, DM or past history of dyslipidemia
by lipid profile and regular intake of hypolipidemic
drugs were considered among selection criteria for
metabolic syndrome. These data and distribution
of other metabolic risk factors are shown in Table
(2).
3- Clinical examination and laboratory investigations:
All patients underwent clinical examination,
where blood pressure, waist circumference in cm,
height in meters, body weight in kg were measured
and body mass index was calculated and LAB
evaluation of blood sugar and lipid profile. It was
found that systolic and diastolic blood pressures
were higher in group III, TG, female W.C, BMI
and FBS were highest in group II while HDL-C
was lowest in group III. Data are shown in Table
(3).
43
Table 2: Distribution of risk factors within the study groups.
Smoking
FH
HTN
DM
Dyslipidemia
(+ve
history)
No (%)
TG
(increased)
No (%)
HDL-C
(decreased)
W.C
(increased)
Table 3: Quantitative analysis of risk factors of the study
groups by using mean and SD.
Systolic BP
Diastolic BP
DUR of HTN
FBS
DUR of DM
TG
HDL-C:
Males
Females
W.C.:
Males
Females
BMI
Group I
(no=12)
3 (25%)
1 (8.3%)
10 (83.3%)
5 (41/7%)
1 (8.3%)
8 (66.7%)
10 (83.3%) 15 (88.2%) 21 (100%) 3.38
5 (41.7%)
Group I
(no=12)
Mean (SD)
135.83+
(20.54)
83.33+
(11.93)
2.83+
(3.49)
147.5+
(78.47)
2.67+
(4.47)
170.42+
(23.69)
37.26+
(5.6)
44.2+
(7.9)
106+
(9.41)
95.21+
(8.31)
28.68+
(3.12)
Group II
(no=17)
7 (41.7%)
1 (5.9%)
15 (88.2%)
8 (47.1%)
4 (23.5%)
17 (100%)
FH = Family history.
TG = Triglycerides.
HDL-C = High density
lipoprotein-cholesterol.
BP = Blood pressure.
FBS = Fang blood pressure.
TG = Triglycerides.
HDL-C = High density
lipoprotein cholesterol.
Group III
(no=21)
6 (32.0%)
5 (23.8%)
21 (100%)
8 (38.0%)
9 (42.9%)
21 (100%) 13.77 0.001
15 (88.2%) 21 (100%) 18.28 0.000
Group II
(no=17)
Mean (SD)
127.29+
(22.45)
81.17+
(9.44)
3.35+
(5.80)
152.47+
(64.59)
3.41+
(4.03)
191.35+
(13.49)
35.1
(6.91)
45.3+
(8.3)
108.36+
(12.31)
99.21+
(7.81)
31.83+
(3.65)
F
1.04
2.92
3.38
0.31
4.77
0.59
0.23
0.19
0.86
0.09
0.19
W.C = Waist circumference.
HTN = Hypertension.
DM = Diabetes mellitus.
Group III
(no=21)
Mean (SD)
150.0+
(9.49)
94.52+
(9.73)
6.47+
(5.42)
149.8+
(48.83)
2.33+
(3.75)
181.71+
(16.55)
33.3+
(6.72)
41.7+
(8.31)
112.38+
(11.45)
98.61+
(10.81)
31.31+
(4.17)
W.C = Waist circumference.
BMI = Body mass index.
DUR = Duration.
p

Metabolic Syndrome & its Impact on Vascular Damage Extent
4- Distribution of (IHD, PVD, CVA) within the
study groups:
It was found that 11 patients of group I, 13 of
group II and 21 of group III had IHD,2 patients of
group I, 8 group II and 12 of group III had CVA,
2 patients of group I, 3 of group II and 7 of group
III had PVD, these data are shown in Fig. (2).
25
20
15
10
5
0
IHD
CVA
PVD
Gr I Gr II Gr III
Figure 2: Distribution of IHD, PVD and CVA in the three
studied groups.
5- Echocardiography:
Echocardiography was done while the patient
in left lateral position. M-mode was used for detection
of left ventricular internal dimension measurements
in end diastolic (LVEDD) and end systolic
(LVEDD), ejection fraction (EF), left ventricle
posterior wall thickness (LVPW) and interventricular
septal thickness (IVS) were measured and
resting segmental wall motion abnormality was
assessed, these data are shown in Table (4).
Table 4: Comparing echocardiography parameters within the
study groups.
Increased
LV-IVS
thickness
Increased
LV-PWT
Diastolic
dysfunction
Resting
SWMA
Increased
LVEDD
Increased
LVESD
LV
IVS
PWT
SWMA
LVEDD
LVESD
Group I
(no=12)
7 (58.3%)
7 (58.3%)
10 (83.3%) 15 (88.2%) 20 (95.2%) 1.29 0.52
2 (16.7$)
0 (0.0%)
0
Group II
(no=17)
12 (70.6%) 18 (85.7%) 3.13 0.20
12 (70.6%) 18 (85.7%) 3.13 0.20
5 (29.4%)
2 (11.8%)
1 (5.9%)
= Left ventricle.
= Interventricular septum.
= Posterior wall thickness.
Group III
(no=21)
8 (38.1%)
7 (33.3%)
7 (33.3%)
= Segmental wall motion abnormality.
= Left ventricular end diastolic dimension.
= Left ventricular end systolic dimension.
F
p
1.67 0.43
6.42 0.04
8.27 0.016
44
6- Common Carotid and common femoral intima
media thickness (CIMT and FIMT):
All patients underwent carotid and femoral
ultra-sonography where the common carotid and
common femoral intima media thickness of both
sides were measured and it was found that there
is a significant difference in RCIMT, LCIMT and
LFIMT between the study groups (p0.05). These data are shown in Table
(5).
Table 5: Comparing R-CIMT, L-CIMT, R-FIMT and L-FIMT
within the study groups.
R-CIMT
L-CIMT
R-FIMT
L-FIMT
Group I
(no=12)
0.97+
(0.17)
0.97+
(0.19)
0.98+
(0.23)
0.90+
(0.23)
Group II
(no=17)
1.13+
(0.14)
1.12+
(0.12)
1.11+
(0.18)
1.1+
(0.09)
Group III
(no=21)
1.18+
(0.17)
1.19+
(0.19)
1.09+
(0.20)
1.08 +
(0.15)
R-CIMT = Right carotid intima-media thickness.
L- CIMT = Left carotid intima-media thickness.
R-FIMT = Right femoral intima-media thickness.
L-FIMT = Left femoral intima-media thickness.
6.87
6.74
2.60
6.5
7- Carotid plaques:
There were no pathological carotid plaques in
group (I). 29.4 % of group II had pathological
carotid plaques, whereas 57.1% of group III had
plaques (p0.05). These data are
shown in Table (6).
F
p
0.002
0.003
0.78
0.003
Table 6: Comparison between the study groups regarding
presence or absence of carotid and femoral plaques.
Positive
carotid
plaque
Positive
femoral
plaque
Group I
(no=12)
0 (0.0%)
3 (25.0%)
Group II
(no=17)
5 (29.4%)
4 (23.5%)
Group III
(no=21)
12 (57.1%)
8 (38.1%)
F
11.36
1.14
p
0.023
0.56

Ayman Sadek, et al
8- Micro albuminuria:
There was a significant difference between the
study groups and it was found to be 52.4% in group
III, 23.5% in group II and 8.3% in group I (p

Metabolic Syndrome & its Impact on Vascular Damage Extent
4- Common carotid and common femoral IMT:
There was a significant difference in L-CIMT,
carotid plaque and L-FIMT (p0.05) between patients with one, two
and three vascular beds affected, these data are
shown in Table (9).
Table 9: Relation between carotid and femoral IMT and
number of vascular beds affected in the form of
mean + SD.
R-CIMT
L-CIMT
R-FIMT
L-FIMT
One
(no=25)
1.072 +
(0.15)
1.06 +
(0.15)
1.06 +
(0.19)
0.90 +
(0.22)
Number of vascular beds affected
Two
(no=23)
1.13 +
(0.19)
1.15 +
(0.21)
1.13 +
(0.22)
1.09 +
(0.08)
Three
(no=2)
1.33 +
(0.21)
1.36 +
(0.28)
1.12 +
(0.17)
1.09 +
(0.15)
5- Microalbuminuria:
There was a significant difference in presence
of microalbuminuria between patients with one,
two and three vascular beds affected, these data
are shown in Table (11).
F
2.47
3.36
0.53
6.5
p
0.09
0.043
0.59
0.003
Table 10: Relation of carotid and femoral plaques to number
of vascular beds affected.
Positive
carotid
plaque
Positive
femoral
plaque
One
(no=25)
4 +
(16.0%)
4 +
(16.0%)
Number of vascular beds affected
Two
(no=23)
11 +
(47.8%)
10 +
(43.5%)
Three
(no=2)
2 +
(100%)
1 +
(50.0%)
F
9.84
4.7
p
0.043
0.095
Table 11: Relation of microalbuminuria to number of vascular
beds affected.
Positive
Microalbuminuria
One
(no=25)
2 (8.0%)
Number of vascular beds affected
Two
(no=23)
12 (52.2%)
Three
(no=2)
2 (100%)
F p
15.16
0.001
46
Case number 11 Group II:
Left carotid duplex:
Figure 5: Show increased left carotid IMT (1.28mm) in female
patient aged 55 with recent MI.
Right carotid duplex:
Figure 6: Show increased right carotid IMT (1.29mm) in
female patient aged 55 with recent MI.
Left femoral duplex:
Figure 7: Show increased left femoral IMT (1.46mm) and
femoral plaque in female patient aged 55 with
recent MI.

Ayman Sadek, et al
Discussion
Although the metabolic syndrome unequivocally
predisposes to type 2 diabetes mellitus. Many
investigators of cardiovascular diseases consider
this syndrome to be a multidimensional risk factor
for ASCVD [21,22].
Measurements of IMT are used in pathophysiological
studies of the atherosclerotic process, e.g.
in studies of the factors regulating the early development
of atherosclerosis in the carotid and femoral
arteries. An increase IMT is also used as a marker
of generalized atherosclerosis including coronary
atherosclerosis and carotid artery IMT has also
been shown to be associated with coronary atherosclerosis
as measured by coronary angiography in
several studies [23].
The appearance of trace amounts of albumin
(micro-albuminuria, 30 to 300mg/d) and larger
amounts (frank proteinuria, ≥1g/d) are associated
with an increased risk for renal failure, heart disease,
stroke and cardiovascular mortality [6,8,10,24].
The introduction of digital techniques for creating
continuous loops, split-screen and quad screen
presentations enhanced the utility of echocardiography
for assessment of asymptomatic individuals
[25].
I- Relation of number of single components of
metabolic syndrome and echocardiography:
In this study it was found that there is non
significant difference with increase in the number
of metabolic components as regard presence of
DD and LVH in the form of increased LVPWT and
IVST (p>0.05) this may be due to small number
of the study population however the LVEDD and
LVESD showed significant difference (p

Metabolic Syndrome & its Impact on Vascular Damage Extent
of the metabolic syndrome is associated with an
increase in mean CIMT, Patients who had all five
criteria constituting the metabolic syndrome had
the largest IMT (1.07mm) compared to patients
with less than five components this was supported
by the study of Wendy et al, which was done to
investigate the association of metabolic syndrome
with sub-clinical atherosclerosis in young adults
with metabolic syndrome according to NCEP and
WHO criteria and was conducted on 507 non diabetic
subjects and found that increasing numbers
of metabolic syndrome components were directly
associated with higher composite CIMT (p

Ayman Sadek, et al
cantly across categories (14.3, 18.2, 31.6, 34.1,
32.6%, respectively; p

Metabolic Syndrome & its Impact on Vascular Damage Extent
proper conditions, carotid IMT could be used to
identify person at higher risk than that revealed
by the major risk factors alone [1].
VI- Relation between microalbuminuria and extent
of vasculopathy:
In the present study it was found that there is
a significant difference (p=0.001) in the presence
of micro-albuminuria and extent of vasculopathy
in the form of number of vascular beds affected.
The Monitoring Trends and Determinants of
Cardiovascular Diseases (MONICA) study investigators
established in 2782 Danish participants
that albuminuria was a potent predictor for the
development of ischemic heart disease, independent
of other traditional risk factors such as male gender,
hypertension, lipids, advancing age and obesity
[10].
Miettinen et al (1996) found an association
between amount of urinary protein excretion and
risk of stroke and lower extremity amputation in
a cohort of subjects that was independent of diabetes
status and traditional risk factors [8].
Assessment of microalbuminuria in the first
week after a myocardial infarction was a strong
predictor for 1-year mortality [40].
In the PREVEND Study the presence of microalbuminuria
in patients with ST-T segment abnormalities
on a resting ECG conferred an increased
(cardiovascular) mortality risk [41].
VII- Study limitations:
It included a single medical center (Ain Shams
University hospitals) with few patients referred
from other centers all-over Egypt.
The method of selecting patients included in
the study does not ensure proper randomization.
Limitations of duplex scanning: A number of
technical difficulties remain to be overcome in
vascular ultrasound technology. The methodology
is extremely operator and machine dependent and
images can be varied by changing the gain settings
on the machine. Tortuous and deep vessels may
be difficult to visualize accurately. It is unable to
penetrate areas of heavy calcification. This limits
the effectiveness of vascular ultrasound in advanced
lesions that are often heavily calcified.
50
Conclusions
From the present sudy, the followings are concluded:
Metabolic syndrome is a constellation of risk
factors for atherosclerosis and the increase in traits
of metabolic syndrome is associated with increase
in extent of vascular damage (CHD-CVA-PVD).
The increase in number of metabolic syndrome
traits is associated with increase in LV dimensions.
The increase in number of metabolic syndrome
traits is associated with increase in carotid and
femoral IMT and microalbuminurea.
The presence of thickened carotid and femoral
IM and presence of carotid plaque is associated
with significant increase in extent of vascular
damage.
The presence of microalbuminurea is associated
with significant increase in extent of vascular
damage.
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34- Linhart, Ales, Gariepy, Jerome, Massonneau, Mare, et al:
Carotid intima-media thickness: The ultimate surrogate
end-point of cardiovascular involvement in atherosclerosis.
Applied radiology (March) 2000; S.25-39.
35- Barth J, Encino CA: IMT plaque tissue typing and its
relationship to myocardial infarcion. Identifying subclinical
atherosclerotic disease: An evaluation of emerging
techniques. International task force for prevention of
coronary heart disease, task force Symposium Scuol 2003;
February 23.

Metabolic Syndrome & its Impact on Vascular Damage Extent
36- Hollander M, Bots ML, Del Sol AI, et al: Carotid plaques
increase the risk of stroke and subtypes of cerebral infarction
in asymptomatic elderly: The Rotterdam Study.
Circulation 2002; 105: 2872-2877.
37- Chen TT: Essentials of cardiac roentgenology. Boston,
Little Brown, 1987. In heart disease, edited by Eugen
Braunwald et al, Vol. 1. W.B. Saunders 1992.
38- Madis Suurkula, et al: Atherosclerotic disease in the
femoral artery in hypertensive patients at high cardiovascular
risks; arteriosclerosis. Thrombosis and Vascular
Biology 1996; 16: 971.
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39-Antonio Iglesias del Sol, MD, Karel GM Moons, MD,
PhD, et al: Is Carotid Intima-Media Thickness Useful in
Cardiovascular Disease Risk Assessment? The Rotterdam
Study. Stroke 2001; 32: 1532.
40- Berton G, Cordiano R, Palmieri R, et al: Micro-albuminuria
during acute myocardial infarction; a strong predictor for
1-year mortality. Eur Heart J 2001; 22 (16): 1466-75.
41- Diercks GF, Hillege HL, van Boven AJ, et al: Microalbuminuria
modifies the mortality risk associated with
electrocardiographic ST-T segment changes. J Am Coll
Cardiol 2002; 40 (8): 1401.

Egypt Heart J 62 (1): 53-61, March 2010
Cardiovascular Risk Factors in Patients with End Stage Renal Failure
on Regular Hemodialysis
YASER AA EL-HENDY, MD; MOHAMED ABDOU, MD*
Aim of the Work: To investigate the relation between both fibrinogen, C-reactive protein (CRP), homocysteine (Hcy),
lipoprotein a (Lpa), as a non traditional cardiovascular (CV) risk factors, plasma lipids, hypertension, smoking and the occurrence
and severity of ischemic heart disease (IHD) in patients with end stage renal failure (ESRF) on regular hemodialysis (HD) and
weather diabetic patients are a high risk than non diabetic.
Patients and Methods: 50 ESRF patients on regular HD divided into 3 groups: Group 1 included 10 patients free from IHD
as control.Group II: Included 20 non-diabetic patients. Group III: Included 20 type 2 diabetic patients. Both group II, III suffer
from IHD. All patients were subjected to full history, clinical examination, routine investigations, evaluation of fibrinogen,
quantitative CRP, serum Hcy, Lp(a), HDL, LDL cholesterol, triglycerides. 12-leads surface ECG, resting and dobutamine stress
echocardiography (DSE) were also done.
Results: Plasma fibrinogen was significantly higher in group III compared to both group I, II and in group II compared to
group I (F=20.3, p

Cardiovascular Risk Factors in Patients with End Stage Renal Failure
This study aimed to detect the relationship
between cardiovascular risk factors as fibrinogen,
CRP, homocysteine, Lp(a), lipid profile, blood
sugar, hypertension, smoking and occurrence and
severity of ischemic heart disease in uraemic patients
and whether diabetic patients on regular
hemodialysis are at high risk of ischemic heart
disease than non diabetic.
Patients and Methods
This study included 50 chronic renal failure
patients on regular hemodialysis 12 hours per week
divided into 3 sessions for variable periods of time
from 3 years to 15 years using filter of polysulfone
membrane with effective surface area 1.3m 2 during
the study.
They were divided into 3 groups:
Control group (Group 1):
Comprises 10 subjects (5 females and 5 males)
with their ages ranged from 30 to 64 years. They
were free from ischemic heart disease diagnosed
by history, clinical examination, 12-leads surface
ECG, resting echocardiography and dobutamine
stress echocardiography.
Ischemic heart disease group:
This include a total number of 40 patients with
chronic renal failure of variable etiologies complaining
of recurrent chest pain proved to be of
cardiac origin by character of pain clinically, 12leads
surface ECG, resting echocardiography and
dobutamine stress echocardiography.
The patient group was classified according to
the presence or absence of diabetes mellitus
into:
Non-diabetic patients (Group II):
Include 20 subjects with chronic renal failure
(14 males and 6 females) with ages ranged from
40 to 65 years.
Diabetic patients (Group III):
Include 20 subjects with chronic renal failure
(12 males and 8 females), with ages ranged from
40 to 65 years. They were type 2 diabetes mellitus
as diabetes started late in age, they were diagnosed
by history, fasting and two hours post-prandial
blood glucose level and glycosylated hemoglobin;
4 of them were on oral hypoglycemic and 9 on
insulin therapy and 7 patients did not need treatment.
54
Methods:
All patients were subjected to the followings:
1- Thorough history and clinical examination:
Assessment of mean arterial pressure:
Mean arterial pressure =
Systolic blood pressure + 2 (diastolic blood pressure)
–––––––––––––––––––––––––––––––––––––––––––––
3
2- 12-Leads surface ECG.
3- Routine laboratory investigations: Blood urea
nitrogen, serum creatinine, serum albumin,
complete blood picture, fasting blood sugar,
serum calcium and phosphorous.
4- Special laboratory investigations: Blood samples
were collected from all 12-hours fasting
subjects and before starting the dialysis session;
plasma and serum samples were collected for
estimation of:
• Serum total homocysteine with Chemiluminescent
method using Immulite competitive
Immunoassay (DPC, New York, USA).
• Quantitative Lipoprotein (Lpa) and C-reactive
protein (CRP) determination with latex turbidimetry,
Spinreact, S.A., Spain.
• Total cholesterol, LDL cholesterol, HDL cholesterol,
triglycerides.
• Quantitative determination of fibrinogen in
plasma by modification of the Clauss method.
5- Resting echocardiography: The following data
were assessed in each study:
A- Measurement of LV dimensions and LV volumes:
M-mode was used to measure septal (IVS) and
posterior wall thickness (PWT) in diastole as well
as LV end systolic diameter (LVSd) and LV end
diastolic diameter (LVDd). We used the most commonly
used algorithm to calculate LV volumes
(Modified Simpson rule) which derives measurements
by dividing the LV by parallel planes into
a number of small segments (usually referred as
disks) and summating the area of the individual
disks. The approach has the advantage of making
no assumption about the geometry of the left ventricle.
B- Assessment of left ventricular regional systolic
function as follow (Fig. 1):
The left ventricular wall was divided into 16
segments according to the recommendations of the
American Society of Echocardiography to evaluate

Yaser AA El-Hendy & Mohamed Abdou
regional LV function. The septal, lateral, anterior
and inferior walls of the left ventricle were divided
into basal, mid and apical thirds from apical 4chambers
and apical 2-chambers views. The posterior
and anteroseptal walls were divided into
basal and mid segments only from the parasternal
long axis view [6].
Long-Axis
Anteroseptal
Mid Base
Mid
Base
Posterior
LAD
LAD (PROX)
A4C
Short-Axis
LAX
A2C
Four Chamber Two Chamber
Apex
Septal
Apex
Lateral
Mid
Apex
Apex Anterior
Mid
Base
Base
Mid
Base
Base
LCX
RCA
Figure 1: Shows 16-segments model of the left ventricle and
its related blood supply.
Wall motion for each segment was visually
graded using both endocardial motion and wall
thickness with a semiquantitative four-points scoring
system as follow:
Normal or hyperkinesis=1, hypokinetic, marked
reduction of endocardial motion or thickening=2,
a kinetic, absence of inward motion and thickening=
3, dyskinetic, paradoxic wall motion away from
the center of the left ventricle in systole=4.
The sum of these individual segmental scores
is divided by the total number of the interpretable
16 segments to obtain the total wall motion score
index.
6- Dobutamine Stress Echocardiography (DSE):
• All studies were performed on a Hewlett-Packard
Sonos 5500 ultrasound system equipped with a
2.5-MHz transducer and were recorded on halfinch
VHS tape.
55
The patients were instructed about the test (how
to perform, risk and benefits of the test) and a
written consent was taken.
β-blockers and rate slowing calcium channel
blockers were withdrawn 48-hours before performing
the test.
Blood pressure was recorded at the start of the
test and at the end of each stage with continuous
ECG monitoring all through the test.
After the test the patient was observed for 15
min with continuous ECG monitoring.
Echocardiographic protocol:
• DSE was performed using a standard protocol.
First, a resting echocardiogram was performed
with the patient lying in left lateral recumbent
position.
• Echocardiographic imaging was then performed
during the intravenous infusion of dobutamine
starting at a dose of 5μg/kg per minute, which
was increased every 3 minutes to 10 (Low dose),
20 (Intermediate dose), 30 and then 40μg/kg per
minutes (High Dose).
• Images were obtained from the standard parasternal
long-axis and short-axis views as well as the
apical four- and two-chamber views.
DSE images were arranged in quad screen,
continuous loop display, so that the baseline, low
dose, peak dose and recovery images of each of
the four standard views were displayed simultaneously
for analysis [7]. The test was terminated
prematurely if there was significant new wall
motion abnormalities, significant ST segment depression
or elevation, severe angina pectoris, significant
reduction or elevation in blood pressure,
significant tachyarrhythmia [8].
Propranolol IV (1-3mg) and/or sublingual nitrate
was given if there was side effects.
All studies were read by 2 experienced investigators,
unaware to clinical information. A wall
motion score was assigned to each of the 16 segments
at every stage of the test.
Results
The results shown in the following Figs. (2-9)
and Tables (1-5).

Cardiovascular Risk Factors in Patients with End Stage Renal Failure
mg/dl
400
350
300
250
200
150
100
50
0
Fibrinogen FBG
Groups
Figure 2: Mean values of plasma fibrinogen and fasting blood
glucose between the 3 studied groups.
Fibrenogen (mg/dl)
0
1 1.1 1.2 1.3
WMSI
1.4 1.5 1.6 1.7
Figure 4: Correlation between WMSI and plasma fibrinogen
in group II + III.
Serum tHCY (μmol/l)
600
500
400
300
200
100
80
70
60
50
40
30
20
10
r=0.520, p=0.001
r=0.320, p=0.04
0
1 1.1 1.2 1.3
WMSI
1.4 1.5 1.6 1.7
Figure 6: Correlation between WMSI and serum total Hcy
in group II + III.
I
II
III
56
mg/dl
200
180
160
140
120
100
80
60
40
20
0
S.
cholesterol S.HDL
S.TG S.LDL S.Lp(a)
Groups
Figure 3: Mean values of lipid parameters between the 3
studied groups. Application of LSD for comparison
in between groups revealed non-significant differences
in all studied lipid parameters in group II
compared to group III, but ANOVA test revealed
significant difference between the three-studied
groups.
CRP (mg/dl)
120
100
80
60
40
20
0
1 1.1 1.2 1.3 1.4 1.5 1.6 1.7
WMSI
Figure 5: Correlation between WMSI and serum CRP in
group II.
Lp(a) (md/dl)
80
70
60
50
40
30
20
10
r=0.695, p=0.001
r=0.539, p=0.014
0
1 1.05 1.1 1.15 1.2 1.25 1.3 1.35 1.4
WMSI
Figure 7: Correlation between WMSI and Lp(a) in group III.
I
II
III

Yaser AA El-Hendy & Mohamed Abdou
Duration of DM/years
25
20
15
10
5
r=0.585, p=0.007
0
1 1.05 1.1 1.15 1.2
WMSI
1.25 1.3 1.35 1.4
Figure 8: Correlation between WMSI and duration of DM in
group III.
57
Figure 9: Factorial analysis for cardiovascular risk factors in
hemodialysis patients.
Table 1: Comparison of mean values ± SD of some studied parameters between the
three groups of the study.
Sex:
Male
Female
Age:
± SD
Range (years)
MAP:
± SD X
Range (mmHg)
Smoking:
± SD X
Range (Cigarette/day)
Median
5
5
I
N=10
48.7±10.8
30-64
93.8±13.8
73-123
0.8±2.5
0-8
0.0
50
50
14
6
II
N=20
70
30
52.95±7.5
40-65
111.1±16.4
83-140
12.1±20.8
0-90
2
12
8
III
N=20
54.1±7.4
40-65
110.1±15.8
83-150
13.1±18
0-60
10
60
40
1.19
F
X 2
1.46
4.58
K
7.48
p
0.55
0.23
0.014
Table 2: Comparison of mean Values ± SD of some studied laboratory parameters
between the three groups of the study.
CRP:
± SD X
Range (mg/l)
Fibrinogen:
± SD X
Range (mg/dl)
Homocysteine:
± SD X
Range (mmol/l)
FBG:
± SD X
Range (mg/dl)
S.Lp (a):
± SD X
Range (mg/dl)
I
N=10
7.8±7.2
3-26
249.3±63.9
180-398
16.9±6.6
6-28
85.8±8.4
75-100
27.6±4.7
22-36
II
N=20
39.7±28
5-96
337.4±44.4
245-410
34±13.3
15-72
86.9±10.1
70-105
48.6±6.9
40-65
Lp(a)
18.97
III
N=20
22.15±22.1
3-96
377.8±52.9
273-484
35±10.8
20-61
130.5±36.4
70-180
49.75±8.1
41-72
Dyslipidemia
11.58
Fibrinogen
20.014
F
19.57
20. 3
9.72
19.2
6.9
0.02
p
0.001
0.001
0.001
0.001
0.001
FBG
49.436

Cardiovascular Risk Factors in Patients with End Stage Renal Failure
Table 4: Comparison of mean values ± SD in dobutamine
stress echocardiography between the three studied
groups.
WMAS:
± SD X
Range
WMS:
± SD X
Range
WMS1:
± SD X
Range
I N=10
0
16±0.0
1±0.0
II N=20
4.15±1.66
2-7
20.6±2.1
18-25
1.28±0.13
1.11-1.6
WMAS : Wall motion abnormal segments.
WMS : Wall motion score.
WMSI : Wall motion score index.
Table 3: Comparison of mean values ± SD in resting echocardiography between the
three studied groups.
IVS:
± SD X
Range (mm)
LVPW:
± SD X
Range (mm)
LVDd:
± SD X
Range (mm)
LVSd:
± SD X
Range (mm)
F.S:
± SD X
Range (%)
Discussion
III N=20
3.65±1.26
1-6
19.8±1.3
17-22
1.23±0.08
1.06-1.37
I
N=10
10.1±1.97
8-14
10.2±2.1
6-13
50.8±6.1
38-58
29.5±4.4
20-36
41.3±4.8
35-48
1.6
28.8
27.4
The traditional coronary risk factors are older
age, diabetes, male gender, family history of coronary
disease, hypertension, elevated LDL-C decreased
HDL-C, history of smoking, physical inactivity,
menopause and psychosocial stress. But
uraemia-related risk factors are other cardiovascular
disease (CVD) risk factors that increase in prevalence
or severity as renal function declines. These
include, among others, albuminuria or proteinuria,
extracellular fluid volume overload, electrolyte
F
p
0.29
0.001
0.001
II
N=20
12.3±2
8-18
12.25±2.1
9-17
52.7±10.2
32-76
31.2±7.96
17-46
41.2±7.2
31-53
IVS : Interventricular septal thickness.
LVPW:
Left ventricular posterior wall thickness.
LVDd : Left ventricular diastolic diameter.
58
Table 5: Multiple regression analysis for cardiovascular risk
factors in hemodialysis patients.
Dyslipidemia
Fibrinogen
t Hcy
Lp(a)
CRP
FBG
III
N=20
11.3±1.3
8-13
10.95±1.96
9-17
52.6±7.2
46-76
31.75±7.5
22-46
39.3±9.3
28-55
β ± SE
4.2±0.002
4.54±0.001
4.52±0.006
2.22±0.008
1.63±0.003
7.4±0.002
F
5.2
3.86
0.19
0.33
0.36
2.19
3.26
0.746
2.76
0.49
3.527
0.034
0.002
0.46
0.008
0.62
0.001
95% CI
0.0-0.008
0.002-0.007
0.008-0.017
0.006-0.039
0.005-0.008
0.003-0.012
• It shows that fasting blood glucose, fibrinogen, Lpa and dyslipidemia
are independent cardiovascular risk factors in CRF patients on
hemodialysis treatment.
imbalance, hypertriglyceridemia, elevated Lp (a),
hyperhomocysteinaemia, markers of inflammation
or infection; CRP, increased oxidant stress, thrombogenic
factors, malnutrition, anaemia and other
uraemic toxins [9].
Hypertension appeared as a major risk factor
for occurrence of ischemic heart disease as there
was significant increase in the mean arterial blood
pressure in both group II and III compared to the
control group. This was in consistent with Takeda
et al (2004) [10] who found that hypertension is a
t
p
0.009
0.02
0.82
0.72
0.7
LVSd:
Left ventricular systolic diameter.
FS : Fractional shortening.
p
S
S
NS
S
NS
S

Yaser AA El-Hendy & Mohamed Abdou
potent risk factor for cardiovascular disease in
hemodialysis patients, as in the general population,
whereas there is no association of hypertension
with mortality. Conversely, a low incidence of CV
death has been noted in dialysis patients with
optimal blood pressure control [11].
The obtained significant association between
cigarette smoking and ischemic heart disease in
group II and group III compared to control group
obviate the role of smoking in susceptibility to
IHD as smoking may be especially atherogenic in
uraemic patients because it enhances free radical
generation and subsequent lipid peroxidation [12],
which is already increased in uraemic patients [13].
There was significant increase in serum LDLcholesterol
with significant decrease HDLcholesterol
level in group II and group III in comparison
to the control group. This result is in
agreement with findings of Avram et al (1992) [14].
Dyslipidemia, was an independent risk factor
in multiple regression analysis for ischemic heart
disease in hemodialysis patients in the present
work.
In uremia, the catabolism of Lp(a) is diminished
[15]. The highly significant increase in serum Lp(a)
in group II, III compared to the control group may
be due to decreased excretion of apolipoprotein(a)
degradation products in patients with CRF as well
as inflammation and the phenotype difference of
apolipoprotein(a) in the studied group. In our study
Lp(a) concentration was an independent risk factor
for ischemic heart disease in hemodialysis patients
in multiple regression analysis and a significant
positive correlation between wall motion score
index and Lp(a) was present in group III. This was
in agreement with findings of Longenecker et al
(2004) [16] who found that both high Lp(a) concentration
and low molecular weight (LMW) Apoa
isoforms predicted atherosclerotic cardiovascular
disease events in dialysis patients.
The obtained significant increase in plasma
fibrinogen level and in IHD patients on hemodialysis
in group II and group III compared to
control group could be partially related to inflammation
as hemodialysis acts as a repeated stimulus
for an inflammatory response. This was in agreement
with findings of Zoccali et al (2003) [17] who
found that fibrinogen is an independent risk factor
for overall and cardiovascular mortality in patients
with ESRD. Hyperfibrinogenaemia revealed a
59
strong independent atherogenic risk factor in
hemodialysis patients, as already observed in the
general population [18].
An increased plasma fibrinogen level has been
consistently reported in dialysis patients in association
with evidence of endothetial dysfunction
characterized by concomitant high plasma concentrations
of proconvertin and type 1 plasminogen
activator inhibitor, (PAI-1); all factors that contribute
to the initial steps of atherogenesis [19]. Fibrinogen
and PAI-1 are acute phase proteins which
rise in response to various stimuli including cytokines,
especially IL-1 and TNFα, which indeed are
released following monocyte activation, a process
which has recently be shown to be part of the
uraemia-associated immune dysregulation [20]. The
obtained elevation of plasma fibrinogen level was
an independent risk factor for ischemic heart disease
in hemodialysis patients in multiple regression
analysis and a significant positive correlation
between wall motion score index and plasma fibrinogen
was present in all ischemic patients (group
II, III).
In 2003 Lee BJ et al [21] demonstrated that
hyperhomocysteinemia is a prominent risk factor
of atherosclerotic cardiovascular accidents. The
elevated serum Hcy in ischemic patients (group
II, III) could be due to accumulation of uraemic
toxins that lead to impairment in the enzymes of
Hcy metabolism. These results go in harmony with
the results obtained by Chauveau et al (1993) [22]
who realized an increased serum total Hcy level
in non-dialysed and in dialysis CRF patients and
a relationship between elevated plasma homocysteine
concentration and occurrence of atherosclerotic
cardiovascular accidents was evidenced in
dialysis patients [23]. In the present study a significant
positive correlation between WMSI and serum
total Hcy was present in all ischemic patients
(group II, III).
Buccianti et al (2004) [24] found that Hcy is a
strong independent mortality predictor in HD patients
with a 3% increase in mortality for each
1μmol/L increase in plasma Hcy concentration.
The significant increase in serum CRP in
hemodialysis patients with cardiac ischemia in
group II and group III compared to control group
could be related to inflammation as hemodialysis
acts as a repeated stimulus for an inflammatory
response. This was in agreement with Zimmermann
et al (1999) [25] who found that a considerable

Cardiovascular Risk Factors in Patients with End Stage Renal Failure
number of hemodialysis patients exhibit an activated
acute phase response (CRP), which is closely
related to high levels of atherogenic vascular risk
factors and cardiovascular death.
Genetic factors may significantly influence the
immune response, the levels of inflammatory markers,
as well as the prevalence of vascular calcification
in this patient group [26].
The prognostic value of serum CRP on the
occurrence of myocardial infarction, sudden death,
and stroke has been reported in the general population
[27]. Consequently, CRP is a possible predictor
of death in dialysis patients [28].
The significant positive correlation between
WMSI and serum CRP in group II clarify its role
in the development of myocardial ischemia.
Foley et al (1997) [29], found that diabetic
dialysis patients had higher rates of do novo
ischemic heart disease, overall mortality and cardiovascular
mortality than non-diabetic dialysis
patients. The 2-3 fold increase in CVD risk (attributable
to diabetes) multiplied by the risk associated
with ESRD results in an increased CVD risk of
around 50-fold in patients with ESRF caused by
diabetic nephropathy [30]. In the present study,
there was significant increase in fasting blood
glucose level in diabetic ischemic heart disease
patients on hemodialysis compared to the control
group. Blood glucose level was an independent
risk factor for ischemic heart disease in
hemodialysis patients in multiple regression analysis
and a significant positive correlation between
WMSI and the duration of diabetes was present
in group III.
The significant increase in inter-ventricular
septum dimension in hemodialysis patients with
cardiac ischemia (group II, III) compared to the
control group and in left ventricular posterior wall
dimension in group II compared to the control
group may be due to uncontrolled hypertension.
On the other hand left ventricular hypertrophy
(LVH) predisposes to ischemic symptoms by reducing
coronary reserve as reported by Yasuda et
al [31].
There was non significant difference in left
ventricular end systolic and end diastolic dimensions
in hemodialysis patients with cardiac ischemia
compared to the control group.
Lastly, factorial analysis for CV risk factors in
60
hemodialysis patients concluded that diabetes
mellitus was the most important cardiovascular
risk factor for occurrence of cardiac ischemia in
hemodialysis patients, fibrinogen is the second
one, Lp(a) is the third and dyslipidemia is the
fourth one risk factor for occurrence of cardiac
ischaemia in haemodialysis patients.
In conclusion, a considerable number of traditional
and non traditional risk factors for CV ischemia
may be present in hemodialysis patients;
usually one patient can be affected simultaneously
by several risk factors leading to poor long term
survival. Uncontrolled DM, elevated plasma fibrinogen,
Lp(a), dyslipidemia are the most risk factors.
So it can be recommended that early evaluation
and management of the specific cardiovascular
risk profile of each patient with ESRF may improve
long term survival.
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Yaser AA El-Hendy & Mohamed Abdou
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antioxidants, lipid peroxidation, and coronary heart disease.
Ann N Y Acad Sci 1993; 686: 120.
13- Maggi E, Bellazzi R, Falaschi F, et al: Enhanced LDL
oxidation in uraemic patients: An additional mechanism
for accelerated atherosclerosis? Kidney Int 1994; 45: 876.
14- Avram MM, Goldwasser P, Burrell DE, et al: The uraemic
dyslipidemia: A cross-sectional and longitudinal study.
Am J Kidney Dis 1992; 20: 324.
15- Frischmann ME, Kronenberg F, Trenkwalder E, et al: In
vivo turnover study demonstrates diminished clearance
of lipoprotein(a) in hemodialysis patients. Kidney Int
2007; 71: 1036-1043.
16- Longenecker JC, Klag MJ, Marcovina SM, et al: High
lipoprotein(a) levels and small apolipoprotein(a) size
prospectively predict cardiovascular events in dialysis
patients. J Am Soc Nephrol 2004; 16 (6): 1539.
17- Zoccali C, Mallamaci F, TripepI G, et al: Fibrinogen,
mortality and incident cardiovascular complications in
end-stage renal failure. Journal of Internal Medicine 2003;
254: 132.
18- Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, et al:
Fibrinogen as a risk factor for stroke and myocardial
infarction. N Engl J Med 1984; 311: 501.
19- Tomura S, Nakamura Y, Doi M, et al: Fibrinogen, coagulation
factor VII, tissue plasminogen activator, plasminogen
activator inhibitor-1 and lipid as cardiovascular risk
factors in chronic haemodialysis and continuous ambulatory
peritoneal dialysis patients. Am J Kidney Dis 1996;
27: 848.
20- Descamps-Latscha B, Herbelin A, Nguyen AT, et al:
Balance between IL-1 beta, TNF-alpha and their specific
inhibitors in chronic renal failure and maintenance dialysis.
Relationships with activation markers of T cells, B cells
and monocytes. J Immunol 1995; 154: 882.
61
21- Lee BJ, Lin PT, Liaw YP, et al: Homocysteine and risk
of coronary artery disease. Nutrition 2003; 19: 577-83.
22- Chauveau P, Chadefaux B, Coudé M, et al: Hyperhomocysteinemia,
a risk factor for atherosclerosis in chronic
uraemic patients. Kidney Int 1993; 43 (Suppl 41): S72.
23- Bostom AG, Shemin D, Verhouf P, et al: Elevated fasting
total plasma homocysteine levels and cardiovascular
disease outcomes in maintenance dialysis patients. Arterioscler
Thromb Vasc Biol 1997; 17: 2554.
24- Buccianti G, Baragetti I, Bamonti F, et al: Plasma homocysteine
levels and cardiovascular mortality in patients
with end-stage renal disease. J Nephrol 2004; 17: 405.
25- Zimmermann J, Herrlinger S, Pruy A, et al: Inflammation
enhances cardiovascular risk and mortality in haemodialysis
patients. Kidney Int 1999; 55: 648.
26- Stenvinkel P, Pecoits-Filho R, Lindholm B: For the
DialGene Consortium: Gene polymorphism association
studies in dialysis: The nutrition-inflammation axis. Semin
Dial 2005; 18: 322-330.
27- Ridker PM, Glynn RJ, Henneken CH: C-reactive protein
adds to the predictive value of total and HDL cholesterol
in determining risk of first myocardial infarction. Circulation
1998; 97: 2007.
28- Bergstrom J, Heimburger O, Lindholm B, et al: Elevated
serum C-reactive protein is a strong predictor of increased
mortality and low serum albumin in haemodialysis (HD)
patients. J Am Soc Nephrol 1995; 6: 573.
29- Foley RN, Culleton BF, Parfrey PS, et al: Cardiac disease
in diabetic end-stage renal disease. Diabetologia 1997;
40: 1307.
30- Jardine AG, McLaughlin K: Cardiovascular complication
of renal disease. Heart 2001; 86: 459.
31- Yasuda K, Kasuga H, Aoyama T, et al: Comparison of
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the Treatment of Coronary Artery Disease in Hemodialysis
Patients J Am Soc Nephrol 2006; 17: 2322-2332.

Egypt Heart J 62 (1): 63-68, March 2010
White Coat Hypertension and Target Organ Damage
HAMZA KABIL, MD; METWALLY EL-EMARY, MD; AHMED ABDEL-MONEIM, MD;
ABDEL-RAHMAN SAMRA, MBCh
Introduction: Twenty-four hour non-invasive ambulatory blood pressure monitoring (ABPM) has evolved as a research
tool of limited clinical use into an important tool for stratifying cardiovascular risk and guiding therapeutic decisions. Its clinical
use focuses on identifying patients with white coat hypertension (WCH), but accumulated evidence now points to greater
prognostic significance in detecting risk for target organ damage compared with that of office blood pressure measurement.
Aim: This study is planned to evaluate the impact of WCH on the target organs in order to determine if this type of
hypertension is really a benign condition or not.
Patients and Methods: This study was conducted in the Cardiology department in Benha University Hospitals. It included
20 patients with white coat hypertension diagnosed by both office and ambulatory blood pressure measurements, and another
20 patients with known sustained hypertension with blood pressure ≥140/90mmHg and not receiving any medical treatment.
All patients underwent a history-taking, clinical examination taking into consideration office and home blood pressure
measurement, ambulatory blood pressure monitoring for 24 hours, a 12-lead electrocardiogram, echocardiography, and laboratory
investigations.
Results: When taking the demographic data of the patients into consideration, the two groups were equally matched, with
a significantly lower age prevalent in those with WCH (37±13.3 years Vs. 52.1±8.4, p

White Coat Hypertension & Target Organ Damage
2- At least two measurements outside the physicians
office with blood pressure lower than 140/
90mmHg.
3- Daytime ambulatory blood pressure lower than
135/85mmHg (Verdecchia et al, 2003).
Patients with white-coat hypertension may
receive an incorrect diagnosis of sustained hypertension,
this phenomenon has been reported in as
many as 15-30% of patients labeled and treated as
hypertensives, nearly one in every five patients,
may receive antihypertensive drugs inappropriately
(Pickering et al, 1988).
Patients and Methods
This study was conducted in the Cardiology
Department in Benha University Hospital included
20 patient with White Coat hypertension diagnosed
by both clinic and ambulatory blood pressure
measurements. This group was compared with
sustained hypertension (SH) group which included
20 patients diagnosed as having S.H. equal or
above 140/90mmHg and have not received any
antihypertensive treatment before.
All patients underwent: Full history-taking,
thorough clinical examination with stress on office
and home Blood pressure measurements, ambulatory
Blood Pressure Monitoring using a non invasive
recorder (SCHILIER Blood Pressure Recorder
BR-102) for consecutive 24-h, resting 12-lead
electrocardiogram (ECG), microalbuminuria and
echo-doppler study.
Results
The present study included a group of 40 patients
who presented to our out patient clinics of
Benha University Hospital by hypertension. By
non-invasive ambulatory blood pressure monitoring
they were classified into white Coat Hypertension
(WCH) including 20 patients (13 females and 7
males) and Sustained Hypertension group, including
20 patients (9 females and 11 males).
There was a statistically significant difference
between both groups regarding age distribution
(p

Hamza Kabil, et al
24-h heart rate: There was a statistically significant
difference between both groups (p

White Coat Hypertension & Target Organ Damage
Table 5: Complications of hypertension among the studied
groups.
Studied Groups
Complications
Retinopathy
C.V. Stroke
Ischemic Heart
Disease
Renal Impairment
WCH
(n=20)
No.
11
1
2
0
%
55.0
5.0
10.0
0.0
Discussion
SH
(n=20)
No.
White-coat hypertension is a phenomenon
whereby some patients who apparently have raised
BP actually have normal BP when measurement
is repeated away from medical environment
(Michael et al, 2002). Those patients may receive
an incorrect diagnosis of sustained hypertension.
This phenomenon has been reported in as many as
15-35% of patients labeled and treated as hypertensive
(Pickering et al, 1988). Target organ damage
was observed in a population with white-coat
hypertension (Verdecchia et al, 1996).
This study was planned to evaluate the impact
of WCH on the target organs in order to determine
if this type of hypertension is really benign or not?.
This study showed that there was a statistically
significant difference between both WCH group
and SH groups (p0.05), in relation to smoking among males as
shown in Table (1), these results were supported
by the study carried out by Hernandez del Rey et
al, 1997, who showed that there was no difference
between WCH and SH regarding prevalence of
smoking.
13
3
6
1
%
65.0
15.0
30.0
5.0
Z
0.645
1.054
2.372
1.013
p
>0.05
>0.05
>0.05
>0.05
66
This study showed that there was a statistically
significant difference between both groups
(p

Hamza Kabil, et al
group and the SH group (p0.05), where the mean value of clinic
HR in the WCH group was (90.9±6.4) and that in
the SH group was (91.3±5.6), and the mean value
of nighttime HR in the WCH group was (71.9±5.7)
and that in the SH group was (72.1±6.4). Also,
there was a statistically significant difference
between both the WCH group and the SH group
regarding, 24-h and daytime ambulatory HR values
(p

White Coat Hypertension & Target Organ Damage
2- Bjorklund K, Lind L, Vessby B, et al: Different metabolic
predictors of white-coat and sustained hypertension over
a 20-year follow-up period: A population-based study of
elderly men, Circulation 2002; 106: 63-68.
3- Cerasola G, Cottone S, Nardi E, D'Ignoto G, et al: Chair
of Internal Medicine and Hypertension Center, University
of Palermo, Italy 1995.
4- Fondo de Investigation Sanitaria Ministerio de Sanidad
Y Consumo: (Proyecto 95/26: 0-10); Beca VITA de Invetigacion
en Atencion Primaria 1995.
5- Greece: 1 st Cardiology Department of Athens University,
Hippokration Hospital, Athens Greece.
6- Hernandez R del Ray, Armario P, Cardenas G, et al: Red
Cross Hospital Liobregat. Barcelona. Spain 1997.
7- Jose A Alzpunja, Egle Silva, Glodys Masstre, et al: Cardiovasculares,
Maracaibo, Venezuela, La Universidad del
Zulla. Maracaibo, Venezuela 2002.
8- Julius S, Mejia A, Jones K, et al: "White coat 'versus'
sustained" borderline hypertension in Tecumseh Mi Hypertens
1990; 16: 617-62.
9- Karponou EA, Vyssoulis GP, Chrysohoou CA, et al: 1 st
Cardiology Department, Onassis Cardiac Surgery Center,
Athens 2004.
10- Kazue Eguchi, Kazuomi Kario, Satoshi Hoshide, Masato
Morinari Joji Ishikawa, Kazuyuki Shimada, et al: Department
of Cardiology. Jichi Medical School, Tochigi-Ken,
Japan 2004.
11- Khattar RS, Senior R, Lahiri A: Cardiovascular outcome
68
in white-coat versus sustained mild hypertension: A 10year
follow-tip study, Circulation 1998; 89: 1892-1897.
12- Michael E, Ernst, Pharm D, George R, Bergus: Non inasive
24-hour Ambulatory Bp monitoring overview of Technology
clinical application, Pharmacotherapy 2002; 22 (5)
© 2002 Pharmacotherapy Publications.
13- Mancia G, Parti G, Pomidossi G, et al: Altering reaction
and rise in blood pressure during measurements by physician
and nurse, Hypertension 1987; 9: 209-215.
14- Opsahl JA, Abraham PA, Halstenson CE, Keane WF:
Correlation of office and ambulatory blood pressure
measurements with urinary albumin and N-acetyl-B-Dglucosaminidase
excretions in essential hypertension ,
Am J Hypertens 1988; 11: 7S-120S.
15- Peckering TG, James GD, Boddie C, et al: How common
is white coat hypertension? JAMA 1988; 259 (2): 225-
228.
16- Pierdomenico SD, Guglielmi MD, Lopenna D, et al:
Hypertension Unit, chair of Internal Medicine, University
of Chieti, Italy 1995.
17- Verdecchia P, O'Brein E, Pickering, et al: When can the
practicing physician suspect white coat hypertension?
Statement from the Working Group on Blood Pressure
Monitoring of the European Society of Hypertension, Am
J Hypertens 2003; 16: 87-91.
17- Erdecchia P, Schillaci G, Borgioni C, Ciucci A, et al:
White Coat hypertension. Lancet 1996; 348: 1444-5.
18- Sasaki K, Kushiro T, Jin Inoue, Asgami T, Takahashi A,
et al: Surugadai Nihon University Hospital, International
Christian University Tokyo, Japan 1997.

Egypt Heart J 62 (1): 69-76, March 2010
Microalbuminuria and Subclinical Cardiac Structural Changes
Relation to Isolated Systolic Hypertension in Elderly Patients
HAMZA KABIL, MD*; EL-METWALLY EL-SHAHAWY, MD; AMR AFIFI, MD;
HSASSAN GALAL, MD; ASHRAF TALAAT, MD
Isolated systolic hypertension is common in elderly people and accounts for more than 50% of all cases with hypertension
above the age of 65 years. Microalbuminuria represents an early marker of cardiac structural damage.
The Aim of this Work: Is to study the relationship between micro albuminuria and subclinical cardiac structural changes
septal wall thickness (SWT), left ventricular mass (LVM) and left ventricular mass index (LVMI) in isolated systolic hypertension
in elderly patients.
Results: Showed significant positive correlation between microalbuminuria and cardiac structural changes (LVMI-p=0.01,
SWT-p=0.01 and LVM-p=0.01). There was a significant positive correlation between the duration of hypertension and
microalbuminuria, LVM (p=0.02) and LVH (p=0.01). Also, there was a significant positive correlation between age of patients
and LVM (p=0.01) and LVH (p=0.01).
Conclusion: Taken together this study showed that microalbuminuria represents an early marker of cardiac structural
changes in isolated systolic hypertension in elderly patients. It is considered one of the new associated risk factors of hypertension.
Cardiovascular prognosis depends not only on the blood pressure level but also on the presence of target organ damage. So we
recommend early detection of microalbuminuria in every hypertensive patient as it is an early sign of endothelial dysfunction
and damaged blood vessels.
Key Words: Microalbuminuria – Subclinical cardiac structural changes – Isolated systolic hypertension – Elderly patients.
Introduction
Hypertension is a major public health problem
all over the world. Its prevalence among Egyptians
is 26.3% (Ibrahim, 2001). As the population ages,
the prevalence of hypertension will increase. Isolated
systolic hypertension is common in elderly
people and probably accounts for more than 50%
of all cases of hypertension above the age of 65
years (Padfield, 2001). As arterial compliance
declines with age, systolic blood pressure increases,
diastolic blood pressure declines and pulse pressure
increases. This is a strong predictor of cardiovascular
disease (Blacher et al, 2000).
The Departments of Cardiology* and Internal Medicine,
Benha Faculty of Medicine, Benha University, Egypt.
Manuscript received 10 Sep., 2009; revised 12 Oct., 2009;
accepted 13 Oct., 2009.
Address for Correspondence: Dr. Hamza Kabil, 92 El-Sikka
El-Kadima street, Mansoura, Dakahlia, Egypt.
69
Microalbuminuria represents a marker of vascular
damage so, its presence is a signal from the
kidney that cardiovascular risk is increased and
vascular responses are altered (Garg and Bakris,
2002).
Microalbuminuria is usually defined as a urinary
albumin excretion rate of 30 to 300mg in a 24-h
urine collection, or as a urinary albumin excretion
rate of 20 to 200ug/min in a timed overnight urine
collection. More than one consecutive urine collection
is preferred given the high day to day
variability of urinary albumin excretion (Diercks
et al, 2002).
The prevalence of microalburninuria is 5-8%
in the general population and 6-24% in hypertensive
patients (Hornych et al, 2000).
In essential hypertension, microalbuminuria
represents an early marker of cardiac structural
damage e.g. left ventricular hypertrophy (Plavink
et al., 2002).

Microalbuminuria & Subclinical Cardiac Structural Changes Relation
Although microalbuminuria is useful and cost
effective but is still too often neglected in clinical
practice (Leoncini et al, 2002).
Aim of the work:
To study the relationship between microalbuminuria
and subclinical cardiac structural changes
(interventricular septum thickness, left ventricular
wall thickness and left ventricular mass index) in
isolated systolic hypertension in elderly patients.
Patients and Methods
The study was done in the Nephrology Unit-
Benha Faculty of Medicine, where 100 patients
were selected (61 females and 39 males) and 50
apparently healthy persons aged 60 years or older
(27 females and 23 males) as a control group.
The inclusion criteria were:
1- Patients aged 60 years or older.
2- Isolated systolic hypertensive patients with
systolic blood pressure ≥160mmHg and diastolic
blood pressure ≥95mmHg (Amery et al, 1991).
The exclusion criteria were:
1- Renal failure or any renal disease, liver disease
or collagen disease.
2- Diabetes mellitus.
3- Hypertensive patients with manifest heart failure.
All subjects (patients-control group) have been
subjected to the following:
1- History taking with stress on: Age, sex, smoking,
duration of hypertension, antihypertensive
drugs, cardiovascular or cerebrovascular complications
and family history of hypertension,
cardiovascular or cerebrovascular disease.
2- Thorough clinical examination including:
• Weight, height, body mass index.
• Blood pressure measurement by the cuff method,
using the 1 st and 5 th Korotkoff sounds for identification
of systolic and diastolic blood pressures
respectively. The average of three readings taken
in different times of three consecutive days was
recorded.
• Pulse (rhythm-rate-special character-peripheral
pulses-equality on both sides-vessel wall).
• Complete heart, chest, abdomen and neurologic
evaluation.
70
3- Laboratory investigations:
a- Dipstick urine analysis:
For rapid determination of urobilinogen, bilirubin,
glucose, protein, blood, pH and gravity (combiscreen,
analyticon Biotechnologies AG), only a
fresh samples and compare the reagent areas on
the strip with the corresponding colour chart after
60 seconds.
b- Dipstick for microalbuminuria:
For rapid detection of microalbuminuria by
using an Accu-Check-Product-MICRAL-Test.
Procedure:
• Three urine samples were tested.
• The first morning urine is collected.
• Normal fluid intake prior testing is important
(1.5-2 litre/day).
• The screening result is positive when at least two
of the three samples produce a reaction colour
corresponding to 20mg/L albumin (threshold for
microalbuminuria) or more as the dipstick is
graded into 20, 50 and 100mg/L.
N.B: If proteinuria was confirmed by dipstick
for urine analysis, it was not necessary to screen
for microalbuminuria.
c- 24-hour urinary Protein:
For all subjects with proteinuria and microalbuminuria
(El-Khodary, 2000).
d- Hematological parameters:
Hemoglobin content, hematocrite value and
complete blood picture.
e- Biochemical tests:
1- Fasting and 2 hours-post-prandial blood sugar
levels.
2- Serum creatinine.
3- Blood urea.
4- Serum uric acid.
5- Serum triglycerides and cholesterol.
6- Serum calcium.
7- Serum sodium and potassium.
4- Electrocardiogram.
5- Echocardiographic assessment.
Two dimensional and M-mode echocardiography
was performed with the patients in the
partial left lateral decubitus position using Hewled

Hamza Kabil, et al
Packard (HP) Sonos 1000 system with 2.5MHz
transducer. Left ventricular measurements were
made at end-diastole and end-systole, according
to the recommendations of the American Society
of Echocardiography (ASE).
Left ventricular mass (LVM) was calculated by
the equation:
LVM (ASE) = 0.8 (1.04 (IVS + LVID + PWT)3 – LVID3) +
0.6 gm (Devereux et al., 1986).
IVS = Interventricular septum.
LVID = Left ventricular internal dimension.
PWT = Posterior wall thickness.
Table 1:
Variables
Mi (Dipstick)/mg/L
Protein in 24-hr urine (vol)/L
Protin in 24-hr urine (amount)/gm
HB (gm/dl)
HT (%)
WBCs/mm 3
Platelets/mm 3 (x1000)
Triglycerides mg/dl
Cholestesterol mg/dl
Creatinine mg/dl
Urea mg/dl
Uric acid mg/dl
Serum Na mg/dl
Serum K mg/dl
Serum Ca++ mg/dl
SBP = Systolic blood pressure.
Mi = Microalbuminuria.
WBCs = White blood cells.
Compared to control group, patients with ISH
tended to have significantly greater SWT (1.2±0.3
Vs 0.9±0.08, p

Microalbuminuria & Subclinical Cardiac Structural Changes Relation
There was significant positive correlation between
the duration of hypertension and both microalbuminuria
and cardiac structural changes as
shown in Table (3).
Table 3:
Variables
Mi mg/l
SWT/cm
PWT/cm
LVM/gm
LVMI gm/m 2
LVH
Mi
PWT
LVMI
SWT
LVM
LVH
There was a significant positive correlation
between age and both microalbuminuria and cardiac
structural changes.
Table 4:
Variables
Mi mg/l
SWT/cm
PWT/cm
LVM/gm
LVMI gm/m 2
LVH
Mi
PWT
LVMI
SWT
LVM
LVH
Coefficient regression
2.3
0.009
0.004
2.3
0.17
0.21
= Microalbuminuria.
= Posterior wall thickness.
= Left ventricular mass index.
= Septal wall thickness.
= Left ventricular mass.
= Left ventricular hypertrophy.
Coefficient regression
–0.13
0.003
–0.0003
0.08
0.59
0.08
= Microalbuminuria.
= Posterior wall thickness.
= Left ventricular mass index.
= Septal wall thickness.
= Left ventricular mass.
= Left ventricular hypertrophy.
This table showed the relation between the level
of albuminuria regarding dipstick for urine and
microalbuminuria and cardiac structural changes
regarding echocardiography and ECG.
There was a significant difference between
normoalbuminuric, microal buminuric and macroalbuminuric
regarding cardiac structural changes
(SWT - PWT - LVM - LVMI).
Results of regression analysis between the level
of microalbuminuria and cardiac structural changes
as shown in Table (6).
r 2
0.05
0.01
0.005
0.02
0.0004
0.09
r 2
0.0006
0.008
0.0001
0.05
0.02
0.05
p
0.04
0.2
0.4
0.02
0.8
0.01
p
0.8
0.4
0.9
0.01
0.2
0.01
72
Table 5:
Cardiac
structural
change
SWT/cm
PWT/cm
LVM/g
LV MI/gm/m 2
* SWT
* PWT
* LVMI
* LVM
* S
* MA
* NA
* Mi
NA
(N=22)
Mean ± SD
1.02±0.18
0.95±0.15
154.9±48.6
83.8±23.2
Albuminuria
Mi
(N=67)
Mean ± SD
1.25±0.25
1.06±0.19
223.9±54.2
119.6±25.2
= Septal wall thickness.
= Posterior wall thickness.
= Left ventricular mass index.
= Left ventricular mass.
= Standard deviation.
= Macroalbuminuria.
= Normoalburninuria.
= Microalburninuria.
Normal values:
SWT = Up to 1.1 cm.
PWT = Up to 1.1 cm.
LVMI = Male: 136gm/m 2 female: 112 gm/m 2
Table 6:
Variables
SWT/cm
PWT/cm
LVM/gm
LVMI gm/m 2
MA
(N=11)
Mean ± SD
1.33±0.3
1.2±0.28
271.5±66.2
148±37.7

Hamza Kabil, et al
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding cardiac structural changes.
There was highly positive significant correlation
between the level of microalbuminuria and both
LVM and LVMI and significant with SWT and
tendency to be significant with PWT.
SWT
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding SWT as shown in Table (7).
LVMI
100
90
80
70
60
50
40
30
20
10
0
100
90
80
70
60
50
40
30
20
10
0
95.5%
4.5%
NA (22%)
* NA = Normoalbuminuria.
* Mi = Microalbuminuria.
Figure 1: Distribution of studied cases according to the level
of albuminuria and SWT.
95.5%
4.5%
NA (22%)
* NA = Normoalbuminuria.
* Mi = Microalbuminuria.
55.2%
55.2%
44.8%
44.8%
36.4%
38.4%
Absent
Present
63.6%
MI (67%) MA (11%)
* MA = Macroalbuminuria
* SWT = Septal wall thickness
Absent
Present
63.6%
MI (67%) MA (11%)
* MA = Macroalbuminuria
* LVMI = Left ventricular mass index
Figure 2: Distribution of studied cases according to the level
of albuminuria and LVMI.
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding LVMI as shown in Table (7).
73
PWT
100
90
80
70
60
50
40
30
20
10
0
95.5%
4.5%
NA (22%)
* NA = Normoalbuminuria.
* Mi = Microalbuminuria.
77.6%
22.4%
45.5%
Absent
Present
54.5%
MI (67%) MA (11%)
* MA = Macroalbuminuria
* LVMI = Left ventricular mass index
Figure 3: Distribution of studied cases according to the level
of albuminuria and PWT.
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding PWT as shown in Table (7).
LVH
100
90
80
70
60
50
40
30
20
10
0
81.8%
18.2%
NA (22%)
* NA = Normoalbuminuria.
* Mi = Microalbuminuria.
58.2%
41.8%
45.5%
Absent
Present
54.5%
MI (67%) MA (11%)
* MA = Macroalbuminuria.
* LVH = Left ventricular hypertrophy.
Figure 4: Distribution of studied cases according to the level
albuminuria and LVH.
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding LVH as shown in Table (7).
Table (8) showed the relation between LVH,
serum cholesterol level, serum triglycerides level
and uric acid level regarding mean and standard
deviation.
There was a difference between patients having
normal left ventricular wall and patients having
LVH regarding (Cholesterol level-triglycerides
level-uric acid level), however this difference was
not statistically significant.

Microalbuminuria & Subclinical Cardiac Structural Changes Relation
Table 8:
Table (9) showed the relation between the level
of albuminuria, cholesterol level, triglycerides
level and uric acid level.
There was a significant difference between
normoalbuminuric, microalbuminuric and macroalbuminuric
regarding uric acid level.
Table 9:
Variables
Cholesterol
mg/dl
Triglycerides
mg/dl
Uric acid
mg/dl
Variables
Cholesterol mg/dl
Triglycerides mg/dl
Uric acid mg/dl
NA
Mean ± SD
196.1±49.6
148.9±62.1
4.9±1.8
NA = Normoalbuminuria.
MI = Microalbuminuria.
No LVH
Mean ± SD
208.4±44.9
151.5±36.7
5.7±1.6
Mi
Mean ± SD
2 16.7±39.4
156.5±32.4
6.1±1.6
Discussion
LVH
Mean ± SD
218.5±38.2
154.1±48.5
5.7±1.7
MA
Mean ± SD
217.1±42.1
136±43.7
5.6±1.4
MA = Macroalbuminuria.
SD = Standard deviation.
>0.05
>0.05
0.05
>0.05
>0.05
p
74
sive increases in UAE may result in better protection
against hypertension induced morbidity and
mortality (Redon, 2006).
This work was done to determine the relationship
between microalbuminuria and subclinical
cardiac structural changes (septal wall thickness,
posterior wall thickness and left ventricular mass
index) in elderly isolated systolic hypertensive
patients.
Table (1) showed highly significant differences
(p

Hamza Kabil, et al
microalbuminuria, LVM and LVH. Gerstein et al
(2000) stated that the relation between microalbuminuria
and the duration of hypertension was
present. Hypertrophic growth of myocytes occur
in response to pressure or volume overload especially
with increased duration.
There was a significant positive correlation
between age of the patients and LVM and LVH as
shown in Table (4). It can be explained by Dannenberg
et al (1989) who mentioned that age-LVM
relation is a function of multiple factors such as
elevated blood pressure, obesity, valvular heart
disease and occult coronary artery disease which
tend to increase with age.
There were insignificant positive correlations
between age and microalbuminuria, SWT, and
LVMI. These results are in agree with those reported
by Lydakis and Lip (1998) but in contrast with
those reported by Ritz et al (1994) who mentioned
that urinary albumin excretion was positively correlated
with age, possibly due to a degree of nephrosclerosis.
Tables (5,6,7) and Figs. (1- 4) showed highly
significant positive correlation between the albuminuria
level and cardiac structural changes. It
was confirmed between albuminuria (detected by
urine analysis or dipstick) and PWT (p=0.004) and
LVMI (p0.01)
and LVMI (r=0.42, p

Microalbuminuria & Subclinical Cardiac Structural Changes Relation
8- Fang J, Alderman MH: Serum uric and cardiovascular
mortality, the NHANE-SI epidemiologic follow-up study
1971-1992. JAMA 2000; 283: 2404-2410.
9- Garg JP, Bakris GL: Microalbuminuria: marker of vascular
dysfunction, risk factor for cardiovascular disease. Vascular
Medicine 2002; 7: 35-43.
10- Gerstein HS, Mann JF, Pogue J: Prevalence and determinants
of microalbuminuria in high risk diabetic and nondiabetic
patients (HOPE Study). Diabetes Care 2000; 23:
Suppl. 2: 35-79.
11- Hornych A Marre M, Mimran A: Microalbuminuria in
arterial hypertension. Measurement, variables, interpretation,
recommendations. Arch Mal Coeur Viass 2000; 93
(11): 1304-8.
12- Ibrahim MM: Epidemiology of hypertension in Egyptains,
In: Manual of hypertension 2001; Chapter 15, Page. 182.
13- James MA, Fatherby MD, Patter JF: Screening tests for
microalbuminuria in nondiabetic elderly subjects and
their relation to blood pressure. Clinical Science 1995;
88: 185-140.
14- Leoncini G, Sacchi G, Pontremoli R: Microalbuminuria
is an integrated marker of subclinical organ damage in
primary hypertension. J Hum Hyperten 2002; 16 (6): 344-
404.
15- Leoncini G, Sacchi G, Pontremoli R: Microalbuminuria
identifies overall cardiovascular risk in essential hypertension:
An artificial neural network-based approach. J
Hypertension 2002; 20: 1315-1321.
76
16- Liebson PR, Grandits G, Prineas R: Echocardiographic
correlates of left venmtricular structure among 844 mildly
hypertensive men and women in the treatment of mild
hypertensive study (TOMHS). Circulation 1993; 87: 476-
486.
17- Lydakis C, Lip GYH: Microalbuminuria and cardiovascular
risk QJ Med 1998; 91: 381-391.
18- Padfield PL: Further reading on systolic blood pressure
and isolated systolic hypertension: Epidemiology. The
Hypertension Letter (41) 2001.
19- Parving HH Anderson S, Jacobsen P, et al: Semin Nephrol
2004; 24: 147-57.
20- Pedrinelli R: Microalbuminuria in essential hypertension.
A marker of systemic vascular damage. Nephrol Dial
Transplant 1997; 12: 379-398.
21- Pontremoli R, Dahlof B, Hansson L: Prevalence and
clinical correlates of microalbuminuria in essential hypertension.
The MAGIC study. Hypertension 1997; 30: 1135-
1143.
22- Redon J: Nephrol Dial Transplant 2006; 21: 573-6.
23- Ritz E, Nowicki M, Klin HP: Proteinuria and hypertension.
Kid Intern 1994; 46 (Suppl. 47): 576-580.
24- Tsioufis C, Marinakis N, Toutouz A: Microalbuminuria
is closely related to impaired arterial elasticity in untreated
patients with essential hypertension. Nephron Exp Nephrol
2003; 93 (3): 85-6.

Egypt Heart J 62 (1): 77-81, March 2010
Urinary Albumin Excretion is Associated with Arterial Stiffness in
Hypertensive Adults
MOHAMMED A ABDEL WAHAB, MD; MOHAMED M SAAD, MD; AMR S AMIN, MD;
KHALID A BARAKA, MD; NASSER M TAHA, MD
Background: Microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and
therefore it is an integrated marker of cardiovascular risk.
Aim: To Verify whether the urinary albumin/creatinine ratio (UACR), a measure of albuminuria, is associated with arterial
stiffness in hypertensive adults.
Patients and Methods: 50 hypertensive patients (group 1) and 20 normo-tensive healthy subjects (group 2) (used as a
control) were included in this study. Office and 24h systolic and diastolic blood pressure measurement was done for both groups
and from it ambulatory arterial stiffness index (AASI) was calculated. Urinary albumin and creatinine concentrations were
determined on a morning spot-urine sample. The urinary albumin-to-creatinine ratio (ACR) was then calculated. Microalbuminuria
was defined as an ACR of 30 to 299mg/g. Patients with macroalbuminuria (defined as ACR ≥300g/mg). We also assessed the
intima-media thickness (IMT) of the common carotid, and left ventricular mass index (LVMI) for correlation study.
Results: The mean level of microalbuminuria was significantly increased in group 1 than in group 2 (35.91±43.95 versus
8.25±2.544, p=0.007). There is significant correlation between AASI and microalbuminuria (r=0.312, p=0.009). Furthermore,
significant correlation was found between microalbuminuria and left ventricular mass index (LVMI) (r=0.486, p

Urinary Albumin Excretion is Associated with Arterial Stiffness
All the participant were subjected to: History
taking, clinical examination, Office blood pressure
measurement (Patients with blood pressure 140/90
and above were considered hypertensive), measurement
of body mass index and body surface area,
Laboratory investigation (Fasting and post prandial
blood sugar, lipogram, blood urea nitrogen, serum
creatinine, and quantification of albumin in urine),
and Ambulatory blood pressure monitoring
(ABPM) using Space Labs TM 2430 device (Space
Labs Inc., USA).
Calculation of the ambulatory arterial stiffness
index (AASI):
From 24-hour recordings, for each participant
the regression slope of diastolic on systolic blood
pressure was calculated, the regression line was
not forced through the origin (intercept 0), because
during diastole when flow drops to 0, such a phenomenon
does not occur for blood pressure [5].
The rationale underlying this is that, for any
given increase in distending arterial pressure,
systolic and diastolic pressures tend to increase in
a parallel fashion in a compliant artery, whereas
in a stiff artery, the increase in systolic pressure is
Table 1: Classification of abnormal urinary albumin execration (UAE).
Normal
High Normal
Microalbuminuria
Macroalbuminuria
24-H Urine
Albumin
(mg/24 h)

Mohammed A Abdel Wahab, et al
Statistical method:
Data was analyzed by the Statistical Package
for the Social Sciences (SPSS), version 16 for
Window. All data were reported as mean ± SD. A
Student t test was used to compare variables for
testing statistical significant difference between
two groups and the differences were considered
significant at a two-tailed p≤0.05 and Mann-
Whitney Test used to study the correlations of the
non parametric variables.
Results
Table (2) show the mean level of microalbuminuria
was 35.91±43.95 in group 1 whoever the
mean level of microalbuminuria was 8.25±2.54 in
group 2, there is statistically significant difference
between both groups as regard the value of microalbuminuria
(p=0.007).
Table 2: Microalbuminuria among the study groups.
Microalbuminuria
Group 1
(n=50)
Mean
35.91
SD
43.95
Group 2
(n=20)
Mean
8.25
SD
2.54
p value
0.007
Furthermore, a significant correlation (r=0.312,
p=0.009) between AASI and microalbuminuria was
found as shown in Fig. (1).
Microalbuminuria
250
200
150
100
50
0
-50
Microalbuminuria
p=0.009
0.00 .10 .20 .30 .40 .50 .60 .70 .80 .90 1.0
AASI
Figure 1: Shows significant positive correlation between
AASI and the level of microalbuminuria.
Also, there is significant correlation between
microalbuminuria and left ventricular mass index
(LVMI) Table (3).
Also, there is significant correlation between the
microalbuminuria and the intima-media thickness of
right and left common carotid arteries. Moreover,
there is significant correlation between the microalbuminuria
and mean common carotid arteries intimal
thickness (Table 3).
79
Table 3: Correlations of the microalbuminuria.
AASI
LCCA
RCCA
MCCA
LVMI
LVMI
LCCA IMT
RCCA IMT
MCCA IMT
Pearson coefficient
0.486
0.210
0.323
0.311
Discussion
0.000
0.081
0.006
0.009
= Ambulatory Arterial Stiffness Index.
= Left common carotid artery intima media thickness.
= Right common carotid artery intima media thickness.
= Mean common carotid artery intima media thickness.
= Left ventricular mass index.
Results of this study revealed that there is
significant increase in the level of microalbuminuria
in hypertensive subjects compared to controls.
Similar results obtained in another study which
concluded that microalbuminuria is highly prevalent
in hypertensive population, its prevalence varies
from 10 to 40% [7]. This is also agree with the
result of another trial which concluded that microalbuminuria
prevalence is low in the absence
of cardiovascular risk factors and progressively
increases with the number cardiovascular risk
factors and that the main correlate of microalbuminuria
is blood pressure, either systolic or diastolic
pressure. The relation between blood pressure and
microalbuminuria is continuous and graded because
the microalbuminuria prevalence increases with
the severity of hypertension [3].
Results of this study revealed that microalbuminuria
is significantly correlated with AASI as
an index of arterial stiffness.
The same result was obtained when compared
pulse wave velocity as a marker of arterial stiffness
with microalbuminuria [8]. Furthermore, another
study detected that Albuminuria was significantly
associated with lower small artery elasticity [9].
In agreement with the current study Multe` et
al, examined the correlation of the aortic pulse
wave velocity (PWV) as a measure of arterial
stiffness in comparison with the urinary albumin
excretion in hypertensive patients, and found that
the PWV found to be higher in hypertensive patients
having albumin excretion rate higher than median,
when compared with those with those below the
median [10].
Also Tsioufis et al, studied the relation of the
microalbuminuria and the augmentation index
(AIx) as a measure of arterial stiffness, in a group
p

Urinary Albumin Excretion is Associated with Arterial Stiffness
of 130 untreated hypertensive subjects and they
found the higher the level of microalbuminuria the
more increased the augmentation index [11].
Also Leoncini et al, studied the association of
the AASI and target organ damage in patients with
primary hypertension, the results demonstrated
significant correlation between the AASI and microalbuminuria
[12].
Moreover, Munakata et al, considered the brachial-ankle
pulse wave velocity as a measure of
arterial stiffness. Thy examined the hypothesis that
higher brachial-ankle pulse wave velocity is associated
with a much greater risk of albuminuria in
718 never-treated hypertensive patients. The prevalence
of microalbuminuria increased with a graded
increase in brachial-ankle pulse wave velocity
(p

Mohammed A Abdel Wahab, et al
10- Multe G, Cottone S, Vadala A, Olope V, Mezzatesta V,
Mongivoi R, Piazza G, Nardi E, Andronica G, Cerasola
G: Relationship between albumin excretion rate and aortic
stiffness in untreated essential hypertensive patients.
Journal of Internal Medicine 2004; 256: 22-29.
11- Tsioufis C, Tzioumis C, Marinakis N, Toutouzas K,
Tousoulis D, Kallikazaros I, Stefanadis C, Toutouzas P:
Microalbuminuria Is Closely Related to Impaired Arterial
Elasticity in Untreated Patients with Essential Hypertension.
Nephron Clin Pract 2003; 93: c106-c111.
12- Leoncini G, Ratto E, Viazzi f, Vaccaro V, Parodi A, Falqui
V, Conti N, Tomolillo Cinzia, Deferrari G, Pontremoli
R: Increased Ambulatory Arterial Stiffness Index Is associated
with Target Organ Damage in Primary Hypertension.
Hypertension 2006; 48: 397-403.
13- Munakata M, Nunokawa T, Yoshinaga K, Toyota T:
Brachial ankle pulse wave velocity is an independent risk
factor for microalbuminuria in patients with essential
hypertension-a Japanese trial on the prognostic implication
of pulse wave velocity. Hypertens Res 2006; 29 (7): 515-
21.
81
14- Post WS, Blumenthal RS, Weiss JL, Levine DM, Thiemann
DR, Gerstenblith G: Spot urinary albumin-creatinine ratio
predicts left ventricular hypertrophy in young hypertensive
African-American men. Am J Hypertens 2000; 13 (11):
1168-72.
15- Leoncini G, Sacchi G, Viazzi F, Ravera M, Parodi D,
Ratto E, Vettoretti S, Tomolillo C, Deferrari G, Pontremoli
R: Microalbuminuria identifies overall cardiovascular
risk in essential hypertension: An artificial neural networkbased
approach. J Hypertens 2002 Jul; 20 (7): 1315-21.
16- Gatzka CD, Reid CM, Lux A, Dart AM, Jennings GL:
Ventricular mass and microalbuminuria: Relation to ambulatory
blood pressure. Hypertension Diagnostic Service
Investigators", Clin Exp Pharmacol Physiol 1999; 26 (7):
514-6.
17- Ponteremoli R, Leoncini G, Ravera M, Viazzi F, Vettoretti
S, Ratto E, Parodi D, Tomolillo C, Deferrari G: Microalbuminuria,
Cardiovascular, and Renal Risk in Primary
Hypertension. Journal of American Society of Nephrology
2002; 13: S169-S172.

Egypt Heart J 62 (1): 83-88, March 2010
Early Vascular Changes Preceding Morphological Cardiac Changes in
Hypertensive Patients
MOHAMMED A ABDEL WAHAB, MD
Background: Left ventricular hypertrophy (LVH) has been identified as a powerful independent risk factor not only for
total and cardiovascular mortality, but also for sudden cardiac death.
Aim: To Verify the vascular changes occurring before morphological changes in LV geometry in hypertensive patients.
Patients and Methods: 50 hypertensive patients and 20 normo-tensive subjects were divided into three groups as follows:
normo-tensive subjects with normal LV geometry (Group I, n=20), hypertensive patients with normal LV geometry (Group II,
n=18); hypertensive patients with abnormal LV geometry (Group III, n=32). 24h systolic and diastolic blood pressure was
carried out for all groups to calculate the ambulatory arterial stiffness index (AASI).
Endothelial function was assessed by endothelium-dependent flow-mediated dilatation (FMD) and -independent vasodilatation
(after sublingual administration of nitroglycerin) of the brachial artery using high-resolution vascular ultrasound. We also
assessed the intima-media thickness (IMT) of the common carotid, and left ventricular mass index (LVMI).
Results: Compared to group I, Group II patients had a higher AASI and IMT and lower FMD (p≤0.001, 0.001 and 0.046
respectively). Same changes were noticed when group II was compared to group III (p≤0.011, 0.013 and 0.049 respectively.
Conclusion: Increased IMT with reduced vasodilator capacity and increased arterial stiffness represent important vascular
changes that precede changes in LV geometry in hypertensive patients that might be markers for early detection of high risk
patients. These markers may also prove useful in the assessment of the efficacy of different therapeutic modalities in prevention
of structural and morphological cardiac changes.
Key Words: Hypertension – Arterial stiffness – Endothelial dysfunction.
Introduction
Left ventricular hypertrophy (LVH) and the
geometric shape of the left ventricle are wellestablished
important risk factors for cardiovascular
morbidity and mortality in the hypertensive population
[1]. Four distinct geometric patterns were
described [2]; normal geometry (normal LVMI with
a relative wall thickness (RWT) 0.45),
concentric hypertrophy (increased LVMI with RWT
>0.45) and eccentric hypertrophy (increased LVMI
associated with RWT

Early Vascular Changes Preceding Morphological Cardiac Changes
• Group 3: Includes 32 hypertensive subjects with
abnormal LV geometry.
All the participant were subjected to: History
taking, clinical examination, Office blood pressure
measurement (Blood pressure 140/90 and above
was considered hypertensive), Laboratory investigation
(Fasting and post prandial blood sugar,
lipogram, blood urea nitrogen, serum creatinine,
and quantification of albumin in urine), and Ambulatory
blood pressure monitoring (ABPM) using
the ABPM device (model: TM 2430 Space Labs
Inc).
Calculation of the ambulatory arterial stiffness
index (AASI):
From 24-hour recordings, the regression slope
of diastolic on systolic blood pressure for each
participant was computed according to the criteria
described by Li and his co-workers [6]. AASI was
defined as 1 minus the regression slope. The stiffer
the arterial tree, the closer the regression slope and
AASI are to 0 and 1, respectively.
Colored duplex ultrasound to measure the Intimamedia
thickness (IMT):
The end-diastolic IMT of both common carotid
artery was measured from the leading edge of the
1 st echogenic line to the leading edge of the 2 nd
echogenic line 10mm caudal to the bulb using
Hewlett Packard Sonos 1000 system, with 7.5Hz
linear array transducer, with the patient in the
supine position and the neck in slight hyperextension.
Plaques were sought in the entire extra-cranial
carotid tree and were defined as presence of a focal
thickening greater than 1.5mm.
Colored duplex ultrasound to test the endothelial
function:
Colored duplex ultrasound was done for all
subjects. The mean right brachial artery anteroposterior
diameter was measured 3-5cm above the
elbow, between media and adventitia from 4 cycles
synchronized with the end-diastole at the R wave
peaks [7].
• A basic scan of the flow was taken.
• 2 nd scan was taken after applying a pneumatic
tourniquet of 250-300mmHg. (Using mercurial
sphygmomanometer) for about 4.5sec. The scan
was taken 60 seconds after releasing the tourniquet
measuring the maximum FMD.
• 3 rd scan was taken after 15 minutes of rest to
allow recovery of the artery after FMD and that
84
was the basic of Glyceryl trinitrate (GTN)mediated
dilatation (GTN-MD) reading.
• 4 th scan was taken 4 minutes after administration
of 400μg of GTN spray sublingually.
o FMD percentage was calculating by the following
equation:
2 nd Scan – 1 st scan
FMD % = –––––––––––––––––– x 100
1 st scan
o GTN percentage was calculating by the following
equation:
4 th Scan – 3 rd scan
GTN – MD% = –––––––––––––––––– x 100
3 rd scan
o Dilatation percentage was calculating by the
following equation:
FMD%
DilRatio = –––––––––––––––––– x 100
GTN – MD%
Echocardiography evaluation of the LVMI
and geometric pattern: Was done according to the
recommendations of the American Society of
Echocardiography (ASE) as follows:
LV mass in grams = 0.8 (1.04 ([LVIDD +
PWTD + IVSTD]3 – [LVIDD]3)) + 0.6.
And then indexing the LVM to height 2.7 and
BSA.
Determining the geometric pattern from by
calculating the relative wall thickness (RWT) as
follows: RWT = 2 x PWTD/LVIDD.
Statistical method:
Data was analyzed by the Statistical Package
for the Social Sciences (SPSS), version 16 for
Window. All data were reported as mean ± SD. A
Student’s t-test was used to compare means of two
groups. Mann-Whitney Test was used to compare
non parametric variables. Differences were considered
significant at a two-tailed p≤0.05.
Results
As shown in Table (1), the study groups were
all age matched.
Table 1: Comparison of the age between in the study groups.
Age (y)
Group 1
(n=20)
Mean
45.25
SD
7.88
Group 2
(n=18)
Mean
47.39
SD
8.22
Group 3
(n=32)
Mean
48.78
SD
5.19
G1
vrs
G2
0.419
p
G2
vrs
G3
0.466

Mohammed A Abdel Wahab
There is a statistically significant difference
between group 1 and 2 as regards the office and
mean 24 hours systolic and diastolic blood pressure,
while there is no significant difference between
group 2 and 3 in these parameters. Meanwhile
there is significant differences in AASI between
both group 1&2 and group 2&3 (Table 2).
There is significant increase in IMT of the
carotid arteries in group 2 compared to group 1
and in group 3 compared to group 2 (Table 3).
100
75
50
LVMI 125
25
85
There is significant decrease in FMD and dilatation
ratio in group 2 compared to group 1 while
there is tendency of FMD to decrease significantly
in group 3 compared to group 2 (Table 4).
Furthermore, AASI was significantly correlated
with LVM and LVMI (Fig. 1), as well as with the
right (Fig. 2) and left common carotid artery IMT
(Fig. 3). AASI was negatively correlated with FMD
(Fig. 4) and the dilatation ratio (Fig. 5).
Table 2: Comparison if the blood pressure data and AASI in between the study groups.
Office SBP
Office DBP
Mean 24h SBP
Mean 24h DBP
AASI
Group 1
(n=20)
Mean
127.35
77.50
123.05
74.8
0.52
SBP = Systolic Blood Pressure.
DBP = Diastolic Blood Pressure.
SD
5.32
6.39
6.65
6.63
.062
Mean
165.56
97.78
152.11
94.33
0.73
Group 2
(n=18)
SD
19.31
10.03
22.36
10.63
0.104
Mean
170.72
97.67
148.59
92.03
0.79
Group 3
(n=32)
SD
13.68
11.57
9.09
7.1
0.08
G1 vrs G2

Early Vascular Changes Preceding Morphological Cardiac Changes
Left CCA-IMT
Figure 3: Correlation between the AASI and the left CCA
IMT.
Dil Ratio
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
0.00 .10 .20 .30 .40 .50 .60 .70 .80 .90 1.0
250
200
150
100
50
Left CCA-IMT
p

Mohammed A Abdel Wahab
decrease in FMD with progression of geometry to
abnormal forms. This agrees with a previous study
[15] that showed that the endothelium-dependent
vasodilatation is impaired progressively as LV
hypertrophy advances. Also it was detected that
FMD was considerably higher in the normo-tensive
than in hypertensive patients with left ventricular
hypertrophy [12].
We also found that AASI is significantly correlated
with LVMI. The same data obtained from
[16] that concluded that as vascular resistance and
left ventricular mass are also related. These findings
could speak for a parallel development of total
peripheral resistance and left ventricular hypertrophy
in essential hypertension.
Our results showed that AASI is negatively
correlated with FMD, dilatation ratio and positively
correlated with IMT of both carotid arteries. In
agreement with result of the current study, previous
study investigated the relationship between endothelial
damage/dysfunction, arterial stiffness (measured
using digital volume photoplethysmography
and expressed as the stiffness index) and found
that significant correlation between circulating
endothelial cells and the stiffness index [17]. Meanwhile,
endothelial cell function and vascular smooth
muscle cell tone do also have a strong influence
on arterial stiffness. Arterial tone is affected by a
number of factors like shear mechanical stress as
well as paracrine mediators such as angiotensin II,
endothelin, and NO [18]. Furthermore, it was found
that, aortic pulsed wave velocity (PWV) as a marker
as arterial stiffness correlated inversely with FMD
in a group of patients with isolated systolic hypertension
[19].
The magnitudes of carotid intima-medial thickness
and lumen diameter parallel levels of LV mass
and geometry, and are directly related to stroke
volume and arterial stiffness [9].
Evidence from both animal and human studies
suggests that the endothelium is an important
regulator of arterial stiffness, both functionally
and structurally. Inhibition of basal nitric oxide
(NO) production in the endothelium with Lmonomethyl-NG-arginine
(L-NMMA) increases
iliac PWV in sheep and, in humans, increases
augmentation index and brachial artery stiffness
[20].
Nitric oxide (NO) may play a role in the pathogenesis
of hypertension and its complications.
87
Agents that inhibit NO through enzyme nitric oxide
synthetase (eNOS) cause endothelium dependant
contraction, and reduction in the blood flow. A
continuous inhibition of NO-dependant vasodilatation
results in hypertension and its related organ
damage [20]. Also endothelins have additional
effects in vascular hypertrophy and increasing
blood pressure, in addition to its systemic vasoconstrictor
effect endothelin-1 (E-1) is a growth factor
in the cardiovascular system, in vitro studies demonstrated
that endothelins stimulates mitogenesis,
hypertrophy including vascular and cardiac hypertrophy
and protein synthesis in vascular smooth
muscle cells [20].
From all the above data we can conclude that
early vascular changes in the form of increased
IMT, reduced vasodilator capacity and increased
arterial stiffness precedes changes in LV geometry.
The result that AASI is increased with the progression
of LV geometry into abnormal geometry inspite
of no significant change in blood pressure measurement
may suggest that arterial stiffness (rather
than increased blood pressure levels) is the cause
of the progression of LV geometry and that endothelial
dysfunction may be the cornerstone in this
story through its effect on arterial stiffness.
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Early Vascular Changes Preceding Morphological Cardiac Changes
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11- Muiesan ML, Salvetti M, Zulli R, Pasini GF, Bettoni G,
Monteduro C, Rizzoni D, Castellano M, Agabiti-Rosei
E: Structural association between the carotid artery and
the left ventricle in a general population in Northern Italy:
the Vobarno study. J Hypertens 1998 Dec; 16 (12 Pt 1):
1805-12.
12- Tsai WC, Lin CC, Huang YY, Chen JY, Chen JH: "Association
of increased arterial stiffness and inflammation
with proteinuria and left ventricular hypertrophy in nondiabetic
hypertensive patients", Blood Press 2007; 5: 1-
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13- Libhaber E, Woodiwiss AJ, Libhaber C, Maseko M,
Majane OH, Makaula S, Dessein P, Essop MR, Sareli P,
Norton GR: Gender-specific brachial artery blood pressureindependent
relationship between pulse wave velocity
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and left ventricular mass index in a group of African
ancestry. J Hypertens 2008 Aug; 26 (8): 1619-28.
14- Palmieri V, Bella JN, Roman MJ, Gerdts E, Papademetriou
V, Wachtell K, Nieminen MS, Dahlöf B, Devereux RB:
Pulse pressure/stroke index and left ventricular geometry
and function: The LIFE Study. J Hypertens 2003 Apr; 21
(4): 781-7.
15- Sekiya M, Funada J, Suzuki J, Watanabe K, Miyagawa
M, Akutsu H: The influence of left ventricular geometry
on coronary vasomotion in patients with essential hypertension.
Am J Hypertens 2000 Jul; 13 (7): 789-95.
16- Schulte KL, Liederwald K, Meyer-Sabellek W, van Gemmeren
D, Lenz T, Gotzen R: Relationships between ambulatory
blood pressure, forearm vascular resistance, and
left ventricular mass in hypertensive and normotensive
subjects. Am J Hypertens 1993 Sep; 6 (9): 786-93.
17- Boos CJ, Lane DA, Karpha M, Beevers G, Haynes R, Lip
GYH: "Circulating Endothelial Cells, Arterial Stiffness,
and Cardiovascular Risk Stratification in Hypertension",
Chest 2007; 132: 1540-1547.
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the vascular endothelium". New England Journal of
Medicine 1990; 323: 27-36.
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AD, Cockcroft JR, Wilkinson IB: "Isolated Systolic
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Egypt Heart J 62 (1): 89-101, March 2010
Metabolic Syndrome as A Predictor of Non Dipping Hypertension
ISLAM MOHAMED MAHDY EL-HELALY, MD; MOHAMED AYMAN SALEH, MD;
AYMAN SADEK, MD; AHMED ONSY, MD
Introduction: Metabolic syndrome (MS) and non-dipping hypertension both increase cardiovascular mortality. Although
both clinical modalities share common pathophysiologic factors in their etiologies, previous studies did not find any association
between them [1]. Metabolic syndrome is a complex disorder considered a "multiplex" cardiovascular risk factor, in that each
component of the cluster of abnormalities is a risk factor in its own right. Introduced as Syndrome X and also termed insulin
resistance syndrome [2,3]. It is known that blood pressure varies markedly over 24-h period but the prognostic significance of
these changes is still a matter for dispute. In particular, much attention has been paid to blood pressure changes associated with
the sleep-wake cycle. Most individuals have a substantial fall in blood pressure when they sleep accompanied by a decrease
in heart rate. It appeared that some individuals have little or no fall in blood pressure when they sleep. This has led to classification
of subjects into dippers and non-dippers [4]. Nocturnal non dipping refers to a 10% or lesser magnitude reduction in average
systolic blood pressure SBP and/or diastolic blood pressure DBP at nighttime compared to daytime SBP average values, The
remainder defined as dipper [5]. Reduced nocturnal blood pressure fall is considered one of clinical traits associated with a
greater cardiovascular risk and end organ damage [6,7].
Aim of work: This work aimed at investigating the association between metabolic syndrome according to International
Diabetes Federation criteria 2006 and non-dipping blood pressure as assessed by 24h ambulatory blood pressure.
Patients and Methods: This study included 100 consecutive patients referred to the clinic in Mubarak Police Hospital with
recently diagnosed essential hypertension for evaluation of blood pressure with ambulatory blood pressure monitoring (ABPM).
These patients were subdivided into two groups according to the International Diabetes Federation 2006 (IDF 2006) criteria
of metabolic syndrome. 1) 50 patients had metabolic syndrome. 2) 50 patients did not have metabolic syndrome.
Exclusion criteria: Patients who had any of the following conditions are excluded from the study such as: Secondary
hypertension, Congestive heart failure, Previous myocardial infarction, Cardiac valve disease, Chronic renal failure, Any
conditions preventing technically adequate ABPM as atrial fibrillation.
All of the Patients were Evaluated as Follow: I-A detailed history taking, II-A careful physical examination was done with
search for evidence of organ damage and signs suggesting secondary hypertension, III-Laboratory investigations, IV-
Electrocardiogram: 12 leads ECG was done under resting condition, V-All the patients with metabolic syndrome were evaluated
according to Metabolic syndrome score (MS-Score) and VI-Ambulatory blood pressure monitoring (ABPM).
Results: Study included 56 male representing 56% and 44 female, Dippers were 61 patients (61%) while non dippers were
39 patients (39%) who showed a 10% or lesser magnitude reduction in average SBP and/or DBP at nighttime compared to
daytime SBP and/or DBP average value. The WC was above normal range in (17 subjects) 35.4% of dippers and (31 subjects)
64.6% of non dippers (p

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
and male gender. The MS-score level was the most strong independent predictor of non dipping status with Odds ratio (OR)
12.3, 95% Confidence Interval (CI) 4.371-29.245, (p

Islam M.M. El-Helaly, et al
study such as: Secondary hypertension, Congestive
heart failure, Previous myocardial infarction, Cardiac
valve disease, Chronic renal failure, Any
conditions preventing technically adequate ABPM
as atrial fibrillation.
All of the patients were evaluated as follow:
I- A detailed history taking was done and provided
information about:
(A) Risk factors such as smoking, diabetes mellitus
which is a group of metabolic diseases characterized
by hyperglycemia due to defects in
insulin secretion, action or both (ADA, 2008),
hypertension, medical treatment, lifestyle factors
such as dietary intake and physical activity.
(B) Past history or current symptoms of coronary
disease, heart failure, cerebrovascular or peripheral
vascular disease, renal disease, gout,
dyslipidemia, asthma or any other significant
illnesses.
(C) Symptoms suggestive of secondary causes of
hypertension and intake of drugs or substances
that can raise blood pressure such as nasal
drops.
(D) Family and environmental factors that may
influence blood pressure.
II- A careful physical examination was done with
search for evidence of organ damage and signs
suggesting secondary hypertension:
Office Arterial blood pressure was measured
by a physician in the hospital clinic, using a mercury
sphygmomanometer, after the subject sat for
≥5 min and at least 30 minutes after caffeine, and
smoking and without any stress. Measurements
were done with appropriate Cuff size; the bladder
encircled and covered two-thirds of the length of
the arm. A stethoscope placed lightly over the
brachial artery. The cuff was at the level of the
heart. Systolic pressure was defined as the pressure
reading at the onset of the sounds described by
Korotkoff (Phase one). Diastolic pressure was then
recorded as the pressure at which the sounds disappeared
(K5). The average of six or more measurements
for three sessions within a week was
considered for the analysis with two measurements
made at least 5 minutes apart each session, the
patients were not on any adrenergic stimulants,
such as those found in many cold medications. An
initial measurement included both arms. In elderly
patients aged 60 years or more blood pressure was
measured in the lying, sitting and standing position
[1].
91
Waist circumference was measured at the midpoint
between the bottom of the rib cage and above
the top of the iliac crest from patient in standing
position at breath hold after full expiration using
a flexible tape measure and maintaining close
contact with the skin without compression of the
underlying tissue [1].
III- Laboratory investigations were done as follow:
Fasting blood sugar: blood sample was taken
from the patient after fasting for 8 hours and analyzed
with enzymatic ultraviolet test (N: 70-100
mg/dl) (ADA, 2008).
Fasting serum triglycerides: (N

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
V- All the patients with metabolic syndrome
were evaluated according to Metabolic syndrome
score (MS-Score) developed by [10] which was
modified according to International Diabetes Federation
2006 for Middle East (Arab) populations
Waist circumference and then all the points that
were assigned for the different 6 risk factors are
summed. These 6 risk factors were shown in the
Table (2) as the following: (I) Male gender, (II)
Age >50 years, (III) Waist circumference, (IV)
Fasting HDL-C, (V) Fasting Triglycerides, (VI)
Fasting blood glucose.
Table 2: Metabolic syndrome score.
Risk factor
Men
Age >50 years
Waist circumference:

Islam M.M. El-Helaly, et al
Table 3: Gender and smokers frequency in the whole study.
Male/female
Smokers/non-smokers
Total
Frequency
56/44
33/67
100
Percent
Table (4) describes age, waist circumference,
biochemical data and metabolic score in the whole
study and showed that the mean age of the whole
populations was 49.2±7.1 years and ranged between
(28-68) years, the mean waist circumference was
92±9.7 cm and ranged between (75-109) cm, the
mean fasting blood sugar was 122±59.4 mg/dl and
ranged between (48-408) mg/dl, the mean fasting
triglycerides was 199±124.3 mg/dl and ranged
between (48-855) mg/dl, the mean fasting high
density lipoproteins was 47.1±14.2 mg/dl and
ranged between (13-99) mg/dl, the mean fasting
low density lipoproteins was143±45.1 and ranged
between (56-260) mg/dl.
All the patients were evaluated according to
metabolic syndrome score, the mean score was
38.6±8.3 and ranged between (17-53).
Table 4: Age, WC, biochemical data and MSscore
in the whole study population.
AGE (yrs)
WC (cm)
FBS (mg/dl)
TG (mg/dl)
HDL (mg/dl)
LDL (mg/dl)
MS-score
Mean
49.2±7.1
92±9.7
122.9±59.4
199±124.3
47.1±14.2
143±45.1
38.6±8.3
Range
28-68
75-109
84-408
48-855
13-99
56-260
17-53
56-44
33-67
100
The mean clinic systolic blood pressure was
153±8.1 mmHg and ranged between (140-170)
mmHg, the mean clinic diastolic blood pressure
was95.1±6.4 mmHg and ranged between (80-115)
mmHg, the mean average day systolic blood pressure
was 141.7±6.1 mmHg and ranged between
(135-161) mmHg, the mean average day diastolic
blood pressure was 83.1±6.7 mmHg and ranged
between (70-99) mmHg, the mean average night
systolic blood pressure 128±13.5 mmHg and ranged
between (111-174) mmHg, the mean average night
diastolic blood pressure was 74.8±8.7 mmHg and
ranged between (62-99) mmHg.
93
II- Analysis of dippers and non dippers data of
the whole study population:
Dippers were 61 patients (61%) while non
dippers were 39 patients (39%) who showed a 10%
or lesser magnitude reduction in average SBP
and/or DBP at nighttime compared to daytime SBP
and/or DBP average value as shown in Chart (1).
Dippers %
Table (5) describes the number and age in
dippers and non dippers of the whole study population
and showed that the mean age of dippers
was 48.8±6.6 and that of non dippers was 49.6±7.8
and there was no significant difference between
the two groups.
Table 5: Number and mean age in dippers and non dippers
of the study.
Number
Mean age (yrs)
70
60
50
40
30
20
10
0
Non-dippers %
Chart 1: Dippers and non dippers frequency in the whole
study population.
Dippers
61
48.8±6.6
Frequency
Non dippers
39
49.6±7.8
p
–
0.597
Table (6) describes Frequency and percentage
of MS risk factors in dippers and non dippers of
the whole study and showed that:
The WC was above normal range in (17 subjects)
35.4% of dippers and (31 subjects) 64.6%
of non dippers. There was a highly significant
difference between the two groups.
The HDL level was below normal range in (22
subjects) 47.8% of dippers and (24 subjects) 52.2%
of non dippers, there was a significant difference
between the two groups. The TG level was above
normal range in (27 subjects) 47.4% of dippers
and (30 subjects) 52.6% of non dippers, there was
a highly significant difference between the two
groups.
61
61
39
39

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
The FBS was above normal range in (28 subjects)
41.8% of dippers and (39 subjects) 58.2%
of non dippers. There was a highly significant
difference between the two groups.
Table 6: Frequency and percentage of MS risk factors in
dippers and non dippers of the whole study.
WC ANR
HDL BNR
TG >150 mg/dl
FBS >100 mg/dl
Dippers
17 (35.4%)
22 (47.8%)
27 (47.4%)
28 (41.8%)
Non dippers
31 (64.6%)
24 (52.2%)
30 (52.6%)
39 (58.2%)
(ANR: Above normal range, BNR: Below normal range).

Islam M.M. El-Helaly, et al
Dippers %
50
40
30
20
10
0
Non-dippers %
17
Chart 2: Number of dippers and non dippers with and without
the metabolic syndrome.
Table (9) describes the age, WC, biochemical
data and MS-score in dippers and non dippers
patients with metabolic syndrome and showed that:
The mean age of dippers was 47.2±6.7 years
and that of non dippers was 49.3±8.1 years. There
was no significant difference between the two
groups.
The mean waist circumference of dippers was
99.2±3.9 cm and that of non dippers was 99.5±6.5
cm. There was no significant difference between
them.
The mean fasting TG of dippers was 225.5±
106.5 mg/dl and that of non dippers was 250.9±
119.3 mg/dl. There was no significant difference
between the two groups.
The mean fasting HDL of dippers was 44.4±17.1
mg/dl and that of non dippers was 41.4±11.4 mg/dl.
There was no significant difference between the
two groups.
The mean fasting LDL of dippers was 147.9±
47.6 mg/dl and that of non dippers was 161.4±45.1
mg/dl. There was no significant difference between
the two groups.
The mean fasting blood sugar of dippers was
97.4±10.1 mg/dl and that of non dippers was
170.1±85.3 mg/dl. There was a highly significant
difference between the two groups.
There was no subject with DM (0%) in dippers
while 8 subjects (24%) of the non dippers had DM.
There was a highly significant difference between
the two groups.
33
44
Metabolic Non
17
33
44
6
6
95
The mean metabolic score of dippers was 28.9±
5.1 and that of non dippers was 43.6±4.2 and there
was a highly significant difference between the
two groups.
Table 9: Age, WC, biochemical data and MS-score in dippers
and non dippers patients with metabolic syndrome.
Age (yrs)
WC (cm)
TG (mg/dl)
HDL (mg/dl)
LDL (mg/dl)
FBS (mg/dl)
DM
MS-score
Dippers
47.2±6.7
99.2±3.9
225.5±106.5
44.4±17.1
147.9±47.6
97.4±10.1
0 (0%)
28.9±5.1
Non dippers
49.3±8.1
99.5±6.5
250.9±119.3
41.4±11.4
161.4±45.1
170.1±85.3
8 (24%)
43.6±4.2
p
0.375
0.830
0.463
0.463
0.333

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
Table 10: Age, WC, biochemical data and MS-score in dippers
and non dippers of patients without metabolic syndrome.
Age (yrs)
WC (cm)
TG (mg/dl)
HDL (mg/dl)
LDL (mg/dl)
FBS (mg/dl)
MS-score
Dippers
49.5±6.6
84.7±6.7
139.7±65.7
50.5±11.7
133.6±39.1
98.1±6.8
23.7±6.4
Non dippers
51.7±6.5
83±7.5
139.2±62.5
60.3±21.9
119.8±17.6
117.8±12.7
37.5±4.6
0.451
0.562
0.984
0.094
0.403

Islam M.M. El-Helaly, et al
Table (13) describes the age, frequency and
percent of gender and smokers in subjects with
high score MS and that of low score MS of the
whole study population and showed that:
The mean age was 49.2±7.8 cm in high MSscore
and 49.1±6.7 cm in that of low MS-score.
There was no significant difference between the
two groups.
Males constituted 62% (23 patients) of subjects
with high MS-score and 54% (34 patients) of
subjects with low MS-score. There was no significant
difference between the two groups.
Females constituted 38% (14 patients) of subjects
with high MS-score and 46% (29 patients)
of subjects with low MS-score. There was no
significant difference between the two groups.
Smokers constituted 32% (12 patients) of subjects
with high MS-score and 33% (21 patients)
of subjects with low MS-score (33%). There was
no significant difference between the two groups.
Table 13: Age, gender, smokers in high MS-score and low
MS-score of the whole study.
Age (yrs)
Gender (M)
Gender (F)
Smokers
70
60
50
40
30
20
10
0
High score
Low score
Chart 4: Percentage of high MS-score and low MS-score of
the whole study population.
High score
49.2±7.8
23 (62%)
14 (38%)
12 (32%)
37
Number
37
63
63
Low score
49.1±6.7
34 (54%)
29 (46%)
21 (33%)
p
0.960
0.104
0.244
0.171
97
Table (14) describes the WC, biochemical data
and metabolic score in high MS-score and low
MS-score of the whole study and showed that:
The mean waist circumference was 98.1±7.6
cm in subjects with high MS-score and 88.3±9 cm
in that of low MS-score. There was a highly significant
difference between the two groups.
The mean fasting blood sugar in subjects with
high MS-score was 164.5±82.1 mg/dl and in that
of low MS-score was 98.5±8.5 mg/dl. There was
a highly significant difference between the two
groups.
The mean fasting TG was 238.3±118.5 mg/dl
in subjects with high MS-score and 163.3±87.6
mg/dl in that of low MS-score. There was a highly
significant difference between the two groups.
The mean fasting HDL was 43.1±12 mg/dl in
subjects with high MS-score and 49.4±14.9 mg/dl
in that of low MS-score. There was a significant
difference between the two groups.
The mean fasting LDL was 157.2±44.7 mg/dl
in subjects with high MS-score and 136.8±41.3
mg/dl in that of low MS-score. There was a significant
difference between the two groups.
The mean metabolic score was 43.2±4.2 in
subjects with high MS-score and 25.4±6.5 in that
of low MS-score. There was a highly significant
difference between the two groups.
Table 14: WC, biochemical data and MS-score in high MSscore
and low MS-score of the whole study population.
Waist circumference
(cm)
LDL (mg/dl)
HDL (mg/dl)
TG (mg/dl)
FBS (mg/dl)
MS-score
High score
98.1±7.6
157.2±44.7
43.1±12
238.3±118.5
164.5±82.1
43.2±4.2
Low score
88.3±9
136.8±41.3
49.4±14.9
163.3±87.6
98.5±8.5
25.4±6.5
p

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
score. There was a significant difference between
the two groups.
The mean average day diastolic blood pressure
was 84.1±6.3 mmHg in subjects with high MSscore
and 82.6±6.9 mmHg in that of low MS-score.
There was no significant difference between the
two groups.
The mean average night systolic blood pressure
was 141±12.8 mmHg in subjects with high MSscore
and 121.4±6.8 mmHg in that of low MSscore.
There was a highly significant difference
between the two groups. The mean average night
diastolic blood pressure was 80.4±9.7 mmHg in
subjects with high MS-score and 71.5±6 mmHg
in that of low MS-score. There was a highly significant
difference between the two groups.
Table 15: ABPM data in high MS-score and low MS-score
of the whole study population.
Daytime SBP
Daytime DBP
Nighttime SBP
Nighttime DBP
High score
143.9±7.4
84.1±6.3
141.8±12.8
80.4±9.7
Low score
140.3±4.4
82.6±6.9
121.4±6.8
71.5±6
0.002
0.274

Islam M.M. El-Helaly, et al
that it can be precipitated by multiple underlying
risk factors. The most important of these underlying
risk factors are abdominal obesity and insulin
resistance. Other associated conditions include
physical inactivity, aging, hormonal imbalance,
and genetic or ethnic predisposition [8].
It is known that blood pressure varies markedly
over 24-h period but the prognostic significance
of these changes is still a matter for dispute. In
particular, much attention has been paid to blood
pressure changes associated with the sleep-wake
cycle. Most individuals have a substantial fall in
blood pressure when they sleep accompanied by
a decrease in heart rate. It appeared that some
individuals have little or no fall in blood pressure
when they sleep. This has led to classification of
subjects into dippers and non-dippers [4].
Nocturnal non dipping refers to a 10% or lesser
magnitude reduction in average systolic blood
pressure SBP and/or diastolic blood pressure DBP
at nighttime compared to daytime SBP and/or DBP
average values, the remainder defined as dipper
[5].
Reduced nocturnal blood pressure fall is considered
one of clinical traits associated with a
greater cardiovascular risk and end organ damage
[6,7].
The present study aimed at investigating the
association between metabolic syndrome according
to International Diabetes Federation criteria 2006
and non-dipping blood pressure as assessed by 24
h ambulatory blood pressure.
This study included one hundred consecutive
patients referred to our clinic in Mubarak Police
Hospital with recently diagnosed essential hypertension
for evaluation of blood pressure with ambulatory
blood pressure monitoring (ABPM).
These patients subdivided into two groups
according to the International Diabetes Federation
2006 (IDF 2006) criteria of metabolic syndrome.
These groups are:
1- 50 patients had metabolic syndrome.
2- 50 patients did not have metabolic syndrome.
All the patients had been evaluated with a
detailed history taking and a physical examination,
History taking provided information about risk
factors such as smoking, past medical history,
99
diabetes mellitus, hypertension, its duration and
medical treatment.
Patients are excluded from the study if they
have Secondary hypertension, Congestive heart
failure, previous myocardial infarction, Cardiac
valve disease, chronic renal failure, any conditions
preventing technically adequate ABPM as atrial
fibrillation and other arrhythmia.
All the patients underwent laboratory investigations
for FBS, TG, HDL, and LDL. Waist circumference
had been measured and Twenty-fourhour
ABPM had been carried out for the entire
patients and then evaluated according to MS-score.
Dippers constituted (61%) of the population
studied while non dippers constituted (39%). There
were more non-dippers with the metabolic syndrome
(66%) than patients in those without the
metabolic syndrome (12%) and these results are
in agreement with [11].
Hassan MO et al [11] examined the circadian
changes in blood pressure and their relation to the
metabolic syndrome and its components in 1124
subjects in Omani Arabs. According to the International
Diabetes Federation's definition, 264
subjects had the metabolic syndrome, a prevalence
of 23%. Non-dippers with the metabolic syndrome
were 131 of 264 (50%), compared with 265 of 860
(31%) without the metabolic syndrome.
There were no significant differences in age,
sex, smoking, lipids profile and FBS between
dippers and non dippers and this goes with the
results of [1].
Tartan et al [1] studied 132 patients with newly
diagnosed essential hypertension in order to investigate
the association between MS and non dipping
blood pressure.
There were highly significant differences
(p

Metabolic Syndrome as A Predictor of Non Dipping Hypertension
We hypothesize that the important determinants
of a non dipping BP in this study were obesity,
DM and high MS-score in addition to higher 24
hour systolic blood pressure.
In patients with metabolic syndrome there were
no significant differences in age, WC and lipids
profile between dippers and non dippers and this
goes with the results of [11].
In patients with metabolic syndrome there were
highly significant differences in FBS, DM and
MS-score between dippers and non dippers and
this goes with the results of [1].
In patients with metabolic syndrome there were
significant differences in average day SBP and
average night SBP and DBP and no significant
difference in average day DBP between dippers
and non dippers and it goes with the results of [11].
In this study non dipping state in patients with
metabolic syndrome is closely related to elevated
FBS, DM and high MS-score in addition to higher
24 hour systolic blood pressure.
In the present study High MS-score was defined
as a MS-score >34 which was the optimal cut-off
point to differentiate the patients having non dipping
feature, based on the curve analysis as shown
in chart 3, and thus, this study was able to show
that a high MS-score, but not MS-IDF, predicts
non dipping blood pressure.
High MS-score subjects showed highly significant
differences in WC, FBS, TG, HDL, and MSscore
than those with low MS-score and this goes
with the results of [1].
A highly significant relationship was present
between increasing MS-score and all systolic blood
pressure particularly with night SBP and this goes
with the results of [1].
In this study multivariate logistic regression
analysis was used to determine the independent
factors related to the development of non dipping
status and showed that the MS-score level was the
strongest independent predictor of non dipping
status with Odds ratio (OR) 12.3, 95% Confidence
Interval (CI) 4.371-29.245, (p

Islam M.M. El-Helaly, et al
blood pressure reproducibility: results of the HARVEST
trial. Hypertension 1994; 23: 211-216.
5- Takakuwa H, Ise T, Kato T, Izumiya Y, Shimizu K, Yokoyama
H, Kobayashi KI: Diurnal variation of hemodynamic
indices in non-dipper hypertensive patients. Hypertens
Res 2001; 24: 195-203.
6- Bianchi S, Bigazzi R, Baldari G, Sgherri G, Campese
VM: Diurnal variation of blood pressure and microalbuminuria
in essential hypertension. Am J Hypertens 1994;
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7- Cuspidi C, Amroioni E, Mancia G, Pessina AC, Trimarco
B, Zanchetti A: Role of echocardiography and carotid
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8- Grundy SM: Metabolic Syndrome Scientific Statement
by the American Heart Association and the National Heart,
Lung, and Blood Institute Arterioscler. Thromb Vasc Biol
November 2005; 1, 25 (11): 2243-2244.
9- American Heart Association: New approaches to treating
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10- Macchia A, Levantesi G, Borrelli G, Franzosi MG, Maggioni
AP, Marfisi R, Scarano M, Tavazzi L, Tognoni G,
Valagussa F, Marchioli R: A clinically practicable diagnostic
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Studio della Sopravvivenza nell'Infarto miocardico (GIS-
SI)-Prevenzione scoring. Associazione Nazionale Medici
Cardiologi Ospedalieri; Istituto di Ricerche Farmacologiche
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Maria Imbaro; Gruppo Italiano per lo Studio della Sopravvivenza
nell'Infarto miocardico (GISSI)-Prevenzione
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9.

Egypt Heart J 62 (1): 103-110, March 2010
Quantitative Power Doppler Technique of Myocardial Contrast
Echocardiography: For the Detection of Segmental Myocardial
Perfusion Profile
YOUSSEF FM NOSIR, MD* , **; ASHRAF A ALI, MD* , **; ALI A ABD-ELMAGID, MD**;
MAMDOUH ALTAHAN, MD**; MANSOUR MOSTAFA, MD**;
ABDELMAKSOUD S AHMED, MD**; AYMAN KHOLIEF, MD**;
HASSAN CHAMSI PASHA, MD*; EZZ EL-SSAWY, MD**
Background: Myocardial contrast echocardiography (MCE) is a relatively new method of visualizing the perfusion territory
of a coronary artery using an intravenous (IV) injection of microbubbles. Harmonic power Doppler imaging (HPD) with IV
contrast agents can qualitatively identify myocardial perfusion defects in patients with ischaemic heart disease (IHD), however,
there is still a need to study the ability of HPD imaging to detect perfusion defect areas quantitatively (Q).
Objectives: The aim of the present study was to detect the feasibility of myocardial contrast echocardiography (MCE) using
Q-HPD technique for the assessment of left ventricular (LV) myocardial perfusion profile.
Methods: Twenty-one patients with a recent LV myocardial infarction were recruited for this study. Patients underwent both
MCE and coronary arteriography. MCE studies were performed using Phillips 75000 with IV infusion of sonicated diluted
Definity. Images were acquired from the apical window with stepwise increase triggering intervals (1 to 9 beats) at end-systole.
Images were scored for LV wall motion (WM) [16 segments model, (1=normal, 2=mild hypokinetic, 3=severe hypokinetic,
4=akinetic and 5=dyskinetic)] as well as for subjective visual estimation (VS) of LV perfusion profile (1=normal, 0.5=partial
and 0.0=no perfusion).
Results: Coronary arteriography showed that 18 out of the 21 patients had significant coronary artery stenosis (CAD), (5
one vessel, 12 with 2 vessels and 1 with 3 vessels CAD). The mean ± SD of Q-HPD (db) with MCE were 32±7.8, 9.3±3.4 and
3.5±1.6 for LV cavity, LV myocardial segments with normal and abnormal perfusion respectively. There was significant difference
between Q-HPD of LV cavity and normal segments (p=0.00001), and between segments of normal and abnormal perfusion
(p=0.0001). Significant difference was also found when Q-HPD measurements obtained from segments with abnormal perfusion
score were compared to measurements obtained from normal segments (p=0.003 and p=0.00001 for segments with VS score
of 0.5 and 0.0 respectively). When segments were compared according to WM score, the mean ± SD of Q-HPD (db) were
8.1±3.5 and 3.5±2.1 (p=0.00001) for normal and abnormal segments respectively. Significant difference was also found when
Q-HPD measurements obtained from abnormal segments were compared with values obtained from normal segments (p=0.0002,
p=0.0001 and p=0.004, for segments with WM score 2, 3 and 4, respectively. Q-HPD of MCE has very good sensitivity 100%
(100-100), specificity 67% (47-87) and overall accuracy of 95% (86-104) for detecting CAD. WM score has good sensitivity
88% (74-102), specificity 75% (56-94) and overall accuracy of 86% (71-101) for detecting CAD.
Conclusion: Quantitative analysis of myocardial perfusion images obtained with HPD technique is feasible and could be
performed in all patients recruited in this study with very good sensitivity, specificity and overall accuracy for detecting CAD.
Therefore, Q-HPD analysis is recommended for objective differentiation between normal and abnormal perfusion profile of
LV myocardium.
Key Words: Myocardial perfusion imaging – Harmonic power Doppler echocardiography – Myocardial infarction.
From Cardiac Service, Kng Fahd Armed Force Hospital,
Jeddah, KSA* and The Cardiology Department, Al-Hussein
University Hospital, Al-Azhar University, Cairo, Egypt**.
Manuscript received 2 Jan., 2010; revised 10 Feb., 2010;
accepted 12 Feb., 2010.
Address for Correspondence: Dr. Youssef FM Nosir,
From Cardiac Service, Kng Fahd Armed Force Hospital,
Jeddah, KSA* and The Cardiology Department, Al-Hussein
University Hospital, Al-Azhar University, Cairo, Egypt**.
103
Appreviation list:
MCE = Myocardial Contrast echocardiography.
IV = Intravenous.
HPD = Harmonic Power Doppler.
ECG = Electrocardiogram.
SD = Standard Deviation.
WM = Wall Motion.
SPECT = Single Photon Emission Computed Tomography.

Quantitative Power Doppler Technique of Myocardial Contrast Echocardiography
Introduction
There is a growing interest in recent years in
preserving acutely ischaemic myocardium which
led to the development of thrombolitic and interventional
techniques for restoring coronary perfusion
to the jeopardized myocardium [1-3]. Coronary
arteriography was used to evaluate the success of
these techniques, however it does not provide an
assessment of myocardial perfusion [4-6]. Thallium
scintigraphy has been widely used as a method to
study the myocardial perfusion [7-8], however, the
technique is rather expensive and necessitates the
exposure of the patient to ionized radiation.
Myocardial contrast echocardiography (MCE)
is a relatively new method of visualizing the perfusion
territory of a coronary artery through an
intravenous (IV) injection of microbubbles [9-14].
Intermittent second harmonic and pulse inversion
imaging can identify myocardial perfusion defect
in gray scale [12-14]. Microbubbles are known to
produce characteristic signals when exposed to
high amplitude of ultrasound. Harmonic power
Doppler (HPD) imaging had the potential to record
the broad band signal during dissolution of the
microbubbles in the myocardial microcirculation.
Preliminary results demonstrated that HPD imaging
with transvenous contrast agents can qualitatively
identify myocardial perfusion defects in patients
with ischaemic heart disease [9-14]. However, there
is still a need to detect segmental perfusion defects
quantitatively using MCE with HPD imaging.
Therefore the aim of the present study was to
detect the feasibility of the quantitative (Q) HPD
technique with MCE for detecting myocardial
perfusion profile. Quantitative data were then
compared with the results obtained from both
segmental visual estimation of MCE and segmental
wall motion score.
Subjects
Twenty one patients with a recent myocardial
infarction, referred to the echocardiographic laboratory
(King Fahd Hospital from September 2007
till January 2009) for the assessment of left ventricular
function. Patients were pre-selected for
optimal apical echocardiographic image quality.
Myocardial infarction was defined on the basis of
a classic history, ST elevation >2mm in two contiguous
ECG leads and increase of creatinine phosphokinase
of >2 SD units. Patients were 16 males
and 5 females with a mean age of 57±12 years. All
104
patients were in sinus rhythm with a mean heart
rate of 76±13b/m. Subjects included 12 patients
with anterior wall and 9 patients with inferior wall
myocardial infarction. Verbal consent was obtained
from each patient after full explanation of the
procedure.
Methods:
Each patient underwent coronary arteriography
and two-dimensional echocardiographic examination
using Phillips 7500 with harmonic mode for
the assessment of left ventricular function. Images
were obtained from the apical window with the
patient in 45º left recumbent position. Apical 4chamber,
2-chamber and long axis views were
recorded for the assessment of left ventricular wall
motion using the 16-segments model (Fig. 1). Each
segment was scored using the 5 score index model
(1=normal wall motion, 2=mild hypokinesia,
3=severe hypokinesia, 4=akinesia & 5=dyskinesia).
Myocardial contrast echocardiography:
Myocardial contrast echocardiography was
performed with Phillips 7500 during continuous
IV infusion of Sonicated diluted Definity (Schering
AG, Duitsland) using the HPD mode.
Echocardiographic settings for contrast: The
gain setting of the echo machine should be adjusted
for grey scale myocardial visualization prior to IV
infusion of the contrast. The focus should be at the
level or just above the mitral annulus. Second
harmonic mode and power Doppler mode for image
acquisition were selected. Triggering mode is
adjusted at end-systole (peak of T wave). To avoid
colour artifact the gain setting is adjusted for HPD,
so that no colour artifact appears in the myocardium
at baseline before the contrast injection.
Image acquisition: Images were acquired from
the apical window using harmonic mode for both
grey scale and power Doppler with stepwise increase
triggering intervals from 1 to 9 beats at endsystole.
Apical 4-chamber, 2-chamber and apical
long axis views were obtained, recorded and stored
digitally for further off line qualitative and quantitative
analysis with the Phillips off-line quantitative
workstation (Q-laboratory).
Image analysis: HPD images were subjected
into qualitative and quantitative analysis using the
16 segments model.
Visual analysis: The recorded HPD images
were analyzed using the 3 score index (0=no per-

Youssef FM Nosir, et al
fusion, 0.5=delayed/partial perfusion & 1=complete
normal perfusion).
Quantitative analysis: Quantitative analysis of
the HPD images was performed off-line. For each
apical view and for each segment of the 16-segment
model, an area of interest (5mm X 5mm) was
selected within the myocardium for quantitative
analysis. In addition, quantitative HPD analysis
was also obtained from the left ventricular cavity
of the three apical views and then averaged (Fig.
2). Quantitative data were obtained from 5 successive
frames without echo dropouts, at peak triggering
intervals and data averaged.
Coronary arteriography:
Coronary arteriography for the identification
of the infarct-related coronary artery was performed,
for each patient after myocardial contrast
echocardiographic study, on the same day in 15
patients and within 48 hours in 6 patients. Clinical
condition and medications remained stable between
the two tests. The infarct related coronary artery
was identified as the one with reduced TIMI flow
and/or the artery with the more severe stenosis, if
the patient had more than one artery affected.
Mid post
sept
(10)
Basal post
sept
(5)
Apical
sept
(11)
4-chamber
Apical
lat
(13)
Mid
lat
(8)
Basal
lat
(3)
Apical
inf
(14)
Mid inf
(9)
Basal inf
(4)
105
Statistical analysis:
For each patient, analysis of wall motion score,
visual estimation of myocardial contrast echocardiographic
data and quantitative analysis was performed
blindly to all other technique results with
one week interval and without knowing the coronary
arteriographic results. Quantitative data were
presented as the mean ± standard deviation of each
segment in 5 successive frames without echo dropout.
Results obtained from the quantitative analysis
of HPD were then classified and compared according
to both the wall motion score index and according
to visual scoring of the myocardial perfusion
images. Paired student T-test was performed to
compare quantitative data obtained from the left
ventricular cavity to the normal perfused segments
and normal to total number of abnormal perfused
segments. In addition, T-test was used to compare
normal segments to abnormal segments when classified
according to both abnormal wall motion
score and abnormal visual estimation score. Significance
was stated at

Quantitative Power Doppler Technique of Myocardial Contrast Echocardiography
Results
Myocardial contrast echocardiographic study
was performed successfully in all patients recruited
in this study. There were no adverse events.
Coronary arteriography:
Coronary arteriographic data revealed that 18
out of the 21 patients had significant coronary
(A) (B)
Figure 2: Myocardial perfusion image of apical 2-chamber view obtained from a patient having anterior wall myocardial
infarction. Displays are in gray scale (panel A) and power Doppler (panel B). There is a perfusion defect involving
the anterior wall and part of the apex while the inferior wall shows normal perfusion. This figure demonstrated that
power Doppler image could reflect the myocardial segments with normal and abnormal perfusion.
(A) (B)
Figure 3: Myocardial perfusion image of a patient with anterior wall myocardial infarction, using harmonic power Doppler
mode is demonstrated. Panel A shows the apical 2-chamber view with perfusion defect involving the posterior septum
and septal part of the apex. while lateral wall shows normal perfusion profile. The number in the rectangles represents
the MCE power reflected from each selected area of interest in db. Panel B shows the coronary arteiography (left
system) of this patient revealing significant proximal left anterior descending (LAD) and distal circumflex (CX)
coronary artery stenosis.
106
artery stenosis. Five patients had one vessel, 12
patients had two vessels and 1 patient had 3 vessels
coronary artery disease.
Wall motion score:
Wall motion analysis with the 16 segments
score index of the echocardiographic examination,
revealed the presence of abnormal wall motion in
16 out of the 21 patients. Among these 16 patients,

Youssef FM Nosir, et al
15 had significant coronary artery disease by coronary
arteriography. Out of the 5 patients with no
wall motion abnormality 3 had significant coronary
artery disease by coronary arteriography.
Myocardial perfusion imaging:
Analysis of the myocardial perfusion echocardiographic
images with HPD after intravenous
injection of contrast agent revealed that 19 out of
the 21 patients had segmental myocardial perfusion
defects. Eighteen out of these 19 patients had
significant coronary artery disease by coronary
arteriography. The angiographic data from the two
patients with normal myocardial perfusion profile
revealed no significant coronary artery lesion.
The mean ± SD of Q-HPD (db) with MCE were
32±7.8, 9.3±3.4 and 3.5±1.6 for left ventricular
cavity, left ventricular myocardial segments with
normal and abnormal perfusion respectively. There
107
was significant difference between Q-HPD of left
ventricular cavity and segments with normal perfusion
(p=0.00001), and between segments of
normal and abnormal perfusion (p=0.0001).
Quantitative HPD data of myocardial perfusion
echocardiography were classified and studied according
to both segmental wall motion score and
visual estimation of segmental myocardial perfusion
profile (Table 1).
Comparison between echocardiographic and coronary
arteriographic data:
Data obtained from wall motion score and
myocardial perfusion analysis were compared with
coronary arteriographic data. Sensitivity, specificity
and accuracy of both wall motion and myocardial
perfusion analysis to detect coronary artery disease
were calculated and presented in Table (2).
Table 1: Comparison between QHPD measurements of normal segments and measurements obtained
from abnormal segments when LV myocardial segments classified according both WMS
index and visual estimation of perfusion profile.
Mean ± SD
p
1
8.1±3.5
HPD according to WM
QHPD = Quantitative harmonic power Doppler.
LV = Left ventricle.
2
3.9±2.2
0.0002
3
3.4±1.1
0.0001
4
2.9±2.1
0.004
5
–
–
9.3±3.4
WMS = Wall motion score.
VS = Visual estimation.
1
HPD according to VS
0.5
4.3±2.1
0.003
0.0
2.3±1.1
0.00001
SD = Standard deviation.
p = p value.
Table 2: Comparison between QHPD and WMS in predicting CAD as compared to coronary
arteriography.
QHPD
WMS
Sensitivity
100 (100-100)
88 (74-102)
Specificity
67 (47-87)
75 (56-94)
Negative PA
100 (100-100)
60 (39-81)
Positive PA
95 (85-104)
94 (83-104)
CAD = Coronary artery disease. PA = Predictive accuracy, all other abbreviations as in table.
Discussion
In patients with acute myocardial infarction
who have undergone attempted reperfusion, the
cardiologist needs to know whether the myocardium
has been successfully reperfused, how much of the
myocardium has been salvaged and how much can
still potentially be salvaged. The current methods
of evaluating infarct size are indirect and do not
provide a complete assessment of both the infarct
size and area at risk [15]. Cardiac enzymes [16] and
electrocardiogram [17,18] are useful clinical tools
in the diagnosis of acute ischaemic syndromes.
Electrocardiogram is less valuable in determining
Overall Accuracy
95 (86-104
86 (71-101)
the success of reperfusion or the extent of myocardial
salvage. Cardiac enzymes do provide an accurate
estimate of infarct size, however they do so
without reference to the risk area that can expand
and result in left ventricular dilation and heart
failure [16].
Wall motion abnormality is a valuable tool for
the diagnosis of prior infarction and resting or
inducible ischemia. However, in patients with acute
myocardial infarction who have recently undergone
reperfusion therapy wall motion abnormality is
likely to be present with or without successful
reperfusion. Regional function will be normal if

Quantitative Power Doppler Technique of Myocardial Contrast Echocardiography
the period of ischaemia was very brief, which is
uncommon in the clinical practice [19].
Coronary arteriography can be used to indicate
restoring the patency of the coronary arteries [4].
However recent studies demonstrated that coronary
arteriography has very limited value in determining
the success of myocardial reperfusion as one sixth
to one fourth of all patients with Timi grade 3 flow
have poor tissue perfusion due to loss of microvascular
integrity. This has recently been defined as
no-reflow phenomenon [20]. Therefore, in order to
study myocardial perfusion and/or reperfusion one
has to assess myocardial capillary blood flow [5,21].
Of the currently available and developing techniques
capable of assessing capillary blood flow
are single-photon emission computed tomography
(SPECT) and MCE [22-23].
SPECT technique has been used for detection
of CAD and risk stratification [7,8]. It has also
provided valuable data of coronary physiology and
pathophsiology. However the technique is limited
because of the need to inject radioisotopes, exposure
to radiation, time consuming and expense [12].
MCE proved to be the most promising technique
since it uses microbubbles, which are pure intravascular
tracers [9-14,22,23].
The results of this study demonstrated that HPD
of MCE is a feasible technique for detection of
segmental myocardial perfusion profile. Segment
to segment concordance between MCE scoring
and WMA scoring was excellent and both showed
concordance with the infarct related artery. However,
HPD of MCE showed higher sensitivity,
specificity and predictive accuracy for detection
of coronary artery disease, than that obtained from
WMA score when compared with coronary arteriography.
One out of the 19 patients with myocardial
perfusion defects had normal coronary arteriogram,
this could be explained by the no-reflow phenomena
with the possible loss of microvascular integrity.
Segmental quantitative analysis of HPD images
with MCE is feasible. Significant difference was
found between quantitative HPD of left ventricular
cavity and segments with normal perfusion
(p=0.00001), and between segments with normal
and abnormal perfusion (p=0.0001). Significant
difference was also found when HPD measurements
obtained from segments with partial and segments
with no perfusion were compared to measurements
obtained from segments with normal perfusion
108
(Table 1). In addition, significant difference was
found when HPD measurements obtained from
segments with abnormal wall motion were compared
with values obtained from segments with
normal wall motion (p=0.0002, p=0.0001 and
p=0.004, for segments with WM score 2, 3 and 4,
respectively.
Our results demonstrated that the assessment
of myocardial perfusion profile of HPD images
with MCE could be performed quantitatively. Quantitative
HPD data reflected from the left ventricular
cavity was around (= ~ 30db), normal perfused myocardial
segment (= ~ 9db), myocardial segments
with partial perfusion (= ~ 4db) and myocardial
segment with no perfusion (≤2.3db).
Study limitations, clinical implications and future
directions:
Echocardiographic examination with intravenous
infusion of contrast agents can be used with
harmonic mode for left ventricular opacification
and HPD mode for the assessment of myocardial
perfusion.
Left ventricular opacification is used for endocardial
border delineation for calculation of left
ventricular volume and mass, as well as for the
assessment of wall motion abnormality at rest and
during stress echocardiography.
Myocardial perfusion imaging with contrast
echocardiography can be used in-patients with
myocardial infarction to determine the infarct size
and area at risk. In-patients who underwent coronary
revascularization, myocardial contrast echocardiography
can be used to assess reperfusion efficacy
and to diagnose the no-reflow phenomena.
Myocardial contrast echocardiography can be
used in conjunction with stress echocardiography
to study myocardial viability at low dose dobutamine,
myocardial ischaemia at peak stress and/or
with IV administration of vasodilators to determine
the coronary flow reserve. In addition, myocardial
contrast echocardiography can assess the collateral
flow.
The present study was designed to study the
feasibility of quantitative HPD of myocardial contrast
echocardiography for detection of myocardial
perfusion profile as compared to both visual estimation
of MCE and wall motion score index. It
shoes its superiority over wall motion score using
coronary arteriographic data as the anatomical

Youssef FM Nosir, et al
reference. However there is still a need to compare
quantitative HPD echocardiographic data to data
obtained from other imaging technique like SPECT.
Patients were pre-selected for good apical image
quality, there is still a need to study MCE independent
from image quality or by using transeosophageal
echocardiographic technique.
Moreover, myocardial contrast echocardiography
with HPD technique is at its infancy and
there is still a need to reach an optimal clinical
protocol. There is still a need to optimize the dose
required for each available contrast agent in order
to visualize the myocardial perfusion. Recent advances
in ultrasound technology such as flash
imaging allows continuous myocardial perfusion
imaging. The optimal technique for detection of
segmental perfusion defect is not well established
yet. Disagreement concerning the mode of administration
of the contrast agents at different scenarios
is still present. Is it better to use continuous intravenous
infusion or bolus injection, particularly
during stress echocardiography.
In addition, controversy still exists whether
image analysis using harmonic grey scale or HPD
should be used. Data presented in this study shows
that if HPD imaging is used, analysis should be
performed quantitatively.
Conclusion
Quantitative analysis of myocardial perfusion
images obtained by HPD technique could be performed
in all patients with myocardial infarction
recruited in this study. Therefore, quantitative HPD
analysis is recommended for objective differentiation
between normal and abnormal perfusion
profile of LV myocardium.
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Egypt Heart J 62 (1): 111-116, March 2010
The Carotid-Femoral Arterial Index and the Severity of
Coronary Atherosclerosis
MAHMOUD SOLIMAN, MD*; HESHAM HASAN, MD*; TAMER GAZY, MSc*;
WALAA FAREED, MD*; ASHRAF REDA, MD*; SAID SHALABY, MD*
Although extensively investigated, the value of carotid intima media thickness as surrogate marker of coronary atherosclerosis
is still a matter of debate. Examination of other vascular beds and hence more atherosclerotic burden may have more impact
than examination of carotids alone.
Aim: Detection of coronary atherosclerosis and assessment of its severity non-invasively by examination of the common
carotid and superficial femoral arteries.
Subjects and Methods: This study included 120 patients; (30 with normal coronary arteries, group 1, 30 patients with single
vessel disease group 2, 30 with two vessel disease group 3, 30 with three vessel disease group 4). The severity of coronary
atherosclerosis calculated according to Gensini score.
All patients underwent a vascular duplex scan of the right and left carotid arteries and the right and left femoral superficial
arteries by means of transcutaneous high axial resolution B-mode ultrasound imaging, the Carotid femoral index (CARFEM)
in mm was determined as follows: (Intima media thickness of right common carotid + IMT left common carotid + Total width
of right femoral + Total Width left femoral)/4.
Results: The CARFEM index was: 0.54±0.06 in group 1, 0.87±0.04 in group 2, 1.22±0.08 in group 3 and 1.54±0.1 in group
4 and the difference was highly significant, p value

The Carotid-Femoral Arterial Index & the Severity of Coronary Atherosclerosis
Whether examination of more vascular beds
(like femoral arteries) and hence more atherosclerotic
burden could affect this correlation is still
unclear.
Aim of the work: Detection of coronary atherosclerosis
and assessment of its severity noninvasively
by examination of the common carotid
and superficial femoral arteries.
Subjects and Methods
The present study included 120 patients; 90
with coronary atherosclerosis; (30 with single
vessel disease, 30 with two vessel disease, 30 with
three vessel disease), 30 with normal coronary
angiography; (10 preoperative assessment, 12 with
typical chest pain and highly suggestion of angina
pectoris, combined with electrocardiographic aberrations
during an exercise test, 8 with positive
either stress ECG test or dobutamine Echocardiography),
63 males (52.5%) and 57 females (47.5%)
with age ranged from (35-68) years. All subjects
underwent coronary arteriography by the Judkins
method.
According to the findings from coronary angiographic
exploration we divided our patients into
four groups: Group 1 with normal coronary arteries;
Group 2 with one-vessel coronary artery disease;
Group 3 with two-vessel coronary artery disease;
and Group 4 with three-vessel coronary artery
disease.
The severity of coronary atherosclerosis calculated
according to (Gensini score) [6]. The Gensini
score was computed by assigning a severity score
to each coronary stenosis according to the degree
of luminal narrowing and its geographic importance.
Reduction in the lumen diameter were evaluated;
(reductions of 25%, 50%, 75%, 90%, 99%, and
complete occlusion were given scores of 1, 2, 4,
8, 16, and 32, respectively). Each principal vascular
segment was assigned a multiplier in accordance
with the functional significance of the myocardial
area supplied by that segment: The left main coronary
artery, x 5; the proximal segment of left
anterior descending coronary artery (LAD), x 2.5;
the proximal segment of the circumflex artery, x
2.5; the mid-segment of the LAD, x 1.5; the right
coronary artery, the distal segment of the LAD,
the posterolateral artery, and the obtuse marginal
artery, x 1; and others, x 0.5.
112
Gensini score of each lesion = (score of reduction
x score of vascular segment).
All patients included in the study underwent a
vascular duplex scan of the right and left carotid
arteries and the right and left femoral superficial
arteries by means of transcutaneous high axial
resolution B-mode ultrasound imaging.
The Carfem index in mm was determined as
follows [7]:
(IMThCR + IMThCL + TWThFR + TWThFL)/4.
Where: IMThCR denotes intima media thickness
of Rt. Common carotid artery, IMThCL denotes
intima media thickness of Lt. Common carotid
artery, TWThFR denotes the total wall
thickness of the right femoral superficial artery
and TWThFL denotes the total wall thickness of
the left femoral superficial artery.
Statistical methodology:
The data collected were tabulated and analyzed
by SPSS statistical package version 13 on IBM
compatible computer.
Quantitative data were expressed as mean and
standard deviation (X ± SD) analyzed by applying
ANOVA test (f-test) for comparison of more than
two groups of normally distributed variables; and
krauskal wallis test for non normally distributed
variables.
Qualitative data were expressed as number and
percentage (No & %) and analyzed by applying
chi-square (X 2) test.
Pearson correlation (r) was used to detect association
between quantitative variables.
All these tests were used as tests of significance
at p0.05, but there was significant difference for the
systolic blood pressure & diastolic blood pressure
p value

Mahmoud Soliman, et al
Table 1: Clinical characteristics and basic data in studied groups.
Variable
Age (years)
Sex:
Male
Female
SBP (mmHg)
DBP (mmHg)
DM:
+Ve
–Ve
WM:
+Ve
–Ve
Total Chol: mg/dl
HDL: mg/dl
LDL: mg/dl
TG: mg/dl
Group 1
(No. 30)
53.3±6.89
14 (46.7%)
16 (53.3%)
138.3±17.2
86.3±10.3
13 (43.3%)
17 (56.7%)
7 (23.3%)
23 (76.7%)
171±20.7
37.6±3.5
94.7±11.9
158±19.9
SBP : Systolic blood pressure.
DBP : Diastolic blood pressure.
DM : Diabetes Mellitus.
WM : Wall motion abnormalities.
Comparison between all studied group as regards
CARFEM index & Gensini score (Table
2):
CARFEM index showed highly significant
difference between all groups, p value

The Carotid-Femoral Arterial Index & the Severity of Coronary Atherosclerosis
CARFEM
CARFEM
1.9
1.8
1.7
1.6
1.5
1.4
Group: 4.00
Table 2: Comparison between all studied groups as regard to CARFEM index & Gensini score.
Variable
CARFEM mm.
Gensini score
Group 1
(No. 30)
0.54±0.06
0
CARFEM: Carotid-Femoral vascular index.
Group 2
(No. 30)
0.87±0.04
17.6±10.92
114
Group 3
(No. 30)
1.22±0.08
66±25.13
Group 4
(No. 30)
1.54±0.1
181.33±37.11
p. value

Mahmoud Soliman, et al
Figure 5: Lfeft common croatid, supper femoral arteries and
coronary angio of the same Patient.
Discussion
The value of Carotid intima media thickness
as surroguate of coronary atherosclerosis is still a
matter of debate. Many studies and even postmortem
studies documented high correlation between
carotid and coronary atherosclerosis [8-11]. However
other studies showed that the correlation between
carotid intima media thickness and severity of
coronary atherosclerosis is relatively weak [12].
115
Examination of more vascular beds (like femoral
arteries) and hence more atherosclerotic burden
may have more impact than examination of carotids
alone. In this study, the carotid femoral index
(CARFEM) was measured and correlated with
severity of coronary atherosclerosis detected by
quantitative coronary angiography according to
GENSINI score. In this study, all patients were
matched for age and sex to avoid possible effects
on atherosclerosis process.
There was significant difference between the
studied groups as regards: SBP, DBP, HDL, and
LDL which considered risk factors for atherosclerosis.
As regards CARFEM vascular index; there was
highly significant difference between all studied
groups, even group 3 & 4 p value 0.05.

The Carotid-Femoral Arterial Index & the Severity of Coronary Atherosclerosis
But, among patients with three vessels disease
there was significant positive correlation between
CARFEM index and Gensini score r: 0.4 & p value

Egypt Heart J 62 (1): 117-124, March 2010
Value of Contrast Echocardiography for the Diagnosis of
Hepatopulmonary Syndrome in Patients with Chronic Liver
Disease Due to Hepatitis C Virus
AMAL SHAWKY BAKIR, MD; GHADA EL-SHAHED, MD*
Background: Hepatopulmonary syndrome (HPS), a triad of liver disease, pulmonary gas exchange abnormalities and
widespread pulmonary vascular dilatation, is most commonly seen in patients with liver cirrhosis. Contrast-enhanced twodimensional
echocardiography (CEE) using agitated saline can be used to detect the presence and degree of intra or extracardiac
right-to-left shunting.
Aim: The aim of this work was to evaluate HPS in patients with chronic liver disease due to hepatitis C virus (HCV) using
CEE and to determine its relation to their clinical and laboratory profile.
Methods: Sixty patients with chronic liver disease due to hepatitis C virus underwent thorough clinical and laboratory
assessment for evaluation and Child classification of liver disease, and to confirm HCV virus infection. Arterial blood gas
analysis, abdominal ultrasonography, pulmonary function testing and upper GI endoscopy were done for all patients. CEE was
performed by injecting agitated saline into an antecubital vein. An intrapulmonary shunt (IPS) was considered present if
microbubbles appeared in the left atrium (LA) at least four heart beats after their appearance in the right side of the heart. It
was graded semi- quantitatively (grades I-IV) according to the relative opacification of the LA.
Results: The mean age of the patients was 48.28±5.3 years, and 90% were males. Thirty-one patients (51.67%) showed
positive echo findings, reflecting the presence of IPS. Twelve patients (20%) had grade II echo findings, 7 (11.67%) had grade
III, and 12 (20%) had grade IV echo findings. Sixteen patients (26.67%) showed the clinical picture and criteria of HPS, while
15 patients (25%) had positive echo findings without the clinical picture. There was a highly significant correlation between
echo grading and each of Child's score, shrunken liver, splenomegaly, collaterals, dyspnea, platypnea, cyanosis, clubbing,
orthodeoxia, impaired FEV 1 and esophageal varices (p0.05). The most sensitive predictors for HPS were increase portal vein diameter,
clubbing and cyanosis p25mmHg with a normal pulmonary capillary
wedge pressure in the setting of portal hypertension.
(Ioachimescu et al, 2007).
HPS is defined as the triad of liver disease,
pulmonary gas exchange abnormalities leading to

Value of Contrast Echocardiography for the Diagnosis of Hepatopulmonary Syndrome
arterial deoxygenation (PO 2

Amal S Bakir & Ghada El-Shahed
Pulmonary function test. Simple spirometeric
function test including FEV 1 (forced expiratory
volume in the 1 st second) was done to assess the
airway function. The respirometer used was (spirometrics
1986, Model 2500, version 3.1. USA).
Upper GIT endoscopy was done for all patients,
using pentax EG-2940 endoscope (videoscope),
with the patient fasting for at least 6 hrs.
Transthoracic contrast enhanced echocardiography
(CEE) was performed using a 2.5MHz
transducer attached to a commercially available
VINGMED VIVID V machine equipped with a
harmonic imaging capability.
CEE was performed by injecting 8mL agitated
saline solution through an antecubital 18-gauge
cannula and two 10-mL syringes connected by a
three-way stopcock. In the apical 4-chamber view,
the appearance of microbubbles in the right cardiac
chambers was noted. An intrapulmonary shunt
(IPS) was considered present if microbubbles
appeared in the LA at least four heart beats after
the initial appearance of contrast in the right side
of the heart (Rodriguez-Roision et al, 2004).
The relative opacification of the LA was assessed
semiquantitatively as follows: Grade 0, no
microbubble in LA; grade I, a few bubbles in LA
indicating small IPS; grade II, moderate bubbles
without complete filling of the LA (moderate IPS);
grade III, many bubbles filling the LA completely
(large IPS); and grade IV, extensive bubbles as
dense as in the right atrium (extensive IPS). Three
repeated contrast injections were performed. The
next injection was started after complete removal
of microbubbles from RA and LA cavities. An IPS
was considered present if any of the three injections
119
was positive (Vedrinne et al, 1997). Studies performed
during involuntary Valsalva maneuver or
coughing were excluded to avoid an increase of
RA pressure which may cause shunting across a
patent foremen ovale after three or more cardiac
cycles, therefore giving a false-positive result.
All patients had a chest X-ray to exclude the
presence of pulmonary disease, and high resolution
CT chest was done in cases with abnormal X-ray
findings. Pateints with any lung abnormalities were
excluded from the study.
A rectal snip was taken from all patients to
exclude Bilharziasis. Liver biopsy was done in
cases suitable for biopsy to exclude any other
etiology than HCV for chronic liver disease.
Results
Sixty patients were included in the study, with
a mean age of 48.28±5.3 years. Fifty-four patients
(90%) were males.
Tweny-nine patients (48.33%) showed negative
echo findings (grade 0) indicating absence of
intrapulmonary vascular dilatation (IPVD), while
31 patients (51.67%) showed positive echo findings,
which reflected presence of IPVD.
Sixteen patients (26.67%) showed the clinical
picture and criteria of HPS (IPVD and hypoxia),
while 15 patients (25%) had positive echo findings
but were lacking the clinical picture i.e. subclincal
HPS. None of the patients showed grade I echo
findings, while 12 (20%) had grade II, 7 patients
(11.67%) had grade III, and 12 patients (20%) had
grade IV echo findings, with presence of extensive
bubbles in the left side of the heart equivalent to
that of the right side (Fig. 1).
Figure 1: Transthoracic 2-dimensional echocardiogram, apical 4 chamber view. Left: Presence of contrast in the right chambers;
Right: Presence of contrast in the left chambers after 5 cardiac cycles, compatible with intrapulmonary vascular
dilatations.

Value of Contrast Echocardiography for the Diagnosis of Hepatopulmonary Syndrome
As regards the correlation between Child's
scoring and echo findings (Table 1), there was a
highly significant correlation between echo grading
and Child's score, showing that the more progressed
the stage of liver disease is, the more the number
of cases with positive echo findings, and the grade
of echo findings is higher (p

Amal S Bakir & Ghada El-Shahed
Table 5: Correlation between platypnea, cyanosis, clubbing,
and echo grading.
Platypnea,
cyanosis &
clubbing
–ve
+ve
Total
Zero
28
(65.12%)
1
(5.88%)
29
Echo grading
CHI-SQUARE = 23.527 PROB.

Value of Contrast Echocardiography for the Diagnosis of Hepatopulmonary Syndrome
feasible parameter to detect HPS in cirrhotic patients
(Zamirian et al, 2007). Also, Karabulut et al
(2006) showed that right ventricular diastolic dysfunction
was notably more common in cirrhotic
patients with HPS than those without HPS. We did
not use any of these measurements, as we think
they can be non-specific (e.g. LA dilatation can
be caused by systemic hypertension, and RV diastolic
dysfunction can be part of the normal aging
process). More recently, Lenci et al (2009) showed
that standard echocardiographic parameters did
not distinguish between patients with and those
without HPS.
Transesophageal echocardiography was proposed
for better visualization of bubbles in the
left-sided cardiac chambers, as it allows the contrast
to be seen entering from the pulmonary veins
(Vedrinne et al, 1997). However, TTE is diagnostic
in the majority of cases. In addition, the presence
of esophageal varices, which is considered a relative
contraindication to the performance of TEE, is
relatively common in these patients (Rollan et al,
2007). Moreover, we did not wish to expose patients
with decompensated liver to the sedation needed
for TEE.
There are, however, some limitations of contrast-enhanced
echocardiography. Most notably it
does not accurately quantify the degree of intrapulmonary
shunting, allowing only a semiquantitative
grading (Wang and Lin 2005). Although
99Technetium macroaggregated albumin
perfusion lung scanning overcomes this limitation
and permits quantification of the degree of shunting
(Abrams et al, 1998), contrast enhanced ecardiography
has been shown to be more sensitive
than lung perfusion scanning for the detection of
IPVD (Abrams et al, 1995). It has the additional
advantage that it can be performed as part of routine
echocardiographic screening for pulmonary hypertension.
The European Respiratory Society Task
Force on Pulmonary-Hepatic vascular disorders
has recommended contrast-enhanced echocardiography
as the first line screening modality for HPS
(Rodriguez-Roision et al, 2004).
The prevalence of HPS varies widely between
different reports (4-47%) (Colle et al, 2007) and
a definitive diagnosis of HPS varies between 4%
and 19% in cirrhotic patients. This shows the
presence of intrapulmonary vascular dilatations
(IPVD) in cirrhotic patients without HPS (Lima et
al, 2004). In our study 31 patients (51.67%) showed
positive echo findings of IPVD. Sixteen patients
122
(26.67%) showed the clinical picture and criteria
of HPS, and 15 (25%) had positive echo findings
but not the clinical picture i.e. subclincal HPS.
Our study agrees with the results of Vedrinne et al
(1997), who studied 37 cirrhotic patients and found
that 51% had positive echocardiographic findings.
The prevalence found in our study was lower
than that of Byung et al (2004) who studied 130
cirrhotic patients, and found that 61% had positive
echocardiographic findings and 47% had HPS.
On the other hand, Lenci et al (2009) showed
late right-to-left shunting in 26% of patients, while
only 16% had a definite diagnosis of HPS i.e. CEE
detected intrapulmonary shunting before a change
in arterial blood gases.
The present study clearly showed a significant
correlation between the severity of hepatopulmonary
syndrome and the Child-pugh classification
and score. This is in agreement with Abrams et al
(1995), who showed greater shunt fractions in
Child Pugh A cirrhosis compared with Child Pugh
B and C classes, and Vardereli et al (2001), who
found that hypoxemic cirrhotic patients had a
significantly higher Child-pugh score than those
without hypoxemia. In addition, Ferreira et al
(2008) showed that more advanced liver disease
was associated with HPS. This study also agrees
with that of Byung et al (2004) and Amir et al
(2006), who suggested that the hepato-pulmonary
syndrome is related to the development of cirrhosis.
The present study found a direct correlation
between orthodeoxia and hepatopulmonary syndrome
with high statistical significance. We found
that orthodeoxia was present in 51.67% of patients,
while Amir et al (2006) found it in 66% with no
significant statistical relation. This may be due to
their cut off value for hypoxia, which was PO 2

Amal S Bakir & Ghada El-Shahed
This study found a significant correlation between
portal hypertension detected by abdominal
ultrasound and HPS. This agrees with Amir et al
(2006), who found a relation between portal hypertension
and HPS. We also found a direct correlation
between the presence of esophageal varices
detected by UGIT endoscopy and hepatopulmonary
syndrome. Schenk et al (2002) agreed with our
study. They found esophageal varices more often
in the groups with positive contrast echocardiography,
but the difference did not reach statistical
significance. This may be due to the small number
of patients with HPS found in their study (9 patients).
Our results agree with Lima et al (2004), who
found no significant difference between HPS and
abnormal pulmonary function.
We used PaO 2 as a measure of hypoxia for
prediction of HPS. Amir et al (2006) used both
PaO 2

Value of Contrast Echocardiography for the Diagnosis of Hepatopulmonary Syndrome
sepatopulmonary syndrome. Mayo Clin Proc 2004; 79:
42-50.
23- Lucey MR, Brown KA, Everson GT, et al: Minimal criteria
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American Society of Transplant Physicians and the American
Association for the Study of Liver Diseases. Liver
Transpl Surg 1997; 3 (6): 628-637.
24- Martinez G, Barbera J, Visa J, et al: Hepato-pulmonary
syndrome in candidates for liver trans-plantation. J Hepatol
2001; 34: 756-758.
25- Miguel RA, Britt B, Ashwani K, et al: Carboxyhemoglobin
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26- Moller S, Henriksen JH: Cardiopulmonary complications
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27- Moorman JP, Joo M, Hahn YS: Evasion of host immune
surveillance by hepatitis C virus: Potentian roles in viral
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189-194.
28- Regev A, Yeshurun M, Rodriguez M, et al: Transient
hepatopulmonary syndrome in a patient with acute hepatitis
A. J Viral Hepat 2001; 8: 83-86.
29- Rodriguez-Roision R, Krowka MJ, Herve P, et al: Pulmonary
Hepatic vascular disorders (PHD). Eur Respir J 2004;
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30- Rodriguez-Roisin R, Krowka MJ: Hepatopulmonary
Syndrome-A Liver-Induced Lung Vascular Disorder.
NEJM 2008; 358: 2378-2387.
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31- Rollan MJ, Munoz AC, Perez T, et al: Value of contrast
echocardiography for the diagnosis of hepatopulmonary
syndrome. European Journal of Echocardiography 2007;
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32- Schenk P, Fuhrman V, Madl C, et al: Hepatopulmonary
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33- Taille C, Cadranel J, Bellocq A, et al: Liver trans-plantation
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34- Umeda A, Tagawa M, Kohsaka T, et al: HPS can show
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Egypt Heart J 62 (1): 125-133, March 2010
Cardiac Output Measurement by a New Transesophageal Doppler Probe
in Circulatory Shock
NASHWA ABED, MD; MOHAMED AFIFY
Introduction: We conducted a prospective observational study from August 2007 to August 2008 to evaluate efficacy of
esophageal Doppler monitoring (EDM) in monitoring cardiac output (CO) and tailoring of vasoactive drugs doses in patients
with septic shock.
Methods: EDM used in 18 patients with septic shock in which CO measured using cardio Q doltex monitor every 48 hours
and values compared to those taken by pulmonary artery catheter (PAC) and transthoracic echo (TTE). Also safety of EDM
and its value in tailoring doses of IV fluids and vasoactive drugs were assessed.
Reuslts: A good correlation was present between CO measured by EDM & TTE and that by PAC. No significant complications
with the use of EDM in contrast to that of PAC; 2 cases of pneumothorax no mortality related to the procdures in both PAC or
EDM.
Conclusion: The EDM showed an excellent correlation to TTE & PAC, the bedside simplicity 3-8min for insertion and
interpretaion safety and continous real time on screen monitoring make it a promising technique for critically ill patients.
Key Words: PAC – EDM – TTE – CO.
Introduction
The transesophaseal Doppelr is currently the
most promising non invasive technique for monitoring
cardiac output (CO) in ICU patients.
The esophageal Doppler first described in 1971
and subsequently refined by Singer provides a
minimally invasive means of continuously monitoring
cardiac function in the ICU [1].
Doppler signals can be obtained by an ultrasound
probe placed externally at the suprasternal
notch and directed at ascending aorta. However,
esophageal Doppler monitoring has a number of
advantages over the transcutaenous noute. The
close proximity of descending aorta to the esophagus
probe is an excellent window for obtaining
Doppler signals. Furthermore, once positioned the
The Department of Critical Care Medicine, Cairo University.
Manuscript received 10 Dec., 2009; revised 15 Jan., 2010;
accepted 16 Jan., 2010.
Address for Correspondence: Dr. Nashwa Abed,
The Department of Critical Care Medicine, Cairo University
125
transeophageal probe is stabilized by the esophagus,
thereby permitting continuous monitoring.
A good correlation has been demonstrated between
the CO measured by esophageal doppelr
and simultaneously by thermodilution and fick
methods [2].
Esophageal Doppler monitoring (EDM) would
be of limited clinical utility if it only provided an
estimate of CO. However, the characteristics of
the Doppler flow velocity waveform provides
information on both cardiac preload and contractility.
The peak velocity that's identified as the apex
of the wave form is a good indicator of myocardial
contractility and the base of wave form which is
the flow time is indictor for the volume status and
preload of the heart [3].
Aim of the study:
• The aim of this study is to evaluate the efficacy
of EDM to evaluate CO monitoring compared to
CO measured by transthroacic echocardiography
(TTE).

Cardiac Output Measurement by a New Transesophageal Doppler Probe
• To evaluate the efficacy of EDM for tailoring the
doses of vasoactive drugs and monitoring of
hemdoynamics in patients with septic shock.
• To assess the overall safety of EDM as applied
to critical care patients.
Methods and Material
The study was done at Critical Care Medicine
Department Cairo University in one year period
(2007-2008), all critically ill patients with septic
shock.
Eighteen patients were included in the study
10 males and 8 females.
Exclusion criteria:
• Patients with esophageal pathology as cancer,
achalsia, varices.
• Patients with hematemesis if upper endoscopy
not done to exclude varices or cancer.
• Patients with severe coagulopathy.
• Also cardiac patients with ejection fraction less
than 45% or severe valve dysfunction.
Study design and data collection:
• A prospective observational cohart study design
was used.
• For all patients the following characteristics were
prospectively recorded.
• Full consent taken by patients relatives.
• Age, weight, height, body surface area.
• PO2/FiO2 ratio.
• Coagulation profile.
• Complete blood count.
• Liver function tests.
• Severity of illness as indicated by Acute Physiology
and Chronic Health evaluation (APACHE)
II as well as sequential organ failure assessment
(SOFA) score.
• Hemdoynamic variables as heart rate central
venous pressure (CVP), arterial blood pressure.
• Cardiac output and systemic vascular resistance
by EDM and TTE.
• Also monitoring of possible complications as
esophageal perforations or O 2 desaturation less
than 90% by oximetry, atrial or ventricular ar-
126
rhythmias, gastrointestinal bleeding and unintentional
tracheal extubation or accidental tracheal
insertion or accidental removal of nasogastric
tube.
Measurement of CO:
EDM probe consists of continuous wave Doppler
transducer (4MHz) mounted at 45º at the tip
of the probe (diameter 8mm). The probe is connected
to a monitor (Deltex medical Ltd, England)
that display the blood flow velocity wave form
after spectral analysis of the reflected doppelr shift
signal [4]. After oral introduction the probe is
advanced gently until 35cm from the incisors is
reached, and a good wave form is obtained. Gain
& Filler settings were optimized to eliminate the
noise related to low frequency motion of the vessels
wall.
The monitor was preset to calculate CO (Litters
per minutes) by averaging stroke volume over 12
beats and multiplying the value obtained by the
HR.
The left ventricular flow time (i.e. ejection
time) corrected for heart rate provide an index of
left ventricular preload [4].
Cardiac output normally 3-7 litres/min [5] below
3 considered low CO and above 7 considered high
CO.
Corrected flow time (FTc) less than 300 m.sec
were considered low i.e. preload and values greater
than 360 msec were considered high [8].
CO & FTc as well as other hemodynamic variable
were measured every 12 hours for 48 hours.
CO measured by EDM compared to that measured
by TTE using transaortic flow and left ventricular
outflow diameter and getting velocity time
integral (VTI) across the left ventricular outflow
using the velocity equation:
SV = VTI x BSA
SV = VTI x πr 2
CO = SV x HR
Were r is radius of LV outflow.
π = 3.14
Statistical analysis:
All comparisons between EDM measures and
by TTE correlation determined by using simple
linear regression analysis.

Nashwa Abed & Mohamed Afify
Results
A total of 18 patients with septic shock underwent
hemdoynamic variables monitoring via EDM
& TTE the patients characteristics were shown in
the above table.
EDM was successfully applied to all patients
with average time for interpretation about 8 minute
ranging from 7 to 15 minutes.
Safety of the EDM: Accidental removal of
nasogastric tube in two patients and the need for
sedation with intermittent doses of propofol caused
reversible hypotension with fluid boluses in two
Table 1: Characteristic of the simple.
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
CO-EDM
12.00
10.00
8.00
6.00
4.00
Age
28
60
68
75
80
50
38
58
99
65
45
29
60
52
60
65
63
60
Sex
M
M
M
M
M
F
M
F
F
F
F
F
M
M
M
F
F
M
SOFA
score
11
11
8
10
10
7
12
8
10
11
8
19
10
10
18
16
12
12
APACHE II
25
27
24
25
27
24
39
25
27
35
25
30
19
17
40
30
36
36
CVP
CmH 2 O
5
10
14
13
8
10
18
10
16
8
3
13
3
16
9
9
7
6
CO
EDM
7.7
6.4
11
8
7.2
8.9
7.9
9
4.8
4
10.8
5.7
4.6
6.2
11.4
6.1
9.5
10
4.00 6.00 8.00 10.00 12.00 14.00
CO-ECHO
Figure 1: Show correlation between CO measured by TTE
and esophageal Doppler probe.
127
patients no accidental endotracheal tube extubation
nor false insertion of the probe into trachea, desaturation,
GIT bleeding nor arrhythmias.
Comparison between Co measured by EDM &
TTE: EDM measurement of CO were compared
with TTE in all patients the correlation between
the 2 types of measurement was significant (p:
0.0005).
Comparison between Co measured by EDM &
CO by PAC: EDM measurement of CO were compared
with PAC in all patients the correlation
between the 2 types of measurement was significant
(p: 0.0005).
CO
Echo
7.8
6
10
7.9
8
8.3
7.5
9.5
4.5
4.8
9.5
6
4.5
6.4
12.5
5.8
8.4
9.4
CO-EDM
12.00
10.00
8.00
6.00
4.00
FTc
m.sec
372
272
360
329
275
270
361
329
320
497
330
270
359
280
280
360
395
335
Complications
Nasogastric tube
Nasogastric
No
No
No
Hypotension
Hypotension
No
No
No
No
No
No
No
No
No
No
No
Need for
sedation
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
CO by PAC
8.5
6.5
11
8
8.2
8.5
7.8
9.2
5
9.5
10
6
4.5
6.9
11.2
6
9.8
11.2
4.00 6.00 8.00 10.00 12.00
CO-PAC
Figure 2: Correlation between CO measured by pulmonary
artery catheter and esophageal Doppler probe.

Cardiac Output Measurement by a New Transesophageal Doppler Probe
Table 2: Summary Studies comparing hemodynamics measured by EDM and conventional protocols.
Author/Year
Noblett, et al,
2006 [15]
NR: Not reported.
Table 3.
Author/Year
Wakeling, et al,
2005 [16]
Study
Design/Purpose
Design: RCT
Purpose: to assess the
effect of optimizing
hemodynamic status,
using a protocoldriven
intraoperative
fluid regimen, on
outcome following
elective colorectal
resection.
ECRI Quality Score
(Rating): 9.1 (High)
Study
Design/Purpose
Design: RCT
Purpose: to determine
whether using
intraoperative
esophageal Doppler
guided fluid
management to
minimize
hypovolemia
would reduce
postoperative hospital
stay and the time
before
return to gut function
after colorectal
surgery.
ECRI Quality Score
(Rating): 9.0 (High)
Intervention/
Outcomes
Treatment group
Intervention:
EDM (CardioQ) +
CVP + conventional
protocol
Control Group
Intervention:
CVP + conventional
protocol
Intervention/
Outcomes
Treatment Intervention:
EDM (CardioQ) +
CVP + conventional
protocol
Control Intervention:
CVP + conventional
protocol
128
Demographics
54 in treatment group
54 in control group
Age (median ± IQR)
Treatment: 62.3±14.0
Control: 67.6±15.
% female: Treatment:
NR Control: NR Type of
surgery: Elective bowel
surgery
Inclusion Criteria:
Patients requiring
elective bowel surgery
Exclusion Criteria:
Severe esophageal
disease, recent
esophageal or upper
airway surgery,
systemic steroid
medication, moderate
or severe aortic valve
disease, bleeding
diathesis and patient
choice
Demographics
Total Enrolled:
128 (64) in treatment
group (64) in control
group Age (median ±
IQR) Treatment:
69.1±12.3 Control:
69.6±10.2% female:
Treatment: 40.6
Control: 46.9 Type of
surgery: Elective or
semi-elective bowel
surgery
Inclusion Criteria:
Patients requiring
elective or semi-elective
bowel surgery
Exclusion Criteria:
Patients with age

Nashwa Abed & Mohamed Afify
Table 4.
Author/Year
Conway, et al,
2002 [17]
Table 5.
Author/Year
Gan, et al,
2002 [18]
Study
Design/Purpose
Design: RCT
Purpose: to examine
the effect of esophageal
Doppler guided fluid
administration during
colorectal resection on
hemodynamic
performance, hospital
stay, and post-operative
complications ECRI
Quality Score (Rating):
8.5 (High)
Study
Design/Purpose
Design: RCT
Purpose: to investigate
whether goal-directed
intraoperative plasma
volume expansion
guided by the EDM
would shorten the
length of hospital stay
and improve
postoperative outcomes
in patients undergoing
moderate risk surgery
ECRI Quality Score
(Rating): 8.1 (Moderate)
Intervention/
Outcomes
Treatment Intervention:
EDM (TECO 2) + CVP
+ conventional protocol
Control Intervention:
CVP + conventional
protocol
Intervention/
Outcomes
Treatment Intervention:
EDM (EDMTM) + CVP
+ conventional protocol
Control Intervention:
CVP + conventional
protocol
129
Demographics
Total Enrolled:
57 29 in treatment group
28 in control group Age
(mean ± SD) Treatment:
66.5±12.5 Control:
67.5±10.1 % female:
Treatment: NR Control: NR
Type of surgery: Major
non-emergent bowel
surgery
Inclusion Criteria:
Patients undergoing major
bowel resections
Exclusion Criteria:
Patients undergoing
emergency, intrathoracic,
or esophageal surgery,
patients with known
sensitivity to starch-based
colloid or history of
esophageal disease
Demographics
Total Enrolled:
100 50 in treatment group
50 in control group Age
(mean ± SD) Treatment:
56±13 Control: 59±12
% female: Treatment: 38
Control: 48 Type of surgery:
Major elective general,
urologic, or gynecologic
surgery
Inclusion Criteria:
Patients with American
Society of Anesthesiologists
(ASA) physical status I, II,
and III who were to undergo
major elective general,
urologic, or gynecologic
surgery with an anticipated
blood loss of >500ml.
Exclusion Criteria:
Patients with age 50% or liver enzymes
>50% upper limit of normal
values), congestive heart
failure, and esophageal
pathology (avoid potential
complications of the
esophageal probe), and
those undergoing gastric or
esophageal surgery or who
were on antiemetic
medication within 3 days of
surgery
Results
Mortality Treatment:
0% (0/29) Control: 3.6%
(1/28) p-value: 0.49
Major complications:
Treatment: 0% (0/30)
Control: 17.9% (5/30)
p-value: 0.02
Total complications:
Treatment: 17.2% (5/29)
Control: 32.1% (9/28)
p-value: 0.23a
Length of hospital stay:
Mean ± SD in days
Treatment: 18.7±20.2
Control: 12.7±6.0
Median (range):
Treatment: 12
(7-103) Control:
11 (7-30)
p-value: NR
Results
Mortality:
Treatment: 0% (0/50)
Control: 0% (0/50)
p-value: 1.0
Major complications:
Not reported separate
from total complications
Total complications:
Treatment: 42% (21/50)
Control: 76% (38/50)
p-value: 0.001a
Length of hospital stay:
Mean ± SD in days
Treatment: 5±3 Control:
7±3 Median Treatment: 6
Control: 7 p-value: 0.03

Cardiac Output Measurement by a New Transesophageal Doppler Probe
Table 6.
Author/
Year
Venn et al,
2002 [19]
Table 7.
Author/
Year
Sinclair,
et al,
1997 [20]
Study
Design/Purpose
Design: RCT
Purpose: to investigate
whether repeated colloid
fluid challenges to
optimize the circulation
intraoperatively, guided
by CVP or esophageal
Doppler ultrasonography,
would benefit high-risk
patients admitted with
fractured hips to a
London teaching hospital
ECRI Quality Score
(Rating): 9.0 (High)
Study
Design/Purpose
Design: RCT
Purpose: to examine the
possible benefits of
intraoperative circulatory
optimization using EDM in
patients with fractured neck
of femur ECRI Quality
Score (Rating): 8.9 (High)
Intervention/
Outcomes
Treatment Intervention:
EDM (CardioQ) +
conventional protocol
Control Intervention:
CVP + conventional
protocol
Other Intervention:
Conventional protocol
alone
Intervention/
Outcomes
Treatment Intervention:
EDM (ODM 2) +
conventional protocol
Control Intervention:
Conventional protocol
130
Demographics
Total Enrolled:
90 30 in treatment group 31
in control group 29 in other
group Age (mean ± SD)
Treatment: 82±8.7 Control:
85±6.2 Other: 84.5±9.3 %
female: Treatment: 80
Control: 87.1 Other: 79.3
Type of surgery: Proximal
femoral fracture repair
Inclusion Criteria:
Patients admitted with
fractured hips
Exclusion Criteria:
Patients with age

Nashwa Abed & Mohamed Afify
Table 8.
Author/
Year
Mythen and
Webb 1995
[20]
Table 9.
Author/
Year
McKendry,
et al, [22]
Study
Design/Purpose
Design: RCT
Purpose: to test the
hypothesis that
perioperative plasma
volume expansion with
colloid (guided by EDM+
CVP) would maintain pHi
during elective cardiac
surgery ECRI Quality
Score (Rating): 8.9 (High)
Study
Design/Purpose
Design: RCT
Purpose: to assess whether
a nurse led, flow
monitored
protocol for optimizing
circulatory status in
patients after cardiac
surgery reduces
complications and
shortens stay in intensive
care and hospital ECRI
Quality Score (Rating):
8.5 (High)
Intervention/
Outcomes
Treatment Intervention:
EDM (ODM 1) + CVP
+ conventional protocol
Control Intervention:
CVP + conventional
protocol
Intervention/
Outcomes
Treatment Intervention:
EDM (CardioQ) +
conventional protocol
Control Intervention:
Conventional protocol
131
Demographics
Total Enrolled:
60 30 in treatment group 30
in control group Age (mean
and range) Treatment: 63
(42-89) Control: 64 (44-86)
% female: Treatment: NR
Control: NR Type of
surgery: Elective cardiac
surgery (CABG or single
valve replacement)
Inclusion Criteria:
Patients scheduled for
elective coronary artery
bypass grafts (CABG) or
single heart valve
replacement) who had a
preoperative left ventricular
ejection fraction (LVEF)
estimated to be ≥50% and
graded by the anesthesiologist
in charge as ASA grade III.
Exclusion Criteria:
Patients with age

Cardiac Output Measurement by a New Transesophageal Doppler Probe
Discussion
Transesophageal Doppler is minimally invasive
method for continuous monitoring of cardiac output
in critically ill patients.
In this study it was used for monitoring of
cardiac output and SVR in patients with severe
septic shock that's refractory to catecholomines
therapy.
The probe was successfully introduced in all
patients without any significant complication and
was used to follow hemodynamics at bedside along
all the hospital stay of the patient without need for
transfer to the echocardiography lab for optimizing
CO nor systemic vascular resistance.
The cardiac output value was correlated well
with measures taken by pulmonary artery catheter
and transthoracic echocardiography at bed side.
The average insertion time to interpretation
was about 7-8min for EDM and 10-12min for PAC
and about 8.5 minutes for TTE.
Clinical assessment of CO at bed side by physician
can be problematic especially patients with
underlying cardiac disease. These previous studies
indicated that physician could estimate CO correctly
only in 50% of patients [4].
Another study done at Barnes Jewish hospital
2 decade before showed that PCWP was correctly
predicted 30% of the time, and CO, SVR and right
atrial pressure were correctly predicted approximately
50% of the time [5].
The limitations of the currently available techniques
as PAC, dye dilation and transthroacic
electrical impedance for measuring CO suggest a
need for tansesophageal Doppler monitoring.
Thermodilution is affected by variety of external
factors and patients related conditions (e.g., tricuspid
regurgitation intracardiac shunts and low cardiac
output state) [6,7].
Similarly, estimation of CO obtained by using
fick methods e.g. dye dilution can be adversely
affected by the lack of hemdoynamic instability
often encountered in patients on mechanical ventilation
[8,9]. Which is common situation in critically
ill patients.
More important patient outcome may be adversely
affected by these techniques to assess the
132
hemdonamic status as shown by the Study to Understand
Prognosis and Preference for Outcomes
and Risk of Treatment (SUPPORT) that examined
more than 5000 patients and found by case matching
analysis that patients with right sided heart
catheterization had an increased 30 day mortality
(odds ratio, 1.24; 95% CI, 1.03-1.99) [10,11]. These
investigator also found that the mean cost per
hospital study was higher in patients received PAC
for monitoring of hemodynamcis. This view was
supported by a recent consensus panel.
Also, the need for multiple steps in obtaining
hemdoynamic data including catheter placement,
calibration of transducers, interpretation of wave
form, increase the likelihood for error in interpretation
[12,13]. On the other hand EDM provided an
easy and rapid time for interpretation without all
these steps in addition to provide a continuous real
time monitoring of CO [11].
Our study may be a leading one in using EDM
in monitoring of CO and SVR in patients with
septic shock receiving hemodynamic supportive
drugs in addition to fluid replacement therapy. The
other studies used EDM intra-operative and postoperatiave
purpose for monitoring volume status
of patient underwent hip replacement, bowel resection
or proximal femoral fracture [15-18].
Compared to our study these studies compared
volume status and fluid replacement therapy in
two groups in one using EDM +CVP. To monitoring
therapy and another group using only CVP monitoring
yet in our study we used EDM & CVP to
monitor CO, SVR to optimize filling pressure and
doses of noraderaline and terlipressin in those
patients with severe septic shock.
In the study of Noblette, et al [15] EDM was
used to asses effect of optimizing hemodynamic
status using a protocol driven intra-operative fluid
regimen on outcome following elective colorectal
resection.
In which EDM caused significant decrease in
length of hospital stay and less major complications
yet no effect on mortality.
Compared to our study the aim was to use EDM
as bed side technique for measuring CO & SVR
and by which we could wean noradrenaline and
adjust doses of dobutamien and terlipressin. EDM
could help in weaning of vasoactive drugs in 7 out
18 patients with severe catecholamine dependency.

Nashwa Abed & Mohamed Afify
In our study no reported significant complications
only accidental removal of nasogastric tube
in one case.
We can conclude that EDM can be a good and
cost effective alternative to PAC for obtaining
hemdoynamic data.
The EDM showed an excellent correlation to
echocardiography & PAC. The bed side simplicity
3-8min for insertion and interpretation safety and
continuous real time monitoring of CO make EDM
show a promises as a reliable method for critically
ill patients need continuous monitoring and support.
References
1- Side CD, Gosling RJ: Non-surgical assessment of cardiac
function. Nature 1971; 232: 335-336.
2- Singer M, Clarke J, Bennett ED: Continuous hemodynamic
monitoring by esophageal Doppler. Crit Care Med 1989;
17: 447-452.
3- Cuschien J, Rivers E, Caruso J, et al: A comparison of
transesophageal Doppler, thermodilution and Fick cardiac
output measurements in critically ill patients [abstract].
Crit Care Med 1998; 26 (Suppl), A62.
4- Connors AF Jr, McCaffree DR, Gray BA: Evaluation of
right-heart catheterization in the critically ill patient
without acute myocardial infarction. N Engl J Med 1983;
308: 263-267. [Medline].
5- Eisenberg PR, Jaffe AS, Schuster DP: Clinical evaluation
compared to pulmonary artery catheterization in the
hemodynamic assessment of critically ill patients. Crit
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6- Levett JM, Replogle RL: Thermodilution cardiac output:
A critical analysis and review of the literature. J Surg Res
1979; 27: 392-404. [Medline].
7- Wessel HU, Paul MH, James GW, Grahn AR: Limitations
of thermal dilution curves for cardiac output determinations.
J Appl Physiol 1971; 30: 643-652. [Free Full Text].
8- Taylor SH: Measurement of the cardiac output in man.
Proc R Soc Med 1966; 59 (Suppl): 35-53.
9- Taylor SH, Silke B: Is the measurement of cardiac output
useful in clinical practice? Br J Anaesth 1988; 60 (8 Suppl
1): 90S-98S. [Medline].
10- Connors AF Jr, Speroff T, Dawson NV, et al: The effectiveness
of right heart catheterization in the initial care
of critically ill patients. SUPPORT Investigators. JAMA
1996; 276: 889-897. [Abstract].
11- Bernard GR, Sopko G, Cerra F, et al: Pulmonary artery
133
catheterization and clinical outcomes: National Heart,
Lung, and Blood Institute and Food and Drug Administration
Workshop Report. Consensus statement. JAMA
2000; 283: 2568-2572. [Abstract/Free Full Text].
12- Gnaegi A, Feihl F, Perret C: Intensive care physicians’
insufficient knowledge of right-heart catheterization at
the bedside: Time to act? Crit Care Med 1997; 25: 213-
220. [Medline].
13- Marini JJ: Obtaining meaningful data from the Swan Ganz
catheter. Respir Care 1985; 30: 572-585.
14- Marik PE: Pulmonary artery catheterization and esophageal
Doppler monitoring in the ICU. Chest 1999; 116: 1085-
1091. [Abstract/Free Full Text].
15- Noblett SE, Snowden CP, Shenton BK, Horgan AF:
Randomized clinical trial assessing the effect of Doppleroptimized
fluid management on outcome after elective
colorectal resection. The British Journal of Surgery 2006;
93 (9): 1069-76.
16- Wakeling HG, McFall MR, Jenkins CS, Woods WG, Miles
WF, Barclay GR, Fleming SC: Intraoperative oesophageal
Doppler guided fluid management shortens postoperative
hospital stay after major bowel surgery Br J Anaesth
2005; 95 (5): 634-42.
17- Conway DH, Mayall R, Abdul-Latif MS, Gilligan S,
Tackaberry C: Randomised controlled trial investigating
the influence of intravenous fluid titration using oesophageal
Doppler monitoring during bowel surgery. Anaesthesia
2002 Sep; 57 (9): 845-9.
18- Gan TJ, Soppitt A, Maroof M, El-Moalem H, Robertson
KM, Moretti E, Dwane P, Glass PS: Goal-directed intraoperative
fluid administration reduces length of hospital
stay after major surgery. Anesthesiology 2002; 97: 820-
6.
19- Venn R, Steele A, Richardson P, Poloniecki J, Grounds
M, Newman P: Randomized controlled trial to investigate
influence of the fluid challenge on duration of hospital
stay and perioperative morbidity in patients with hip
fractures. Br J Anaesth 2002 Jan; 88 (1): 65-71.
20- Sinclair S, James S, Singer M: Intraoperative intravascular
volume optimisation and length of hospital stay after
repair of proximal femoral fracture: Randomized controlled
trial. BMJ 1997; Oct 11, 315 (7113): 909-12.
21- Mythen MG, Webb AR: Perioperative plasma volume
expansion reduces the incidence of gut mucosal hypoperfusion
during cardiac surgery. Arch Surg 1995 Apr; 130
(4): 423-9.
22- McKendry M, McGloin H, Saberi D, Caudwell L, Brady
AR, Singer M: Randomised controlled trial assessing the
impact of a nurse delivered, flow monitored protocol for
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BMJ 2004; Jul 31, 329 (7460): 258.

Egypt Heart J 62 (1): 135-140, March 2010
Comparison between Double Intravenous Bolus, Intracoronary Bolus,
and Conventional Intravenous Bolus Dose of Tirofiban in Patients with
Acute Anterior Myocardial Infarction Treated by Primary
Coronary Intervention
AHMED IBRAHIM NASSAR, MD; NAGWA NAGI EL-MAHALLAWY, MD;
BASSEM WADEI HABIB, MD; ADEL GAMAL HASSANIN, MD;
IMAN ESMAT, MD; HAYTHAM GALAL, MSc
Primary percutaneous coronary intervention (PCI) in patients with AMI has been shown to be preferable to thrombolytic
therapy in terms of patient survival, higher rates of patency in the infarcted arteries, and lower rates of reinfarction and stroke
(Zijlstra et al, 1999). Tirofiban stands out as a potentially useful adjunct to PCI because it is a small non-peptide molecule,
somewhat similar to eptifibatide, and does not elicit an adverse immune reaction. Compared with abciximab, its advantages
as an adjunct therapy for PCI are lower cost and no overt bleeding complications (Gunasekara et al, 2005).
Aim of the Study: To compare the efficacy of different ways of bolus dose administration of Tirofiban in patients with acute
anterior ST segment elevation MI treated with primary percutaneous coronary intervention (1ry PCI) by comparing the
angiographic results, and the size of infarction in the three regimen groups.
Patients and Methods: The study was conducted on 60 patients who presented to the emergency room at Ain Shams
University Hospitals, in the period between April 2007 and April 2009, complaining of acute chest pain and were diagnosed
as having acute anterior ST segment elevation myocardial infarction. All patients were treated by primary percutaneous coronary
intervention. The patients divided randomly into three groups according to the bolus dose of Tirofiban:
• Group (I): It included 20 patients who received the conventional single intravenous bolus dose of Tirofiban upstream in the
CCU prior to primary PCI (0.4μg/kg/min for 30min).
• Group (II): It included 20 patients who received a high (double) intravenous bolus dose of Tirofiban upstream in the CCU
prior to primary PCI (25μg/kg).
• Group (III): It included 20 patients who received 0.4μg/kg bolus dose Tirofiban intracoronary downstream in the catheterization
laboratory in addition to the upstream intravenous bolus dose.
The bolus dose was given randomly to the patients according to the group and all patients continued on Tirofiban in the
dose of 0.15μ/kg/min continuous infusion for 48 hours, in addition to half dose unfractionated heparin or low molecular weight
heparin.
Echocardiographic examination was done for all patients during their hospital stay to evaluate:
1- Ejection fraction (EF).
2- LV dimensions.
3- Segmental wall motion abnormalities.
Complications of acute MI such as ventricular septal rupture (VSR), acute mitral regurgitation (MR), aneurysms, LV
thrombus etc.
The Department of Cardiology, Ain Shams University,
Cairo, Egypt.
Manuscript received 10 Oct., 2009; revised 5 Nov., 2009;
accepted 6 Nov., 2009.
Address for Correspondence: Dr. Ahmed Ibrahim Nassar,
The Department of Cardiology, Ain Shams University, Cairo,
Egypt.
Iman Esmat, Ain Shams University, Cairo, Egypt,
E-mail: i_esmat@yahoo.com
135

Comparison between Double Intravenous Bolus, Intracoronary Bolus
Statistics: Data were collected, revised and then edited on the P.C. The data were analyzed statistically by using SPSS
statistical package version (12).
Results: Our results Showed that two vessel disease was present in 35% of group I, 25% of group II and 10% of group III.
Three vessel disease was present in 10% of group II and 15% of group III and no 3 vessel disease was present in group I. This
was statistically non-significant among the three groups (p>0.05). No reflow phenomenon was present in 25% of patients in
group I, 15% of patients in group III and although there was not any patient who developed no reflow in group II. LV systolic
function; ejection fraction (EF); was estimated by using the Simpson method. The mean and SD of EF in group I was 41.65±7.82,
in group II was 48.95±8.69 and in group III was 41.20±8.21. This was statistically highly significant in between groups (p0.05).
Conclusion: In patients presented with acute anterior STEMI and treated with primary PCI, the high bolus dose tirofiban
given intravenously upstream prior to PCI seems to be a safe and effective regimen to improve the angiographic and clinical
outcomes in comparison to the conventional bolus dose regimen and the intracoronary bolus dose regimen, without increasing
the risk of bleeding.
Key Words: Acute MI – Primary PCI – Tirofiban.
Introduction
Primary percutaneous coronary intervention
(PCI) in patients with AMI has been shown to be
preferable to thrombolytic therapy in terms of
patient survival, higher rates of patency in the
infarcted arteries, and lower rates of reinfarction
and stroke (Zijlstra et al, 1999).
These benefits of PCI can be further enhanced
by administration of platelet glycoprotein IIb/IIIa
inhibitors abciximab (Antoniucci et al, 2003). The
conventional dose of Tirofiban may not achieve
adequate platelet aggregation inhibition compared
with abciximab (Goto et al, 2003). Timing of the
administration of Tirofiban before PCI also varied,
and patients with different clinical scenarios of
acute coronary syndrome were studied (De Luca
et al, 2005).
Aim of the work:
To compare the efficacy of different ways of
bolus dose administration of Tirofiban in patients
with acute anterior ST segment elevation MI treated
with primary percutaneous coronary intervention
(1ry PCI) by comparing the angiographic results
and the size of infarction as assessed by echocardiography.
Patients and Methods
The study was conducted on 60 patients who
came to the emergency room at Ain Shams University
Hospitals, in the period between April 2007
and April 2009, complaining of acute chest pain
and were diagnosed as having acute anterior ST
segment elevation myocardial infarction. All patients
were treated by primary percutaneous coronary
intervention.
136
Inclusion criteria:
1- Males and females with age between 20-70
years presenting with acute chest pain and ST
elevation indicative of myocardial infarction,
as proposed by the Joint Committee of the
European Society of Cardiology (ESC) and
American College of Cardiology (ACC), is a
new ST segment elevation in 2 or more contiguous
leads of at least 1mm at the J point in the
anterior leads (V1-V6, I, aVL) (Alpert et al,
2000).
2- Feasibility to perform PCI within 6 hours from
onset of symptoms.
Exclusion criteria:
Patients who have one or more of the following
were excluded from the study:
1- Contraindications for antiplatelets such as bleeding
disorder including gastrointestinal bleeding,
hematuria, or known presence of occult blood
in the stool prior to randomization.
2- Thrombocytopenia (Platelet count

Ahmed I Nassar, et al
The patients were divided randomly into three
groups according to the bolus dose of Tirofiban:
• Group (I): It included 20 patients who received
the conventional single intravenous bolus dose
of Tirofiban upstream in the CCU prior to primary
PCI (0.4μg/kg/min for 30min).
• Group (II): It included 20 patients who received
a high (double) intravenous bolus dose of
Tirofiban upstream in the CCU prior to primary
PCI (25μg/kg).
• Group (III): It included 20 patients who received
0.4μg/kg bolus dose Tirofiban intracoronary
downstream in the catheterization laboratory in
addition to the upstream intravenous bolus dose.
All patients were subjected to the following:
1- Thorough history taking and complete physical
examination.
2- 12 leads surface ECG.
3- Laboratory investigations, including lipid profile,
fasting and post prandial blood sugar, serial
evaluation of cardiac enzymes including CK,
CKMB, Troponin levels.
4- Patient preparation by antiplatelets and heparin.
5- Tirofiban (R/Aggrastat): Bolus dose according
to the patient group.
6- Emergency coronary angiography and coronary
angioplasty of the infarct related artery (1ry
PCI) to the culprit lesion of the infracted artery
(LAD). TIMI flow and myocardial blush grade
(MBG) will be evaluated.
7- Transthoracic Echocardiography.
8- In-hospital clinical follow-up for MACE.
Patient preparation by antiplatelets:
All patients received 300mg aspirin, 8 tablets
of clopidogrel (600mg) and 10.000 iu unfractionated
heparin intravenously in the catheterization
laboratory.
Time to treatment:
The door to needle time (time from admission
till administration of the Tirofiban) and the door
to balloon time (time from admission till opening
of the occluded artery by balloon angioplasty) were
calculated.
Tirofiban (R/Aggrastat):
The bolus dose was given randomly to the
patients according to the group and all patients
continued on Tirofiban in the dose of 0.15μ/kg/min
137
continuous infusion for 48 hours, in addition to
half dose unfractionated heparin or low molecular
weight heparin.
Primary percutaneous coronary intervention:
By using the modified Seldinger technique,
coronary angiography was done by using femoral
artery puncture, and Target Vessel Revascularization
(TVR) was performed by using balloon dilatation
and stenting.
(TIMI) flow grades were observed (TFGs):
Grade 0, no perfusion (no antegrade flow beyond
the point of occlusion); grade 1, penetration without
perfusion (contrast material passes beyond the area
of obstruction but fails to opacify the entire coronary
bed distal to the obstruction for the duration
of the cineangiographic filming sequence); grade
2, partial perfusion (contrast material passes across
the obstruction and opacifies the coronary artery
distal to the obstruction-however, the rate of entry
of contrast material into the vessel distal to the
obstruction or its rate of clearance from the distal
bed (or both) is slower than its flow into or clearance
from comparable areas not perfused by the
occluded vessel (for example, the opposite coronary
artery or the coronary bed proximal to the obstruction);
and grade 3, complete perfusion (antegrade
flow into the bed distal to the obstruction occurs
as promptly as antegrade flow into the bed proximal
to the obstruction, and clearance of contrast material
from the involved bed is as rapid as clearance from
an uninvolved bed in the same vessel or the opposite
artery) Successful reperfusion is defined as the
establishment of TIMI grade 3 flow in the infarctrelated
artery on the final coronary arteriogram
(The TIMI Study Group, 1985).
MBG myocardial blush grade was evaluated
as follows on the final left coronary angiogram in
the lateral view after reperfusion: 0=no myocardial
blush or contrast density; 1=minimal myocardial
blush or contrast density; 2=moderate myocardial
blush or contrast density, but less than that obtained
during angiography of the contra-lateral or ipsilateral
non-infarct-related coronary artery; and
3=normal myocardial blush or contrast density,
comparable to that obtained during angiography
of a contra-lateral or ipsilateral non-infarct-related
coronary artery. When myocardial blush persisted,
this finding will be graded as 0. MBG 2 or 3 will
be defined as good myocardial tissue-level perfusion
(Van’t Hof et al, 1998).

Comparison between Double Intravenous Bolus, Intracoronary Bolus
No reflow defined as reduction of 1 or more in
the TIMI grade in the final angiogram compared
to the post PTCA angiogram or patients with TIMI
3 flow and low TIMI myocardial perfusion grade
(0-1) was observed (Piana et al, 1994).
Transthoracic echocardiography:
Echocardiographic examination was done for
all patients using a 2.5MHz mechanical transducer
mounted in a Vingmed CFM-800 machine (HP in
specialized hospital) with the patient in the left
lateral position from multiple windows. The followings
were measured:
1- Ejection fraction (EF).
2- LV dimensions.
3- Segmental wall motion abnormalities.
4- Complications of acute MI such as ventricular
septal rupture (VSR), acute mitral regurgitation
(MR), aneurysms, LV thrombus….etc.
In-hospital course:
All patients were followed-up during their
hospital stay for development of any major adverse
cardiovascular event (MACE) such as death, recurrent
ischemia, and target vessel revascularization
(TVR). Also they were followed-up for development
major bleeding, minor bleeding and puncture
site bleeding.
Data management:
Data were collected, revised and then edited
on the P.C. The data were then analyzed statistically
by using SPSS statistical package version (12).
The following tests were used:
• X = Mean.
• SD = Standard deviation.
• t test for independent samples.
• ANOVA= Analysis of variance.
• X 2 = Chi square test.
• Post Hoc test.
• p value >0.05 = Non-significant (NS). p value
0.05).

Ahmed I Nassar, et al
Time to treatment:
The mean and SD of door to needle time in
group I was 26.35±4.81, in group II was 27.25min
±8.34 and in group III was 28.25min ±7.99 and it
was statistically not significant between the study
groups (p>0.05). The mean and SD of door to
balloon time in group I was 84.20min ±8.44, in
group II was 86.65min ±21.34 and in group III
was 86.85min ±15.61, and it was statistically not
significant between the study groups (p>0.05).
Coronary angiographic data: Post PCI TIMI
flow assessment revealed achievement of TIMI III
flow in 90% of group II, and 70% of patients in
group I and group III. TIMI II was present in 20%
of group I, 10% of group II, and 15% of group III.
TIMI I was present in 10% of patients in group I
and group III, while TIMI 0 was present in only
5% of group III patients.
PTCA and stenting: PTCA and stenting was
done for all patients in group I, and all patients in
group II except one patient who had recanalized
LAD. Whereas in group III, PTCA was done for
all patients but only 18 patients underwent stenting
as PTCA only was angiographically satisfactory
in the remaining 2 patients. All stents were bare
metal stents. PTCA and stenting were statistically
non-significant among the study groups (p>0.05).
No reflow phenomenon: No reflow phenomenon
was present in 25% of patients in group I, 15%
of patients in group III and although there was not
any patient who developed no reflow in group II
but it was non-significant statistically (p>0.05).
Myocardial perfursion: Myocardial perfusion
was assessed by using myocardial blush grading
(MBG) and it revealed that MBG 0 was present in
20% of group I patients and 30% of group III
patients while there was no MBG 0 among group
II. MBG I was present in 30% of group I patients,
15% of group II patients and 20% of group III
patients. MBG II was present in 30% of group I
patients, 15% of group II patients and 20% of
group III patients. MBG III was present in 20% of
group I patients, 70% and 30% of group III patients
while most of patients in group II had MBG III
(70%). There was significant difference value
between the study groups regarding the MBG
(p0.05).
Minor bleeding: Three patients (15%) in group
I developed minor bleeding, two patients (10%)
in group III developed minor bleeding and no any
patient in group II developed minor bleeding.
Minor bleeding was statistically non-significant
in-between groups (p>0.05).
Post PCI TIMI flow: Assessment revealed
achievement of TIMI III flow in 90% of group II,
and 70% of patients in group I and group III. TIMI
II was present in 20% of group I, 10% of group II,
and 15% of group III. TIMI I was present in 10%
of patients in group I and group III, while TIMI 0
was present in only 5% of group III patients.
Although TIMI III flow post PCI was more prevalent
in group II in comparison to groups I and III
but it was statistically non-significant (p>0.05).
No reflow phenomenon:
No reflow phenomenon was present in 25% of
patients in group I, 15% of patients in group III
and although there was not any patient who developed
no reflow in group II.
Conclusion
In patients presented with acute anterior STEMI
and treated with primary PCI, the high bolus dose
tirofiban given intravenously upstream prior to

Comparison between Double Intravenous Bolus, Intracoronary Bolus
PCI seems to be a safe and effective regimen to
improve the angiographic and clinical outcomes
in comparison to the conventional bolus dose
regimen and the intracoronary bolus dose regimen,
without increasing the risk of bleeding.
This effect could be explained by the early
reach of high drug concentration in the blood and
subsequently early higher degree of inhibition of
platelet aggregation.
References
1- Alpert JS, Thygesen K, Antman E, et al: Myocardial
infarction redefined a consensus document of the Joint
European Society of Cardiology/American College of
Cardiology Committee for the redefinition of myocardial
infarction. J Am Coll Cardiol 2000; 36: 959-969.
2- Antoniucci D, Rodriguez A, Hempel A, et al: A randomized
trial comparing primary infarct artery stenting with or
without abciximab in acute myocardial infarction. J Am
Coll Cardiol 2003; 42: 1879-1885.
3- De Luca G, Smit JJ, Ernst N, et al: Impact of adjunctive
tirofiban administration on myocardial perfusion and
mortality in patients undergoing primary angioplasty for
140
ST-segment elevation myocardial infarction. Thromb
Haemost 2005; 93: 820-823.
4- Goto S, Tamura N, Li M, et al: Different effects of various
anti-GPIIb-IIIa agents on shear-induced platelet activation
and expression of procoagulant activity. J Thrombosis
Haemostasis 2003; 1: 2022-2030.
5- Gunasekara AP, Walters DL, Aroney CN: Comparison of
abciximab with "high-dose" tirofiban in patients undergoing
percutaneous coronary intervention. Int J Cardiol
2006; Apr 28, 109 (1): 16-20.
6- Piana RN, Paik GY, Moscucci M, et al: Incidence and
treatment of ''no-reflow'' after percutaneous coronary
intervention. Circulation 1994; 89: 2514-8.
7- The TIMI Study Group: Thrombolysis in myocardial
infarction (TIMI) trial. N Engl J Med 1985; 312: 932-6.
8- van’t Hof AW, Ernst NM, de Boer MJ, et al: On-TIME
study group: Facilitaiton of primary 2480 Editorial coronary
angioplasty by early start of a glycoprotein 2b/3a
inhibitor: Results of the ongoing tirofiban in myocardial
infarction evaluation (On-TIME) trial. Eur Heart J 2004;
25: 837-846.
9- Zijlstra F, Hoorntje JCA, de Boer M-J, et al: Long-term
benefit of primary angioplasty as compared with thrombolytic
therapy for acute myocardial infarction. N Engl
J Med 1999; 341: 1413-1419.

Egypt Heart J 62 (1): 141-145, March 2010
Safety and Feasibility of Transradial Versus Transfemoral Approach for
Diagnostic Coronary Angiography During Early Phase of
the Learning Curve
MAHMOUD M SABBAH, MBBCh; MOHAMED A ORABY, MD;
GAMELA M NASR, MD; AHMED A EL HAWARY, MD
Background: The radial approach has been increasingly used as an alternative to femoral access as it improves patients’
comfort and permits earlier ambulation and discharge. Our aim was to assess the feasibility, and safety of transradial approach
(TRA) versus transfemoral approach (TFA) for diagnostic coronary angiography, during early phase of the learning curve.
Methods: This is a prospective single-centre comparative study carried out at the catheterization laboratory at Suez Canal
University hospital. We enrolled 203 consecutive patients referred to our centre for diagnostic coronary angiography. Patients
were divided into TRA or TFA groups. We compared the two groups regarding access/procedure success and time, fluoroscopy
time, contrast volume, length of hospital stay and complications. All studies were performed by only 3 angiographers.
Results: There was no significant difference in access success between the two groups. However, TFA was associated with
significantly higher procedure success than TRA (96.7% versus 76.7% respectively, p-value=0.002). TRA was more time
consuming than transfemoral one (23.2±8.4min. versus 19.4±5.9min. respectively, p-value=0.007). Compared with TFA group,
TRA had a significantly longer X-ray exposure time (8.9±2.27min. versus 7.1±1.6min. respectively, p-value=0.002) and associated
with larger amount of contrast (148.04±23.1ml. versus 132.4±22.7ml. respectively, p-value=0.001). Total length of hospital
stay was significantly shorter in the TRA group than in TFA (5.1±1.2 hour Vs 8.9±1.5 hour respectively. p=0.0001). TFA had
higher access site haematoma while arterial spasm was encountered only with TRA.
Conclusions: Compared with transfemoral approach, transradial approach for coronary angiography is a safe and feasible
alternative that is associated with lower local vascular complication rates and shorter hospital stay. However, transradial approach
is associated with some technical difficulties at the early phase of the learning curve that may improve with accumulating
experience.
Key Words: Transradial access – Transfemoral access – Coronary angiography.
Introduction
For the last 2 decades, femoral access has been
the dominant access site for coronary angiography
[1]. Then transradial access emerged as an excellent
alternative to femoral access as this artery has a
superficial course with no nerves or veins of significant
size near the usual site of puncture [2].
Moreover transradial access is associated with less
The Department of Cardiology, Faculty of Medicine,
Suez Canal University.
Manuscript received 28 Nov., 2009; revised 20 Dec., 2009;
accepted 21 Dec., 2009.
Address for Correspondence: Dr. Mohamed A Oraby,
Cardiology Department, Suez Canal University Hospital,
Ismailia, Egypt, Email: maoraby@yahoo.com
141
access site complications (local ischemia, large
haematoma, minor or major hemorrhagic complications)
[3]. Also in transradial access, post procedural
bed rest is not required, permitting immediate
ambulation, more comfort and early discharge [2,3].
This last advantage has shown to improve quality
of life for patients 4 and to reduce the costs of
hospitalization in comparison to transfemoral access
[4,5]. Many interventional cardiologists perceive
that the decrease in minor vascular complications
with radial access3 is balanced by technical difficulties
and increased radiation exposure required
for radial access [5,6].
So, our study was designed to compare the
feasibility and safety of transradial versus transfemoral
approaches for diagnostic coronary angiog-

Safety & Feasibility of Transradial Versus Transfemoral Approach
raphy and to describe the complications and difficulties
associated with the transradial approach
during the early phase of learning curve.
Subjects and Methods
This was a comparative study between the TRA
and TFA approaches in patients undergoing first
time diagnostic coronary angiography in Suez
Canal University hospital cardiac catheterization
laboratory during the period from January 2008,
to January 2009.
Allen's test 7 was performed in all patients and
patients with abnormal test were excluded from
the study. Patients were then sequentially randomized
to either TRA or TFA and all patients had the
same probability to be included in either group.
Five minutes before each procedure, the patients
were premedicated with intravenous 2-4mg midazolam
for sedation.
Angiographic procedures:
TRA was started with the patient lying down
with the right wrist placed in a hyperextended
position. After local anesthesia with 1ml lidocaine,
the radial artery was punctured using a 3.8cm
arterial needle. Then, a 6Fr (8.5cm in length)
introducer sheath was advanced over a 0.025 inch
straight guidewire. To reduce spasm and discomfort,
a drug ''cocktail'' containing 200μg of nitroglycerine,
and 2.5mg of verapamil (unless the patient
had bradycardia or heart failure) and 5000 IU of
heparin were administered through the sheath side
arm. Standard left and right Judkins catheters were
introduced over a 0.035 inch (150cm) guidewire.
The sheath was removed immediately after the
procedure and an elastic band was used to secure
bleeding. The patients were asked to stay for two
hours, during which access site was frequently
checked and patients were discharged if there was
no complications [1,5,8].
Transfemoral catheterization using standard
Seldinger technique was performed and coronary
arterial cannulation was performed using 6Fr diagnostic
Judkins catheters. After the procedure,
the 6Fr sheath was removed immediately and homeostasis
was achieved by digital pressure on the
access site for 10 minutes. Patients were asked to
stay for six hours after the procedure and the access
site was checked frequently. Patients were discharged
if no complication occurred [1,5,8].
All the studies had been performed by 3 interventional
cardiologists who had a limited experi-
142
ence in performing transradial procedures and
under the supervision of a highly experienced
interventional cardiologist in doing this procedure.
Study endpoints:
Both approaches were compared for the following
endpoints: Access and procedure success rates,
access and procedure times, fluoroscopy time,
contrast volume, procedure-related complications,
and post-procedural hospital stay. Access time
was defined as the interval between local anesthetic
injection and sheath introduction, and procedural
time was defined as the interval between local
anesthetic injection and completion of coronary
angiography.
Statistics:
Analysis of the results was performed using
the Statistical Package for Social Sciences, version
15.0 software for Windows. Continuous variables
were expressed as mean ± standard deviation, and
categorical variables as percentages. Continuous
variables of normal and non-normal distribution
were compared with an independent t-test. Categorical
variables were assessed using the chisquare
test. Statistical significance was defined as
a p value of less than 0.05.
Results
Our study included 203 patients, 57.5% of them
were males with mean age 53.5±9.7 years (Table
1), 101 patients had coronary angiography through
the radial approach (TRA group) and the other 102
had angiography performed through the femoral
approach (TFA group). Hypertension was the most
prevalent risk factor (68.3%) and 50% of our
patients were currently smokers (Fig. 1). Access
success was achieved in 98.34% of the patients in
the femoral group versus 93.3% in radial group
(p-value=0.1). Procedure success was significantly
higher In TFA than in TRA (96.7% versus 76.7%
respectively, p-value=0.002) (Fig. 2).
Procedure time was significantly shorter with
femoral access than with radial access (19.4±
5.9min. versus 23.2±8.4min., p-value=0.007). Patients
with transradial approach had also longer
X-ray exposure time than patients in TFA (8.9±
2.27min. versus 7.1±1.6min., p-value=0.002) and
received larger amount of contrast material (148.04
±23.1ml. versus 132.4±22.7ml. p-value=0.001)
(Table 2). Regarding procedure related complications,
arterial spasm was encountered only in patients
with transradial approach (26.1%). There

Mahmoud M Sabbah, et al
was a higher rate of access site haematoma in TFA
group (32.8% Versus 2.2%, p=0.002) (Table 4).
TRA was associated with significantly shorter post
procedural hospital than TFA (5.1±1.2 versus
8.9±1.5 hours. p=0.0001).
The number of catheters used for engagement
of the right and left coronary arteries did not vary
significantly between the two groups. The most
frequently used catheter for cannulation of RCA
in TRA group was JR 3.5 (71.7%) while the most
commonly used catheter for cannulation of RCA
in TFA group was JR 4 (86.2%). For the left coronary
system, JL 3.5 catheter was the most frequently
used in TRA group (67.4%) while JL 4 was the
most frequently used in TFA group (87.9%).
Regarding comparison between both Lt and Rt
radial approaches, left radial artery was accessed
more frequently than the right one according to
the operator preference. There was no significant
difference between the two sides regarding procedure
success (92.9% versus 93.5% in Rt and Lt
radial artery respectively). Despite a smaller number
patients in the Rt radial group; access time, procedure
time, fluoroscopy time and contrast volume
were similar between the two sides (Table 5).
Table 1: Baseline characteristics of the study population.
Sex:
Male
Female
Age:
Mean ± SD
Range
Height (cm):
Mean ± SD
Weight (Kg):
Mean ± SD
BMI (Kg/m 2 ):
Mean ± SD
Radial access
(n=60)
51.7%
48.3%
51.9±8.1
[30-74]
171.2±11.3
85.3±9.8
27.5± 2.8
Femoral access
(n=60)
63.3%
36.7%
54.7±10.3
[31-76]
168.9±6.1
86.9±12.3
28.6±3.9
*Statistically significant difference (p-value

Safety & Feasibility of Transradial Versus Transfemoral Approach
%
100
90
80
70
60
50
40
30
20
10
0
p-value=0.1 p-value=0.002
93.3 100
Access success
Figure 2: Procedure and access success/failure among the
studied Population.
Discussion
This study was designed to assess feasibility
and safety of transradial versus transfemoral approaches
to diagnostic coronary angiography in
our center during the early phase of the learning
curve. We showed no significant difference in the
access success between either groups (i.e. TRA
and TFA), and this was matched with the results
of Fernández et al [9] and Labrunie et al [5]. We
found also that TRA was associated with more
procedure failure (23.3%) than TFA (3.3%).
A systemic review (including 14 randomized
studies published up to 2004) by Agostoni et al
[1], reported a failure rate with TRA of 7.2%, and
they refer to the lack of adequate previous learning
curve as the major cause of the failure of this
procedure. More recent studies reported success
rates higher than 97%, comparable to those
achieved with TFA [6,9,10]. The lower TRA success
rate in our study compared with others could be
attributed to the lower experience and familiarity
of our operators with this technique as they were
still in the early phase of the learning curve, also
deficiency of well settled transradial programme
and dedicated materials could play a role in increasing
failure rate. Labrunie et al [5] showed that
the most important improvement in TRA was related
to operator skill. In fact, there is clear evidence
in all the examined trials that a learning curve is
essential for this technique [11].
The causes of procedure failure in TRA group
in our study included: Access failure, severe radial
77
96.7
Procedure success
Radial access Femoral access
144
arterial spasm (that occurs before or during coronary
procedures) and failed cannulation of the
coronary arteries. Both Hildick-Smith et al [12]
and Amoroso et al [13] reported similar causes for
the failure of TRA. In our study the failed transradial
cases were crossed over to alternate arterial
access according to operator preference.
In our study TRA was more time consuming
and associated with longer X-ray exposure than
TFA. Similarly, larger amount of contrast material
was used in TRA than in TFA. Similar findings
were reported by, Louvard et al [14], Lange et al
[15] and Hildick-Smith et al [16]. They attributed
these findings to the technical difficulties related
to this technique during the early phase of the
learning curve and assured that when the right
skills are grasped, the technique become much
easier and reliable and take less time and dye.
We showed also that patients with TRA had
significantly shorter post-procedural hospital stay
compared to patients with TFA. Other investigators
[4,10,13] reported the same observation and concluded
that TRA leads to favorable post-procedural
quality of life, presumably due to the near absence
of required bed rest and the rapid return to a normal
level of functioning.
Arterial spasm was the most commonly encountered
complication with TRA as it occurred in one
every four procedures and attributed to procedure
failure in the majority of cases. This was supported
by the findings of Coppola et al [17] and Saito et
al [18], both showed that, even in centers having
an extensive experience with the radial access,
radial spasm occurs in 15% to 30% of the procedures
and suggested more effective sedation, intraarterial
vasodilator cocktails and smaller catheters,
as means to overcome this phenomenon. On the
other hand, access site haematoma was the main
complication of TFA as it occurred in more than
one fourth of the procedures and more commonly
encountered in obese and female patients.
Comparing Rt. and Lt. Radial approaches, there
was no significant difference regarding procedure
success, access time, procedure time, and fluoroscopy
time and contrast volume. There was also no
significant difference in procedure related complications
or in length of hospital stay between the
two sides. Bodi et al [19] reported similar findings,
while Wu et al [20] pointed out that passage through
the right common brachiocephalic trunk, primarily
in elderly patients, could generate difficulties for

Mahmoud M Sabbah, et al
right transradial catheterization. So the Left transradial
catheterization offers the theoretical advantage
of avoiding this passage and permitting a more
direct access to ascending aorta [20]. These differences
have been reflected in clinical terms in certain
studies such as those of Kawashima et al [21] in
which the left transradial catheterization shortened
the procedure and the examination time. Fernández
et al [22] reported that the right transradial catheterization
was associated with a higher failure rate
due to problems with the tortuosity and atherosclerosis
of the right common brachiocephalic trunk.
Conclusion
Compared with transfemoral approach, transradial
approach for coronary angiography is a safe
and feasible alternative that is associated with
lower local vascular complication rates and shorter
hospital stay. However, TRA is associated with
some technical difficulties at the early phase of
the learning curve that may improve with accumulating
experience.
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21- Kawashima O, Endoh N, Terashima M, Ito Y, Abe S,
Ootomo T, et al: Effectiveness of right or left radial
approach for coronary angiography. Catheter Cardiovasc
Interv 2004; 61: 333-7.
22- Fernández-Portales J, Valdesuso R, Carreras R, Jiménez-
Candil J, Serrador A, Romaní S: Vía radial derecha o
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Egypt Heart J 62 (1): 147-154, March 2010
Correlation between Clinical Presentation, ECG and
Echocardio-Graphic Findings and Those of Angiography in Patients
Undergoing Coronary Angiography
FATHI A MAKLADY, MD,FRCP; HANAN M KAMAL, MD; AZZA Z EL-ERAKY, MD;
OMAR M SALEH, MBBCh
Background: Coronary artery disease (CAD) is the most important among cardiovascu-lar diseases, both CAD mortality
and the prevalence of risk factors continue to rise rap-idly in developing countries. The cardinal symptom of patients with CAD
is chest pain that initiates clinical evaluation. The 12-lead ECG and the echocardiography are the core to the diagnostic and
triage pathway for ACS and provides important prognostic infor-mation. Coronary angiography (CA) remains the standard for
identifying the presence or absence of atherosclerotic CAD it helps to delineate coronary anatomy for determining the appropriate
therapy in patients with ischemic CAD.
Aim of the Work: To correlate the risk factors, the complaint, the ECG and the echocar-diographic findings with those of
the coronary angiography.
Subjects and Methods: A total of 150 patients who were referred electively to the CA procedure. All of them were subjected
to a thorough clinical assessment using Rose questionnaire and Framingham risk score, ECG and echocardiography.
Results: The results showed that the proportion of males was found to be more than fe-males (66% and 44% respectively.
(The ECG findings showed that 40% of patients with normal coronaries had ECG changes indicative of ischemia and 63% of
patients with dis-eased coronaries had no resting ECG changes. The echocardiography findings showed that 44% of those with
CAD had SWMA and 9.5% had SWMA with normal coronaries. Various sensitivities and specificities were calculated and
revealed that chest pain has a good sensitivity and positive predictive value, the ECG had an equal sensitivity and specificity
and echocardiography had the highest specificity and positive predictive value in diagnosing CAD.
Conclusion: The overall correlation between the studied parameters showed that the Framingham risk score came in first
place followed by the echocardiography. The chest pain character came in third place and finally the ECG findings.
Key Words: Chest pain – Echocardiography – ECG – Coronary angiography.
Introduction
Coronary artery disease (CAD) is the most
important among cardiovascular diseases, it kills
more than 7 million people each year worldwide.
Both CAD mortality and the prevalence of risk
factors continue to rise rapidly in developing countries
partly as a result of in-creasing longevity,
The Department of Cardiology, Faculty of Medicine,
Suez Canal University.
Manuscript received 5 Jan., 2010; revised 14 Feb., 2010;
accepted 15 Feb., 2010.
Address for Correspondence: Dr. Hanan Mohamed Kamal,
The Department of Cardiology, Faculty of Medicine, Suez
Canal University, Ismailia, Email: hananmkamal@yahoo.com
147
urbanization, and lifestyle changes [1,2]. Survivors
of myocardial infarction (MI) continue to have a
poor prognosis, and their risk of mortality and
morbidity is 1.5-15 times greater than that of the
rest of the population. This fact remains true despite
a 30% reduction in mortality from coronary artery
disease over the past 3 decades in the western
communities [3].
The cardinal symptom of patients with CAD is
chest pain that initiates clinical evaluation. It is
common among the general population [4]. The
(ACC/AHA) guidelines (2007) empha-size that
the patient with symptoms consistent with acute
coronary syndrome (ACS) should be referred to
facilities that allow rapid evaluation by a physician
and the recording of a 12 lead electrocardiogram

Correlation between Clinical Presentation, ECG & Echocardio-Graphic Findings
(ECG). The 12-lead ECG is central to the diagnostic
and triage pathway for ACS and provides important
prognostic information [5]. In a number of studies,
the presence of ischemic changes in the resting
ECG, that is, ST-segment depression and T-wave
inversion, has been reported to be a strong predictor
of fatal ischemic heart disease (IHD) in men without
clinical evidence of IHD, independent of major
conventional risk factors of IHD [6,7].
Echocardiography is the most frequently used
imaging test to evaluate all cardiovascular diseases.
Evaluation of CAD is the most common use of
echocardiography. Its strength is the assessment
of myocardial thickness, thickening, and motion
at rest. Its usage ranges from the diagnosis with
resting or stress echo to the detection of a complication
and prognosis using wall motion score [8].
CA remains the standard for identifying the
presence or absence of atherosclerotic CAD it
helps to delineate coronary anatomy for determining
the appropriate therapy in patients with ischemic
CAD [9]. In addition to defining the site, severity,
and morphology of lesions, it helps provide a
qualitative assessment of coronary blood flow and
helps identify collateral vessels [10].
The aim of this study was to correlate the risk
factors, clinical presentation, electrocardiography
and echocardiographic findings with the angiographic
findings in patients undergoing coronary
angiography.
Subjects and Methods
The study was a descriptive cross sectional
study conducted in Suez Canal University Hospital,
cardiac catheterization laboratory, Cardiology
department. The target population are patients
attending the hospital, who were referred for elective
coronary angiography.
The inclusion criteria include, history of chest
pain prior to procedure which was due to suspected
ischemic heart disease, history of angina equivalent
symptoms (e.g.: Dyspnea, fatigue), and patients
who were referred for coronary angiography for
the first time. The study excluded patients undergoing
percutanous coronary intervention (PCI).
patients with valvular heart disease due to any
cause other than ischemic one, patients in clinical
heart failure, and patients with history of coronary
artery bypass graft (CABG).
148
Each individual was subjected to the following:
1- Personal information about the patient, including:
Age, sex, occupation, marital status, special
habits (e.g.: Smoking, alcohol intake), waist
circumference and body mass index (BMI). The
latter is calculated as: Weight (in kg)/(height
[in meters]) 2.
2- History and clinical examination of the patient,
including: Past history of any chronic illness,
clinical presentation of the present complaint.
The chest pain was analyzed by using the WHO
Rose questionnaire [11] and was subdivided into
four categories: No chest pain, non-exertional
chest pain, possible angina, and definite angina.
Complete clinical examination was done.
3- Laboratory findings of the following investigations:
Random blood sugar, total cholesterol,
triglycerides, LDL level, and HDL level.
4- Risk score classification: All the patients’ data
was grouped by the Framingham risk score [12]
and assigned to either had very low, low, intermediate
or high risk score.
5- Twelve-leads ECG (using Fukuda Denshi, Cardimax
FX 2111 device): Preprocedural ECG was
analyzed for ST-T abnormalities that correlate
to coronary artery disease including: ST depression
more than 0.1mV, or ele-vation and symmetrical
T-wave inversion >0.2mV. Changes
were grouped according to relevant territories
supplied by native coronary ar-teries [13].
6- Echocardiography: 2D and Doppler echocardiogaphy
were performed prior to the procedure in
the standard views. Regional function assessment
according to the 16 segment model of the
American Society of Echocar-diography: Grade
1=normal, grade 2=hypokinesia, grade 3=akinesia,
grade 4=dyskinesia. LVEF was determined
with Teich method in the short axis view at the
level of the papillary muscles. It was then classified
into: Normal: ≥55%, mildly de-pressed:
45%-54%, moderately de-pressed: 30%-44%,
severely de-pressed: 50% in LM artery and >70% in all other

Fathi A Maklady, et al
vessels, patients were categorized into four
groups: Group 1: Normal coronaries, Group 2:
Single vessel disease, Group 3: Two vessel
disease, Group 4: Multivessel disease.
Statistical analysis:
Data was tabulated and analyzed using SPSS
ver. 16 software to determine the statistical inference
of the variables in question. Discrete variables
were presented in the form of frequency and percentage
tables. Inferences were done using Pearson’s
chi-square test of significance and Yates’
correction for 2x2 tables to determine the statistical
significance among them. Continuous variables
were presented in the form of mean and standard
deviation. t-test of independence was used to analyze
inferences about them. ANOVA tables were
used to determine the level of significance between
multiple variables. Spearman's correlation coefficient
was used to estimate different correlations
between variables. p-value less than 0.05 was
considered significant. The sensitivity, specificity,
positive predictive value and negative predictive
value of different variables in relation to the gold
standard coronary angiography for diagnosing
CAD were calculated.
Results
A random sample of 150 participants was enrolled
in the study after fulfilling the inclusion
criteria. The majority of them were males (66%).
Table (1) shows the data of the studied population
distributed among the CA findings. Most of the
studied group lies within the age range of 40-69
years with mean age of 55.5±10. Twenty seven
percent of the study group were smokers and all
of them are males. Hypertension was more prevalent
than diabetes among the studied population
(60% vs. 43% respectively). Most of the study
group were dyslipidemic (77%) and obese (46%).
Using the Framingham risk score the studied population
was categorized most.
Considering the clinical presentation of patients,
chest pain was the most common presenting complaint
(62%) rather than angina equivalent (10.7%).
Further evaluation by using Rose questionnaire
revealed that 35% of the population presented by
definite anginal pain. The ECG findings shows
that 55% of the studied population had changes
suggestive of ischemia. Thirty four percent had
segmental wall motion abnormalities by
echocardiography and most of the population (77%)
had normal ejection fraction (Table 1).
149
Fig. (1) shows the distribution of the studied
population among the findings of the coronary
angiography procedure. The majority of the patients
(29%) lies in the multivessel disease group and
only 16% lies in the two vessel disease group.
Analysis of the risk factors in conjunction with
these findings (Table 1) showed that male gender
had higher proportion of CAD rather than females
(75% vs. 25%) and the relation was significant
(p

Correlation between Clinical Presentation, ECG & Echocardio-Graphic Findings
Figure 1: Coronary angiography diagnosis among the studied
population of them (34%) lie within the intermediate
risk score.
Table 1: Characteristics of the studied population.
Item
Gender:*
Male
Female
Age groups:*
30-39
40-49
50-59
60-69
> 70
Smoker*
Ex-smoker*
Hypertensive
Diabetic
Dyslipidemic
FRS:*
Very low
Low
Intermediate
High
Presenting complaint:*
Chest pain
Angina equivalent
Both
Rose questionnaire:
No chest pain
Non-exertion pain
Possible angina
Definite angina
ECG changes*
SWMA*
28%
27%
No CAD
Two vessel
EF: Normal
Mildly depressed
Moderately depressed
Severely depressed
CAD
No (%)
81 (75)
27 (25)
9 (8)
16 (15)
35 (32)
38 (35)
10 (9)
34 (32)
30 (28)
62 (46)
50 (46)
89 (82)
13 (12)
21 (19)
42 (39)
32 (30)
72 (67)
8 (7)
14 (13)
22 (20)
16 (15)
25 (23)
45 (42)
65 (60)
47 (44)
78 (72)
18 (17)
10 (9)
2 (2)
* Significant at p

Fathi A Maklady, et al
Table 2: The overall correlation between coronary angiography
and other parameters.
Item
Risk score
Echocardiography
Chest pain
ECG
* Significant at p0.05). Valenzuela LF et al [20] and
Kato et al [21], found also in their study that diabetes
had an insignificant relation with the coronary
artery diagnosis in patients with ACS. Kalantzi et
al [22] found hypertension to have a significant
relation with CA diagnosis in patients with ACS.
The difference may be attributed to the selection
r
Coronary angiography
0.343
0.3
0.262
0.224
p-value
0.000*
0.000*
0.001*
0.006*
151
of patients, as the studied population in their study
was young; below the age of 50 years, whereas we
studied all the age groups and so the prevalence
of hypertension in our study was more. The
Framingham risk score was used extensively before
for assessing the risk for coronary heart disease
and prediction of cardiovascular risk. The higher
proportion of patients with normal CA (64%) lies
in the very low and low risk categories while only
14% lies in the high risk category. By increasing
the extent of the disease, the number of patients
in the very low and low categories falls down and
most of the patients are grouped between the intermediate
and the high risk categories.
The clinical presentation:
The relation between the presenting complaint
and the CA diagnoses showed that the majority of
patients were complaining of chest pain that was
variable among gender and showed different distribution
among the chest pain character with Rose
questionnaire. In normal subjects, 50% had chest
pain only and 26% had the chest pain combined
with angina equivalent symptoms. The majority
of them were females (66%). Normal angiography
in patients with chest pain was found to be five
times more common in women than in men, this
may be attributed to abnormalities of the microcirculatory
vessels [23], abnormality of both endotheliumdependent
and independent vasodilatation [24],
occult atherosclerosis [25], or peripheral coronary
microembolization [26]. On the other hand, the
percentage of patients with CAD diagnosed by CA
and were presented without symptoms was 13%,
the majority of them had single vessel disease
(50%). The concept of silent myocardial ischemia,
has emerged long years ago, several studies have
proposed that patients with diabetes mellitus are
subgroup, estimating the prevalence of silent ischemia
in them to be 29-69% compared with 5-
35% for non-diabetic patients [27-29]. The overall
value of the chest pain as a diagnostic tool for
CAD in our study was 80% sensitive and 24%
specific. It has a low ability to role out CAD
between both sexes but much more less in females
than males (13% vs. 39% respectively).
The ECG:
The results of the coronary angiography pose
a significant relation with ischemic ECG changes
found in the patients before undergoing the procedure.
It was found that 63% with abnormal coronary
arteries had no ECG changes. Also, 40% of the
patients with normal CA had ECG changes indic-

Correlation between Clinical Presentation, ECG & Echocardio-Graphic Findings
ative of ischemia. Welch RD et al [30] stated that
8% of patients with confirmed transmural myocardial
infarction will have an entirely normal ECG.
In patients with diagnosis of CAD by CA, more
than 50% had normal or non-diagnostic ECGs.
Other studies also found the same results as ours.
[20,31] The value of the ECG in predicting the CAD
in the present study was variable. It shows an
overall equal sensitivity and specificity with low
negative predictor value than a positive predictor
value. Among gender, the values are almost the
same for males with higher positive predictive
value. In females the values were less than males
but with higher negative predictor value.
The echocardiogram:
Two-Dimensional echocardiography is well
accepted for evaluation of cardiac function [32].
The association of echo features with underlying
CAD is less well established [33]. In this study we
studied the relation of the ejection fraction (EF)
assessed by M-mode and the segmental wall motion
abnormalities (SWMA) assessed by 2-D with the
extend of CAD. The extent of CAD influence the
ejection fraction of the studied population. The
mean EF was found to be higher in patients with
normal coronaries than those with multivessel
disease. The presence of SWMA in our study was
significantly associated with the extend of CAD
and with individual coronary artery. It was mentioned
in previous studies that regional wall motion
abnormalities may also occur without history or
clinical and ECG signs of coronary artery disease
[34]. In our study, there was a percentage of patients
(9.56%) with normal coronary arteries and had
SWMA by 2-D echocardiography. This could be
explained by the presence of microvascular and
endothelial dysfunction that could cause ischemia
to the myocardium without detected major occlusions
[35], also post-ischemic dysfunction, or myocardial
stunning, which is the mechanical dysfunction
that persists after reperfusion despite the
absence of irreversible damage and despite restoration
of normal or near-normal coronary flow.
Implicit in this definition is that post-ischemic
dysfunction is a fully reversible abnormality, provided
of course that sufficient time is allowed for
the myocardium to recover [36]. It has been mentioned
by others that SWMA could occur with
normal coronaries due to either transient ischemic
dysfunction, myocardial scar, stunning/hibernation,
cardiomyopathy, or different combinations of these
conditions [34].
152
The overall correlation:
In the overall correlation of the studied parameter,
the risk score assessment was the mostly
correlated parameter with coronary angiographic
findings. Recent studies mentioned that global risk
assessment has become an important tool in the
primary prevention of CVD and has led to a paradigm
shift in the clinical management of risk factors
[37,38]. Most authors agreed that the first and internationally
most widely used risk prediction tools
were developed with data from the Framingham
Heart Study [39,40] which was used in our study.
The echocardiography is the second parameter
in order significantly correlated with coronary
angiography. Previous studies have shown that
some isolated echo features are associated with
underlying CAD either using marker of CAD like
SPECT, stress Echo or angiography [41,42].
The chest pain character was found to be in the
third order of correlation with coronary angiography.
Several cardiac or non-cardiac diseases may
cause chest pain, which makes the differential
diagnosis of these diseases a great challenge. However,
Diamond and Forrester [43] demonstrated that
the type of chest pain is the best determination
indicative of pre-test probability of coronary disease
in these patients, more predictive than the basic or
stress electrocardiogram.
The ECG was the least correlated parameter
with coronary angiography. Miranda CP et al [44]
found that the occurrence of ST-segment depression
and T-wave inversion in the resting ECG appears
to correlate with the severity of the underlying
heart disease, including the number of vessels
involved and the presence of left ventricular dysfunction.
However, Ischemic changes in the ECG
(ST changes, T wave changes and new arrhythmias
or bundle branch block) are seen in only half of
the patient population presenting with suspected
ACS. Hence the ECG is non-diagnostic in at least
half of the patients [45,46].
Conclusion
• The constellation of risk factors pose a strong
correlation with the extent of CAD.
• The echocardiography is a mainstay in diagnosing
CAD, it has a good specificity and positive predictive
value.
• The chest pain has a reliable sensitivity and a
positive predictive value.

Fathi A Maklady, et al
• The ECG has a poor sensitivity and specificity
in diagnosing CAD hence it is useful for exclusion
of high risk patients.
Recommendations
The following measures are recommended:
Using a risk score system in all patients under risk
of developing CAD for early detection and management.
• Applying a chest pain questionnaire for patients
presenting by chest pain.
• Training of all physicians dealing with chest pain
patients in ECG interpretation.
• Echocardiography should be used for all patients
routinely either for detection or for follow-up.
• Carry on a nation-wide study for determining
the exact prevalence of the disease in our country
and the ways of diagnosis.
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Egypt Heart J 62 (1): 155-164, March 2010
Measurement of Fractional Flow Reserve (FFR) for Guiding Percutaneous
Coronary Intervention in Clinical Practice
HUSSEIN SHAALAN, MD
Background: FFR, calculated from coronary pressure measurement, is a reliable invasive index to indicate if a stenosis is
ischemia-related and can be determined in the catheterization laboratory in a simple and rapid way.
Aim of the Work: Study the role of measurement of FFR before PCI in daily practice with regards to decision making and
procedure outcome.
Patients and Methods: 80 patients with CAD referred for coronary angiography with possible PCI were included. Patients
were divided into two equal groups: FFR guided group in whom coronary pressure wire was part of the procedure and FFR
had an impact on decision making, and angiographic guided group or the standard (control) group. The cut-off point for FFR
group was 0.75 above which no PCI was done; while diameter stenosis of 70% was the cut-off point in the control group below
which the decision for PCI was left for the operator discretion. Accordingly, each group was further divided into 3 subgroups;
PCI, medically treated, and mixed subgroups (relevant lesions underwent PCI, and irrelevant ones were managed medically).
All patients were followed-up both in-hospital and for at least one month after discharge. Both groups were compared with
regards to; MACE (composite of death, MI, and repeat revascularizations), as the primary end points, and procedure time,
fluoroscopic time, contrast volume, functional status (angina or dyspnea), and total procedure cost as secondary end points.
Results: Both groups were matched with regards to demographic data and clinical presentations. PCI was performed in 55
(68.8%) patients in both groups (25 in FFR group and 30 in angiograph group); the rest of patients were managed medically.
All patients received DES. FFR was measured successfully in 60 vessels of FFR guided group. FFR significantly increased in
PCI patients from 0.70 to 0.88 (p0.05). However, procedure time and contrast consumption were significantly higher in FFR guided group Vs. the control
group (p

Measurement of Fractional Flow Reserve (FFR)
[3]; FFR can reliably interrogate any individual
stenosis, and therefore, can be used for immediate
decision-making in the catheterization laboratory
whether to stent or not [4,5,6].
Compared with intravascular ultrasound
(IVUS), which shows anatomical lesion characteristics,
FFR localizes the ischemia producing lesion
among different morphologic lesions seen by
IVUS.Similarly, not all angiographic ally relevant
lesions as decided visually by experienced interventional
cardiologist or even by quantitative
coronary angiography (QCA) are ischemia producing
lesions (especially those of moderate severity)
and need to be treated.
It is to be noted that, some previous studies
suggested that acute ischemic events not frequently
occur at the site of previously insignificant or mild
stenosis [7,8]. This has been extended into the
general belief that a mild stenosis could have a
worse prognosis and that use of PCI in such a
lesion might be beneficial [9]. However, in the
defer study [1] it was shown that PCI of such lesions
without functional significance did not improve
outcome or anginal status and did not reduce the
use of antianginal medications.
Coronary artery disease patients with nonischemia
producing lesions have total event rate
of 21% for the next 5 years which is still higher
than normal people. Risk factor modification and
adequate medical treatment are probably of greater
prognostic value than mechanical coronary intervention.
According to the current guidelines, PCI
should be performed after having documented
inducible ischemia [10,11]. Nevertheless, a prior
non-invasive evidence of ischemia is present in a
minority of patients underlying PCI [12].
In the era of drug eluting stent (DES), FFR
measurement holds its value for guiding PCI as
stenting non-ischemia-related lesion with bare
metal stent (BMS) has worse outcome than the
defer approach but better than stenting ischemic
lesion. DES does reduce target vessel revascularization
(TVR), but not mortality or myocardial
infarction (MI).
Compared with BMS, treatment of intermediate
lesions with DES rather than BMS appears safe
and results in a marked reduction in clinical and
angiographic re-stenosis. The efficacy of DES may
require re-evaluation of current treatment paradigm
for intermediate lesions.
156
Aim of the study:
Study the role of measurement of fractional
flow reserve (FFR) using coronary pressure wire
for guiding PCI in daily practice with regards to
decision making (to stent or not) and its impact on
procedure outcome.
Patients and Methods
The present study included 80 patients with
CAD referred for coronary angiography with possible
PCI. Patients were divided into two equal
groups: Group I (FFR or study group) in whom
coronary pressure wire was part of the cardiac
catheterization procedure to estimate lesion severity
by FFR, and group II (control or angiography
group) in whom the whole procedure was guided
angiographically.
According to the coronary anatomy seen during
diagnostic coronary angiography and fractional
flow reserve measurement results, patients were
further subdivided into 3 subgroups: Subgroup A
(PCI group guided by either FFR if ≤0.75 or angiography
if ≥70% diameter stenosis), subgroup
B (medical treatment group when FFR is >0.75 or

Hussein Shaalan
Catheter findings: Standard coronary angiography
was done for all patients using the standard
technique with ad hoc PCI after reviewing the
angiographic findings.
Clearly significant lesions (≥70%) as seen in
all projections were tackled immediately whenever
suitable for PCI without further evaluating the
lesion severity by FFR. while intermediate coronary
lesions (between 50-70%), either they were left
for medical treatment or stented according to FFR
result in the study group or as decided by the
operator in the angiography control group).
In case coronary pressure wire was not available,
the decision to do PCI is left for the operator
after correlating patient symptoms to catheter
findings or whenever non-invasive test is available.
This study is a single centre, single operator randomized,
controlled study. The overall Coronary
morphology and lesion complexity were described
according to the SYNTAX score.
Fractional flow reserve measurement: FFR is
defined as the ratio of the maximal blood flow
achievable in a stenotic vessel to the theoretical
maximal flow in the same vessel if no stenosis was
present. In a normal coronary artery there should
be no pressure gradient between the aorta and the
distal artery resulting in a FFR value of 1. These
simultaneous measurements can be made in a
stenosed coronary artery using a pressure tipped
coronary guide wire to record distal pressure and
a guide catheter to record pressure in the aorta.
The cut-off value of FFR is ≤0.75 (ischemic
zone); and value between 0.75 and 0.8 (the grey
zone) was also considered for PCI whenever there
is another lesion with FFR ≤0.075 in need of PCI
in the same patient [13]. Coronary pressure guide
wire (RadiMedical system) was used at maximal
hyperemia induced by IC (in most cases) adenosine
or IV infusion (140ug/kg/min) in a central vein.
However, big doses of adenosine (70-90ug at
least and up to 150ug) should be given for each
lesion to get a reliable result. The effect starts to
appear within 10sec and remains only for 20sec.
The effect of IV adenosine starts within 1min and
disappear in 1min after cessation of infusion.
Calculation of FFR: Unfractionated heparin (5000
units) is given initially; the transducer of the coronary
pressure should be in the left main stem or
in a healthy area proximal to the lesion. The piezoelectric
crystal is located 30mm from the wire tip
157
i.e. at the beginning of the radio-opaque distal
segment. Nitroglycerine IC (200ug) is injected
first followed by IC adenosine to achieve maximal
hyperemia. Caffeine intake prior to the procedure
is not yet proved to alter FFR measurements [14].
If the recorded aortic pressure is damping (ventricularized)
upon catheter engagement smaller sized
catheter is preferred [15].
FFR=mean distal coronary pressure (measured
with the pressure wire)/mean aortic pressure (measured
simultaneously with the guiding catheter)
using maximal hyperemia. FFR is checked before
and after PCI to ensure adequate stent deployment
(if FFR >0.90). The higher the post stenting FFR
value the lower the event rate [16].
PCI: PCI was performed using the standard
technique, and usually via the femoral approach.
PCI patients received only DES. However, PCI
with DES was not planned for more than 2-vessels
in one session. All consumables during PCI were
collected at the end of the procedure and each item
price is included to get the total procedure cost
(namely; guide wires, guiding catheters, balloons,
stents, coronary pressure wires, adenosine, and 1year
clopidogrel therapy). The mean procedure
time (defined as the total time starting from puncture
site till removal of the guiding catheter),
fluoroscopic time, and contrast volume were reported
and compared between the two groups.
Repeat cardiac markers were rechecked after PCI.
Follow-up: All patients were given appointment
in the outpatient clinic within 1 month post procedure,
3 months, and lastly 6 months. Patients should
attend at least once in the outpatient clinic to be
included in this study.
End points: All patients will be followed-up
post procedure both in-hospital and during followup
period in outpatient clinic for major adverse
cardiac events (MACE); death (all cause mortality),
MI (diagnosed by ≥3 folds rise of cardiac markers
or new Q-waves in 2 contiguous leads), and repeat
revascularization (PCI or CABG). Functional status
(angina and/or shortness of breath), procedure
time, contrast volume, and total cost were also
compared between groups.
Statistical analysis:
Data was analyzed on an IBM personal computer,
using Statistical Package for Special Science
(SPSS) software computer program version 15.

Measurement of Fractional Flow Reserve (FFR)
• Data were described as mean ± standard deviation
(SD) for quantitative (Numerical) variables and
as frequency and percentage for qualitative (Categorical)
variables.
• Independent Student t test was used for comparison
of quantitative variables among two independent
groups.
• Paired t test was used for comparison of quantitative
variables among two dependent groups.
• One-way ANOVA test was used for comparison
of quantitative variables among more than two
independent groups. Least significant difference
test (LSD) test was used as post-hoc test.
• Chi-square test (or Fisher’s exact test when
appropriate) was used for comparison of distribution
of qualitative variables among different
group.
• Correlation between continuous variables was
performed using person correlation coefficient.
• Kaplan–Meier estimate and logrank test was
used for assessment of survival of different outcomes.
Table 1: Patient’s demographic data between both groups.
Parameter
Age (mean ±SD) (range:27-85)
M: F ratio
Smoking
DM
(on insulin)
Hypertension
Hyperlipidemia
Family history
BMI (mean ± SD)
FFR guided
58.50±11.99
24 (60%):16 (40%)
19 (47.5%)
27 (67.5%)
9 (22.5%)
26 (65%)
18 (45%)
2 (5%)
29.16±5.74
Table 2: The clinical presentations of the studied groups.
Parameter
Stable CAD
Unstable CAD
NSTEMI
Old MI (>3 months)
Recent MI (>5 days)
Renal impairment
Previous PCI
EF (mean ± SD)
FFR guided
18 (45%)
7 (17.5%)
11 (27.5%)
11 (27.5%)
10 (25%)
4 (10%)
16 (40%)
45.62±9.94
158
• Significance level (p) value: p>0.05 is insignificant
(NS). p≤0.05 is significant (S).
Results
A total of 80 patients were enrolled in this
study. Of the total 55 (68.8%) PCI patients, 25
(45.5%) patients were assigned for FFR guided
strategy and 30 (54.5%) patients were assigned for
the standard angiographic strategy. The rest of the
patients were followed-up medically. Each group
was divided into 3-subgroups: (A) PCI was performed
in 7 (17.5%) patients guided by FFR measurement
versus 14 (35%) patients guided by angiography,
(B) medically treated patients in 15
(37.5%) patients guided by FFR measurement
versus 10 (25%) patients guided by angiography,
and (C) mixed group with PCI performed in relevant
lesions while the non relevant ones were left
untreated in 18 (45%) patients in FFR group versus
16 (40%) in angiography group (p value=0.17).
Both groups were matched with regards to
demographic data and clinical presentations (except
patients with previous PCI) with no statistical
differences among main groups or the three subgroups,
as shown in Tables (1,2).
Angiographic guided
56.67±13.88
30 (75%):10 (25%)
16 (40%)
22 (55%)
8 (20%)
24 (60%)
17 (42.5%)
3 (7.5%)
29.86±5.84
Angiographic guided
19 (47.5%)
7 (17.5%)
9 (22.5%)
6 (15%)
13 (32.5%)
2 (5%)
4 (10%)
45.37±9.63
0.05
0.00
0.26
1.86
0.54
0.72
9.6
Chi-square
0.62 (t-test)
2.05
0.45
1.31
0.07
0.21
0.05
0.21
–0.54 (t-test)
Chi-square
0.11 (t-test)
p value
0.53
0.15
0.45
0.25
0.78
0.64
0.82
0.64
0.58
p value
0.82
1.0
0.60
0.17
0.45
0.39
0.002
0.90

Hussein Shaalan
Non-invasive tests were not frequently requested
in the present study, 14 (17.5%) patients; in
other words, the decision to send the patient to the
invasive service was made mainly on clinical basis.
Out of total FFR guided procedure (>80 patients)
done in our centre (from January 2007 till June
Table 3: Shows the catheter findings among both groups.
Parameter
(mean ± SD)
Lesion: Patient ratio
Vessel: Patient ratio
Rx vessel: Patient ratio
(50% to 0.75
Vessel (2) ≤0.75
Total
Vessel
Vesse 1&2 >0.75
Vessel 1&2 ≤0.75
0.93
0.71±0.07
0.89
0.70±0.1
0.88
0.70
N=40 (100%)
N=20 (50%)
FFR
guided
FFR pre PCI
3.0±1.4
In the FFR guided group, 8 vessels out of 60
measured had their value in the grey zone (>0.75-
≤0.80); half of them were followed-up medically,
and the other half underwent PCI because of concomitant
PCI planned for another vessel.
Cardiac biomarkers were measured before and
after PCI, the results are shown in Table (5) which
illustrates the PCI outcomes between both groups.
There was no difference between both groups with
2.37±1.0
1.28±0.45
1.72±1.1
1.3±1.0
1.1±0.90
1.37±1.1
11.23±5.9
38.45±21.25
n=29 (72.5%)
n=11 (27.5%)
n=14 (35%)
n=6 (15%)
n=43 vessels
n=17 vessels
159
2009), only 40 patients were included, the other
patients were excluded because of exclusion criteria.
There were more patients with borderline
lesions (50%-

Measurement of Fractional Flow Reserve (FFR)
Table 5: PCI outcomes between both groups.
Parameter
Ck-MB pre PCI
Ck-MB post PCI (3-5X N)
TNT (I) pre PCI
TNT (I) post PCI (3-5X N)
DES: Patient ratio
DES size ≥2.75
DES size

Hussein Shaalan
Table 8: Comparison of total cost (a) and hospital stay (b) between 3 subgroups.
Parameter
FFR group (a)
(b)
Angiographic group (a)
(b)
t-test (a) (b)
p value (a) (b)
PCI sub G
7208±1873
6.2±4.2
4843±2048
3.8±2.38
2.5 1.6
0.01 0.1
Rx sub G
On follow-up, coronary angiography was performed
in 4 (10%) patients of FFR guided group
(two of them had PCI, and the other two were
followed up medically) versus 3 (8%) patients of
angiographic guided group (none of them was in
need of PCI or CABG, (p=0.69). The follow-up
duration was significantly longer in FFR-guided
group, 7.59±8.3 months compared with the angiography
guided group, 3.83±2.0 months (p=0.008).
Since the present study enrolled patients with
multiple lesions and diseased vessels, although
with low SYNTAX score (as shown in Table 3),
some patients continue to have chest pain and/or
shortness of breath; 7 (17.5%) and 10 (25%) patients
in FFR guided group versus 9 (22.5%) and
6 (15%) patients in angiographic guided group
respectively (p=0.24). Kaplan-Meier survival functional
curves addressing the results of the functional
status between both groups are shown below together
with the patients who had follow up coronary
angiography (CAG) ± PCI. The number of patients
reached the hard end points was too little to plot
the curves for them.
The cost of procedures and the duration of
hospital stay are shown in Tables (7,8). Although
2140±414
2.4±0.9
1000±0.0
2.9±1.5
10.66 –0.8

Measurement of Fractional Flow Reserve (FFR)
Decision making only on anatomic finding
(including IVUS) is more likely to waist resources
and make the role of PCI in stable patients only
for cosmetic purpose [18]. Interventional cardiologist
is not only responsible for mechanical revascularization
by PCI, but also optimization of medical
therapy and life style modifications. According
to the Courage trial [19], PCI benefits the subsets
of patients who demonstrated ischemia reduction
by ≥5% as documented by non-invasive tests; while
the 5 years follow-up failed to demonstrate any
benefit of PCI over optimum medical therapy in
reducing all cause mortality or MI.
Why would we need FFR and/or IVUS if the
lesion is clearly significant? The probability of
having non ischemic lesion when the lesion looks
significant angiographically (≥90%) is nil if FFR
measurements is applied, and it rises when the
diameter stenosis gets less (≥70-

Hussein Shaalan
FAME trial versus 81% in FFR guided group with
no statistical difference, (p=0.20). The same findings
were documented in the present study (77.5%
of patients free from angina in angiographic guided
group versus 82.5% in FFR guided group, p=0.24).
Procedure time (but not fluoroscopic time) and
contrast volume were higher-in the present studyin
FFR guided group compared with angiographic
guided group; this is in contrast to the FAME
results which showed less cost and less consumption
of contrast material in FFR guided group
compared with angiographic guided group.
In FAME trial the mean number of stent deployment
per patient was 2.7±1.2 in angiographic
guided group versus 1.9±1.3 in FFR guided group,
p

Measurement of Fractional Flow Reserve (FFR)
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13- Ross J, McGeoch, MB/chB, MRCP, Keith G Oldroyd,
MB/chB, MRCP: Pharmacological options for inducing
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AE: Effect of caffeine administered intravenously on
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measurement after stenting predicts adverse events at
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2950-2954.
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NJ Schork, MA Schork, FD Loop: Analysis of coronary
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19- William E Boden, Robert A O'Rourke, Koon K Teo, et al:
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20- Atsushi Takagi, Yukio Tsurumi, Yasuhiro Ishii, Kazuhito
Suzuki, et al: Clinical Potential of Intravascular Ultrasound
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Nicolas Meneveau, Hu Wei, Katy Didier, Marie-Cecile
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FAME Study Investigators). Fractional Flow Reserve
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Egypt Heart J 62 (1): 165-171, March 2010
Angiographic Coronary Artery Disease in Women with Chest Pain and
History of Anxiety Disorders
KHALED E DARAHIM, MD, MRCP*; MONA IBRAHIM AWAAD, MD**
Background: Among women, the presentation of angina symptoms is neither a sensitive nor a specific marker for coronary
artery disease.
Objective: This study aimed to evaluate the ability of psychiatric anxiety-disorder history to discriminate between women
with and without angiographic coronary artery disease (CAD) in a population with chest pain.
Methods: We included 50 women who were referred for coronary angiogram to evaluate chest pain or suspected myocardial
ischemia. Participants completed the Hamilton Rating Scale for Anxiety (HAM-A), a five-item behavioral avoidance scale, and
the Beck Depression Inventory (BDI). Coronary artery disease covariate measures included analysis of chest pain, coronary
artery disease risk factors, quantitative coronary angiography analysis including modified Gensini score.
Results: Women with a history of anxiety disorders [9 of 50 (18%) participants] were younger (48.0 Vs. 60.7 years of age;
p

History of Anxiety & Coronary Angiography
Chest pain symptoms may also be related to
noncardiac causes, including psychological disorders
(Freedland et al, 1996; Smith et al, 1996;
Freedland et al, 1991 and Freeman et al, 1987).
Although some studies showed that anxiety is more
common in patients with normal anatomy than
those with coronary disease, there is often considerable
overlap (Chambers and Bass, 1998). Crosssectional
studies have demonstrated relationships
between psychological factors such as high anxiety
and life stress with chest pain symptoms in women
(Stansfeld et al, 1993; Fisher et al, 1996 and Costa,
1987). These associations, however, may be interpreted
to suggest that stress and anxiety contribute
to increased CAD risk (Rozanski et al, 1999 and
Musselman et al, 1998), or that chest pain promotes
increased stress and anxiety resulting from symptom-related
concerns of illness or death.
Studies showed that generalized anxiety disorder
and major depression were more common in
cardiac patients than in the general community
(Frasure-Smith, 2006). Furthermore, some studies
showed that Generalized Anxiety Disorder appeared
to be associated with elevated coronary heart disease
risk relative to major depressive disorder
(Barger and Sydeman, 2005). Evidence pertaining
to the relationship between psychological factors
and an objective measure of CAD among women
with chest pain symptoms would aid in the interpretation
of these data, but we are unaware of such
findings to date.
In this study, we hypothesize that women with
chest pain and a psychiatric history of anxiety
disorders are less likely to have angiographic CAD
than are those women with chest pain symptoms
and no anxiety history.
Objective:
This study aimed to evaluate the ability of
psychiatric anxiety-disorder history to discriminate
between women with and without angiographic
coronary artery disease (CAD) in a population with
chest pain.
Methodology
Study population:
The study included 50 women who were referred
for coronary angiogram to evaluate chest
pain or suspected myocardial ischemia. Participants
completed a battery of symptom and psychological
questionnaires at baseline testing, along with quantitative
coronary angiography.
166
The inclusion criteria were:
1- Women older than 18 year of age.
2- Referred for a coronary angiogram.
Exclusion criteria included patients with:
1- Current pregnancy.
2- Recent myocardial infarction, cardiomyopathy.
3- Revascularization procedure (percutaneous transluminal
coronary angioplasty or coronary artery
bypass graft).
4- Congenital heart disease.
5- Language barrier preventing questionnaire completion.
The study protocol was approved by the research
committee of our institution and informed
consent of all subjects was obtained.
Methods:
Coronary artery disease assessment:
Coronary artery disease covariate measures
included age, body mass index, obesity (BMI
>30kg/m 2), menopausal status, family history of
coronary artery disease, diabetes status, smoking
status, hypertension status, and hypercholesterolemia
status (positive/negative history). Risk
factors (when not previously known) were defined
according to the European Society of Cardiology
guidelines as follows: Hypertension as blood pressure
>140/90mmHg in three consecutive readings,
at rest; hypercholesterolemia as total and low LDL
cholesterol level >5mmol/L (>190mg/dL) and
3mmol/L (>114mg/dl), respectively; diabetes as
fasting glucose level >7.0mmol/L (>125mg/dl);
obesity as body mass index (BMI) >30kg/m 2; and
family history of CAD as parents with CAD at age

Khaled E Darahim & Mona I Awaad
multiple projections, and reference vessel diameter,
minimal lumen diameter, and percent diameter
stenosis were measured from the 'worst' angiographic
view.
Coronary disease severity was judged by three
criteria. First, using the quantitative angiogram
results, we assigned each participant to a group:
"no CAD" (20mm of normal artery segment was
classified as 2-VD.
In addition, a total of 10 (16.7% of the noanxiety-history
participants and 37.5% of the positive-anxiety-history
group) participants also completed
noninvasive tests for myocardial ischemia
(exercise stress testing).
Left CA Right CA
Figure 1: Schematic drawing of the GENSINI score (left). The method assigned a different severity score depending on the
degree of stenosis, its location (proximal, middle or distal tract) along the target vessel and the type of coronary
vessel involved (left anterior descending, left circumflex, or right coronary artery). An example of Gensini score
calculation is shown on the right part of the figure. MLCA, main left coronary artery; LAD, left anterior descending;
CFx, left circumflex; RCA, right coronary artery.
Psychiatric and covariate measures: Participants
completed the Hamilton Rating Scale for
Anxiety, a five-item behavioral avoidance scale,
and the Beck Depression Inventory.
Prox
X1
lurnen diameter Severity score
PD
x1
LAD: Patent
Score: 0
CFx: 99% concentric (16), proximal (2)
Score: 2 X 16=32
RCA: 90% eccentric (8), proximal (1)
Score: 8 X 1=8
Final Gensini score: 0 + 32 + 8 = 40
The Hamilton Rating Scale for Anxiety (HAM-
A) was developed in the late 1950s to assess anxiety
symptoms, both somatic and cognitive. Because
conceptualization of anxiety has changed consid-

History of Anxiety & Coronary Angiography
erably, the HAM-A provides limited coverage of
"worry" required for DSM-IV diagnosis of generalized
anxiety disorder and does not include the
episodic anxiety found in panic disorder. There
are 14 items, each of which is rated 0 to 4 on an
unanchored severity scale, with the total score
ranging from 0 to 56. A score of 14 has been
suggested as the threshold for clinically significant
anxiety, but scores of 5 or less are typical in individuals
in the community.
The avoidance scale contained five questions
(scores range from 5 to 50; higher scores equal
greater avoidance) assessing the avoidance of
common situations (traveling by bus, walking alone
on busy streets, going into crowded shops, going
alone far from home, and large open spaces) because
of fear.
Finally, the Beck Depression Inventory (BDI)
(Beck et al, 1996): Created by Dr. Aaron T. Beck,
is a 21-question multiple-choice (scores range from
0 to 63) self-report inventory that is one of the
most widely used instruments for measuring the
severity of depression. The most current version
of the questionnaire is designed for individuals
aged 13 and over and is composed of items relating
to depression symptoms such as hopelessness and
irritability, cognitions such as guilt or feelings of
being punished, as well as physical symptoms such
as fatigue, weight loss, and lack of interest in sex.
There are three versions of the BDI-the original
BDI, first published in 1961 and later revised in
1971 as the BDI-1A, and the BDI-II, published in
1996. The BDI is widely used as an assessment
tool by healthcare professionals and researchers
in a variety of settings. Scores of 0 to 9 are considered
minimal; 10 to 16 mild; 17 10 29 moderate;
and 30 to 48 severe. A BDI score of 17 is frequently
used to mark the presence of "subclinical" (i.e.,
not Diagnostic and Statistical Manual of Mental
Disorders [DSM-IV] (American Psychiatric Association,
1994) diagnostic for a mood disorder)
depression.
Additional questions assessed whether participants
had ever received treatment from a psychologist
or psychiatrist for an anxiety disorder (we
did not collect data regarding the length, type,
precipitating factors or success of the treatment).
Statistical analysis:
The data were analyzed statistically using the
software Statistical Package for Social Science
168
(SPSS) version (9). Chi square test for categorical
variables. Using independent sample t tests, we
compared participants with and without a history
of anxiety disorders on measured CAD risk factors,
angina symptoms and other pain indices (e.g.,
headaches, back pain, etc.) and anxiety symptoms
experienced at baseline testing (i.e., scores on the
above HAM-A, avoidance and depression scales).
p value ≤0.05 (2 tailed) is considered significant
and ≤0.01 is highly significant.
Results
The study included 50 women who were referred
for coronary angiogram to evaluate chest
pain or suspected myocardial ischemia.
Clinical characteristics of the study group:
Table (1) compares women with and without a
history of anxiety disorders across measured CAD
risk factors, angina and other physical symptoms.
Women with a history of anxiety disorders [9 of
50 (18%) participants] were younger (48.0 Vs.
60.7 years of age), more likely to smoke and had
lower cholesterol blood levels. Symptom profiles
also differed between groups. Women with a positive
anxiety history more frequently endorsed
sensations of "sharp, knife-like pain" in describing
their chest pain.
Table 1: A Comparison of patients with and without an anxiety
disorder history on angina and other physical symptoms,
CAD risk factors.
Age (years)
% Current smokers
% Hypertensive
% Diabetic
% Hypercholesterolemic
% FH of CAD
Body mass index
% Obesity
% Angina from exertion
% Sharp, knife-like pain
% Tightness
% Left arm pain
% rest pain
% Using nitroglycerin
% Headaches
% Positive exercise test
With
anxiety
history
(n=9)
48.0±12.2
33.3
44.4
33.3
33.3
33.3
32.99±7.46
55.6
33.3
33.3
55.6
22.2
66.7
11.1
44.4
33.3
Without
anxiety
history
(n=41)
60.7±10.4
2.4
65.9
41.5
70.7
14.6
32.19±5.87
48.8
43.9
4.9
87.8
14.6
51.2
12.2
29.3
34.1
p
value
0.002
0.006
NS
NS
0.034
NS
NS
NS
NS
0.01
0.023
NS
NS
NS
NS
NS
Data are expressed as a mean ± standard deviation or percent (%).
CAD = Coronary artery disease.
FH = Family history of CAD.
NS = Non-significant.

Khaled E Darahim & Mona I Awaad
A positive anxiety-disorder history was not
associated with a lower likelihood of having inducible
ischemia on noninvasive stress testing (33%
Vs. 34%, p=NS).
Table (2) showed that women with a past history
of anxiety history still experience higher anxiety
symptoms, both somatic and cognitive. The positive
anxiety group expressed significantly greater distress
levels at baseline, as indicated by higher
behavioral avoidance scores and more depressive
symptoms.
Table 2: A comparison of patients with and without an anxiety
disorder history on psychological characteristics.
HAM-A
BDI
Avoidance scale
Table 3: A comparison of women with and without a history
of anxiety disorders on three indices of CAD.
CAD
CAD groups:
%Normal
%Non-obstructive
%Obstructive
VD Number:
%Normal
%Single
%Double
%Triple
Gensini score
With anxiety
history (n=9)
29.4±9.8
11.7±7.1
13.6±7.4
With anxiety
history (n=9)
22.2
66.7
11.1
22.2
77.8
0
11.1
11.1
4.4±8.5
Without anxiety
history (n=41)
5.8±4.3
2.9±2.6
5.6±2.4
Data are expressed as a mean ± standard deviation.
HAM-A = Hamilton Rating Scale for Anxiety.
BDI = Beck Depression Inventory.
NS = Non-significant.
Without anxiety
history (n=41)
41.5
53.7
4.9
41.5
58.5
22
9.8
9.8
13.3±20.6
p
value
0.000
0.006
0.013
p
value
NS
NS
NS
0.047
Data are expressed as a mean ± standard deviation or percent (%).
CAD = Coronary artery disease.
CAD groups: Normal = Maximum stenosis

History of Anxiety & Coronary Angiography
Furthermore, the symptom profiles also differed
between the two groups. Women with a positive
anxiety history more frequently endorsed sensations
of tightness and sharp, knife-like pain in describing
their chest pain. Rutledge et al, also demonstrated
that women with past history of anxiety described
their pain more frequently as sharp knife-like chest
pain, besides they demonstrated that their pains
last longer and had a greater chance of experiencing
angina while at rest. (Rutledge et al, 2001).
Although previous studies have explored relationships
between psychological factors and endpoints
such as angina during exercise testing (Freedland
et al, 1996), the prevalence of psychological
distress among patients with angina (Smith et al,
1996) and the role of psychological factors in silent
myocardial ischemia (Freedland et al, 1991), few
reports investigated the association between a
history of anxiety disorders and angiographic CAD
in women with chest pain.
Our findings suggest that a history of anxiety
disorders is associated with a less severe angiographic
CAD among women presenting with chest
pain symptoms. Rutledge et al, demonstrated that
the presence of an anxiety-disorder history was
associated with a significantly lower likelihood of
significant angiographic CAD among women with
angina, also they demonstrated that women with
a history of anxiety disorders evidenced significantly
less severe disease (Rutledge et al, 2001).
Our study did not show significant difference
as regard the presence of coronary artery disease,
or number of diseased vessels. Although not statistically
significant, based on CAD groupings,
women in the positive-anxiety-history group were
less than twice as likely (22.2% Vs. 41.5%) to
show obstructive CAD. Failure to show statistical
significance may reflect that the study is underpowered
to show this difference.
Although we observed a low prevalence of
obstructive CAD among women with chest pain
who reported a history of anxiety disorders, it is
notable that a 22.2% of this group nevertheless did
show angiographic evidence of obstructive CAD
(i.e., >50% stenosis). Therefore, this result reinforces
the need to carefully evaluate symptoms in
women irrespective of psychological history and
to consider anxiety-history variables as a topic in
future investigations.
Furthermore, our results do not suggest that
women as a group are immune to have severe CAD
170
(which is the leading cause of death among both
women and men), or even that an anxious female
patient is less likely to show evidence of severe
CAD (i.e., our results reflect a known anxietydisorder
history, not current symptoms).
Limitations of the study:
Our observation of an association between a
previous anxiety disorder and current angiogram
results also raises questions concerning the temporal
nature of this relationship. However, we believed
that concurrent anxiety symptoms assessed at
baseline testing before or after angiogram may
reflect more transient factors (e.g., concern about
health or potential test results or current life difficulties)
and may therefore offer less insight into
the long-term symptom reporting style we have
shown to be linked to a less severe disease.
Our measure of anxiety history was also rather
global and did not allow us to examine relationships
with specific anxiety conditions. Although the
sample size and prevalence rate of anxiety disorders
found in our population would have limited such
an examination, most of the cases included in the
study were diagnosed according to the Diagnostic
and Statistical Manual of Mental Disorders, Fourth
Edition (DSM-IV) as generalized anxiety disorder,
two cases have panic disorder and one case has
mixed anxiety and depression.
There is a possibility of a referral bias (i.e.,
participants may not represent a random sample
of women with angina, and anxiety characteristics
may affect treatment-seeking behavior) that may
constrain the generalizability of these results.
Conclusion
Our study demonstrates that the presence of an
anxiety-disorder history was associated with a
significantly less severe angiographic CAD among
women with chest pain. Determining a patient’s
anxiety-disorder history may assist the clinician
in identifying women with chest pain having less
severe CAD.
References
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Egypt Heart J 62 (1): 173-179, March 2010
Depression Post Acute Coronary Syndromes: Incidence and Predictors
MONA IBRAHIM AWAAD, MD; KHALED E DARAHIM, MD, MRCP
Depression occurs comorbidly in patients hospitalized for a range of cardiac conditions and procedures. To date, few
predictors of persistent depression in cardiac patients have been identified, apart from a past history of depression. This study
assess the incidence of depressive symptoms and predictors of depression within 3 months post acute coronary syndromes. This
study included 72 patients with acute coronary syndromes; 25 patients diagnosed with MI and 47 patients diagnosed with
unstable angina. Depression was measured using the Beck Depression Inventory (BDI). Predictor variables were assessed and
included demographic details and clinical cardiac and depression risk factors. The incidence of depressive symptoms was 41.7%,
while the severity of depression according to the BDI score was; 16.7% for mild depression, 20.8% for moderate depression
and 4.2% for severe depression. The independent predictors for depression (moderate and severe) within 3 months after acute
coronary syndromes were; having a past history of depression (OR 20.4), female gender (OR 17), marital separation (OR 4.6),
and having past history of cardiac condition (OR 3.5). In conclusion, these predictors in this study may assist physicians in
identification of cardiac patients who are at risk of depression and who may require active intervention.
Key Words: Depression – Acute coronary syndromes.
Introduction
Depression occurs comorbidly in patients hospitalized
for a range of cardiac conditions and
procedures. Most commonly, research has focused
on the relationship between depression and myocardial
infarction (MI); previous studies showed
that post-MI patients have an incidence of 18%
for meeting the criteria for major depressive disorder
and an incidence of 27% for having significant
depressive symptoms (Roose, 2001). However,
similar high prevalence rates of depression have
been reported in patients experiencing unstable
angina and congestive heart failure (Friedman and
Griffin, 2001) and in patients undergoing cardiac
procedures such as coronary artery bypass graft
(CABG) and angioplasty (Blumenthal et al, 2003).
In the last decade many large-scale, wellcontrolled
studies, in which initially healthy subjects
were followed-up prospectively, have identified
depression as a significant independent risk
The Departments of Psychiatry and Cardiology, Ain Shams
University.
Manuscript received 30 Sep., 2009; revised 3 Nov., 2009;
accepted 4 Nov., 2009.
Address for Correspondence: Dr. Mona Ibrahim Awaad,
The Department of Psychiatry, Ain Shams University.
173
factor for both first myocardial infarction (MI) and
cardiovascular mortality, with an adjusted relative
risk in the range of 1.5 to 2. Similarly, among
individuals with established ischemic heart disease,
depression has been found to be associated with
an approximately 3- to 4-fold increase in the risk
of subsequent cardiovascular morbidity and mortality
(Glassman et al, 2002).
Moreover, hospitalization for cardiac disease
is associated with an increased risk for depression,
which itself confers a poorer prognosis (Mayou et
al, 2000). Few prospective studies have examined
the determinants of depression after hospitalization
in cardiac patients, and even fewer have examined
depression within weeks after hospital discharge
(Kaptien et al, 2006).
Previous studies have reported that depression
is associated with an increased risk of cardiac
events in cardiovascular disease (CVD) patients
and is known to increase the cost of patient care
and decrease the quality of life. Even at low levels
of severity, depressive symptoms are associated
with increased risk for the incidence and recurrence
of acute coronary syndromes (Bush et al, 2001),
as well as all-cause mortality risk in patients with
known heart disease increased by 60% (Roose,
2003). Moreover, prospective epidemiologic studies
have shown that depression is associated with an

Depression Post Acute Coronary Syndromes
increase in risk independent of other known medical
prognostic markers in this population (Davidson
et al, 2006).
The pathways to such negative outcomes for
depressed cardiac patients are unclear. Both biological
and psychological explanations have been
advanced, including serotonin-mediated platelet
disturbances, sympathetic nervous system dysfunction,
poor treatment compliance, and low motivation
to change smoking habits or lifestyle (Lane
et al, 2001). Findings indicative of hyperactivity
of the hypothalamic-pituitary-adrenocortical axis,
including elevated cerebrospinal fluid corticotropinreleasing
factor levels, elevated plasma cortisol
concentrations, and nonsuppression of cortisol
secretion in response to dexamethasone administration,
have been repeatedly reported in patients
with major depression. In addition to elevated
cortisol, many patients with depression also have
elevated plasma and urinary catecholamine levels,
indicating dysregulation of the autonomic nervous
system. Imbalance between sympathetic and parasympathetic
tone that results in sympathetic overdrive
predisposes patients with IHD to arrhythmia,
ventricular fibrillation, and sudden cardiac death.
Increased catecholamine activity may also increase
platelet activation and aggregation, contributing
to thrombus formation and may trigger an ischemic
event (Carney et al, 2002).
To date, few predictors of persistent depression
in cardiac patients have been identified, apart from
a past history of depression (Schrader et al, 2004).
The recognition of factors connected with post
infarct depressive symptoms has a significant role
for rehabilitation in coronary heart disease (Krzyzkowiak,
2007). Moreover, this will lead to identifying
better treatments for depression in this population
which could lead to improved medical,
financial, and psychosocial outcomes for those
patients (Taylor et al, 2005).
This study aimed to assess the incidence and
predictors of depression after hospitalization for
acute coronary syndromes (myocardial infarction
and unstable angina) and to compare the incidence
of depression in patients with acute myocardial
infarction (MI) and patients with unstable angina.
Methodology
Study population:
The inclusion criteria included Patients older
than 18 years of age, hospitalized for acute coronary
174
syndromes (including acute myocardial infarction
or unstable angina).
Exclusion criteria included patients with alcohol
or substance abuse or dependence; psychotic symptoms,
history of psychosis, organic brain syndrome.
The study protocol was approved by the research
committee of Alzhra Hospital, Almadina
Almunawara, Kingdom Saudi Arabia, and informed
consent of all subjects was obtained.
Methods:
For a diagnosis of acute MI, a patient must
have met at least 1 criterion from each of the
following 2 categories. Category 1 criteria were:
(a) creatine kinase isoenzyme MB (CK-MB) level
greater than the upper limit of normal; (b) CK or
troponin T or troponin I level more than 2 times
the upper limit of normal; or (c) a total lactate
dehydrogenase (LDH) level more than 1.5 times
the upper limit of normal (with LDH 1 greater than
LDH 2). Category 2 criteria were: (a) typical
ischemic symptoms (chest pain or shortness of
breath) lasting for more than 10 minutes; or (b)
electrocardiographic (ECG) evidence of ischemic
ST-segment depression, ST-segment elevation, or
new pathological Q waves.
Alternatively, patients could enter the study if
they met the following criteria for unstable angina:
(a) experienced angina or anginal equivalent symptoms
at rest, with episodes lasting for at least 10
minutes and leading to hospitalization, and had
ECG documentation of transient ST-segment elevation
or depression of more than 0.5mm, or had
T-wave inversion of greater than 1mm within 12
hours of an episode of chest pain; or (b) were
hospitalized for symptoms of unstable angina and
had known coronary artery disease with a documented
history of a prior MI, had undergone a
prior revascularization procedure, or had documented
coronary artery stenosis greater than 75% in
one of the major epicardial vessels.
Psychiatric and covariate measures:
Depression was measured using the Beck Depression
Inventory (BDI) within 3 months after
hospitalization for acute coronary syndromes. The
Beck Depression Inventory (BDI) (Beck et al,
1996): Created by Dr. Aaron T. Beck, is a 21question
multiple-choice (scores range from 0 to
63) self-report inventory that is one of the most
widely used instruments for measuring the severity
of depression. The most current version of the

Mona I Awaad & Khaled E Darahim
questionnaire is designed for individuals aged 13
and over and is composed of items relating to
depression symptoms such as hopelessness and
irritability, cognitions such as guilt or feelings of
being punished, as well as physical symptoms such
as fatigue, weight loss, and lack of interest in sex.
There are three versions of the BDI-the original
BDI, first published in 1961 and later revised in
1971 as the BDI-1A, and the BDI-II, published in
1996. The BDI is widely used as an assessment
tool by healthcare professionals and researchers
in a variety of settings. Scores of 0 to 9 are considered
minimal; 10 to 16 mild; 17 10 29 moderate;
and 30 to 63 severe. A BDI score of 17 is frequently
used to mark the presence of "subclinical" depression.
Predictor variables, chosen with regard to evidence
from previous research on comorbid depression,
included demographic details (e.g. age, gender,
marital status, employment, education) and
cardiac and depression risk factors (e.g. selfreported
smoking status, medical history "including;
hypertension, diabetes, dyslipidymia, thyroid disorders,
renal failure, and liver failure", past history
of "including; myocardial infarction, angina, cardiac
procedures, depression, anxiety or other psychiatric
disorders") from the baseline questionnaire administered
during hospitalization, as well as information
from hospital administrative records on the index
admission and other hospital admissions in the
previous 2 years.
Patients are also interviewed for the social
readjustment rating scale (SRRS), this scale is
based on the premise that good and bad events in
one's life can increase stress levels and make one
more susceptible to illness and mental health problems.
Each event should be considered if it has
taken place in the last 12 months, then add values
to the right of each item to obtain the total score,
scores

Depression Post Acute Coronary Syndromes
Table 2: Comparison of the demographic, cardiac and psychiatric
risk factors for depression.
Age (years)
Age category:
18-54 years
55-64 years
>65 years
Gender:
Males
Females
Marital status:
Not married
Married
Marital separation
Education:
Not educated
Low education
High education
Occupation:
Employed
Unemployed
Retired
Smokers:
Current smoker
Ex smoker
Never smoked
Obesity (BMI >30)
Hypertensive
Diabetic
Hypercholesterolemic
PH of cardiac condition
PH of cardiac procedure
Other medical condition
PH of depression
FH of Cardiac condition
FH of depression
Cardiac diagnosis:
MI
Unstable angina
Depression
(n=30)
54.7±11.87
18 (39.1%)
8 (44.4%)
4 (50%)
21 (35%)
9 (75%)
1 (100%)
19 (33.9%)
10 (66.7%)
19 (57.6%)
2 (25%)
9 (29%)
15 (31.3%)
9 (75%)
6 (50%)
10 (34.5%)
7 (50%)
13 (44.8%)
13 (46.4%)
11 (37.9%)
13 (48.1%)
25 (44.6%)
10 (55.6%)
16 (45.7%)
1 (50%)
5 (83.3%)
7 (50%)
1 (50%)
11 (44%)
19 (40.4%)
No depression
(n=42)
50.6±8.92
28 (60.9%)
10 (55.6%)
4 (50%)
39 (65%)
3 (25%)
0 (0%)
37 (66.1%)
5 (33.3%)
14 (42.4%)
6 (75%)
22 (71%)
33 (68.7%)
3 (25%)
6 (50%)
19 (65.5%)
7 (50%)
16 (56.2%)
15 (53.6%)
18 (62.1%)
14 (51.9%)
31 (55.4%)
8 (44.4%)
19 (54.3%)
1 (50%)
1 (16.7%)
7 (50%)
1 (50%)
14 (56%)
28 (59.6%)
p
value
NS
NS
0.022
0.036
0.041
0.019
NS
NS
NS
NS
NS
0.1
NS
NS
0.042
NS
NS
NS
Data are expressed as a mean ± standard deviation or percent (%).
FH = Family history.
BMI = Body mass index.
PH = Past history.
NS = Non-significant.
Table (3) presents the variables found to be
statistically significant in the multivariate analysis;
it showed that the independent predictors of depression
post acute coronary syndrome were; having
a past history of depression (OR 8.2), female
gender (OR 5.6), and marital separation (OR 4.3).
176
Table 3: Multivariate predictors of depression post acute
coronary syndrome.
Predictors
PH of Depression
Gender (female)
Marital status
(unmarried/marital separation)
Odds
Ratio
8.2
5.57
4.28
Confidence
interval
0.91-74.29
1.36-22.82
1.29-14.13
p
value
0.026
0.037
0.039
However the independent predictors of moderate
to severe depression post acute coronary syndrome
were; having a past history of depression
(OR 20.4), female gender (OR 17), marital separation
(OR 4.6), and having past history of cardiac
condition (OR 3.5) as shown in Table (4).
Table 4: Multivariate predictors of moderate to severe depression
post acute coronary syndrome.
Predictors
PH of Depression
Gender (female)
Marital status
(unmarried/marital separation)
Past history of cardiac condition
Susceptibility to illness and mental health problems
assessed by the social readjustment rating
scale showed that in the group of patients with
depression; low susceptibility was 40%, mild susceptibility
was 56.7% and moderate susceptibility
was 3.3%. While the group of patients without
depression showed only low susceptibility (100%)
as shown in Table (5).
Table 5: Social readjustment rating scale of depressed patients
post acute coronary syndrome.
Social readjustment
rating scale
Low
Mild
Moderate
Depression
(n=30)
12 (40%)
17 (56.7%)
1 (3.3%)
Odds
Ratio
20.38
17
4.6
3.5
Data are expressed as a number (percent of the groups with or
without depression)
Discussion
Confidence
interval
2.19-189.79
3.84-75.16
1.39-15.19
1.11-11.18
No depression
(n=42)
42 (100%)
0 (0%)
0 (0%)
p
value
0.001
0.000
0.020
0.056
p
value
0.0001
Depression in cardiac patients is well documented
in the literature, studies have reported a low
level of identification by physicians and very low
levels of psychiatric intervention for this group
(Graham and Hogg, 2002). Findings from recent
intervention studies of depressed cardiac patients
have underlined the need to identify cardiac patients

Mona I Awaad & Khaled E Darahim
whose depression persists and who may be at risk
of adverse health outcomes (Schrader et al, 2004).
Moreover, depression in patients with cardiovascular
disease is a significant risk factor for developing
symptomatic and fatal ischemic heart disease
(van Melle, et al, 2004) and they have higher than
expected rate of sudden death (Roose, 2001). Few
prospective studies have examined the determinants
of depression after hospitalization in cardiac patients,
and even fewer have examined depression
within the weeks after hospital discharge (Davidson
et al, 2006).
Our results illustrate considerable fluidity in
the level of depressive symptoms during the first
3 months after hospitalization for acute coronary
syndromes, where 41.7% had depressive symptoms
and 25% of them had moderate to severe depression
according to the BDI score. These results matched
the results of Ellis et al (2005), as they found
depressive symptoms in 40.2%of patients diagnosed
with acute coronary syndrome, and with Schrader
et al (2004), who found that 40% of patients experienced
moderate to severe depression at 3 months
after cardiac hospitalization, and were in consistent
with Kaptein et al (2006), who found that 22.7%
of patients had severe depressive symptoms post
MI and the presence of these depressive symptoms
was relatively stable at 3 months and 12 months
post MI. However, our study showed no statistical
significance as regard the incidence of depression
in patients with MI and those with unstable angina,
and they did not contribute to the prediction of
depression. This result was in agreement with a
previous study reported that patients with unstable
angina had similar prevalence rates of depression
as patients with MI (Lesperance et al, 2000).
Analysis of the social readjustment scale
showed that patients with mild to moderate susceptibility
to mental health problems were all
having depressive symptoms, while only 22% of
those with low susceptibility showed depressive
symptoms. It should be noted that marital separation,
personal illness (including acute coronary
syndromes), and unemployment (which we noted
as predictors for depression in our study) are strong
stressors in this scale with the highest point score.
In our study the predictors of depression at 3
months (for both mild and moderate to severe
depression) were; female gender, marital separation
(either unmarried, divorced or widowed), not educated,
unemployment and having past history of
177
depression. However, our multinomial regression
model showed that the independent predictors for
both mild and moderate to severe depression were;
female gender, marital separation and having past
history of depression. The finding that female
gender was a predictor of depression at 3 months
post acute coronary syndrome was confirmed by
a previous study that showed that female gender
predicted depression in the early recovery period
after hospitalization for acute coronary syndrome
(Dunn et al, 2006).
The finding that past history of depression was
a strong predictor of depression at 3 months was
in agreement with Lesperance et al (1996), who
found that people with a history of previous major
depression were more likely to be depressed after
infarction both in hospital and after discharge.
They argued that most efforts in settings with
limited psychiatric resources should be directed
toward post-MI patients with a history of depression.
Furthermore, Glassman et al (2002), reported
in the SADHART study that sertraline was found
to be robustly superior to placebo only in cardiac
patients who had a history of at least two prior
episodes of depression.
However, the independent predictors of mild
depression post acute coronary syndrome were less
clear, therefore, we analyzed the independent predictors
for patients with moderate to severe depression
which showed that the significant predictors
were female gender, marital separation, having
past history of depression, and having past history
of cardiac condition. These results were in consistent
with a previous study which found that significant
variables associated with prevalence of depression
post acute coronary syndrome were;
female gender, past history of MI, and smoking
(Nagvi et al, 2007).
However, as regard the other variables we
assessed (age, smoking status, obesity, hypertension,
diabetes, past history of cardiac procedure,
past history of anxiety or other psychiatric conditions,
and family history of cardiac condition or
psychiatric condition), we did not find significant
correlations between them and the incidence of
depression after acute coronary syndromes. These
results were not in agreement with, The Identifying
Depression as a Comorbid Condition IDACC)
study (2003) prospectively examined depression
in patients with a range of cardiac conditions,
young age, female, divorced or separated, not

Depression Post Acute Coronary Syndromes
employed, living alone, having a lower level of
education, and having poor health and quality of
life were risk factors for depression after admission
for a cardiac condition. But most of the risk factors
identified by the IDACC study have individually
been associated with depression in other studies,
and they have not been reported as a group.
Moreover, Schrader et al (2004), who found in
their study that younger age, smoking status and
past history of a cardiac condition were also significant
predictors for depression after cardiac
hospitalization. The association between smoking
and an increased risk of depression at 3 months
was consistent with evidence of increased risk of
major depression being associated with smoking
(Ziegelstien et al, 2000). Such disagreement between
our study and previous studies is perhaps
attributable to the small sample size.
In conclusion, our study demonstrated that the
independent predictors for depression (moderate
to severe) within 3 months after acute coronary
syndromes were; female gender, marital separation,
having a past history of depression and having a
past history of cardiac condition. It is noteworthy
that these 4 variables are routinely sought during
patient history taking and therefore are readily
accessible to clinicians. Screening hospitalized
cardiac patients using a short checklist of risk
factors in conjunction with a measure of depression
severity may be a more efficacious method of
identifying those at risk of persistent depression
than mass screening using a measure of depression
severity alone. Targeting this group for close monitoring
and management of depression may provide
most benefits to patients and may represent a costefficient
means of preventing adverse outcomes
associated with depression in cardiac patients.
Therefore, there is a need to develop practical ways
to identify this substantial segment of population
and provide pragmatic general-practitioner-based
interventions for managing depression as a comorbid
condition.
References
1- Beck AT, Steer RA, Brown GK: Manual for the BDI-II.
San Antonio, TX, The Psychological Corporation 1996.
2- Blumenthal JA, Lett HS, Babyak MA, White W, Smith
PK, Mark DB, Jones R, Mathew JP, Newman MF, for the
NORG investigators: Depression as a risk factor for
mortality after coronary artery bypass surgery. Lancet
2003; 362: 604-9.
3- Bush DE, Ziegelstein RC, Tayback M, Richter D, Stevens
S, Zahalsky H, Fauerbach JA: Even minimal symptoms
178
of depression increase mortality risk after acute myocardial
infarction. Am J Cardiol 2001; 88: 337-41.
4- Carney RM, Freedland KE, Miller GE, et al: Depression
as a risk factor for cardiac mortality and morbidity: A
review of potential mechanisms. J Psychosom Res 2002;
53: 897-902.
5- Cheok F, Schrader G, Banham D, Marker J, Hordacre A-
L: Identification, course and treatment of depression
following admission for a cardiac condition: Rationale
and patient characteristics for the IDACC (Identifying
Depression as a Comorbid Condition) project. Am Heart
J 2003; 146: 978-84.
6- Chew-Graham CA, Hogg T: Patients with chronic physical
illness and co-existing psychological comorbidity: GPs’
views on their role in detection and management. Prim
Care Psychiatry 2002; 8: 35-9.
7- Davidson KW, Kupfer DJ, Bigger JT, Califf RM, et al:
Assessment and Treatment of Depression in Patients With
Cardiovascular Disease: National Heart, Lung, and Blood
Institute Working Group Report Psychosomatic Medicine
2006; 68: 645-650.
8- Dunn SL, Corser W, Stommel M, Holmes-Rovner M:
Hopelessness and depression in the early recovery period
after hospitalization for acute coronary syndrome. J
Cardiopulm Rehabil 2006; May-Jun 26 (3): 152-9.
9- Ellis JJ, Eagle KA, Kline-Rogers EM, Erickson SR:
Depressive symptoms and treatment after acute coronary
syndrome. Int J Cardiol 2005; Mar 30 (3): 443-7.
10- Friedman MM, Griffin JA: Relationship of physical
symptoms and physical functioning to depression in
patients with heart failure. Heart Lung 2001; 30: 98-104.
11- Glassman AH, O'Connor CM, Califf RM, Swedberg K,
Schwartz P, J Thomas Bigger JT, Krishnan KRR, Zyl LT,
Swenson JR, Finkel MS, Landau C, Shapiro PA, Pepine
CJ, Mardekian J, and Harrison WM, for the Sertraline
Antidepressant Heart Attack Randomized Trial
(SADHART) Group: Sertraline Treatment of Major Depression
in Patients With Acute MI or Unstable Angina;
JAMA 2002; 288: 701-709.
12- Holmes TH, Rahe RH: The social readjustment rating
scale. Journal of Psychosomatic Research 1967; 11: 213-
218.
13- Hosmer DW, Lemeshow S: Applied logistic regression.
New York: John Wiley & Sons, Inc 2000.
14- Kaptein KI, Jonge P, Brink RHS, Korf J: Course of
Depressive Symptoms After Myocardial Infarction and
Cardiac Prognosis: A Latent Class Analysis Psychosomatic
Medicine 2006; 68: 662-668.
15- Krzyzkowiak W: Depression after myocardial infarction
and its psychosocial conditions. Psychiatr Pol 2007; 41
(5): 679-91.
16- Lane D, Carroll D, Ring C, Beevers DG, Lip GY: Predictors
of attendance at cardiac rehabilitation after myocardial
infarction. J Psychosom Res 2001; 51: 497-501.
17- Lespérance F, Rieckmann N, Sheps DS, MSPH, Suls JM:
Assessment and Treatment of Depression in Patients With

Mona I Awaad & Khaled E Darahim
Cardiovascular Disease: National Heart, Lung, and Blood
Institute Working Psychosomatic Medicine 2006; 68:
645-650.
18- Lesperance F, Frasure-Smith N, Juneau M, Theroux P:
Depression and 1-year prognosis in unstable angina. Arch
Intern Med 2000; 160: 1354-60.
19- Lesperance F, Frasure-Smith N, Talajic M: Major depression
before and after myocardial infarction: Its
nature and consequences. Psychosom Med 1996; 58:
99-110.
20- Mayou RA, Gill D, Thompson DR, Nicolas Hicks AD,
Volmink J, Neil A: Depression and anxiety as predictors
of outcome after myocardial infarction. Psychosom Med
2000; 62: 212-9.
21- Naqvi TZ, Rafique AM, Andreas V, Rahban M, Mirocha
J, Naqvi SS: Predictors of depressive symptoms postacute
coronary syndrome. Gend Med 2007; Dec 4 (4):
339-51.
22- Roose SP: Depression, anxiety and cardiovascular system:
The psychiatrist 's perspective. J Clin Psychiatry 2001;
62 (Suppl 8): 19-22.
179
23- Rosse SP: Depression: Links With Ischemic Heart Disease
and Erectile Dysfunction. J Clin Psychiatry 2003; 64
(Suppl 10): 26-30.
24- Schrader G, Cheok F, Hordacre A, Guiver N: Predictors
of Depression Three Months After Cardiac Hospitalization
Psychosomatic Medicine 2004; 66: 514-520.
25- Taylor CB, Youngblood ME, Catellier D, Veith RC, Carney
RM, et al, for the ENRICHD Investigators: Effects of
antidepressant medication on morbidity and mortality in
depressed post-MI patients. Arch Gen Psychiatry 2005;
62: 792-8.
26- van Melle JP, de Jonge P, Spijkerman TA, Gijssen JGP,
Ormel J, van Veldhuisen DJ, van den Brink RHS, van
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events: A meta-analysis. Psychosom Med 2004;
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27- Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J,
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likely to follow recommendations to reduce cardiac risk
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Med 2000; 160: 1818-23.

Egypt Heart J 62 (1): 181-186, March 2010
Coronary Ectasia: Risk Markers and Risk Factors
MAHMOUD ALI SOLIMAN, MD*; HOSAM M EL EZZAWY, MD**
Introduction: Coronary artery ectasia represents a not uncommon entity of coronary artery disease. However, many
unanswered questions remain regarding its aetiology, clinical sequalae and management.
Aim of the Work: To assess risk markers namely high sensitivity CRP (HsCRP) and risk factors in patients with coronary
ectasia and to compare them with those in patients with atherosclerotic coronary artery disease.
Subjects and Methods: The present study included 49 patients with coronary ectasia constituted the first group. Another
49 patients with atherosclerotic coronary artery disease were randomly selected and constituted the second group.
All patients underwent:
• History taking, through clinical examination, ECG, Echocardiography.
• Lab. Investigations: FBs & PPS, S. creatinine anti HCV & HBs antigen Lipidprofile, high sensitivity CRP, Coronary angiography
by judkins's technique.
Patients with acute coronary syndromes, peripheral arterial disease, valvular heart disease, local or systemic infectious,
malignancies were excluded from the study.
Results: There was no significant difference as regards age and sex between patients with coronary ectasia (group I) and
patients with atherosclerotic heart disease (group II) (p value >0.05).
Patients with coronary ectasia have higher levels of Hs CRP (2.94±2.33 Vs 1.86±1.27, p

Coronary Ectasia: Risk Markers & Risk Factors
Introduction
Coronary artery ectasia was first described by
Morgani many years ago [1]. Coronary artery ectasia
has been defined as localized or diffuse non obstructive
lesions of the epicardial coronary arteries,
with a luminal dilation ≥1.5 times normal of the
adjacent segments or vessel diameter [2]. Coronary
artery ectasia has been found in 1-5% during coronary
angiography.
In the largest series from the CASS registry,
Swaye et al [2] found CAE in 4.9% of more than
20000 coronary angiograms they reviewed. The
incidence of CAE in an Indian patients cohort with
ischaemic heart disease has been reported to exceed
10% [3]. The incidence of coronary ectasia among
Egyptian patients is unknown and only a limited
number of studies addressed this issue [4].
The exact mechanism of coronary ecdtasia is
still unknown and evidences suggest a combination
of genetic predisposition, common risk factors for
coronary artery disease and abnormal vessel wall
metabolism [5].
Aim of the Work:
To assess risk markers namely high sensitivity
CRP (HsCRP) and risk factors in patients with
coronary ectasia and to compare them with those
in patients with atherosclerotic coronary artery
disease.
Subjects and Methods
The present study included 49 patients with
coronary ectasia (group I) and 49 patients with
atherosclerotic coronary artery disease (group II)
randomly selected from patients who underwent
coronary angiography in our hospital.
All patients underwent:
History taking through clinical examination
ECG. Echo cardiography.
Lab. Investigations:
FBs & PPS S. creatinine anti HCV & HBs
antigen.
Lipid profile (total cholesterol, TG, HDL, LDL)
was performed in Beckman Colter Synchron system
CX9 ALX manufacture by Beckman Coulter Inc.
California (UAS).
High sensitivity CRP was performed in Turbi
Quick manufacture by Vital Diagnostics S.r.l.
(ITALY).
182
Coronary angiography was done by judkins's
technique in multiple projections.
Exclusion criteria:
Patients with acute coronary syndromes, peripheral
artery disease, valvular heart disease, local
or systemic infections, malignancies were excluded
from the study.
Statistical analysis:
The data collected were tabulated and analyzed
by SPSS (statistical pakage for the social science
soft ware) version II on IBM compatible computer.
Quantitative data were expressed as mean &
standard deriation (X±SD) and analyzed by applying
t-test for comparison of two groups of normally
distributed variables and mann whiteny U test for
non normally distributed ones.
Quatitative data were expressed as number &
percentage and analyzed by applying chi-square
test.
Results
There was no significant difference between
patients coronary ectasia (group I) and patients
with atherosclerotic coronary artery disease (group
II) as regards age and sex p value >0.05) Table
(1).
In patients with coronary ectasia (group I)
hypertension and dyslipidaemia were more prevalent
than in group II (79.6% Vs 59.2%, 59.1% Vs
38.8% respectively, p value

Mahmoud Ali Soliman & Hosam M El Ezzawy
When we compare patients with single vessel
ectasia with those with single vessel disease the
former have more triglyceride levels (p0.05) Tables (7,9).
When we compare patients with two or more
vessel ectasia with those with two or more vessel
disease, the former were older, more hypertensive
& have significantly higher HsCRP p0.05
>0.05
0.05
>0.05
0.05
p
value
0.05
>0.05
>0.05
0.05
0.05
>0.05
>0.05
>0.05
p
value
>0.05
0.05
>0.05
>0.05
0.05
Odds
ratio
(95%CI)
1.35
0.42
1.02
1.28
Odds
ratio
(95%CI)
0.37
5.0
1.15
0.28
0.95
2.17

Coronary Ectasia: Risk Markers & Risk Factors
Table 5: Single vessel & two or more vessel affected among
stable angia group regarding lipid profile & CRP.
Lipid
profile
Age
Chol
TG
HDL
LDL
Hs CRP
* Mann whitey test.
Single vessel
(n=15)
No. %
52±5.55
186.31±48.25
111.46±26.53
38.77±7.56
123.77±51.03
2.62±1.42
Two or more
(n=34)
No. %
54.44±8.03
199.92±41.36
152.42±57.43
35.56±9.21
131.56±44.06
1.59±1.12
t-test
1.01
0.97
2.59*
1.13
0.37*
2.36*
p
value
>0.05
>0.05
0.05
>0.05
0.05
>0.05
>0.05
>0.05
>0.05
>0.05
p
value
0.05
0.05
>0.05
>0.05
Odds
ratio
(95%CI)
1.29
0.54
2.4
2.4
184
Table 8: Comparison between two or more vessel affected
among group 1 & 2 regarding risk factors.
Risk
factors
HTN:
No
Yes
DM:
No
Yes
Smoking:
No
Yes
Lipid:
No
Yes
FH:
No
Yes
Statin use:
No
Yes
Table 9: Single vessel among G1 & G2 regarding lipid profile
& CRP.
Lipid
profile
Age
Chol
TG
HDL
LDL
Hs CRP
* Mann whitey test.
Single vessel
in group I
(n=15)
53.67±7.14
213.93±42.79
158.33±45.69
35.8±6.28
150.8±39.33
3.67±3.39
Single vessel
in group II
(n=13)
52±5.55
186.31±48.25
111.46±26.53
38.77±7.56
123.77±51.03
2.62±1.42
t-test
0.68
1.61
3.25
1.14
0.13*
0.75*
p
value
>0.05
>0.05
0.05
>0.05
>0.05
Table 10: Two or more vessel affected among G1 & G2
regarding lipid profile & CRP.
Lipid
profile
Age
Chol
TG
HDL
LDL
Hs CRP
Two or
more
vessels in
group I
(n=34)
No. %
4
30
30
4
12
22
14
20
34
0
26
8
11.8
88.2
88.2
11.8
35.3
64.7
41.2
58.8
100
00
76.5
23.5
2 or more VS in
Group I
(n=34) X±SD
58.65±6.3
215.47±49.59
122.53±35.55
40.0±9.18
146.88±41.79
2.62±1.62
Two or
more
vessels in
group II
(n=36)
No.
14
22
27
9
6
30
22
14
31
5
16
20
%
38.9
61.1
75
25
16.7
83.3
61.1
38.9
86.1
13.9
44.4
55.6
X 2
6.74
2.03
3.18
2.78
5.09
7.47
2 or more VS in
Group II
(n=36) X±SD
54.44±8.03
199.92±41.36
152.42±57.43
35.56±9.21
131.56±44.06
1.59±1.12
p
value
0.05
>0.05
>0.05

Mahmoud Ali Soliman & Hosam M El Ezzawy
Figure 1: Ecstatic LCX.
Discussion
Coronary artery ectasia has been defined as
dilatation of a part or whole of the coronary artery
1.5 times ore more the normal adjacent segment
or the normal corresponding artery.
Coronary ectasia has been found in 1-5% of
patients undergoing coronary angiography. It is
commonly associated with atherosclerotic artery
disease, therefore it is considered as a variant of
coronary atherosclerosis.
Also, many studies have documented the association
of coronary ectasia with the presence of
aneurysm in other vascular beds like the abdomenal
aorta and popliteal arteries, probably owing to a
common underlying pathogenetic mechanisms [6].
However, many questions remain unanswered
regarding its aetiology, pathogenesis, clinical sequala
and management. In the present study, 49
patients with coronary ectasia and 49 patients with
atherosclerotic coronary artery disease were enrolled.
We assess risk markers namely HsCRP and
other risk factors in both groups. There was no
difference between both groups as regards age &
sex so, any possible effect of age and gender could
be excluded. The main finding is that patient with
coronary ectasia have significantly higher levels
of HsCRP than patients with atherosclerotic artery
disease in agreement with the results of Turbon H
et al [7] in a series of 32 patients with isolated
coronary ectasia and 32 patients with obstructive
coronary artery disease.
This finding support the potential role of inflammation
in the pathogenesis of ectasia and may
185
open the door to anti-inflammatory agents and/or
statins to be used in its management.
Previous studies have reported inflammation
to be an important component of abdominal aneurysm
formation as illustrated by extensive medial
and advential inflammatory cell infiltrations [8,9].
Also, Powell et al, showed that patients with
abdominal aortic aneurysms had increased CRP
[10]. Analysis of these findings suggest a potential
role of inflammation in the pathogenesis of both
coronary ectasia & abdominal aortic aneorysms.
Another important findings in the present study
is that in patients with coronary ectasia, hypertension
then dyslipidaemia were more prevalent than
in patients with atherosclerotic coronary artery
disease.
These findings agree with those reported by
Nyamup et al [11] who studies 134 patients with
coronary ectasia and reported hypertension in 54%
and dyslipidaemia in 48% but, in there study hypertnglycerdemia
was the most common lipid
abnormality (65% of patients). In our study, hypercholesterolemia
was the most common abnormality
and hypertriglyceridemia was only in those with
signle vessel ectasia.
These findings may point to the role of lipid
abnormalities in the genesis of ectasia which come
in agreement with Sudhirk et al [12] who reported
increased prevalence of coronary ectasia in patients
with familial hypercholesterolemia.
Limitations of the study:
First, matching for Statin use was not optimal
because patients in atherosclerotic disease group
were more on statin therapy than ectasia group.
Second, exclusion of peripheral artery disease was
done on clinical basis only, but this was for both
groups.
In conclusion patients with coronary ectasia
have higher levels of HsCRP, also hypertension
and dyslipidaemia are more prevalent than in patients
with atherosclerotic coronary artery disease,
whether this higher inflammatory state affect the
total risk and/or can be modulated by anti inflammatory
agents, statins and ACE inhibitors, needed
to be investigated.
References
1- Morgagni JB DE Sedbus, et al: Causis Morborum Per
Anatomen Indaytis. Tomus Primus, Liber II, Epist 27,
Article 28, Venetlis, 1761.

Coronary Ectasia: Risk Markers & Risk Factors
2- Swaye PS, Fisher LD, Litwin P, Vignola PA, et al: Aneurysmal
Coronary Artery Disease. Circulation 1983; 67:
134-138.
3- Sharmo SN, Kaul U, Wasiv HS, Rajani M, et al: Coronary
Angiographic Profile in Yaing and Old Indian Patients
with Ischaemic Heart Disease: A Xomparative Study.
Indion Theart J 1990; 42: 365-369.
4- Waly HM, Elyda, MA, Lee VV, El Said G, Reul, GJ, Hall
RJ: Coronary Artery Ectasia in Patients with Coronary
Artery Disease. Tex Heart Ins J 1997; 24 (4).
5- Athana Ssios M, Dennis V: Coronary Artery Ectasia:
Imaging, Functional and Clinical Implications. Eur Heart
J 2006; 27: 1026-1031.
6- Befeler B, Aronda JM, Embi A, et al: Coronary Artery
Aneusysms: Study of Their Aetiology Clinical Course,
and Effect on Left Ventricular Function and Prognosis.
Am J Med 1977; 62: 597-607.
7- Turban H, Eraby A, Yasar A, et al: Comparison of C-
186
Reacdive Protein Levels In Patients Arith Coronary Artery
Ectasia Versus Patients With Obstructive Coronary Artery
Disease. Am J Cardial 2004; 94: 1303-1306.
8- Brophy CM, Reilly JM, et al: The Role of Inflammation
in Non Specific Abdominal Aortic Aneurysm Disease.
Ann Vasc Surg 1991; 5: 229-233.
9- Patel MI, Hardman DT, et al: Current Views of the Pathogenesis
of Abdominal Aortic Aneurysm. J Am Collsury
1995; 181: 371-382.
10- Powell T, Muller BR, et al: Acute Phase Porticos in
Patients with Abdominal Aortic Aneuryms. J Cardiovasc
Surg 1987; 28: 528-530.
11- Myamu P, Mullasori S, Joseph P, et al: The Prevalence
and Clinical Profile of Angiographic Coronary Ectasia.
Asian Cardiovasc Thorac Ann 2003; 11: 122-126.
12- Sudhir K, Ports TA, Amidon TM, et al: Increased Prevalence
of Coronary Ectasia in hetrozygous Familial Hypercholesterolemia.
Circulation 1995; 19: 1375-80.

Egypt Heart J 62 (1): 187-195, March 2010
Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index
as a New Technique for Assessment of Mitral Stenosis Severity:
Comparison with Planimetry and PHT Methods
HANY YOUNAN, MD
Objective: To determine the usefulness of 2-Dimensional mitral valve leaflets separation index as a new technique for
assessment of mitral stenosis severity.
Patients and Methods: Our study included 55 patients with mitral stenosis who had undergone echocardiographic examination
from July 2008 to March 2009 at Fayoum University hospital. Maximum separation of mitral leaflet tips in diastole in parasternal
long-axis and apical 4-chamber views was measured and averaged to yield the mitral leaflet separation index. The index
was compared with mitral valve area determined by planimetry and pressures half-time methods.
Results: Of the 55 study subjects, Eighteen patients had mild mitral stenosis (MVA 2.26±0.42cm 2 by PHT and 2.19±0.43cm 2
by planimetry), 20 patients had moderate mitral stenosis (MVA 1.30±0.12cm 2 by PHT and 1.20±0.09cm 2 by planimetry) and
17 patients had severe mitral stenosis (MVA 0.90±0.09cm 2 by PHT and 0.84±0.10cm 2 by planimetry). A MLS index of 0.975cm
or more identified mild MS with 94.4% sensitivity, 78.4% specificity, 68% PPV, 96.7% NPV and 83.6% total accuracy, MLS
index of 1.025cm or more identified mild MS with 88.9% sensitivity, 94.6% specificity, 88.9% PPV, 94.6% NPV and 92.7%
total accuracy, and MLS index of 1.225cm or more identified mild MS with 83.3% sensitivity, 97.3% specificity, 93.8% PPV,
92.3% NPV and 92.7% total accuracy. On the other hand, MLS index of 0.775cm or less identified severe MS with 88.2%
sensitivity, 100% specificity, 100% PPV, 95% NPV and 96.4% total accuracy, and MLS index of 0.925cm or less identified
severe MS with 94.1% sensitivity ,76.3% specificity, 64% PPV, 96.7% NPV and 81.8% total accuracy.
Conclusions: The MLS index is an easy, accurate and reliable measure to estimate severity of MS, it provides a quick
estimate of MS severity from standard 2D echocardiographic views without having to resort to tedious measurements.
Key Words: Mitral leaflet separation index and mitral stenosis severity.
Introduction
In nearly all patients, valvular mitral stenosis
(MS) is caused by rheumatic involvement of mitral
valve. Echocardiography is the gold standard method
for evaluating MS, obviating cardiac catheterization
(Jorge Solis et al, 2009 and Vimal Raj BS
et al, 2008). Two-dimensional echocardiographic
(2D) planimetry of the mitral valve orifice and
pressure half-time (PHT) are the two most commonly
used methods to estimate mitral valve orifice
The Department of Cardiology, Faculty of Medicine,
Fayoum University.
Manuscript received 5 Nov., 2009; revised 10 Dec., 2009;
accepted 12 Dec., 2009.
Address for Correspondence: Dr. Hany Younan,
Department of Cardiology Faculty of Medicine,
Fayoum University, Email: azerhany@yahoo.com.
187
area. These two methods have an excellent concordance
and, in most cases, can be used interchangeably
(Jagdish C Mohan et al, 2004).
Several studies have demonstrated that current
echocardiographic techniques for estimating valve
area in mitral stenosis have important limitations.
In particular, the reliability of the pressure halftime
method is reduced by conditions that alter
left preload, Furthermore, because of the acute
atrio-ventricular compliance changes, the PHT
method is reputed invalid immediately after percutaneous
mitral commisurotomy (PMC) (Messika-
Zeitouna D et al, 2005; Nishimura R et al, 1994;
Abascal VM et al, 1988; Loyd D et al, 1988 and
Grayburn PA et al, 1987).
Similarly, leaflet calcification and poor parasternal
windows impair the accuracy and feasibility

Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index
of orifice planimetry (Martin RP et al, 1979 and
Smith MD et al, 1986).
Therefore, a simple and accurate method for
the assessment of MS severity is desirable. The
mitral leaflet separation (MLS) index, measuring
the distance between the tips of the mitral leaflets
in para-sternal long-axis and four-chamber views
was recently presented as a reliable measure of
MS severity and as a surrogate for MVA (Caroline
Holmin et al, 2007).
Aim of the work:
Our study aimed to determine the usefulness
of 2-Dimensional mitral valve leaflets separation
index as a new technique for assessment of mitral
stenosis severity.
Patients and Methods
The study sample included 55 consecutive
consenting patients with various grades of mitral
stenosis undergoing echo Doppler study at Fayoum
university hospital between July 2008 and March
2009.
Exclusion criteria:
Patients were excluded:
• If they were not in sinus rhythm.
• Heavily calcified mitral valve.
• Associated moderate or severe mitral regurgitation.
• Associated moderate or severe aortic valve disease.
• Prior mitral commisurotomy in the preceding 6
months.
• Estimated right ventricular systolic pressure
>75mmHg with right ventricular dilatation.
• A suboptimal acoustic window.
Each patient included in the study was subjected
to:
1- Careful history taking and thorough physical
examination.
2- Echo Doppler study.
• Echocardiograms were recorded at rest, using
General Electric-Vivid 3 expert and ACUSON
CV70 Echo-Doppler machines equipped with
a 2.5/3.25-MHz annular array transducer.
188
• Patients underwent a complete echocardigraphic
examination including 2-D transthoracic
imaging, pulsed wave Doppler, continuous
wave Doppler, and color flow mapping.
• Two-dimensional echocardiographic planimetry
of the mitral valve orifice area was carefully
performed in para-sternal short-axis view
at the leaflets tips with adjustment of the
probe for optimal mitral valve orifice.
• Doppler examination of the mitral valve in
the apical 4-chamber view to obtain diastolic
trans-mitral velocity-time integral, peak and
mean trans-mitral pressure gradients, and
MVA by PHT.
• Doppler interrogation of the regurgitant jet in
2 orthogonal views (mild MR: mean color
flow jet area in the left atrium 8cm 2 (Jagdish Mohan et al, 2004 and Zoghbi
et al, 2003).
• MS severity was determined using a combination
of planimetry and PHT methods. Severe
MS was defined as a MVA of 1cm 2 or less by
planimetry or pressure half-time method
and/or a mean trans-mitral gradient of greater
than 10mmHg. Moderate MS was defined as
a MVA between 1cm 2 and 1.5cm 2 by planimetry
or pressure half-time method, with a mean
trans-mitral gradient of 5 to 10mmHg. Mild
MS was defined as a MVA of greater than
1.5cm 2 by planimetry or pressure half-time
and/or a trans-mitral gradient of less than
5mmHg (Seow et al, 2006).
• The MLS index was estimated by measuring
the maximal separation of tip of the mitral
leaflets in end diastole in para-sternal long
axis (PLAX) view and in apical 4-chamber
view (A4C view). 3 measurements were obtained
in PLAX view and three in A4C view.
A mean of this was taken as MLS index. MLS
index was compared with MVA assessed by
planimetry and PHT.
Statistical analysis:
Statistical analyses were performed using the
Statistical Program for Social Sciences (SPSS Inc,
version 12.0).

Hany Younan
Quantitative data were expressed as mean ±
standard deviation.
Qualitative data were expressed as absolute
number (percentage).
The MLS index was correlated using linear
regression analysis against MVA by planimetry
and the pressure half-time methods.
Receiver operating characteristic (ROC) curves
were used to determine the values of MLS index
that predicted mild and severe MS with the best
sensitivity and specificity. The diagnostic values
of various thresholds of MLS index were expressed
as sensitivity, specificity, positive predictive value
(PPV), and negative predictive value (NPV).
Results
In this study 55 patients were enrolled. The
mean age of the patients was 32.7±8.9 years, and
60% were female. All the patients were in sinus
rhythm, 20% of patients were in New York Heart
Association functional class II, 40% in class III
and 20% in class IV; four patients were pregnant
at the time of echocardiographic examination.
Eighteen patients had mild mitral stenosis (MVA
2.26±0.42cm 2 by PHT and 2.19±0.43cm 2 by
planimetry), 20 had moderate mitral stenosis (MVA
1.30±0.12cm 2 by PHT and 1.20±0.09cm 2 by
planimetry) and 17 had severe mitral stenosis
(MVA 0.90±0.09cm 2 by PHT and 0.84±0.10cm 2
by planimetry) (Figs. 3,4).
The PG was significantly different for patients
with mild (9.38±1.75mmHg), moderate (15.15±
2.18mmHg), and severe MS (22.52±3.42mmHg
cm) and was significantly higher in patients with
severe MS compared with mild MS (p

Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index
4.1
3.1
2.1
1.1
0.1
Mild stenosis Moderate stenosis Severe stenosis
Figure 4: Comparison of MVA by planimetry in the study
group.
MSI index (cm)
MSI index (cm)
1.50
1.00
0.50
0.00
1.50
1.25
1.00
0.75
0.50
Mild MS Moderate MS Severe MS
MS severity
Figure 5: Correlation between MLS index and MS severity.
p-value

Hany Younan
Image 1-A: MVA by PHT in a patient with mild MS. Image 1-B: MVA by Planimetry in the same patient with mild
MS.
Image 1-C: MLS in PLX in the same patient with mild MS. Image 1-D: MLS in apical 4-C view in the same patient with
mild MS.
Image 2-A: MVA by PHT in a patient with moderate MS. Image 2-B: MVA by Planimetry in the same patient with
moderate MS.
191

Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index
Image 2-C: MLS in PLX in the same patient with moderate
MS.
A MLS index of 0.975cm or more identified
mild MS with 94.4 % sensitivity, 78.4% specificity,
68% PPV, 96.7% NPV and 83.6% total accuracy,
MLS index of 1.025cm or more identified mild
MS with 88.9% sensitivity, 94.6% specificity,
88.9% PPV, 94.6% NPV and 92.7% total accuracy,
and MLS index of 1.225cm or more identified mild
192
Image 2-D: MLS in apical 4-C view in the same patient with
moderate MS.
Image 3-A: MVA by PHT in a patient with severe MS. Image 3-B: MVA by Planimetry in the same patient with
severe MS.
Image 3-C: MLS in PLX in the same patient with severe MS. Image 3-D: MLS in apical 4-C view in the same patient with
severe MS.
MS with 83.3% sensitivity, 97.3% specificity,
93.8% PPV, 92.3% NPV and 92.7% total accuracy
(Table 1).
On the other hand, MLS index of 0.775cm or
less identified severe MS with 88.2% sensitivity,
100% specificity, 100% PPV, 95% NPV and 96.4%

Hany Younan
total accuracy, and MLS index of 0.925cm or less
identified severe MS with 94.1% sensitivity, 76.3%
Table 1: MLS index cut off points for detection of mild M.
MLS index
Cut-off
points
0.975 cm
1.025 cm
1.225 cm
Sensitivity Specificity PPV
0.944
0.889
0.833
0.784
0.946
0.973
Discussion
68%
88.9%
93.8%
NPV
96.7%
94.6%
92.3%
Total
accuracy
83.6%
92.7%
92.7%
MVA is most often measured non-invasively
by Doppler echocardiography. Four different methods
can be used: Planimetry, PHT, continuity equation
and the proximal iso-velocity surface area
method (PISA), each method has its specific limitations
(Messika-Zeitouna D et al, 2008).
Planimetry provides an anatomical measurement
of the mitral valve orifice; it is considered to be
the reference method and correlates closely with
anatomical findings (Faletra F et al, 1996 and
Palacios IF, 1994). The procedure requires an
experienced operator because minor changes to
the depth or angle of the ultrasound beam may
lead to significant MVA overestimation (Binder
TM et al, 2000). Planimetry may not be feasible
in approximately 5% of patients because of a poor
echocardiographic window or massive calcifications
(Lung B et al, 1994).
The PHT is the time interval between the maximum
early diastolic gradient and the point at
which the gradient is half this maximum value.
The main advantage of PHT is its simplicity (MVA=
220/PHT); However tachycardia and non-linear
Doppler velocity curves affect the accuracy and
reliability of PHT measurements (Voelker W et al,
1992 and Gonzalez MA et al, 1987). In addition,
a major assumption of the PHT method is that the
rate of pressure decline is only determined by the
valve area (and not by the left atrial and ventricular
compliance) consequently, the PHT method is
reputed invalid immediately after percutaneous
mitral commisurotomy (PMC) (Thomas JD et al,
1988).
In clinical practice, correlation between planimetry
and PHT is only fair, with discrepancies greater
than or equal to 0.3cm 2 observed in 20% of patients.
Fisher et al, in 1979 had first suggested that
the separation of mitral leaflets could be used to
193
specificity, 64% PPV, 96.7% NPV and 81.8% total
accuracy (Table 2).
Table 2: MLS index cut off points for detection of severe
MS.
MLS index
Cut-off
points
0.775 cm
0.925 cm
Sensitivity Specificity
0.882
0.941
1.000
0.763
PPV
100%
64%
NPV
95%
96.7%
Total
accuracy
96.4%
81.8%
measure severity of MS, He measured the maximum
diastolic separation of the mitral valve leaflets
by M-mode echocardiography in 44 patients and
found a good correlation with MVA obtained invasively
using Gorlin formula. As the mitral valve
is a 3-dimensional structure, measuring leaflet
separation using 2D echocardiography would be
more accurate.
In our study we found that MLS index measured
by 2-D echocardiography is an easy, accurate and
reliable measure to estimate the severity of MS
and correlated well with MVA by planimetry and
pressure half-time method. The MLS index was
significantly different for patients with mild MS
(1.34±0.19cm), moderate MS (0.96±0.11cm), and
severe MS (0.68±0.12cm), significantly lower in
patients with severe MS compared with mild MS
(p.001) and demonstrated excellent correlation
with MVA by pressure half-time and planimetry
(r=0.809 and p

Usefulness of 2-Dimensional Mitral Valve Leaflets Separation Index
planimetry (r=0.93, p

Hany Younan
16- Palacios IF: What is the gold standard to measure mitral
valve area post-mitral balloon valvuloplasty? Catheter
Cardiovascular Diagnosis 1994; 33 (4): 315-6.
17- Smith MD, Handshoc R, Handshoe S, Kwan OL De-Maria
AN: Comparative accuracy of two dimensional echocardiography
and Doppler pressure halftime methods in
assessing the severity of mitral stenosis in patients with
and without prior commisurotomy. Circulation 1986; 73:
100-7.
18- Seow SC, Koh LP, Yeo TC: Hemodynamic significance
of mitral stenosis: Use of a simple, novel index by 2dimensional
echocardiography. J Am Soc Echocardiography
2006 Jan; 19 (1): 102-6.
19- Thomas JD, Wilkins GT, Choong CY: Inaccuracy of mitral
pressure half-time immediately after percutaneous mitral
195
valvotomy. Dependence on trans-mitral gradient and left
atrial and ventricular compliance. Circulation 1988; 78
(4): 980-93.
20- Vimal Raj BS, Paul George, Jacob Jose V: Mitral Leaflet
Separation Index-A Simple Novel Index to Assess the
Severity of Mitral Stenosis. Indian Heart J 2008; 60: 563-
566.
21- Voelker W, Regele B, Dittmann H: Effect of heart rate on
trans-mitral flow velocity profile and Doppler measurements
of mitral valve area in patients with mitral stenosis.
Eur Heart J 1992; 13 (2): 152-9.
22- Zoghbi WA, Enriquez-Sarano M, Foster E: Recommendations
for evaluation of the severity of native valvular
regurgitation with two-dimensional and Doppler echocardiography.
Am Soc Echocardiography 2003; 16 (7): 77.

Egypt Heart J 62 (1): 197-204, March 2010
Thrombin-Activatable Fibrinolysis Inhibitor Thr325Ile Polymorphism
as a Risk Factor of Myocardial Infarction in Egyptians
HANAN M KAMAL, MD; AMAL S AHMED, MD*; MANAL S FAWZY, MD**;
FATEN A MOHAMED, MD***; AMANI A ELBAZ, MD***
Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis that decreases plasminogen
binding to the fibrin surface. The plasma TAFI concentration is almost entirely genetically determined. We investigated whether
TAFI Thr325Ile polymorphisms could constitute a risk marker of myocardial infarction (MI) in Egyptian patients.
Patients and Methods: Forty six unrelated patients with acute myocardial infarction (MI) aged 37-67 years, (mean age
55.7±8.1 years, male: female 33:13) and age, sex-matched unrelated healthy volunteers (n=54) as a control group were included
in this study. All study groups subjected to thorough clinical and laboratory investigation, electrocardiographic examination
and/or echocardiography. TAFI Thr325Ile (reference sequence: rs1926447) polymorphism was genotyped in both studied groups
using TaqMan SNP (single nucleotide polymorphism) genotyping assay. We also examined the impact of this variant on the
studied clinical and laboratory traits.
Results: TAFI Ile325Ile (TT) genotype was significantly more frequent in patients with acute MI compared to control group
[OR: 4.95; (95% CI: 1.80-13.63); p=0.0001]. Also high risk T allele frequency was significantly higher in MI patients compared
to controls, [OR: 3.26 (95% CI: 1.82-5.83); p=0.001]. No statistically significant relation was found between TAFI Thr325Ile
polymorphism and either the type nor the site of MI. In MI patients high risk T allele frequency was significantly higher in
diabetics compared to non-diabetics (p=0.04). Other risk factors showed no relation with the genotyping in studied patients.
Conclusions: This study indicated that TAFI Thr325Ile (rs1926447) could have a contribution to MI risk in Egyptian
population. Further investigation of the interaction between this gene and other susceptibility genes in large scale association
studies in this region, will provide useful information for better understanding of the impact of this gene in the development
of acute coronary syndrome (ACS).
Key Words: Thrombin activatable fibrinolytic inhibitor – Myocardial infarction – Genetic polymorphism – Egyptians.
Introduction
Discovering the mechanisms that determine the
grade or persistence of coronary thrombosis in
acute coronary syndrome (ACS) would have implications
for the prevention and treatment of
coronary atherosclerosis. The hemostatic system
plays a central role in the pathogenesis of ACS
and many studies suggest that vulnerability to
The Departments of Cardiology, Clinical Pathology*,
Biochemistry** and Physiology***, Faculty of Medicine,
Suez Canal University, Ismailia, Egypt.
Manuscript received 2 Jan., 2010; revised 30 Jan., 2010; accpted
2 Feb., 2010.
Address for Correspondence: Dr. Hanan Mohamed Kamal,
Department of Cardiology, Faculty of Medicine, Suez Canal
University, Ismailia, Egypt,
E-mail: hananmkamal@yahoo.com.
197
atherothrombosis may be modulated by individual
variations in the balance between coagulation and
fibrinolysis [1].
Impaired fibrinolysis might be a risk factor for
arterial thrombotic events [2] and a common feature
of ACS in comparison with stable angina [3]. The
main inhibitors of fibrinolysis are PAI-1 (type-1
plasminogen activator inhibitor) and TAFI (thrombin-activatable
fibrinolysis inhibitor). TAFI is a
procarboxypeptidase that attenuates fibrinolysis
by removing carboxy-terminal lysine residues from
partially degraded fibrin, inhibiting the assembly
of fibrinolytic factors on the fibrin surface [4].
The plasma TAFI concentration is almost entirely
genetically determined. Non-modifiable
factors such as polymorphisms in the genes encoding
these proteins that may affect their structure,

Thrombin-Activatable Fibrinolysis Inhibitor Thr325Ile Polymorphism
concentration, or function, might have an influence
in the balance between coagulation and fibrinolysis
and should be investigated to help identify a subset
of patients at higher risk.
Several single nucleotide polymorphisms
(SNPs) of the TAFI gene have been identified [5].
Plasma TAFI levels or function have been related
to these polymorphisms, of which the mostthoroughly-studied
are two polymorphisms in the
coding region that result in amino acid substitutions,
Ala147Thr (505A/G), and Thr325Ile (1040C/T)
[6,7].
The genotype, 1040C/T SNP, which results in
the conversion of a threonine codon (ACU) to an
Isolucine codon (AUU) at a position 325
(Thr325Ile) is of particular interest since it is
associated with increased antifibrinolytic activity
[7-9]. Pharmacological inhibition of the TAFI pathway
may constitute a novel strategy to prevent
thrombosis or to increase the efficacy of thrombolytic
therapy [10].
Recently, biological functions of TAFI distinct
from fibrinolysis regulation have been described,
including regulation of inflammation, blood pressure,
cell migration, and wound healing [10]. These
functions may depend on substrates of TAFI other
than fibrin, for instance bradykinin, the anaphylatoxins
C3a and C5a, annexin II, and osteopontin
[11,12].
As there are a limited number of studies on the
genetic basis of ACS in Egyptian population, this
study aimed to determine the frequency of allelic
variant in the TAFI Thr325Ile (rs1926447) gene
in Suez Canal region. In combination with other
genetic and non-genetic data, this could be helpful
in refining a risk profile for coronary heart disease
patients in order to determine the need for and the
intensity of follow-up or to influence decisions
about staged implementation of preventive interventions
with behavioral or drug therapy.
Subjects and Methods
Patient group: We prospectively recruited forty
six unrelated Egyptian patients with acute myocardial
infarction [33 (72%) male, 13 (28%) female,
aged 37-67 years, mean age 55.7±8.1 years] from
the Cardiology Department of Suez Canal University
Hospital (Egypt). Diagnosis of patients with
acute MI was based on full history taking, clinical
examination, resting ECG, cardiac enzymes and
echocardiography. Myocardial infarction (MI) was
198
defined either by presence of ST-segment elevation
(STE) or depression (non-STE) ≥1mm in two or
more contiguous leads. In leads V 2 and V 3, 2mm
of ST elevation in men and 1.5mm in women was
required, and troponin I levels >0.1ng/mL. In the
acute setting all the patients received aspirin,
nitroglycerin, morphine and thrombolytic therapy
as indicated [4,13].
Control group: Fifty four unrelated healthy
blood donors were included as control (38 males,
16 females) they had no history of coronary heart
disease and had normal resting ECG. Their ages
range from 38 to 64 years (mean 50.2±6.2 years).
The following variables were recorded: Diabetes
(defined as patients receiving insulin or oral
hypoglycemic drugs or with fasting glycemia
>200mg/dL at admission or >126mg/dl in two
determinations); hypertension (defined as repeated
blood pressure ≥140/90mmHg or previous treatment
with antihypertensive drugs); dyslipidemia
(defined as total cholesterol >220mg/dl, triglycerides
>150mg/dl or treatment with lipid lowering
drugs), smoking and family history of cardiovascular
disease. The study was approved by the
institutional review board (IRB) of Suez Canal
University. Written informed consent was obtained
from all participants.
Echocardiography was performed in the
echocardiography laboratory of Suez Canal University
Hospital using Vivid-7 Dimension echocardiographic
unite (GE Vingmend Ultrasound,
Horten, Norway) with a multi-frequency probe
ranging between 1.7 and 3.4 MHz. M-mode, Two-
Dimensional and Doppler echocardiographic measurements
with color flow imaging were made. All
cardiac dimensions and functions were calculated
[14].
Laboratory methods: Fasting blood glucose
(FBG) was determined by glucose oxidase method
[15] (Trinder, 1969). Fasting serum total cholesterol
(TC), high density lipoprotein (HDL)-cholesterol
and serum triglycerides (TG) were determined by
the enzymatic method using Hitachi 912 system.
Low density lipoprotein cholesterol (LDL-C) value
was calculated with the Friedewald's equation [16]
(Onaka, 1993).
Genotyping: Genomic DNA was extracted from
peripheral blood leukocytes using the Wizard®
Genomic DNA Purification Kit (Promega Co.),
quantified by absorbance at 260nm using Nano-

Hanan M Kamal, et al
drop-1000 spectrophotometer (NanoDrop Tech.,
Wilmington, USA) and stored at –20°C. TAFI
Thr325Ile SNP, rs1926447 was genotyped using a
real-time PCR allelic discrimination TaqMan assay
(Applied Biosystems, California, USA) [17] (Livak,
et al, 1999). The primer sequences were AGCT-
CAAAGTTCTCTAA-GATCATAAGAAGA (forward)
and AGTCTCTAGTAGCCAGTGAAG-
CAGTTC (reverse) and the TaqMan probe
sequences were Thr-probe: (VIC)-TTTACTA
GTTT-TCTCAATAGCA-(MGB) and Ile-probe:
(FAM)-TTTTACTAATTTTCTCAATAG-CA-
(MGB) (polymorphism in bold) [18]. PCR reaction
was carried out in a 25ml containing 20ng of sample
DNA, 12.5ml of TaqMan Universal PCR Master
Mix, and 1.25ml of TaqMan SNP genotyping assay
Mix. Appropriate negative controls were also run.
Real-time PCR was performed on Rotor-Gene 6000
(Corbett Research, Australia) using the following
conditions: two initial holds (50°C for 2min and
95°C for 10min) followed by a 40-cycle two-step
PCR (95°C denaturation for 15 s and annealing/extension
60°C for 1min) [18]. Genotyping was
performed blinded to case/control status. Ten per
cent of the randomly selected samples were regenotyped
in separate runs to exclude the possibility
of false genotype calls.
Statistical analysis: The genotypes and alleles
frequencies of the studied polymorphism in TAFI
gene were calculated by counting. Consistency of
genotype frequencies at TAFI (C1040T) Polymorphism
with Hardy-Weinberg equilibrium was tested
on a contingency table of observed and expected
genotype frequencies using the Markov simulationbased
goodness of fit. Continuous trait data are
shown as mean ± SD unless otherwise specified.
Comparison of allelic and genotypes frequencies
between groups, and association of polymorphism
with quantitative traits were examined for statistical
significance using standard Pearson chi-square test
(χ 2) or Fisher’s exact test where appropriate. The
odds ratio (OR) was calculated by means of logistic
regression and the confidence interval (CI) was
calculated at the 95% level. Data were analyzed
by Texasoft WINKS, 4.651 software (Texasoft,
Texas, USA). Statistical significance was assumed
for P values less than 0.05.
Results
Study population characteristics: Table (1)
showed the demographic details and basic laboratory
parameters of the MI patients and controls.
Patients were insignificantly different from controls
199
as regards age and sex. However, as compared
with normal subjects, MI patients had significant
higher levels of FBG, total cholesterol, TG and
LDL-C. Also, BMI was significantly increased in
MI patients.
Forty (87%) patients had STEMI, and only 6
(13%) had non-STEMI. Seventeen (36%) had anterior
MI, 21 (45%) had inferior MI and 2 (4%)
has lateral MI. All patients with STE developed a
Q-wave MI. Twenty three (50%) patients were
smokers, 22 (48%) had diabetes, 34 (74%) had
dyslipidemia, 26 (56%) had hypertension, and 15
(32%) had a recorded family history of cardiovascular
disease.
The Echocardiographic characteristics of the
study population was shown in Table (2). Left
ventricular systolic function was estimated to be
normal in 23 (50%) patients, mildly depressed in
9 (20%) patients, moderately depressed in 12 (26%)
and severely depressed in only 2 (4%) patients.
Diastolic dysfunction was diagnosed in 44 (95%)
patients, 24 (52%) had grade I diastolic dysfunction,
12 (26%) had grade II dysfunction and 3 (7%)
patients had grade III dysfunction. Left ventricular
dilatation was reported in 20 (43%) of patients.
Genotype and Allele Frequencies among MI patients
and controls:
Table (3) Summarized the genotype and allele
frequencies among MI patients and controls and
the results of genotypic association analysis for
the studied SNP. In MI patient group, the distribution
of three genotypes CC, CT, and TT were 13%,
54.4%, and 32.6%, respectively, and the frequency
of high risk allele T was 60%. In healthy control
group, the genotype distribution of CC, CT, and
TT were 42.6%, 51.8%, and 5.6% respectively,
and the T allele frequency was 31.5%. It was
confirmed that the genotype proportions of both
studied groups fit the Hardy-Weinberg equilibrium
estimated with a χ 2 test (p>0.05). The genotype
carrying the risk allele [Thr/Ile (CT) and Ile/Ile
(TT)] was significantly more frequent in patients
with acute MI compared to control group (OR:
4.95; [95% CI: 1.80-13.63]; p=0.0001). High risk
T allele frequency was higher in CHD patients
compared to controls, [OR=3.26, 95% (CI=1.82-
5.83), p=0.001].
Genotype and MI patients: No significant
relation was found between TAFI polymorphism
and both type or site of MI (p>0.05).

Thrombin-Activatable Fibrinolysis Inhibitor Thr325Ile Polymorphism
Genotype and risk factors: High risk T allele
frequency was significantly higher in diabetic
compared to non-diabetic in MI patients (p=0.04).
However other risk factors showed no significant
relation regarding the patients' genotyping.
Table 1: Clinical and laboratory characteristics of study
population.
Sex (male/female)
Age at study (years)
Systolic blood pressure*
Diastolic blood pressure
BMI (kg/m 2 )*
FBG (mg/dl)*
Cholesterol (mg/dl)*
TG (mg/dl)*
HDL-C (mg/dl)
LDL-C (mg/dl)*
Patient (n=46)
(mean ± SD)
33/13
55.7±8.1
(37.0-67.0)
136.7±17.8
(100-180)
89.1±10.9
(65-110)
28.1±3.7
(22.0-38.0)
173.3±74.6
(78.0-340.0)
211.1± 52.8
(120.0-424.0)
142.4±73.5
(47.0-473.0)
42.1±13.4
(20.0-77.0)
137.1±46.9
(65.0-339.0)
Control (n=54)
(mean ± SD)
38/16
50.2±6.2
(38.0-64.0)
123±1.7
(95-150)
81.2±8.3
(61-100)
25.1±1.6
(21.6-27.1)
100.3±14.6
(53.0-130.0)
202.1±16.7
(179.0-241.0)
100.2±30.2
(61.0-182.0)
78. 6±13.6
(54.0-123.0)
103.2±19.6
(63.0-155.0)
Abbreviations: BMI Body mass index, FBG fasting blood glucose,
TG triglycerides, HDL high density lipoprotein cholesterol, LDL low
density lipoprotein cholesterol. * p

Hanan M Kamal, et al
centrations were more frequent in cases in France,
but more frequent in controls in Northern Ireland
[20].
This polymorphism is of particular interest
because, besides its association with TAFI plasma
levels, studies using recombinant proteins have
demonstrated a functional effect of the Thr325Ile
substitution on the stability of activated TAFI
(TAFIa species with a prolonged half-life at 37°C),
resulting in altered antifibrinolytic activity [9]. The
presence of the Ile at position 325 results in a 30-
60% greater antifibrinolytic effect for TAFIa than
the Thr at this position [9]. Many studies showed
that The TT (Ile/Ile) genotype of the Thr325Ile
polymorphism showed lower TAFI Ag and TAFI
activity levels.
The increased antifibrinolytic potential of Ile-
325-containing TAFIa variants reflects the fact that
these variants have an increased ability to suppress
the up-regulation in plasminogen activation that
normally occurs during fibrinolysis. In turn, differences
in plasminogen activation are explained
by TAFIa mediated lysine release. Thus, TAFIa
variants containing Ile at position 325 release twice
as much lysine during fibrinolysis as variants
containing Thr at this position. It is possible in
vivo that if the ability to suppress plasminogen
activation and the antifibrinolytic potential of TAFI
were to be increased, the dynamic balance between
accretion and lysis of a clot could be shifted toward
accretion and therefore thrombosis [9].
In the case of the Ile-325 variant of TAFI,
changing the hydrophilic Thr residue to a hydrophobic
Ile residue may diminish the effect of the
favorable entropic change that accompanies the
inactivation process, thereby stabilizing TAFIa.
Possibly, this increased stability of TAFIa compensates
for the decreased levels of the protein.
Discrepant findings have also been reported
with respect to the association of TAFI concentrations
or genotype and arterial vascular disease.
Early studies found slight elevations in plasma
TAFI concentrations (measured as total potential
TAFIa by an activity assay) in patients with stable
angina pectoris [21]. In some studies, high TAFI
levels were found to be protective against MI [22],
while in others they were associated with increased
risk of coronary disease [20,23] or no association
with arterial thrombosis has been found [24,25].
In Egypt El-Shafie, et al (2008), compared the
effect of TAFI gene polymorphism (Ala 147Thr)
201
with the severity of coronary artery disease in
patients with IHD, they concluded that polymorphism
of TAFI gene had influence on plasma TAFI
level but was not associated with the risk of CHD
or with coronary events [26].
Two studies have examined the TAFI pathway
as a risk factor for restenosis after coronary angioplasty
or stenting: Both lower plasma TAFI antigen
concentrations and the more stable Ile/Ile genotype
at position 325 were associated with a lower rate
of restenosis [27,28].
A partial explanation for these discrepancies
could be differences in the type of patient included
(young survivors of a MI [22], patients with ACS
[23,25], or angina [20], the time of sampling (baseline
[20,25] or acute phase [23,25] or in the methods
used to measure TAFI antigenic [20] or functional
[23]. The effect of TAFI polymorphisms on TAFI
antigen levels is unclear, since variable antibody
reactivity to TAFI isoforms in some TAFI antigen
ELISA techniques underestimates real plasma TAFI
levels when an Ile is located at position 325 [29-
31].
Since we have no TAFI levels in this study to
show the association between its levels and MI,
the interpretation for our results is limited. We
explored only the associations between the polymorphism
and MI by genotype analysis.
Importantly, underestimation of the Ile/Ile in
the commercially available antigen assays will
result in erroneous conclusions with regard to TAFI
levels in patients samples. Obviously, this has to
be taken into account for any analysis on the association
between TAFI levels and cardiovascular
pathologies [29].
The importance of this phenomenon is even
more stressed because the most stable variant,
exhibiting a more pronounced antifibrinolytic effect
is being underestimated [9].
Meltzer, et al proposed that a dose response
association was found between TAFI levels and
myocardial infarction. In other words, there might
be a threshold, above which levels of TAFI protect
against myocardial infarction [19].
In the present study no statistically significant
relation was found between TAFI Thr325Ile polymorphism
and either the type nor the site of MI.
Tàssies, et al, 2009, found that TAFI allele
325Ile, associated with lower TAFI levels, were

Thrombin-Activatable Fibrinolysis Inhibitor Thr325Ile Polymorphism
associated with non-STE ACS (non Q wave MI
and unstable angina) in comparison with STE ACS.
This study showed that in patients with MI high
risk T allele frequency was significantly higher in
diabetics compared to non-diabetics. However
other risk factors showed no significant relation
regarding the patients' genotyping.
The contradictory results from epidemiological
studies may be explained by two opposite effects
of TAFI on the development of arterial thrombosis.
While the association between high levels of TAFI
and arterial thrombosis may be the result of a
hypofibrinolytic state, the association between low
TAFI levels and arterial thrombosis may be explained
by a defective regulation of inflammation.
Another explanation of the contradictory results
could be the use of different methods for measuring
TAFI. Several different antigen assays as well as
distinct activity assays have been used in epidemiological
studies.
With the discovery that some enzyme linked
immunosorbent assays of TAFI antigen are dependent
on the 1040C/T polymorphism, revealing a
lack of reactivity with the 1040T variant [19], even
more caution is required in the interpretation of
results.
Although TAFI has been shown to inhibit fibrinolysis
in vivo, recent studies suggest that TAFI
plays an important role in regulating complementmediated
vascular inflammation in vivo. TAFI
inhibits inflammation in vivo by inactivating the
inflammatory mediators bradykinin and the anaphylatoxins
C3a and C5a [11]. Furthermore,
TAFI–/– plasminogen+/– mice expressed increased
leukocyte migration compared with their wild-type
counterparts in a model of peritoneal inflammation
[32]. In another study, TAFI-deficient mice, primed
by lipopolysaccharide, showed increased mortality
after infusion of cobra venom factor, which is a
potent non-specific activator of complement proteins
[33]. Based on these results, one might expect
that TAFI-deficient mice would have a more rapid
progression of atherosclerosis, in which inflammation
plays a pivotal role. However, no data on
atherosclerosis progression in TAFI knockout mice
are available. As inflammation plays an important
role in the development of atherosclerosis and
arterial thrombosis [34] it is not implausible that
increased TAFI levels decrease the risk of myocardial
infarction by decreasing the inflammatory
response. These two counteracting effects may
202
also explain the conflicting study results on TAFI
and arterial thrombosis, and, because inflammation
is less important in venous disease, the consistent
relation between high TAFI levels and venous
thrombosis risk.
There is also evidence that TAFI binds to collagen
resulting in reduced platelet adhesion to
collagen under flow conditions, [35] which could
also contribute to the protective effect of TAFI.
With the advent of more accurate assays for
measurement of plasma TAFI concentrations, the
stage is set for major advances in our understanding
of the contribution of the TAFI pathway to vascular
disease, and of the molecular genetics of CPB2,
the gene encoding TAFI. This will form the basis
for the development of therapeutic strategies to
manipulate the TAFI pathway in order to ameliorate
or prevent vascular disease. Moreover, CPB2 genotype,
plasma TAFI concentrations, and functional
TAFI levels may be able to be used to identify
individuals at high risk for developing vascular
disease.
Conclusion
These data provide evidence that TAFI
Thr325Ile SNP, (rs1926447) could be one of the
genetic factors that increase the risk for MI in
Egyptian population. However, to assess the applicability
of these findings to the general population,
further extensive large scale and prospective cohort
studies with functional analysis in several localities
are recommended in Egyptians. In addition, many
further studies will be required to examine the
efficacy of preventive measures in groups with
high-risk genotypes before any immediate rush to
use this information to give individual predictions
of disease risk.
Acknowledgements: We thank all the patients
and control subjects for agreeing to join this work.
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