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Biomedical subjects

H Boudoulas

Publications and source records attributed to H Boudoulas.

At least 55 records · Page 3Linked to original sources

A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1-1q1.

Longitudinal evaluation of a seven generation kindred with an inherited conduction system defect and dilated cardiomyopathy demonstrated autosomal dominant transmission of a progressive disorder that both perturbs atrioventricular conduction and depresses cardiac contractility. To elucidate the molecular genetic basis for this disorder, a genome-wide linkage analysis was performed. Polymorphic loci near the centromere of chromosome 1 demonstrated linkage to the disease locus (maximum multipoint lod score = 13.2 in the interval between D1S305 and D1S176). Based on the disease phenotype and map location we speculate that gap junction protein connexin 40 is a candidate for mutations that result in conduction system disease and dilated cardiomyopathy.

Adult↗

Distensibility of the ascending aorta in coronary artery disease and changes after nifedipine administration.

To study the effect of nifedipine on aortic distensibility in patients with coronary artery disease, ascending aorta distensibility was measured before and 10 min after 10 mg of nifedipine was given sublingually in 13 patients with coronary artery disease and 12 control subjects. Aortic distensibility was calculated as a function of changes in the aortic diameter and pulse pressure. Aortic diameters were measured by echocardiography and aortic pressures were measured directly by catheterization of the ascending aorta. At baseline, aortic distensibility was lower in patients with coronary artery disease compared with control (0.922 +/- 0.367 vs 2.456 +/- 0.588 10(-6).cm2.dyn-1, respectively, p < 0.001). After nifedipine administration, aortic distensibility increased significantly both in normal subjects (by 0.812 +/- 0.316 10(-6).cm2.dyn-1-36.5 +/- 19 percent; p < 0.001) and in patients with coronary artery disease (by 0.296 +/- 0.203 10(-6).cm2.dyn-1-36.6 +/- 28.2 percent; p < 0.001). These results indicate that nifedipine administration increases aortic distensibility in both normal subjects and patients with coronary artery disease.

Adult↗

Factors determining and prevention of atherosclerotic plaque rupture.

Stable atherosclerotic plaques may become unsuitable at any time during the course of the disease. Unstable atherosclerotic plaques often rupture resulting in platelet activation and intravascular thrombosis which may lead to acute ischaemic syndromes. Factors which contribute to the plaque's instability are the amount of lipids contained in the central core of the plaque, the weakening of the fibrous cap of the plaque and pulsative stresses. Aggressive cholesterol reduction and control of factors which produce endothelial injury and contribute to the development and progression of atherosclerosis such as smoking and hypertension, and prevention of intravascular thrombosis such as aspirin, may prevent plaque rupture, intravascular thrombosis and acute ischaemic syndromes.

Coronary Artery Disease↗

Valvular heart disease: the influence of changing etiology on nosology.

The many changes in classification of cardiovascular disease during the twentieth century reflect changing etiology of diseases, clinical comprehension and technological advances. In particular, the etiology of valvular heart disease has changed dramatically in the last five decades. The significant reduction of acute rheumatic fever and its sequelae, and the recognition of non-rheumatic causes of valvular disease are responsible for the metamorphosis in the etiology of valvular disorders. Valvular heart disease can be classified as follows: 1) Heritable-congenital causes of valvular heart disease e.g., floppy mitral valve with mitral valve prolapse, bicuspid aortic valve, and the Marfan syndrome; 2) Inflammatory-immunologic causes such as rheumatic fever, acquired immune deficiency syndrome, endocardial proliferative disorders, and antiphospolipid syndrome; 3) Myocardial dysfunction-ischemic cardiomyopathy, dilated or hypertrophic cardiomyopathy-resulting in valvular heart disease; 4) Diseases and disorders of other organs as causes of valvular heart disease, e.g., chronic renal failure and carcinoid heart disease; 5) Valvular heart disease related to aging: calcific aortic stenosis and mitral annular calcification; 6) Valvular disease following interventions such as valvuloplasty, valve reconstructive surgery and valve replacement; and 7) Valvular disease related to drugs and physical agents, such as chronic ergotamine use, radiation therapy and trauma. In clinical practice the most common causes of mitral regurgitation are floppy mitral valve with mitral valve prolapse, ischemic heart disease, dilated cardiomyopathy and mitral annular calcification, while the most common cause of mitral stenosis is rheumatic fever. The most common causes of isolated aortic regurgitation are bicuspid aortic valve and floppy aortic valve, while the most common causes of isolated aortic stenosis are related to the bicuspid aortic valve and the development of calcific senile aortic stenosis. The most common causes of tricuspid regurgitation are dilated cardiomyopathy, ischemic cardiomyopathy, floppy tricuspid valve with tricuspid valve prolapse and infectious endocarditis. Combined mitral and tricuspid regurgitation occur with heritable connective tissue disorders, dilated or ischemic cardiomyopathy, while the most common cause of mitral stenosis plus aortic regurgitation is rheumatic fever. Statistics obtained from cardiac surgery and necropsy may underestimate the true incidence of certain valvular diseases by selection bias. This is particularly so with valvular disease associated with significant ventricular dysfunction, or in the elderly who may not be surgical candidates, or in cases where the valvular disease is not severe enough to require surgical intervention. Recent advances in hemodynamic and imaging technology allow clinicians to define valvular structure and function and to accurately classify valvular heart disease in clinical practice.

Heart Valve Diseases↗

Exercise-induced QRS prolongation in patients with coronary artery disease: a marker of myocardial ischemia.

The objective of this study was to investigate the effect of myocardial ischemia on the QRS duration in patients with coronary artery disease since acute myocardial ischemia decreases conduction velocity through the ischemic myocardium and may produce QRS prolongation on the surface electrocardiogram. One hundred fifty patients who underwent cardiac catheterization and exercise radionuclide ventriculography within 1 month of each other were studied. Forty patients had normal coronary arteries and 110 had coronary artery disease. QRS duration decreased with exercise in patients with normal coronary arteries (-3.0 msec, confidence limits -6.2 to 0.2), but increased in patients with coronary artery disease; exercise-induced QRS prolongation was directly related to the number of diseased vessels (4.8 msec in patients with one, 7.8 msec in patients with two, and 13.3 msec in patients with three-vessel disease, p < 0.001). Likewise, QRS duration decreased with exercise in patients without exercise-induced segmental contraction abnormalities (-1.8 msec, confidence limits -3.7 to 0.1), but increased in patients with segmental contraction abnormalities (6.7 msec in patients with one, 13.5 msec in patients with two, and 21 msec in patients with three segmental contraction abnormalities, p < 0.0001). Exercise-induced QRS prolongation was better related to the number of segmental contraction abnormalities than to the number of diseased vessels (p < 0.01). It was concluded that exercise produces QRS prolongation in patients with coronary artery disease in direct relation to the number of diseased vessels and to exercise-induced segmental contraction abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Timing of recipient atrial contraction: a major determinant of transmitral diastolic flow in orthotopic cardiac transplantation.

The effect of recipient left atrial contraction on diastolic transmitral flow was studied in eight asymptomatic heart transplant patients (seven men and one woman, mean age 51.8 +/- 9.7 years) with normal left ventricular systolic function. The transmitral flow velocity profile was evaluated in 326 beats (mean 40.8 +/- 12 beats, range 20 to 58 beats/patient). Recipient left atrial contraction was classified as early diastolic, late diastolic, and systolic. Results showed: (1) early diastolic transmitral flow velocity integral (in centimeters) was lower (p < 0.05) following late diastolic recipient left atrial contractions (7.5 +/- 2.1) compared with early diastolic (10.1 +/- 2.7) or systolic (8.5 +/- 1.5) recipient left atrial contractions; (2) late diastolic transmitral flow velocity integral was higher following late diastolic (4.7 +/- 1.8) compared with systolic (4.1 +/- 1.9) recipient left atrial contractions and was virtually abolished (0.45 +/- 14) following early diastolic recipient left atrial contractions; and (3) total diastolic transmitral flow velocity integral was significantly higher (p < 0.05) following late diastolic and systolic (12.2 +/- 2.8 and 12.0 +/- 2.5) compared with early diastolic left atrial contractions (10.5 +/- 2.8). Thus recipient left atrial contraction is a significant determinant of the transmitral diastolic flow pattern in heart transplant patients. Variations in the timing of recipient left atrial contraction may lead to fluctuations of diastolic flow and may compromise cardiac output.

Adult↗

Left atrial volume and function in valvular aortic stenosis.

To assess left atrial volume and function in aortic stenosis, 20 patients with this condition and 10 normal controls were studied. Atrial volumes were measured by echocardiography at mitral valve opening (maximal), onset of atrial systole (P wave of the electrocardiogram) and mitral valve closure (minimal), using biplane techniques. The maximal volume was greater in those patients with aortic stenosis as compared to the controls (74.8 +/- 26.4 cm3 vs. 46.4 +/- 11.9 cm3, p < 0.005), and was directly related to left ventricular mass (r = 0.77). The passive emptying volume (maximal minus onset of atrial systole) was similar in the two groups (21 +/- 8 cm3 vs. 18.7 +/- 5.9 cm3, p = NS), while active emptying volume (onset of atrial systole minus minimal) was higher in aortic stenosis (16.8 +/- 5.2 cm3 vs. 10.2 +/- 2.5 cm3, p < 0.001). The total emptying volume (sum of passive and active) was slightly higher amongst those with aortic stenosis (37.4 +/- 10.2 cm3 vs. 28.9 +/- 7.5 cm3, p < 0.05). The passive emptying fraction (passive emptying volume/maximal) was lower in the aortic stenosis group (0.28 +/- 0.08 vs. 0.40 +/- 0.05, p < 0.001), while the active emptying fraction (active emptying volume/volume at onset of atrial systole) was similar between the two groups (0.33 +/- 0.09 vs. 0.37 +/- 0.05, p = NS). Increased left atrial size in aortic stenosis is directly related to left ventricular mass and restores left atrial total emptying volume, despite the depressed passive emptying fraction. Left atrial dilatation thus represents an important compensatory mechanism, contributing to the maintenance of left ventricular stroke volume and cardiac output in severe aortic stenosis.

Aortic Valve↗

Mitral valve prolapse: left ventricular hemodynamics in patients with chest pain, dyspnea or both.

Patients with mitral valve prolapse may present with chest pain and dyspnea. Left ventricular hemodynamics as a cause for these symptoms have not been completely evaluated in these patients. The present study was undertaken to investigate left ventricular hemodynamics in symptomatic patients with mitral valve prolapse. One hundred and three patients with mitral valve prolapse (female 72, male 31, age 56 +/- 11 years) had diagnostic cardiac catheterization for evaluation of chest pain (n = 44), dyspnea (n = 10) and for chest pain plus dyspnea (n = 49). All patients had diagnostic auscultatory findings and angiographic documentation of mitral valve prolapse. Patients with coronary artery disease and mitral regurgitation greater than mild were excluded from the study. Left ventricular end diastolic pressures before (chest pain 9.3 +/- 3.7 mmHg; dyspnea 8.2 +/- 4.2 mmHg; chest pain plus dyspnea 9.3 +/- 4.1 mmHg) and after left ventriculography (chest pain 11.6 +/- 5.5 mmHg; dyspnea 10.2 +/- 2.3 mmHg; chest pain plus dyspnea 11.7 +/- 5.6 mmHg) were normal in the majority of patients and similar in all three groups. Likewise, the left ventricular end diastolic volume index (chest pain 72.0 +/- 16 cm3, dyspnea 69.1 +/- 20 cm3, chest pain plus dyspnea 70.0 +/- 16 cm3) and ejection fraction (chest pain 64.0 +/- 8.4%, dyspnea 64.1 +/- 6.1%, chest pain plus dyspnea 64.3 +/- 6.1%) were normal in the majority of patients and similar in the three groups. Symptomatic patients with mitral valve prolapse without significant mitral regurgitation had normal left ventricular hemodynamics, and their symptoms cannot be explained on the basis of hemodynamic abnormalities alone.

Adult↗

Exercise-induced S-wave prolongation in left anterior descending coronary artery stenosis.

Myocardial ischemia may decrease conduction velocity and produce QRS prolongation in the surface electrocardiogram. In cases with normal intraventricular conduction, areas of the myocardium contributing to the development of the S wave receive blood from all 3 major coronary arteries, whereas in left anterior hemiblock or right bundle branch block, most of the blood supply to the areas of the myocardium contributing to the development of the S wave is from the left anterior descending (LAD) coronary artery. To test the hypothesis that the S wave will be prolonged with exercise only in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block, 88 patients with normal intraventricular conduction, 66 with left anterior hemiblock and 36 with right bundle branch block were studied. Sixty-four, 32 and 21 patients had LAD, right and left circumflex coronary artery stenoses, respectively. In patients with normal coronary arteries, S-wave duration decreased with exercise regardless of the status of ventricular conduction. In patients with coronary artery disease and normal intraventricular conduction, the S wave was prolonged slightly with exercise, but in those with left anterior hemiblock and right bundle branch block, it was prolonged significantly (12.5 +/- 6 and 10.4 ms, respectively) only in those with LAD, but not in those with circumflex or right coronary artery stenosis. S-wave prolongation in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block most likely is related to exercise-induced ischemia in the areas of the myocardium contributing to the development of the S wave.

Blood Pressure↗

T-cell receptor gene polymorphisms in familial cardiomyopathy: correlation with anti-beta-receptor autoantibodies.

Cardiac autoantibodies have been detected in a significant proportion of patients with dilated cardiomyopathy, but their relation to the pathogenesis of the disease remains unknown. This issue was examined in 41 members of an Ohio family with a heritable disorder of the cardiac conduction system and the myocardium. In 41.5% of all members studied, serum anti-beta-receptor antibodies were identified by a combination of techniques: ligand binding inhibition assay, enzyme-linked immunoassay of a beta 1-receptor peptide, and adenylate cyclase inhibition. The prevalence of autoantibodies was significantly higher (p < 0.01) in the affected (64.7%) than in the unaffected (25.0%) members. A 10.0 kb restriction fragment length polymorphism of the C beta region of the T-cell receptor gene was also overrepresented in affected males (60% versus 30% unaffected males, p < 0.01). In males, the presence of anti-beta-receptor antibodies was linked to the 10.0 kb C beta polymorphism. In affected males, a BlgII C alpha 2.14 kb polymorphism was also more frequent (62% versus 32% in unaffected, p < 0.01) and was linked to the presence of anti-beta-receptor antibodies. The distribution of haplotypes defined by V beta 8, C alpha, and C beta probes was significantly different between affected and unaffected (p < 0.04) and between antibody-positive and antibody-negative individuals. Since the major function of the T-cell receptor is the recognition of processed autoantigens, these results provide additional support for the role of autoimmunity in dilated cardiomyopathy.

Adult↗

The Marfan syndrome: cardiovascular physical findings and diagnostic correlates.

Correlations among cardiac symptoms and auscultatory and phonoechocardiographic findings in Marfan syndrome have not been completely defined. A total of 24 patients with Marfan syndrome (16 men and 8 women; mean age 28.2 +/- 8.6 years) were studied. Mitral valve prolapse was noted in 22, of whom 19 had either nonejection systolic click or mitral regurgitation murmur. Mitral regurgitation was noted in 12 patients by Doppler imaging. Aortic root dilatation was noted in 20 patients and aortic regurgitation in six, five of whom had aortic regurgitation murmur (5 of 20 patients had undergone surgery). Proximal aortic dissection was noted in two. Dyspnea (n = 12) was associated with progressive mitral or aortic regurgitation in four, but in the others dyspnea could not be explained by valvular or ventricular abnormalities. Chest pain was related to pneumothorax in five and aortic dissection in two but was not associated with either in 15 patients. Palpitations (n = 12) and lightheadedness (n = 6) were not associated with specific arrhythmias. In conclusion, mitral valve prolapse and aortic root dilatation were the most common cardiovascular abnormalities in Marfan syndrome. Mitral valve prolapse was frequently associated with typical auscultatory findings and symptoms including dyspnea, chest pain, palpitations, and lightheadedness, whereas aortic root dilatation could be clinically silent unless complicated by aortic regurgitation or aortic dissection.

Adult↗

Ascending aorta distensibility abnormalities in hypertensive patients and response to nifedipine administration.

PURPOSE: The purpose of the present investigation was to study the distensibility of the ascending aorta in patients with arterial hypertension and normal subjects before and after administration of a calcium antagonist, nifedipine. PATIENTS AND METHODS: The distensibility of the ascending aorta was measured before and after nifedipine administration in 22 male hypertensive patients and 12 age-matched male normotensive subjects. Aortic distensibility was calculated as a function of changes in aortic diameter and pulse pressure, using the formula: 2 x (pulsatile change in aortic diameter)/[(diastolic aortic diameter) x (aortic pulse pressure)]. Aortic diameters were measured by echocardiography and aortic pressures were obtained by catheterization of the ascending aorta. RESULTS: In the basal state, the distensibility of the ascending aorta and aortic strain were lower in hypertensive patients than in normotensive subjects (p < 0.001); the lower aortic distensibility, however, was associated with a greater distending pressure. A good inverse correlation (r = -0.81) was found between mean aortic pressure and aortic distensibility. The aortic distensibility was increased after nifedipine administration in both groups; this increase in aortic distensibility, however, was lower in the patients with hypertension compared with normotensive subjects (p < 0.001). CONCLUSIONS: Aortic distensibility is decreased in patients with arterial hypertension. Nifedipine administration increased the distensibility of the ascending aorta both in patients with arterial hypertension and in normotensive subjects. The increase of aortic distensibility after nifedipine administration was lower in hypertensive patients.

Adult↗

Syncope.

Syncope is a clinical entity of diverse cause. The historical features surrounding the syncopal event and the presence or absence of heart disease are the most important features in establishing the cause for syncope. Passive head-up tilt study provides a means of identifying many patients with vasodepressor syncope. Electrophysiologic study is important in the elucidation of syncope in patients who have syncope undefined after noninvasive evaluation. With proper use of the modalities available, few patients will have an undefined cause for syncope.

Cardiac Pacing, Artificial↗

Mitral valve prolapse: etiology, clinical presentation and neuroendocrine function.

Based on our experience and the experience of others, the following classification of patients with mitral valve prolapse has been proposed. Mitral valve prolapse - Anatomic includes patients with a wide spectrum of mitral valve abnormalities from mild to severe. Symptoms, physical findings and laboratory abnormalities in these patients are directly related to mitral valve dysfunction and progressive mitral regurgitation. Complications related to abnormal mitral valve include infective endocarditis, thromboembolic events, cardiac arrhythmias, progressive mitral regurgitation, rupture of chordae tendineae and congestive heart failure. Individuals with thick mitral leaflets and mitral systolic murmur are at higher risk of developing complications. The term mitral valve prolapse syndrome refers to the occurrence of symptoms such as palpitation, chest pain, fatigue, poor exercise tolerance, dyspnea, orthostatic phenomena and syncope or presyncope in patients with mitral valve prolapse which cannot be explained on the basis of mitral valve abnormality alone. The pathogenesis of these symptoms in patients with mitral valve prolapse syndrome appears to be related to metabolic neuroendocrine abnormalities. Preventing infective endocarditis is a major consideration in patients with mitral valve prolapse. Significant mitral regurgitation with the development of congestive heart failure often requires mitral valve surgery. The most important therapeutic approach in patients with mitral valve prolapse syndrome is to explain the mechanisms of symptoms and to reassure the patient.

Autonomic Nervous System↗

Acecainide pharmacokinetics in normal subjects of known acetylator phenotype.

The purpose of this study was to determine the pharmacokinetics of acecainide (formerly N-acetylprocainamide) in six normal subjects of known acetylator phenotype. Three subjects were fast acetylators and three slow acetylators by sulfapyridine phenotyping criteria. Each subject received a 20-min, 3 mg kg-1 intravenous acecainide infusion. Concentrations of acecainide, procainamide, and their deethylated metabolites were measured in serum and urine samples using HPLC. Acecainide renal clearance, nonrenal clearance, steady-state volume of distribution, and other pharmacokinetic parameters were estimated using standard approaches. Acecainide renal clearance and steady-state volume of distribution were (mean +/- SD) 13.6 +/- 1.581 h-1 and 135 +/- 20.31, respectively, and were not significantly different in fast and slow acetylators. Acecainide nonrenal clearance in the six subjects was 3.0 +/- 1.01 h-1; however, nonrenal clearance in slow acetylators was 1.8 times that in fast acetylators (3.9 vs 2.21 h-1, p = 0.012) with clear separation of the subjects into two groups when the data were grouped by acetylator phenotype. The nonrenal clearance of acecainide was inversely correlated with percentage sulfapyridine acetylation. Computer simulations were conducted to explore possible explanations for the observed difference in nonrenal clearance.

Acecainide↗

The Marfan syndrome: abnormal aortic elastic properties.

Aortic distensibility and aortic stiffness index were measured at the ascending aorta (3 cm above the aortic valve) and the mid-portion of the abdominal aorta from the changes in echocardiographic diameters and pulse pressure in 14 patients with the Marfan syndrome and 15 age- and gender-matched normal control subjects. The following formulas were used: 1) Aortic distensibility = 2(Changes in aortic diameter)/(Diastolic aortic diameter) (Pulse pressure); and 2) Aortic stiffness index = ln(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic diameter)/Diastolic aortic diameter. Pulse wave velocity was also measured. Compared with normal subjects, patients with the Marfan syndrome had decreased aortic distensibility in the ascending and the abdominal aorta (2.9 +/- 1.3 vs. 5.6 +/- 1.4 cm2 dynes-1, p less than 0.001 and 4.5 +/- 2.1, vs. 7.7 +/- 2.5, cm2 dynes-1, p less than 0.001, respectively) and had an increased aortic stiffness index in the ascending and the abdominal aorta (10.9 +/- 5.6 vs. 5.9 +/- 2.2, p less than 0.005 and 7.1 +/- 3.1 vs. 3.9 +/- 1.2, p less than 0.005, respectively). Aortic diameters in the ascending aorta were larger in these patients than in normal subjects, but those in the abdominal aorta were similar in the two groups. Linear correlations for both aortic distensibility and stiffness index were found between the ascending and the abdominal aorta (r = 0.85 and 0.71, respectively). Pulse wave velocity was more rapid in the patients than in the normal subjects (11.6 +/- 2.5 vs. 9.5 +/- 1.4 m/s, respectively, p less than 0.01). Thus, aortic elastic properties are abnormal in patients with the Marfan syndrome irrespective of the aortic diameter, which suggests an intrinsic abnormality of the aortic arterial wall.

Adult↗