Charles F. Wooley

Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony.

Eighteen patients with isolated left bundle branch block (LBBB) were compared with 10 normal control subjects. Apexcardiograms, phonocardiograms, electrocardiograms, two-dimensional and dual M-mode echocardiograms, and radionuclide ventriculograms (RNV) were performed. There were no differences in the timing of right ventricular events between LBBB and normal subjects; however, striking delays in left ventricular systolic and diastolic events were apparent in the LBBB group. The delay was associated with shortening of left ventricular diastole and resultant increase in the ratio of right to left ventricular diastolic time in LBBB (1.2 +/- 0.08) compared with normal (1.0 +/- 0.06), p less than 0.0001. First heart sound (S1) amplitude, expressed as the ratio S1/S2, was decreased in LBBB compared with normal (0.67 +/- 0.2 compared with 1.34 +/- 0.25, p less than 0.01), in part due to wide separation of the valvular contributors to S1. The abnormal interventricular septal motion in LBBB corresponded to periods of asynchrony in contraction, ejection, end systole, and end diastole between right and left ventricles. Radionuclide ventriculograms revealed decreased regional ejection fraction of the septum in LBBB (40 +/- 16%) compared with 67 +/- 7% in normal subjects (p less than 0.001), while the apical and lateral regional ejection fractions were similar in the two groups. This loss of septal contribution resulted in a reduction in global ejection fraction in LBBB compared to normals (54 +/- 7% compared with 62 +/- 5%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic distensibility abnormalities in coronary artery disease.

Vasodilatory capacity of nonstenotic arteries in experimental animals with atherosclerosis is decreased. It was postulated that aortic distensibility may be abnormal in patients with coronary artery disease (CAD). Aortic distensibility was determined in 24 normotensive patients with CAD and an angiographically normal aorta and values were compared with those in 18 age-matched normal subjects. Aortic diameters were measured at 3 levels--2, 4 and 6 cm above the aortic valve--by angiographic techniques. The area of the first 6 cm of the aorta above the aortic valve was planimetered and mean aortic diameters were calculated. Distensibility was calculated using the formula: [2 X (changes of the aortic diameter)/(diastolic aortic diameter) X (changes of the aortic pressure)]. CAD patients had similar aortic pressures but markedly lower distensibility than normal subjects: 0.7 +/- 0.2 vs 1.7 +/- 0.3 (p less than 0.02); 1.5 +/- 0.3 vs 4.0 +/- 0.6 (p less than 0.02); and 1.2 +/- 0.2 vs 5.3 +/- 0.6 (p less than 0.001) at 2, 4 and 6 cm above the aortic valve, respectively. Distensibility was also calculated from the mean aortic diameters and was greater in normal subjects than in CAD patients (3.4 +/- 0.4 vs 1.6 +/- 0.1, p less than 0.001). Decreased aortic distensibility in CAD may be related to the common atherosclerotic process or to reduced ascending aorta vasa vasorum flow from coronary arteries.

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.

Cardiovascular Abnormalities Associated with Adult Polycystic Kidney Disease

In a combined retrospective and prospective study, 11 patients with adult polycystic kidney disease were found to have one or more cardiac or aortic lesions. Seven patients had primary dilatation of the aortic root and annulus with aortic regurgitation. The severity of the aortic regurgitation necessitated aortic valve replacement in 2. Mitral regurgitation was present in 3 patients, of whom 2 had documented redundant mitral leaflets and ruptured chordae tendinae, and the third had mitral valve prolapse. Histologic analysis of available aortic and mitral valve tissue from these acquired lesions showed myxomatous degeneration with loss and disruption of collagen. Four patients had congenital bicuspid aortic valves with aortic regurgitation; 1 of these patients also had mild valvular stenosis, and 1 had coarctation of the aorta.

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

Symptomatic patients with mitral valve prolapse (MVP) frequently mimic thyrotoxicosis, hyperadrenergic states or hypoglycemia. Twenty symptomatic patients with auscultatory and echocardiographic MVP were studied in the clinical research unit. T8, T, and plasma cortisol were normal. Patients with MVP had normal responses to oral glucose administration but higher glucose levels than the controls (p < 0.05). Twenty-four-hour urinary epinephrine (E) and norepinephrine (NE) were greater than normal (E + NE excretion, 44 ± 2 vs 29.5μg/g creatinine, p < 0.001). The short electromechanical systole corrected for heart rate (529 ± 3.9 vs normal 548 ± 2 msec, p < 0.01) also reflected high adrenergic tone. Frequent premature ventricular complexes (PVCs) with couplets and triplets were found in 14 patients. Catecholamine excretion and frequency of PVCs were parallel and both decreased significantly at night (p < 0.001). Plasma catecholamine increase with exercise was greater in patients in whom the number of PVCs increased more than 10 per minute compared with patients in whom the number of PVCs remained relatively unchanged (620 ± 80 vs 98 ± 20 msec, p <0.01).We conclude that symptomiatic patients with MVP have high adrenergic tone that may be responsible for or contribute to the multiple symptoms.

Occult constrictive pericardial disease. Diagnosis by rapid volume expansion and correction by pericardiectomy.

Significant pericardial disease can exist without overt manifestations. Occult constrictive pericardial disease (OCPD) is identified by normal baseline hemodynamics and normal left ventricular systolic function with a characteristic response to rapid volume infusion. Following the intravenous administration of 1000 ml of normal saline over six to eight minutes, striking elevations of filling pressures are seen; however, diagnosis depends specifically upon a) the development of typical pressure pulse morphology of constriction, b) loss or reversal of respiratory variation of right atrial pressure, and c) precise diastolic equilibration of intracardiac pressures. Nineteen patients with OCPD have been identified in a five year period. Unexplained fatigue, dyspnea and chest pain was the uniform pattern of presentation. Eleven have undergone pericardiectomy resulting in a dramatic symptomatic improvement in all. Each demonstrated gross and/or microscopic evidence of pericardial disease. Recatheterization with volume infusion in five patients following pericardiectomy has revealed return to normal or near normal hemodynamics. This study describes the method for diagnosis of OCPD and recommends pericardiectomy for the management of disabling symptoms.

The Spectrum of Cardiac Defects in the Ehlers-Danlos Syndrome, Types I and III

Nineteen patients with types I and III Ehlers-Danlos syndrome were hospitalized at our institution between 1973 and 1978. Chest roentgenogram, electrocardiogram, and echocardiogram were done; 11 patients underwent cardiac catheterization. Thirty-five cardiac or great vessel abnormalities were detected. Fifteen patients had nitral valve prolapse; six also had tricuspid valve prolapse. Dilatation of the aortic root or extasia of the sinuses of Valsalva, or both, occurred in six patients. Dilatation of the pulmonary artery and annulus caused pulmonary regurgitation in one patient. Congenital heart defects included bicuspid aortic valve (two), pulmonary valvular stenosis (one), ventricular septal defect (two), and an atrial septal defect (one). The apparent high prevalence of cardiovascular abnormalities in hospitalized patients with types I and III Ehlers-Danlos syndrome necessitates a careful cardiovascular evaluation. Conversely, Ehlers-Danlos syndrome types I and III should be excluded in patients with mitral or tricuspid valve prolapse, great vessel dilatation, and congenital heart defects.

The Varying Clinical Spectrum of the Systolic Click-Late Systolic Murmur Syndrome

Striking auscultatory variations with changes in posture were observed in 30 individuals with either mid-late systolic clicks, late systolic murmurs, or both, particularly in the upright position. Twenty-seven patients had late systolic murmurs; in nine, however, the murmur was not heard until assumption of the sitting position. Mid-late systolic clicks were heard in 20 patients while supine and in three only on sitting. Click movement (usually toward the first sound) was common during sitting or standing. Late systolic murmurs became holosystolic in 25 patients. In 20, the murmur did not become holosystolic until standing. Systolic whoops, not heard in the supine position, developed on assumption of the sitting position (three patients) or standing (three patients). With prompt squatting, the auscultatory findings reverted to those heard in the supine position in eight of nine patients. All observations were confirmed with phonocardiograms. Structural alterations in the mitral valve complex resulting in systolic prolapse of leaflets into the left atrium occur in these patients. Posture related changes in mitral valve function most likely explain the auscultatory phenomena.

Mitral valve prolapse and the mitral valve prolapse syndrome: A diagnostic classification and pathogenesis of symptoms☆

Abstract A clinical classification for patients with MVP is not well defined and the pathogenesis of symptoms in symptomatic patients with MVP remains poorly understood. To this end, 399 patients from our MVP (auscultation/echocardiographic-angiographic) population were analyzed. Symptoms were primarily or directly related to progressive valvular dysfunction in 86 patients (mean age 67). Following a long clinical course, 76 of these patients eventually had mitral valve surgery with pathologic confirmation of “floppy, myxomatous” mitral valves in all. Three hundred thirteen patients (mean age 30) with MVP and normal left ventricular function had symptoms (chest pain, palpitations, fatigue, exercise intolerance, dyspnea, syncope or presyncope, postural phenomena, neuropsychiatric symptoms) that could not be explained on the basis of valvular dysfunction alone. Studies in subsets of 65 of these patients showed: (1) increased urine catecholamine excretion and hypersensitivity to isoproterenol infusion; (2) abnormal plasma catecholamine response after volume expansion; (3) abnormal renin and aldosterone response after volume depletion; or (4) decreased exercise tolerance associated with decreased left ventricular volumes with upright exercise. Thus two groups of symptomatic patients with MVP were defined: (1) patients with MVP in whom symptoms were directly related to mitral valve dysfunction and complications (at present we refer to this group as MVP-anatomic) and (2) patients with MVP in whom symptoms were related primarily to neuroendocrine-autonomic dysfunction (at present we refer to this group as MVP-syndrome). This classification is clinically useful in the stratification of MVP patients in general and to separate MVP patients with symptoms related to or associated with autonomic dysfunction from patients whose symptoms are related primarily to progressive mitral valve dysfunction.

Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.