Adam Schneeweiss

The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure.

Conventional hemodynamic indexes (cardiac index (CI), and pulmonary capillary wedge pressure) are of limited value in the diagnosis and treatment of patients with acute congestive heart failure (CHF).

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

Effect of sotalol on arrhythmias and exercise tolerance in patients with hypertrophic cardiomyopathy.

The effect of sotalol on exercise tolerance and incidence of arrhythmias was studied in 30 patients with hypertrophic cardiomyopathy (HCM). In this short-term, double-blind, cross-over study, exercise time on sotalol (320 mg/day) was significantly longer than on placebo (10.6 +/- 4.0 vs. 9.4 +/- 3.6 min; p < 0.01). Sotalol eliminated supraventricular arrhythmias in 6 of 7 patients (p < 0.03) and suppressed ventricular arrhythmias in 7 of 13 patients in whom they were present on placebo (p < 0.05). Ventricular tachycardia was abolished in 4 of 8 patients, but appeared during sotalol treatment in 1 patient who was free of repetitive arrhythmias on placebo. Twenty-five patients who had better exercise tolerance on sotalol than on placebo and did not experience aggravation of arrhythmia entered a 6-month prospective, open-label treatment with sotalol (160-480 mg/day, mean +/- SD 377 +/- 94). One patient was withdrawn after 1 month because of bronchospasm. Mean exercise time improved from 9.8 +/- 3.6 min on placebo to 12.7 +/- 3.2 min (p < 0.01) after 6 months of treatment with sotalol. During the prospective follow-up, sotalol abolished ventricular tachycardia in all 6 patients after 1 month (p = 0.022), and in 4 of 6 patients (p > 0.2) after 6 months of treatment. It is concluded that sotalol significantly improves exercise tolerance and is effective in suppressing both supraventricular and ventricular arrhythmias in patients with HCM.

A Single Dose of Cilazapril Improves Diastolic Function in Hypertensive Patients

We studied the effect of a single dose of cilazapril, 5.0 mg orally, on systolic and diastolic cardiac function in eight hypertensive patients using a double-blind crossover placebo-controlled design. All patients had concentric left ventricular hypertrophy (measured by echocardiography), unimpaired systolic function (measured by radionuclide ventriculography), and long-standing hypertension treated by a combination of beta-blockers and diuretics. Radionuclide scintigraphy was performed with cilazapril and placebo, given one week apart. A two-week washout period of all cardioactive drugs preceded the study. Within three hours after oral administration of cilazapril, the time to peak filling rate of the left ventricle, expressed as a percentage of diastole, was reduced from 44.5 +/- 13.2 percent to 31.2 +/- 7.2 percent (p less than 0.05). Systolic blood pressure was also significantly reduced by cilazapril. Heart rate was slightly reduced. Left ventricular ejection fraction, peak filling rate, and the absolute time to peak filling rate were not significantly altered. Cilazapril improves a sensitive index of diastolic cardiac function in hypertensive patients.

Transdermal nitroglycerin patches for silent myocardial ischemia during antianginal treatment

Because silent ischemia is not associated with an increase in heart rate and, being asymptomatic, its treatment requires constant therapeutic plasma levels of the drug used, a transdermal nitroglycerin patch (Deponit) was selected for treatment of this condition. Eight patients with documented silent ischemia were studied. All patients also had angina on effort treated with calcium antagonists (n = 8) and beta blockers (n = 6). They were evaluated by 24-hour ambulatory electrocardiographic monitoring. The transdermal nitroglycerin patch, 20 to 30 mg/24 hours, reduced the number of silent ischemic episodes from 9.25 +/- 5.52 to 2.4 +/- 2.0 episodes per 24 hours (p less than 0.001). The maximal ST-segment depression was reduced from 3.1 +/- 0.7 to 0.9 +/- 0.7 mm (p less than 0.001). Ventricular premature beats were significantly reduced, by 50%. Symptomatic ischemic episodes were completely suppressed. Thus, transdermal nitroglycerin, in moderate doses, is effective in suppressing silent ischemia in patients with angina pectoris who have silent ischemic episodes despite treatment with other antianginal agents.

Corrected transposition of the great arteries without associated defects — study of 10 patients

Abstract In about 80 percent of the cases of corrected transposition of the great arteries reported in the literature, other primary lesions, mainly ventricular septal defect and/or pulmonic stenosis were present, and the isolated lesion is only rarely found [1–3]. We studied 10 cases of corrected transposition of the great arteries without shunt or obstructive lesions.

Segmental study of the terminal coronary vessels in coarctation of the aorta: A natural model for study of the effect of coronary hypertension on human coronary circulation

An electron microscopic study of the coronary terminal circulation (starting with the small coronary arteries) was carried out on small pieces of myocardium operatively resected from the left ventricle on 11 patients with coarctation of the aorta. The patients were 4 to 20 years of age. Structural modifications were found in the small coronary arteries and arterioles. Two patterns of morphologic alterations were noted in these small resistance vessels. In the first pattern, seen in most of the children, the components of the arterial wall were still distinguishable, and well represented portions of smooth muscle layers were visualized together with muscle cells showing signs of degeneration and more or less widespread collagenous islets. The second pattern, seen in young adults, was characterized by a total collagenous transformation of the arterial wall. In contrast, the smaller microvessels (precapillary sphincter, metarterioles and capillaries) appeared free of pathologic change. It is postulated that the precapillary sphincters play a special protecting and regulating role in the coronary microcirculation in such cases with elevated coronary pressure. It is suggested that surgery should be performed at an early age to prevent further development of structural changes in the microvessels. The microcirculatory damage may contribute to the increased surgical mortality in patients with coarctation of the aorta operated on at a later age. These findings should trigger further research on the small coronary vessels in systemic hypertension.

Subaortic stenosis: An unrecognized problem in transposition of the great arteries

Right ventricular (subaortic) obstruction has only rarely been described in complete transposition of the great arteries. five patients with complete transposition of the great arteries in whom subaortic stenosis was angiocardiographically demonstrated were studied. All had a pressure gradient of 30 to 55 mm Hg across the aortic outflow tract. Two of the patients manifested mild tricuspid insufficiency, and another two had coarctation of the aorta. The etiologic, anatomic, hemodynamic and prognostic aspects of this unusual anomaly are discussed. An angiocardiographically demonstrated series of this anomaly has not been reported on before.

Cardiovascular drugs in children. II. Angiotensin-converting enzyme inhibitors in pediatric patients

Nearly two years ago a review on angiotensin-converting enzyme (ACE) inhibitors was published in Pediatric Cardiology (9:109-115, 1988). The number of patients in the series reviewed was very small. Since then tremendous progress has taken place in this field. This review attempts to summarize this progress and update the previous one. Once the role of the pressor renin-angiotensin system in the regulation of blood pressure and systemic resistance had been recognized, it became desirable to treat hypertension and congestive heart failure by inhibition of this system. The accurate determination of the enzymatic cascade involved in the activity of this system triggered the development of specific inhibitors to its various components. Peripheral vasodilatation is the end result of inhibition of this system at any stage proximal to the final component--aldosterone. Inhibition of the renin-angiotensin system also has complex renal effects, evident mainly as an increase in renal blood flow.

Frequency and Clinical Significance of Anomalous Origin of Septal Perforator Coronary Artery

Abstract The reported incidence of anomalous origin of coronary arteries ranges from 0.6 to 1.2%. 1–3 The most common variations reported are anomalous origin of the circumflex and conal arteries and, less often of the left anterior descending and right coronary arteries. 1–5 Anomalous origin of first septal perforator coronary artery (ASA) has been reported in only 3 living patients, 3 and its clinical significance is not known. We reviewed 2,100 consecutive angiograms from adult patients to determine the incidence of an ASA and its role as a collateral vessel in patients with obstructive coronary heart disease.