Effects of omapatrilat on hemodynamics and safety in patients with heart failure.

Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction < or = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by approximately 6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an approximately 2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.

Racial differences in platelet survival time in patients with symptomatic coronary atherosclerosis.

Platelet survival times were studied in 40 patients (21 white and 19 black) with coronary artery disease and stable effort induced angina pectoris. The platelet survival times of 19 white controls (9.27 +/- 0.49 days; mean +/- SD) were not significantly different from those of 12 black controls (8.88 +/- 0.81 days), and the platelet survival times for 21 white patients with coronary artery disease (8.46 +/- 0.65 days) were lower than the times for both the white controls (p less than 0.01) and the combined control group (p less than 0.01). However, the difference between the mean platelet survival times of 19 black patients (9.22 +/- 0.68) and the control groups was not significant, and the difference between the mean platelet survival times of the 21 white patients and the 19 black patients was significant (p less than 0.01). Stepwise multiple linear regression analysis indicated that race was the most significant factor in predicting shortened platelet survival (r = 0.4783; p less than 0.01). It is concluded that racial background should be considered in the interpretation of platelet studies and that reported racial differences in the rate and extent of atherosclerotic lesions may be related to racial differences in platelet consumption.

Short-term effects of intravenous clonidine in congestive heart failure.

After intravenous bolus injections of clonidine HCl (150 micrograms) to 12 patients with congestive heart failure, peak effects appeared in 5 to 20 min. Clonidine reduced heart rate from 94 +/- 14 to 82 +/- 14 bpm (mean +/- SD, P less than 0.05), left ventricular filling pressure from 31 +/- 5 to 23 +/- 5 mm Hg (P less than 0.001), mean systemic arterial pressure from 98 +/- 13 to 82 +/- 13 mm Hg (P less than 0.001), mean pulmonary artery pressure from 46 +/- 6 to 38 +/- 6 mm Hg (P less than 0.001), and right atrial pressure from 14 +/- 5 to 11 +/- 5 mm Hg (P less than 0.05). Cardiac index increased from 1.6 +/- 0.4 to 1.8 +/- 0.6 l/min/m2 (P less than 0.05) and stroke volume from 32 +/- 10 to 43+/- 12 ml/beat (P less than 0.05). Systemic vascular resistance decreased from 2,342 +/- 800 to 1,795 +/- 345 dynes sec cm-5 (P less than 0.05) and pulmonary vascular resistance from 365 +/- 158 to 263 +/- 114 dynes sec cm-5 (P less than 0.05). We conclude that clonidine decreases heart rate and left ventricular preload and afterload in congestive heart failure.

The prolonged effect of pentaerythritol tetranitrate on exercise capacity in stable effort angina pectoris.

We studied the effect of a single oral dose of 40 mg of pentaerythritol tetranitrate (PETN) on the exercise capacity of ten patients with angina pectoris. The study design was a randomized double-blind crossover comparing the effects of 40 mg of oral PETN with placebo on exercise tolerance. Patients were exercised to moderate angina pectoris before and 2 1/2 and 4 1/2 hours after receiving the placebo or PETN at seven-day intervals during the double-blind crossover period. Exercise tolerance time was measured using a multistage, progressive treadmill test. Exercise times were greater 2 1/2 hours and 4 1/2 hours following PETN compared with placebo (P less than 0.05). Heart rate, systolic and diastolic blood pressure, and double product at rest (supine and standing) and at point of angina pectoris did not change significantly.

Coronary artery spasm: a mechanism of chest pain in selected patients with the mitral valve prolapse syndrome.

A group of 14 patients with mitral valve prolapse syndrome was referred for coronary angiographic study. The group was selected on the basis that all members had recurrent chest pain as their chief complaint and all had interpreted their chest pain as serious enough to warrant at lest two previous emergency visits to medical facilities in the six months preceding the study. All were found to have normal left ventricular function, and only one had a significant fixed obstructive coronary lesion. Seven of 14 patients (50 percent) showed evidence of coronary artery spasm during the catheterization study, five of whom had histories highly suggestive of coronary vasospasm. During the catheterization, spasm occurred spontaneously in three patients, ws ergonovine-induced in two, and was catheter-tip-induced in two. Ergonovine was administered to nine of the 14 patients. The drug induced vasospasm in two patients but failed in seven (two of whom had previously demonstrated catheter tip spasm). Of those seven patients who showed evidence of spasm, four had typical chest pain in association with reversible ST segment elevation and manifested a variant anginal syndrome.

The cardiomyopathy of hypoparathyroidism. Another reversible form of heart muscle disease.

A patient with traumatic hypoparathyroidism had cardiomyopathy and congestive heart failure. The patient had no history of preexisting cardiac disease, alcohol abuse, hyperthyroidism, or hypothyroidism and improved greatly with treatment of hypoparathyroidism. We suggest that the cardiomyopathy seen in hypoparathyroidism. We suggest that the cardiomyopathy seen in hypoparathyroidism is due to many factors, but that hypocalcemia and possibly hypomagnesemia are especially important, and that correction of calcium and magnesium deficiencies may result in near-normal cardiac function.

Acute nontraumatic cardiac tamponade.

A 33-year-old man presented with acute nontraumatic cardiac tamponade as a result of pneumococcal pericarditis in association with pneumococcal pneumonia. Hypotension, tachycardia and pulsus paradoxicus, 50 mm Hg, were present. Echocardiographic findings were compatible with cardiac tamponade. Pericardiocentesis was performed. Acute nontraumatic pericardial tamponade in the emergency department presents special problems of diagnosis and management. Diagnosis is based on correlation of data from the history, physical examination, electrocardiogram, chest x-ray films, and a high index of suspicion. Echocardiography to confirm the diagnosis of tamponade and aid in correct placement of the needle in pericardiocentesis is especially helpful.