No abstract

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced ( failure who had been symptomatic for at least 3 months despite treatment with digitalis and diuretics were selected for study. The diagnosis of congestive heart failure was based on a histo-y of symptoms on exertion and the presence of a ventricular gallop sound, jugular venous distention, pulmonary rales, or otherwise unexplained peripheral edema. In addition, all patients were required to have at least one of the following during the month preceding enrollment into the study: (1) cardiothoracic ratio on standard chest x-ray of greater than 0.55, (2) left ventricular ejection fraction less than 40% by radionuclide angiography, (3) echocardiographic left ventricular end-diastolic dimension greater than 2.7 cm/m2, or (4) resting cardiac index by carbon dioxide rebreathing below 2.5 liters/min/m2.The cause of congestive heart failure was coronary artery 63

Angiotensin-converting enzyme inhibitors are effective vasodilators in the treatment of congestive heart failure. Enalapril, a new angiotensin-converting enzyme inhibitor, or placebo, in addition to digoxin and diuretic drugs, were given to 17 patients with chronic congestive heart failure who were followed up for 12 weeks. In random double-blind fashion, nine patients received enalapril and eight received placebo. Cardiac dimensions and function improved slightly but insignificantly in both groups. Treadmill exercise duration increased from a mean value (+/- standard deviation) of 9.1 +/- 3.2 to 12.0 +/- 3.5 minutes during enalapril administration (p less than 0.025) and was unchanged during placebo administration (10.1 +/- 3.7 versus 11.1 +/- 5.2 minutes). Maximal oxygen consumption also increased during enalapril therapy (15.8 +/- 3.4 to 18.4 +/- 4.4 ml/min per kg, p less than 0.05) and remained unchanged during placebo treatment (16.0 +/- 6.4 versus 17.0 +/- 4.6 ml/min per kg). Clinical functional class (Yale scale) improved 3.1 +/- 1.9 points (p less than 0.01) during enalapril treatment but not during placebo treatment (0.8 +/- 3.5 points, no significant difference). No significant side effects were observed. Thus, enalapril appears to be a clinically effective and useful new angiotensin-converting enzyme inhibitor for the management of chronic congestive heart failure.

No abstract

The dose requirements and duration of effect of transdermal nitroglycerin in patients with heart failure are not clearly established. In a first series of eight patients with chronic heart failure we gave transdermal nitroglycerin in incremental doses until pulmonary capillary wedge pressure fell at least 30% within 4 hr in three consecutive patients. Thus we found that a single dose of 60 mg/24 hr (120 cm2) was the minimal effective dose. Transdermal nitroglycerin or placebo was then given as a single application of 60 mg/24 hr in random double-blind fashion to 15 additional patients with heart failure (eight received transdermal nitroglycerin and seven received placebo), and hemodynamics were monitored for up to 24 hr. After administration of transdermal nitroglycerin, the control pulmonary capillary wedge pressure of 22 + 7 mm Hg fell by 6 + 6 mm Hg at 2 hr (p < .05) and reached maximal reduction of 8 + 6 mm Hg (p < .01) at 4 hr. The reduction in wedge pressure remained significant through 12 hr but was no longer statistically significant by 18 hr after administration of the drug. Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures as well as pulmonary vascular resistance from 4 through 12 hr but did not affect systemic hemodynamics. No significant hemodynamic changes occurred after administration of placebo. Thus transdermal nitroglycerin is an effective vasodilator in patients with heart failure, but a dose of at least 60 mg/24 hr is needed. Even with this dose, hemodynamic effects do not last beyond 18 hr, suggesting altered absorption or development of tolerance. Circulation 71, No. 5, 980-986, 1985. VASODILATORS are commonly used for the treatment of acute and chronic congestive heart failure. Among the presently available vasodilator agents, only nitrates and angiotensin-converting enzyme inhibitors have produced sustained hemodynamic improvement along with increased exercise tolerance in placebo-controlled trials in patients with chronic heart failure.1-6 Both captopril and nitrates require frequent dosing, so that practical problems related to drug delivery and patient compliance still exist. The duration of action of sublingually administered nitroglycerin is far