Angiotensin Inhibition in Severe Heart Failure: Acute Central and Limb Hemodynamic Effects of Captopril with Observations on Sustained Oral Therapy

The systemic, pulmonary, and limb circulatory responses to the angiotensin-converting enzyme inhibitor, captopril, were determined in 10 patients with severe, chronic heart failure. Immediate effects include sustained reductions in arterial pressure and pulmonary capillary wedge pressure and improvement in cardiac output, as reported with other vasodilator drugs. Calf vascular resistance did not change despite substantial lowering of total systemic vascular resistance, indicating that arteriolar dilatation occurred on a selective basis. Transient reduction in mean right atrial pressure paralleled slight calf venodilatation, but effects upon the resistance vasculature predominated. Plasma renin activity and norepinephrine concentrations increased after therapy in the acute phase as plasma aldosterone levels consistently fell. During maintenance oral treatment over 7 to 15 months (median, 11.5 months), patients displayed symptomatic benefit, improved functional capacity, and greater exercise tolerance. No major adverse reactions developed. These findings suggest that angiotensin converting enzyme inhibition with captopril in congestive heart failure patients improved cardiocirculatory function through selective arteriolar dilatation. The reordering of regional blood flow which appears to result from release of angiotensin-mediated vasoconstriction, as well as the suppression of aldosterone, may underlie the prolonged benefit observed in these patients. This oral vasodilator appears to represent an effective adjunct for the treatment of advanced, chronic heart failure refractory to conventional measures.