Scientific insights from clinical studies of converting-enzyme inhibitors in the failing heart.

Recent clinical studies of therapy for chronic heart failure have yielded unexpected results; for example, only two classes of vasodilators, the converting-enzyme inhibitors and a drug combination that includes nitrates, have so far been shown to improve survival in this lethal condition. Evidence that other vasodilators, as well as most inotropic drugs, worsen prognosis indicates that the underlying problem in chronic heart failure involves more than energy starvation and depressed contractility. These counterintuitive findings can be explained if the fundamental problem in these patients reflects the fact that adult cardiac myocytes are terminally differentiated cells having little or no capacity to divide, so that the shortened life expectancy associated with overload-induced hypertrophy (which I have called the cardiomyopathy of overload) represents an unnatural growth response. Although the mechanism by which chronic overload leads eventually to maladaptive hypertrophy remains speculative, the ability of converting-enzyme inhibitors and nitrates to improve prognosis in heart failure may reflect growth inhibitory effects of these two classes of vasodilator drugs.