Restoring function in failing hearts: The effects of beta blockers

Until recently, clinical management of congestive heart failure was purely palliative. The drugs used in patients with failing hearts-digoxin, vasodilators, and positive inotropic agents-improved contractility, reversed hemodynamic abnormalities, and enhanced functional status, but they failed to confer a survival benefit. Indeed, the use of inotropic agents often resulted in excess mortality-a paradox explained in part by the pharmacological properties of these agents, which increase production of cAMP, the intracellular messenger for the beta-adrenergic system. The short-term pharmacological benefits of these drugs may be offset by deleterious long-term biological effects on the heart muscle itself. The use of beta-blockers in heart failure is counterintuitive, given that their initial pharmacological effect is to reduce heart rate and contractility in a faltering heart, thus producing an effect diametrically opposed to that of inotropic agents. However, it is becoming more clear that betablocker therapy in patients with heart failure not only improves left ventricular function, but may actually reverse pathological remodeling in the heart. Accumulating clinical evidence indicates that these beneficial changes are the result of secondary biological changes in the myocardium rather than a response to the pharmacological effects of the drugs themselves. Mounting evidence suggest that these agents may prolong survival in patients with heart failure, and ongoing clinical trials may soon confirm these preliminary findings. (C) 1998 by Excerpta Medica, Inc.