Current perspectives on beta-receptor antagonists in the treatment of symptomatic ventricular dysfunction

Even though therapeutic advances have occurred, heart failure is still associated with significant morbidity and mortality. Digitalis, diuretics, and angiotensin-converting enzyme inhibitors have proven effective, but in many patients still do not prevent progressive and debilitating heart failure. Many hormonal factors are involved, but two, the renin-angiotensin-aldosterone (RAA) axis and the autonomic nervous system, apparently are critical in the pathophysiology of progressive ventricular dysfunction. Pharmacologic suppression of the RAA system is associated with significant clinical benefit, suggesting that antagonism of sympathetic nervous activity with beta-receptor-blocking agents might also be efficacious. Major alterations of the autonomic nervous system are characteristic of heart failure, with excessive sympathetic activity one of the earliest adaptations to the condition, and important in promoting the heart failure state and the progression of ventricular dysfunction. Certain beta-antagonists administered by careful and slow up-titration from small starting dosages proved effective in small trials. Large-scale, randomized, placebo-controlled studies continue to document that beta-blockers improve ventricular function and symptoms, and preliminary results suggests mortality and morbidity reductions as well. Although intolerance to beta-antagonism does occur, the majority of patients can be successfully treated with these agents.