CURRENT PERSPECTIVES ON BETA-RECEPTOR-ANTAGONISTS IN THE TREATMENT OFSYMPTOMATIC VENTRICULAR DYSFUNCTION

Even though therapeutic advances have occurred, heart failure is still associated with significant morbidity and mortality. Digitalis, diure tics, and angiotensin-converting enzyme inhibitors have proven effecti ve, but in many patients still do not prevent progressive and debilita ting heart failure. Many hormonal factors are involved, but two, the r enin-angiotensin-aldosterone (RAA) axis and the autonomic nervous syst em, apparently are critical in the pathophysiology of progressive vent ricular dysfunction. Pharmacologic suppression of the RAA system is as sociated with significant clinical benefit, suggesting that antagonism of sympathetic nervous activity with beta-receptor-blocking agents mi ght also be efficacious. Major alterations of the autonomic nervous sy stem are characteristic of heart failure, with excessive sympathetic a ctivity one of the earliest adaptations to the condition, and importan t in promoting the heart failure state and the progression of ventricu lar dysfunction. Certain beta-antagonists administered early by carefu l and slow up-titration from small starting dosages proved effective i n small trials. Large-scale, randomized, placebo-controlled studies co ntinue to document that beta-blockers improve ventricular function and symptoms, and preliminary results suggest mortality and morbidity red uctions as well. Although intolerance to beta-antagonism does occur, t he majority of patients can be successfully treated with these agents.