PHARMACOLOGICAL TREATMENT OF CONGESTIVE-HEART-FAILURE

Congestive heart failure is a clinical syndrome producing symptomatic deterioration, functional impairment, and shortened life span. The syn drome is complex in that it includes both peripheral and cardiac effec ts which contribute to the progression of heart failure. In the periph ery, elevations in the sympathetic nervous system and renin-angiotensi n system increase afterload and contribute to further salt and water r etention. The central cardiac abnormalities include remodeling of the heart and downregulation of beta receptors. Traditional heart failure therapy has included treatment of fluid retention with diuretics, alth ough their effect on mortality has never been addressed. The most prov en therapy in heart failure is treatment with vasodilators, particular ly angiotensin-converting enzyme (ACE) inhibitors. Improved survival w ith ACE-inhibitor therapy has been demonstrated in patients with sever e heart failure (CONSENSUS), mild to moderate heart failure (SOLVD), a nd in comparison with vasodilator therapy with hydralazine isosorbide dinitrate (VHeFT II). Improved survival has also been noted in postmyo cardial infarction when the ejection fraction is decreased (SAVE). The ACE inhibitors have now become standard therapy for heart failure reg ardless of severity. Additive vasodilator therapy with calcium-channel antagonists is under investigation. Inotropic therapy is controversia l at present because of disappointing mortality results. The clinical mainstay digitalis remains without convincing mortality reduction data . Other inotropic agents, particularly phosphodiesterase inhibitors, h ave shown uniformly negative survival results. However, the new mixed action agents vesnarinone and pimobenden have shown favorable data, wi th vesnarinone demonstrating a mortality reduction effect. Beta-blocke r therapy in heart failure has also found renewed interest, particular ly with the new agents carvedolol and bucindolol which also have vasod ilating properties.