Mediators of Chronic Heart Failure: How Drugs Work

Abstract

OBJECTIVE: To critically review the pathophysiology of chronic heart failure at the neurohormonal level, and discuss the effect of present and future therapeutic options on these neurohormones. DATA SOURCES: A MEDLINE search (1986–November 2000) was used to identify important primary literature and reviews. Additional references were obtained from these articles. DATA SYNTHESIS: Chronic heart failure is a common, progressive disorder with high morbidity and mortality. Progression is due in large part to several redundant neurohormonal responses. The neurohormones include angiotensin II, norepinephrine, aldosterone, endothelin-1, arginine vasopressin, and tumor necrosis factor. These responses are initially adaptive, but become maladaptive in the long term, impairing the function of the heart, vasculature, and kidneys. Counter-regulatory hormones, such as bradykinin and natriuretic peptides, are insufficient to offset the adverse effects of the other neurohormones. Most drugs used to treat chronic heart failure, such as angiotensin-converting enzyme inhibitors, β-adrenergic antagonists, and spironolactone, achieve their benefits through altering the neurohormonal pathways. New agents that affect more or different neurohormones may soon be available. CONCLUSIONS: Multiple agents are required for treatment of chronic heart failure, as no single agent can counteract all of the various adverse pathways. The appropriate prescription and use of such inherently complex regimens require significant physician and patient education.