Evolution of the neurohormonal hypothesis to explain the progression of chronic heart failure.
During the last 20 years, physicians have generally regarded heart failure as a haemodynamic disorder in an attempt to explain patients' symptoms and disability. This model led to the widespread evaluation of peripheral vasodilators and the development of novel positive inotropic agents, but long-term use of these drugs failed to improve symptoms and was frequently accompanied by an increase in the risk of death. These clinical observations raised concerns about the validity of the haemodynamic hypothesis and led to the development of alternative models of heart failure--most importantly, the neurohormonal hypothesis. According to the neurohormonal model, heart failure develops and progresses because endogenous neurohormonal systems that are activated by the initial injury to the heart exert a deleterious effect on the circulation. Recognition of the importance of neurohormonal activation has led to the intense interest in the use of neurohormonal antagonists--converting--enzyme inhibitors and beta-adrenergic blockers--in the treatment of chronic heart failure. The results of randomized clinical trials with a variety of neurohormonal antagonists have been encouraging, and widespread acceptance of these drugs is expected to lead to clinical benefits for many patients.
Packer
M
M
Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000502:physiology*; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D018377:Neurotransmitter Agents