title: Mechanistic and clinical rationales for using beta-blockers in heart failure.
abstract: In the 1980s and early 1990s, evidence suggesting a pivotal role for chronic neurohormonal stimulation in the pathophysiology of heart failure began to emerge, which has now produced a dramatic change in the way heart failure is viewed and treated. Preclinical data and results from clinical trials revealed that blocking the actions or generation of norepinephrine or angiotensin II positively affected the course of left ventricular dysfunction and myocardial failure, despite the fact that this inhibition had minimal or negative effects on hemodynamics. Angiotensin-converting enzyme (ACE) inhibitors have been used for heart failure for many years, but only recently have beta-blockers been recommended as part of standard treatment for heart failure. The negative inotropic effects of beta-blockers are well known; these agents must be used with caution in patients with heart failure. However, after several months of treatment, left ventricular ejection fraction (LVEF) gradually increases, and a reversal of the pathological remodeling associated with chronic heart failure occurs: left ventricular mass decreases, chamber shape becomes more elliptical, and mitral regurgitation decreases. Data from clinical trials have shown that long-term beta-adrenergic blockade halts the progression of pump dysfunction, substantially improves left ventricular function, and reduces morbidity and mortality rates in patients with mild-to-moderate heart failure. This article provides a detailed rationale for the use of beta-blockers in patients with chronic heart failure, based on the current understanding of pathophysiology and recent clinical trial data.
authors.affiliation: University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D018579:Patient Selection; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors