Search

Although pharmacological therapy has ameliorated symptoms and improved the survival of patients with chronic heart failure (CHF), this chronic syndrome remains a progressive disease causing incremental morbidity and early mortality. A new therapy for the treatment of CHF should ideally decrease mortality, alleviate symptoms, and improve functional capacity. A growing body of evidence suggests that the use of implantable devices to resynchronize ventricular contraction may be a beneficial adjunct in the treatment of CHF.The Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial is a randomized, open-label, 3-arm study of patients in New York Heart Association class III or IV with an ejection fraction of 35% or less and a QRS duration of 120 milliseconds or less. The COMPANION study objectives are to determine whether optimal pharmacological therapy used with (1) ventricular resynchronization therapy alone or (2) ventricular resynchronization therapy combined with cardioverter-defibrillator capability is superior to optimal pharmacological therapy alone in reducing combined all-cause mortality and hospitalizations; reducing cardiac morbidity; improving functional capacity, cardiac performance, and quality of life; and increasing total survival.

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.

Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function.One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P.05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004).The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.