Beneficial effects of metoprolol treatment in congestive heart failure. Reversal of sympathetic-induced alterations of immunologic function.

Abstract

BACKGROUND Little information is available to explain why beta-blockers are beneficial in certain patients with congestive heart failure (CHF). Since catecholamines alter immune function, we asked whether beta-blocker treatment leads to enhancement of immune function. METHODS AND RESULTS Fifteen patients with New York Heart Association class III-IV CHF secondary to dilated cardiomyopathy were titrated to a minimum dose of metoprolol 25 mg BID on a background therapy of digoxin, diuretic, and angiotensin-converting enzyme inhibitors. Cardiac and immunologic studies were done before and 6 months to 1 year after treatment. While these patients served as their own controls, an additional population of patients with heart failure was followed for a similar time period on traditional medications. A panel of seven delayed hypersensitivity skin tests were placed at 6- to 12-month intervals on the patient's forearm. Seventy percent of all CHF patients were anergic (unable to respond to more than 1 antigen). The 30% who could respond averaged 2.2 antigens. After treatment with metoprolol, only 20% remained anergic (P < .001). The 80% of responders averaged 4.2 antigens (P < .001). Additionally, patients treated with metoprolol had an increased percentage of T cells, natural killer cells, and increased interleukin-2 receptor density upon stimulation with concanavalin A. These changes correlated to increases in ejection fraction. Patients not treated with metoprolol remained anergic and had no beneficial immunologic changes. CONCLUSIONS It appears that patients with dilated cardiomyopathy who are treated with metoprolol have enhancement of cell-mediated immunity and improvement of T-cell function; these improvements are correlated to improvement in ejection fraction.