Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial.

Abstract

It has been suspected that the increased sympathetic activity seen in patients with chronic congestive heart failure from dilated cardiomyopathy may be harmful. We therefore tested the long-term effect of metoprolol on eight patients in a double-blind, randomized protocol and 12 patients in an unblinded, crossover protocol who were treated for 12 months (range 10 to 24), and compared them with 16 similar subjects who were treated with placebo for 10 months (range 6 to 12) in a doubleblind, randomized protocol. Patients were followed by serial clinical assessment, treadmill testing, radionuclide ventriculography, and echocardiography. Metoprolol-treated patients had an improvement in mean exercise capacity by 3 mets (p < .0001) while experiencing a significant improvement in functional classification (p < .001) during both the double-blind and open-label crossover studies and had an improved ejection fraction during the double-blind study (p < .02). These improvements were not seen in matched control subjects receiving placebo. Seven of 20 patients receiving long-term metoprolol therapy had resolution of nearly all symptoms of heart failure, doubled their exercise capacity, and had progressive improvement in resting radionuclide left ventricular ejection fraction (12.6 3% to 26.9 + 6%) and echocardiographic left ventricular end-diastolic dimension (7.7 0.5 to 6.5 0.5 cm). Only one of 21 patients treated was intolerant of metoprolol. We conclude that metoprolol can be given safely to a select group of patients with dilated cardiomyopathy in doses that substantially reduce both resting and exercise heart rates. Long-term /3-blockade improved functional class and exercise capacity in 14 of 20 patients while producing an exceptional clinical response in seven that was accompanied by improved resting parameters of left ventricular function. Circulation 72, No. 3, 536-546, 1985. DILATED CARDIOMYOPATHY is a disease of heart muscle characterized by left ventricular dilatation and congestive heart failure. ' It affects a younger population than does ischemic heart disease and frequently results in functional impairment and premature death. The reflex neurohumoral responses that accompany the syndrome of congestive heart failure are useful in maintaining short-term compensation of cardiac function.2' 3 Norepinephrine is released from sympathetic nerve endings to activate myocardial /3-receptors that increase both the heart rate and force of ventricular contraction.4 Stimulation of a-receptors results in peripheral vasoconstriction to help maintain critical end-

Improved Survival of Idiopathic Dilated Cardiomyopathy in the 1990s

“…Many studies, including prospective double-blind placebo-controlled trials, have reported that -blockers contributed to the improvement of survival or symptoms in patients with DCM. [8][9][10][11][12][13]17 In our study, the survival curve of patients treated with -blockers began to separate from that of patients treated without -blockers at the 10th month. The late expression of the -blocking effect may be due in part to the gradual increase of the daily dose of metoprolol, which we carefully employed to avoid acute exacerbation of pump failure because most patients were treated in an outpatient clinic.…”

Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice.

“…DBA/2 mice were inoculated with the virus and were given carteolol at a dose of 1 (n=12) or 10 mg/kg (n=16), or distilled water (n =27) subcutaneously daily starting on day 14 after inoculation. Mice were killed on day 28.…”

Effects of chronic beta-blockade on compensatory mechanisms during acute isovolaemic haemodilution in patients with coronary artery disease

“…1A). This might be because of increased numbers of myocardial ␤-adrenergic receptors, as observed during long-term ␤-adrenergic blocker therapy, 7 8 resulting in increased exercise capacity 10 and an exaggerated response to exogenous catecholamines such as dobutamine. 8 As endogenous catecholamines increase during acute isovolaemic haemodilution 16 17 and this is considered an important mechanism for the increase in cardiac index, 1 it is conceivable that after long-term oral ␤-blocker therapy patients may respond with a greater increase in cardiac index compared with non-␤-blocked patients.…”