Beneficial Effects of Metoprolol on Myocardial Sympathetic Function: Evidence from a Randomized, Placebo-controlled Study in Patients with Congestive Heart Failure

Background: We sought to investigate whether beta-blockers exert a presynaptic effect in the myocardium as measured by 123I-metaiodobenzylguanidine.

Methods: The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters.

Results: We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 +/- 11 mm to 67 +/- 10 mm (P <.05, within-group comparison) and LVEF increased from 25.3% +/- 7.4% to 32.6% +/- 9.6% (P <.05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2).

Conclusions: This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy.