The Effects of β 1 -Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction

Abstract

Background —The mechanism for the beneficial effect of β-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MV̇ o 2 ). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. Methods and Results —The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure×SVI×heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061±0.022 to 0.054±0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062±0.024 to 0.045±0.015 per minute; P =0.002). The work-metabolic index did not change with placebo (from 5.29±2.46×10 6 to 5.14±2.06×10 6 mm Hg · mL/m 2 ), but it increased with metoprolol (from 5.31±2.15×10 6 to 7.08±2.36×10 6 mm Hg · mL/m 2 ; P <0.001). Conclusions —Selective β-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with β-blocker therapy in this patient population.