The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction - A double-blind, placebo-controlled, positron-emission tomography study

Background-The mechanism for the beneficial effect of beta -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 efficie ncy. C-11 acetate kinetics, measured using positron-emission tomography (PE T), area proven noninvasive marker of oxidative metabolism and myocardial o xygen consumption (MVo(2)). This approach can be used to measure the work-m etabolic index, which is a noninvasive estimate of cardiac efficiency. Methods and Results-The aim of this study was to determine the effect of me toprolol on oxidative metabolism and the work-metabolic index in patients w ith LV dysfunction, Forty patients (29 with ischemic and 11 with nonischemi c heart disease; LV ejection fraction <40%) were randomized to receive meto prolol or placebo in a treatment protocol of titration plus 3 months of sta ble therapy. Seven patients were not included in analysis because of withdr awal from the study, incomplete follow-up, or nonanalyzable PET data, The r ate of oxidative metabolism (k) was measured using C-11-acetate PET, and st oke volume index (SVI) was measured using echocardiography, The work-metabo lic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with place bo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidat ive 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+/-2.46x10(6) to 5.14+/-2.06x10(6) mmHg . mL/m(2)), but it increased with metoprolol (from 5.31+/-2.15x10(6) to 7.08+/-2.36x10(6) mm Hg . mL/m(2); P<0.001). Conclusions-Selective beta -blocker therapy with metoprolol leads to a redu ction in oxidative metabolism and an improvement in cardiac efficiency in p atients with LV dysfunction. It is likely that this energy-sparing effect c ontributes to the clinical benefits observed with beta -blocker therapy in this patient population.