Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure

Background-Use of beta -adrenoreceptor blockade in the treatment of heart failure has been associated with a reduction in myocardial oxygen consumption and an improvement in myocardial energy efficiency. One potential mechanism for this beneficial effect is a shift in myocardial substrate use from increased free fatty acid (FFA) oxidation to increased glucose oxidation, Methods and Results-We studied the effect of carvedilol therapy on myocardial FFA and glucose use in 9 patients with stable New York Heart Association functional class III ischemic cardiomyopathy (left ventricular ejection fraction less than or equal to 35%) using myocardial positron emission tomography studies and resting echocardiograms before and 3 months after carvedilol treatment. Myocardial uptake of the novel long chain fatty acid metabolic tracer 14(R, S)-[F-18]fluoro-6-thiaheptadecanoic acid ([F-18]-FTHA) was used to determine myocardial FFA use, and [F-18] fluoro-2-deoxy-glucose ([F-18]-FDG) was used to determine myocardial glucose use. After carvedilol treatment, the mean myocardial uptake rate for [F-18]-FTHA decreased (from 20.4+/-8.6 to 9.7+/-2.3 ml . 100 g(-1) . min(-1); P<0.005), mean fatty acid use decreased (from 19.3+/-7.0 to 8.2+/-1.8 <mu>moL . 100 g(-1) . min(-1); P<0.005), the mean myocardial uptake rate for [F-18]-FDG was unchanged (from 1.4+/-0.4 to 2.4+/-0.8 mL . 100 g(-1) . min(-1); P=0.14), and mean glucose use was unchanged (from 11.1+/-3.1 to 18.7+/-6.0 <mu>moL . 100 g(-1) . min(-1); P=0.12), Serum FFA and glucose concentrations were unchanged, and mean left ventricular ejection fraction improved (from 26+/-2% to 37+/-4%; P<0.05), Conclusions-Carvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure.