Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure

Abstract

Background —Use of β-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 ≤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)-[ 18 F]fluoro-6-thia-heptadecanoic acid ([ 18 F]-FTHA) was used to determine myocardial FFA use, and [ 18 F]fluoro-2-deoxy-glucose ([ 18 F]-FDG) was used to determine myocardial glucose use. After carvedilol treatment, the mean myocardial uptake rate for [ 18 F]-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 μmoL · 100 g –1 · min –1 ; P <0.005), the mean myocardial uptake rate for [ 18 F]-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 μmoL · 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.