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

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)-[¹⁸F]fluoro-6-thiaheptadecanoic acid ([¹⁸F]-FTHA) was used to determine myocardial FFA use, and [¹⁸F]fluoro-2-deoxy-glucose ([¹⁸F]-FDG) was used to determine myocardial glucose use. After carvedilol treatment, the mean myocardial uptake rate for [¹⁸F]-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 [¹⁸F]-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.