Altered systemic ketone body metabolism in advanced heart failure

Heart failure is a systemic disease in which both myocardium and skeletal muscle exhibit alterations of energy metabolism. Failing myocardium exhibits impaired utilization of free fatty acids and glucose, which are major substrates for myocardial energy production. Ketone bodies normally provide a modest contribution to energy balance, but serum concentrations of ketone bodies are elevated in heart failure. To profile ketone body metabolism in advanced heart failure, we directly measured ketone body utilization by heart and skeletal muscle. Metabolite concentrations in arterial, coronary sinus, and central venous beds were measured to derive myocardial and skeletal-muscle ketone body utilization in 11 patients with advanced heart failure and 10 healthy control subjects who were undergoing electrophysiologic procedures. As expected, the mean myocardial arteriovenous oxygen difference was significantly increased in the heart-failure patients (8.3 ± 0.4 mL/dL, vs 7 ± 0.5 mL/dL in the control subjects; P=0.05). Although the mean myocardial ketone body extraction ratio was relatively unchanged (0.49 ± 0.05 in heart-failure patients vs 0.54 ± 0.06 in control subjects, P=0.53), skeletal-muscle ketone body utilization was markedly lower in the heart-failure patients (0.18 ± 0.06, vs 0.4 ± 0.04 in control subjects; P=0.01). In this preliminary study, heart failure was associated with tissue-specific alteration of ketone body metabolism. In advanced heart failure, skeletal-muscle ketone body utilization was impaired, whereas myocardial ketone body utilization was preserved. Future studies are needed to determine whether ketone body metabolism serves as a dynamic quantitative biomarker of skeletal myopathy and fatigue in heart failure.