Myocardial Ketones Metabolism in Heart Failure

Ketone bodies can become a major source of adenosine triphosphate production during stress to maintain bioenergetic homeostasis in the brain, heart, and skeletal muscles. In the normal heart, ketone bodies contribute from 10% to 15% of the cardiac adenosine triphosphate production, although their contribution during pathologic stress is still not well-characterized and currently represents an exciting area of cardiovascular research. This review focuses on the mechanisms that regulate circulating ketone levels under physiologic and pathologic conditions and how this impacts cardiac ketone metabolism. We also review the current understanding of the role of augmented ketone metabolism as an adaptive response in different types and stages of heart failure. This analysis includes the emerging experimental and clinical evidence of the potential favorable effects of boosting ketone metabolism in the failing heart and the possible mechanisms of action through which these interventions may mediate their cardioprotective effects. We also critically appraise the emerging data from animal and human studies which characterize the role of ketones in mediating the cardioprotection established by the new class of antidiabetic drugs, namely sodium-glucose co-transporter inhibitors.