Ketones Step to the Plate

I t is increasingly recognized that metabolic remodeling is integral to heart failure (HF) development and progression.1,2 In particular, impairments in the ability of cardiac mitochondria to oxidize fatty acids have been noted, along with an increase in glycolysis that is uncoupled from glucose oxidation.3,4 This overall reduction in the myocardial oxidative capacity is purported to be the root cause of energy deficiency in the failing heart.Although past research has focused primarily on myocardial use of glucose and fatty acids, the heart is an omnivore and capable of oxidizing other substrates such as lactate, ketone bodies, and amino acids.The current understanding of the contribution of lactate, ketone bodies, and amino acids to cardiac metabolism is limited, particularly in the setting of HF.In this issue of Circulation, 2 independent studies provide new insights into the reliance of the failing heart on ketone bodies for energy supply.Proteomics analysis in mouse models of HF by Aubert et al 5 and metabolomics analysis of end-stage human failing hearts by Bedi et al 6 demonstrate strong and concordant evidence of increased ketone oxidation in the failing heart.