Figure 2 Metabolic shift in heart failure Figure 2 | Metabolic shift in heart failure. In advanced heart failure, cardiomyocyte fatty acid uptake and β-oxidation, which in the healthy adult heart generates most of the cardiac ATP, and the oxidative function of mitochondria decrease. In failing myocardium, the electron transport chain has significantly lower respiration capacity compared with normal hearts, and the mitochondrial oxidative capacity remains reduced after left ventricular assist device (LVAD) unloading37. In the failing heart, the predominant fuel source shifts from mitochondrial fatty acid oxidation towards glycolytic pathways. The increased glycolysis remains elevated after LVAD support, which together with the defect in mitochondrial oxidation leads to increased cytosolic lactate rather than the increased pyruvate that enters the Krebs cycle. In patients with advanced heart failure, elevations in the serum concentration of ketone bodies (such as β-hydroxybutyrate) are accompanied by alterations in metabolites, such as increased levels of acetoacetate and acetoacetyl-CoA, and enzymes, such as increased expression levels of genes coding for the enzymes implicated in ketone oxidation D-β-hydroxybutyrate dehydrogenase (BDH1) and succinyl-CoA:3-oxoacid-CoA transferase (SCOT), consistent with the upregulation of the ketone oxidation pathway in the heart35,36. Kim, G. H. et al. (2017) Reverse remodelling and myocardial recovery in heart failure Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.139