Chapter 7 - Cardiac energy metabolism in heart failure

Abstract

The heart must continually produce large amounts of adenosine triphosphate to sustain contractile function. In the failing heart there are dramatic changes in energy production that contribute to the severity of contractile failure. However, there is a lack of consensus as to what actual changes in cardiac energy metabolism occur in heart failure. There is a general agreement that the failing heart is “energy starved,” but disagreement as to whether this is due to an impaired metabolism of fatty acids, or due to impaired carbohydrate metabolism. This confusion may be due to potential differences in energy metabolism in different types of heart failure. It is now clear that cardiac energy metabolism changes in heart failure can be substantially different between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). While there are similar changes in mitochondrial oxidative capacity in HFpEF and HFrEF, mitochondrial oxidation of fatty acids is increased in HFpEF and reduced in HFrEF. In contrast, the mitochondrial oxidation of glucose is decreased in both HFpEF and HFrEF. Emerging evidence suggests that cardiac ketone oxidation is increased in HFrEF but is decreased in HFpEF. The oxidation of branched-chain amino acids is also impaired in both HFrEF and HFpEF. Combined, these metabolic changes in both HFrEF and HFpEF result in an energy deficit, cardiac insulin resistance, and a decreased cardiac efficiency in the failing heart. It is important to obtain a better understanding of what changes in cardiac energy metabolism occur in heart failure, as it is becoming clear that optimizing energy metabolism is a potential therapeutic approach to treat heart failure. For instance, stimulating cardiac glucose oxidation may be a novel approach to increase energy production, insulin sensitivity, cardiac efficiency, and contractile function in both HFrEF and HFpEF.