Complex Energy Metabolic Changes in Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction

Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex, and are dependent not only on the severity and type of heart failure present, but also on the coexistence of common comorbidities such as obesity and type 2 diabetes. In this article we review the cardiac energy metabolic changes that occur in heart failure. An emphasis is made on distinguishing the differences in cardiac energy metabolism between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) and in clarifying the common misconceptions surrounding the fate of fatty acids and glucose in the failing heart. The major key points from this article are: (1) mitochondrial oxidative capacity is reduced in HFpEF and HFrEF; (2) fatty acid oxidation is increased in HFpEF and reduced in HFrEF (however, oxidative metabolism of fatty acids in HFrEF still exceeds that of glucose); (3) glucose oxidation is decreased in HFpEF and HFrEF; (4) there is an uncoupling between glucose uptake and oxidation in HFpEF and HFrEF, resulting in an increased rate of glycolysis; (5) ketone body oxidation is increased in HFrEF, which might further reduce fatty acid and glucose oxidation; and finally, (6) branched chain amino acid oxidation is impaired in HFrEF. The understanding of these changes in cardiac energy metabolism in heart failure are essential to allow the development of metabolic modulators in the treatment of heart failure.