Energy metabolism in the normal and failing heart: potential for therapeutic interventions

Heart Fail Rev. 2002 Apr;7(2):115-30. doi: 10.1023/a:1015320423577.


The chronically failing heart has been shown to be metabolically abnormal, in both animal models and in patients. Little data are available on the rate of myocardial glucose, lactate and fatty acid metabolism and oxidation in heart failure patients, thus at present, it is not possible to draw definitive conclusions about cardiac substrate preference in the various stages and manifestations of the disease. Normal cardiac function is dependent on a constant resynthesis of ATP by oxidative phosphorylation in the mitochondria. The healthy heart gets 60-90% of its energy for oxidative phosphorylation from fatty acid oxidation, with the balance from lactate and glucose. There is some indication that compensated NYHA Class III heart failure patients have a significantly greater rate of lipid oxidation, and decreased glucose uptake and carbohydrate oxidation compared to healthy age-matched individuals, and that therapies that acutely switch the substrate of the heart away from fatty acids result in improvement in left ventricular function. Clinical studies using long-term therapy with beta-adrenergic receptor antagonists show improved left ventricular function that corresponds with a switch away from fatty acid oxidation towards more carbohydrate oxidation by the heart. These findings suggest that chronic manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less fatty acid oxidation may improve ventricular performance and slow the progression of left ventricular dysfunction in heart failure patients. At present, this intriguing hypothesis requires further evaluation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology*
  • Heart Failure / therapy
  • Humans
  • Myocardium / metabolism*
  • Prevalence
  • Severity of Illness Index
  • United States / epidemiology
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / therapy