Targeting myocardial substrate metabolism in heart failure: Potential for new therapies

Hossein Ardehali*, Hani N. Sabbah, Michael A. Burke, Satyam Sarma, Peter P. Liu, John G.F. Cleland, Aldo Maggioni, Gregg C. Fonarow, E. Dale Abel, Umberto Campia, Mihai Gheorghiade

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

107 Scopus citations

Abstract

The incidence and prevalence of heart failure have increased significantly over the past few decades. Available data suggest that patients with heart failure independent of the aetiology have viable but dysfunctional myocardium that is potentially salvageable. Although a great deal of research effort has focused on characterizing the molecular basis of heart failure, cardiac metabolism in this disorder remains an understudied discipline. It is known that many aspects of cardiomyocyte energetics are altered in heart failure. These include a shift from fatty acid to glucose as a preferred substrate and a decline in the levels of ATP. Despite these demonstrated changes, there are currently no approved drugs that target metabolic enzymes or proteins in heart failure. This is partly due to our limited knowledge of the mechanisms and pathways that regulate cardiac metabolism. Better characterization of these pathways may potentially lead to new therapies for heart failure. Targeting myocardial energetics in the viable and potentially salvageable tissue may be particularly effective in the treatment of heart failure. Here, we will review metabolic changes that occur in fatty acid and glucose metabolism and AMP-activated kinase in heart failure. We propose that cardiac energetics should be considered as a potential target for therapy in heart failure and more research should be done in this area.

Original languageEnglish (US)
Pages (from-to)120-129
Number of pages10
JournalEuropean Journal of Heart Failure
Volume14
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • AMP-activated kinase
  • Cardiac metabolism
  • Energetics
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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