Combined metabolomic and proteomic analysis of human atrial fibrillation

J Am Coll Cardiol. 2008 Feb 5;51(5):585-94. doi: 10.1016/j.jacc.2007.09.055.


Objectives: We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia.

Background: Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail.

Methods: Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach.

Results: High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting.

Conclusions: The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to post-operative AF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / metabolism*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / metabolism*
  • Coenzyme A-Transferases / metabolism*
  • Coronary Artery Bypass
  • Coronary Disease / complications
  • Coronary Disease / metabolism
  • Coronary Disease / surgery
  • Humans
  • Ketone Bodies / metabolism*
  • Magnetic Resonance Spectroscopy
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Postoperative Complications / etiology
  • Postoperative Complications / metabolism
  • Proteomics


  • Ketone Bodies
  • Coenzyme A-Transferases
  • 3-ketoacid CoA-transferase
  • 3-Hydroxybutyric Acid