Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation

Hany S. Abed, Chrishan S. Samuel, Dennis H. Lau, Darren J. Kelly, Simon G. Royce, Muayad Alasady, Rajiv Mahajan, Pawel Kuklik, Yuan Zhang, Anthony G. Brooks, Adam J. Nelson, Stephen G. Worthley, Walter P. Abhayaratna, Jonathan M. Kalman, Gary A. Wittert, Prashanthan Sanders

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203 Citations (Scopus)

Abstract

Background: Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown. Objective: To examine the effect of progressive weight gain on the substrate for AF. Methods: Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor. Results: Increasing weight was associated with increasing left atrial volume (P =.01), fibrosis (P =.02), inflammatory infiltrates (P =.01), and lipidosis (P =.02). While there was no change in the effective refractory period (P =.2), there was a decrease in conduction velocity (P<.001), increase in conduction heterogeneity index (P<.001), and increase in inducible (P =.001) and spontaneous (P =.001) AF. There was an increase in atrial cardiomyocyte endothelin-A and -B receptors (P =.001) and endothelin-1 (P =.03) with an increase in adiposity. In association, there was a significant increase in atrial interstitial and cytoplasmic transforming growth factor β1 (P =.02) and platelet-derived growth factor (P =.02) levels. Conclusions: Obesity is associated with atrial electrostructural remodeling. With progressive obesity, there were changes in atrial size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF.

Original languageEnglish
Pages (from-to)90-100
Number of pages11
JournalHeart Rhythm
Volume10
Issue number1
DOIs
Publication statusPublished or Issued - Jan 2013

Keywords

  • Atrial fibrillation
  • Conduction velocity
  • Fibrosis
  • Obesity
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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