Heart, Lung and Circulation

Obesity Results in Progressive Atrial Electrical and Structural Remodeling: Implications for Atrial Fibrillation

      Background: Obesity has been associated with the development of atrial fibrillation (AF); however the mechanisms by which it results in a pro-arrhythmic substrate remain unknown.
      Methods: Thirty sheep were studied at baseline, four months and eight months, following an ad libitum calorie dense diet. Ten were sampled at each time point for cardiac MRI, invasive haemodynamic evaluation (left atrial and arterial pressure) and detailed electrophysiologic study. An additional six maintenance-fed control sheep were sampled at four and eight months to control for time/age-related effects. A custom made 128-electrode plaque applied to the right and left atria was used to quantify; bi-atrial effective refractory periods (ERP); conduction velocity (CV); conduction heterogeneity index (CHI) at four pacing cycle lengths (PCL) from four sites; and AF inducibility. Quantitative myocardial histology was performed for myocardial fibrosis, inflammation and lipidosis.
      Results: Weight increased from 58 ± 7 kg to 77 ± 5 kg to 105 ± 13 kg (P < 0.001). With increasing weight there was: progressive decrement in atrial CV (P = 0.01), increasing atrial volumes (P = 0.01), atrial fibrosis (P = 0.007) and lipidosis (P = 0.049). There was regional variation in conduction heterogeneity (P = 0.04) with increasing weight. Electrophysiologic disturbances persisted after adjusting for haemodynamic variables. No changes were observed in the control cohort (ERP; P = 0.5, CV; P = 0.8, CHI; P = 0.9). With increasing adiposity, AF event number (P = 0.001) and duration (P < 0.001) significantly increased. No significant change was observed in ERP with increasing adiposity (P = 0.198).
      Conclusion: Obesity induces early and progressive atrial structural and electrophysiological remodelling. These electrophysiological abnormalities were independent of adverse haemodynamic changes and occurred with a step-wise increase in AF burden.