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

BACKGROUND Obesity is associated with atria L 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 beta 1, and connective tissue growth factor. RESULTS Increasing weight was associated with increasing Left atria L 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 = .02), 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 atria L 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 beta 1 (P = .02) and platelet-derived growth factor (P = .02) levels. CONCLUSIONS Obesity is associated with atria L electrostructural remodeling. With progressive obesity, there were changes in atria L size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF.