Atrial Fibrillation and Obesity: Reverse Remodeling of Atrial Substrate With Weight Reduction.

Abstract

OBJECTIVES\nThis study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF).\n\n\nBACKGROUND\nWhether weight loss can reverse the atrial substrate of obesity is not known.\n\n\nMETHODS\nThirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72\xa0weeks. Animals were randomized to 3 groups: sustained obesity and 15% and 30% weight loss. The animals randomized to weight loss underwent weight reduction by reducing the quantity of hay over 32\xa0weeks. Eight lean animals served as controls. All were subjected to the following: dual-energy x-ray absorptiometry, echocardiogram, cardiac magnetic resonance, electrophysiological study, and histological and molecular analyses (fatty infiltration, fibrosis, transforming growth factor β1, and connexin 43).\n\n\nRESULTS\nSustained obesity was associated with increased left atrium (LA) pressure (p\xa0<\xa00.001), inflammation (p\xa0<\xa00.001), atrial transforming growth factor β1 protein (p\xa0<\xa00.001), endothelin-B receptor expression (p\xa0=\xa00.04), atrial fibrosis (p\xa0=\xa00.01), epicardial fat infiltration (p\xa0<\xa00.001), electrophysiological abnormalities, and AF burden (p\xa0=\xa00.04). Connexin 43 expression was decreased in the obese group (p\xa0=\xa00.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p\xa0<\xa00.001), LA pressure (p\xa0=\xa00.007), inflammation (p\xa0<\xa00.001), endothelin-B receptor expression (p\xa0=\xa00.01), atrial fibrosis (p\xa0=\xa00.01), increase in atrial effective refractory period (cycle length: 400 and 300\xa0ms; p\xa0<\xa00.001), improved conduction velocity (cycle length: 400 and 300\xa0ms; p\xa0=\xa00.01), decreased conduction heterogeneity (p\xa0<\xa00.001), and decreased AF inducibility (p\xa0=\xa00.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p\xa0=\xa00.34).\n\n\nCONCLUSIONS\nWeight loss in an obese ovine model is associated with structural and electrophysiological reverse remodeling and a reduced propensity for AF. This provides evidence for the direct role of obesity in AF substrate and the role of weight reduction in patients with AF.