Key result
Sustained obesity in sheep induces biatrial remodeling and fibrosis, increasing AF episodes and duration.
Why the study?
Obesity and AF are major public health issues, but the development of global electrophysiological and structural substrates for AF in sustained obesity required delineation.
Does sustained obesity induce electrophysiological and structural remodeling of the atria increasing vulnerability to AF in a sheep model?
Does sustained obesity induce electrophysiological and structural remodeling of the atria increasing vulnerability to AF in a sheep model?
Sustained obesity in a sheep model leads to significant biatrial endocardial remodeling, epicardial fat infiltration, and increased propensity for atrial fibrillation.
Sustained obesity induces atrial remodeling and AF substrate in sheep; leaves open reversibility with weight loss in humans.
BACKGROUND: Obesity and atrial fibrillation (AF) are public health issues with significant consequences. OBJECTIVES: This study sought to delineate the development of global electrophysiological and structural substrate for AF in sustained obesity. METHODS: Ten sheep fed ad libitum calorie-dense diet to induce obesity over 36 weeks were maintained in this state for another 36 weeks; 10 lean sheep with carefully controlled weight served as controls. All sheep underwent electrophysiological and electroanatomic mapping; hemodynamic and imaging assessment (echocardiography and dual-energy x-ray absorptiometry); and histology and molecular evaluation. Evaluation included atrial voltage, conduction velocity (CV), and refractoriness (7 sites, 2 cycle lengths), vulnerability for AF, fatty infiltration, atrial fibrosis, and atrial transforming growth factor (TGF)-β1 expression. RESULTS: Compared with age-matched controls, chronically obese sheep demonstrated greater total body fat (p < 0.001); LA volume (p < 0.001); LA pressure (p < 0.001), and PA pressures (p < 0.001); reduced atrial CV (LA p < 0.001) with increased conduction heterogeneity (p < 0.001); increased fractionated electrograms (p < 0.001); decreased posterior LA voltage (p < 0.001) and increased voltage heterogeneity (p < 0.001); no change in the effective refractory period (ERP) (p > 0.8) or ERP heterogeneity (p > 0.3). Obesity was associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration (p = 0.02) of AF. Epicardial fat infiltrated the posterior LA in the obese group (p < 0.001), consistent with reduced endocardial voltage in this region. Atrial fibrosis (p = 0.03) and TGF-β1 protein (p = 0.002) were increased in the obese group. CONCLUSIONS: Sustained obesity results in global biatrial endocardial remodeling characterized by LA enlargement, conduction abnormalities, fractionated electrograms, increased profibrotic TGF-β1 expression, interstitial atrial fibrosis, and increased propensity for AF. Obesity was associated with reduced posterior LA endocardial voltage and infiltration of contiguous posterior LA muscle by epicardial fat, representing a unique substrate for AF.
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Mahajan et al. (2015) studied Obesity and Atrial Fibrillation (n=20). Sustained obesity (calorie-dense diet) vs. Lean sheep (controlled weight) was evaluated on Electrophysiological, electroanatomic, and structural remodeling. Sustained obesity in sheep induced biatrial endocardial remodeling, increased atrial fibrosis (p=0.03), and resulted in more episodes (p=0.02) and greater cumulative duration (p=0.02) of AF.
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