Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity

Mahajan, Rajiv, Lau, Dennis H., Brooks, Anthony G., Shipp, Nicholas J., Manavis, Jim, Wood, John P.M., Finnie, John W., Samuel, Chrishan, Royce, Simon G., Twomey, Darragh J., Thanigaimani, Shivshankar, Kalman, Jonathan M., and Sanders, Prashanthan (2015) Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. Journal of the American College of Cardiology, 66 (1). pp. 1-11.

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Abstract

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.

Item ID: 62533
Item Type: Article (Research - C1)
ISSN: 1558-3597
Keywords: atrial fibrillation, epicardial fat, fibrosis, obesity, TGF-β1
Copyright Information: Copyright ©2020. Elsevier Inc. All rights reserved
Date Deposited: 16 Mar 2020 01:14
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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