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

Rajiv Mahajan, Dennis H Lau, Andrew G Brooks, Nicholas J Shipp, Jim Manavis, John P M Wood, John W Finnie, Chrishan S Samuel, Simon G Royce, Darragh J Twomey, Shivshanker Thanigaimani, Jonathan M Kalman, Prashanthan Sanders

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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)-beta1 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-beta1 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-beta1 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.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalJournal of the American College of Cardiology
Volume66
Issue number1
DOIs
Publication statusPublished - 2015

Cite this

Mahajan, Rajiv ; Lau, Dennis H ; Brooks, Andrew G ; Shipp, Nicholas J ; Manavis, Jim ; Wood, John P M ; Finnie, John W ; Samuel, Chrishan S ; Royce, Simon G ; Twomey, Darragh J ; Thanigaimani, Shivshanker ; Kalman, Jonathan M ; Sanders, Prashanthan. / Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. In: Journal of the American College of Cardiology. 2015 ; Vol. 66, No. 1. pp. 1 - 11.
@article{af3df0b55b284b02802fa542d70cd14f,
title = "Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity",
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)-beta1 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-beta1 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-beta1 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.",
author = "Rajiv Mahajan and Lau, {Dennis H} and Brooks, {Andrew G} and Shipp, {Nicholas J} and Jim Manavis and Wood, {John P M} and Finnie, {John W} and Samuel, {Chrishan S} and Royce, {Simon G} and Twomey, {Darragh J} and Shivshanker Thanigaimani and Kalman, {Jonathan M} and Prashanthan Sanders",
year = "2015",
doi = "10.1016/j.jacc.2015.04.058",
language = "English",
volume = "66",
pages = "1 -- 11",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier",
number = "1",

}

Mahajan, R, Lau, DH, Brooks, AG, Shipp, NJ, Manavis, J, Wood, JPM, Finnie, JW, Samuel, CS, Royce, SG, Twomey, DJ, Thanigaimani, S, Kalman, JM & Sanders, P 2015, 'Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity', Journal of the American College of Cardiology, vol. 66, no. 1, pp. 1 - 11. https://doi.org/10.1016/j.jacc.2015.04.058

Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. / Mahajan, Rajiv; Lau, Dennis H; Brooks, Andrew G; Shipp, Nicholas J; Manavis, Jim; Wood, John P M; Finnie, John W; Samuel, Chrishan S; Royce, Simon G; Twomey, Darragh J; Thanigaimani, Shivshanker; Kalman, Jonathan M; Sanders, Prashanthan.

In: Journal of the American College of Cardiology, Vol. 66, No. 1, 2015, p. 1 - 11.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity

AU - Mahajan, Rajiv

AU - Lau, Dennis H

AU - Brooks, Andrew G

AU - Shipp, Nicholas J

AU - Manavis, Jim

AU - Wood, John P M

AU - Finnie, John W

AU - Samuel, Chrishan S

AU - Royce, Simon G

AU - Twomey, Darragh J

AU - Thanigaimani, Shivshanker

AU - Kalman, Jonathan M

AU - Sanders, Prashanthan

PY - 2015

Y1 - 2015

N2 - 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)-beta1 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-beta1 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-beta1 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.

AB - 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)-beta1 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-beta1 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-beta1 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26139051

U2 - 10.1016/j.jacc.2015.04.058

DO - 10.1016/j.jacc.2015.04.058

M3 - Article

VL - 66

SP - 1

EP - 11

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 1

ER -