TY - JOUR
T1 - Atrial Fibrillation and Obesity
T2 - Reverse Remodeling of Atrial Substrate With Weight Reduction
AU - Mahajan, Rajiv
AU - Lau, Dennis H.
AU - Brooks, Anthony G.
AU - Shipp, Nicholas J.
AU - Wood, John P.M.
AU - Manavis, Jim
AU - Samuel, Chrishan S.
AU - Patel, Krupesh P.
AU - Finnie, John W.
AU - Alasady, Muayad
AU - Kalman, Jonathan M.
AU - Sanders, Prashanthan
PY - 2021/5
Y1 - 2021/5
N2 - Objectives: This study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF). Background: Whether weight loss can reverse the atrial substrate of obesity is not known. Methods: Thirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72 weeks. 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 weeks. 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). Results: Sustained obesity was associated with increased left atrium (LA) pressure (p < 0.001), inflammation (p < 0.001), atrial transforming growth factor β1 protein (p < 0.001), endothelin-B receptor expression (p = 0.04), atrial fibrosis (p = 0.01), epicardial fat infiltration (p < 0.001), electrophysiological abnormalities, and AF burden (p = 0.04). Connexin 43 expression was decreased in the obese group (p = 0.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p < 0.001), LA pressure (p = 0.007), inflammation (p < 0.001), endothelin-B receptor expression (p = 0.01), atrial fibrosis (p = 0.01), increase in atrial effective refractory period (cycle length: 400 and 300 ms; p < 0.001), improved conduction velocity (cycle length: 400 and 300 ms; p = 0.01), decreased conduction heterogeneity (p < 0.001), and decreased AF inducibility (p = 0.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p = 0.34). Conclusions: Weight 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.
AB - Objectives: This study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF). Background: Whether weight loss can reverse the atrial substrate of obesity is not known. Methods: Thirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72 weeks. 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 weeks. 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). Results: Sustained obesity was associated with increased left atrium (LA) pressure (p < 0.001), inflammation (p < 0.001), atrial transforming growth factor β1 protein (p < 0.001), endothelin-B receptor expression (p = 0.04), atrial fibrosis (p = 0.01), epicardial fat infiltration (p < 0.001), electrophysiological abnormalities, and AF burden (p = 0.04). Connexin 43 expression was decreased in the obese group (p = 0.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p < 0.001), LA pressure (p = 0.007), inflammation (p < 0.001), endothelin-B receptor expression (p = 0.01), atrial fibrosis (p = 0.01), increase in atrial effective refractory period (cycle length: 400 and 300 ms; p < 0.001), improved conduction velocity (cycle length: 400 and 300 ms; p = 0.01), decreased conduction heterogeneity (p < 0.001), and decreased AF inducibility (p = 0.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p = 0.34). Conclusions: Weight 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.
KW - atrial fibrillation
KW - connexin
KW - endothelin
KW - epicardial fat
KW - obesity
KW - TGF-β1
KW - weight loss
UR - http://www.scopus.com/inward/record.url?scp=85103276477&partnerID=8YFLogxK
U2 - 10.1016/j.jacep.2020.11.015
DO - 10.1016/j.jacep.2020.11.015
M3 - Article
C2 - 33640353
AN - SCOPUS:85103276477
SN - 2405-500X
VL - 7
SP - 630
EP - 641
JO - JACC: Clinical Electrophysiology
JF - JACC: Clinical Electrophysiology
IS - 5
ER -
