Rajiv Mahajan1, Dennis H Lau2, Anthony G Brooks3, Nicholas J Shipp3, John P M Wood4, Jim Manavis4, Chrishan S Samuel5, Krupesh P Patel5, John W Finnie4, Muayad Alasady2, Jonathan M Kalman6, Prashanthan Sanders7. 1. Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia; Department of Cardiology, Lyell McEwin Hospital, Adelaide, Australia. 2. Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia; Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia. 3. Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia. 4. Discipline of Anatomy and Pathology, Adelaide Medical School, University of Adelaide; SA Pathology, Adelaide, Australia. 5. Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Melbourne, Australia. 6. Department of Cardiology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia. 7. Centre for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia; Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia. Electronic address: prash.sanders@adelaide.edu.au.
Abstract
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. Crown
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. Crown
Authors: Jonathan P Ariyaratnam; Adrian D Elliott; Ricardo S Mishima; Celine Gallagher; Dennis H Lau; Prashanthan Sanders Journal: Heart Rhythm O2 Date: 2021-12-17
Authors: Jorge Enrique González-Casanova; Samuel Durán-Agüero; Nelson Javier Caro-Fuentes; Maria Elena Gamboa-Arancibia; Tamara Bruna; Valmore Bermúdez; Diana Marcela Rojas-Gómez Journal: Int J Mol Sci Date: 2021-11-10 Impact factor: 5.923
Authors: Nele Gessler; Stephan Willems; Daniel Steven; Jens Aberle; Ruken Oezge Akbulak; Nils Gosau; Boris A Hoffmann; Christian Meyer; Arian Sultan; Roland Tilz; Julia Vogler; Peter Wohlmuth; Susanne Scholz; Melanie A Gunawardene; Christian Eickholt; Jakob Lüker Journal: Europace Date: 2021-10-09 Impact factor: 5.214