Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation
Introduction
Obesity is recognized to be associated with the development of atrial fibrillation (AF) and has been proposed as a contributor to the expanding epidemic of this arrhythmia.1, 2 Atrial structural and electrical remodeling have been implicated in the AF substrate associated with many conditions predisposing to the development of this arrhythmia3, 4, 5, 6; however, whether weight gain and obesity result in atrial remodeling is not known. Moreover, induction of this substrate along the adiposity spectrum of normal weight to obesity, and its relationship to hemodynamic disturbances, remains unknown. In this study, by using a sheep model of progressive weight gain, we aimed to characterize the atrial functional, structural, and electrophysiological changes accompanying increasing adiposity.
Section snippets
Animals
Thirty-six sheep (Merino Cross Wethers) were studied in accordance with guidelines outlined in the “Position of the American Heart Association on Research Animal Use,” adopted in November 11, 1984. This study was approved by the Animal Ethics Committees of the University of Adelaide and SA Pathology, Adelaide, Australia.
Study protocol
Thirty animals underwent ad libitum feeding to induce obesity, as previously described.7 At baseline, 4 months, and 8 months, 10 of the cohort were randomly selected for cardiac
Results
There was progressive weight gain with feeding duration from 58±7 kg at baseline to 77±5 kg (“overweight”) at 4 months and 105±13 kg (“obese”) at 8 months (P<.001). There was no weight change in the control group: 58±6 kg at baseline, 50±4 kg at 4 months, and 54±5 kg at 8 months (P = .2). Electrolyte, acid-base, and glucose levels remained within normal range throughout the overfeeding process.
Major findings
Progressive weight gain resulted in atrial functional, structural, and electrophysiological remodeling characterized by the following:
- 1.
Increased atrial volumes, LA and systemic pressures, ventricular mass, and pericardial fat volumes.
- 2.
Increased atrial interstitial fibrosis, inflammation, and myocardial lipidosis.
- 3.
Progressive conduction abnormalities with slowing of atrial conduction and increased conduction heterogeneity, which was amplified at shorter coupling intervals and CLs with greater
Conclusions
Progressive obesity predisposes to a greater burden of AF by forming an electropathological substrate. This is disproportionate to the progressive hemodynamic impact of obesity and suggests a direct pathogenic role of obesity on the AF substrate.
Acknowledgments
The authors thank Ms Samar Babkair and Mr Krupesh Patel for their assistance with immunohistochemistry and morphometric analysis, respectively.
References (30)
- et al.
The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women's health study)
J Am Coll Cardiol
(2010) - et al.
Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model
Heart Rhythm
(2010) - et al.
Dynamic and static phases of severe dietary obesity in sheep: food intakes, endocrinology and carcass and organ chemical composition
J Nutr
(1992) - et al.
Pericardial fat is associated with atrial fibrillation severity and ablation outcome
J Am Coll Cardiol
(2011) - et al.
Coronary artery disease affecting the atrial branches is an independent determinant of atrial fibrillation after myocardial infarction
Heart Rhythm
(2011) - et al.
Left atrial remodeling in patients with atrial septal defects
Heart Rhythm
(2009) - et al.
Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation
Heart Rhythm
(2012) - et al.
Paroxysmal lone atrial fibrillation is associated with an abnormal atrial substrate: characterizing the "second factor."
J Am Coll Cardiol
(2009) - et al.
Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure
J Am Coll Cardiol
(2005) - et al.
Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation
Heart Rhythm
(2012)
Endothelin-1 as a predictor of atrial fibrillation recurrence after pulmonary vein isolation
Heart Rhythm
Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence
Circulation
Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort
Circulation
Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation
Circulation
Atrial remodeling in an ovine model of anthracycline-induced nonischemic cardiomyopathy: remodeling of the same sort
J Cardiovasc Electrophysiol
Cited by (287)
The relationship between atrial fibrillation and coronary artery disease: Understanding common denominators
2024, Trends in Cardiovascular MedicineAging and atrial fibrillation: A vicious circle
2024, International Journal of CardiologyLeft atrial cardiomyopathy: Pathophysiological insights, assessment methods and clinical implications
2024, Archives of Cardiovascular DiseasesComparing Inducibility of Re-Entrant Arrhythmia in Patient-Specific Computational Models to Clinical Atrial Fibrillation Phenotypes
2023, JACC: Clinical Electrophysiology
This article was presented in part by Dr Abed, who was awarded the Ralph Reader Young Investigator Award by the Cardiac Society of Australia and New Zealand. It was published as an abstract in Heart Rhythm 2012;112:S190, Heart Rhythm 2012;93:S183, and Heart Lung and Circulation 2011;20:S2.
Dr Abed and Dr Mahajan were supported by the Australian Postgraduate Award from the University of Adelaide. Drs Abed and Alasady were supported by the Earl Bakken Electrophysiology Scholarships from the University of Adelaide. Dr Samuel was supported by the RD Wright Fellowship jointly funded by the National Heart Foundation of Australia (NHFA) and the National Health and Medical Research Council (NHMRC) of Australia. Dr Lau was supported by an NHMRC Postdoctoral Fellowship. Dr Alasady was supported by a Postgraduate Scholarship from the NHMRC. Dr Mahajan was supported by the Leo J Mahar Electrophysiology Scholarship from the University of Adelaide. Drs Kuklik, Brooks, and Sanders were supported by the NHFA.
Dr Sanders served on the advisory board of Bard Electrophysiology, Biosense Webster, Medtronic, St Jude Medical, Merck, and Sanofi-Aventis. He also received lecture fees or research funding from Bard Electrophysiology, Biosense Webster, Medtronic, and St Jude Medical.