Obesity is associated with atrial fibrillation. Mechanisms resulting in a proarrhythmic substrate remain unknown. Methods: Thirty sheep commenced on a high caloric energy-dense diet, along with 6 weight-maintenance controls were samples at baseline, 4 and 8 months for cardiac MRI, invasive hemodynamic measures (LA and systemic pressure) and detaild electrophysiologic studies. A custom-made 128-electrode plaque applied to the LA and RA was used to quantify effective refractory periods (ERP), conduction velocity (CV) and conduction hererogeneity index (CHI) at 4 pacing cycle lengths (CL) from 4 sites. AF indicibility by ramp pacing was recorded. Quantitative histology was performed for fibrosis, inflammation and intramyocardial lipidosis. Results: Increased weight resulted in global conduction slowing, increased CHI and atrial volumes, fibrosis and lipidosis. Changes in CV persisted following adjustment for hemodynamic variables and were amplified by faster pacing CL. Obesity-induced changes in CHI were ameliorated following adjustment for hemodynamic variables - but were again amplified by greater pacing CL. No changes were observed in ERP with increasing obesity. There were no corresponding observed changes in the control group. With increasing adiposity, AF indicibility and duration increased exponentially. Conclusion: Obesity induces early changes in tissue conduction and later structural remodelling. Electrophysiologic abnomrlaities were only in-part explained by the hemodynamic disturbaces. This occured with a step-wise increase in AF events and duration.
- animal model
- atrial fibrillation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine