Abstract 11048: Obesity is Associated with Atrial Conduction Abnormalities, Fibrosis and Endothelin Receptor Over-expression: Implications for Atrial Fibrillation
Introduction Obesity is an independent risk factor for atrial fibrillation (AF). The mechanisms behind the electro-structural remodeling remain unknown.
Methods Thirty sheep were fed a calorie dense diet over 8 months to achieve a state of obesity. Samples were taken at baseline, 4 months and 8 months for cardiac MRI, high density epicardial mapping (at the free wall and appendage of each atrium at drive train pacing cycle lengths of 500 and 200msec; effective refractory period [ERP], conduction velocity [CV], conduction heterogeneity index [CHI]), atrial histological (fibrosis, inflammation and lipid) and morphometric IHC analysis (Endothelin-1 [ET-1] peptide and receptors [ETA/ETB], transforming growth factor-β1 [TGF-β1], platelet-derived growth factor-BB [PDGF-BB] and connective tissue growth factor [CTGF]). Spontaneous and inducible (by standardized programmed electrical stimulation) AF and the duration of cumulative AF episodes (mins) was recorded during invasive EP mapping.
Results P vales in parentheses Weight (kg) increased from 58±7 to 77±5 then 105±13 (0.001), with a parallel significant rise in mean arterial (0.02) and left atrial pressure (<0.001). There was progressive increase in atrial volumes (0.01) and ventricular mass (<0.001). There was slowing in conduction velocity (0.003), increased CHI (0.008) but no change in ERP (0.5). Microscopically, there was increased collagen (0.02), inflammatory infiltrates (0.01) and myocardial lipidosis (0.02). With increasing weight, there was over-expression of ETA (0.001) and ETB (0.001) on cardiomyocyte plasma membranes and ET-1 (0.03) cytoplasmic levels in the obese cohort. Furthermore, progressive weight resulted in increase cytoplasmic CTGF (0.03) and a stepwise increase in interstitial and cytoplasmic TGF-β1 (0.02) and PDGF-BB (0.02). In association, spontaneous (<0.001) and inducible AF episodes increased (0.001) and duration of AF also increased (0.01).
Conclusion Progressive weight gain is associated with macro/micro structural and electrical abnormalities. In conjunction, there is increased pro fibrotic markers and marked over expression of ET receptors. Further studies are required to elucidate the role of ET receptor blockade in the obesity-AF disease complex.
- © 2012 by American Heart Association, Inc.