Characterization Of Substrate For Atrial Fibrillation In Obesity And Reversibility with Weight Reduction: An Ovine Study — ASN Events
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Characterization Of Substrate For Atrial Fibrillation In Obesity And Reversibility with Weight Reduction: An Ovine Study (#224)

Rajiv Mahajan 1 , Anthony Brooks 2 , Nicholas Shipp 2 , Jim Manavis 3 , John Wood 3 , John Finnie 3 , Chrishan Samuel 4 , Muayad Alasady 1 , Kurt C Roberts Thomson 1 , Prashanthan Sanders 1
  1. CHRD, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
  2. CHRD, University of Adelaide, Adelaide, Australia
  3. SA Pathology, Adelaide, Australia
  4. Department of Pharmacology, Monash University, Melbourne, Australia

Introduction: Reversibility of obesity-related AF risk with weight reduction is not known.

Methods: 20 sheep had induced obesity by ad-libitum calorie dense diet. 10 lean sheep served as control. 10 obese animals were then subject to weight reduction. 10 animals in obese state and after weight reduction and controls underwent: bi-atrial endocardial electroanatomic mapping, hemodynamic assessment, and imaging. Electrophysiological evaluation included: ERP (7 sites), conduction velocity (CV), voltage mapping and AF inducibility. Fatty infiltration, atrial fibrosis, TGFβ1 and Connexin-43 expression were analyzed.

Results: Obese sheep weighed 110±9 kg and reduced to 79±7 kg (p<0.001) but not control levels (60±7 kg). Weight loss was associated with reduction in total body fat, atrial size, atrial and PA pressures and fractionation (p=0.01). CV increased (p<0.001) to control levels with weight loss; however, regional CV heterogeneity persisted (p=0.49).  Although, the mean voltage did not change significantly, the heterogeneity persisted despite weight loss. The mean ERP and ERP heterogeneity did not change.  AF episodes were significantly more in obese sheep (vs controls p<0.001) and did not reduce with weight loss (p=0.76).  Epicardial fat infiltrated posterior LA in obese group (vs controls p<.001) and did not regress upon weight loss (p=.98). Fibrosis (p=.003) and atrial TGFβ1 protein (p=.002) were increased and Connexin43 expression depressed (p=.01) in obese group as compared to controls. Fibrosis regressed (p=.009), atrial TGFβ1 protein trended to regress (p=.07) and atrial connexin-43 expression improved (p=.004) with weight loss.

Conclusion: The elevation of atrial TGFβ1 protein, reduced connexin43 expression and increased fibrosis with obesity and reversal upon weight loss suggest their role in creating AF substrate in obesity. Epicardial fat infiltrates underlying atrial muscle potentially altering conduction by forming areas of electrical silence, promoting reentry. Its persistence could account for maintained AF vulnerability. This also demonstrates the mechanism by which epicardial fat predisposes to AF. Importantly, weight reduction resulted in partial AF substrate reversal underling its role in AF management in obesity.