PO-455617-17 PIRFENIDONE MITIGATES THE DEVELOPMENT OF ARRHYTHMOGENIC ATRIAL FIBROSIS DUE TO PREMATURE ATRIAL COMPLEXES IN A SWINE MODEL

Atrial fibrosis is one of the major pathophysiologic mechanisms underlying progression atrial arrhythmias. We previously demonstrated in a swine model that frequent premature complexes (PACs) promote fibrillation (AF) via and slow conduction. Whether such can be reversed or prevented unknown. To evaluate effect (1) PAC eradication (2) antifibrotic drug pirfenidone (PFD) on frequent, dyssynchronous PACs. Thirty-five were exposed to 50% paced PACs from lateral left atrium (LA) coronary sinus for 16 weeks 4 groups: controls without (CTRL, n=10); group (PAC; 3) followed by additional 6 cessation (Rec-PAC, (4) treated with oral PFD (801mg 2 times per day) (PFD-PAC; n=5). Detailed EP study echocardiography performed at baseline prior sacrifice blinded histological quantification LA fibrosis. In group, peak strain declined significantly compared CTRL. Compared both Rec-PAC PFD-PAC groups had less significant decline (terminal - baseline: -17.7±3.3% vs. -8.3±3.2% -11.5±3.0% CTRL -0.7±4.2%; p<0.001). Conduction velocity (CV) was decreased Rec-PAC, but this decrease attenuated (PAC CV 1.1±0.2m/s 1.2±0.1 m/s 1.3±0.1m/s 1.5±0.2m/s; Posterior wall increased no change after recovery However, showed lower than either (Figure, Panel A). The also AF inducibility (Panel B). model, produce arrhythmogenic substrate. This fibrotic substrate did not regress treatment development inducibility. These findings suggest: early management may important preventing ectopy-induced adverse remodeling, pharmacological therapy targeted play an important, novel role prevention remodeling developing AF.