Abstract 12313: Uncovering Functional and Structural Remodeling Progression of Persistent Atrial Fibrillation Over Time in a Rapid Atrial Pacing Canine Model - New Mechanistic Insights in Persistent Atrial Fibrillation

Abstract

Introduction: The specific underlying persistent AF mechanisms are complex, and their development and remodeling processes over time are still not well understood. Hypothesis: We hypothesized that continuous rapid atrial pacing (RAP) in dogs induces persistent AF by affecting electrogram measures, fibrosis and oxidative stress (OS). Methods: AF was induced in 15 dogs (25-35 kg, 1 year) by RAP (3-14 weeks RAP, 600 beats/min), and 7 control dogs were used. We performed high-resolution epicardial mapping in 15 dogs and 8 controls using a high-density epicardial mapping plaque (6 regions, 130 electrodes, electrode distance 2.5mm) ( Figure A ). We analyzed the electrogram measures cycle length (CL) and dominant frequency (DF) in the 6 atrial regions in the left (LA) and right atrium (RA). MRI native T1 mapping was performed using a 1.5T clinical scanner (Siemens Aera) in 7 persistent AF dogs and in 8 dogs at baseline in the posterior left atrium (PLA). We quantified in 6 atrial regions in both atria the oxidative stress (OS) levels as the ratio of oxidatively damaged nuclei against the total number in 8-OHdG staining in (N=36 samples in 6 animals) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24 in 4 animals) using Qupath in all 6 regions in both atria. Results: Rapid atrial pacing (RAP) weeks correlated with CL (R=0.6, P 0.05) in the PLA ( Figure B ). Native T1 signal intensity increased with RAP days (R=0.6, P 0.05) in the PLA (less than 142 pacing days) ( Figure C ). Highest degree of dense focal fibrosis/ fat was in the left atrial free wall (LAFW) (49+/-14%) and in the PLA (47+/-19%) ( Figure F ). OS levels, highest in the LAFW, lowest in the appendages increased with the degree fibrosis (R=0.6, P<0.05) and with decreasing cycle length (R=0.5, P<0.05) in all atrial regions ( Figure D,E,G,H,I ). Conclusions: Continuing persistent AF is associated with smaller CL, increasing fibrosis, and oxidative injury rapid atrial pacing time.