Abstract

Introduction: Recently, electrogram-based ablation strategies aiming at reentrant atrial fibrillation (AF) sources have demonstrated substantial efficacy. Still, the mechanisms by which these strategies modulate AF dynamics are unknown. Objective: Here, we employed advanced optical mapping approaches to examine AF dynamics before and after two distinct electrogram-based ablation strategies: highest dominant frequency sites/rotor ablation (DFmax/rotor, “on-target”); and complex fractionated atrial electrograms ablation (CFAE, “nearly-missed”). Methods: We implemented a high-resolution optical mapping set-up that enabled simultaneous epicardial and endoscopy guided endocardial recordings in Langendorff-perfused sheep hearts. After inducing AF in the presence of continuous perfusion of acetylcholine (ACh), we recorded optical movies from the left atrial free wall (LAFW) as well as the posterior left atrium (PLA). Then, DFmax regions (n=4) or CFAE regions harboring the highest wavebreak density (HWD, n=5) were targeted with a 4F ablation catheter (5-15W, 30-60 sec/point). Results: On-target DFmax/rotor point ablation resulted in a significant decrease in bi-atrial DFmax values (18.02±3.16 to 12.9±2.6, p<0.05, n=4) and AF termination after that a high frequency rotor was targeted (n=1). In contrast, LAFW point ablation in nearly-missed HWD regions- located at the boundaries of DFmax domains, in the vicinity of AF sources - did not significantly modulate AF frequency of excitation, (LAA DFmax: 15.16±4.98 to 14.26±3.38 Hz, n=5; p=0.205). Rather, DFmax domains relocated to PV-PLA regions (3/5 hearts) and to the roof (2/5 hearts). In another group of hearts (n=12), we examined 3-dimensional rotors- a.k.a scroll waves - dynamics during a progressive increase in ACh concentration from 0 to 0.2 μM. Under these conditions, scroll waves formed at the PLA reproducibly drifted to the LAFW along the free wall pectinate muscles, or other structures characterized by large myocardial thickness gradients. Conclusions: On-target DFmax/rotor ablation leads to large decreases in AF frequency and AF termination. In contrast, nearly-missed CFAE/HWD ablation leads to scroll wave relocation and/or drift along large myocardial thickness gradients.

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