Abstract 17206: Targeted Ablation at Regions of High Oxidative Injury in Persistent Atrial Fibrillation in a Canine Model — A New Electrogram Based Therapeutic Strategy in Atrial Fibrillation?

Abstract

Introduction: Oxidative stress (OS) plays an important role in the development of atrial fibrillation (AF). However, it is currently not possible to detect regions of high OS in the atria of individual AF patients. Hypothesis: We hypothesized that in persistent AF, electrograms (EGMs) at sites of high OS, are uniquely sensitive to acute reactive oxygen species (ROS) scavenging with N-acetylcysteine (NAC), both in a large animal model and in patients and that ablation at these NAC-sensitive ‘hotspots’ can terminate or slow AF. Methods: We performed high-density mapping (both atria, pre/post-NAC, intravenous, 100mg/kg) in 17 persistent AF dogs (3-14 weeks rapid atrial pacing) using an epicardial mapping-plaque (6 regions, both atria, 130 electrodes, electrode-distance 2.5mm) (Figure 1) and in 5 patients (HD-grid, Abbott). We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-regions (>10% change pre vs. post-NAC). In 4 dogs we performed epicardial ablation (Atricure) at 3 quadrants of the mapping fields with the largest NAC hotspots of all 6 mapped regions (Figure 2). Results: NAC led to preferential organization of AF (>10% DF decrease) at several sites in both atria (NAC hot spots). In patients, NAC (Figure 3) increased CL in the left atrium in the left lateral wall and in the right atrium in the posterior lateral wall. The largest DF hotspots were in the left atrium in the superior wall. In dogs, ablation at the largest hotspots terminated AF in 50% of the cases (2/4). In all cases, ablation significantly increased CL in the left atrium and decreased DF in all atrial regions (Figure 2). Conclusions: Acute administration of NAC preferentially organizes AF electrograms in subregions of both atria (‘hotspots’). Ablation at these NAC-sensitive hotspot regions terminated or slowed AF. We have discovered a unique method to target identified atrial sub-regions of high OS in the atria. These ‘hotspots’ may be a new therapeutic target in patients with persistent AF.