Abstract 12592: Acute Administration of N-Acytylcysteine Leads to Highly Specific Sub-Regional Changes in AF Electrogram Characteristics - A New Way to ‘Uncover’ Regions of High Oxidative Injury in the Fibrillating Atrium?

Abstract

Introduction: It is currently not possible to measure and therapeutically target oxidative injury (OI) in the intact fibrillating atrium. Hypothesis: We postulated that measurement of AF electrogram characteristics after acute administration of a reactive oxygen species (ROS) scavenger can help ‘uncover’ regions of high OI in the fibrillating human atrium. Methods: We mapped in both atria pre/post NAC (intravenous, 100mg/kg) in 15 persistent AF dogs (3-14 weeks rapid atrial pacing) using a high-density epicardial mapping-plaque (6 atrial regions in both atria, 130 electrodes, electrode-distance 2.5mm) and in 4 patients using the HD-grid catheter. We quantified the OS-levels as ratio of oxidatively damaged nuclei ( Figure A ) against the total number in 8-OHdG staining (N=36) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24) using Qupath. We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-region sizes with >10% change pre vs. post NAC. Results: Oxidative stress (OS) levels, highest in the left atrial free wall, lowest in the appendages increased with increasing degree of fibro-fatty tissue (R=0.6,P<0.05) and with decreasing cycle length (R=0.5, P<0.05) in all regions ( Figure C ). NAC selectively reduced AF characteristics in ‘hot spot’-sub-regions ( Figure D ). OS level correlated with delta CL, delta DF, and delta Organization Index in delta maps (NAC - baseline) (R=0.5, P<0.05, all comparisons) ( Figure E) . In patients, NAC ( Figure G) reduced AF characteristics in subregions ( Figure H) and increased cycle length from 210±50ms to 252±18ms (P<0.05) in the left atrium ( Figure I ). Conclusions: OS-level correlated with the degree of dense fibro-fatty tissue and with electrogram measures in both atria. Acute scavenging of ROS reduced AF characteristics in the left atrium in dogs and patients. We might have found a new way to target regions of high OS in the atrium in the individual patient.