Abstract 4143965: Reactive Oxygen Species Scavenging Reduces Complex Fractionated Atrial Electrograms (CFAEs) In Persistent Atrial Fibrillation Patients - A New Smart Mechanism Guided CFAE Targeting Approach in Atrial Fibrillation

Background: It is known that oxidative stress (OS) and complex fractionated atrial electrograms play an important role in AF. However, the effect of reactive oxygen species (ROS) on complex fractionated atrial electrograms (CFAEs) in persistent atrial fibrillation patients remains unsettled. While previous CFAE ablation studies have mixed results, it is currently also unclear which types of CFAEs should be targeted with ablation during the clinical electrophysiological (EP) study. Objective We hypothesized that ROS are dynamically involved in the creation of a vulnerable substrate leading to overlying CFAEs and that regions of CFAEs that may reflect high OS are uniquely sensitive to acute ROS scavenging with N-acetylcysteine (NAC) in persistent AF patients. Methods: We performed in 5 patients with persistent AF high-density mapping in the left and right atrium (LA, RA) pre/post-NAC (intravenous, dose 100mg/kg) (Figure 1A) using the HD-grid catheter (EnSite, Abbott) (Figure 1B). We analyzed cycle length (CL) and dominant frequency (DF), organization index (OI), fractionation index (FI), and regions demonstrating >10% change in these parameters and CFAEs (definition EnSite) >50% change post-NAC. Results: NAC (Figure 2) affected AF electrogram measures in atrial sub-regions, increasing CL in the left lateral free wall, right atrial free wall, affecting DF/OI preferentially in the left atrial superior wall and CFAEs (Figure 3A, B) in the left atrial inferior wall (Figure 3C). Acute administration of NAC caused significantly greater percentage changes in CFAEs in the LA (165%) pre vs post-NAC compared to percentage changes in CL (40%), DF (33%), OI (37%) and FI (16%) (P=0.002) (Figure 3D). 35% of all CFAEs in the LA and 21% in the RA were sensitive (>50% change, P=0.02) to ROS scavenging. Conclusion: Acute administration of NAC organizes AF electrogram characteristics in subregions in the left and right atrium and has a greater effect on CFAEs in the left atrium compared to other established AF electrogram characteristics. About one third of all CFAEs are ROS dependent. These uniquely sensitive CFAE regions to ROS scavenging may constitute a new smart therapeutic target in patients with persistent AF.