Abstract 15689: Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes

Abstract

Introduction: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF), with or without overt ventricular involvement. The efficacy of AF ablation in these patients is unknown. Research Questions/Hypothesis: To test the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have a higher risk of recurrence following AF ablation, and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM [ARVC], dilated CM [DCM], hypertrophic CM [HCM], or a channelopathy) have a higher risk of recurrence. Methods: We performed a prospective observational cohort study in participants referred for AF catheter ablation who underwent whole exome sequencing. Our primary outcome was AF recurrence, defined as >30 seconds of AF, atrial flutter, or atrial tachycardia that occurred at least 90 days after AF ablation. Results: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely-pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15 (0.84-1.60), p=0.53, Figure 1A ). When analyzed according to gene group, P/LP variants in the ALVC gene group, predominantly LMNA , were associated with increased recurrence (N=10; HR 3.75 (1.84-7.63), p<0.001), compared to those in the ARVC gene group (N=6; HR 1.97 (0.62-6.27), p=0.25), DCM gene group (N=50; HR 0.98 (0.59-1.63), p=0.94), HCM gene group (N=33; HR 1.28 (0.76-2.17), p=0.35), and channelopathy gene group (N=17; HR 0.58 (0.21-1.56), p=0.28), as shown in Figure 1B, 1C . Conclusions: Our results support the continued use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN . However, patients with ALVC variants, such as in LMNA , may be at a significantly higher risk for arrhythmia recurrence.