Abstract 18309: Familial Atrial Fibrillation - Common Atrial Fibrillation Susceptibility Alleles and Response to Catheter Ablation

Abstract

Background: Familial atrial fibrillation (AF) is common but AF-causing rare genetic variants are infrequently found supporting the multigenetic nature of this arrhythmia. On the other hand, genome-wide association studies have identified common AF susceptibility alleles, but their possible relation with familial AF is unknown. The aim of this study was to compare familial and sporadic AF with respect to common alleles on chromosomes 1q21 (rs13376333), 4q25 (rs10033464 and rs2200733) and 16q22 (rs7193343) and rhythm outcome after radiofrequency catheter ablation (CA). Methods: A total of 393 patients (mean age 59 +/- 10 years, 68 % males, 38 % persistent AF), who underwent CA were studied. The family history of AF was considered positive if at least one of the first-degree family members had AF based on patient's interviews, chart and ECG reviews. Genotypes were determined using real-time polymerase chain reaction and fluorescence resonance energy transfer. AF recurrence > 30 sec was detected using serial 7-day Holter ECG recordings after a blanking period between 3 and 12 months after radiofrequency CA. Results: Familial AF was found in 14.2 % and was associated with the absence of structural heart disease (OR 1.888, 95 % CI 1.017 - 3.505, p=0.042) and age (OR 0.964, 95 % CI 0.938 - 0.991, p=0.009). In familial AF, minor allele frequency of AF risk alleles on chromosomes 1q21 (40.0 % vs. 32.8 %) and 4q25 (rs10033464: 26.4 % vs. 11.0 % and rs2200733: 39.4 % vs. 27.2 %) tended to be higher compared with non-familial AF. Using a dominant genetic model, rs2200733 on chromosome 4q25 showed the strongest association with familial AF (OR 2.222, 95 % CI 1.015 - 4.865, p=0.042). AF recurrence was observed in 27.6 % of non-familial AF and in 30.9 % of familial AF patients (p=0.621). Conclusion: This study, for the first time, shows a dominant modulating function of a common AF susceptibility allele on chromosome 4q25 also in familial AF. Ablation outcome is comparable in familial and non-familial AF highlighting the role of the pulmonary veins in AF development.