Genetic determinants of recurrence following successful direct current cardioversion in patients with persistent atrial fibrillation

Direct current electrical cardioversion (DCCV), is an effective treatment method in patients with symptomatic persistent atrial fibrillation (AF). However, recurrence may occur following successful DCCV in nearly half of the patients. Although some genome- wide association studies have shown that several single nucleotide polymorphisms (SNP) are associated with recurrences after successful DCCV in other populations, there is not enough data on this subject. In our study, we aimed to investigate whether 11 SNPs previously associated with AF were predictive for recurrence after successful DCCV in patients with persistent AF in our society. We included 75 patients with persistent AF who had sinus rhythm after successful DCCV. The patients were followed up prospectively for the development of AF recurrence in the follow-up. Baseline clinical features and 11 AF-related SNPs were compared between patients with and without AF recurrence. The association between SNPs and AF recurrence was evaluated with the additive model (wild type/heterozygous variant/homozygous variant), the dominant model (wild type/heterozygous and homozygous variant), and the recessive model (wild type and heterozygous variant/homozygous variant). At a median follow-up of 17.0 (11.0-25.0) months, 38 patients (50.7%) developed AF recurrence. In the additive model, one SNP at the PITX2 gene locus (rs17570669_T: OR 9.00, 95% CI 1.28-63.02, p=0.027) and one SNP at the ZFHX3 gene locus (rs2106261_T: OR 8.96, 95% CI 1.03-77.66, p=0.047) were significantly associated with AF recurrence. A multivariate Cox regression analysis showed that a SNP (rs17570669_T) was an independent predictor of AF recurrence following successful DCCV in the additive model (HR: 3.59, 95% CI: 1.05-12.21, p=0.04). In conclusion, a SNP (rs17570669_T) at the PITX2 locus is an independent predictor of long-term AF recurrence after successful DCCV in patients with persistent AF. Such individuals may be more closely monitored for the development of AF recurrence after successful DCCV. Key Words: Cardioversion, atrial fibrillation, single nucleotide polymorphism