A genetic polymorphism on chromosome 4q25 (rs17570669_T) may predict atrial fibrillation recurrence after successful electrical cardioversion
Authors: Ulus T , Aliyev I , Aslan S , Cilingir O , Colak E 
Published: November 2023

Abstract

Background
Direct current electrical cardioversion (DCCV), is an effective treatment method in patients with symptomatic persistent atrial fibrillation (AF). However, AF recurrence may occur following successful DCCV in nearly half of the patients. There is not enough data investigating the association between single nucleotide polymorphisms (SNP) and AF recurrence after DCCV.

Purpose
We aimed to investigate whether 11 SNPs previously associated with AF (rs2200733, rs10033464, rs6838973, rs3853445 and rs17570669 SNPs in PITX2 gene; rs2106261 SNP in ZFHX3 gene; rs751141 SNP on chromosome 8q21; rs3807989 SNP in CAV1 gene; rs10570248 SNP in TBX5 gene; rs1800469 SNP in TGF-1 gene; and rs6795970 SNP in SCN10A gene) were predictive for recurrence after successful DCCV in patients with persistent AF in Turkish society.

Methods
We included 75 patients with sinus rhythm after direct current electrical cardioversion (DCCV). Baseline clinical features and 11 AF-related SNPs were compared between patients with and without AF recurrence during the follow-up. The association between SNPs and AF recurrence was evaluated with the additive model (wild type vs heterozygous variant vs homozygous variant), the dominant model (wild type/heterozygous vs homozygous variant), and the recessive model (wild type vs heterozygous variant/homozygous variant).

Results
The mean age of the patients was 61.9 ± 11.5 years. At a mean follow-up of 17.0 (11.0-25.0) months, 38 patients (50.7%) developed AF recurrence. The frequency of the female gender was higher (55.3% vs. 32.4%), AF duration before DCCV was longer [9.2 (5.5-11.6) vs 5.0 (2.7-11.0) months], and left atrial volume index before DCCV was higher (43.6 ± 8.8 ml/m2 vs. 38.2 ± 12.9 ml/m2) in patients who developed AF recurrence than those without it (p=0.046, 0.029 and 0.036, respectively) (Figure 1a). In the additive model, a SNP at the PITX2 gene (rs17570669_T: OR 9.00, 95% CI 1.28-63.02, p=0.027) and a SNP at the ZFHX3 gene (rs2106261_T: OR 8.96, 95% CI 1.03-77.66, p=0.047) were significantly associated with AF recurrence. Female gender (HR: 1.99, 95% CI: 1.05-3.79, p=0.035) and the rs17570669_T SNP (HR: 4.16, 95% CI: 1.22-14.11, p=0.022) were predictors for AF recurrence in univariate analysis. A multivariate Cox regression analysis showed that the rs17570669_T SNP 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) (Figure 1b). A Kaplan-Meier curve showed that AF-free survival was significantly lower in patients who had rs17570669_T SNP in the additive model (Figure 2).

Conclusion
A SNP at the PITX2 locus (rs17570669_T) may predict AF recurrence after successful DCCV in patients with persistent AF in Turkish society. Such individuals may be closely monitored for the development of AF recurrence after DCCV. In addition, reversible risk factors associated with AF recurrence may be more tightly controlled in such patients.Baseline features and Cox analysisKaplan-Meier curve