Common Genetic Variants and Response to Atrial Fibrillation Ablation

Abstract

Background Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio, 1.3 [95% confidence intervals, 1.1–1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Good responders to catheter ablation for long-standing persistent atrial fibrillation: Clinical and genetic characteristics

“…Over the last few years, several common genetic variants have been demonstrated to be associated with AF in GWAS performed in European ancestry [14] and the Chinese Han GeneID cohort [13]. Some reports have suggested that these genetic polymorphisms are associated with an increased risk of AF recurrence after RFCA [6][7][8][9]24]. However, there are ethnic differences in the frequency of these SNPs and their association with clinical phenotypes [10,13].…”

“…Therefore, we sought to identify patient factors predicting favorable success rates, and hypothesized that better patient selection criteria may improve clinical outcomes, reduce unnecessary cardiac tissue damage, or avoid unnecessary ablation procedures and reduce medical costs and procedure-related complications. Recently, there were several reports for the relationship between genetic polymorphism and clinical outcome of AF ablation [6][7][8][9]. Although there are significant ethnic differences [10], genetic polymorphism can be utilized as an innate biomarker to identify good responders for AF catheter ablation.…”

Gene-guided therapy for catheter-ablation of atrial fibrillation: are we there yet?

“…While clinical variables such as age, hypertension, and lone AF failed to predict maintenance of sinus rhythm, rs10033464 (chr4q25) SNP did predict successful rhythm control in patients with typical AF carrying the wild-type (WT) allele with an odds ratio of 4.7 (95 % CI 1.83 to 12, P <0.001). We and others [14] also showed that the same AF locus predicted a 24 % shorter recurrence-free time from AF than did the presence of the WTSNP after AF ablation [15], and this association was more recently confirmed in a meta-analysis [16]. A chr4q25 SNP also independently predicted AF recurrence after restoration of sinus rhythm after electrical cardioversion [17].…”

Maintenance of low inflammation level by the ZFHX3 SNP rs2106261 minor allele contributes to reduced atrial fibrillation recurrence after pulmonary vein isolation

“…However, both Shoemaker et al and Choi et al reported that ZFHX3 polymorphisms did not predict clinical recurrence of AF after catheter ablation among PAF and persistent AF patients [10, 17]. Thus, the contributions of ZFHX3 SNPs to AF recurrence after RFCA remain controversial.…”