Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation

Common single nucleotide polymorphisms at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical atrial fibrillation (AF). Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5%-30% of AF cases.

To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases.

Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years; 71% men; 89% typical AF) between 2004 and 2011. The primary end point was time to recurrence of any nonsinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF).

Two-hundred atrial tachycardia, atrial flutter, or AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76; 95% confidence interval [CI] 0.6-0.95; P = .016) compared with wild type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio 0.79; 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio 0.61; 95% CI 0.37-1.0; P = .037).

Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of patients with predominately typical AF. Our findings suggest that the rs2200733 polymorphism may hold promise as an objectively measured patient characteristic that can be used as a clinical tool for selecting patients for AF ablation.