Abstract 17002: Common Atrial Fibrillation Risk Alleles at 4q25 and 1q21 Predict Recurrence after Catheter-Based Atrial Fibrillation Ablation
Background: Common single nucleotide polymorphisms (SNPs) at 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with atrial fibrillation (AF). Risk alleles at 4q25 have been shown to predict response to AF ablation in a population of predominately lone AF, but lone AF comprises only 5-30% of AF cases. Therefore, we sought to test the hypothesis that common AF susceptibility alleles can modulate response to AF ablation in patients with concomitant comorbid disease (typical AF) that comprise the majority of AF cases.
Methods: Patients enrolled in the Vanderbilt AF Registry who underwent catheter-based AF ablation between 2004 and 2011 were included. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (AT/AF) after a 3-month blanking period over an 18-month follow-up. The primary analysis tested the effect of 4q25 risk allele status on AT/AF recurrence-free time utilizing a log normal survival model with multivariable adjustment for other covariates associated with AT/AF recurrence. An exploratory analysis examined the effect of risk alleles at 1q21 and 16q22.
Results: The final cohort consisted of 378 ablations (age 60 years, 71% male, 89% typical AF). A total of 200 AT/AF recurrences (53%) were observed. The 4q25 risk allele rs2200733 was found to confer a 24% shorter recurrence-free time (survival time ratio 0.76, 95% CI 0.6-0.95, P=0.016). The second 4q25 SNP (rs10033464) did not affect recurrence-free time. In exploratory analyses, the 1q21 rs13376333 risk allele was found to confer a 22% shorter recurrence-free time (survival time ratio = 0.78, 95% CI 0.62-0.97, P=0.026) whereas the 16q22 rs7193343 risk allele did not.
Conclusion: The ability of common AF susceptibility SNPs at the 4q25 and 1q21 loci to predict clinical response to AF ablation persists in the presence of predisposing comorbid disease as evidenced by our findings in a population of patients with predominately typical AF. Our findings suggest that common AF susceptibility alleles at the 4q25 and 1q21 loci hold promise as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation.
- © 2012 by American Heart Association, Inc.