Common Genetic Variants and Response to Atrial Fibrillation Ablation. (April 2015)

• Record Type: Journal Article
• Authors: Shoemaker, M. Benjamin; Bollmann, Andreas; Lubitz, Steven A.; Ueberham, Laura; Saini, Harsimran; Montgomery, Jay; Edwards, Todd; Yoneda, Zachary; Sinner, Moritz F.; Arya, Arash; Sommer, Philipp; Delaney, Jessica; Goyal, Sandeep K.; Saavedra, Pablo; Kanagasundram, Arvindh; Whalen, S. Patrick; Roden, Dan M.; Hindricks, Gerhard; Ellis, Christopher R.; Ellinor, Patrick T.; Darbar, Dawood; Husser, Daniela
• Is Part Of: Circulation. Volume 8:Number 2(2015)
• Publication Date: 2015-04
• Subjects: Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.128
• DOI: 10.1161/CIRCEP.114.001909
• Languages: English
• ISSNs: 1941-3149

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near <italic>PITX2</italic>), 1q21 (rs13376333 in <italic>KCNN3</italic>), and 16q22 (rs7193343 in <italic>ZFHX3</italic>) 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.</p> </sec> <sec> <title>Methods and Results—</title> <p>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]; <italic>P</italic>=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence.</p> </sec> <sec> <title>Conclusions—</title> <p>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.</p> </sec> </abstract>