Genetic Variant Linked with Recurrent Atrial Arrhythmias Following Ablation

Journal Wrap | Among the three genetic loci most strongly associated with atrial fibrillation, a risk allele found on chromosome 4q25 is significantly associated with arrhythmia recurrence after catheter ablation for atrial fibrillation (AF), according to results of a new study published in Circulation: Arrhythmia and Electrophysiology.

The observational study was based on 991 patients (59% with paroxysmal AF) undergoing their first ablation procedure for AF at three centers, two in the U.S. and one in Europe. All patients underwent pulmonary vein (PV) isolation. Additional linear ablation or ablation of sites harboring complex electrograms was performed at the discretion of the operator. The primary outcome was recurrence of atrial arrhythmias at 12 months, based on symptoms, and either 48-hour Holter or 7- to 21-day event monitor. The single nucleotide polymorphisms (SNPs) that were examined included those at chromosome 4q25 (rs2200733 and rs10033464), 1q21 (rs13376333), and 16q22 (rs7193343).

The study results showed the primary outcome occurred in 36-60% of patients, depending on the institution, with a mean of 42%. In multivariable analysis, the presence of a chromosome 4q25 risk allele (rs2200733) was associated with arrhythmia recurrence (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.6; p = 0.011). The absolute rate of recurrence in patients with this allele versus those without was 67% vs. 55%, 38% vs. 37%, and 49% vs. 37% at the three participating centers. Moving forward, the authors speculate that such genotype-phenotype association studies might help identify optimal candidates for AF ablation by improving outcomes and reducing costs.

“Inclusion of a heterogeneous population (substrate in paroxysmal and persistent AF patients are very different), lack of a standardized ablation approach (extra-PV ablation was performed at the operator’s discretion), and monitoring protocol are significant limitations of the study,” says Aman Chugh, MD, in an ACC Journal Scan. “The ability to identify the arrhythmia mechanism(s) in a given patient, as opposed to an empiric approach, will go a long way in improving ablation outcomes in patients with AF.”


Shoemaker M, Bollmann A, Lubitz S, et al. Circ Arrhythm Electrophysiol. 2015;doi:10.1161/CIRCEP.114.001909.

Keywords: CardioSource WorldNews, ACC Publications


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