Chromosome 4q25 variants and recurrence after second-generation cryoballoon ablation in patients with paroxysmal atrial fibrillation

Abstract

BackgroundChromosome 4q25 single-nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation, however the underlying mechanism is unknown. Pulmonary vein (PV) reconnections are common post-radiofrequency ablation. We explored the pre-procedural parameters, including AF susceptibility SNPs, predicting the response to PV isolation (PVI) using second-generation cryoballoons. MethodsOne hundred fifty-seven paroxysmal AF patients undergoing PVI using second-generation cryoballoons and genetic testing were enrolled. The top 6 AF-associated Japanese ancestry SNPs were evaluated. Fourteen-day consecutive monitoring was performed to detect AF recurrences. ResultsEarly recurrence of AF (ERAF) was detected in 74(47.1%) patients, and the AF-free survival at 12-months after single procedures was 72.1%. Cox's proportional models determined that higher pro-BNP values (hazard ratio [HR]=1.001; 95% confidence interval [CI]=1.000–1.001; p=0.003) and the rs1906617 risk allele (HR=2.440; 95% CI=1.062–5.605; p=0.035) were independently associated with ERAFs, and the rs1906617 risk allele (HR=4.339; 95% CI=1.044–18.028; p=0.043) was the sole factor significantly associated with AF recurrence. Second procedures were performed in 41 patients a median of 6.0[5.0–9.5] months later, and 42/162(25.9%) PVs were reconnected. Reconnections were similarly observed in rs1906617 risk allele carriers and wild-type patients. Risk allele carriers at rs1906617 were more likely to have non-PV foci, but did not reach statistical significance (10/35 vs. 0/6, p=0.132). ConclusionsAF risk alleles on chromosome 4q25 modulated the risk of AF recurrence after PVI using second-generation cryoballoons in patients with paroxysmal AF. Our study results suggested that non-PV foci might be the more likely mechanism of a high AF recurrence in chromosome 4q25 variant carriers.