Genetic background of sinus node dysfunction requiring permanent pacemaker implantation after atrial fibrillation catheter ablation

Abstract

Funding Acknowledgements Type of funding sources: None. Introduction Atrial fibrillation catheter ablation (AFCA) improves sinus node function and may defer a permanent pacemaker (PPM) implantation. We explored the clinical and genetic characteristics of the patients with AF and sinus node dysfunction (SND) who eventually needed PPM implantation after AFCA. Methods Among 2,732 AF patients with genome-wide association study (GWAS, PMRA, Thermofisher scientific, MA, USA) data who underwent the first AFCA, 244 patients (65.0, IQR [59.0, 72.0] years, male 58.2%, paroxysmal AF 79.5%) had underlying SND before AFCA (class I indication for PPM). We retrospectively investigated clinical factors, single-nucleotide polymorphisms (SNPs), and their polygenic risk score (PRS) associated with PPM-AFCA. We defined the cut-off of PRS using the Youden index. Results During median 37.9 (IQR 20.3-77.9) months follow-up, 36 out of 244 patients (16.1%) with underlying SND eventually underwent PPM implantation after AFCA (PPM-AFCA). PPM-AFCA group a had a higher body mass index (p=0.013) and large left atrial (LA) dimension (p=0.006) than their counterpart. Among 44 SNPs related to AF and SND, the rs3922844 (p=0.003) near SCN5A and rs9320841 (p=0.011) and rs1015451 (p=0.046) near CJA1 were significantly associated with PPM-AFCA. The rate of PPM-AFCA implantation was significantly higher in the high PRS group (≥1.175, 25.6%) compared to the low PRS group (<1.175, 9.38%, p=0.002, Log-rank p=0.002). LA dimension (adjusted HR 1.06, 95% CI [1.00-1.13], p=0.044) and PRS (adjusted HR 2.69, 95% CI [1.68-4.31], p<0.001) were associated with a higher risk for PPM-AFCA after adjusting clinical factors including age, sex, AF type, beta blocker, and antiarrhythmic drugs after AFCA. Conclusions In AF patients with SND, 16% with the genetic background of SCN5A and CJA1 or large atrium eventually needed PPM implantation after AFCA.