Left common trunkus pulmonary veins have genetic background and poorer rhythm outcome after paroxysmal atrial fibrillation catheter ablation

Background The genetic traits of pulmonary vein (PV) variants and rhythm outcomes after atrial fibrillation (AF) catheter ablation (AFCA) remain unclear. We explored the genetic and clinical characteristics and long-term rhythm outcomes of patients with AF and left common trunkus (LCT)-PVs or accessory PVs. Methods We included 2,829 patients with AF (74.0% men, age 59.1±10.7 years, 66.3% paroxysmal AF) and available genome-wide association study, cardiac computed tomography, and protocol-based regular rhythm follow-up results from the Yonsei AF ablation cohort database. We examined 1,223 single nucleotide polymorphisms in 12 genetic loci associated with AF and long-term rhythm outcomes after AFCA. Results We found LCT-PVs in 91(3.2%) and accessory PVs in 189(6.7%) patients. Rs9871453 ( SCN10A ) and rs1979409 ( NEO1 ) were significantly associated with LCT-PV occurrence, and polygenic risk score (PRS) differed significantly between patients with LCT-PVs (p=1.64e-05) and normal PVs, but not those with accessory PVs (p=0.939). Patients with LCT-PVs had a higher proportion of the female sex(p=0.046) and CHA2DS2VASc score (p=0.026). After follow-up for 39.7±4.7 months, patients with LCT-PVs exhibited significantly greater LCT anterior wall thicknesses (p<0.001) and higher recurrence rate than those with normal PVs, particularly patients with paroxysmal AF (log-rank, p=0.042). LCT-PVs were independently associated with AF recurrence after AFCA (hazard ratio[HR], 2.26 [1.01–4.42]; p=0.046). Patients with LCT-PVs and higher PRSs had a higher risk of recurrent AF (adjusted HR 1.78, 95% CI 1.10–2.88, p=0.019). Conclusions Patients with LCT-PVs have a significant genetic background. Post-AFCA recurrence rate was significantly higher in patients with LCT-PVs and higher PRSs, particularly in those with paroxysmal AF. What Is New? This study identifies specific genetic variants associated with the occurrence of LCT-PVs in AF patients undergoing catheter ablation. Higher AF recurrence rates were observed in LCT-PV patients, particularly those with paroxysmal AF. High-genetic risk LCT-PV patients exhibited increased AF recurrence and a thicker anterior wall of the left pulmonary vein compared to normal PV patients. What Are the Clinical Implications? The findings enhance our understanding of the genetic basis of AF and its anatomical manifestations, enabling personalized treatment approaches. Further research is needed to identify additional genetic variants associated with LCT-PV and to understand the recurrence of AF when using methods other than catheter ablation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a grant [HI21C0011] from the Ministry of Health and Welfare and a Korea Medical Device Development Fund grant [Project number 1711174471; RS-2022-00141473] funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, Ministry of Health & Welfare, and Ministry of Food and Drug Safety of the Korean government. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of the Yonsei University Health System I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying this article will be shared on reasonable request to the corresponding author. * AAD : Anti-arrhythmic drug AF : Atrial fibrillation AFCA : AF catheter ablation CPVI : Circumferential pulmonary vein isolation CT : Computed tomography ECG : Electrocardiography/electrocardiogram LA : Left atrium/atrial LAVI : Left atrial volume index LCT : left common trunkus LV : Left ventricle/ventricular PV : Pulmonary vein PRS : Polygenic risk score