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

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. BACKGROUND: There is a genetic background in pulmonary vein (PV) development and atrial fibrillation (AF). However, the genetic trait of PV variations and their rhythm outcome after AF catheter ablation (AFCA) is unclear. OBJECTIVE: We explored the genetic and clinical characteristics and long-term rhythm outcomes of AF patients with PV variation or left common trunkus (LCT)-PV. METHODS: We included 2,897 AF patients (74.0% male, age 59.0 ± 10.7 years, 66.3% paroxysmal AF) with available genome-wide association study results, cardiac computed tomogram data, and protocol-based regular rhythm follow-up from the Yonsei AF ablation cohort database. We defined LCT-PV when the upper and lower PV separate at >10 mm distal to the left PV antrum margin. PV variations included both LCT-PV and accessory PVs. We analyzed the polygenic risk score (PRS) of 12 AF-associated genes (DSP, GJA1, HCN4, KCNQ1, NPPA, PITX2, RYR2, SCN5a, SHOX2, ATP2A2, TBX3, and TBX5) and long-term rhythm outcomes after AFCA. RESULTS: We found PV variation in 296 (10.2%) and LCT-PV in 102 (3.5%). PRS of 1,227 single nucleotid polymorphisms (SNPs) was significantly higher in PV variation patients (p=4.93e-08) and LCT-PV patients (p=1.95e-20). The patients with LCT-PV had higher CHA2DS2VASc scores (p=0.024) and lower atrial epicardial adipose tissue volume (p=0.034). During 39.7 ± 34.8 months follow-up period, LCT-PV patients had a significantly higher recurrence rate than their counter part in the paroxysmal AF sub-group (Log-rank p=0.036), but not in overall PV variations. LCT-PV with the highest 10% PRS was independently associated with AF recurrence after AFCA (HR 2.10, 95% CI 1.21-3.63, p=0.008). CONCLUSIONS: Among the patients who underwent AFCA, PV variation, including LCT-PV, has a significant genetic background. The post-AFCA recurrence rate was significantly higher in patients with LCT-PV and high PRS, especially in paroxysmal AF. [Figure: see text] [Figure: see text]