Stage-dependent predictors of atrial fibrillation recurrence after catheter ablation: a proof-of-concept analysis

Abstract

Risk models for atrial fibrillation (AF) recurrence after catheter ablation apply the same predictor structure to every patient. This overlooks the biological differences between early and advanced disease. We examined whether the clinical predictors of 12-month recurrence differ across four disease-stage phenotypes. This retrospective cohort study enrolled 419 consecutive patients who underwent first-time radiofrequency ablation at Xiangya Hospital, Central South University, between October 2021 and June 2024. The institutional protocol was pulmonary vein isolation (PVI) alone, and patients undergoing concurrent left atrial appendage occlusion were excluded. Patients were classified by AF type and duration into four groups: early paroxysmal (Phenotype 1, ≤ 12 months, n  = 225), long-standing paroxysmal (Phenotype 2, > 12 months, n  = 86), recent-onset persistent (Phenotype 3, ≤ 18 months, n  = 62), and long-duration persistent AF (Phenotype 4, > 18 months, n  = 46). We performed phenotype-specific logistic regression, predictor × phenotype interaction testing, Kaplan–Meier and restricted mean survival analysis, and ROC analysis. Twelve-month recurrence occurred in 88 patients (21.0%) and differed significantly across phenotypes (17.3%, 20.9%, 16.1%, and 45.7% in P1–P4; p  < 0.001). Recurrence-free survival was worst in P4 (log-rank p  < 0.001). In the overall model (AUC 0.672), the independent predictors were persistent AF type, longer duration, and hypertension, the last associated with lower recurrence. Phenotype-specific models revealed distinct profiles, and the sex × phenotype interaction was formally significant ( p  = 0.0042). In P1, younger age was the only predictor (AUC 0.701). In P3, female sex and hypertension were apparent predictors (apparent AUC 0.862; recurrence 43.8% in women vs. 6.5% in men), although this estimate is subject to optimism given only 10 events. In P4, no clinical variable was associated with recurrence despite its 45.7% rate, though power was insufficient to exclude moderate associations. The protective direction of hypertension strengthened across P1–P3 before disappearing in P4. In this exploratory, single-center analysis, the clinical predictors of post-ablation AF recurrence appeared to shift across the four disease-stage phenotypes, with formal statistical support for sex. We propose the Predictor Lifecycle as a testable hypothesis for prospective, multicenter validation. These findings are hypothesis-generating and do not constitute a validated risk-stratification framework for clinical use.