Background and Aim: AF recurrence after ablation is a major clinical challenge driven by heterogeneous atrial remodeling not fully captured by single-domain predictors. Current models typically evaluate structural or electrical parameters in isolation, limiting predictive accuracy and interpretability. We propose a Multidomain Atrial Damage Index (MADI), a structured phenotyping framework, and evaluate its association with one-year AF recurrence.
Methods: In a retrospective cohort of 143 patients undergoing first-time AF ablation, MADI (composite score 0–8) integrated four domains: electrical substrate (voltage quintiles from high-density mapping), geometric remodeling (CT-derived volume tertiles), diabetes mellitus, and AF type. Patients were stratified into Stage 1 (≤2), Stage 2 (3–5), and Stage 3 (≥6).
Results: Recurrence increased with stage, most markedly in Stage 3: 28% (14/50) in Stage 1, 32% (22/68) in Stage 2, and 68% (17/25) in Stage 3 (Stage 2 vs 3, p=0.002). Discriminative performance was modest (AUC=0.646, 95% CI 0.55–0.74; OR=1.29, 95% CI 1.08–1.52). Joint phenotype analysis identified E4+G1 (advanced electrical remodeling, intermediate geometric dilation) as the highest-recurrence subgroup (71%, 5/7).
Conclusions: MADI enables interpretable multidomain phenotyping of AF patients. Recurrence rose sharply with cumulative remodeling burden, and specific electrical-geometric interactions were associated with disproportionate risk. This proof-of-concept framework warrants validation in larger, prospective, multi-center cohorts.