Digital twin virtual atrial fibrillation dynamics predict clinical atrial arrhythmia recurrence after catheter ablation

Abstract

The maximal slope of the action potential duration restitution curve (Smax) reflects electrical instability and relates to fibrillation maintenance. However, the clinical significance of digital twin–derived high-density (HD) Virtual Restitution properties and Virtual atrial fibrillation (AF) sustainability in patients undergoing AF catheter ablation (AFCA) remains unclear. To determine whether digital twin–derived left atrial (LA) HD-Virtual Restitution patterns (>0.4 million nodes) and Virtual AF sustainability are associated with Clinical atrial arrhythmia (AA) recurrence after AFCA. We included 323 patients undergoing AFCA (76.2% male, 60.6±9.9 years old, 78.6% persistent AF). Using bipolar electroanatomical mapping data (>1,000 points), we constructed patient-specific LA digital twin models and evaluated the relationships among low voltage area (LVA <0.5 mV) burden, Virtual AF sustainability, and quantified HD-Virtual Restitution properties. Patients with LVA ≥40% and mean Smax <1 were considered the Extremely Remodeled group (n=32) and evaluated separately in downstream analyses, given their deviation from the overall LVA–Smax relationship. Among the remaining 291 patients, Virtual Restitution patterns were classified into Overall-Low, Average-Homogeneous, Average-Heterogeneous, and Overall-High Smax, and Virtual AF sustainability was grouped into Sustained and Non-sustained groups. Virtual AF was Sustained in 79.9% and Non-sustained in 20.1%. Virtual AF sustainability was similar across the four Smax patterns (p=0.290). In multivariable Cox models using the Extremely Remodeled group as the reference, Non-sustained Virtual AF was independently associated with a significantly lower risk of clinical recurrence (aHR 0.18, 95% CI 0.06–0.55; p=0.003). The Overall-Low (aHR 0.31, 95% CI 0.12–0.85; p=0.022) and Average-Homogeneous Smax patterns (aHR 0.48, 95% CI 0.24–0.95; p=0.036) were independently associated with lower clinical AA recurrence. The Extremely Remodeled group was significantly older, more frequently female, had larger LA size, and higher E/e′. Despite significantly lower Virtual AF sustainability (15.6% vs 86.9%; p<0.001) and Smax <1, this group showed higher Clinical AA recurrence, but mostly AT recurrence (6/15, 40%) than others (Log rank p=0.003). Digital twin–derived restitution patterns and Virtual AF sustainability increased Harrell’s C-index beyond clinical covariates for Clinical AA recurrence by 0.044 (p=0.034). Patient-specific digital twin–derived HD-Virtual Restitution patterns and Virtual AF sustainability were associated with Clinical AA recurrence after AFCA. However, the Extremely Remodeled subgroup with a large LVA burden exhibited discordant behavior due to a low critical mass.Figure1_ESCFigure 2