Genotype-specific digital twins for arrhythmia ablation targeting in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a severe genetic heart disease that predominantly affects young athletic individuals and carries a high risk of ventricular tachycardia (VT) and sudden cardiac death. Catheter-based radiofrequency ablation is the state-of-the-art treatment for VT; however, its effectiveness in ARVC is limited by high recurrence rates. This study aims to develop a personalized approach to improve ablation outcomes in ARVC.

We developed a non-invasive digital twin-based framework, termed GenDIRECT, that simulates cardiac electrical activity on patient-specific heart models to predict the optimal VT ablation targets. This retrospective study included 30 patients with ARVC of two common ARVC genotypes (GE and PKP2). Among them, 25 underwent a single clinical ablation, and 5 had repeat ablation within 12 months of the initial ablation. Predicted targets were compared with clinically delivered ablation lesions in patients who underwent initial and/or repeat procedures.

Here, we show that GenDIRECT-predicted ablation targets closely align with clinical ablation lesions (Dice score = 89.47%) in patients with successful initial procedures (n = 25) and are associated with significantly smaller lesion volumes (p = 5.39*10^-5). In patients with VT recurrence requiring repeat procedures (n = 5), predicted targets correspond to the combined lesions from both initial and repeat ablations. GenDIRECT-guided ablation targets eliminate VT inducibility in all simulations.

GenDIRECT has the potential to guide clinical VT ablation procedures in ARVC by identifying comprehensive patient-specific targets. This approach may improve procedural efficacy, reduce arrhythmia recurrence, and decrease the need for repeat ablation and subsequent hospitalizations.