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

Abstract 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. Although catheter-based radiofrequency ablation is the state-of-the-art treatment for VT, its success in ARVC is limited by high recurrence rates. Here, we present Genotype-specific Digital-twin Ablation Targeting (GenDIRECT), a personalized, non-invasive technology that predicts, prior to the clinical procedure, the optimal VT ablation targets using patient-specific heart digital twins. The GenDIRECT-predicted target set is devised to eliminate, with minimum lesion size, the ability of the ARVC ventricles to sustain any reentrant arrhythmias. Comparison of GenDIRECT target lesions with the clinical ablation lesions demonstrated excellent co-localization in both ARVC patients who had undergone index ablation and in those with redo procedures many months later, regardless of genotype. Thus, should GenDIRECT be used to guide clinical procedures, it is expected that existing VTs will be terminated, and post-ablation arrhythmias will be prevented, thereby increasing the efficacy of the ablation procedure and reducing redo procedures and re-hospitalization.