# Genotype-specific Digital Twins for Arrhythmia Ablation Targeting in Arrhythmogenic Right Ventricular Cardiomyopathy

**Authors:** Yingnan Zhang, Adityo Prakosa, Kelly Zhang, Richard Carrick, Jonathan Chrispin, Stefan L Zimmerman, Konstantinos Aronis, Eugene G. Kholmovski, Crystal Tichnell, Brittney Murray, Cynthia James, Hugh Calkins, Natalia Trayanova

PMC · DOI: 10.21203/rs.3.rs-8006874/v1 · Research Square · 2025-11-05

## TL;DR

A new digital twin technology called GenDIRECT predicts optimal ablation targets for heart disease patients, improving treatment outcomes and reducing repeat procedures.

## Contribution

GenDIRECT introduces a personalized, non-invasive method for predicting ablation targets in ARVC patients using digital twins.

## Key findings

- GenDIRECT targets co-localize with clinical ablation lesions in ARVC patients.
- The method is effective for both initial and redo ablation procedures.
- Using GenDIRECT could reduce arrhythmia recurrence and re-hospitalizations.

## 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.

## Linked entities

- **Diseases:** Arrhythmogenic Right Ventricular Cardiomyopathy (MONDO:0016587), ventricular tachycardia (MONDO:0005477), sudden cardiac death (MONDO:0007264)

## Full-text entities

- **Diseases:** genetic heart disease (MESH:D006331), sudden cardiac death (MESH:D016757), ARVC (MESH:D019571), VT (MESH:D017180), arrhythmias (MESH:D001145)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12637826/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12637826/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12637826/full.md

---
Source: https://tomesphere.com/paper/PMC12637826