Browse the corpus

Patients with myocardial infarction history are at increased risk for ventricular tachycardia (VT).1 Catheter ablation reduces VT,2 yet current strategies increase the risk of hemodynamic instability and lead to inaccurate ablation targets and extensive lesions. Medical digital twins are mechanistic computational models of organs that mimic system behavior and have predictive capabilities. Our team developed a patient-specific heart digital twin capable of evaluating arrhythmogenic propensity to guide ablation procedures with minimal lesions.3–5 We conducted the TWIN-VT study, a Food and Drug Administration (FDA) investigational device (G180087/A001) exemption clinical trial (NCT03536052) to prospectively test the heart digital twin’s ability to guide ischemic VT ablation procedures. The FDA limited the study to one institution in the United States and 10 subjects. The Johns Hopkins Institutional Review Board approved the study and all participants signed informed consent.

n clinical trial (NCT03536052) to prospectively test the heart digital twin’s ability to guide ischemic VT ablation procedures. The FDA limited the study to one institution in the United States and 10 subjects. The Johns Hopkins Institutional Review Board approved the study and all participants signed informed consent. Participants underwent a contrast-enhanced cardiac MRI to generate a cardiac digital twin reflecting the distribution of structural remodeling. Rapid pacing established VT circuits, whose critical components were then targeted for virtual ablation to render the digital twin non-inducible (Supplementary Video available online with the full text of this Letter to the Editor at NEJM.org and Figure 1). The digital twin predicted targets were imported into the electroanatomical mapping system to guide clinical ablation. Ventricular tachycardia was induced via programmed stimulation, and radiofrequency ablation was performed to each digital twin ablation location. Following ablation of all digital twin targets, repeat VT induction was performed. The primary end point of VT non-inducibility was adjudicated by the operator.

cal ablation. Ventricular tachycardia was induced via programmed stimulation, and radiofrequency ablation was performed to each digital twin ablation location. Following ablation of all digital twin targets, repeat VT induction was performed. The primary end point of VT non-inducibility was adjudicated by the operator. Baseline characteristics are summarized in Table S1 in the Supplementary Appendix available online at NEJM.org. The representativeness of the trial population is shown in Table S2. Eight of ten participants had inducible VT, and all underwent successful digital twin-guided ablation. Seven participants underwent programmed stimulation following ablation of digital twin targets. Programmed stimulation after ablation was not performed in one participant due to hemodynamic instability concerns. Six of the 7 patients were rendered non-inducible following ablation of digital twin targets. The one participant with inducible VT following digital twin-guided ablation in the left ventricular septum was non-inducible for VT following ablation on the right ventricular septum at the digital twin target (Fig. S2). All 10 participants were non-inducible for any VT at the end of the procedure. There were no periprocedural complications.

inducible VT following digital twin-guided ablation in the left ventricular septum was non-inducible for VT following ablation on the right ventricular septum at the digital twin target (Fig. S2). All 10 participants were non-inducible for any VT at the end of the procedure. There were no periprocedural complications. Over a mean follow-up period of 405.4 days (range, 90 to 909 days), 8 of 10 participants remained free of VT off anti-arrhythmic drug therapy. Of the two participants with a recurrence of VT, both experienced one episode of VT that terminated with antitachycardia pacing within one month of ablation. They remain free of VT and their anti-arrhythmic drug therapy has been de-escalated (Table S3). No participant received an implantable-cardioverter defibrillator shock. This study demonstrates the feasibility and clinical outcomes of utilizing personalized heart digital twins to guide clinical VT ablation.