Interim efficacy analysis of the phase 2 dose de-escalation trial of stereotactic arrhythmia radioablation for ventricular tachycardia (StAR-VT)

Abstract Background Cardiac radioablation (CRA) for refractory ventricular tachycardia (VT) was introduced in 2017 following the success of the ENCORE-VT trial (1). The current standard of care radiation therapy dose is 25 Gy in 1 fraction, however, the optimal therapeutic dose is being explored. Previous studies have shown fibrosis, reduced bipolar voltage, and scar formation in areas treated with radioablation at doses above 15 Gy. A study suggest that CRA upregulates connexin-43 and sodium channel, NaV1.5, thereby enhancing conduction velocity through cellular reprogramming, even at lower doses (2). Aim In this interim analysis of a single institution, phase 2, dose de-escalation clinical trial, we report the early efficacy in managing refractory ventricular tachycardia. Methods Eligible patients with ischemic or non-ischemic cardiomyopathy experiencing recurrent, monomorphic VT unresponsive to standard medical therapy were offered participation in the study. Patients unable to undergo or contraindicated to invasive electrophysiology study were included if their arrhythmic substrate could be identified non-invasively. Exclusion criteria included prior thoracic radiation therapy, active connective tissue disease, or interstitial pulmonary fibrosis. The CRA workflow is summarised in Figure A. Implantable defibrillators were programmed at the physician’s discretion, with an anti-tachycardia pacing (ATP) zone set, typically set 20 msec slower than the documented arrhythmia. Following treatment, a 6-week blanking period was allowed. During this blanking period, arrhythmia events were tracked but were not included in the efficacy analysis. Follow-ups, including device interrogation, were conducted at 6 weeks, 3 and 6 months. Results Five patients (4 males [80%], mean age 77 ± 3.2 years) have received CRA of 20 Gy in 1 fraction. The median left ventricular ejection fraction was 25% (range 19%-35%). Four patients had an ischemic substrate, and one had a non-ischemic substrate (valvular disease). The average planning target volume was 187.5 ml (IQR 95.9–209.3 ml). After a median follow-up of 6 months, four patients remained stable, and one patient died (secondary to septic shock). Two patients had recurrent VT, one of which presented as a VT storm within the 6-week blanking period but subsequently stabilised. The total VT burden, defined as any sustained VT episodes requiring ICD therapies (both ATP and/or shocks), decreased significantly from 14 episodes to 1 (p = 0.042; Graph A). Episodes requiring an ICD shock reduced from 6 to 0, while those requiring ATP decreased from 14 to 1. VT storm events decreased from 3 to 0. Conclusion This interim analysis demonstrates that a 20 Gy dose effectively reduces VT burden. Preliminary efficacy results for a single 20 Gy dose of CRA are promising; however, data remain too limited for definitive conclusions.Figure A:Workflow for CRA Graph A:6-month ventricular arrhythmia