A step towards routine for stereotactic radioablation in refractory ventricular tachycardia – interim analysis on short term safety of the first prospective, multi-centre, multi-platform study RAVENTA

Abstract

Background: Ventricular tachycardia (VT) is a potentially life-threatening heart rhythm disorder originating in heterogeneous conduction velocity in the ventricular myocardium, e.g. by scar formation in ischaemic or dilated cardiomyopathy. Current guideline-directed medical therapy comprises implantable cardioverter defibrillator (ICD), antiarrhythmic drugs, and endocardial/ epicardial catheter ablation. There is a serious recurrence rate for example due to diffuse fibrosis, progress of disease, or insufficient ablation depth or volume. In cases when Catheter ablation and antiarrhythmic medication failed to reduce VT burden, stereotactic body radiation therapy (SBRT) may become an additional treatment option. To date there have been several small retrospective case series and some single-centre prospective studies showing promising results. Purpose(s): For the purpose of obtaining the authorization of a randomized trial, a feasibility study was designed. The primary objective is to demonstrate sufficient safety of cardiac SBRT for the non-invasive treatment of VT and whether the dose needed can be delivered while sparing sensitive surrounding structures (e.g. stomach, oesophagus, vena cava, coronary arteries, ICD). Secondarily, the effect on VT burden is reported. Method(s): The RAVENTA study (RAdiosurgery for VENtricular TAchycardias) is the first prospective, multicentre study on SBRT in patients suffering from refractory VTs worldwide. Patients were enrolled according to strict inclusion criteria. First, an electrophysiology study using a high definition mapping system was performed to identify the substrate (target region). In order to plan SBRT a planning computed tomography scan was obtained. Finally, a single dose of 25 Gy was administered to the target region. Neither sedation nor anaesthesia is necessary during SBRT. Primary endpoint is feasibility defined as complete dose application and absence of severe (grade >=3) treatment-related toxicity within 30 days of treatment. RAVENTA is powered to reject the hypothesis of 70% feasibility, if in fact feasibility is 95%. This is a pre-defined interim analysis with the aim of stopping early for futility. Result(s): Between October 2019 and December 2021, the first 5 patients (characteristics shown in Table 1) could be enrolled and radiotherapy was delivered without major complications. Cardiac SBRT took on average 30 minutes. There was no treatment-related severe toxicity. Furthermore, we could not record any negative effect on functionality of the ICD: Constant sensing amplitude and pacing capture threshold. In the short-term, patients showed a clear decrease in VT burden. Conclusion(s): These preliminary data of the first multi-centre, multi-platform study on cardiac SBRT on refractory VT demonstrated sufficient short-term feasibility to continue the RAVENTA study. Meanwhile the study has been expanded to 6 centres in Germany.