Radiosurgery for Ventricular Tachycardia (RAVENTA): Subgroup Analysis for a German Multicenter Multiplatform Feasibility Trial

A. Zaman (Kiel)¹, D. Krug (Kiel)², M. Grehn (Kiel)², J. Boda-Heggemann (Mannheim)³, B. Rudic (Mannheim)⁴, F. Mehrhof (Berlin)⁵, L.-H. Boldt (Berlin)⁶, S. Hohmann (Hildesheim)⁷, R. Merten (Hannover)⁸, D. Rades (Lübeck)⁹, J. Vogler (Hamburg)¹⁰, S. Corradini (München)¹¹, M. F. Sinner (München)¹², O. Wittenstein (Kiel)², D. Buergy (Mannheim)³, F. Hohendanner (Berlin)¹³, F.-A. Siebert (Kiel)², A. Schweikard (Lübeck)¹⁴, C. G. Veltmann (Bremen)¹⁵, D. Duncker (Hannover)¹⁶, G. Hindricks (Berlin)¹⁷, J. Dunst (Kiel)², D. Frank (Kiel)¹, E. Lian (Kiel)¹, R. R. Tilz (Lübeck)¹⁸, O. Blanck (Kiel)^2
1Universitätsklinikum Schleswig-Holstein Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin Kiel, Deutschland; ²Universitätsklinikum Schleswig-Holstein Klinik für Strahlentherapie Kiel, Deutschland; ³Universitätsmedizin Mannheim Klinik für Strahlentherapie und Radioonkologie Mannheim, Deutschland; ⁴Universitätsklinikum Mannheim GmbH I. Medizinische Klinik Mannheim, Deutschland; ⁵Charité - Universitätsmedizin Berlin Kaufmännische Centrumsleitung, Charité Centrum 14 Berlin, Deutschland; ⁶Charité - Universitätsmedizin Berlin CC11: Med. Klinik m.S. Kardiologie Berlin, Deutschland; ⁷St. Bernward Krankenhaus Med. Klinik I - Kardiologie Hildesheim, Deutschland; ⁸Medizinische Hochschule Hannover Klinik für Strahlentherapie Hannover, Deutschland; ⁹Universitätsklinikum Schleswig-Holstein Klinik für Strahlentherapie Lübeck, Deutschland; ¹⁰Asklepios Klinik St. Georg Kardiologie & internistische Intensivmedizin Hamburg, Deutschland; ¹¹Ludwig-Maximilians-Universität München, Klinikum der LMU Klinik für Strahlentherapie und Radioonkologie München, Deutschland; ¹²LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ¹³Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin | CBF Berlin, Deutschland; ¹⁴Universität zu Lübeck Institut für Robotik und kognitive Systeme Lübeck, Deutschland; ¹⁵Elektrophysiologie Bremen Lilienthal, Deutschland; ¹⁶Medizinische Hochschule Hannover Klinik für Kardiologie und Angiologie Hannover, Deutschland; ¹⁷Charité - Universitätsmedizin Berlin CC11: Med. Klinik m. S. Kardiologie und Angiologie Berlin, Deutschland; ¹⁸Universitätsklinikum Schleswig-Holstein Klinik für Rhythmologie Lübeck, Deutschland

Background
Stereotactic Arrhythmia Radioablation (STAR) has been used as a bail-out treatment strategy for patients with refractory ventricular tachycardia (VT). We now report a subgroup analysis for patients with non-ischemic (NIC) and ischemic (IC) cardiomyopathy in the multicenter RAdiosurgery for VENtricular TAchycardia (RAVENTA) study (NCT03867747) as part of the STOPSTORM project (EU-Horizon-2020 Grand No. 945119).

Methods
Between 11/2019 and 10/2023, 20 patients (male: 17, female: 3; age: 49-84 [median: 64] years; prior catheter ablations: 0-8 [median 2.5]; left ventricular ejection fraction [LVEF]: 10-60% [median: 31.5%]) were treated at six German university centers. Eleven patients had NIC and nine patients had IC as precondition, respectively. Median cardiac target volume (CardTV_EP/IMG) was 20.5 ml (range: 7.0-64.9 ml) and 14.9 ml (range: 6.0-87.8 ml) in the NIC and IC group, and median planning target volume (PTV) was 80.1 ml (range: 39.9-144.3 ml) and 44.4 ml (range: 31.7-113.2 ml) in the NIC and IC group, respectively. Prescription dose was 25 Gy in all cases with median PTV near minimum/maximum doses of 24.6/29.5 Gy and 24.6/29.6 Gy in the NIC and IC group, respectively. The primary endpoint of the study was safety, and secondary endpoints included the occurrence of VT and treatment-related toxicity up to one year after treatment.

Results
All treatments were successfully completed and no possibly treatment-related severe periprocedural complications were noted in the first 30 days after STAR (primary endpoint). Three patients died during follow-up, two in the NIC group, one in electrical storm at 7 weeks and one from underlying heart disease at 10 months, and one in the IC group from retroperitoneal hemorrhage at 8 months. One patient in the NC group received a heart transplant directly after STAR and one patient in the NIC group developed the only grade ≥ 3 toxicity possibly related to STAR and required a heart transplantation at 7 months after STAR due to progression of the heart disease 2 months after treatment (both alive at study end). Fifteen patients reached the regular study end at one year, fourteen of them VT free, ten without further intervention after STAR, with an overall median LVEF of 34.5% (range: 27-55%), separated to the NIC and IC group in Figure 1. Overall, six patients required further catheter/alcohol ablation or sympathectomy (three in each NIC and IC group), four of them with recurrences in or near the STAR treatment locations (three in the NIC and one in the IC group), resulting in a total local efficacy (freedom from index VT) of 50.0% (4/8) for the NIC group and of 85.7% (6/7) in the IC group (Figure 2).

Conclusion
RAVENTA is the world's first multicenter multiplatform study of STAR for patients with refractory VT. Possibly treatment-related side effects were mild, regardless of the underlying heart diseases. Higher increase in LVEF and higher reductions in VT burden were noted for patients with ischemic cardiomyopathy who generally had lower LVEF and higher VT burden before STAR as compared to patients with non-ischemic cardiomyopathy. Analysis in larger cohorts and further optimization of the target definition for non-ischemic cardiomyopathy is warranted. 

Figures

Figure 1: LVEF before and after STAR in the NIC (left) and IC (right) group


Figure 2: VT burden before and after STAR in the NIC (top) and IC (bottom) group. § Slow VT; ((_)) Heart Transplant, + Ablation/Intervention; † Death.