Standardized processing of explanted hearts after stereotactic arrhythmia radiotherapy (Bio-STAR): a STOPSTORM framework and first human findings

Nedios, Sotirios; Hüttemeister, Judith; Heil, Emanuel; Büttner, Petra; Bode, Kerstin; Nicolay, Nils Henrik; Nägler, Franziska; Moustakis, Christos; Dashkevich, Alexey; Nozdrzykowski, Michal; Borger, Michael; Neef, Martin; Wachter, Rolf; Laufs, Ulrich; Jadczyk, Tomasz; Vandenberk, Bert; Ismail, Tevfik; Rohrer, Ursula; Herrera Siklódy, Claudia; Sinner, Moritz; Giaj Levra, Niccolò; Maria De Ferrari, Gaetano; Scherr, Daniel; Zaman, Adrian; Kovacs, Boldizsar; Hohmann, Stephan; Andratschke, Nicolaus; Hausmann, Franziska; Mehrhof, Felix; Pruvot, Etienne; Zeppenfeld, Katja; Blanck, Oliver; Hindricks, Gerhard; Hohendanner, Felix

doi:10.1093/ehjopen/oeag086

Published June 22, 2026 | Version v1

Journal article Open

Standardized processing of explanted hearts after stereotactic arrhythmia radiotherapy (Bio-STAR): a STOPSTORM framework and first human findings

1. Department of Electrophysiology, Heart Center Leipzig, University of Leipzig, Strümpellstraße 39, 04289 Leipzig, Germany
2. Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Charitéplatz 1, 10117 Berlin, Germany
3. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
4. DZHK (German Center for Cardiovascular Research), partner Site Berlin, Berlin, Germany
5. Department of Cardiology, Heart Center Leipzig at University of Leipzig, Strümpellstraße 39, 04289 Leipzig, Germany
6. Department of Radiation Oncology, University Hospital Leipzig, Stephanstraße 9a, 04103 Leipzig, Germany
7. Department of Cardiac Surgery, Leipzig Heart Center, Strümpellstraße 39, 04289 Leipzig, Germany
8. Clinic and Policlinic for Cardiology, University Hospital Leipzig, Strümpellstraße 39, 04289 Leipzig, Germany.
9. Clinic and Policlinic for Cardiology, University Hospital Leipzig, Strümpellstraße 39, 04289 Leipzig, Germany
10. Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, ul. Ziołowa 45-47, 40-635 Katowice, Poland
11. Interventional Cardiac Electrophysiology Group, International Clinical Research Center, St.Anne's University Hospital Brno, Pekařská 53, 602 00 Brno, Czech Republic
12. Department of Cardiovascular Sciences, University of Leuven, Herestraat 49, 3000 Leuven, Belgium
13. Cardiology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
14. School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Campus, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK
15. Department of Cardiology, Guy's and St Thomas' Hospitals, Westminster Bridge Road, London SE1 7EH, UK
16. Division of Cardiology, Medical University Graz, Auenbruggerplatz 15, 8036 Graz, Austria
17. Department of Cardiology, CHUV, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland
18. Department of Medicine I, University Hospital Munich, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
19. Department of Advanced Radiation Oncology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 37024 Negrar di Valpolicella, Italy
20. Division of Cardiology, Cardiovascular and Thoracic Department, Città Della Salute e Della Scienza Hospital, Corso Bramante 88/90, 10126 Torino, Italy
21. Department of Medical Sciences, University of Turin, Via Verdi 8, 10124 Torino, Italy
22. Department of Internal Medicine, Karl-Franzens-University Hospital, Auenbruggerplatz 15, 8036 Graz, Austria
23. Department of Internal Medicine III, Cardiology and Angiology, University Hospital Schleswig-Holstein, Arnold-Heller-Straße 3, 24105 Kiel, Germany
24. Department of Cardiology, Universitätsspital Zürich, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland
25. St.Bernhard Krankenhaus, Hildesheim, Treibestraße 9, 31134 Germany
26. Department of Radiation Oncology, University Hospital of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
27. Department of Radiation Oncology, Charité University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
28. Heart and Vessel Department, Service of Cardiology, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
29. Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
30. Department of Radiation Oncology, University Hospital Schleswig-Holstein Campus Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany
31. Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany

Abstract

Aims: Stereotactic arrhythmia radiotherapy (STAR) is an emerging non-invasive option for refractory ventricular tachycardia (VT); yet, the underlying myocardial effects in humans remain poorly understood. Within the STOPSTORM consortium, we developed the Bio-STAR framework for standardized ex vivo assessment of STAR-treated myocardium and here report its feasibility and initial findings in human samples.

Methods and results: Bio-STAR standardizes myocardial sampling into non-irradiated control (NFNI), minimally fibrotic irradiated, and fibrotic irradiated zones, guided by visual inspection, electroanatomical maps, and radiotherapy dose overlays. Recommended analyses span ex vivo MRI, histology, immunohistochemistry/-fluorescence, molecular panels, and live-cell assays. Application to two explanted non-ischaemic cardiomyopathy hearts (transplantation 3-5 months post-STAR) confirmed the protocol's applicability to end-stage remodelling. In exploratory analyses of irradiated regions, patient-specific patterns emerged, including stress marker upregulation, and altered NaV1.5, SERCA2a, and CaV1.2 when normalized to cardiomyocyte content. Functional analyses in a limited number of viable cardiomyocytes from the respective regions demonstrated heterogeneous excitability, supporting the feasibility of isolating live cells from STAR-treated regions in which Ca²⁺ signalling can be quantitatively assessed in future studies involving larger patient cohorts.

Conclusion: Bio-STAR provides a reproducible framework for multimodal analysis of STAR-treated myocardium, enabling harmonized cross-centre research. Early human data demonstrate that cardiomyocyte viability and isolatability are preserved across all assessed regions and that STAR-exposed areas may exhibit region-specific structural features, while functional data on Ca²⁺ handling remain exploratory and require validation in larger datasets. Broad adoption will be the key to delineating dose-time-substrate relationships and disentangling radiation effects from underlying cardiomyopathy.

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