Standardized Processing of Explanted Hearts After Stereotactic Arrhythmia Radiotherapy (Bio-STAR): A STOPSTORM Framework and First Human Findings
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, electro-anatomical 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 remodeling. 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 key to delineating dose–time–substrate relationships and disentangling radiation effects from underlying cardiomyopathy.
Authors
- Martin Neef
- Emanuel Heil (ORCID: https://orcid.org/0000-0001-9782-8311)
- Boldizsar Kovacs (ORCID: https://orcid.org/0000-0002-7972-5199)
- Adrian Zaman
- Christos Moustakis (ORCID: https://orcid.org/0000-0002-8879-2350)
- Sotirios Nedios (ORCID: https://orcid.org/0000-0003-4222-6633)
- Tomasz Jadczyk (ORCID: https://orcid.org/0000-0002-7955-9100)
- Felix Hohendanner (ORCID: https://orcid.org/0000-0002-0194-4615)
- Kerstin Bode (ORCID: https://orcid.org/0000-0002-1657-7897)
- Ursula Rohrer (ORCID: https://orcid.org/0000-0002-5278-6362)
- Nils H. Nicolay (ORCID: https://orcid.org/0000-0003-2550-1410)
- Franziska Nägler
- Judith Hüttemeister
- Michal Nozdrzykowski
- Alexey Dashkevich (ORCID: https://orcid.org/0000-0001-6166-7210)
- Franziska Hausmann
- U Laufs
- Tevfik Ismail
- Etienne Pruvot
- Moritz Sinner (ORCID: https://orcid.org/0000-0002-6660-796X)
- Felix Mehrhof
- Stephan Hohmann
- Gaetano Maria De Ferrari
- Katja Zeppenfeld (ORCID: https://orcid.org/0000-0001-6645-082X)
- Gerhard Hindricks (ORCID: https://orcid.org/0000-0002-0132-0773)
- Claudia Herrera Siklódy (ORCID: https://orcid.org/0000-0001-6881-3073)
- Nicolaus Andratschke (ORCID: https://orcid.org/0000-0003-3647-5916)
- Rolf Wachter (ORCID: https://orcid.org/0000-0003-2231-2200)
- Petra Büttner (ORCID: https://orcid.org/0000-0003-0799-4725)
- Bert Vandenberk (ORCID: https://orcid.org/0000-0001-8296-920X)
- Oliver Blanck (ORCID: https://orcid.org/0000-0003-1391-1308)
- Michael A Borger (ORCID: https://orcid.org/0000-0003-1046-1364)
- Niccolo Giaj Levra
- Daniel Scherr (ORCID: https://orcid.org/0000-0001-5868-5493)
Institutions
- St Thomas' Hospital (GB)
- University of Graz (AT)
- Medical University of Silesia (PL)
- Medical University of Graz (AT)
- Leiden University Medical Center (NL)
- Centre Hospitalier Universitaire Vaudois (CH)
- Humboldt-Universität zu Berlin (DE)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- University Hospital of Zurich (CH)
- Ospedale Sacro Cuore Don Calabria (IT)
- Deutsches Herzzentrum der Charité (DE)
- St. Bernward Krankenhaus (DE)
- Department of Medical Sciences (RU)
- University Hospital Schleswig-Holstein (DE)
- Leipzig Heart Institute (DE)
- University Hospital Leipzig (DE)
- German Centre for Cardiovascular Research (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Lübeck (DE)
- University of Lausanne (CH)
- KU Leuven (BE)
Publication Details
- Journal
- European Heart Journal Open
- Published
- 2026-05-21
- DOI
- https://doi.org/10.1093/ehjopen/oeag086
- Primary Topic
- Cardiac Arrhythmias and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00