Standardized Processing of Explanted Hearts After Stereotactic Arrhythmia Radiotherapy (Bio-STAR): A STOPSTORM Framework and First Human Findings
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2026
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Abstract
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.
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| Authors | Sotirios Nedios, Judith Hüttemeister, Emanuel Heil, Petra Büttner, Kerstin Bode, Nils H. Nicolay, Franziska Nägler, Christos Moustakis, Alexey Dashkevich, Michal Nozdrzykowski, Michael A Borger, Martin Neef, Rolf Wachter, U Laufs, Tomasz Jadczyk, Bert Vandenberk, Tevfik Ismail, Ursula Rohrer, Claudia Herrera Siklódy, Moritz Sinner, Niccolo Giaj Levra, Gaetano Maria De Ferrari, Daniel Scherr, Adrian Zaman, Boldizsar Kovacs, Stephan Hohmann, Nicolaus Andratschke, Franziska Hausmann, Felix Mehrhof, Etienne Pruvot, Katja Zeppenfeld, Oliver Blanck, Gerhard Hindricks, Felix Hohendanner |
| Journal | European Heart Journal Open |
| Year | 2026 |
| DOI |
10.1093/ehjopen/oeag086
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| Keywords | Keywords not found |
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