Standardized processing of explanted hearts after stereotactic arrhythmia radiotherapy (Bio-STAR): a STOPSTORM framework and first human findings
European Heart Journal Open, vol. 6, pp. oeag086
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, 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.
Authors 34
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Affiliation as printed
Department of Electrophysiology, Heart Center Leipzig, University of Leipzig , Strümpellstraße 39, 04289 Leipzig ,
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Humboldt-Universität zu Berlin · Deutsches Herzzentrum der Charité · German Centre for Cardiovascular Research · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
DZHK (German Center for Cardiovascular Research), partner Site Berlin , Berlin ,
Deutsches Herzzentrum der Charité , Department of Cardiology, Angiology and Intensive Care Medicine, Charitéplatz 1, 10117 Berlin ,
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Humboldt-Universität zu Berlin · Deutsches Herzzentrum der Charité · German Centre for Cardiovascular Research · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
DZHK (German Center for Cardiovascular Research), partner Site Berlin , Berlin ,
Deutsches Herzzentrum der Charité , Department of Cardiology, Angiology and Intensive Care Medicine, Charitéplatz 1, 10117 Berlin ,
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Leipzig Heart Institute · University Hospital Leipzig · Leipzig University
Affiliation as printed
Department of Cardiology, Heart Center Leipzig at University of Leipzig , Strümpellstraße 39, 04289 Leipzig ,
Department of Radiation Oncology, University Hospital Leipzig , Stephanstraße 9a, 04103 Leipzig ,
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Affiliation as printed
Department of Electrophysiology, Heart Center Leipzig, University of Leipzig , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Department of Radiation Oncology, University Hospital Leipzig , Stephanstraße 9a, 04103 Leipzig ,
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Affiliation as printed
Department of Radiation Oncology, University Hospital Leipzig , Stephanstraße 9a, 04103 Leipzig ,
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Affiliation as printed
Department of Radiation Oncology, University Hospital Leipzig , Stephanstraße 9a, 04103 Leipzig ,
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Affiliation as printed
Department of Cardiac Surgery, Leipzig Heart Center , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Department of Cardiac Surgery, Leipzig Heart Center , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Department of Cardiac Surgery, Leipzig Heart Center , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Clinic and Policlinic for Cardiology, University Hospital Leipzig , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Clinic and Policlinic for Cardiology, University Hospital Leipzig , Strümpellstraße 39, 04289 Leipzig ,
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Affiliation as printed
Clinic and Policlinic for Cardiology, University Hospital Leipzig , Strümpellstraße 39, 04289 Leipzig ,
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Medical University of Silesia · International Clinical Research Center, St. Anne's University Hospital Brno
Affiliation as printed
Department of Cardiology and Structural Heart Diseases, Medical University of Silesia , ul. Ziołowa 45-47, 40-635 Katowice ,
Interventional Cardiac Electrophysiology Group, International Clinical Research Center, St.Anne’s University Hospital Brno , Pekařská 53, 602 00 Brno ,
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Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Cardiology, University Hospitals Leuven , Herestraat 49, 3000 Leuven ,
Department of Cardiovascular Sciences, University of Leuven , Herestraat 49, 3000 Leuven ,
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St Thomas' Hospital · King's College London · Guy's and St Thomas' NHS Foundation Trust
Affiliation as printed
Department of Cardiology, Guy’s and St Thomas’ Hospitals , Westminster Bridge Road, London SE1 7EH ,
School of Biomedical Engineering and Imaging Sciences, King’s College London , St Thomas’ Campus, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH ,
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St Thomas' Hospital · King's College London · Medical University of Graz
Affiliation as printed
Division of Cardiology, Medical University Graz , Auenbruggerplatz 15, 8036 Graz ,
School of Biomedical Engineering and Imaging Sciences, King’s College London , St Thomas’ Campus, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH ,
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Centre Hospitalier Universitaire Vaudois
Affiliation as printed
Department of Cardiology, CHUV, Lausanne University Hospital , Rue du Bugnon 46, 1011 Lausanne ,
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LMU Klinikum · Ludwig-Maximilians-Universität München
Affiliation as printed
Department of Medicine I, University Hospital Munich, Ludwig Maximilians University , Marchioninistr. 15, 81377 Munich ,
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Ospedale Sacro Cuore Don Calabria
Affiliation as printed
Department of Advanced Radiation Oncology, IRCCS Sacro Cuore Don Calabria Hospital , Via Don A. Sempreboni, 37024 Negrar di Valpolicella ,
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Azienda Ospedaliera Citta' della Salute e della Scienza di Torino · University of Turin
Affiliation as printed
Department of Medical Sciences, University of Turin , Via Verdi 8, 10124 Torino ,
Division of Cardiology, Cardiovascular and Thoracic Department, Città Della Salute e Della Scienza Hospital, Corso Bramante 88/90, 10126 Torino ,
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University of Graz · Medical University of Graz
Affiliation as printed
Department of Internal Medicine, Karl-Franzens-University Hospital , Auenbruggerplatz 15, 8036 Graz ,
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Internal Medicine III, Cardiology and Angiology, University Hospital Schleswig-Holstein , Arnold-Heller-Straße 3, 24105 Kiel ,
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Affiliation as printed
Department of Cardiology, Universitätsspital Zürich, University Hospital Zürich , Rämistrasse 100, 8091 Zurich ,
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Affiliation as printed
St.Bernhard Krankenhaus , Hildesheim, Treibestraße 9, 31134
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University of Zurich · University Hospital Zurich
Affiliation as printed
Department of Radiation Oncology, University Hospital of Zurich , Rämistrasse 100, 8091 Zurich ,
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Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
Department of Radiation Oncology, Charité University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin , Charitéplatz 1, 10117 Berlin ,
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Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
Department of Radiation Oncology, Charité University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin , Charitéplatz 1, 10117 Berlin ,
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Centre Hospitalier Universitaire Vaudois · University of Lausanne
Affiliation as printed
Heart and Vessel Department, Service of Cardiology, Lausanne University Hospital and University of Lausanne , Rue du Bugnon 46, 1011 Lausanne ,
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Leiden University Medical Center · Humboldt-Universität zu Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
Department of Cardiology, Leiden University Medical Center , Albinusdreef 2, 2333 ZA Leiden ,
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University Hospital Schleswig-Holstein
Affiliation as printed
Department of Radiation Oncology, University Hospital Schleswig-Holstein Campus Kiel , Arnold-Heller-Straße 3, 24105 Kiel ,
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Humboldt-Universität zu Berlin · Deutsches Herzzentrum der Charité · German Centre for Cardiovascular Research · Charité - Universitätsmedizin Berlin
Affiliation as printed
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
DZHK (German Center for Cardiovascular Research), partner Site Berlin , Berlin ,
Deutsches Herzzentrum der Charité , Department of Cardiology, Angiology and Intensive Care Medicine, Charitéplatz 1, 10117 Berlin ,
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Felix Hohendanner corresponding
Humboldt-Universität zu Berlin · Deutsches Herzzentrum der Charité · German Centre for Cardiovascular Research · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Berlin Institute of Health, Charité-Universitätsmedizin Berlin , Anna-Louisa-Karsch-Straße 2, 10178 Berlin ,
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Charitéplatz 1, 10117 Berlin ,
DZHK (German Center for Cardiovascular Research), partner Site Berlin , Berlin ,
Deutsches Herzzentrum der Charité , Department of Cardiology, Angiology and Intensive Care Medicine, Charitéplatz 1, 10117 Berlin ,
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