Standardized processing of explanted hearts after stereotactic arrhythmia radiotherapy (Bio-STAR): a STOPSTORM framework and first human findings.
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Ошибки и ограничения
История · было → стало
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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, Siklódy Claudia Herrera, Sinner Moritz, Giaj Levra Niccolò, De Ferrari Gaetano Maria, Scherr Daniel, Zaman Adrian, Kovacs Boldizsar, Hohmann Stephan, Andratschke Nicolaus, Hausmann Franziska, Mehrhof Felix, Pruvot Etienne, Zeppenfeld Katja, Blanck Oliver, Hindricks Gerhard, Hohendanner Felix
Аннотация
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.