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, 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.