From rejection detection to immune-risk surveillance: Integrating molecular diagnostics across heart transplant...

Rejection surveillance in heart transplantation (HT) has evolved beyond reliance on histologic grading alone to incorporate circulating biomarkers and tissue-based molecular diagnostics, including gene-expression profiling (GEP), donor-derived cell-free DNA (dd-cfDNA), and transcriptomic assessment. These tools have expanded the ability to detect biologic signals of alloimmune injury that may not be fully captured by morphology alone. At the same time, evidence that their routine use improves long-term clinical outcomes remains limited, and adoption has been uneven across healthcare systems. In several North American programs, dd-cfDNA testing and transcriptomic platforms have been incorporated into surveillance pathways, although implementation remains heterogeneous across centers and clinicians. In many European healthcare settings, availability is increasing, but integration into routine practice remains more variable, and comprehensive tissue-based profiling is still largely restricted to selected clinical scenarios. These differences in access and implementation may influence how rejection, graft stability, and longitudinal risk are interpreted in clinical practice. The next phase of the field will likely depend not on replacing histology, but on integrating molecular diagnostics into multimodal, longitudinal risk-based surveillance strategies. Coordinated validation efforts, prospective outcome-linked studies, and context-sensitive implementation frameworks will be essential to clarify the clinical role of these tools and to support equitable integration across diverse healthcare environments.