Heart failure & cardiomyopathies

Heart allograft rejection: molecular diagnosis using intra-graft targeted gene expression profiling

Eur Heart JPublished Diagnostic accuracy study

Authors' conclusion

A novel FFPE-based molecular diagnostic system accurately identified cardiac allograft rejection.

Study context

Population
Heart transplant recipients with formalin-fixed, paraffin-embedded (FFPE) endomyocardial biopsies
Participants
671 biopsies
Comparison
Molecular antibody-mediated rejection (AMR) and acute cellular rejection (ACR) classifiers vs pathologic grading
Outcome
Discrimination (ROC-AUC) and calibration of molecular classifiers for AMR and ACR
Methodological detailsinternational, internal and external validation, Gene expression by Banff Human Organ Transplant Panel, Main cohort 591 biopsies (AMR n = 188, ACR n = 289, matched non-rejection n = 114); derivation set n = 475, External validation cohort: AMR n = 20, ACR n = 32, non-rejection n = 28
  • International
  • Internal and external validation
  • Gene expression by Banff Human Organ Transplant Panel
  • Main cohort 591 biopsies (AMR n = 188, ACR n = 289, matched non-rejection n = 114); derivation set n = 475
  • External validation cohort: AMR n = 20, ACR n = 32, non-rejection n = 28

Performance

As reported in the abstract

Identification of rejection (ROC-AUC)
Test or modelAUC, internal validationAUC, external validation
AMR model0.8120.822
ACR model0.8490.815

AUC, internal validation

AMR model0.812
ACR model0.849

AUC, external validation

AMR model0.822
ACR model0.815

Further findings

Transcript profiles

AMR: interferon-gamma pathway, endothelial activation, monocyte-macrophage recruitment transcripts
ACR: T-cell receptor signalling, CD3 receptor activation, CD28 signalling transcripts

Original publication

Heart allograft rejection: molecular diagnosis using intra-graft targeted gene expression profiling. Eur Heart J. Published 4 December 2025. doi:10.1093/eurheartj/ehaf949

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