FFPE-based molecular diagnosis of heart allograft rejection

Results from an international, multicenter diagnostic study (NCT06436027), evaluating targeted gene expression profiling on formalin-fixed, paraffin-embedded (FFPE) endomyocardial biopsies (EMBs) for the diagnosis of heart allograft rejection, were published in the European Heart Journal by Giarraputo et al. A total of 671 biopsies were analyzed, including a derivation cohort (n = 475), an internal validation cohort (n = 116), and an external validation cohort (n = 80). Histopathology was the reference standard.

Key data: Gene expression-based molecular classifiers for antibody-mediated rejection (AMR) and acute cellular rejection (ACR) demonstrated strong discrimination in validation cohorts. In internal validation, receiver operating characteristic area under the curves (ROC‑AUCs) were 0.82 for AMR (95% confidence interval [CI], 0.73–0.90) and 0.82 for ACR (95% CI, 0.75–0.90). In external validation, ROC‑AUCs were 0.82 (95% CI, 0.70–0.95) for AMR and 0.82 (95% CI, 0.72–0.91) for ACR. Molecular scores increased with histologic severity for both rejection types (p < 0.001).

Key learning: FFPE-based targeted gene expression profiling using EMBs may help refine the assessment of heart allograft rejection in addition to histology in heart transplant recipients, and may serve as a complementary diagnostic approach.