Serial Cardiac Troponin I Kinetics Do Not Improve Detection of Acute Cellular Rejection Beyond Concurrent Troponin Levels After Heart Transplantation

Background/Objectives: High-sensitivity cardiac troponin I (hs-cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized hs-cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥ 2R and whether this association varies with time after transplantation. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log2-transformed hs-cTnI, whereas M2 additionally included the time-normalized change in log2-transformed hs-cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation with patient-level cluster bootstrap confidence intervals. Exploratory analyses examined early (≤90 days), late (>90 days), and continuous post-transplant time. Results: In the overall cohort, M1 showed modest discrimination (AUC 0.641, 95% CI 0.592–0.689), whereas M2 provided no improvement (AUC 0.635; ΔAUC −0.007). Within 90 days, neither model was informative (M1 AUC 0.503; M2 AUC 0.494). Beyond 90 days, M1 showed moderate discrimination (AUC 0.758, 95% CI 0.664–0.838), but M2 again provided no improvement (AUC 0.746; ΔAUC −0.012). Continuous-time modeling showed that the association between concurrent hs-cTnI and ACR strengthened with increasing time after transplantation, whereas the kinetic term remained non-informative. Conclusions: Time-normalized hs-cTnI kinetics did not provide incremental diagnostic value beyond concurrent hs-cTnI. Concurrent hs-cTnI may warrant further evaluation as an adjunctive late-period marker, but the 90-day threshold remains exploratory and requires external validation. Neither hs-cTnI concentration nor its kinetics should replace endomyocardial biopsy.