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.

Background/Objectives: Cardiac troponin I (cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥2R. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients after exclusion of ambiguous measurements and episodes without a preceding confirmed cTnI value. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log₂-transformed cTnI, whereas M2 additionally included the time-normalized change in log₂-transformed cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation; 95% confidence intervals were obtained from 2000 patient-level cluster bootstrap resamples. 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, 95% CI 0.584–0.685; ΔAUC −0.007, 95% CI −0.021 to 0.007). Within 90 days after transplantation, 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, 95% CI 0.654–0.828; ΔAUC −0.012, 95% CI −0.037 to 0.008). Conclusions: Concurrent cTnI showed no discrimination within 90 days and moderate discrimination thereafter in exploratory stratified analyses. The kinetic term provided no incremental value. cTnI cannot replace endomyocardial biopsy but may warrant further evaluation as an adjunctive late-period marker.