Association Between High Sensitivity Troponin I and NTproBNP With Rejection and Graft Loss in Pediatric Heart Transplant Recipients.

Abstract

Troponin I is a blood biomarker of cardiac injury and levels measured using a high-sensitivity assay after pediatric heart transplantation (HT) have not been described. We sought to assess the association between high-sensitivity troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NTproBNP) with treated acute rejection (AR) and graft loss in pediatric heart transplant (HT) recipients. Serum was collected and banked from pediatric HT recipients prior to cardiac catheterization. Patients with samples drawn within 365 days post-HT were included and followed for up to 5 years. Generalized linear mixed-effect models examined the association between hsTnI and treated AR using a random intercept per patient. Cox proportional hazards models tested the association between maximal hsTnI and NT-proBNP and death/graft loss. HsTnI and NTproBNP values decline in the weeks following HT, after which these biomarkers stabilize. HsTnI was higher in AR versus no AR (6.2 vs. 3.5 ng/L, p < 0.001); doubling of hsTnI increased the odds of AR by 33% (p = 0.004). HsTnI showed moderate discrimination for AR with an AUC of 0.811 (95% CI 0.76, 0.87) and a NPV of 96.4% (95% CI 93.0, 98.1). Elevation in NT-proBNP was not associated with AR. In multivariable Cox modeling, a doubling of maximal NT-proBNP was associated with graft loss (HR 8.96, p = 0.014). In this pediatric HT cohort, HsTnI was moderately discriminative for AR and higher maximal NT-proBNP was associated with graft loss. HsTnI may add value in pediatric HT non-invasive AR surveillance, and elevated NTproBNP could suggest an increased risk of graft loss.