Sustained elevated concentrations of cardiac troponin T during acute allograft rejection after heart transplantation in children1

Background. The diagnosis of acute rejection after heart transplantation is made on the basis of endomyocardial biopsy. In children, where the method may be associated with complications, a noninvasive alternative would be desirable. We evaluated the myocardial damage marker cardiac troponin T (cTnT) as a marker of rejection in children who have undergone heart transplantation. Methods. Peripheral venous blood was collected in 124 endomyocardial biopsies in 14 children who had undergone heart transplantation (1–20 years of age). Serum levels of cTnT were compared with histologic rejection according to the International Society of Heart and Lung Transplantation (ISHLT) (grades 0–4). Results. Seven children experienced nine episodes of acute rejection. During rejection, cTnT increased from 0.05±0.07 (mean±SD) μg/L to 0.26±0.27 μg/L and remained elevated 7 and 30 days thereafter (0.10±0.11 and 0.36±0.38 μg/L, respectively) before returning to normal after 50 to 430 days. In surveillance biopsies, cTnT displayed considerable variation at all rejection grades: ISHLT grade 0, median 0.03 μg/L (range 0.01–2.04 μg/L); ISHLT grade 1, median 0.06 μg/L (range 0.01–0.67 μg/L); ISHLT grade 2, median 0.10 μg/L (range 0.01–1.42 μg/L); and ISHLT grade 3, median 0.17 μg/L (range 0.01–0.93 μg/L). A receiver operating characteristics analysis for cTnT versus rejection grade revealed an area under the curve of 0.69, indicating a moderate predictive value for cTnT. However, a cutoff of 0.015 μg/L yielded a specificity of only 36%, with a sensitivity of 89%, whereas a cutoff of 0.1 μg/L resulted in sensitivity and specificity of 53% and 77%, respectively. Conclusions. Cardiac troponin T increased and remained elevated for at least 1 month during acute rejection. The diagnostic power of a single cTnT measurement was not sufficient to replace endomyocardial biopsy.