High-Sensitivity Cardiac Troponin I Assay to Screen for Acute Rejection in Patients With Heart Transplant

Abstract

Background— A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Methods and Results— Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P <0.0001) and increased in a graded manner with higher biopsy scores ( P trend <0.0001). The c -statistic to discriminate AR was 0.82 (95% confidence interval, 0.76–0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. Conclusions— A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications

“…These cardiac biomarkers for injury represented in Table 2 are for autologous hearts. A high-sensitivity troponin has been retrospectively correlated to biopsy-based acute rejection events in heart transplants (21). The biological variability was not computed, but the range of troponin from a reference population (n = 88) with no history of acute rejection was relatively wide: the median troponin was 9.45 ng/L, the 60th percentile was 15 ng/L, and 10 outliers that ranged from 60.9 to 268 ng/L were excluded from the main data analyses (21).…”

“…A high-sensitivity troponin has been retrospectively correlated to biopsy-based acute rejection events in heart transplants (21). The biological variability was not computed, but the range of troponin from a reference population (n = 88) with no history of acute rejection was relatively wide: the median troponin was 9.45 ng/L, the 60th percentile was 15 ng/L, and 10 outliers that ranged from 60.9 to 268 ng/L were excluded from the main data analyses (21). In contrast, our current study of a renal transplant reference population indicated that ddcfDNA has a narrower range between its median of 0.21% and 96th percentile cutoff of 1%, and we did not exclude outliers.…”

High sensitivity cardiac troponin assays in the clinical laboratories

“…While impractical in the general population, a number of settings may warrant repeat cTn testing. As the rise in cTn has been shown to predict rejection of a transplanted heart, serial cTn testing might be warranted in transplant recipients [109]. Similarly, patients who are about to undergo potentially cardiotoxic therapy may benefit from serial cTn testing and a switch to a different therapy when a predetermined allowable increase in cTn is exceeded [32].…”

Effect of treatment with rosiglitazone on high-sensitivity cardiac troponin levels among patients with type 2 diabetes mellitus

“…HscTnT and hscTnI have been evaluated in retrospective studies and found useful in surveillance of cardiac sarcoidosis activity and a biomarker for ruling out acute rejection in cardiac transplant recipients. 27,28 In this study, we used hscTnT as a biomarker for subclinical myocardial injury to determine whether 6 months of treatment with rosiglitazone causes an increase in levels when compared to a placebo. We observed that despite an increase in hscTnT levels from baseline to follow-up, there was no difference between the rosiglitazone and placebo group, suggesting that use of rosiglitazone is not associated with any significant increase in myocardial injury.…”