Utility of troponin assays for exclusion of acute cellular rejection after heart transplantation: A systematic review.

ABSTRACT

BACKGROUND: Acute cellular rejection (ACR) is a common complication in the first year after heart transplantation (HT). Routine surveillance for ACR is undertaken by endomyocardial biopsy (EMB). Measurement of cardiac troponins (cTn) in serum is an established diagnostic test of cardiac myocyte injury. This systematic review aimed to determine whether cTn measurement could be used to diagnose or exclude ACR. METHODS: PubMed, Google Scholar and the JHLT archive were searched for studies reporting the result of a cTn assay and a paired surveillance EMB. Significant ACR was defined as International Society for Heart and Lung Transplantataion (ISHLT) Grade ≥3a/≥2R. Considerable heterogeneity between studies precluded quantitative meta-analysis. Individual study sensitivity and specificity data were examined and used to construct a pooled hierarchical summary receiver-operator characteristic (ROC) curve. RESULTS: Twelve studies including 993 patients and 3,803 EMBs, of which 3,729 were paired with cTn levels, had adequate data available for inclusion. The overall rate of significant ACR was 12%. There was wide variation in diagnostic performance. cTn assays demonstrated sensitivity of 8% to 100% and specificity of 13% to 88% for detection of ACR. The positive predictive value (PPV) was low but the negative predictive value (NPV) was relatively high (79% to 100%). High-sensitivity cTn assays had greater sensitivity and NPV than conventional cTn assays for detection of ACR (sensitivity 82% to 100% vs 8% to 77%; NPV 97% to 100% vs 81% to 95%, respectively). CONCLUSIONS: cTn assays do not have sufficient specificity to diagnose ACR in place of EMB. However, hs-cTn assays may have sufficient sensitivity and negative predictive value to exclude ACR and limit the need for surveillance EMB. Further research is required to assess this strategy.