Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue

摘要

Objectives High sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study. Design and methods Analytical verification included assessment of critical outlier frequency, for hs-cTnI and cTnI assays. Concordance for paired cTnI and hs-cTnI measurements ( n =1096) was verified using 99th percentiles for both genders (cTnI: 30ng/L, hs-cTnI: 25ng/L) and for men and women separately (hs-cTnI: M: 34;F: 16ng/L). Discordant data was correlated with clinical and laboratory information. Diagnosis of Acute Coronary Syndrome (ACS) or Non-ACS was adjudicated by two cardiologists independently. Results The hs-cTnI assay showed a lower (10-fold) critical outlier rate (0.091%) and more detectable results above the limit of detection (LOD) (23.4%) and 99th percentile (2.4%), compared to cTnI. Analytical concordance between the two assays was high (94.5%) but decreased (91.7%) when gender-specific hs-cTnI cut-offs were used. The hs-cTnI assay gave fewer false negatives (up to 1.0%) but disproportionately more false positives (up to 6.7%) overall, which improved (3.9%) for serial measurements. Conclusions Laboratories should analytically and clinically verify hs-cTn assays before use, with attention to performance and the clinical and diagnostic algorithms that support appropriate testing and result interpretation. Work in the pre- and post-analytical phases is necessary to augment the analytical improvement in the new era of troponin testing.