Analytical and clinical characterization of a novel high-sensitivity cardiac troponin assay in a United States population

Background: Cardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and clinical diagnostic characteristics of the ACCESS hsTnI assay in a United States (US) population. Methods: All measurements and studies were conducted using a lithium heparin matrix. Sex-specific 99th percentile upper reference limits (URLs) were determined for 1089 healthy women (54.6%) and men using non-parametric statistics. High-sensitivity (hs) performance was assessed to determine if the total CV was <= 10% at sex-specific URLs, and if >= 50% of cTnI values for each sex exceeded the assay's limit of detection (LoD). Precision, analytical measurement range, high-dose hook effect, and endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization included serial sampling of 1854 suspected AMI subjects presenting to 14 US Emergency Departments. AMI was adjudicated by a panel of expert cardiologists. The study's only exclusion was end stage renal disease. Results: 99th percentile URLs were 11.6-, 19.8- and 17.5-ng/L for respective female, male and all-subject populations. Total %CV was <8% from 6.8 to 19,000 ng/L, and <6% at sex-specific 99th percentiles; >= 99% of ACCESS hsTnI values for each sex exceeded the LoD. No high-dose hook effect or endogenous/exogenous interferences were identified. A comparison of Baseline samples collected at <= 1 h and any-time after presentation, found 4% lower sensitivity for AMI than with earlier sampling. For 1-9 h post presentation, the sensitivity was >90%, specificity >85%; and negative and positive predictive value were >= 99% and >60%, respectively. Conclusion: Analytical and clinical performance of the ACCESS hsTnI assay meets the definition of a hs cTn method. The ACCESS hsTnI assay has good precision over a wide range, no significant interferences, and sensitivity > 90% and NPV >= 99%. Performance is appropriate for aiding in AMI diagnosis.