Pivotal findings for a high-sensitivity cardiac troponin assay: Results of the HIGH-US study

•Analytical characteristics are reported for the novel Atellica IM TnIH assay.•The Atellica TnIH assay met criteria as a high-sensitivity cardiac troponin assay.•1007 women & 1000 men established sex-specific 99th % upper reference limits.•HIGH-US is cohort of nearly of 2494 suspected acute myocardial infarction subjects.•1.0 to 3.5 h post presentation Atellica's TnIH's negative predictive value was 99%. Cardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and diagnostic accuracy of the Atellica IM TnIH assay to determine high-sensitivity performance and appropriate diagnostic performance for clinical use. Sex-specific 99th percentile upper reference limits (URLs) were determined for a healthy cohort of 1007 women and 1000 men using non-parametric statistics. High-sensitivity performance was assessed by examining if imprecision was ≤10% at sex-specific URLs and if ≥50% of cTnI values for each sex exceeded the assay’s limit of detection (LoD) with the AACC Universal Sample Bank. Precision, high-dose hook effect, endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization was with 2494 suspected AMI subjects presenting to emergency departments across the United States. AMI was adjudicated by expert cardiologists and emergency medicine physicians. There were no comorbidity exclusions. 99th percentile URLs were 34 ng/L, 53 ng/L and 45 ng/L for the female, male and overall populations, respectively. Total imprecision was 90%; negative and positive predictive value were ≥98% and >60%, respectively. Non-AMI subjects with comorbidities and values exceeding 99th percentile URLs had absolute and percent change at 2–4 h that were lower than AMI patients with comorbidities (p = 0.001). The Atellica IM TnIH assay is a high-sensitivity method and demonstrates clinical performance appropriate for AMI diagnosis.