Evaluation of imprecision for cardiac troponin assays at low-range concentrations

Area of Science:

• Clinical Chemistry
• Cardiovascular Diagnostics
• Biomarker Assay Validation

Background:

• The 99th percentile of cardiac troponin is the recommended threshold for diagnosing myocardial infarction (MI).
• A coefficient of variation (CV) of ≤10% at this decision limit is advised for assay imprecision.
• Limited peer-reviewed data exists on the imprecision of commercially available cardiac troponin assays.

Purpose of the Study:

• To evaluate the imprecision profiles of various commercial cardiac troponin assays.
• To determine the lowest concentration with a 10% CV for each assay.
• To assess assay performance against the recommended MI diagnostic criteria.

Main Methods:

• Eight serum pools with varying cardiac troponin concentrations were prepared and stored.
• Measurements were performed using a standardized protocol: two replicates per specimen, one run daily for 20 days.
• Assays were run using two reagent lots and three calibrations, with data analyzed per NCCLS EP5-A guidelines.

Main Results:

• Significant variability in the lowest concentration achieving a 10% CV was observed across assays.
• Notable results included Elecsys (0.04 µg/L), Access (0.06 µg/L), and Liaison (0.065 µg/L).
• Other assays like AxSYM (1.22 µg/L) and Opus (0.90 µg/L) showed higher concentrations for 10% CV.

Conclusions:

• None of the evaluated cardiac troponin assays met the recommended 10% CV at the manufacturer-defined 99th percentile reference limit.
• This highlights a critical gap in assay performance for accurate MI diagnosis.
• Assay imprecision remains a significant challenge in adhering to current MI diagnostic guidelines.