Specificity of a High-Sensitivity Cardiac Troponin I Assay Using Single-Molecule–Counting Technology

Abstract

Cardiac troponin is the standard for diagnosis or exclusion of acute myocardial infarction. Recent guidelines recommend a cutoff value at the upper 99th percentile (99th%)1 of values for a reference population of healthy individuals and assay imprecision (CV) ≤10% at this cutoff (1). Many commercial assays cannot meet these criteria, and values below the 99th% cutoff appear to supply diagnostic and prognostic information (2)(3). Recently the Erenna™ cardiac troponin I (cTnI) immunoassay (Singulex) has been shown to provide sensitivity and precision that meet these goals (4), with a preliminary 99th% cutoff value at 8 ng/L and 10% CV of 1.8 ng/L (5). This novel assay uses single-molecule counting technology and has been previously described. However, we could not fully exclude the possibility that, with such sensitive limits of detection, low-level nonspecific binding (NSB) events might contribute to cTnI measurements. We explored this issue by testing potential sources of NSB events. To test for NSB of serum or plasma constituents, cTnI was quantified in 4 specimen types from 20 healthy individuals, serum, EDTA, lithium heparin, and sodium-citrated plasma. The protocol was approved by the University of California Committee on Human Research. All 20 individuals were free of cardiac disease or symptoms (13 female, 7 male, mean age 43 years, …