Abstract

Macrotroponin is increasingly recognised as a cause of confusion in interpreting high-sensitivity cardiac troponin (hs-cTnI) results. In this study, we sought to evaluate two practical approaches to detecting macrotroponin. These two approaches are PEG precipitation and SVM (support vector machine) analysis to classify discrepancies between hs-cTn assays. Residual serum and heparin plasma specimens (n = 483) with initially elevated hs-cTnI from hospital and community laboratories were retested on multiple hs-cTn platforms before and after PEG precipitation and Protein A immunoglobulin depletion. SVM analysis was conducted to identify a linear equation that best discriminated specimens with macrotroponin using a combination of results from two different hs-cTn assays. The diagnostic performance of PEG precipitation was carried out using Protein A immunoglobulin depletion as the reference comparator. When a cutoff residual activity after PEG precipitation of ≤ 20% was used, this threshold carried a high specificity of 92% (confidence interval 83-98%; n = 189) using the Siemens hs-cTnI Vista assay and 95% specificity (86%-98%; n = 242) using the Abbott hs-cTnI Architect assay. SVM analysis generated a linear equation identifying macrotroponin specimens from results obtained on two hs-cTn assays. This approach can be highly specific, comparable to PEG precipitation when certain assay combinations and concentrations are used. We describe and identify practical alternatives to detecting macrotroponin. These approaches can be optimised for high specificity, reducing the need for more complex laboratory methods.

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