Practical approaches to the detection of macrotroponin

Introduction: 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. Method: 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. Findings: 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. Conclusion: 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.