Advancements and challenges in high-sensitivity cardiac troponin assays: diagnostic, pathophysiological, and clinical perspectives

Abstract Although significant progress has been made in recent years, some important questions remain regarding the analytical performance, pathophysiological interpretation and clinical use of cardiac troponin I (cTnI) and T (cTnT) measurements. Several recent studies have shown that a progressive and continuous increase in circulating levels of cTnI and cTnT below the cut-off value (i.e. the 99th percentile upper reference limit) may play a relevant role in cardiovascular risk assessment both in the general population and in patients with cardiovascular or extra-cardiac disease. International guidelines recommend the use of standardized clinical algorithms based on temporal changes in circulating cTnI and cTnT levels measured by high-sensitivity (hs) methods to detect myocardial injury progressing to acute myocardial infarction. Some recent studies have shown that some point-of-care assays for cTnI with hs performance ensure a faster diagnostic turnaround time and thus significantly reduce the length of stay of patients admitted to emergency departments with chest pain. However, several confounding factors need to be considered in this setting. A novel approach may be the combined assessment of laboratory methods (including hs-cTn assay) and other clinical data, possibly using machine learning methods. In the present document of the Italian Study Group on Cardiac Biomarkers, the authors aimed to discuss these new trends regarding the analytical, pathophysiological and clinical issues related to the measurement of cardiac troponins using hs-cTnI and hs-cTnT methods.