Circulating forms of cardiac troponin: a review with implications for clinical practice

Cardiac troponin I (cTnI) and T (cTnT) became the gold-standard biomarkers for diagnosing myocardial infarction (MI) due to their cardiac-specific amino acid sequence. Currently, both cTnI and cTnT are considered equivalent as their diagnostic performance is comparable. The introduction of highsensitivity (hs-)cTn immunoassays allowed a more accurate assessment of cTn concentrations in the lower analytical range resulting in a higher number of non-ST-elevated MI (NSTEMI) diagnoses. However, the increased sensitivity also resulted in hs-cTn elevations in other (non-)cardiac pathologies and even in physiological conditions, such as vigorous exercise. To differentiate acute MI from these other conditions it was suggested that the circulating form of cTn might serve useful, since research illustrated different circulating cTnI and cTnT forms in the blood circulation. Studies in acute MI patients have shown that cTnI appears to be mostly present in a binary (cTnI-C) complex. Also, a variety of different cTnI fragments was observed post-MI, but no time-dependent cTnI degradation effect was found dependent on symptom onset. For cTnT, mainly larger forms were found in MI, while in other conditions with elevated hs-cTnT concentrations, the smallest fragments were almost exclusively present. Based on this preliminary data it might be clinically relevant to develop a novel hs-cTnT immunoassay which solely targets specific cTnT forms observed in acute MI that could help to further increase the specificity of hs-cTnT immunoassay for the diagnosis of acute MI. The present traditional literature review provides an overview of research on circulating cTn forms performed thus far.