Characterization of Cardiac Troponin Fragment Composition Reveals Potential for Differentiating Etiologies of Myocardial Injury

BACKGROUND: Increased cardiac troponin (cTn) concentrations occur in acute myocardial injury and chronic diseases. Characterization of cTn composition in the circulation may assist in differentiating etiologies of myocardial injury. Our goal was to study cTn composition and kinetics in patients following type 1 myocardial infraction (T1MI), cardiac procedures, and chronic heart diseases to establish the relationship between cTn composition and clinical diagnosis. METHODS: Plasma samples were collected from 201 patients with T1MI, 78 undergoing cardiac surgeries, and 218 with chronic cardiomyopathy or chronic heart failure. Major cTn forms in the circulation and their ratios were analyzed using cTn composition immunoassays, targeting (a) the long-cTnT cTnI-cTnT-TnC (ITC) ternary complex, short-cTnT ITC complex cleaved at amino acids residues 189-223 of cTnT, and the binary cTnI-TnC (IC) complex, and designated the "high-sensitivity (hs)-cTnI assay;" (b) the long-cTnT ITC complex, and designated the "long-cTnT ITC complex assay;" (c) the long-cTnT ITC complex and short-cTnT ITC complex, and designated the "hs-total ITC complex assay;" and (d) the central part of cTnT of both the long-cTnT ITC complex and free cTnT, and designated the "hs-cTnT assay." RESULTS: Early-stage T1MI patients showed a high ratio of long-cTnT ITC complex to cTnI (long-cTnT ITC complex/cTnI, R1). Similarly, patients after acute cardiac surgery exhibited increased cTn concentrations with high R1, which decreased rapidly. In chronic disease, cTn composition exhibited stable and low R1 and high ratios of cTnT to cTnI (cTnT/cTnI, R3). CONCLUSIONS: Kinetic differences in multiple cTn forms contribute to the differentiation between acute injury and chronic disease, with a high proportion of long-cTnT ITC complex implying occurrence of acute injury.