Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury

Abstract

Background Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. Methods Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. Results Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. Conclusions In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Molecular signatures of myocardial infarction

“…This is in accordance with previous studies, suggesting more elaborate cTn degradation in serum samples through abundant thrombin generation during serum production [17,18,23,245]. Thirdly, the ternary cTn T-I-C complex was only observed in the early presenting patient and disappeared over time, which is in line with previous studies that describe a time dependent composition of cTnT after MI [20,22,23,237,246]. This in vivo process has also been attributed to thrombin [17,18].…”

“…Fourthly, the multi-site sampling setup of the present study enabled the comparison of the cTnI composition throughout the circulation. We found both binary cTn I-C and ternary cTn T-I-C complexes within the coronary venous system and higher cTn concentrations compared to the peripheral samples, suggesting the release of both these forms from the injured myocardium [23,237,247]. Notably, the presence of mostly cTn I-C complexes within the coronary venous system strongly suggest breakdown of cTn T-I-C complexes within the cardiomyocyte.…”

“…Using WB they identified this additional peak as a low molecular weight cTn T-I-C complex, containing truncated forms of cTnT and/or cTnI. More recently, the presence of cTn complexes has been studied using three Pylon immunoassay platforms in a larger subpopulation of the TRAMICI study [237]. Complex cTnI as proportion of total cTnI was 87% in the peripheral baseline sample, whereas large-size cTn T-I-C was 9% (6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…Interestingly, previous research has shown varying cTnT compositions in the abovementioned etiologies [20,25,236,237]. More specifically, in MI patients it has been observed that cTnT circulates as cTn T-I-C complex and cTnT fragments, whereas in non-MI patients only smaller cTnT fragments were present.…”

“…There is less consensus on the composition of cTnI in MI patients [7, 22, 24, 26-30, 237, 239-241]. In MI patients cTnI predominantly circulates as the binary cTn I-C complex, next to a small proportion of ternary cTn T-I-C complex and low-molecular weight forms of the cTn T-I-C complex [22,237,241]. Additionally, multiple degradation forms of cTnI have been observed, but it is unknown whether these circulate in a free form or as part of a complex [239][240][241][242].…”