Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (STEMI, 9.3 ± 3.1 vs 11.8 ± 3.4 h, P < 0.007; TASH, 9.7 ± 1.4 vs 21.6 ± 1.4 h, P < 0.0001), accumulates more rapidly (during first 4 h after TASH, 25.8 ± 1.9 vs 4.0 ± 0.4 ng/L/min, P < 0.0001) and disappears more rapidly (post-CABG, decay half-time 5.5 ± 0.8 vs 22 ± 5 h, P < 0.0001). Our results demonstrate that following defined myocardial injury, the rise and fall in the serum of cMyC is more rapid than that of cTnT. We speculate that these characteristics could enable earlier diagnosis of myocardial infarction and reinfarction in suspected non-STEMI, a population not included in this early translational study.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-015-0478-5) contains supplementary material, which is available to authorized users.
The diagnosis of myocardial infarction (MI) depends on a rise and/or fall of cardiac biomarkers such as troponins in the appropriate clinical context. Conventional troponin assays lack sensitivity and precision at the low serum concentrations observed in the early hours after the onset of chest pain. New, highly sensitive troponin assays may offer improved certainty in these early hours. Many of these assays can detect troponins reliably at serum concentrations that occur in patients with chronic stable heart disease and even in asymptomatic healthy individuals. Indiscriminate use of these previously undetectable concentrations for the early diagnosis of acute MI will be accompanied by reduced specificity. However, they are likely to improve risk stratification of patients with chronic heart disease. This review focuses on the available highly sensitive troponin assays and their likely use in the diagnosis of acute MI and risk stratification of patients with heart disease.
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