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Hugo A Katus, Evangelos Giannitsis, Prognostic Value of Serum Troponin T in Unstable Angina, Clinical Chemistry, Volume 64, Issue 2, 1 February 2018, Pages 396–397, https://doi.org/10.1373/clinchem.2017.272799
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Featured Article: Hamm CW, Ravkilde J, Gerhardt W, Jørgensen P, Peheim E, Ljungdahl L, et al. The prognostic value of serum troponin T in unstable angina. N Engl J Med 1992;327:146–50.2
Our work on biomarkers of myocardial injury started in 1978 when the diagnosis of myocardial infarction (MI)3 was based on the WHO criteria. At that time, total creatine kinase and lactate dehydrogenase enzyme activity assays were commonly used, and creatine kinase isoenzyme (M, muscle; B, brain; CK-MB) measured as either enzyme activity or protein mass was considered the most clinically sensitive and specific biomarker for MI diagnosis. However, clinical studies indicated that patients with chest pain who were sent home from the emergency room with a diagnosis of “myocardial infarction excluded” had a survival rate similar, or even worse, to patients admitted with acute MI (1).
Motivated by the imperfect clinical specificity and sensitivity of cardiac enzyme assays for diagnosis of MI and the advances in antibody technologies, we began, in 1979, to develop immunoassays for sarcomeric proteins. The development of an assay for cardiac myosin light chains utilizing monoclonal antibodies was our first strategy. Importantly, with this assay, we detected increased myosin light chains in patients with suspected MI even when cardiac enzyme measurements were still in the normal range. Although we were convinced that these increases indicated myocardial cell necrosis, others declared these findings as “false-positive myosin light chain bumps.” In fact, our original work for publication was rejected with the reviewers' notion that everybody knew how to diagnose MI and our work would only confuse the medical community. Only years later and with more clinical data were we able to convince the editors of the Journal of the American College of Cardiology of the prognostic significance of increased myosin light chains in patients with unstable angina (2). Thus, it was with the myosin light chain assay that we first described the presence of micro-MIs in 22 of 44 patients (52%) classified as having unstable angina and showed an increase of myosin light chains in all 5 patients who progressed to MI (2).
