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. 2017 May;63(5):990-996.
doi: 10.1373/clinchem.2016.264648. Epub 2017 Apr 4.

Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium

Jack Marjot  1 , Thomas E Kaier  1 , Eva D Martin  1 , Shiney S Reji  2 , O'Neal Copeland  2 , Mohammed Iqbal  3 , Bob Goodson  4 , Sarah Hamren  4 , Sian E Harding  2 , Michael S Marber  5
Affiliations

Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium

Jack Marjot et al. Clin Chem. 2017 May.

Abstract

Background: Myocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm.

Methods: Individual rat cardiac myocytes, rat myocardium, ovine myocardium, or human myocardium were spiked into 400-μL aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocardium. High-sensitivity assays were used to measure cardiac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna®).

Results: The cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 μL of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8-21.2) and 18.9 ng/L (95% CI, 14.7-23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6-4.3), 4.3 ng/L (95% CI, 3.8-4.7), and 41.0 ng/L (95% CI, 38.0-44.0) per μg of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 × 108 times their lower limits of quantification.

Conclusions: Based on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging.

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Conflict of interest statement

Conflicts of Interest

Millipore Sigma (Hayward, California) was contracted to undertake the analyses of cMyC on a fee-for-service basis and hold no commercial interest. Marber is named as an inventor on a patent held by King’s College London for the detection of cMyC as a biomarker of myocardial injury.

Figures

Figure 1
Figure 1
Graph showing linear regression between number of rat cardiomyocytes and resultant cardiac biomarker concentration as measured by high-sensitivity assays (hs-cTnI and hs-cTnT) in 400 µL of human serum; cTnI (n=61, excluding one outlier; y=18.9 [95% CI 14.7–23.1] *x – 44.6 [95% CI -128.8-39.5]) cTnT (n=62; y=19 [95% CI 16.8–21.2] *x - 24.4 [95% CI -18.9-67.7]), both with spikes into serum from 4 different individuals. Light grey shading depicts the boundaries of the 95% confidence intervals, with dark grey illustrating their overlap
Figure 2
Figure 2
Graph showing linear regression between mass of human myocardium and resultant cardiac biomarker concentration as measured by high-sensitivity assays (hs-cTnI and hs-cTnT) in 400 microliters of human serum; n=36 for each biomarker, each with spikes into serum from 3 different individuals. Light grey shading depicts the boundaries of the 95% confidence intervals. Regression equations: cTnI: y = 4.3 [95% CI 3.8-4.7] *x + 4.4 [95% CI -20.1-28.8], cTnT: y = 3.9 [95% CI 3.6-4.3] *x + 19 [95% CI -1.6-39.5], cMyC: y = 41 [95% CI 38.0-44.0] *x + 91.1 [95% CI -79.3-261.4]
Figure 3
Figure 3
Graph demonstrating available serum biomarker concentration after an oral load of cooked ovine myocardium at the following time-points: 0 min, 15 min, 1 hr, 2 hrs, 3 hrs, 4 hrs (missing for cTnI), 22 hrs, 28 hrs; all measured values remained below the Limit of Detection (LoD) for high-sensitivity assays (hs-cTnT and hs-cTnI) for the respective biomarkers (cTnT=5 ng/L, cTnI=1.9 ng/L; indicated on plot with dotted lines)
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References

    1. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581–98. - PubMed
    1. Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC) Eur Heart J. 2016;37:267–315. - PubMed
    1. Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, et al. One-Hour Rule-out and Rule-in of Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T. Arch Intern Med. 2012;172:1211–8. - PubMed
    1. Rubini Giménez M, Twerenbold R, Jaeger C, Schindler C, Puelacher C, Wildi K, et al. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 2015;128:861–4. - PubMed
    1. Twerenbold R, Wildi K, Jaeger C, Gimenez MR, Reiter M, Reichlin T, et al. Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction. Circulation. 2015;131:2041–50. - PMC - PubMed

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