Use of cardiac troponins as strong markers for patients with acute coronary syndrome
Keywords:
acute myocardial infarction, myocardial ischemia, cardiac biomarkers, cardiac troponin, high sensitivity troponinAbstract
Acute myocardial infarction (AMI) is the most important cause of cardiomyocyte necrosis. Cardiac troponin (cTn) T and I are structural proteins unique to the heart and have been used as the preferred cardiac biomarkers in the universal definition of myocardial infarction. Cardiac troponins have demonstrated nearly absolute myocardial tissue specificity and high clinical sensitivity for myocardial ischemia. The recent development of high-sensitivity cardiac troponin (hs-cTn) assays allows detection of very low levels of cTn. The hs-cTn assays have improved the diagnostic accuracy and rapid detection of myocardial infarction. Undetectable hs-cTn rules out AMI with a negative predictive value > 99% on emergency department admission. The diagnosis of acute myocardial damage requires a significant change with serial hs-cTn testing. Current consensus for rapid rule-in proposed a 20% increase within 3 to 6 hours when baseline cTn levels are elevated. In addition, relative increases > 50% above the 99th percentile upper reference limit are found to be the diagnosis of AMI, in the case of negative baseline value. Besides relative change, the absolute values of hs-cTn at emergency department presentation in patients with suspected AMI should be considered as important criteria in the differential diagnosis of the cause of cardiomyocyte damage. Cardiac troponins provide both diagnostic and prognostic information in the setting of acute coronary syndrome (ACS). Elevation of cTn in the absence of ACS should prompt an evaluation for non-thrombotic mechanism of increased cTn levels and direct management at the underlying cause.
References
Agewell, S., Giannitsis, E., Jernberg, T., & Katus, H. (2011). Troponin elevation in coronary vs. non-coronary disease. Eur Heart J, 32(4), 404-411. doi: 10.1093/eurheartj/ehq456
Aksay, E., Yanturali, S., & Kiyan, S. (2007). Can elevated troponin I levels predict complicated clinical cause and in hospital mortality in patients with acute pulmonary embolism? Am J Emerg Med, 25(2), 138-143.
Aldous, S. J., Richards, M., Cullen, L., Troughton, R., & Than, M. (2012). Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain. CMAJ, 184(5), E260-E268.
Ammann, P., Fehr, T., Minder, E. I., Gunter, C., & Bertel, O. (2001). Elevation of troponin I in sepsis and septic shock. Intensive Care Med, 27(6), 965-969).
Anderson, J. L., Adam, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., . . . Riegel, B. (2007). ACC/AHA 2007 guideline for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline. Circulation, 116(7), e148-e304.
Antman, E. M. (2002). Decision making with cardiac troponin tests. N Engl J Med, 346, 2079-2082.
Antman, E. M., Grudzen, C., Mitchell, R. N., & Sacks, D. B. (1997). Detection of unsuspected myocardial necrosis by rapid bedside assay for cardiac troponin T. Am Heart J, 133(5), 596-598.
Apple, F. S. (2009). A New season for cardiac troponin assays: It’s time to keep a scorecard. Clin Chem, 55(7), 1303-1306.
Apple, F. S., & Collinson, P. O. (2012). IFCC Task Force on Clinical Applications of Cardiac Biomarkers: Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem, 58(1), 54-61.
Apple, F. S., Jesse, R. L., Newby, L. K., Wu, A. H., & Christenson R. H. (2007). National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical tissue for biochemical markers of acute coronary syndromes. Circulation, 115(13), e352-e355.
Apple, F. S., Ler, R., & Murakami, M. M. (2012). Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem, 58, 1574-1581.
Apple, F. S., Murakami, M. M., Pearce, L. A., & Herzog, C. A. (2002). Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation,106(23), 2941-2945.
Apple, F. S., Pearce, L. A., Smith, S. W., Kaczmarek, J. M., & Murakami, M. M. (2009). Role of monitoring changes on sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events. Clin Chem, 55(5), 930-937.
Bassand, J. P., Hamm, C. W., Ardissino, D., Boersma, E., & Budaj, A. (2007). Guidelines for the diagnosis and treatment of non ST-segment elevation acute coronary syndromes. Eur Heart J, 28(13), 1598-1660.
Becattini, C., Vedovati, M. C., & Agnelli, G. (2007). Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation, 116(4), 427-433.
Bonaca, M., Scirica, B., Sabatine, M., Dalby, A., Spinar, J., Murphy, S.A., . . . Morrow, D. A. (2010). Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I. J Am Coll Cardiol, 55(19), 2118-2124.
Daubert, M. A., & Jeremias, A. (2010). The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vas Health and Risk Manag, 6, 691-699.
de Lemos, J. A., Drazner, M. H., Omland, T., Ayers, C. R., Khera, A., Rohatgi, A., . . . McGuire, D. K. (2010). Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA, 304(22), 2503-2512.
De Filippi, C. R., de Lemos, J. K., Christenson, R. H., Gottdiener, J. S., Kop, W. J., Zhan, m., & Seliger, S. L. (2010). Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA, 304(22), 2494-2502.
Diris, J. H., Hackeng, C. M., Kooman, J. P., Pinto, Y. M., Hermens, W. T., & van Dieilen-Visser, M. P. (2004). Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients. Circulation, 109(1), 23-25.
Everett, B. M., Cook, N. R., Magnone, M. C., Bobadilla, M., Kim, E., Rifai, N., . . . Pradhan, A. D. (2011). Sensitivity cardiac troponin T assay and the risk of incident cardiovascular disease in women with and without diabetes mellitus: the woman health study. Circulation, 123(24), 2811-2818.
Filusch, A., Giannitsis, E., Katus, H. A., & Meyer, F. J. (2010). High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. Clin Sci (Land), 119(5), 207-213.
Gaze, D. C., & Collinson, P. O. (2008). Multiple molecular forms of circulating cardiac troponin: analytical and clinical significant. Ann Clin Biochem, 45(4), 349-355.
Giannitsis, E., Kurz, K., Hallermayer, K., Jarausch, J., Jaffe, A. S., & Katus, H. A. (2010). Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem, 56(2), 254-261.
Hamn, C. W., Bassand, J. P., Agewall, S., Bax, J., Boersma, E., Bueno, H., . . . Zahger, D. (2011). ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the Europient Society of Cardiology (ESC). Eur heart J, 32(23), 2999-3054.
Hamn, C. W., Giannitsis, E., & Katus, H. A. (2002). Cardiac troponin elevations in patients without acute coronary syndrome. Circulation, 106(23), 2871-2872.
Hammarsten, O., Fu, M. L., Sigurjonsdottir, R., Petzold, M., Said, L., Landin-Wilhelmsen, K., . . . Johnson, P. (2012). Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction. Clin Chem, 58(3), 628-637.
Hammere-Lercher, A., Ploner, T., Neuruer, S., Schratzberger, P., Griesmacher, A., Pachinger, O., & Mair, J. (2013). High-sensitivity cardiac troponin T compared with standard troponin T testing on emergency department admission: how much does it add in everyday clinical practice? J Am Heart Assoc, 2(3), e000204
Hartshorne, D. J., & Mueller, H. (1968). Fractionation of troponin into two distinct proteins. Biochem Biophys Res Commun, 31(5), 647-653.
Hasson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med, 352(16), 1685-1695.
Horwich, T. B., Patel, J., MacLellan, W. R., & Fonarow, G. C. (2003). Cardiac troponin I is associated with impaired hemodynamic, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation, 108(7), 833-838.
Irfan, A., Twerenbold, R., Reiter, M., Reichlin, T., Stelzig, C., Freese, M., . . . Mueller C. (2012). Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain. Am J Med, 125(5), 491-498.
Jaffe, A. S., Apple, F. S., Morrow, D. A., Lindahl, B., & Katus, H. A. (2010). Being rational about (im)precision: a statement from the Biochemistry Subcommittee of the Joint European Society of Cardiology/ American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the definition of myocardial infarction. Clin chem., 56(6), 941-943.
Jaffe, A. S., Babuin, L., & Apple, F. S. (2006). Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol, 48(1), 1-11.
Jeremias, A., & Gibson, C. M. (2005). Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excludes. Ann Tntern Med, 142(9), 786-791.
Keller, T., Zeller, T., Peetz, D., Tzikas, S., Roth, A., Czyz, E., . . . Blankenberg, S. (2009). Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med, 361(9), 868-877.
Keller, T., Zeller, T., Ojeda, F., Tzikas, S., Lillpopp, L., Sinning, C., . . . Blankenberg, S. (2011). Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA, 306(24), 2684-2693.
Korosoglou, G., Lehrke, S., Mueller, D., Hosch, W., Kauczor, H. U., Humpert, P. M., . . . Katus, H. A. (2011). Determination of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart, 97(10), 823-831.
Kusumoto, A., Miyata, M., Kubozono, T., Ikeda, Y., Shinsato, T., Kuwahata, S., . . . Tei, C. (2012). Highly sensitive cardiac troponin T in heart failure: comparison with achocardiographic parameters and natriuretic peptides. J cardiol, 59(2), 202-208.
Macrae, A. R., Kavsak, P. A., Lusting, V., Bhargava, R., Vandersluis, R., Palomaki G. E., . . . Jaffe, A. S. (2006). Assessing the requirement for the 6-hour interval between specimens in the American heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem, 52(5), 812-818.
Marini, M. G., Cardillo, M. T., Caroli, A., Sonnino, C., & Biasucci, L. M. (2013). Increasing specificity of high-sensitivity troponin: New approaches and perspectives in the diagnosis of acute coronary syndromes. J Cardio, 62(4), 205-209.
Morrow, D. A., Cannon, C. P., Jesse, R. L., Newby, L. K., Ravkilde, J., Storrow, A. B., . . . Tang, W. (2007). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem, 53(4), 552-574.
Mueller, M., Biener, M., Vafaie, M., Doerr, S., Keller, T., Blankenberg, S., . . . Giannitsis, E. (2012). Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome. Clin Chem, 58(1), 209-218.
Mueller, M., Vafaie, M., Biener, M., Giannitsis, E., & Katus, H. A. (2013). Cardiac troponin T. Circ J, 77(7), 1653-1661.
Ndrepepa, G., Braun, S., Mehilli, J., Birkmeier, K. A., Byrne, R. A., Ott, I., . . . Kastrati, A. (2011). Prognostic value of sensitive troponin T in patients with stable and unstable angina and undetectable conventional troponin. Am Heart J, 161(1), 68-75.
O’Brien, P. J., Smith, D. E. C., Knechtel, T. J., Marchak, M. A., Pruimboom-Brees, I., Brees, D. J., . . . Reagan, W. J. (2006). Cardiac troponin I is a sensitive, specific, biomarker of cardiac injury in laboratory animals. Lab Anim, 40(2), 153-171.
Ooi, D. S., Zimmerman, D., Graham, J., & Wells, G. A. (2001). Cardiac troponin T predicts long-term outcomes in hemodialysis patients. Clin Chem, 47(3), 412-417.
Parmacek, M. S., & Solaro, R. J. (2004). Biology of the troponin complex in cardiac myocytes. Prog Cardiovasc Dis, 47(3), 159-176.
Parrillo, J. E. (1993). Pathogenic mechanisms of septic shock. N Engl J Med, 328(20), 1471-1477.
Pope, J. H., Aufderheide, T. P., Ruthazer, R., Woolard, R. H., Feldman, J. A., Beshansky, J. R., . . . Selker, H. P. (2000). Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department. N Engl J Med, 342(16), 1163-1170.
Reichlin, T., Hochholzer, W., Bassetti, S., Steuer, S., Stelzig, C., Hartwiger, S., Biedert, S., Schaub, N., . . . Mueller, C. (2009). Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med, 361(9), 858-867.
Reichlin, T., Irfan, A., Twerenbold, R., Reiter, M., Hochholzer, W., Burkhalter, H., . . . Mueller, C. (2011). Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation, 124(2), 136-145.
Reichlin, T., Schindler, C., Drexler, B., Twerenbold, R., Reiter, M., Zellweger, C., . . . Mueller, C. (2012). One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med, 172(16), 1211-1218.
Reiter, M., Twerenbold, R., Reichlin, T., Haff, P., Haff, P., Peter, F., . . . Mueller, C. (2011). Early diagnosis of acute myocardial infarction in the elder using more sensitive cardiac troponin assays. Eur Heart J, 31(11), 1379-1389.
Robert, R., & Sobel, B. E. (1973). Editorial: Isoenzymes of creatine phosphokinase and diagnosis of myocardial infarction. Ann Intern Med, 79(5), 741-743.
Sabatine, M. S. Morrow, D. A., de Lemos, J. A., Jarolim, P., & Braunwald, E. (2009). Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischemia using an ultrasensitive assay: results from TIMI 35. Eur Heart J, 30(2), 162-169.
Saenger, A. K., Beyrau, R., Braun, S., Cooray, R., Dolci, A., Freidank, H., . . . Jaffe, A. S. (2011). Multicenter analytical evaluation of a high-sensitivity troponin T assay. Clin Chim Acta, 412(9-10), 748-754.
Sato, Y., Yamamoto, E., & Sawa, T. (2011). High-sensitivity cardiac troponin T in essential hypertension. J Cardiol,58(3), 226-231.
Sharma, R., Gaze, D. C., Pellerrin, D., Mehta, R. L., Gregson, H., Streather, C. P., . . . Brecker, S. J. (2006). Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T. Heart, 92(6), 804-809.
Shave, R., Baggish, A., George, K., Wood, M., Scharhag, J., Whyte, G., . . . Thompson, P. D. (2010). Exercise-induced cardiac troponin elevation: mechanisms, and implications. J Am Coll cardiol, 56(3), 169-176.
Shayanfar, N., Bestmann, L., Schulthess, G., & Hersberger, M. (2008). False positive cardiac troponin T due to assay interference with heterophilic antibodies. Swiss Med Wkly, 138(31-32), 470.
Smith, S. C., Ladenson, J. H., Mason, J. W., & Jaffe, A. S. (1997). Elevations of cardiac troponin I associated with myocarditis: Experimental and clinical correlates. Circulation, 95(1), 163-168.
Tate, J. R. (2008). Troponin revisited 2008: assay performance. Clin Chem Lab Med, 46(11), 1489-1500.
Thygesen, K., Alpert, J. S., White, H. D., Jaffe, A.S., Apple, F.S., Galvani, M., . . . Al-Attar, N. (2007). Universal definition of myocardial infarction. Circulation, 116(22), 2634-2653.
Thygesen, K., Mair, J., Katus, H., Plebani, M., Venge, P., Collinson, P., . . . Jaffe, A. S. (2010). Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur Heart J, 31(18), 2197-2204.
Thygesen, K., Alpert, J. S., Jaffe, A. S., White, H. D., Simoons, M. L., Chaitman, M. R., . . . Mendis, S. (2012a). Third universal definition of myocardial infarction. J Am Coll Cardiol, 60(16), 1581-1598.
Thygesen, K., Mair, J., Giannitsis, E., Mueller, C., Lindahl, B., Blankenberg, S., . . . Jaffe, A. S. (2012b). How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J, 33(18), 2252-2257.
Todd, J., Freese, B., Lu, A., Held, D., Morey, J., Livingston, R., & Goix, P. (2007). Ultrasensitive flow-based immunoassays using single-molecule counting. Clin Chem, 53(11), 1990-1995.
Twerenbold, R., Jaffe A., Reichlin, T., Reiter, M., & Mueller, C. (2012). High- sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J, 33(5), 579-586.
Vichaibun, V. (2004). Diagnosis of myocardial infarction with cardiac biomarkers. Bull Health Sci & Tech, 7(2), 65-74.
Wang, K., Asinger R. W., & Marriott H. J. (2003). ST-segment elevation in conditions other than acute myocardial infarction. N Engl J Med, 349(22), 2128-2135.
White, H. D. (2010). Higher sensitivity troponin levels in the community: what do they mean and how will the diagnosis of myocardial infarction be made? Am Heart J, 159(6), 933-936.
Yalamanchili, K., Sukhija, R., Aronow, W.S., Sinha, N., Fleisher, A. G., & Lehrman, S. G. (2004). Prevalent of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism. Am J Cardiol, 93(2), 263-264.
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