1,782
Views
43
CrossRef citations to date
0
Altmetric
Review Article

High-sensitivity cardiac troponin assays: From improved analytical performance to enhanced risk stratification

, , &
Pages 143-172 | Received 13 Jul 2016, Accepted 18 Jan 2017, Published online: 01 May 2017

References

  • Aakre KM, Røraas T, Petersen PH, Svarstad E, Sellevoll H, Skadberg Ø, Sæle K, Sandberg S. 2014. Weekly and 90-minute biological variations in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls. Clin Chem. 60:838–847.
  • Adams JE III, Bodor GS, Dávila-Román VG. 1993. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 88:101–106.
  • Agewall S, Giannitsis E, Jernberg T, Katus H. 2011. Troponin elevation in coronary vs. non-coronary disease. Eur Heart J. 32:404–411.
  • Al-Saleh A, Alazzoni A, Al Shalash S, Ye C, Mbuagbaw L, Thabane L, Jolly SS. 2014. Performance of the high-sensitivity troponin assay in diagnosing acute myocardial infarction: systematic review and meta-analysis. CMAJ Open. 2:E199–E207.
  • Analytical characteristics of commercial cardiac troponin I and T assays declared by the manufacturer. 2016. Available from: http://www.ifcc.org/media/276661/IFCC%20Troponin%20Tables%20ng_L%20DRAFT%20Update%20NOVEMBER%202014.pdf [last accessed 10 Dec 2016].
  • Apple FS. 2009. A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem. 55:1303–1306.
  • Apple FS. 2012. Counterpoint: standardization of cardiac troponin I assays will not occur in my lifetime. Clin Chem. 58:169–171.
  • Apple F, Sandoval Y. 2016. Implementing high sensitivity cardiac troponin assays. Available from: https://www.aacc.org/publications/cln/articles/2015/december/implementing-high-sensitivity-troponin assays [last accessed 10 Dec 2016].
  • Apple FS, Collinson PO. 2012. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 58:54–61.
  • Apple FS, Hollander J, Wu AH, Jaffe AS. 2014. Improving the 510(k) FDA process for cardiac troponin assays: in search of common ground. Clin Chem. 60:1273–1275.
  • Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, Hollander J, Plebani M, Than M, Chan MHM, et al. 2015. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem. 48:201–203.
  • Apple FS, Ler R, Murakami MM. 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 FS, Sandoval Y, Jaffe AS, Ordonez-Llanos J. 2017. Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care. Clin Chem. 63:73–81.
  • Aw TC, Phua SK, Tan SP. 2013. Measurement of cardiac troponin I in serum with a new high-sensitivity assay in a large multi-ethnic Asian cohort and the impact of gender. Clin Chim Acta. 422:26–28.
  • Blankenberg S, Salomaa V, Makarova N, Ojeda F, Wild P, Lackner KJ, Jørgensen T, Thorand B, Peters A, Nauck M, et al. 2016. Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium. Eur Heart J. 37:2428.
  • Bohula May EA, Bonaca MP, Jarolim P, Antman EM, Braunwald E, Giugliano RP, Newby LK, Sabatine MS, Morrow DA. 2014. Prognostic performance of a high-sensitivity cardiac troponin I assay in patients with non-ST-elevation acute coronary syndrome. Clin Chem. 60:158–164.
  • Braga F, Panteghini M. 2016. Generation of data on within-subject biological variation in laboratory medicine: an update. Crit Rev Clin Lab Sci. 53:313–325.
  • Cardiac troponin I. 2016. Available from: https://www.hytest.fi/sites/52cd5c487653512f63000004/content_entry52cd6295765351528d000020/541aa02a7653519314002a6a/files/Troponin_Booklet.pdf [last accessed 10 Dec 2016].
  • Carlton E, Greenslade J, Cullen L, Body R, Than M, Pickering JW, Aldous S, Carley S, Hammett C, Kendall J, et al. 2016. Evaluation of high-sensitivity cardiac troponin I levels in patients with suspected acute coronary syndrome. JAMA Cardiol. 1:405–412.
  • Chaitman BR. 2015. Is the 99th percentile the optimal reference limit to diagnose myocardial infarction with high-sensitivity cardiac troponin assays in patients with chronic kidney disease? Circulation. 131:2029–2031.
  • Chenevier-Gobeaux C, Bailleul S, Mzabi A, Blanc MC, Lefevre G. 2013. Upper reference limits of high-sensitivity cardiac troponin T in a general population: comparison with those of sensitive cardiac troponin I. Clin Lab. 59:333–336.
  • Christenson RH, Duh SH, Apple FS, Bodor GS, Bunk DM, Dalluge J, Panteghini M, Potter JD, Welch MJ, Wu AH, et al. 2001. Standardization of cardiac troponin I assays: round robin of ten candidate reference materials. Clin Chem. 47:431–437.
  • Christenson RH, Duh SH, Apple FS, Bodor GS, Bunk DM, Panteghini M, Welch MJ, Wu AH, Kahn SE. 2006. Toward standardization of cardiac troponin I measurements. Part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays. Clin Chem. 52:1685–1692.
  • Christenson RH. 2007. National academy of clinical biochemistry laboratory medicine practice guidelines for utilization of biochemical markers in acute coronary syndromes and heart failure. Clin Chem. 53:545–546.
  • Clinical Laboratory Standards Institute. 2010. Defining, establishing and verifying reference intervals in the clinical laboratory; approved guideline. 3rd ed. EP28-A3c. Wayne (PA): Clinical and Laboratory Standards Institute.
  • Collinson PO, Gaze D, Goodacre S. 2015. The clinical and diagnostic performance characteristics of the high sensitivity Abbott cardiac troponin I assay. Clin Biochem. 48:275–281.
  • Collinson PO, Heung YM, Gaze D, Boa F, Senior R, Christenson R, Apple FS. 2012. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem. 58:219–225.
  • Conrad MJ, Jarolim P. 2014. Cardiac troponins and high-sensitivity cardiac troponin assays. Clin Lab Med. 34:59–73.
  • Corte Z, García C, Venta R. 2015. Biological variation of cardiac troponin T in patients with end-stage renal disease and in healthy individuals. Ann Clin Biochem. 52:53–60.
  • Costa, FM, Ferreira J, Aguiar C, Dores H, Figueira J, Mendes M. 2012. Impact of ESC/ACCF/AHA/WHF universal definition of myocardial infarction on mortality at 10 years. Eur Heart J. 33:2544–2550.
  • Cullen L, Mueller C, Parsonage WA, Wildi K, Greenslade JH, Twerenbold R, Aldous S, Meller B, Tate JR, Reichlin T, et al. 2013. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol. 62:1242–1249.
  • Cummins B, Auckland ML, Cummins P. 1987. Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am Heart J. 113:1333–1344.
  • Dati F, Panteghini M, Apple FS, Christenson RH, Mair J, Wu AH. 1999. Proposals from IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): strategies and concepts on standardization of cardiac marker assays. Scand J Clin Lab Invest. 59:113–123.
  • de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, Hashim I, Berry JD, Das SR, Morrow DA, et al. 2010. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 304:2503–2512.
  • deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan M, Seliger SL. 2010. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA. 304:2494–2502.
  • Di Somma S, Zampini G, Vetrone F, Soto-Ruiz KM, Magrini L, Cardelli P, Ronc C, Maisel A, Peacock FW. 2014. Opinion paper on utility of point-of-care biomarkers in the emergency department pathways decision making. Clin Chem Lab Med. 52:1401–1407.
  • Dupuy AM, Lozano C, Badiou S, Bargnoux AS, Kuster N, Cristol JP. 2013. Biological variability of hs-cardiac troponin T on the Roche Cobas 8000/e602® immunoanalyzer. Clin Chim Acta. 425:62–63.
  • Eggers KM, Johnston N, Lind L, Venge P, Lindahl B. 2015. Cardiac troponin I levels in an elderly population from the community: the implications of sex. Clin Biochem. 48:751–756.
  • Eggers KM, Lind L, Venge P, Lindahl B. 2013. Factors influencing the 99th percentile of cardiac troponin I evaluated in community-dwelling individuals at 70 and 75 years of age. Clin Chem. 59:1068–1073.
  • Eggers KM, Lindahl B, Melki D, Jernberg T. 2016. Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry. Eur Heart J. 37:2417–2424.
  • Executive summary: Scientific Division 56th Meeting. 2015 Nov 20–21. Milan, Italy. Available from: http://www.ifcc.org/media/410758/IFCC_SD_Minutes_56_Milan_summary.pdf
  • Fahim MA, Hayen AD, Horvath AR, Dimeski G, Coburn A, Tan K-S, Johnson DW, Craig JC, Campbell SB, Hawley CM, et al. 2015. Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice. Clin Chem Lab Med. 53:715–722.
  • Feng H-Z, Biesiadecki BJ, Yu Z-B, Hossain MM, Jin J-P. 2008. Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis. J Physiol (Lond). 586:3537–3550.
  • Frankenstein L, Wu AHB, Hallermayer K, Wians FH, Giannitsis E, Katus HA. 2011. Biological variation and reference change value of high-sensitivity troponin T in healthy individuals during short and intermediate follow-up periods. Clin Chem. 57:1068–1071.
  • Franzini M, Lorenzoni V, Masotti S, Prontera C, Chiappino D, Latta DD, Daves M, Deluggi I, Zuin M, Ferrigno L, et al. 2015. The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: a multicenter study in Italy. Clin Chim Acta. 438:376–381.
  • Fraser CG. 2016. Interpretation of differences in serial troponin results. Available from: https://www.westgard.com/troponin-interpretations.htm
  • Gaggin HK, Dang PV, Do LD, deFilippi CR, Christenson RH, Lewandrowski EL, Lewandrowski KB, Truong BQ, Pham VQ, Vu VH, et al. 2014. Reference interval evaluation of high-sensitivity troponin T and N-terminal B-type natriuretic peptide in Vietnam and the US: the North South East West Trial. Clin Chem. 60:758–764.
  • Giannitsis E, Katus HA. 2013. Cardiac troponin level elevations not related to acute coronary syndromes. Nat Rev Cardiol. 10:623–634.
  • Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. 2010. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 56:254–261.
  • Giannoni A, Giovannini S, Clerico A. 2009. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal? Clin Chem Lab Med. 47:1167–1177.
  • Goldberg J, Iriate B, Prostko J. 2011. Short and long-term biological variation of troponin-I determined using the Architect STAT high sensitive troponin-I assay. Clin Chem. 57:A97.
  • Gomes AV, Potter JD, Szczesna-Cordary D. 2002. The role of troponins in muscle contraction. IUBMB Life. 54:323–333.
  • Gore MO, Seliger SL, Defilippi CR, Nambi V, Christenson RH, Hashim IA, Hoogeveen RC, Ayers CR, Sun W, McGuire DK, et al. 2014. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol. 63:1441–1448.
  • Greene DN, Leong TK, Collinson PO, Kamer SM, Huang K, Lorey TS, Go AS. 2015. Age, sex, and racial influences on the Beckman Coulter AccuTnI +3 99th percentile. Clin Chim Acta. 444:149–153.
  • Haaf P, Reichlin T, Twerenbold R, Hoeller R, Rubini Gimenez M, Zellweger C, Moehring B, Fischer C, Meller B, Wildi K, et al. 2014. Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays. Eur Heart J. 35:365–375.
  • Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D; ESC Committee for Practice Guidelines. 2011. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 32:2999–3054.
  • Hamm CW, Giannitsis E, Katus HA. 2002. Cardiac troponin elevations in patients without acute coronary syndrome. Circulation. 106:2871–2872.
  • Hausner EA. 2015. Cardiac muscle and the troponins. In: Gowraganahalli J, Pitchai B, Khin MU, editors. Pathophysiology and pharmacotherapy of cardiovascular disease. Switzerland: Springer International Publishing; p. 179–192.
  • Hickman PE, Potter JM, Aroney C, Koerbin G, Southcott E, Wu AHB, Roberts MS. 2010. Cardiac troponin may be released by ischemia alone, without necrosis. Clin Chim Acta. 411:318–323.
  • Hillinger P, Twerenbold R, Jaeger C, Wildi K, Reichlin T, Rubini Gimenez M, Engels U, Miró O, Boeddinghaus J, Puelacher C, et al. 2015. Optimizing early rule-out strategies for acute myocardial infarction: utility of 1-hour copeptin. Clin Chem. 61:1466–1474.
  • Irfan A, Reichlin T, Twerenbold R, Meister M, Moehring B, Wildi K, Bassetti S, Zellweger C, Gimenez MR, Hoeller R, et al. 2013. Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations. Am J Med. 126:781–788.e2.
  • Jaffe AS, Apple FS, Morrow DA, Lindahl B, Katus HA, et al. 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. 56:941–943.
  • Jaffe AS. The 10 commandments of troponin, with special reference to high sensitivity assays. Heart. 2011;97:940–946.
  • Jaeger C, Wildi K, Twerenbold R, Reichlin T, Rubini Gimenez M, Neuhaus J-D, Grimm K, Boeddinghaus J, Hillinger P, Nestelberger T, et al. 2016. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am Heart J. 171:92–102.e1–5.
  • James S, Flodin M, Johnston N, Lindahl B, Venge P. 2006. The antibody configurations of cardiac troponin I assays may determine their clinical performance. Clin Chem. 52:832–837.
  • Jarolim P. 2015. High sensitivity cardiac troponin assays in the clinical laboratories. Clin Chem Lab Med. 53:635–652.
  • Javed U, Aftab W, Ambrose JA, Wessel RJ, Mouanoutoua M, Huang G, Barua RS, Weilert M, Sy F, Thatai D, et al. 2009. Frequency of elevated troponin I and diagnosis of acute myocardial infarction. Am J Cardiol. 104:9–13.
  • Jeremias A, Gibson CM. 2005. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med. 142:786–791.
  • Ji M, Moon HW, Hur M, Yun YM. 2016. Determination of high-sensitivity cardiac troponin I 99th percentile upper reference limits in a healthy Korean population. Clin Biochem. 49:756–761.
  • Katrukha IA. 2013. Human cardiac troponin complex. Structure and functions. Biochemistry (Mosc). 78:1447–1465.
  • Katus HA, Remppis A, Looser S, Hallermeier K, Scheffold T, Kübler W. 1989. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol. 21:1349–1353.
  • Keller T, Tzikas S, Zeller T, Czyz E, Lillpopp L, Ojeda FM, Roth A, Bickel C, Baldus S, Sinning CR, et al. 2010. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol. 55:2096–2106.
  • Keller T, Zeller T, Ojeda F, Tzikas S, Lillpopp L, Sinning C, Wild P, Genth-Zotz S, Warnholtz A, Giannitsis E, et al. 2011. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA. 306:2684–2693.
  • Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, Bickel C, Baldus S, Warnholtz A, Fröhlich M. 2009. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med. 361:868–877.
  • Khalili H, de Lemos JA. 2014. What constitutes a relevant change in high-sensitivity troponin values over serial measurement? Clin Chem. 60:803–805.
  • Kimenai DM, Henry RMA, van der Kallen CJH, Dagnelie PC, Schram MT, Stehouwer CDA, van Suijlen JDE, Niens M, Bekers O, Sep SJS, et al. 2016. Direct comparison of clinical decision limits for cardiac troponin T and I. Heart. 102:610–616.
  • Klinkenberg LJJ, van Dijk J-W, Tan FES, van Loon LJC, van Dieijen-Visser MP, Meex SJR. 2014. Circulating cardiac troponin T exhibits a diurnal rhythm. J Am Coll Cardiol. 63:1788–1795.
  • Klinkenberg LJJ, Wildi K, van der Linden N, Kouw IWK, Niens M, Twerenbold R, Rubini Gimenez M, Puelacher C, Daniel Neuhaus J, Hillinger P, et al. 2016. Diurnal rhythm of cardiac troponin: consequences for the diagnosis of acute myocardial infarction. Clin Chem. 62:1602–1611.
  • Koerbin G, Abhayaratna WP, Potter JM, Apple FS, Jaffe AS, Ravalico TH, Hickman PE. 2013. Effect of population selection on 99th percentile values for a high sensitivity cardiac troponin I and T assays. Clin Biochem. 46:1636–1643.
  • Koerbin G, Potter JM, Abhayaratna WP, Telford RD, Badrick T, Apple FS, Jaffe AS, Hickman PE. 2012. Longitudinal studies of cardiac troponin I in a large cohort of healthy children. Clin Chem. 58:1665–1672.
  • Koerbin G, Tate J, Potter JM, Cavanaugh J, Glasgow N, Hickman PE. 2012. Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population. Clin Chem Lab Med. 50:871–878.
  • Koerbin G, Tate JR, Hickman PE. 2010. Analytical characteristics of the Roche highly sensitive troponin T assay and its application to a cardio-healthy population. Ann Clin Biochem. 47:524–528.
  • Kozinski M, Bielis L, Wisniewska-Szmyt J, Boinska J, Stolarek W, Marciniak A, Kubica A, Grabczewska Z, Navarese EP, Andreotti F, et al. 2011. Diurnal variation in platelet inhibition by clopidogrel. Platelets. 22:579–587.
  • Koziński M, Bielis L, Wiśniewska-Szmyt J, Sukiennik A, Grabczewska Z, Swiatkiewicz I, Ziołkowski M, Rość D, Kubica J. 2008. Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first ST-segment elevation myocardial infarction: preliminary report. Cardiol J. 15:530–536.
  • Krintus M, Kozinski M, Boudry P, Lackner K, Lefèvre G, Lennartz L, Lotz J, Manysiak S, Shih J, Skadberg Ø, et al. 2015. Defining normality in a European multinational cohort: critical factors influencing the 99th percentile upper reference limit for high sensitivity cardiac troponin I. Int J Cardiol. 187:256–263.
  • Krintus M, Kozinski M, Boudry P, Capell NE, Köller U, Lackner K, Lefèvre G, Lennartz L, Lotz J, Herranz AM, et al. 2014. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay. Clin Chem Lab Med. 52:1657–1665.
  • Krintus M, Kozinski M, Fabiszak T, Kuligowska-Prusinska M, Laskowska E, Lennartz L, Nowak-Los L, Kubica J, Sypniewska G, et al. 2016. Impact of lipid markers and high-sensitivity C-reactive protein on the value of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I. Clin Chim Acta. 462:193–200.
  • Larue C, Calzolari C, Bertinchant JP, Leclercq F, Grolleau R, Pau, B. 1993. Cardiac-specific immunoenzymometric assay of troponin I in the early phase of acute myocardial infarction. Clin Chem. 39:972–979.
  • Layfield C, Rose J, Alford A, Snyder SR, Apple FS, Chowdhury FM, Kontos MC, Newby LK, Storrow AB, Tanasijevic M, et al. 2015. Effectiveness of practices for improving the diagnostic accuracy of Non ST Elevation Myocardial Infarction in the Emergency Department: a Laboratory Medicine Best Practices™ systematic review. Clin Biochem. 48:204–212.
  • Lee G, Liu S. 2015. Monoclonal antibodies against human cardiac troponin I for immunoassays II. Monoclon Antib Immunodiagn Immunother. 34:169–173.
  • Lee GR, Browne TCA, Guest B, Khan I, Murphy E, McGorrian C, Mahon NG, Fitzgibbon MC. 2016. Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: more than just a sensitivity issue. Pract Lab Med. 4:62–75.
  • Leuschner F, Li J, Goser S, Reinhardt L, Ottl R, Bride P, Zehelein J, Pfitzer G, Remppis A, Giannitsis E, et al. 2008. Absence of auto-antibodies against cardiac troponin I predicts improvement of left ventricular function after acute myocardial infarction. Eur Heart J. 29:1949–1955.
  • Lipinski MJ, Baker NC, Escárcega RO, Torguson R, Chen F, Aldous SJ, Christ M, Collinson PO, Goodacre SW, Mair J, et al. 2015. Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis. Am Heart J. 169:6–16.e6.
  • Lipinski MJ, Escárcega RO, D'Ascenzo F, Magalhães MA, Baker NC, Torguson R, Chen F, Epstein SE, Miró O, Llorens P, et al. 2014. A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule-out of acute myocardial infarction. Am J Cardiol. 113:1581–1591.
  • Lippi G, Cervellin G. 2014. Genetic polymorphisms of human cardiac troponins as an unrecognized challenge for diagnosing myocardial injury. Int J Cardiol. 171:467–470.
  • Lu QW, Wu XY, Morimoto S. 2013. Inherited cardiomyopathies caused by troponin mutations. J Geriatr Cardiol. 10:91–101.
  • Macrae AR, Kavsak PA, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, Yerna M-J, Jaffe AS. 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. 52:812–818.
  • Mbagaya W, Luvai A, Lopez B. 2015. Biological variation of cardiac troponin in stable haemodialysis patients. Ann Clin Biochem. 52:562–568.
  • McKie PM, Heublein DM, Scott CG, Gantzer ML, Mehta RA, Rodeheffer RJ, Redfield MM, Burnett JC, Jaffe AS. 2013. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem. 59:1099–1107.
  • Melki D, Lugnegård J, Alfredsson J, Lind S, Eggers KM, Lindahl B, Jernberg T. 2015. Implications of introducing high-sensitivity cardiac troponin T Into Clinical Practice: Data From the SWEDEHEART Registry. J Am Coll Cardiol. 65:1655–1664.
  • Möckel M, Giannitsis E, Mueller C, Huber K, Jaffe AS, Mair J, Plebani M, Thygesen K, Lindahl B; Biomarker Study Group of the European Society of Cardiology Acute Cardiovascular Care Association. 2016. Rule-in of acute myocardial infarction: focus on troponin. Eur Heart J Acute Cardiovasc Care. Forthcoming. doi: 10.1177/2048872616653228.
  • Mockel M, Searle J, Hamm C, Slagman A, Blankenberg S, Huber K, Katus H, Liebetrau C, Muller C, Muller R, et al. 2015. Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study. Eur Heart J. 36:369–376.
  • Mueller T, Egger M, Leitner I, Gabriel C, Haltmayer M, Dieplinger B. 2016a. Reference values of galectin-3 and cardiac troponins derived from a single cohort of healthy blood donors. Clin Chim Acta. 456:19–23.
  • Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, deFilippi C, McCord J, Body R, Panteghini M, Jernberg T, Plebani M, et al. 2016b. Multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med. 68:76–87.
  • Mueller C, Giannitsis E, Möckel M, Mair J, Plebani M, Thygesen K, Jaffe AS, Lindahl B; Biomarker Study Group of the ESC Acute Cardiovascular Care Association. 2016c. Rapid rule out of acute myocardial infarction: novel biomarker-based strategies. Eur Heart J Acute Cardiovasc Care. Forthcoming. doi: 10.1177/2048872616653229.
  • Mueller C. 2014. Biomarkers and acute coronary syndromes: an update. Eur Heart J. 35:552–556.
  • Mueller-Hennessen M, Lindahl B, Giannitsis E, Biener M, Vafaie M, deFilippi CR, Christ M, Santalo-Bel M, Panteghini M, Plebani M, et al. 2016. Diagnostic and prognostic implications using age- and gender-specific cutoffs for high-sensitivity cardiac troponin T – sub-analysis from the TRAPID-AMI study. Int J Cardiol. 209:26–33.
  • Neumann JT, Sörensen NA, Schwemer T, Ojeda F, Bourry R, Sciacca V, Schaefer S, Waldeyer C, Sinning C, Renné T, et al. 2016. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol. 1:397–404.
  • Nordenskjold AM, Ahlstrom H, Eggers KM, Frobert O, Jaffe AS, Venge P, Lindahl B. 2013. Short- and long-term individual variation in cardiac troponin in patients with stable coronary artery disease. Clin Chem. 59:401–409.
  • Omland T, Pfeffer MA, Solomon SD, de Lemos JA, Røsjø H, Šaltytė Benth J, Maggioni A, Domanski MJ, Rouleau JL, Sabatine MS, et al. 2013. Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. J Am Coll Cardiol. 61:1240–1249.
  • Panteghini M, Bunk DM, Christenson RH, Katrukha A, Porter RA, Schimmel H, Wang L, Tate JR, IFCC Working Group on Standardization of Troponin I. 2008. Standardization of troponin I measurements: an update. Clin Chem Lab Med. 46:1501–1506.
  • Panteghini M. 2004. Current concepts in standardization of cardiac marker immunoassays. Clin Chem Lab Med. 42:3–8.
  • Panteghini M. 2005. Standardization of cardiac troponin I measurements: the way forward? Clin Chem. 51:1594–1597.
  • Pecoraro V, Germagnoli L, Banfi G. 2014. Point-of-care testing: where is the evidence? A systematic survey. Clin Chem Lab Med. 52:313–324.
  • Raskovalova T, Twerenbold R, Collinson PO, Keller T, Bouvaist H, Folli C, Giavarina D, Lotze U, Eggers KM, Dupuy A-M, et al. 2014. Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis. Eur Heart J Acute Cardiovasc Care. 3:18–27.
  • Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, et al. 2009. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 361:858–867.
  • Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, Moehring B, Ziller R, Hoeller R, Rubini Gimenez M, et al. 2012. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med. 172:1211–1218.
  • Reichlin T, Twerenbold R, Maushart C, Reiter M, Moehring B, Schaub N, Balmelli C, Gimenez MR, Hoeller R, Sakarikos K, et al. 2013. Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J. 165:371–378.e3.
  • Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti S, Balmelli C, Winkler K, Kurz S, Stelzig C, Freese M, et al. 2012. Introduction of high-sensitivity troponin assays: impact on myocardial infarction incidence and prognosis. Am J Med. 125:1205–1213.e1.
  • Reichlin T, Twerenbold R, Wildi K, Rubini Gimenez M, Bergsma N, Haaf P, Druey S, Puelacher C, Moehring B, Freese M, et al. 2015. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 187:E243–E252.
  • Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, et al. 2016. 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. 37:267–315.
  • Rubini Gimenez M, Twerenbold R, Jaeger C, Schindler C, Puelacher C, Wildi K, Reichlin T, Haaf P, Merk S, Honegger U, et al. 2015. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 128:861–870.e4.
  • Rubini Gimenez M, Twerenbold R, Reichlin T, Wildi K, Haaf P, Schaefer M, Zellweger C, Moehring B, Stallone F, Sou SM, et al. 2014. Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction. Eur Heart J. 35:2303–2311.
  • Ryan JB, Wallace J, Sies CW, Florkowski CM, George PM. 2015. Evaluation of Abbott Architect high-sensitivity troponin I assay for haemolysis interference. Pathology. 47:716–718.
  • Saenger AK, Beyrau R, Braun S, Cooray R, Dolci A, Freidank H, Giannitsis E, Gustafson S, Handy B, Katus H, et al. 2011. Multicenter analytical evaluation of a high-sensitivity troponin T assay. Clin Chim Acta. 412:748–754.
  • Sandoval Y, Apple FS. 2014. The global need to define normality: the 99th percentile value of cardiac troponin. Clin Chem. 60:455–462.
  • Sandoval Y, Apple FS, Smith SW. 2016. High-sensitivity cardiac troponin assays and unstable angina. Eur Heart J Acute Cardiovasc Care. Forthcoming. doi: 10.1177/2048872616658591.
  • Sarko J, Pollack CV. Jr. 2002. Cardiac troponins. J Emerg Med. 23:57–65.
  • Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, Hoogeveen RC, Liu X, Astor BC, Mosley TH, et al. 2011. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation. 123:1367–1376.
  • Savukoski T. 2016. Cardiac troponin specific autoantibodies: analytical tools for exploring their impact on cardiac troponin I testing. PhD thesis. University of Turku. Available from: https://www.doria.fi/bitstream/handle/10024/99057/AnnalesAII293Savukoski.pdf?sequence=2 [last accessed 10 Dec 2016].
  • Scharnhorst V, Krasznai K, van’t Veer M, Michels RH. 2012. Variation of cardiac troponin I and T measured with sensitive assays in emergency department patients with noncardiac chest pain. Clin Chem. 58:1208–1214.
  • Schindler EI, Szymanski JJ, Hock KG, Geltman EM, Scott MG. 2016. Short- and long-term biologic variability of galectin-3 and other cardiac biomarkers in patients with stable heart failure and healthy adults. Clin Chem. 62:360–366.
  • Shah AS, Griffiths M, Lee KK, McAllistar AD, Hunter AL, Ferry AV, Cruikshank A, Reid A, Stoddart M, Strachan F, et al. 2015a. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 350:g7873.
  • Shah ASV, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, Chapman AR, Langdon T, Sandeman D, Vaswani A, et al. 2015b. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort. Lancet. 386:2481–2488., on behalf of the High-STEACS investigators.
  • Simpson AJ, Potter JM, Koerbin G, Oakman C, Cullen L, Wilkes GJ, Scanlan SL, Parsonage W, Hickman PE. 2014. Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values. Clin Chem. 60:848–854.
  • Stacy SR, Suarez-Cuervo C, Berger Z, Wilson LM, Yeh H-C, Bass EB, Michos ED. 2014. Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review. Ann Intern Med. 161:502–512.
  • Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) 2012. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 33:2569–2619.
  • Storrow AB, Nowak RM, Diercks DB, Singer AJ, Wu AHB, Kulstad E, LoVecchio F, Fromm C, Headden G, Potis T, et al. 2015. Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: results of a prospective multicenter trial. Clin Biochem. 48:260–267.
  • Sztefko K. 2011. Troponin measurement by immunoassay – problem of low assay sensitivity and interference from heterophilic antibodies. In: Sztefko K, editor. Immunodiagnostics and patient safety. Berlin: De Gruyter; p. 129–136.
  • Tate JR, Bunk DM, Christenson RH, Barth JH, Katrukha A, Noble JE, Schimmel H, Wang L, Panteghini M, IFCC Working Group on Standardization of Cardiac Troponin I. 2015. Evaluation of standardization capability of current cardiac troponin I assays by a correlation study: results of an IFCC pilot project. Clin Chem Lab Med. 53:677–690.
  • Tate JR, Bunk DM, Christenson RH, Katrukha A, Noble JE, Porter RA, Schimmel H, Wang L, Panteghini M, IFCC Working Group on Standardization of Troponin I. 2010. Standardisation of cardiac troponin I measurement: past and present. Pathology. 42:402–408.
  • Tate JR, Panteghini M. 2013. Measurement of cardiac troponins revisited. Biochim Clin. 32:535–546.
  • Ter Avest E, Visser A, Reitsma B, Breedveld R, Wolthuis A. 2016. Point-of-care troponin T is inferior to high-sensitivity troponin T for ruling out acute myocardial infarction in the emergency department. Eur J Emerg Med. 23:95–101.
  • Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J, Flaws D, Hammett CJ, Beam DM, Ardagh MW, et al. 2012. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 59:2091–2098.
  • Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, Peacock WF, Parsonage WA, Ho HF, Ko HF, et al. 2011. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 377:1077–1084.
  • Than MP, Pickering JW, Aldous SJ, Cullen L, Frampton CMA, Peacock WF, Jaffe AS, Goodacre, SW, Richards AM, Ardagh MW, et al. 2016. Effectiveness of EDACS versus ADAPT accelerated diagnostic pathways for chest pain: a pragmatic randomized controlled trial embedded within practice. Ann Emerg Med. 68:93–102.
  • Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. 2012. Third universal definition of myocardial infarction. Eur Heart J. 33:2551–2567.
  • Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, Huber K, Plebani M, Biasucci LM, Tubaro M, et al. 2012. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 33:2252–2257.
  • Trambas C, Pickering JW, Than M, Bain C, Nie L, Paul E, Dart A, Broughton A, Schneider HG. 2016. Impact of high-sensitivity troponin I testing with sex-specific cutoffs on the diagnosis of acute myocardial infarction. Clin Chem. 62:831–838.
  • Twerenbold R, Jaeger C, Rubini Gimenez M, Wildi K, Reichilin T, Nestelberger T, Boeddinghaus J, Puelacher C, Moehring B, Pretre G, et al. 2016. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 37:3324–3332.
  • Twerenbold R, Wildi K, Jaeger C, Gimenez MR, Reiter M, Reichlin T, Walukiewicz A, Gugala M, Krivoshei L, Marti N, et al. 2015. Optimal cutoff levels of more sensitive cardiac troponin assays for the early diagnosis of myocardial infarction in patients with renal dysfunction. Circulation. 131:2041–2050.
  • Ungerer JP, Tate JR, Pretorius CJ. 2016. Discordance with 3 cardiac troponin I and T assays: implications for the 99th percentile cutoff. Clin Chem. 62:1106–1114.
  • Using high sensitivity cardiac troponin assays in practice. 2016. Available from: http://www.ifcc.org/media/259738/201405_TF_CB_IFCC_practice%20Summary.pdf
  • Vasile VC, Saenger AK, Kroning JM, Klee GG, Jaffe AS. 2011. Biologic variation of a novel cardiac troponin I assay. Clin Chem. 57:1080–1081.
  • Vasile VC, Saenger AK, Kroning JM, Jaffe AS. 2010. Biological and analytical variability of a novel high-sensitivity cardiac troponin T assay. Clin Chem. 56:1086–1090.
  • Weber M, Bazzino O, Navarro Estrada JL, de Miguel R, Salzberg S, Fuselli JJ, Liebetrau C, Woelken M, Moellmann H, Nef H, et al. 2011. Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome. Am Heart J. 162:81–88.
  • Wildi K, Gimenez MR, Twerenbold R, Reichlin T, Jaeger C, Heinzelmann A, Arnold C, Nelles B, Druey S, Haaf P, et al. 2015. Misdiagnosis of myocardial infarction related to limitations of the current regulatory approach to define clinical decision values for cardiac troponin. Circulation. 131:2032–2040.
  • Wildi K, Reichlin T, Twerenbold R, Mäder F, Zellweger C, Moehring B, Stallone F, Minners J, Rubini Gimenez M, Hoeller R, et al. 2013. Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction. Int J Cardiol. 168:4103–4110.
  • Wu AH, Akhigbe P, Wians F. 2012. Long-term biological variation in cardiac troponin I. Clin Biochem. 45:714–716.
  • Wu AH, Christenson RH. 2013. Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care. Clin Biochem. 46:969–978.
  • Wu AH, Feng YJ, Moore R, Apple FS, McPherson PH, Buechler KF, Bodor G. 1998. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization. Clin Chem. 44:1198–1208.
  • Wu AH, Lu QA, Todd J, Moecks J, Wians F. 2009. Short- and long-term biological variation in cardiac troponin I measured with a high-sensitivity assay: implications for clinical practice. Clin Chem. 55:52–58.
  • Zeller T, Ojeda F, Brunner FJ, Peitsmeyer P, Münzel T, Binder H, Pfeiffer N, Michal M, Wild PS, Blankenberg S, et al. 2015. High-sensitivity cardiac troponin I in the general population – defining reference populations for the determination of the 99th percentile in the Gutenberg Health Study. Clin Chem Lab Med. 53:699–706.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.