Jump to ContentJump to Main Navigation
Show Summary Details
More options …


Official Journal of the Society to Improve Diagnosis in Medicine (SIDM)

Editor-in-Chief: Graber, Mark L. / Plebani, Mario

Ed. by Argy, Nicolas / Epner, Paul L. / Lippi, Giuseppe / Singhal, Geeta / McDonald, Kathryn / Singh, Hardeep / Newman-Toker, David

Editorial Board: Basso , Daniela / Crock, Carmel / Croskerry, Pat / Dhaliwal, Gurpreet / Ely, John / Giannitsis, Evangelos / Katus, Hugo A. / Laposata, Michael / Lyratzopoulos, Yoryos / Maude, Jason / Sittig, Dean F. / Sonntag, Oswald / Zwaan, Laura

CiteScore 2018: 0.69

SCImago Journal Rank (SJR) 2018: 0.359
Source Normalized Impact per Paper (SNIP) 2018: 0.424

See all formats and pricing
More options …

Strategies to overcome misdiagnosis of type 1 myocardial infarction using high sensitive cardiac troponin assays

Beatrice von Jeinsen
  • Department of Internal Medicine III, Division of Cardiology, Goethe University Frankfurt, Frankfurt, Germany
  • German Centre for Cardiovascular Research (DZHK), Partnersite RheinMain, Frankfurt, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Till Keller
  • Corresponding author
  • Department of Internal Medicine III, Division of Cardiology, Goethe University Frankfurt, Frankfurt, Germany
  • German Centre for Cardiovascular Research (DZHK), Partnersite RheinMain, Frankfurt, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-11-24 | DOI: https://doi.org/10.1515/dx-2016-0022


High sensitive cardiac troponin assays have become the gold standard in the diagnosis of an acute type 1 myocardial infarction (MI) in the absence of ST-segment elevation. Several acute or chronic conditions that impact cardiac troponin levels in the absence of a MI might lead to a misdiagnosis of MI. For example, patients with impaired renal function as well as elderly patients often present with chronically increased cardiac troponin levels. Therefore, the diagnosis of MI type 1 based on the 99th percentile upper limit of normal threshold is more difficult in these patients. Different diagnostic approaches might help to overcome this limitation of reduced MI specificity of sensitive troponin assays. First, serial troponin measurement helps to differentiate chronic from acute troponin elevations. Second, specific diagnostic cut-offs, optimized for a particular patient group, like elderly patients, are able to regain specificity. Such an individualized use and interpretation of sensitive cardiac troponin measurements improves diagnostic accuracy and reduces the amount of misdiagnosed MI type 1.

Keywords: acute myocardial infarction (AMI); diagnosis; misdiagnosis; NSTEMI; troponin; type 1 myocardial infarction


  • 1.

    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Eur Heart J [Internet] 2012;33:2551–67.CrossrefGoogle Scholar

  • 2.

    Gore MO, Seliger SL, deFilippi CR, Nambi, V, Christenson, RH, Hashim IA, et al. Age and sex dependent upper reference limits for the high sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;141:520–9.Google Scholar

  • 3.

    Ebashi S. Third component participatin in the superprecipitation of “Natural Actomyosin.” Nature 1963;7:1100.Google Scholar

  • 4.

    Greaser ML, Gergely J. Purification and properties of the components from troponin. J Biol Chem 1973;248:2125–33.PubMedGoogle Scholar

  • 5.

    Syska H, Perry SV, Trayer IP. A new methof of preparation of troponin I ( Inhibitory Protein ) using affinity chromatography. Evidence for three different forms of troponin I in striated muscle. FEBS Lett 1974;40:253–7.CrossrefGoogle Scholar

  • 6.

    Katus H, Remppis A, Looser S, Hallermeier K, Scheffold T, Kuebler W. Enzyme Linked detection immune of acute assay of cardiac troponin T for the myocardial infarction in patients. J Mol Cell Cardiol 1989;21:1349–53.CrossrefGoogle Scholar

  • 7.

    Cummins B, Cummins P. Cardiac specific troponin-I release in canine experimental myocardial infarction: development of a sensitive enzyme-linked immunoassay. J Mol Cell Cardiol 1987;19:999–1010.CrossrefPubMedGoogle Scholar

  • 8.

    Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined–a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol [Internet] 2000;36:959–69.CrossrefGoogle Scholar

  • 9.

    Mingels A, Jacobs L, Michielsen E, Swaanenburg J, Wodzig W, Van Dieijen-Visser M. Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays. Clin Chem 2009;55:101–8.PubMedGoogle Scholar

  • 10.

    Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med [Internet] 2009;361:868–77.CrossrefGoogle Scholar

  • 11.

    Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Sc M, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361:858–67.CrossrefPubMedGoogle Scholar

  • 12.

    Wu AH, Quynh AL, Todd J, Moecks J, Wians F. Short- and long-term biological variation in cardiac troponin I measured with a high-sensitivity assay: implications for clinical practice. Clin Chem 2009;55:52–8.Google Scholar

  • 13.

    Frankenstein L, Wu AH, Hallermayer K, Wians FH, Giannitsis E, Katus HA. Biological variation and reference change value of high-sensitivity troponin T in healthy individuals during short and intermediate follow-up periods. Clin Chem 2011;57:1068–71.CrossrefGoogle Scholar

  • 14.

    Vasile VC, Saenger AK, Kroning JM, Jaffe AS. Biological and analytical variability of a novel high-sensitivity cardiac troponin T assay. Clin Chem 2010;56:1086–90.PubMedCrossrefGoogle Scholar

  • 15.

    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 [Internet] 2012;172:1211–8.CrossrefGoogle Scholar

  • 16.

    Mueller M, Biener M, Vafaie M, Doerr S, Keller T, Blankenberg S, et al. 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 2012;58:209–18.PubMedCrossrefGoogle Scholar

  • 17.

    Reichlin T, Irfan A, Twerenbold R, Reiter M, Hochholzer W, Burkhalter H, et al. Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation 2011;124:136–45.PubMedCrossrefGoogle Scholar

  • 18.

    Giannitsis E, Becker M, Kurz K, Hess G, Zdunek D, Katus HA. High-sensitivity cardiac troponin T for early prediction of evolving non-ST-segment elevation myocardial infarction in patients with suspected acute coronary syndrome and negative troponin results on admission. Clin Chem 2010;56:642–50.CrossrefPubMedGoogle Scholar

  • 19.

    Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett CJ, Than M, et al. Delta troponin for the early diagnosis of AMI in emergency patients with chest pain. Int J Cardiol [Internet] 2013;168:2602–8.CrossrefGoogle Scholar

  • 20.

    Body R, Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, de Filippi C, et al. The use of very low concentrations of high-sensitivity troponin T to rule out acute myocardial infarction using a single blood test. Acad Emerg Med 2016;23:1004–13.PubMedCrossrefGoogle Scholar

  • 21.

    Carlton E, Greenslade J, Cullen L, Body R, Than M, Pickering JW, et al. Evaluation of high-sensitivity cardiac troponin I levels in patients with suspected acute coronary syndrome. JAMA Cardiol [Internet] 2016;1:405–412.CrossrefGoogle Scholar

  • 22.

    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. Eur Heart J [Internet] 2016;37:267–315.CrossrefGoogle Scholar

  • 23.

    Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, deFilippi C, McCord J, et al. Multicenter evaluation of a 0-Hour/1-Hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med [Internet] 2015;68:76–87.Google Scholar

  • 24.

    Neumann JT, Sörensen NA, Schwemer T, Ojeda F, Bourry R, Sciacca V, et al. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol 2016;1:1–8.Google Scholar

  • 25.

    Mahler S, Miller S, Hollander J, Nagurney J, Birkhahn R, Singer A, et al. Identifying patients for early discharge: performance of decision rules among patients with acute chest pain. Int J Cardiol 2013;168:795–802.PubMedCrossrefGoogle Scholar

  • 26.

    Mahler SA, Riley RF, Hiestand BC, Gregory B, Hoekstra JW, Lefebvre CW, et al. The HEART pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 2015;8:195–203.CrossrefPubMedGoogle Scholar

  • 27.

    Meller B, Cullen L, Parsonage WA, Greenslade J, Aldous S, Reichlin T, et al. Accelerated diagnostic protocol using high-sensitivity cardiac troponin T in acute chest pain patients. Int J Cardiol 2015;184:208–15.PubMedCrossrefGoogle Scholar

  • 28.

    Hafner G, Thome-Kromer B, Schaube J, Kupferwasser I, Ehrenthal W, Cummins P, et al. Cardiac troponins in serum in chronic renal failure. Clin Chem 1994;40:1789–90.Google Scholar

  • 29.

    Li D, Keffer J, Corry K, Vazquez M, Jialal I. Nonspecific elevation of troponin T levels in patients with chronic renal failure. Clin Biochem 1995;28:474–7.PubMedCrossrefGoogle Scholar

  • 30.

    Musso P, Cox I, Vidano E, Zambon D, Panteghini M. Cardiac troponin elevations in chronic renal failure: prevalence and clinical significance. Clin Biochem 1999;32:125–30.CrossrefPubMedGoogle Scholar

  • 31.

    deFilippi C, Seliger SL, Kelley W, Duh S-H, Hise M, Christenson RH, et al. Interpreting cardiac troponin results from high-sensitivity assays in chronic kidney disease without acute coronary syndrome. Clin Chem [Internet] 2012;58:1342–51.CrossrefGoogle Scholar

  • 32.

    Keddis MT, El-Zoghby ZM, El Ters M, Rodrigo E, Pellikka PA, Jaffe AS, et al. Cardiac troponin T before and after kidney transplantation: determinants and implications for posttransplant survival. Am J Transplant 2013;13:406–14.CrossrefPubMedGoogle Scholar

  • 33.

    Tsutamoto T, Kawahara C, Yamaji M, Nishiyama K, Fujii M, Yamamoto T, et al. Relationship between renal function and serum cardiac troponin T in patients with chronic heart failure. Eur J Heart Fail 2009;11:653–8.CrossrefPubMedGoogle Scholar

  • 34.

    Fahie-Wilson MN, Carmichael DJ, Delaney MP, Stevens PE, Hall EM, Lamb EJ. Cardiac troponin T circulates in the free, intact form in patients with kidney failure. Clin Chem 2006;52:414–20.PubMedCrossrefGoogle Scholar

  • 35.

    Ooi DS, Isotalo PA, Veinot JP. Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology. Clin Chem 2000;46:338–44.PubMedGoogle Scholar

  • 36.

    Wallace TW, Abdullah SM, Drazner MH, Das SR, Khera A, McGuire DK, et al. Prevalence and determinants of troponin T elevation in the general population. Circulation 2006;113:1958–65.PubMedCrossrefGoogle Scholar

  • 37.

    Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, et al. Relation between renal dysfunction and cardiovascular outcomes and myocardial infarction. N Eng J Med 2004;351:1285–95.CrossrefGoogle Scholar

  • 38.

    Apple FS, Pearce LA, Doyle PJ, Otto AP, Murakami MM. Cardiac troponin risk stratification based on 99th percentile reference cutoffs in patients with ischemic symptoms suggestive of acute coronary syndrome: Influence of estimated glomerular filtration rates. Am J Clin Pathol 2007;127:598–603.CrossrefPubMedGoogle Scholar

  • 39.

    Bueti J, Krahn J, Karpinski M, Bohm C, Fine A, Rigatto C. Troponin I testing in dialysis patients presenting to the emergency room: does troponin I predict the 30-day outcome? Nephron Clin Pract 2006;103:129–36.CrossrefGoogle Scholar

  • 40.

    Van Lente F, McErlean ES, DeLuca SA, Peacock WF, Rao JS, Nissen SE. Ability of troponins to predict adverse outcomes in patients with renal insufficiency and suspected acute coronary syndromes: a case-matched study. J Am Coll Cardiol 1999;33:471–8.PubMedCrossrefGoogle Scholar

  • 41.

    Wayand D, Baum H, Schätzle G, Schärf J, Neumeier D. Cardiac troponin T and I in end-stage renal failure. Clin Chem 2000;46:1345–50.PubMedGoogle Scholar

  • 42.

    Chenevier-Gobeaux C, Meune C, Freund Y, Wahbi K, Claessens Y-E, Doumenc B, et al. Influence of age and renal function on high-sensitivity cardiac troponin T diagnostic accuracy for the diagnosis of acute myocardial infarction. Am J Cardiol [Internet] 2013;111:1701–7.CrossrefGoogle Scholar

  • 43.

    Pfortmueller CA, Funk G-C, Marti G, Leichtle AB, Fiedler GM, Schwarz C, et al. Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency. Am J Cardiol [Internet] 2013;112:1968–72.CrossrefGoogle Scholar

  • 44.

    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 [Internet] 2015;131:2041–50.CrossrefGoogle Scholar

  • 45.

    Liebetrau C, Weber M, Tzikas S, Palapies L, Möllmann H, Pioro G, et al. Identification of acute myocardial infarction in patients with atrial fibrillation and chest pain with a contemporary sensitive troponin I assay. BMC Med [Internet] 2015;13:169.CrossrefGoogle Scholar

  • 46.

    Go AS1, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Eng J Med [Internet] 2004;351:1296–305.CrossrefGoogle Scholar

  • 47.

    Zhang S-J, Wang Q, Cui Y-J, Wu W, Zhao Q-H, Xu Y, et al. High-sensitivity cardiac troponin T in geriatric inpatients. Arch Gerontol Geriatr [Internet] 2016;65:111–5.CrossrefGoogle Scholar

  • 48.

    Saenger AK, Beyrau R, Braun S, Cooray R, Dolci A, Freidank H, et al. Multicenter analytical evaluation of a high-sensitivity troponin T assay. Clin Chim Acta [Internet] 2011;412:748–54.CrossrefGoogle Scholar

  • 49.

    Gore MO, Seliger SL, Defilippi CR, Nambi V, Christenson RH, Hashim IA, et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;63:1441–8.CrossrefPubMedGoogle Scholar

  • 50.

    Keller T, Ojeda F, Zeller T, Wild PS, Tzikas S, Sinning CR, et al. Defining a reference population to determine the 99th percentile of a contemporary sensitive cardiac troponin i assay. Int J Cardiol [Internet] 2013;167:1423–9.CrossrefGoogle Scholar

  • 51.

    McKie PM, Heublein DM, Scott CG, Gantzer ML, Mehta RA, Rodeheffer RJ, et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013;59:1099–107.PubMedCrossrefGoogle Scholar

  • 52.

    Eggers KM, Lind L, Ahlström H, Bjerner T, Ebeling Barbier C, Larsson A, et al. Prevalence and pathophysiological mechanisms of elevated cardiac troponin I levels in a population-based sample of elderly subjects. Eur Heart J 2008;29:2252–8.CrossrefGoogle Scholar

  • 53.

    Zethelius B, Johnston N, Venge P. Troponin I as a predictor of coronary heart disease and mortality in 70-year-old men: a community-based cohort study. Circulation 2006;113:1071–8.CrossrefGoogle Scholar

  • 54.

    Reiter M, Twerenbold R, Reichlin T, Haaf P, Peter F, Meissner J, et al. Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays. Eur Heart J 2011;32:1379–89.CrossrefPubMedGoogle Scholar

  • 55.

    Olivieri F, Galeazzi R, Giavarina D, Testa R, Abbatecola AM, Çeka A, et al. Aged-related increase of high sensitive Troponin T and its implication in acute myocardial infarction diagnosis of elderly patients. Mech Ageing Dev 2012;133:300–5.CrossrefPubMedGoogle Scholar

  • 56.

    Mueller-Hennessen M, Lindahl B, Giannitsis E, Biener M, Vafaie M, deFilippi CR, et al. Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T – Sub-analysis from the TRAPID-AMI study. Int J Cardiol [Internet] 2016;209:26–33.CrossrefGoogle Scholar

  • 57.

    Canto JG, Goldberg RJ, Hand MM, Bonow RO, Sopko G, Pepine CJ, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality. Arch Intern Med 2007;167:2405–13.CrossrefPubMedGoogle Scholar

  • 58.

    Elsaesser A, Hamm CW. Acute coronary syndrome: the risk of being female. Circulation 2004;109:565–7.PubMedCrossrefGoogle Scholar

  • 59.

    Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012;58:1574–81.CrossrefGoogle Scholar

  • 60.

    Apple FS, Simpson PA, Murakami MM. Defining the serum 99th percentile in a normal reference population measured by a high-sensitivity cardiac troponin I assay. Clin Biochem [Internet] 2010;43:1034–6.CrossrefGoogle Scholar

  • 61.

    Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010;56:254–61.CrossrefPubMedGoogle Scholar

  • 62.

    Shah AS, Griffiths M, Lee KK, McAllister DA, Hunter AL, Ferry AV, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. Br Med J [Internet] 2015;350:1–8.Google Scholar

  • 63.

    Sörensen NA, Shah AS, Ojeda FM, Peitsmeyer P, Zeller T, Keller T, et al. High-sensitivity troponin and novel biomarkers for the early diagnosis of non-ST-segment elevation myocardial infarction in patients with atrial fibrillation. Eur Heart J Acute Cardiovasc Care [Internet] 2016;5:419–27.CrossrefGoogle Scholar

  • 64.

    Khan S, Dhillion O, O’Brien R, Struck J, Quinn P, Morgenthaler NG, et al. C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study. Circulation 2007;115:2103–10.CrossrefPubMedGoogle Scholar

  • 65.

    Giannitsis E, Kehayova T, Vafaie M, Katus HA. Combined testing of high-sensitivity troponin T and copeptin on presentation at prespecified cutoffs improves rapid rule-out of non-ST-segment elevation myocardial infarction. Clin Chem 2011;57:1452–5.CrossrefPubMedGoogle Scholar

  • 66.

    Keller T, Tzikas S, Zeller T, Czyz E, Lillpopp L, Ojeda FM, et al. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol [Internet] 2010;55:2096–106.CrossrefGoogle Scholar

  • 67.

    Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, et al. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol [Internet] 2009;54:60–8.CrossrefGoogle Scholar

About the article

Corresponding author: Till Keller, MD, FESC, Department of Internal Medicine III, Division of Cardiology, Goethe University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany, Phone: +49 (0) 69 6301 7387, Fax: +49 (0) 69 6301 6546

Received: 2016-06-30

Accepted: 2016-11-01

Published Online: 2016-11-24

Published in Print: 2016-12-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Diagnosis, Volume 3, Issue 4, Pages 189–198, ISSN (Online) 2194-802X, ISSN (Print) 2194-8011, DOI: https://doi.org/10.1515/dx-2016-0022.

Export Citation

©2016 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Evangelos Giannitsis and Hugo A. Katus
Diagnosis, 2016, Volume 3, Number 4, Page 135

Comments (0)

Please log in or register to comment.
Log in