High Sensitivity Troponin Testing

High Sensitivity Troponin Testing

2016-11-11T19:03:27+00:00

Lab_blooddraw copyTroponin testing is an important component of the diagnostic workup and management of acute coronary syndromes (ACS). The increasing sensitivity of troponin assays has lowered the number of potentially missed ACS diagnoses, but this has also created a diagnostic challenge due to a decrease in the specificity of the test. From 1995 to 2007, the limit of troponin detection fell from 0.5 ng/mL to 0.006 ng/mL (see below graph). Robert Jesse summed up this frustration with the following quote:

When troponin was a lousy assay it was a great test, but now that it’s becoming a great assay, it’s getting to be a lousy test.

 

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How good is ECG alone for diagnosis of acute myocardial infarction (AMI)? 2

  • Specificity 97%
  • Sensitivity 28%
  • Due to the poor sensitivity of ECGs, cardiac biomarkers are also needed.

Does an elevated high sensitivity troponin (hsTn) mean acute coronary syndrome (ACS)?

  • hsTn can be found circulating in the plasma as a result of any transient ischemic or inflammatory myocardial injury, such as cardioversion, CHF, aortic dissection, HOCM, tachyarrhythmia, myocarditis/pericarditis 1
  • Non-cardiac causes of elevated hsTn include: PE, renal failure, SAH, sepsis, burns, and extreme exertion (i.e. marathons) 1
Serial Tn Testing 2

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What should a provider do with troponin elevation from non-ACS etiologies? 3

  • Unfortunately, little data is available on management of these patients
  • There is data evolving on elevated Tn levels in conditions such as CHF, PE, sepsis, and renal failure
  • There is a proposed algorithm currently from the best evidence available (has not been validated):

Type 2 MI algorithm

How often is serial troponin testing needed with hsTn to rule out acute MI (every 2, 4, 6, or 8 hours)?

  • 1/5 of patients with normal hsTn at presentation will be diagnosed with AMI on repeat testing 4
  • The National Institute for Health and Clinical Excellence (NICE) Guidelines recommend measuring Tn on admission and 10 – 12 hours after the onset of symptoms (This needs to be updated, due to current use of hsTn testing) 2
  • Most recent guidelines from Global Task Force state Tn testing should be obtained at admission and at 3 – 6 hours after admission, irrespective of the timing of the onset of symptoms 4
  • Lower sensitivity Tn requires at least 6 hours between time of initial lab and repeat Tn to see a conclusive increase to rule in AMI 1
  • High sensitivity Tn requires only 2 to 3 hours between time of initial lab and repeat Tn to see a conclusive increase to rule in AMI 1
  • A normal hsTn at 3 hours has a NPV of 99% in excluding AMI 2
  • Dr Louise Cullen et al have recently published a paper:5
    • 1,635 patients with 30 day follow up for Major Adverse Cardiac Events (MACE)
    • Non-ischemic ECG, TIMI of 0, and negative hsTn (0 and 2 hours): 0% MACE with Sens 100%, Spec 23.1%, NPV 100%
    • Non-ischemic ECG, TIMI of ≤1, and negative hsTn (0 and 2 hours): 0.8% MACE with Sens 99.2%, Spec 48.7%, and NPV 99.7%
    • Conclusion: Early discharge strategy utilizing a hsTn assay, TIMI ≤1, and non-ischemic ECG can safely decrease observation periods and admissions in approximately 40% of patients with suspected ACS
  • Current best EBM: Serial sampling of hsTn at 0 and 2 hours is essential to permit the safe rule-out of AMI and to minimize misdiagnosis in patients with elevated hsTn (Another case of guidelines being behind)

What is considered a “significant change” in hsTn levels? 4

  • According to the European Society of Cardiology (ESC):
    • Increase of ≥20% if first Tn elevated, or
    • Increase of ≥50% in patients with small initial Tn elevations
ESC Tn Testing Recs 2

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Conclusion

hsTn is the preferred biomarker for the diagnosis of AMI, but remember that conditions other than AMI may cause acute and chronic elevations.

1.
Mahajan V, Jarolim P. How to interpret elevated cardiac troponin levels. Circulation. 2011;124(21):2350-2354. [PubMed]
2.
Shah A, Newby D, Mills N. High sensitivity cardiac troponin in patients with chest pain. BMJ. 2013;347:f4222. [PubMed]
3.
de L. Increasingly sensitive assays for cardiac troponins: a review. JAMA. 2013;309(21):2262-2269. [PubMed]
4.
Shah A, Newby D, Mills N. High-sensitivity troponin assays and the early rule-out of acute myocardial infarction. Heart. 2013;99(21):1549-1550. [PubMed]
5.
Cullen L, Mueller C, Parsonage W, et al. 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. 2013;62(14):1242-1249. [PubMed]
Salim Rezaie, MD

Salim Rezaie, MD

ALiEM Associate Editor
Clinical Assistant Professor of EM and IM
University of Texas Health Science Center at San Antonio
Founder, Editor, Author of R.E.B.E.L. EM and REBEL Reviews
  • Derek Sifford

    This is a fantastic summary! Great work (as usual) – it is much appreciated!

    Thanks 🙂

  • Alex Kobzik

    “Most recent guidelines from Global Task Force state Tn testing should be obtained at admission and at 3 – 6 hours after admission, irrespective of the timing of the onset of symptoms” – Why irrespective? Shouldn’t our understanding of troponin physiology be helpful?

    • Salim R. Rezaie

      Hello Alex,
      I agree that we should know that if this is ACS, after two hours of symptoms with our assays we should be able to safely rule in or rule out MI. The 3rd universal definition of MI (http://eurheartj.oxfordjournals.org/content/33/20/2551.full?ijkey=c645f2caa66e112c745624b330ce4310f7afae42&keytype2=tf_ipsecsha) states that we need to see a rise and fall of Tn.

      Serial sampling of troponin is important not just to permit the safe rule-out of myocardial infarction, but also to minimise the potential for misdiagnosis in patients with elevated cardiac troponin concentrations
      “Blood samples for the measurement of cTn should be drawn on first assessment and repeated 3–6 h later.” Later samples are required if further ischaemic episodes occur, or when the timing of the initial symptoms is unclear. To establish the diagnosis of MI, a rise and/or fall in values with at least one value above the decision level is required, coupled with a strong pre-test likelihood.

      Finally, In studies using hs-cTnT for diagnosis of AMI, it has been suggested that some patients will require at least 6 h for a definitive diagnosis (http://www.clinchem.org/content/58/3/628.short).

      I hope this helps. Great question.

      Salim

  • shaz

    When observing for rise or fall of tn, what do you refer to when you say , “a value above descision level.”

    • Salim R. Rezaie

      Hello Shaz,
      Use the hyperlink for image 4 to help with this. But a summary is listed below. Every institution has slightly different cut off levels, so you will have to ask your lab what the cut off levels are at your hospital.

      According to the European Society of Cardiology (ESC):
      Increase of ≥20% if first Tn elevated, or
      Increase of ≥50% in patients with small initial Tn elevations

      Hope this helps.
      Salim

  • Joe Bove

    In the highest risk chest pain patients can 2 sets of the hs troponin rule out MI. As in what percent of patients will rule in on their 3rd troponin.

    • Salim R. Rezaie

      Hello Joe,
      I would argue that in high risk patients, regardless of 2 sets of enzymes, if the story is good they probably would benefit from a cardiology or at least an obs admission. I don’t think that I am cavalier enough to just d/c these patients home based on two sets of enzymes. Also in the post, the patient population that I am referencing had TIMI scores of less than or equal to one (i.e. low risk population). I think this is the population that this is most useful in…no ischemic or new changes on ECG, TIMI of < or = 1, & 2 sets of CE….ok to d/c home. I certainly would not be this aggressive in my higher risk populations. Hopefully that answers the question. Thank you for your comment and reading the post.

      Salim

      • Joe Bove

        Thank you. I would agree as there are certain patients that need admission but it would be interesting to see what the rule in rates are after 2 negative because in the future we may be able to d/c some of these patients especially if you believe the evidence that going to Cath in non MI settings is not beneficial as I do. For now a more conservative approach on high risk patients will remain but the utility of the high sensitivity troponin has certainly helped a great deal with our lower risk patients.