High Sensitivity Troponin Testing

06 Feb
February 6, 2014

High Sensitivity Troponin TestingTroponin 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.

History of Troponin Sensitivity

Image modified from (22105197)

How good is ECG alone for diagnosis of acute myocardial infarction (AMI)? (23878152)

  • 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 (22105197)
  • Non-cardiac causes of elevated hsTn include: PE, renal failure, SAH, sepsis, burns, and extreme exertion (i.e. marathons) (22105197)

Serial Troponin Testing

Image modified from (22105197)

What should a provider do with troponin elevation from non-ACS etiologies? (23736735)

  • 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 Myocardial Infarction 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 AMI will have a normal hsTn at presentation and should have repeat testing (23955806)
  • 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) (23878152)
  • 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 (23955806)
  • 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 (22105197)
  • 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 (22105197)
  • A normal hsTn at 3 hours has a NPV of 99% in excluding AMI (23878152)
  • Dr Louise Cullen et al have recently published a paper: (23583250)
    • 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? (23955806)

  • 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

European Society of Cardiology Troponin Testing Recommendations

Image from (23955806)

Conclusion

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

Bibliography

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Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of R.E.B.E.L. EM
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8 replies
  1. Corey Heitz says:

    Salim,

    Good post about the problems with higher sensitivity, and therefore lower specificity, testing.

    I think, however, instead of saying “⅕ of patients with a normal hsTn will be diagnosed with an MI” it should read “in a study by (ref), 1/5 of patients diagnosed with MIs had normal hsTn on presentation.”

    Reply
  2. HASSAN ALMAATEEQ says:

    thanks for simplifying medicine 🙂

    i didn’t get the last point :”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”

    what is difference between elevation hsTN and small initial Tn elevation ??

    Reply
    • Salim Rezaie says:

      Hello Hassan,
      TY for reading and great question. For pts who have troponins that are elevated but not positive (i.e. less than the 99th %), you need a 50% increase in the second troponin to call this positive. In pts who have troponins that are positive (i.e. greater than the 99th %), you need only a 20% rise in the second troponin to call this positive. By positive I mean acute ACS/Ischemia, if this does not occur, you may not be dealing with acute ischemia, but a troponin leak from other etiologies such as PE, decompensated CHF, etc…..Does this help?

      Salim

      Reply
  3. Mojtaba says:

    I appreciate your effort and attitude to simplify emergency medicine
    Thank you Salim

    Reply
    • Salim Rezaie says:

      TY for taking the time to read this Mojtaba. Hopefully this was a useful post. There are not a lot of guidelines on how to handle non-diagnostic hsTn. Hopefully this post simplifies it a bit.

      Salim

      Reply

Trackbacks & Pingbacks

  1. […] 4. Discharging someone with a single negative troponin is high risk business (unless it was drawn 6 hours after the onset of symptoms). Whenever possible, get two serial troponins to see if there is any significant rise form the baseline. However, serial sampling of hs troponin at 0 and 2 hours can safely rule-out of STEMI and NSTEMI. In case, you happen to discharge home a patient with two negative troponins, document why are you doing that because it can still be Unstable Angina. 5. Troponin might take 6-12 hours to rise from the onset of symptoms and stays elevated upto 2 weeks. Document your concerns while sending these cardiac biomarkers.Attorneys focus on the documentation of HPI, documentation of ECG findings and Medical Decision Making with appropriate reasoning before settling the case. We are going to cover these bits next week. BOTTOMLINE: I think troponin is still a great test, if done with caveats. However, over the last two decades, it has become extremely sensitive and thus non-specific (like d-dimer for PE). Further Reading: http://resuscitation-conference.com/updates/2016/9/20/episode-73-hs-tn-and-exercisehttp://lifeinthefastlane.com/ccc/troponin-in-critical-illness/http://rebelem.com/high-sensitivity-troponin-testing/ […]

  2. […] a negative initial troponin while REBEL EM’s Salim Rezaie gets into the nitty gritty details of high sensitivity troponins. […]

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