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SGEM#160: Oh Baby, You’re Too Sensitive – High Sensitivity Troponin

SGEM#160: Oh Baby, You’re Too Sensitive – High Sensitivity Troponin

Podcast Link: SGEM160

Date: September 8th, 2016

Reference: Body et al. The use of very low concentrations of high sensitivity troponin T to rule out acute myocardial infarction using a single blood test. AEM Sept 2016.

Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the director of simulation education at Markham Stouffville Hospital in Ontario. He is the author of the excellent #FOAMed blog called First10EM.com and is an associate editor of Emergency Medicine Cases.

This is a SGEM Hot Off the Press episode.  Here is a summary of the process but you can click on the SGEMHOP link for more details and previous episodes:

  1. A peer reviewed paper is selected pre-publication from AEM or CJEM that we think will be of interest to the SGEMers.
  2. We do a structured critical review of the paper using the quality check list developed by the Best Evidence in Emergency Medicine (BEEM) group.
  3. The paper is then discussed with one of the paper’s authors to give us a better understanding of the strengths and weaknesses of the paper.
  4. A blog and podcast are posted encouraging the FOAMed world to engage with us and the author over a one week period.
  5. A summary of the critical review and the best social media engagement is then published in AEM or CJEM to help cut that knowledge translation window down.

SGEMHOP from AEM Now has CME Credits


Dr. Corey Heitz

Dr. Corey Heitz

We have some exciting news to start Season# 5 of the SGEM. Hot off the Press papers from AEM will now have continuing medical education (CME) credits attached to the episodes. Dr. Corey Heitz will be writing up the five questions and alternating with Justin as the guest skeptic.

Corey is an associate professor of emergency medicine at the Virginia Tech Carilion School of Medicine in Roanoke Virginia. He has been a member of the executive board of the Clerkship Directors in Emergency Medicine, is co-chair of the National EM M4 Examination committee and sits on the examination development board for the NBME EM-Advanced Clinical Exam. In addition, Corey is the CME editor for Academic Emergency Medicine and the associate editor for emergency medicine simulation at the AAEM MedEdPORTAL.

SGEMers can claim their CME credits by following this process:

  1. Go to the Wiley Health Learning website
  2. Register and create a log in
  3. Search for “Academic Emergency Medicine – September”
  4. Complete the five questions and submit your answers

As this is a new feature there may be some glitches. Please email Corey (coreyheitzmd@gmail.com) with any questions or difficulties.

Case: A 53-year-old woman presents to your emergency department a little less than two hours after her anterior, squeezing chest pain hits its peak. She has a history of hypertension, but is otherwise healthy. Thanks to a medical directive, when you sit down with the patient, she already has a normal ECG and a high sensitivity troponin T (hs-cTnT) test that has come back below the limit of detection. She is feeling a lot better and would like to go home. 

Background: Patients presenting to the emergency department with chest pain are a daily conundrum. There are a number of life threatening conditions that must be efficiently ruled out.

Unfortunately, for the most common acute coronary syndrome, there is no universally agreed on algorithm. In addition to serial ECGs, a variety of different biomarkers are used and repeated at a variety of different intervals.

These biomarkers may or may not be followed by admission or further outpatient provocative testing depending on where you practice.

With the advent of high sensitivity troponin tests, it has been argued that there are probably some patients in whom we can exclude the diagnosis of myocardial infarction with just a single blood test.

The SGEM has done a couple of episodes on high sensitivity troponins in previous seasons:

  • SGEM #43 One is the Loneliest Number: High Sensitivity Troponin
  • SGEM #128 One Hour AMI Rule Out/Rule In (Harder, Better, Faster?)

A recent systematic review determined that a single hs-cTnT below the level of detection resulted in a sensitivity of 97.4% and a specificity of 42.4% (Zhelev 2015).

When a non-ischemic ECG is added to the single negative hs-cTnT, one retrospective study of more than 14,000 patients found a sensitivity for myocardial infarction of 98.3%, and a negative predictive value of 99.8% (Bandstein 2014).

However, many of the existing studies are small, single-center, and/or retrospective.


Clinical Question: Can high sensitivity troponin T (hs-cTnT) levels below the limit of detection on arrival in the emergency department be used to safely exclude acute myocardial infarction in patients with no ECG ischemia?


Reference: Body et al. The use of very low concentrations of high sensitivity troponin T to rule out acute myocardial infarction using a single blood test. AEM Sept 2016.

Dr. Richard Body

Dr. Richard Body

Dr. Rick Body is a Professor of Emergency Medicine who leads the Emergency Medicine & Intensive Care Research Group (EMERGING) in Central Manchester, UK. His PhD was in the derivation of clinical decision rules for suspected cardiac chest pain (2009) and he is currently Chief Investigator for the BEST study and the MACS (Manchester Acute Coronary Syndromes) trial. He developed the Manchester Acute Coronary Syndromes decision rule, the limit of detection rule out strategy with high sensitivity troponin and he was part of the group evaluating a 1-hour troponin-based rule out strategy.  Rick is also a Senior Editor at St. Emlyn’s blog and podcast site and an Associate Editor at the Emergency Medicine Journal.

  • Population: Adult patients presenting to the emergency department with new onset chest pain or symptoms suggestive of acute coronary syndrome that had peaked in the last 6 hours.
    • Exclusions: Acute trauma patients, prehospital thrombolytic or revascularization, prehospital defibrillation or cardioversion, dialysis patients, patients who had undergone cardiac surgery within one month of presentation, patients hospitalized for acute myocardial infarction in the previous three weeks and pregnant or breast-feeding women.
  • Intervention: hs-cTnT on arrival to the emergency department.
  • Comparison/Control: This is a diagnostic cohort study so a control/comparison is not strictly necessary. The aim is to report accuracy of a strategy of interest. There was no zero-hour test comparator here; there was, however, a reference standard to compare to.
  • Outcome: 
    • Primary: Acute myocardial infarction (AMI) at time of initial admission. AMI was defined using the 3rd Universal definition of patients who developed a rise and/or fall of troponin with at least one value above the 99th percentile of a healthy reference population in the appropriate clinical context. Thygesen et al 2012. To diagnose AMI a different troponin assay was used to avoid any potential criticism about incorporation bias, whereby the index test also forms part of the reference standard. The Siemens troponin I Ultra assay was used as a reference standard.
    • Secondary: Major adverse cardiac events (MACE). MACE was defined as AMI, death or re-hospitalization for acute coronary syndrome with coronary revascularization within/determined at 30 days.

Author’s Conclusions: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

checklistQuality Checklist for Observational Studies:

  1. Did the study address a clearly focused issue? Yes
  2. Did the authors use an appropriate method to answer their question? Unsure. A prospective observational study is reasonable, but this is a secondary analysis of data collected for a different primary purpose.
  3. Was the cohort recruited in an acceptable way? Yes
  4. Was the exposure accurately measured to minimize bias? Yes
  5. Was the outcome accurately measured to minimize bias? Unsure. They used an international definitions of AMI, but it still relies on the consensus diagnosis of two cardiologists.
  6. Have the authors identified all-important confounding factors? Unsure. These were not consecutive patients.
  7. Was the follow up of subjects complete enough? Yes
  8. How precise are the results? Good, but potentially borderline for clinical practice. The 95% confidence interval for the sensitivity of the primary strategy below the limit of detection (hs-cTnT <5ng/L) was 95.3-99.5%.
  9. Do you believe the results? Yes
  10. Can the results be applied to the local population? Unsure. The rule in rate for acute myocardial infarction on the initial visit in this study was 16.6%. While sensitivity is not impacted by prevalence, negative predictive value (NPV) is dependent on prevalence. So the NPV will depend on your local prevalence but not the sensitivity.
  11. Do the results of this study fit with other available evidence? Yes

Key Results: The analysis includes a total of 1282 patients. 213 (16.6%) were diagnosed with acute myocardial infarction on their initial visit. Mean age was 62 years and about two thirds being male (62.8%).

For the primary outcome of acute myocardial infarction, using the primary strategy of an initial hs-cTnT below the limit of detection (<5ng/L) and no ECG ischemia (no ST-segment deviation, T-wave inversion, left bundle branch block or a paced rhythm), the test characteristics are:

  • Primary Outcome: Acute Myocardial Infarction
    • Sensitivity 99.1% (95% CI 96.7-99.5%)
    • Specificity 43.9% (95% CI 40.9-46.9%)
    • PPV 26.0% (95% CI 23.0-29.2%)
    • NPV 99.6% (95% CI 98.5-100.0%)
    • LR+ 1.76 (95% CI 1.67-1.86)
    • LR – 0.02 (95% CI 0.01-0.09)
  • Secondary Outcome: MACE
    • Total 30 day MACE for primary strategy: 1.3% (95% CI 0.5- 2.8%).
    • The actual numbers were six MACE events, including only one death, no AMI and three revascularizations.

Screen Shot 2015-04-25 at 3.11.12 PM

We asked Rick five questions about his research. Listen to the podcast to hear his responses.

  1. Secondary Analysis: This was a secondary analysis of data collected for the international, multicenter TRAPID-AMI (High sensitivity cardiac troponin T assay for RAPID rule out of Acute Myocardial Infarction) study. Was this a pre-planned analysis and how do you think this impacts your results?
  2. Gold Standard: As always with these studies, there is a questionable gold standard. Acute myocardial infarction was based on two independent cardiologists using all available clinical data. They were blinded to the hs-cTnT results, as a different sensitive troponin I test was used clinically for all patients. There is some degree of subjectivity with this process. Can you comment on this imperfect gold-standard and how many times a third cardiologist was needed to adjudicate?
  3. Acceptable Miss Rate/Medicolegal Implications: You found a miss rate of 0.7% (4/560) with hs-cTnT being used alone and 0.4% (2/471) if used with no ECG ischemia (no ST-segment deviation, T-wave inversion, left bundle branch block or a paced rhythm).  In addition, the MACE rate at 30 days was 1.3% with most of it being revascularization. So what is an acceptable miss? In addition, your paper mentions medicolegal implications of using hs-cTnT. Can you expand on that point?
  4. ECGs: When do we ever evaluate a patient suspected of ACS without getting an ECG? Adding the ECG decreased the miss rate 0.7% to 0.4%. However, one investigator retrospectively evaluated the ECG and decided if it had any evidence of ischemia. Who was that one investigator and did you consider having more than one individual interpret the ECGs so inter-rater reliability could be determined?
  5. Clinical Judgement: The primary outcome in this study was acute myocardial infarction. We really liked that you emphasized in your paper that clinicians must still use their clinical judgment. Can you comment further on the role you think clinical judgement plays in these cases?

This was an industry sponsored study, which does not make the results wrong but should make us more skeptical of the paper and the interpretation. Rick discusses this issue and conflicts of interest.

Comment on authors conclusion compared to SGEM Conclusion: We generally agree with the authors’ conclusions.


SGEM Bottom Line: hs-cTnT is a new reality for some emergency physicians. We need to know how to use this test correctly to safely evaluate patients presenting with symptoms of ACS.


Case Resolution: The patient is offered serial troponins and ECGs but decides to go home knowing there is no “zero risk”.

Clinically Application: Use of hs-cTnT will all depend on your comfort level, patients’ preferences and your current practice environment.

Dr. Justin Morgenstern

Dr. Justin Morgenstern

What do I tell my patient? We cannot find any evidence of a heart attack. Your ECG is normal. Your blood work using a new highly sensitive test is also normal. However, this does not mean you did not have a heart attack. There is a very small risk (less than 1%) that it could be missed on the ECG and blood test. It also does not mean you do not have heart disease. It is possible you could have a major adverse event (including death) in the next 30 days. That possibility is also very low but not zero percent. With your test results, less than 1/500 people die in the next 30 days, but 1% of people have what we call a major event – mostly meaning they have to come back to the hospital to have a heart intervention like a stent or a surgery. Would you like to stay for a further testing in 1-3 hours or go home now?

Keener Contest: The winner from the last episode of Season#4 was Karen Adler a second year medical student from Israel.  She knew the HAL 9000 computer sang Daisy Bell in the movie 2001: A Space Odyssey.

Listen to the podcast for this weeks’ question. If you think you know the answer send it to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.


Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.


References:

  • Bandstein N, Ljung R, Johansson M, Holzmann MJ. Undetectable high-sensitivity cardiac troponin T level in the emergency department and risk of myocardial infarction. Journal of the American College of Cardiology. 63(23):2569-78. 2014.
  • Zhelev Z, Hyde C, Youngman E. Diagnostic accuracy of single baseline measurement of Elecsys Troponin T high-sensitive assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis. BMJ (Clinical research ed.). 350:h15. 2015.
  • Mueller C, Giannitsis E, Christ M, et al. Multicenter evaluation of a 0h/1h-algorithm in the diagnosis of myocardial infarction using high-sensitivity cardiac troponin T. Annals of Emergency Medicine 2016;Online first.
  • Thygesen K, Alpert JS, Jaffe AS, et al. Third Universal Definition of Myocardial Infarction. Journal of the American College of Cardiology 2012;60(16):1581–98.

Conference Update: