Case: A 57-year-old woman presents with left-sided chest pain that started 90 minutes ago. The pain radiates to her right arm, and she has nausea without vomiting. The pain began while she was doing some yard work. The initial electrocardiogram (ECG) is unremarkable.

Question: Can emergency physicians rule in or out an acute myocardial infarction (AMI) in one hour using a high-sensitivity troponin and ECG?

Background: About 5 percent of all patients presenting to the ED with acute chest pain will have a ST elevated myocardial infarction (STEMI).¹ This leaves the other 95 percent of chest pain patients. Our job in the ED is to figure out whom we will rule in versus rule out for AMI.

Many cardiac biomarkers have been used over the last 60 years to try to identify patients with AMI. A limitation of current troponin assays is that they can take three to four hours to rise. This means the diagnosis of non-STEMI can take many hours of continued monitoring with serial blood sampling.

High-sensitivity troponin assays are now being used in many emergency departments. They offer very high sensitivity but are less specific than prior troponin assays.

Relevant Article: Reichlin T, Twerenbold R, Wildi K, et al. 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. 2015;187(8):E243-E252.

• Population: Patients presenting to the ED within 12 hours of onset of nontraumatic chest pain or symptoms suggestive of AMI.
• Intervention: High-sensitivity troponin T at time 0 and 1 hour with ECG
• Comparison: Two independent cardiologists.
• Outcome: AMI.

Authors’ Conclusions: “This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected AMI by allowing safe rule-out as well as accurate rule-in of AMI in three out of four patients.”

Key Results: There were 1,320 patients who presented to the ED within 12 hours of onset of nontraumatic chest pain or other symptoms suggestive of AMI. AMI was the final diagnosis in 17 percent of those patients.

The researchers divided patients into three different categories: rule-out AMI (60 percent), rule-in AMI (16 percent), and observation zone (24 percent). The one-hour algorithm test characteristics for the 60 percent who were ruled out were:

• Area under the curve 0.96 (95 percent confidence interval [CI], 0.95–0.97)
• Sensitivity of 99.6 percent (95 percent CI, 97.6–99.9 percent) and specificity of 95.7 percent (95 percent CI, 94.3–96.8 percent)
• Negative predictive value 99.9 percent (95 percent CI, 99.3–100 percent) and positive predictive value 78.2 percent (95 percent CI, 72.1–83.6 percent)
• Positive likelihood ratio of 23 and negative likelihood ratio of 0.004

EBM Commentary: This was an attempt to investigate whether a one-hour algorithm can rule out and rule in acute myocardial infarction using a high-sensitivity troponin as a biomarker. There were a number of concerns with this manuscript.

1) Bias: The challenge of conducting high-sensitivity troponin studies is that the diagnosis of non-STEMI is a disease entity based on a test without an independent reference standard. This can lead to a number of biases that can distort the results.²

• Incorporation bias: This occurs when results of the test under study are actually used to make the final diagnosis. This makes the test appear more powerful by falsely raising the sensitivity and specificity.
• Partial verification bias: This happens when only a certain set of patients who under go the index test are verified by the reference standard. This would increase sensitivity but decrease specificity. Patients who were deemed to be low risk did not always proceed to six-hour troponin.
• Spectrum bias: Sensitivity depends on the spectrum of disease, while specificity depends on the spectrum of nondisease. You can falsely raise sensitivity if the clinical practice has lots of very sick people. Specificity can look great if you have no sick patients in the cohort. The researchers included only patients who presented to a cardiac research hospital within 12 hours of pain. These patients potentially could have been more ill.

2) Risk of over-testing: Another concern with this protocol and others based on high-sensitivity troponin assays is the lack of specificity. The initial high-sensitivity troponin was only 48.4 percent specific, with more false positives than true positives. If there were inappropriate use of this test in ultra-low-risk patients, there may be a paradoxical rise in the number of patients being evaluated for chest pain in the emergency department.

3) Imprecision of the assay: The change in high-sensitivity troponin was within the allowable imprecision of the assay. This is really the keystone because if the change is within the assay’s coefficient of variation, all other issues are moot.³

There were 1,320 patients who presented to the ED within 12 hours of onset of nontraumatic chest pain or other symptoms suggestive of AMI. AMI was the final diagnosis in 17 percent of those patients.

Bottom Line: A one-hour protocol utilizing high-sensitivity troponin T cannot be recommended at this time. External validation of this protocol along with a more explicit discussion of how the diagnosis of AMI is arrived at might allow for a rapid rule-out in the future.

Case Resolution: Shared decision making was done with the patient, and she agreed to stay in the ED for six hours. Her troponin at 0 and 6 hours was negative, serial ECGs showed no ischemic changes, and her pain completely resolved. She was discharged to her home with close follow-up with her primary care provider and strict precautions to return if necessary.
Thank you to Daniel McCollum, assistant residency director at Georgia Regents University in Augusta, Georgia, and Andrew Worster, faculty member at McMaster University and part of the Best Evidence in Emergency Medicine group, for their help with this review.^4,5
Remember to be skeptical of anything you learn, even if you learned it on the Skeptics’ Guide to Emergency Medicine.

References

1. Apple FS, Wu AH, Jaffe AS. European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: how to use existing assays clinically and for clinical trials. Am Heart J. 2002;144:981-986.
2. Kohn MA, Carpenter CR, Newman TB. Understanding the direction of bias in studies of diagnostic test accuracy. Acad Emerg Med. 2013;20:1194-1206.
3. Kavsak PA. High-five for high-sensitivity cardiac troponin T: depends on the precision and analytical platform. JAMA Intern Med. 2013;173:477.
4. Worster A. Baseline plus 1-hour high-sensitivity cardiac troponin T improved early rule-out and rule-in of acute MI. Ann Intern Med. 2015;163:JC12.
5. Milne K. One hour AMI rule out/rule in (harder, better, faster?). The Skeptics’ Guide to EM website. Accessed Sept. 24, 2015.