The One-hour High Sensitivity Troponin to Rule-Out MI

July 2016

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You are working your 0irst ever shift as an intern in the Barnes-Jewish Emergency Department on July 1st when you encounter Mrs. P, a forty-year old woman whose chief complaint is chest pain. She reports that 1 hour prior to arrival, while sitting at her desk at work, she developed a sharp, stabbing pain in the left side of her chest. The pain was not worse with deep inspiration or with exertion, but has continued since then. It is currently rated a 7 out of 10 and has not radiated or migrated. She notes mild subjective shortness of breath and denies diaphoresis or lightheadedness.

Mrs. P tells you she a history of hypertension and high cholesterol and takes amlodipine and atorvastatin. She has never had any cardiac issues, but her father had his first MI in his early seventies. Her ROS is negative except as noted above and physical exam is completely normal, including no tenderness to palpation of the chest, no leg swelling, and no calf tenderness. Her ECG has already been performed and is normal, and her initial troponin (ordered in triage) is < 0.03.

After discussion with your attending, you decide she is low risk enough that you can forego a stress test, but your attending does think you should keep her for a repeat troponin to rule out MI. Since her pain began so recently, your attending suggests waiting the prerequisite 6 hours before doing so. As you explain this to the patient, she is baffled at why she has to wait so long. As you explain that it takes time for troponin to reach detectable levels in the bloodstream, you remember that the sensitivity of troponin has increased with newer assays, and that in Europe they use an ultra-high sensitive troponin. You wonder if using such an assay would allow you to rule out MI more quickly without adding the risk of missed disease. After your shift, you head to Google and being your search…

PICO Question

Population: Adult patients presenting to the ED with chest pain

Intervention: One-hour serial troponin using a high sensitivity assay

Comparison: Traditional 6-hour (or 4-hour or 3-hour or 2-hour) serial cardiac enzymes

Outcome: Missed MI, major adverse cardiac event (MACE), or death

Search Strategy
An advances PubMed search was performed using the terms troponin AND high-sensitivity AND myocardial infarction, all limited to article title (http://tinyurl.com/zluqok8). This resulted in 106 articles, from which the following four were chosen.

Articles

Article 1: Jaeger C, Wildi K, Twerenbold R, et al. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am Heart J. 2016 Jan;171(1):92-102.e1-5.
ANSWER KEY

Article 2: Mueller C, Giannitsis E, Christ M, et al; TRAPID-AMI Investigators. Multi center Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T. Ann Emerg Med. 2016 Jul 68(1): 76-87.e4.
ANSWER KEY
PGY-2 Mueller Annals 2016

Article 3: Neumann T, Sorensen N, Schemer T, et al. Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm. JAMA Cardiol. 2016 June.
ANSWER KEY

Article 4: 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 May 19;187(8):E243-52.
ANSWER KEY

Bottom Line

Chest pain is a one of the most common chief complaints among patients presenting to emergency department (ED) in the US, representing around 5% of all ED visits. Despite widespread testing, around 2-3% of patients with myocardial ischemia or infarction are discharged home from the ED, and missed MI accounts for more malpractice dollar awarded than any other single diagnosis. It is likely that risk of malpractice lawsuits has at least in part led to the high admission rates for chest pain seen in the US, which ranges from around 40% to as high as 80% in some institutions according to data from medicare beneficiaries. This is in spite of data suggesting that only 13-23% of patients presenting to the ED will ultimately have a diagnosis of acute coronary syndrome.

The most recent AHA guidelines suggest that patients with symptoms suggestive of myocardial infarction should have serial cardiac troponin I or T levels drawn at presentation AND 3 to 6 hours after symptom onset to detect any rise in the level over that time. However, high-sensitivity troponin assays used in Europe have shown the potential to allow a more rapid rule-out/rule-in approach in which serial enzymes are checked only 1 hour apart. This approach could potentially lead to more rapid disposition of patients from our already overcrowded EDs. The European Society for Cardiology (ESC) has already embraced these newer troponin assays, incorporating a 0/1 hour algorithm into their recommended diagnostic approach. We sought, therefore, to review the evidence supporting these high-sensitivity troponin assays and their use in 0/1 hour algorithms.

The four studies identified were all very similar in design. Two of the studies assessed troponin I assays (Jaeger 2016, Neumann 2016) while two assessed troponin T assays (Mueller 2016, Reichlin 2015). All four studies used some kind of algorithm with specific cut-offs for the assay as well as cut-offs for the change in value between 0 and 1 hour. Using the cut-offs, patients were either assigned a “rule-in” status, a “rule-out” status, or were considered to be in a gray zone if could not be placed in either of these groups. For example, the two studies evaluating high-sensitivity troponin T used the following definitions:

  • Patients with initial hs-cTnT < 12 ng/L and Δ1 hour < 3 ng/L were assigned to rule out status.
  • Patients with initial hs-cTnT ≥ 52 ng/L and Δ1 hour ≥ 5 ng/L were assigned to rule in status.
  • All other patients were considered to be in the observation group.

Use of this algorithm (and similar algorithms in the articles evaluating high-sensitivity troponin I) resulted in high negative predictive values for ruling out patients in all 4 studies, ranging from 98.9% to 100%, and allowed anywhere from 39% to 63.4% of patients to be ruled out within one hour. The positive predictive values for ruling patients in were significantly lower, ranging from 70.4% to 87.1%.

While this evidence suggests that use of high-sensitivity troponin assays would allow the rapid rule-out of many patients presenting to the ED with chest pain, there are some valid concerns remaining. These include the relatively low positive predictive values of the algorithms (which may lead to unnecessary procedures such as cardiac catheterization), and the lack of a clear plan for patients in the observation or gray zones (which may again lead to inappropriate testing in these patients). Additionally, the articles themselves are prone to significant bias, in part because of the heavy use of industry funding in all four studies (Ioannidis 2016). In all of the studies, for example, the adjudicated final diagnosis was based primarily on the results of the serial high-sensitivity cardiac troponin assays themselves, raising the specter of incorporation bias.

Most importantly, the current evidence is limited to providing negative and positive predictive values for the various algorithms. Future studies will need to assess the clinical impact of using the algorithms on decision-making, disposition times, and patient outcomes in order to demonstrate efficacy and safety. It likely the lack of such studies that has kept these algorithms out of our practice in the US, and out of the AHA guidelines.