Washington University Emergency Medicine Journal Club- July 2020
High Sensitivity Cardiac Troponin in the Emergency Department
It’s early July and you’re the teaching resident in TCC when you get a triage patient in 2-right. Your brand-spanking-new intern goes to see the patient and comes back an hour later to tell you the story. Ms. X is a 48-year-old woman with a history of hypertension and diet-controlled diabetes who presents with chest pain that began earlier in the afternoon while watching TV (about four hours prior). The pain was dull and achy, located across the whole chest without radiation, and did not get better when she tried taking Tums. The pain was not noted to be worse when she got up and walked around, but she has otherwise not exerted herself. She denies associated shortness of breath, lightheadedness, diaphoresis, or syncope, but did have some mild associated nausea. The pain resolved after about one hour, but the patient was concerned as her father had a heart attack in his sixties.
The patient has stable vital signs (BP 140/90, HR 86, RR 12, SpO2 99% on room air, temp 37°C). Her physical exam is unremarkable and her ECG has LVH with some nonspecific ST and T-wave changes, with no prior tracing for comparison.
You teach the intern about the HEART score and the two of you calculate a score of 3 for this patient. As you begin to discuss the plan with the intern, which involves ordering a troponin to evaluate for a myocardial infarction, you remember that your institution has recently adopted a new “high sensitivity” troponin I assay. You wonder how this change will effect your management of patients with chest pain. Will a single negative troponin be enough to discharge low-risk patients? Should you expect a high rate of “false positives” given that this assay is less specific? How should you handle these “false positives?” Will there be an increase in unnecessary cardiac catheterizations as a result? And can you still use this new assay with previously developed clinical decision rules like the HEART score?
As you mull over these questions, you decide to use your detective skills to go online and do a little digging into the medical literature, hoping to \igure out how you will incorporate this assay into your current practice…
Population: Adult ED patients with chest pain concerning for possible ACS Intervention: Using high sensitivity troponin to identifying low risk ACS patient who can safely be sent home from ED without extended stay or stress testing Comparison: Admission to Observation unit for serial (6 hour) cardiac enzymes and/or next day stress testing Outcome: Death, MI, need for revascularization, ED length of stay, need for hospital admission
PubMed was searched using the terms “high sensitivity” AND troponin AND emergency, resulting in 811 results (https://tinyurl.com/y4p5c6q2). This was limited further to 409 results by filtering to human studies published in the last 5 years. The four most relevant articles were chosen from among these.
Article 1: Neumann JT, Sörensen NA, Schwemer T, et al. Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm. JAMA Cardiol. 2016;1(4):397-404. Answer Key.
Article 2: Andruchow JE, Boyne T, Innes G, et al. Low High-Sensitivity Troponin Thresholds Identify Low-Risk Patients With Chest Pain Unlikely to Benefit From Further Risk Stratification. CJC Open. 2019;1(6):289-296. Answer Key.
Article 3: Greenslade JH, Carlton EW, Van Hise C, et al. Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome. Ann Emerg Med. 2018;71(4):439-451.e3 Answer Key.
Article 4: Twerenbold R, Jaeger C, Rubini Gimenez M, et al. Impact of high- sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 2016;37(44):3324-3332. Answer Key.
Evaluation of chest pain in the emergency department has traditionally involved measurement of cardiac troponin I or T in order to evaluate for possible acute myocardial infarction (MI). Over time, the sensitivity of these assays has increased, allowing for detection of lower and lower concentrations of circulating troponin. In the last several years, so-called “high sensitivity” assays have become available, potentially allowing earlier detection of acute MI with a decrease in the necessary “rule out” period. There has been skepticism, however, with concerns that in additional to being more sensitive, these assays would also be less specific, potentially leading to increased false positive results and an increase in unnecessary downstream testing.
Studies looking at the diagnostic accuracy of high sensitivity troponin assays have generally been positive. Andruchow et al (2019) found that a single high sensitivity troponin T test (hs-cTnT), with cutoff values ranging from < 3 to <6 ng/l, had a negative likelihood ratio (LR) between 0.09 and 0.17 for a major adverse cardiac event (MACE) at 30 days; when limited to patients presenting within at least 3 hours since onset of symptoms, the negative LR dropped to 0 to 0.12. Neumann et al (2016) found that by repeating the high sensitive troponin at 1 hour, they were able to formulate a “rule out” algorithm with a negative LR of 0.05. This second study also evaluated a “rule-in” algorithm that had a positive LR of 29.9. Unfortunately, using these algorithms nearly 40% of patients were classified into a “gray zone” requiring downstream testing (the exact nature of which was not described in the study).
One downside to both of these studies is that they failed to include any kind of risk stratification to help quantify the pre-test probability of disease (or outcomes) using available clinical decision rules. Greenslade et al (2018), on the other hand, evaluated five different diagnostic pathways using clinical decision rules (m-ADAPT, EDACS, HEART score, Vancouver Chest Pain, and the No Objective Testing rule) in conjunction with 0 and 2 hour hs-cTnI measurements. All five pathways demonstrated low negative LR (ranging from 0 to 0.05). Of these, the m-ADAPT, EDACS, and HEART pathways all allowed for early discharge of over half of included patients, while the Vancouver and NOT pathways would have required further testing in nearly two thirds.
Finally, given concerns that high sensitivity troponin use would result in increased downstream testing (i.e. stress tests and cardiac catheterization), Twerenbold et al (2016) retrospective analyzed data from the APACE trial, looking at testing prior to and following implantation of hs-cTnT assays. They found that while the rate of angiography was the same in both the before and after groups (23%, RR 0.98), the rate of stress testing actually decreased significantly following implementation of hs-cTnT (29% vs. 19%, RR 0.67, 95% CI 0.57 to 0.77).
Overall, this data suggests that high sensitivity troponin assays, particularly when used in conjunction with appropriate clinical decision rules, allow rapid rule out of disease with low 30-day adverse outcomes, which should allow earlier ED discharge for a large number of patients. In addition, these algorithms do not seem to lead to increased downstream testing, and may even reduce the use of stress testing. Care will need to be exercised with those patients who do not “rule in” or “rule out,” which seems to be a large proportion of patients, and algorithms will need to clarify what additional testing is needed in this population.