Annals of Emergency Medicine

High-Sensitivity Troponin: Time to Implement

Judd E. Hollander, MD. judd.hollander@jefferson.edu

After decades of seeking—and failing—to safely “rule out” myocardial infarction with less than a 1% miss rate, we now have that capability.

High-sensitivity cardiac troponin (hs-cTn) assays alter the approach to the evaluation and management of patients presenting to the emergency department (ED) with potential acute coronary syndromes.

European guidelines already incorporate these assays, deploying strategies that can functionally eliminate acute myocardial infarction with a single sample or within a few hours, depending on the specific assay used and time evaluated. Most of the studies informing these guidelines have a similar recommendation: use these newer assays in conjunction with a risk-stratification approach or tool. Coupling these inputs with the time from symptom onset (usually 2 hours) allows a single cardiac troponin T (cTnT) measurement below the limit of detection to exclude acute myocardial infarction. If the initial assay is just above the limit of detection, adding a second measurement 1 to 3 hours later can achieve similar results if the change (Δ value) is below an absolute threshold.

The Food and Drug Administration has been slow to approve these newer assays but recently cleared the first hs-cTnT from Roche Holdings AG.

The benefit of using an approach incorporating high-sensitivity troponin is more efficient care and lower costs for patients presenting with potential acute coronary syndromes. Currently, for every 100 patients presenting to the ED with a potential acute coronary syndrome, approximately 65 are assigned a bed (15 to a cardiology service and 50 to observation or inpatient beds). Use of an assay with 94% sensitivity and 80% specificity could nearly double the discharge rate, from 35 to 69 patients, while maintaining a rate of missed myocardial infarction of approximately 1%.

The theoretic risk of wider use of ED high-sensitivity troponin assays is largely related to an increased number of patients with mild troponin elevations. Terms such as troponin “leak” or a “false-positive” troponin elevation are evidence of confusion laced with fear because many physicians automatically fear acute coronary ischemia and risk of acute decompensation when observing any mild troponin elevation. Although it is true that any troponin is worse than no troponin elevation and that more troponin is worse than less troponin, this does not mean that all patients with a troponin elevation have an acute myocardial infarction. Troponin elevation means the patient has myocardial injury but does not inform whether the injury is acute or chronic, especially when modest. In a 100-patient scenario, only 14 of the 31 patients with a troponin elevation would have an acute myocardial infarction. If all 31 of these patients were sent to cardiologists for investigation of myocardial ischemia, most would not have acute myocardial infarction and would not benefit from catheterization and percutaneous coronary interventions. A second troponin value that shows a persistent elevation without a Δ (the change in values) can distinguish chronic from acute injury. The real value of the newer assay becomes clearer and shows that clinical decisionmaking education is of paramount importance.

One meta-analysis suggests that the duration from symptom onset must be at least 2 hours to achieve 99% negative predictive value. We also need to determine whether unstable angina still exists as a real entity. These hs-cTn assays are so sensitive that almost all acute ischemic events have detectable troponin elevations, meaning these are now classified as non–ST-segment elevation acute myocardial infarction. The experience with transient ischemic attacks is similar because advanced imaging with magnetic resonance imaging uncovers smaller defects showing ischemic stroke actually exits. At some point, symptom duration should result in myocardial injury; otherwise, it was not cardiac in cause. Future research will to help clarify this time frame.

 

I recommend the following 6 steps to successfully implement the changes needed:

  • Investigate what other institutions have done successfully. There are more than 50 medical centers that have already made the transition; speak with them.
  • Convene a small group of empowered and knowledgeable decisionmakers. I recommend a small group (6 maximum) of only 1 to 2 emergency physicians, cardiologists, and laboratorians. Groups of more than 7 people are less efficient than smaller ones. Agree to make a decision before leaving the room, and use your normal laboratory processes for validation. There are subtle, likely clinically irrelevant differences between the possible sampling time frames. I prefer a 0- and 2-hour approach. It lets the answer to almost all of the most common frequently asked questions be “obtain another in 2 hours,” such as when you are asked how long you need to wait after symptom onset to use one troponin level. Other questions include the following: What if the first troponin level was less than the 99th percentile (19 ng/L) but above the limit of detection (6 ng/L)? What if the first troponin level was elevated but it was not clear whether it was acute or chronic myocardial injury? What if the patient had a condition associated with troponin elevations other than acute coronary syndromes (heart failure or renal disease)? This approach is a balance of science and pragmatism.
  • Communicate the change. I recommend holding a series of open town halls, focused conferences, and grand rounds for the services with the highest “need to know.” At a minimum, include emergency medicine, observation medicine, cardiology, internal medicine, family medicine, and critical care, ensuring that partners from quality and nursing also are targeted. Additional messages can come from using hospitalwide “laboratory alerts,” incorporating detailed interpretations into the electronic medical records, and disseminating slide sets and visual abstracts to simplify interpretation.
  • Make the change. I recommend only a 24-hour period of overlap with the old assay and only for patients already in the middle of a rule-out. After that period, clinicians should not have an easy option to use anything but high-sensitivity troponin T.
  • Anticipate uncertainty. In accordance with feedback from multiple sites, there may be some confusion early after the transition. Have someone dedicated to field calls; you don’t need formal consultations but do need someone to help educate when needed.
  • Assess outcomes. Look at the influence on disposition several times during the months after the transition. Make sure you are reducing unnecessary admissions without prolonging time in the ED.

 

Although there are still areas of uncertainty, many institutions have successfully implemented high-sensitivity troponins; it’s time for more. There always will be opportunities to resolve areas of uncertainty, but implementing now allows us to safely discharge patients. Let’s heed the European experiences and new US data, an approach based on good science and a high degree of sensitivity.

 

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