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Myths in Emergency Medicine

Is hs-cTnT Worth the Downstream Testing?

Spiegel, Rory MD

doi: 10.1097/01.EEM.0000604516.77284.98
Myths in Emergency Medicine

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Whether we like it or not, the high-sensitivity troponin assays recently approved by the Food and Drug Administration will soon replace the fourth-generation assays currently being used. Many claims have been made about their clinical utility, as I discussed in a previous piece (EMN. 2019;41[2]:1; http://bit.ly/2DRd9Xu), but the implications for our standard chest pain workflow are unclear. Chew, et al., once again provide us with a glimpse behind the curtain, for a moment revealing the true utility of this new biomarker. (Circulation. 2019 Sep 3. doi: 10.1161/CIRCULATIONAHA; http://bit.ly/2kg3SB8.)

These authors randomized 3378 patients to a high-sensitivity troponin T (hs-cTnT) assay drawn at zero and one hour, a rapid diagnostic strategy, or standard care using an hs-cTnT with a threshold of 29 ng/L. The authors enrolled patients presenting to any of the four participating emergency departments with signs concerning for acute coronary syndrome but who were not considered high risk for acute coronary syndrome based on the clinician's judgment.

Patients randomized to the HS-TN rapid rule-out strategy underwent troponin testing at zero and one hour. Patients were considered ruled out according to the protocol with a baseline troponin less than 5 ng/dL over three hours since the symptom onset or with an initial troponin more than 5 ng/L but less than 12 ng/L and a change in troponin over one hour of less than 3 ng/L. Patients who were ruled out in the ED were discharged to follow-up with a primary care physician.

Patients were considered ruled in and were admitted to the hospital if they had a documented baseline troponin more than or equal to 52 ng/L or a rise over one hour of more than or equal to 5 ng/L. The remainder of the patients were placed in dispositional purgatory, or what the authors called observation, when the baseline troponin was between 13 and 51 ng/L with a change of less than 5 ng/L on repeat or with an initial troponin less than 12 ng/L and a change of 3-4 ng/L over an hour.

Patients randomized to the standard workup received the same hs-cTnT testing, but the clinicians only received values that were consistent with fourth-generation troponin testing and were blinded to any value less than 29 ng/L. The hs-cTnT levels were drawn at baseline and repeated at three hours, with further discretionary testing at six hours. The protocol recommended that patients with an hs-cTnT level less than 29 ng/L at three hours to be discharged with outpatient follow-up; clinician discretion was permitted.

The authors enrolled 3378 patients between August 2015 and April 2019. Overall, a greater proportion of patients in the rapid testing strategy were directly discharged from the ED (45% v. 33%, p<0.001). Patients in the rapid testing strategy group were less frequently referred for functional testing (ECG stress testing, stress echocardiography, or perfusion CMR/nuclear). These gains in early discharge and decreased testing were associated with no change in the rate of missed MI or death at 30 days, occurring in one percent of patients in both arms of the study.

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Improved Outcomes?

This seems at first glance like a win for hs-cTnT and a rapid testing strategy, but one has to inquire, what about the rapid testing strategy led to these improved outcomes?

More patients were directly discharged from the ED and fewer patients received noninvasive testing, but this does not appear to be a result of hs-cTnT's superior diagnostic performance. The rate of death or MI in the subsequent 30 days following ED presentation was essentially identical between the two groups. Patients in the standard workup group with an hs-cTnT level below 29 ng/L had a rate of death or MI of 0.6 percent compared with 0.4 percent in patients in the rapid diagnostic strategy who met the rule-out criteria. A decrease in the rate of noninvasive testing initially seems like an advantage for the rapid diagnostic strategy, but even this is misleading.

The major downside of noninvasive testing are the downstream invasive testing and interventions it leads to, both of which were higher in the rapid diagnostic strategy group. What have we really accomplished if hs-cTnT leads to a decrease in noninvasive testing but increases the number of diagnostic catheterization and revascularization procedures? Seemingly the only true benefit provided by the hs-cTnT was the treating clinician's peace of mind.

As far back as the Pope, et al., study, which famously claimed an excessive number of patients experiencing MIs were inappropriately discharged from the ED, we emergency physicians have been told we are incapable of appropriately managing chest pain patients in the ED. (N Engl J Med. 2000;342[16]:1163; http://bit.ly/2Pgve9a.) Yet when one takes a closer look at that study, only 19 patients who had an MI were sent home—from 10,689 patients evaluated—a miss rate of 0.18 percent. Nineteen years later and with a multitude of decision instruments and high-sensitivity assays at our fingertips, what has changed?

The rapid rule-out strategy missed five, or 0.3 percent, of the 1646 patients in the hs-cTnT arm. Mills, et al., presented the results of their much larger stepwise cluster randomized clinical trial at the recent European Society of Cardiology Congress, which claimed to demonstrate a benefit using a high-sensitivity troponin assay, but the complete results have yet to be published. (ESC 2019. Sept. 1, 2019. Paris.) Certainly, clinicians feel better about discharging someone after a workup that included an hs-cTnT. But is it worth the potential increase in downstream testing associated with its use? Perhaps the solution is simply conceding that we will never achieve perfection, regardless of the sensitivity of our troponin assay.

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Dr. Spiegelis an assistant professor of emergency medicine and critical care at Washington Hospital Center in Washington, D.C. Visit his blog athttp://emnerd.com, follow him on Twitter @emnerd_, and read his past articles athttp://bit.ly/EMN-MythsinEM.

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