Large, US Study Supports Single High-Sensitivity Troponin I Test for Suspected Acute MI
“We have a pretty reasonable base of evidence for use [of single-measurement rule-out] in the United States already,” one expert says.
Many patients presenting to the emergency department with a suspected acute MI could be sent home on the basis of just one measurement of cardiac troponin I using a high-sensitivity assay, suggest findings from the largest US study completed to date.
Testing two high-sensitivity troponin I assays cleared by the US Food and Drug Administration, a cutoff of less than 5 ng/L tagged nearly half of patients as low risk, ruling out acute MI with negative predictive values of 99.7% and 99.8%. The two assays missed only three and two events, respectively.
That threshold also identified patients who were unlikely to die or have an acute MI within 30 days, with a negative predictive value of 99.6% for both assays.
Senior author Fred Apple, PhD (Hennepin County Medical Center, Minneapolis, MN), noted that prior studies assessing the use of a single high-sensitivity troponin measurement—as opposed to serial sampling—to triage patients with suspected acute MI have mostly been done in Europe and that there have been lingering questions about whether the results could be applied to the US system, where troponin testing is used in a broader swath of patients.
“Now we have really the first large US study—HIGH-US—to look at patients coming through United States emergency rooms,” he said, adding that the results obtained in this population are similar to those seen in other parts of the world.
If you can send home 30%, 40%, 50% of patients that could then be re-seen as outpatients, the amount of savings in our healthcare system will be tremendous. Fred Apple
Apple described cardiac troponin measured using a high-sensitivity assay as “the most powerful marker we have in the clinical field right now” and said, “We can then use that to help identify patients who are at strong probability to be able to [be sent] home.” That, he added, has major financial implications. “If you can send home 30%, 40%, 50% of patients that could then be re-seen as outpatients, the amount of savings in our healthcare system will be tremendous.”
The study, with lead author Yader Sandoval, MD (Mayo Clinic, Rochester, MN), was published online ahead of the July 23, 2019, issue of the Journal of the American College of Cardiology.
High-Sensitivity Assays in the US
High-sensitivity troponin assays have been used for several years outside the United States to aid in the triage of patients with suspected acute MI, but they did not become available to American physicians until January 2017; there are now several that have been approved by the FDA.
Still, there has not been much information on how these tests perform in US emergency departments, a gap HIGH-US investigators aimed to fill. The study evaluated use of two high-sensitivity troponin I assays—Atellica IM TnIH and ADVIA Centaur TNIH assays (both Siemens Healthineers)—for risk stratification in 2,212 patients (mean age 57; 44% women) with suspected acute MI enrolled at 29 US centers. Acute MI was ultimately diagnosed in 12%, and the rate of acute MI or death (including index MIs) through 30 days was 13%.
Using either the limit of detection (< 2 ng/L) or limit of quantitation (< 3 ng/L) as the cutoff to determine low-risk status in terms of either acute MI during the index visit or acute MI/death through 30 days, both assays showed high sensitivity for ruling out MI (98.6% or higher) with a single measurement. Negative predictive values exceeded 99%.
The optimal cutoff value for maximizing the number of patients eligible for rule-out while maintaining safety was identified as < 5 ng/L. Using that threshold, 46% to 47% of patients were considered low risk, and there were few acute MIs or deaths in this group.
The investigators also showed that combining the results of a single high-sensitivity troponin test with a 12-lead ECG provided sensitivities and negative predictive values above 99%.
Apple noted that troponin should never be considered in isolation. “Troponin is not a stand-alone test. We need to take a look at the clinical presentation.”
In an algorithm depicted as a ‘central illustration’ in their paper, the authors point out that low-risk patients can be considered for early discharge whereas high-risk patients—those with a troponin level of 120 ng/L or higher—can be considered for admission, a cardiology consult, and evaluation for possible acute MI. Serial troponin testing should be used for anyone who falls in between.
Ready for Wider Use?
Asked what more needs to be done before implementing this type of approach widely in the United States, Apple said, “I think we’re there.” He said physicians looking to get started with it can start out conservatively, using troponin values below the limits or detection or quantitation combined with a normal ECG to send patients home.
David Morrow, MD (Brigham and Women’s Hospital, Boston, MA), agreed, noting that some US centers are already using single troponin measurements combined with clinical information—in the form of risk scores or ECG readings, for example—to rule out MI and discharge patients. “I think we have a pretty reasonable base of evidence for use in the United States already,” Morrow commented to TCTMD.
Like Apple, he stressed that troponin level should not be the sole factor used to determine whether someone is okay to leave the emergency department. “We will always watch someone who we think has higher risk even if their initial troponin is low, but provided that [troponin and clinical risk] are aligned, I think the current evidence is quite strong” in support of using just a single troponin measurement to stratify risk, Morrow said.
It is, I think, a mistake just to plop an entirely new assay into a healthcare system without a very thoughtful rollout and education plan for all the providers. David Morrow
However, there are some remaining areas of uncertainty, he noted, including how best to couple clinical risk stratification with biomarkers and how a “one-and-done” strategy works in various subgroups, such as patients presenting within 3 hours of symptom onset, those with renal insufficiency, and those belonging to various races and ethnicities.
Once centers decide to move forward with implementation of high-sensitivity troponin testing, either with a single measurement or serial sampling, education of the various members of the healthcare team is crucial, both Morrow and Apple said.
“As centers start to adopt high-sensitivity assays, it is very important for the emergency physicians, the cardiologists, and the laboratorians to collaborate in a very comprehensive educational plan for all of the practitioners so that they understand how to interpret the assay, [and]how to apply them optimally in their environments,” Morrow said. “It is, I think, a mistake just to plop an entirely new assay into a healthcare system without a very thoughtful rollout and education plan for all the providers.”
Apple said centers need strong advocates to make adoption of high-sensitivity assays work.
“You need a team that’ll advocate, put the evidence base together, and then present it to the staff and show this is how it works,” he said. “And I think it’ll roll out. But if you don’t have that team together and you don’t have good education and you don’t have the evidence-based science like this paper presents, people are reluctant to move forward with any new paradigms.”
Sandoval Y, Nowak R, deFilippi CR, et al. Myocardial risk stratification with a single measurement of high-sensitivity troponin I. J Am Coll Cardiol. 2019;74:271-282.
- The study was funded and designed by Siemens Healthineers for their 510k US Food and Drug Administration submission.
- Sandoval reports having served on advisory boards for Roche Diagnostics and Abbott Diagnostics.
- Apple reports having served on the board of directors of HyTest Ltd.; having served on Advisory Boards for Siemens Diagnostics and Instrumentation Laboratory; having been a consultant for LumiraDx; having received institutional research funding from Abbott Diagnostics, Abbott Point of Care, Roche Diagnostics, Siemens Healthineers, Quidel/Alere, Ortho Clinical Diagnostics, ET Healthcare, and Beckman Coulter; and serving as associate editor of Clinical Chemistry.
- Morrow reports having received research grant support to Brigham and Women’s Hospital and consulting fees from most of the major manufacturers of high-sensitivity assays for troponin.