EXECUTIVE SUMMARY

Some emergency providers in the United States finally can access a high-sensitivity troponin assay that enables them to detect heart attacks and other cardiac problems faster than older troponin tests. While it can take several months to safely and effectively switch to the new test, the benefits to both patients and providers are considerable. Although evidence from Europe suggests the tests uncover more evidence of cardiac disease, follow-up is required.

  • The University of California San Diego Health was the first health system in California to implement the test following months of planning and preparation. Other hospitals, such as Massachusetts General Hospital and Brigham and Women’s Hospital in Boston and the Mayo Clinic in Rochester, MN, also are implementing the new test.
  • Complicating implementation of the new assay is the fact that consensus guidelines on how to use fifth-generation troponin tests have not been established in the United States, although Europe and other parts of the world have been using the fifth-generation tests for years.
  • With just one high-sensitivity troponin assay approved by the FDA, only hospitals that have acquired Roche testing platforms can use the test, although other companies are seeking approval for similar tests.

It has been more than a year since the FDA finally cleared the way for clinicians to take advantage of a high-sensitivity troponin test, which can be used to detect heart attacks and other heart problems faster than older tests. However, while the new, fifth-generation test offers significant benefits to emergency providers as well as their patients who present with chest pain and other heart problems, hospitals have been slow to adopt the new approach, and there are multiple reasons why.

First, it takes time and education for clinicians and labs to learn how to use the new test. Further, adoption of the new test is only financially feasible at hospitals that use Roche platforms to run their tests because the single, high-sensitivity troponin assay approved by the FDA is the Elecsys Troponin T STAT assay, developed by Roche. The FDA has yet to approve high-sensitivity troponin assays for the other testing platforms. Such barriers are frustrating to clinicians eager to take advantage of high-sensitivity troponin tests because many different assays have been available in Europe and most other parts of the world for years. However, while access to the test remains limited thus far in the United States, some hospitals have begun to implement the improved test and to reap the benefits, giving emergency providers a powerful new tool in their care of chest pain, one of the top diagnoses in the ED. (See also in this issue: New Four-step Protocol Boosts Care, Outcomes for STEMI Patients.)

Prepare for Lengthy Transition

The University of California San Diego (UCSD) Health was the first health system in California to use the new test, but the transition involved months of planning and preparation, explains Lori Daniels, MD, MAS, FACC, FAHA, director of the cardiovascular ICU in the UCSD division of cardiovascular medicine.

“We started maybe even a year before the switch with a planning committee that included myself from cardiology, one of the directors of our labs, and some representatives from the ED as well,” she says. “We began some education talks, and we implemented it in phases where for a while we ran the old test side by side with the new test to give providers in the ED and everyone else a warning that on this new test the numbers are going to look different.”

In fact, results from the side-by-side testing revealed several cases in which the older test produced normal results while the high-sensitivity test showed abnormal results indicating some type of cardiac issue, Daniels explains.

In addition to a comparative testing period, implementation requires collaboration between cardiology, the ED, the lab, and even IT personnel, Daniels observes.

“You have to decide what algorithm you are going to use and how you are going to make sure the time points for drawing blood for the tests are accurate, so it does take some work to get going,” she says. “And it takes a lot of education on how to interpret the results.”

Complicating the process is the fact that consensus guidelines on how to use fifth-generation troponin tests have not been established in the United States.

“The European Society of Cardiology has, and a lot of us are using adaptations of that algorithm, but we don’t have [such guidance] in the U.S. because the test hasn’t been available here,” Daniels notes. “Every hospital for now has to decide on their own which algorithm they are going to use based on the published data and the European recommendations for the most part.”

Since most of the data on high-sensitivity troponin tests are from Europe, professional societies in the United States are waiting for sites here to report on their experience with the new test before issuing recommendations.

“That is happening, but slowly,” Daniels offers. “There are some differences between a European ED population and a U.S. ED population. For example, the incidence of MI [myocardial infarction] among patients with suspected heart attacks is lower here than in Europe.”

The population difference suggests that the negative predictive value of the test probably will be better in the United States than in Europe, but it also may mean that the positive predictive value will not be as good, Daniels shares.

“It affects the interpretation a little bit. Also, the cut points that the lab is allowed to report for the test [which are established by the FDA] are different here than in Europe,” she says. “There are several differences between Europe and the U.S., so you can’t just exactly adapt what they have done in Europe. It has to be altered slightly.”

Consider the Benefits

Despite such complications, the potential payoff for both providers and patients is significant. Experts note that fifth-generation troponin tests can detect a heart attack within one to three hours vs. six to 10 hours for older-generation troponin tests. That means chest pain patients aren’t stuck in the ED for half a day or more before receiving treatment or discharge orders, and clinicians can move on to other patients, thereby improving patient flow and satisfaction. Further, experts note that the newer tests enable gender-specific cut points, making it easier for clinicians to detect heart problems in women.

As of February 2018, every patient who presents to the ED at a UCSD Health medical center complaining of chest pain has been receiving the fifth-generation troponin test.

“It even goes beyond that because heart attacks don’t always present with chest pain,” Daniels notes. “Sometimes, it is just shortness of breath or other vague symptoms, so there [are] a ton of people getting this test.”

Typically, emergency physicians are the first to interpret the data from the new test.

“If they are concerned, they will call a cardiologist for a consultation,” Daniels explains. “The lab has set cut points for what is normal and abnormal, but it really takes more than a yes or no answer. It takes consideration of the entire clinical picture.”

While the fifth-generation troponin test has been fully implemented at UCSD Health, work remains. Cardiologists continue to refine the algorithm clinicians use to interpret the results, and educational initiatives aimed at helping clinicians to optimally interpret the results are ongoing.

“There is a lot of one-on-one education as well,” Daniels notes. “I let people know to call me when they have questions. We will reach out individually and in groups.”

Other hospitals, such as Massachusetts General Hospital and Brigham and Women’s Hospital in Boston and the Mayo Clinic in Rochester, MN, are in the process of implementing the test as well. “In the next few weeks, [many] more will be coming online, so I think [the test] is going to gain momentum,” Daniels predicts. “I think eventually [every hospital] will be using the test, but change doesn’t come quickly in the medical world.”

Understand Regulatory Hurdles

Some experts are not so sanguine about the time it is taking for emergency providers in the United States to get their hands on high-sensitivity troponin tests. W. Frank Peacock, MD, FACEP, FACC, a professor of emergency medicine, associate chair, and research director for emergency medicine at Baylor College of Medicine in Houston, has been researching troponin for years, and he recently published a multi-site study of the efficacy of using high-sensitivity troponin testing to identify low-risk patients with possible acute coronary syndrome.1

However, Peacock is frustrated that he still lacks access to the fifth-generation test in his own ED. “You can go to Nigeria and get a better troponin [test] than we have in the U.S. You can go to any third-world country and get a better troponin test than we have in the U.S.,” he stresses. “We are eight years behind the globe.”

The chief reason why Peacock and most other emergency providers in the United States still lack access to high-sensitivity troponin tests is because the testing platforms used by their hospitals to run such tests cannot run the Roche assay, and the FDA has not yet approved the high-sensitivity troponin assays developed by Siemens, Abbott, or the other companies working in this space.

Peacock, who has consulted for some of the companies that have developed high-sensitivity troponin assays, and has testified before the FDA on this issue, explains that the FDA’s reluctance to approve more high-sensitivity troponin assays is because the agency is concerned about the accuracy level of the test results when very low levels of troponin are detected.

In Peacock’s view, this concern is unnecessary because he maintains that slight differences in results at these very low levels are not clinically important.

“If [the result] is under 6, that is good. If I can get a level that is 4, and two hours later it is 5, I can send the patient home. It is nowhere near an MI, which is 19,” he says. “The FDA is making companies report numbers down to very low levels very accurately, which is a really heavy lift.”

Hospitals are not exactly eager to purchase Roche testing platforms to run the only high-sensitivity troponin assay that has been approved. The machines that run these tests are extremely expensive, and hospitals rely on them to run dozens of tests, Peacock explains.

“No hospital is going to spend another $20 million to be able to run one assay,” he says.

For hospitals that are using Roche testing platforms, adding the newly approved high-sensitivity troponin assay is a relatively simple matter.

But hospitals that use testing platforms developed by other companies are out of luck, at least until the FDA approves the high-sensitivity troponin assays that can run on their machines.

Peacock worries such approvals could take years.

“We are behind the rest of the world by eight to maybe 10 years,” Peacock laments. “I go to conferences all over the world, and I tell people that we are the Third World of troponin. Our [chest pain] patients wait in the ED for 12 hours. I know yours only wait for an hour.”

However, the FDA isn’t the only voice of concern regarding the fifth-generation troponin tests. Some cardiologists in the United States have expressed worries that the test could result in too many false-positive results in patients who are not experiencing heart attacks.

But Peacock notes that elevated troponin levels that do not reach the level of an MI still are a cause for concern.

“Troponin is a structural protein ... and if structural proteins are floating around in the blood at high levels, there is a real problem for the heart,” he says. “But if you don’t know the troponin level is up, you won’t know there is a heart problem ... and the big advantage [of the high-sensitivity troponin tests] is we get to know those levels.”

For example, in Europe, a finding of 14 reflects a normal level of troponin on a high-sensitivity troponin test; a finding of 52 is indicative of a heart attack, Peacock explains. That means that findings anywhere between 19 and 52 are a gray zone, he says.

Traditionally, troponin was only a heart marker, and if it was elevated, the patient would go to the cath lab, and one didn’t have to think, Peacock relates.

“Now, you have to think, and you have to figure out why the troponin was elevated, and cardiologists should be involved. They are the heart doctors,” he says. “When you make the switch to high-sensitivity troponin [tests], you don’t suddenly start sending tons of people to the cath lab, but you do find diseases you didn’t find before, and people do better when you find these diseases.”

That has been the experience of providers in countries that have been using high-sensitivity troponin tests for six to eight years, Peacock observes. “There is not an increased rate of cardiac events or of patients going to the cath lab, but patients have more studies for other reasons, and providers find more diseases, which are then treated,” he says.

While many emergency providers still face access barriers to the test, experts note that they should be following the literature as these new tests are implemented in EDs across the United States, and they should be discussing within their institutions how they will implement the new assays when they do become available.

“Every single company that makes an assay in the U.S. has a high-sensitivity troponin [test] that they are trying to get through the FDA,” Peacock observes.

REFERENCE

  1. Peacock WF, Baumann B, Bruton D, et al. Efficacy of high-sensitivity troponin T in identifying very low-risk patients with possible acute coronary syndrome. JAMA Cardiol 2018;3:104-111.

SOURCES

  • Lori Daniels, MD, MAS, FACC, FAHA, Director, Cardiovascular Intensive Care Unit, University of California, San Diego, Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, La Jolla, CA. Email: lbdaniels@ucsd.edu.
  • W. Frank Peacock, MD, FACEP, FACC, Professor, Emergency Medicine, Associate Chair and Research Director, Emergency Medicine, Baylor College of Medicine, Houston. Email: frankpeacock@gmail.com.