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AACC Publishes High-Sensitivity Troponin Assay Practice Recommendations in Anticipation of More FDA Approvals

NEW YORK (360Dx) – With more high-sensitivity cardiac troponin assays expected to be approved for use in the US this year, the American Association for Clinical Chemistry has published practice recommendations for their use in clinical laboratories.

"We anticipate at least two or three other assays will be approved very soon, and we wanted to make sure the guidance will be out there before they are approved," said Alan H.B. Wu, professor of laboratory medicine at University of California, San Francisco, and clinical chemistry laboratory chief at Zuckerberg San Francisco General Hospital, who was lead author of the practice recommendations published in this month's issue of Clinical Chemistry.

High-sensitivity cardiac troponin tests, immunoassay tests that are used to diagnose myocardial infarction, have been available internationally for years. Currently, though, there is just one high-sensitivity troponin test available for use in the US – Roche's Elecsys Troponin T Gen 5 Stat test, cleared by the US Food and Drug Administration in January 2017.

Companies with high-sensitivity troponin tests that are not yet approved in the US include Siemens Healthineers, Abbott, and Beckman Coulter. Siemens announced its ADVIA Centaur High-Sensitivity Troponin I assay last May. Abbott's Architect Stat High Sensitive Troponin-I assay is available outside the US, and Beckman Coulter announced that its Access hs Tnl high sensitivity assay received a CE mark in November.

Also, Singulex filed a submission in November seeking 510(k) clearance for its Clarity cTnl assay running on the Singulex Clarity system.

AACC's recommendations are intended to aid laboratories that either use or plan to use high-sensitivity troponin assays as more of them become available in the US, said Allan Jaffe, chair of the division of clinical core laboratory services in the department of laboratory medicine and pathology at Mayo Clinic, and a coauthor of the paper.

"The hope is that we provide some consistency, not only for people who are using the assays but for anybody who is evaluating them. When people look and say how ought we think about this, they can use these recommendations as a guide," Jaffe said,

The guidelines were issued by the AACC Academy Laboratory Medicine Practice Guidelines Committee on Cardiac Markers, and endorsed by the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers. As an international group, members of the IFCC could provide perspective on the use of high-sensitivity troponin assays from other countries where these tests have been approved for use for many years.

In addition, the IFCC includes representatives of IVD manufacturers as non-voting participants. As a result, while the manufacturers have not officially endorsed the recommendations, they have seen them and had the opportunity to object to recommendations if they strongly opposed them, Jaffe noted.

One difference in practice recommendations for high-sensitivity troponin assays in comparison to the lower sensitivity assays is on the issue of gender, noted Wu.

"One thing that we are recommending is that we have separate cutoff concentrations for men and for women, which we didn't have before with the lower-sensitivity assays," Wu said. "We are saying that men have higher levels than women, and if you don't choose the sex-specific cutoff you are going to miss cases, because women are going to be misdiagnosed."

The guidelines also presented specific metrics to define high-sensitivity troponin assays, according to Jaffe.

"We put a line in the sand and said this is how you define high-sensitivity assays. There are going to be some assays that don't quite make that metric, so there is going to be unhappiness about some of these things," Jaffe said. "I would argue, in the long run, it's clinical use that will determine what is important and not a specific designation."

The recommendations also introduce different reporting units for high-sensitivity assay than are used for regular troponin assays, Wu said. While troponin is measured in nanograms per milliliter, it is recommended that the high-sensitivity assays be reported in nanograms per liter. The change means results should be reported in whole numbers, rather than decimal point fractions, which can sometimes lead to errors when decimal points are misplaced, he said.

The report also recommends the use of 99th percentile as a cutoff point for measuring troponin, meaning above the 99th percentile is considered elevated. While the 99th percentile level is part of the universal definition of myocardial infarction and has been standard for years, many hospitals use even higher levels.

"There have been a lot of papers about this. A lot of places use higher values and the reason is because clinicians in those institutions are concerned that there are going to be elevated levels and it will lead to problems in the care of patients – increased cost, perhaps even some morbidity from trying to evaluate patients who really don't have indications for being evaluated …[but] simply have a troponin value that is elevated," Jaffe said. "I take issue with that and say if we have an elevated troponin, although we know it to be analytic, the vast majority of times there is something that a good clinician should figure out about that patient."

Wu noted that with higher-sensitivity assays, the 99th percentile cutoff could potentially add to further confusion for clinicians who are accustomed to using an even higher cutoff.

"By using a high-sensitivity assay and lowering the cutoff, we are now picking up cardiac injury due to other diseases besides heart attack," he said.

Key to addressing this issue will be education, according to Wu.

"We believe laboratories have a role in educating their physician colleagues – emergency medicine and cardiology," he said. "What we fear is that that a patient will have an elevated troponin and they'll undergo the expense and the risk of cardiac catheterization only to find that the arteries are clean. Then the interventionalist will call the lab and say you had a false positive. We would argue, no it's a true positive for cardiac injury."