High-Sensitivity Cardiac Tests Find a U.S. Market

High-Sensitivity Cardiac Tests Find a U.S. Market

When the first next-generation cardiac troponin test was cleared for marketing in the United States last year, many physicians hailed it as an important moment. High-sensitivity troponin tests to diagnose heart attacks have been available in Europe, Canada, and other parts of the world for several years, but this marked the first time one would be available in the U.S..

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The 510(k) clearance of Roche’s Elecsys® Troponin T Gen 5 STAT assay in January 2017 opened the door for other manufacturers to seek FDA approval of high-sensitivity troponin tests. An article in 360Dx in April 2018 quoted an expert predicting two or three others may be approved this year.

Among the high-sensitivity troponin tests available outside the U.S. but not yet FDA cleared are:

Some U.S. cardiologists have greeted the arrival of next-generation of troponin tests with caution, fearing the higher sensitivity will result in unnecessary referrals for coronary angiography or stress testing, and could result in confusion over what to do with borderline results. However, many hospital systems have moved quickly to update their emergency department algorithms so they could offer the test.

While the tests are designed to diagnose heart attacks in the emergency department, new studies are evaluating  high-sensitivity troponin tests for other diagnostic uses, such as detecting non-ischemic causes of cardiac damage or for predicting heart failure.

Here is an overview of how clinicians may use the new generation of cardiac troponin tests, now that they are coming to the United States.

Detecting Heart Attacks Faster 

            Much of the excitement over the new generation of troponin tests has focused on their potential to provide a faster result for ruling in or ruling out a heart attack.

More than 8 million emergency department visits a year in the U.S. are related to chest pain, and at least 70 percent of those cases turn out not to be heart attacks, according to a scientific statement from the American Heart Association published in 2010, so improving diagnosis could make a big impact on health care quality and spending.

 Cardiac troponin is a protein that is released into the blood when cardiac cells die. Blood levels rise within one to four hours after a blockage occurs in the heart, so an increase in troponin across two measurements is considered a factor supporting a heart attack diagnosis. Professional guidelines in Europe and the US for standard (not high-sensitivity) cardiac troponin tests recommend taking a troponin measurement when the patient arrives in the emergency department and another measurement three to six hours later. With high sensitivity troponin tests, the waiting time between measurements can be reduced to as little as one hour.

            Studies of the so-called “one-hour algorithm” have shown that measuring high-sensitivity troponin upon the patient’s arrival in the emergency department and again one hour later can safely rule out and rule in heart attacks when used alone and also when combined with patient history and electrocardiogram (ECG) results. The one-hour algorithm may even save money, according to a study funded by Roche Diagnostics International Ltd. and published in 2017 in PLoS One (doi: 10.1371/journal.pone.0187662). It gets heart attack patients into treatment sooner, avoiding costly complications, and also sends healthy people home sooner, thus freeing up space in the emergency department, those authors write. The algorithm does detect more “false positives,” -- patients who have elevated troponin but are not having a heart attack -- but those patients often have another underlying condition that would require coronary angiography  regardless (such as unstable angina or heart failure), they found. The cost savings vary widely depending on the clinical setting, they conclude, but overall the one-hour rule out/rule in algorithm saves approximately 46 percent compared to standard care.

            In practice, hospital systems have taken a variety of approaches to using high-sensitivity troponin assays, according to a two-part report in CAP Today (Nov. 2017 and Dec. 2017). Some hospitals are implementing the one-hour algorithm supplemented with patient history and ECG results, while others are conducting the second high-sensitivity troponin test two or three hours after the first. Meanwhile, some hospitals are setting different cut-off levels for men versus women, while others are using a single cut-off level.

            Laboratory professional organizations published new expert consensus practice recommendations in March 2018 to help guide health care systems in adopting the new tests.

 "While some physicians are cautious, many hospital systems have moved quickly to update their emergency department algorithms so they could offer the test."

Troponin Test Usage - Beyond heart attacks

What cardiologists consider a flaw with high-sensitivity troponin tests -- that they detect troponin in people who are not having a heart attack -- actually opens the door to new uses for this class of tests, argue the authors of a July 2017 editorial in the Journal of Applied Laboratory Medicine (DOI: 10.1373/jalm.2017.023648). Cardiac troponin is a biomarker for any type of cardiac injury, not just heart attacks, they note. It has been explored for use in heart failure, renal failure, sepsis, pulmonary embolism, and cancer chemotherapy.

“It has been consistently shown that an increase in cTn [cardiac troponin] is associated with future adverse cardiac events, suggesting that cardiac injury is never benign,” the authors write. They predict that high-sensitivity troponin tests may prove useful in the future for assessing risk in asymptomatic patients.

In early 2018, a meta-analysis found that high-sensitivity troponin tests were able to predict heart failure risk. A 2011 study showed that troponin detected by highly sensitive assays was associated with incidents of coronary heart disease, mortality, and heart failure in people from the general population without known history of heart disease or stroke.

 Results presented at the annual meeting of the British Society for Rheumatology in May 2018 indicated that high-sensitivity troponin I could predict the risk of death among people with inflammatory arthritis. Scientists at Singulex published an article in the Journal of Applied Laboratory Medicine in May 2018 demonstrating the potential of an ultrasensitive assay for cardiac troponin I (cTnI) that can detect exercise-induced cardiac damage, based on measurements in marathon runners.

While researchers explore new uses for high-sensitivity cardiac troponin tests, the FDA is still grappling with how to regulate them. The agency hosted a workshop in November 2017 to solicit feedback from the laboratory community and discuss unresolved problems, such as how to establish reference ranges and what the standards should be for point-of-care tests. The FDA also reached out to manufacturers in December 2017 to notify them of an effort to modernize the performance evaluation of all cardiac troponin tests, which may require them to conduct further clinical studies to bring older troponin tests up to new standards.

However the regulation shakes out, when it’s all settled several test manufacturers will be waiting eagerly to bring their high-sensitivity troponin tests to the U.S. market and many U.S. clinicians will be waiting eagerly to use them.