In This Article
- High-sensitivity cardiac troponin testing was approved for clinical use in the U.S. in 2017, showing major benefits for the diagnosis and exclusion of acute myocardial infarction
- Massachusetts General Hospital is one of the first institutions in the U.S. to convert to this new blood test
- High-sensitivity troponins allow clinicians to diagnose or exclude a heart attack in as little as one hour. Older assay techniques take more than 12 hours
- Use of high-sensitivity troponin assays present potential diagnostic challenges, requiring collaboration and thoughtful physician education
- The diagnostic role of high-sensitivity troponins outside the emergency department will likely expand in the future
Newer versions of cardiac troponin blood tests can help clinicians identify—and exclude—myocardial infarction (MI) earlier and faster.
While physicians around the world have been using high-sensitivity cardiac troponin (hs-cTn) assays for patients with suspected MI since 2010, the tests have only been available in the U.S. for about a year. High-sensitivity cardiac troponins are the next generation of the sensitive cardiac troponin assays currently in wide use across the U.S.
“These tests are able to detect even minute amounts of heart injury at a much earlier time than the older troponin assays,” explains James Louis Januzzi, MD, a member of the Cardiology Division at Massachusetts General Hospital. “Because of this, we can diagnose or exclude a heart attack in as little as one hour, whereas it used to take more than 12 hours with sensitive troponin assay.”
Mass General is one of the first hospitals in the country to successfully implement hs-cTn protocols. Dr. Januzzi, who helped lead hs-cTn assay implementation efforts at Mass General, stresses that a thoughtful implementation approach is key to optimizing the benefits of the high-sensitivity cardiac troponin assays.
The Evolution of Troponin Assays
The first troponin assays, which measure levels of cardiac troponin T or I in the blood, were approved for clinical use in the 1990s. Troponin is a structural component of heart muscle cells and is released into the bloodstream when the heart muscle is injured in some way.
“One huge advantage of the troponin tests is that they are very cardiac-specific, with near 100% specificity for cardiac injury,” says Dr. Januzzi.
That specificity paired with the sensitivity of troponin assays compared to older tests such as creatine phosphokinase led the Universal Definition Task Force to redefine MI using a troponin standard in 2000. Since then, troponin blood tests have become internationally accepted as the gold standard for diagnosing MI.
Despite this, the original troponin assays are not perfect. “Most importantly, older troponin assays cannot measure down into the lower concentrations without losing precision,” says Dr. Januzzi. “When an assay lacks precision, measuring at very low concentrations can produce unreliable results. This means older troponin assays are not reliable for assessing small changes of troponin levels, especially at lower concentrations.”
As the name implies, the new hs-cTn assays have higher analytical sensitivity—less than 10% imprecision at very low concentrations of troponin. This allows clinicians to detect even small amounts of heart injury and resolve changes at those low levels much more quickly. “Because of this, highly sensitive troponins can identify 25 percent more MIs than previous troponin assays and can do it even faster,” says Dr. Januzzi.
A more efficient diagnosis means patients can be treated in less time, saving valuable heart muscle.
Challenges to High-Sensitivity Cardiac Troponin Assay Implementation
Mass General implemented hs-cTn testing in an effort that extended across the Partners HealthCare system. Dr. Januzzi emphasizes the importance of a cautious, collaborative approach to implementation. The biggest challenge to optimizing the testing, he says, lies in the fact that high-sensitivity troponins can identify cardiac injury even in the absence of an MI.
Used indiscriminately, the test can cause confusion for a physician who is trying to understand abnormal results in a patient who clearly has not suffered an MI. “Because medical stress such as uncontrolled hypertension, diabetes or heart failure can cause cardiovascular injury, clinicians need to suspend their assumption that every elevated troponin level they see is associated with a myocardial infarction. Clinicians must recognize that heart injury may occur from a number of different causes,” he says. “Clinical judgment is important when ordering any test.”
Dr. Januzzi and his team address this potential drawback with a clinician education plan at Mass General that emphasizes:
- How high-sensitivity troponin assays differ from older generation tests
- When the tests are clinically appropriate
- How to interpret the hs-cTn assays across clinical situations, including less common medical circumstances
- How the tests will be used in specific settings (for instance, in the emergency department versus an inpatient unit)
Clinicians should be thinking carefully about the differences between hs-cTn and the previous troponin assays used. Expectations can be simplified down to four important points:
- The numbers look bigger: hs-cTn is reported in ng/L, which is 1000 times larger than the prior troponin tests, which were reported in ng/mL. Understanding this difference is critically important, as "small" MIs may look rather large with hs-cTn. Familiarizing oneself with the fact that an hs-cTn of 52 ng/L is the same as the previous abnormal cut-off of 0.03 ng/mL will lend a point to anchor upon for clinicians.
- Much more myocardial injury will be detected with hs-cTn: By their nature hs-cTn assays are able to reach all the way down to a range that prior assays could not, and in doing so, there may be a measurable amount of cardiac injury that is present due to non-MI situations. This may include chronic kidney disease, hypertension, diabetes or other chronic situations that damage cardiomyocytes. "Clinicians should not, therefore, make rash decisions on the basis of a single hs-cTn unless the clinical picture supports the presence of MI," says Dr. Januzzi.
- Quantitative values are important: Because most patients in the hospital will have a measurable troponin, the concept of a patient being "troponin positive" should be discarded. More importantly, clinicians need to familiarize themselves with the range of hs-cTn seen in specific cardiac and non-cardiac diagnoses, in order to better interpret the results. "Very high concentrations of hs-cTn (e.g. >1000 ng/L) are quite specific for acute MI," says Dr. Januzzi, "but lower values may occur from cardiac injury due to other causes."
- Change in hs-cTn values add substantial value: Because of their high precision, hs-cTn assays may accurately resolve small changes, so that acute heart injury, manifesting as a rise and/or fall in hs-cTn--may be identified in a very short period after onset. "This is one of the great strengths of hs-cTn," Dr. Januzzi notes, "and allows clinicians to 'rule in' or 'rule out' acute myocardial injury in as fast as one to three hours. This is the best way to sort out an ambiguously elevated hs-cTn. If it doesn't rise or fall, it's chronic injury, but if it changes significantly, that's an acute situation."
Optimize the Benefits of Novel Troponin Assays
At Mass General’s Emergency Department and Heart Center, clinicians use an accelerated protocol for identifying or excluding MI. This protocol pairs clinical variables with hs-cTn at presentation and one hour. Patients without MI can have a treatment decision made within this hour, while patients ruling in for MI are triaged even more swiftly. Patients with ambiguous results have a three-hour hs-cTn added to their evaluation and are often able to be discharged home as well; this three-hour protocol for blood sampling is also used on the Inpatient Service.
“The accelerated diagnostic protocol combines clinical judgment and lab testing to rapidly decide on the best triage for patients presenting with suspected MI,” says Dr. Januzzi.
Since implementing high-sensitivity troponin protocols system-wide, Mass General has seen highly encouraging results.
“Anecdotally, we have been able to identify many cases of acute myocardial infarction much faster than before. Our ability to rule out and discharge patients has also been accelerated,” says Dr. Januzzi. “The test has really augmented our clinical workflow, while the concerns we had about potential misinterpretation of results and overdiagnosis of myocardial infarction were not realized.”
“We feel successful use of the novel assays was possible only through a well-planned implementation,” says Dr. Januzzi. “The successful rollout of high-sensitivity troponins across Partners HealthCare emphasizes the importance of a collaborative approach with thoughtful physician education to avoid clinician confusion and optimize patient benefits.”
Promising Potential for Future Troponin Applications
High-sensitivity troponins also hold promise for applications outside of MI diagnosis.
The Mass General Heart Center is currently examining troponins’ potential role in evaluating patients with more stable symptoms and identifying underlying coronary artery disease in an office-based setting—patients with stable coronary artery disease, as well as patients with heart failure. Investigators at Mass General have also conducted studies showing how high-sensitivity troponins could prove useful for identifying cardiac injury from chemotherapy.
“I suspect the future holds many newer applications of hs-cTn, including measurement in less-acute settings, and may help to support clinical decision-making well beyond the concept of acute MI,” notes Dr. Januzzi.
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