Q&A: Heart attack overdiagnosis not benign; ‘mindful interpretation’ of troponin needed
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Key takeaways:
- Due to overreliance on high-sensitivity biomarkers alone, misdiagnosis and overdiagnosis of heart attack have increased.
- Consequences include downstream testing, insurability effects and financial burden.
Overreliance on high-sensitivity troponin as the sole assay to diagnose heart attacks has led to a rise in misdiagnosis, which is not benign and burdens the health system and patients with unnecessary and sometimes invasive testing.
In a viewpoint article published in JAMA, James L. Januzzi, MD, the Hutter Family Professor of Medicine at Harvard Medical School, cardiologist at Massachusetts General Hospital and director of heart failure and biomarker trials at the Baim Institute for Clinical Research in Boston, and colleagues wrote: “More than 750,000 individuals receive a diagnosis of MI each year in the United States. This large number represents a small numerator compared with the massive denominator of the total number of individuals evaluated for the diagnosis. An enormous number of individuals are evaluated for MI because its underdiagnosis has become a major concern for clinicians.”
In their viewpoint, Januzzi, Cian P. McCarthy, MBBCh, BAO, SM, a cardiologist and researcher at Massachusetts General Hospital and an instructor of medicine at Harvard Medical School, and Jason H. Wasfy, MD, MPhil, director of quality and outcomes research at the Massachusetts General Hospital Heart Center and associate professor at Harvard Medical School, wrote, “Emerging evidence suggests that incorrect overdiagnosis of MI is more common than its underdiagnosis.”
Healio spoke with Januzzi about the reasons for MI overdiagnosis, the consequences of misdiagnosis and best practices utilizing the universal definition of MI, published in Circulation, to avoid such mistakes.
Healio: What inspired you and your co-authors to write this viewpoint?
Januzzi: My colleagues and I are clinicians as well as clinical researchers with an interest in testing for diagnostic modalities including biomarker testing. In our clinical practice, we have noticed that the dependence upon measurement of troponin, a commonly measured blood test to diagnose MI, has increased over time.
With increased dependence on the identification of myocardial injury reflected in an abnormal troponin value, the diagnosis of MI has grown, in part, because of the increasing sensitivity of troponin assays.
There has been a global shift over the past 10 years, and the United States has lagged somewhat, but now is catching up, to using more sensitive troponin tests. These tests are incredibly useful. They allow us to recognize myocardial injury earlier and in a larger percentage of patients in whom use of previous versions of troponin might have missed myocardial injury.
When these sensitive tests are abnormal, we are for sure detecting more ‘true positives’, that is, people who have an MI. The problem is that because of the sensitivity of these assays, we’re also recognizing more cardiac injury from other reasons that are not heart attacks. Clinicians, understandably, get confused when they see heart injury on a blood test because their immediate impulse is to assume this is from a heart attack. But to the extent that these tests now can detect injury for other reasons, clinicians really need to be careful about attaching a diagnosis of MI without fulfilling the rest of the universal definition of MI, which is a very important guidance regarding the appropriate diagnosis of heart attack.
Healio: What is the rate of overdiagnosis of MI today?
It’s hard to know the true percentage of overdiagnosis at present because we lack contemporary evidence from more recent studies. This is an area of ongoing research and interest because clearly if there are means by which to refine the approaches that we take to diagnose MI, such as adding other biomarkers or other clinical information, we certainly should be thinking about how we can do so.
Healio: Were there any specific studies or specific clinical experiences of your own that gave you the first signs that MI may be overdiagnosed due to these more sensitive troponin assays?
Januzzi: In clinical practice, we have seen an increase in the concern for MI given the higher percentage of individuals with an abnormal troponin concentration.
If you look at circumstantial evidence, such as in clinical trials, where patients are submitted as having a possible MI but are subjected to rigorous adjudication using the universal definition of MI, we see about one in five individuals actually taken out of that list.
Furthermore, if you look at a study that we published (McCarthy C, et al. JAMA Cardiol; 2019;doi:10.1001/jamacardio.2019.0716), McCarthy, my co-author, evaluated patients that were coded as having a type of heart attack called a type 2 MI. These are folks who have been diagnosed with a heart attack that is triggered by stress on the heart, unlike the so-called type 1 MI, which is related to an obstructed coronary artery.
One can develop a heart attack not because of a clot in an artery reducing flow on the supply side, but related to increased demand on the other side of the equation. For example, a person who has fevers and a high heart rate in the setting of fixed coronary artery disease may develop inadequate supply to the heart muscle and have a heart attack that way.
Upon scrutinizing the patients coded as having type 2 MI, as many as 42% actually did not meet the universal definition of MI criteria, and their diagnosis was largely based on the recognition of myocardial injury with a rise and/or fall in troponin.
This really is just an example of evidence that clinicians may be overdependent on troponin measurement to make the diagnosis of MI. It’s an important tool, but again, the universal definition of MI incorporates not only evidence for myocardial injury through troponin measurement, but also requires the presence of signs or symptoms of coronary ischemia, often lacking in many of the patients who get misdiagnosed with the presence of MI.
Healio: Can you speak more to the importance of applying the recommendations of the universal definition of MI working group?
Januzzi: I keep coming back to it because this is the central message to clinicians who utilize any diagnostic test. It is important to remember that diagnostic tools may be abnormal in disease states other than the one that they may be seeking. Troponin may be abnormal in many other diagnoses besides MI.
When troponin was an inferior assay, pretty much the only thing that made it abnormal was MI.High-sensitivity assays have great strengths in that they allow us to diagnose more true MIs and do it faster. But the downside is that, owing to their increased sensitivity, troponin may be abnormal in many disease states besides MI.
We on the Universal Definition of MI Global Task Force have repeatedly emphasized that the universal definition not only include evidence of myocardial injury as reflected in an increase in cardiac troponin, but also the presence of coronary ischemia as part of that definition.
Healio: In any contemporary clinical research or your personal experience, are you seeing any trends in overdiagnosis by subgroups, such as how a patient presents or their sex, age or race?
Januzzi: This is an area of great interest in ongoing research right now. We hope to have clarity about this question in upcoming studies. It’s reasonable to expect that individuals that are more prone to abnormal troponin concentration may be a greater risk for MI overdiagnosis. This may include older individuals; individuals with social drivers of health that determine higher values of troponin, including Black individuals, individuals with diabetes and chronic kidney disease; and the patients with suspected type 2 MI. These are an important patient population that are at least as common as classical type 1 MI, and overdiagnosis of type 2 MI is problematic for many reasons. One of which is we lack a clear treatment strategy for these patients, and so attaching a diagnosis of MI in someone who doesn’t even have the diagnosis is problematic because it has serious implications from insurability and prognosis perspective. On top of that, misdiagnosis creates therapeutic confusion about how to manage them.
We feel quite strongly that improvements in how clinicians approach suspected MI are needed. The good news is the Universal Definition of MI Task Force will be reconvening imminently. In this next round of the universal definition, there’s great intention to address the increasing reliance on troponins to make the diagnosis of MI, acknowledging their importance, but also emphasizing the need for mindful interpretation of the test when evaluating patients with possible MI.
Healio: What are some of the other consequences of MI overdiagnosis, be it economic, resource allocation, or tolls on the physical and mental health of patients?
Januzzi: If a person is diagnosed with an MI correctly or incorrectly, it typically leads to a cascade of events including further diagnostic testing, therapeutic interventions and even possibly invasive evaluation and treatments.
On the one hand, the improvements in troponin sensitivity have helped us to more rapidly identify and treat people who have a heart attack. But the problem is for those who are overdiagnosed and who lack the diagnosis of MI, the risk is a potential cascade of treatments that follow.
Furthermore, the impact on patient well-being. Being told they’ve had a heart attack, if appropriate, it’s important for them to understand. But if it’s not correct, that can have significant downstream ramifications as well.
Strategies to reduce MI overdiagnosis are critically important. Trying to understand how we can identify the true positives while reducing the risk of overdiagnosing and overtreating the individuals who have an abnormal troponin but do not have MI is a critical next step.
Healio: What do you hope to be the main takeaway from your viewpoint for any clinician who reads it?
Januzzi: Given improvements in troponin, which were much needed, overdiagnosis rather than underdiagnosis is likely to be the more dominant form of misdiagnosis of MI.
Clinicians need to understand that overdiagnosis is not a benign process and could potentially expose patients to risk, and furthermore may have downstream implications with respect to health care, finances and the intended effects of health policies that focus on appropriate treatment of MI among people with the diagnosis.
Misdiagnosis is not a benign situation for patients, hospitals or health care systems, and clinicians should try to understand that troponins are only a single part of the universal definition of MI and be mindful of the need to be certain of the presence of myocardial ischemia in the presence of an abnormal troponin before making a diagnosis of MI.
References:
- McCarthy CP, et al. JAMA. 2024;doi:10.1001/jama.2024.5235.
- Thygesen K, et al. Circulation. 2018;doi:10.1161/CIR.0000000000000617.
For more information:
James L. Januzzi, MD, can be reached at jjanuzzi@mgb.org.
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