Chest Pain, High Troponin, and Clear Coronaries: Is CMR Needed?

BOSTON, MA—When patients come in with chest pain, elevated troponin, and no obstructive coronary disease, use of an advanced imaging modality like cardiac magnetic resonance (CMR) may help differentiate myocardial infarction with nonobstructive coronary arteries (MINOCA) from other conditions like myocarditis and Takotsubo cardiomyopathy. But is it worth it?

Experts at the recent 2023 Society of Cardiovascular Computed Tomography (SCCT) meeting debated that question, agreeing that CMR can help refine the diagnosis but also agreeing that there’s a lack of randomized evidence to guide management in this situation.

Because of that, Andrew Kelion, BMBCh (Oxford University Hospitals NHS Foundation Trust, England), argued that it’s not worth adding advanced imaging in the absence of solid evidence showing that it makes a difference in management and patient outcomes.

“Yes, MRI is a wonderful, powerful technique that gives you beautiful pictures, but it does not alter your management in an evidence-based way,” he said. “Therefore it cannot lead to a better outcome for the patient, and therefore it’s going to cost you money for an extra test without any proof of benefit.”

Chiara Bucciarelli-Ducci, MD, PhD (Royal Brompton and Harefield Hospitals, England), CEO of the Society for Cardiovascular Magnetic Resonance, disagreed, saying that differentiating between true MINOCA, myocarditis, Takotsubo cardiomyopathy, or none of the above does indeed have management implications. Ruling out an infarct, for instance, will avoid treating patients as if they have had one.

Avoid CMR

Kelion noted that MINOCA is just a subset of patients with troponin-positive chest pain and nonobstructive coronary arteries. Some will have had a true MI, but others will have myocarditis, Takotsubo cardiomyopathy, or some other condition.

He acknowledged that the European Society of Cardiology (ESC) provides a class 1 recommendation to perform CMR in all MINOCA patients when there is no obvious underlying cause. “I, however, would argue that a careful history, looking at the ECGs, an echocardiogram, looking at the bloods, and a review of the angiogram—which by definition they will have had to know that the coronaries are unobstructed—will provide a working diagnosis in the overwhelming majority of patients,” Kelion said. “And to justify further expensive advanced imaging, it’ll have to do more than just turn up some interesting abnormalities and adjust the clinical diagnosis in a few cases. It will need to alter the management so as to improve outcomes and, most importantly, be cost-effective.”

Research shows that CMR can reclassify a proportion of patients and provide a more-accurate diagnosis, he said, questioning, however, whether such imaging can provide important prognostic information, too.

There is absolutely no evidence that patients with troponin-positive chest pain who undergo CMR do better than those managed clinically, and hence there’s absolutely nothing to justify the expense. Andrew Kelion

Data from Bucciarelli-Ducci’s group published in 2019 in JACC: Cardiovascular Imaging show that prognosis is relatively similar among patients with true MINOCA, myocarditis, and normal CMR, with significantly worse outcomes among those with Takotsubo cardiomyopathy. “But you know what? They are the easiest to diagnosis clinically, and with an echo,” Kelion said, asserting that CMR shouldn’t be needed to confirm it.

As for how the addition of CMR might change treatment, he said, “For all those diagnoses that CMR could turn up and, yes, might reclassify your clinical diagnosis, there is absolutely no randomized trial-backed treatment for true MINOCA, simple myocarditis, or Takotsubo.”

Although there are some data suggesting that statins or ACE inhibitors might help in MINOCA and that antiplatelets or ACE inhibitors might be beneficial in Takotsubo cardiomyopathy, they come from observational studies, Kelion pointed out. “And for simple myocarditis,” he added, “there’s really no treatment other than just reassurance.”

He closed out his argument by highlighting the dearth of evidence showing that CMR improves patient outcomes over standard management alone.

“There is absolutely no evidence that patients with troponin-positive chest pain who undergo CMR do better than those managed clinically, and hence there’s absolutely nothing to justify the expense,” Kelion said.

CMR Provides Clinically Meaningful Information

Bucciarelli-Ducci conceded that there is a lack of data from trials showing that CMR improves clinical outcomes in this clinical scenario, but she said there is indeed evidence showing “clearly that having an echo, family history, biomarkers, ECG, [and] angiogram is actually not enough, because these patients present in a very similar fashion and they have very different things.”

Up to 15% of patients with ACS have unobstructed coronary arteries, she said, and these patients have a nontrivial mortality rate of about 5% at 1 year. So this is a diagnostic dilemma, and “we ought to understand a bit more what’s going on with these patients,” she said.

Also, there are management implications to determining whether a patient has MINOCA, myocarditis, Takotsubo cardiomyopathy, or something else, Bucciarelli-Ducci said, because these patients are often treated as if they’ve had an MI even if an infarct hasn’t been confirmed. In fact, most of these patients have not had an infarct, she noted.

The Fourth Universal Definition of MI suggests that if there is a troponin rise with an unclear cause, clinicians should perform CMR, which can differentiate between ischemic and nonischemic etiologies and provide tissue characterization to provide a better idea of what’s going on, Bucciarelli-Ducci said.

Having an echo, family history, biomarkers, ECG, [and] angiogram is actually not enough because these patients present in a very similar fashion and they have very different things. Chiara Bucciarelli-Ducci

She presented several case examples to highlight how CMR can provide a more-accurate diagnosis, which will guide treatment choices, when other methods have failed. In one, a 52-year-old man came in with 2 hours of chest pain, an elevated troponin level, and no cardiac risk factors. The ECG showed ST-segment elevation, and a transthoracic echocardiogram revealed no regional wall abnormalities or pericardial effusion. The coronary arteries were unobstructed on an invasive angiogram.

This type of patient, despite the lack of proof of an infarct, would likely end up on secondary prevention medications, Bucciarelli-Ducci said. But further CMR imaging confirmed the echo findings and uncovered evidence of edema and scarring in the epicardial distribution, showing that the patient had not had an MI and in fact had acute myocarditis.

Additional examples showed how CMR can provide an exact diagnosis, allowing for discharge with a clear treatment plan.

Moreover, research from her group has shown that “even when we didn’t change the diagnosis, we changed the management as a result of identifying clinically meaningful data,” Bucciarelli-Ducci said. Other studies have confirmed that only a minority of such patients have MINOCA, and distinguishing this condition from others is not easy to do with just an echo or angiogram, she added.

To bolster her argument in favor of additional CMR, Bucciarelli-Ducci pointed to the class 1 recommendation in the ESC guidelines and also a similar class 1 recommendation in the US chest pain guidelines.

“There is no debate, I’m afraid, because it is a class 1 already for every MINOCA,” she said.

Is It Cost-effective?

Kelion rebutted Bucciarelli-Ducci’s argument by noting that much of what she presented was anecdotal data.

“There’s no doubt that when you do CMR on these people, you will change your diagnosis a bit,” he said. “But ask yourselves: what is the randomized trial-based management of MINOCA? There is none. What is the randomized trial evidence for managing uncomplicated myocarditis? There isn’t any. What is the management of Takotsubo in a decent randomized trial? And bear in mind actually most Takotsubo you’ll pick up very easily on the echo. There is none.”

Kelion also questioned the cost-effectiveness of CMR, but Bucciarelli-Ducci pointed out that the UK’s National Health Service, which heavily focuses on cost-effectiveness, is supportive of the modality, as shown with high use in the country. There are also data, she added, showing that CMR is cost-effective, helping to come to a correct diagnosis and shortening lengths of stay.

Randomized trials in MINOCA are difficult, Bucciarelli-Ducci said, because it’s a mixed bag in terms of diagnosis. But you don’t necessarily need a dedicated RCT, she indicated, because treatment will be guided by the ultimate cause, whether it’s an infarct, myocarditis, or Takotsubo cardiomyopathy, conditions that have established treatment approaches.

“The problem is if you don’t know what’s going on, you’re going to give secondary prevention to a myocarditis patient, which is exactly what’s happening at the moment,” she said, adding that that can waste money. “If you want to be cost-effective, you actually have to do CMR.”