By Deborah Borfitz
November 10, 2021 | Rising incidence of takotsubo or “broken heart” syndrome is highlighting the need to better differentiate the condition from myocardial infarctions involving blocked arteries as well as other types of myocardial infarction with non-obstructive coronary arteries (MINOCA)—and to figure out the root causes. The best that can be done for patients currently is to as quickly as possible get detailed pictures of their heart from cardiac magnetic resonance (CMR) imaging to improve the odds that they’ll be properly diagnosed and treated, according to Peder Sörensson, M.D., Ph.D., a researcher at the Karolinska Institutet and a cardiologist at Karolinska University Hospital in Stockholm, Sweden.
The once-rare condition presents with all the same symptoms of a heart attack, he says. Outside of university hospitals and regional medical centers equipped with CMR capabilities, standard emergency room practice is to diagnose suspected cases using ultrasound and electrocardiogram (ECG) and, in the catheterization lab, left ventricular angiography (LVA) following coronary angiography.
Those imaging methods sometimes result in a misdiagnosis, he adds. Unlike CMR, they can’t fully distinguish broken heart syndrome from myocarditis and coronary artery disease.
Diagnostics are, however, trending in the right direction. The use of CMR has increased significantly over the past two decades, Sörensson notes, together with off-label use of the extracellular contrast agent gadolinium, which can discriminate ischemic and non-ischemic scars in the heart.
Where CMR is available, the test is also more often being done sooner in patients’ diagnostic journey, he adds. It was previously established that CMR imaging preferably happens less than two weeks after hospital admission.
The first Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study, published in 2013 by the Journal of Internal Medicine (DOI: 10.1111/j.1365-2796.2012.02567.x), followed a protocol calling for CMR to be performed a median of 12 days after hospital admission. That allowed researchers to diagnose 19% of enrolled MINOCA patients with a diagnosis of broken heart syndrome.
In SMINC-2, recently published in JACC: Cardiovascular Imaging (DOI: 10.1016/j.jcmg.2021.02.021), moving CMR up to a median of three days after admission and using more sensitive CMR sequences increased the diagnostic yield for broken heart syndrome to 35%. Overall, 77% of MINOCA patients could be given a diagnosis, a considerable improvement over the 47% in SMINC-1.
Given that broken heart syndrome is “almost always reversible,” says Sörensson, this is gamechanger for afflicted patients. In a newly published study in the Journal of the American Heart Association (DOI: 10.1161/JAHA.120.019583), researchers at Cedars-Sinai Medical Center report 135,463 documented cases of the condition between 2006 and 2017 in the U.S. alone.
Actual incidence could be many times higher. A more accurate estimate won’t be possible until MINOCA conditions, in general, are more readily diagnosable.
To that end, the research team at the Karolinska Institutet are now trying to further enhance their CMR protocol by incorporating quantified stress-perfusion CMR, Sörensson shares. The hunch is that some patients who have a normal CMR in fact have some sort of microvascular disease that results in the same set of symptoms—including high levels of troponin in the blood and ST elevation or depression—as other forms of heart damage.
A pilot research study using the revised protocol just launched, says Sörensson. It will not be an entirely pleasant experience for participants. Some people feel a bit claustrophobic going into the long tube-like MRI machine, and the medication (adenosine) administered intravenously for the stress perfusion test has some expected if uncomfortable side effects that individuals may unnecessarily worry about. The drug leaves the system quickly, so the discomfort self-resolves within about half a minute, he notes.
In Sweden, about 2% of patients with an acute case of coronary artery syndrome or heart failure are diagnosed with takotsubo syndrome, Sörensson says. Of these, 90% are women with a mean age of 67 years old.
This likely mirrors its prevalence around the world. It is now common practice to identify cases of takotsubo syndrome using the InterTAK Diagnostic Criteria, an international consensus document published three years ago in the European Heart Journal (DOI: 10.1093/eurheartj/ehy076).
Overall, people with broken heart syndrome have less common cardiovascular risk factors and symptoms that are more characteristic of a lung disease, he adds. It appears to be linked to psychiatric and neurological sicknesses and there is some evidence that it is connected to cancer, hyperthyroidism, and substance abuse.
Broken heart syndrome is “strongly related to stress,” says Sörensson, including both the psychological and physical varieties. Rather than affecting specific regions of the heart, as with coronary artery disease, takotsubo syndrome can impact the apical, middle, or base of the heart.
Alternatively called “apical balloon syndrome,” broken heart syndrome mimics the symptoms of a heart attack—including chest pain, dyspnea, raised troponin, and (though transient) ST-elevation on the ECG. Mid and apical ventricular segments of the heart, sometimes only a few segments, can also be impaired, he continues.
LVA and ultrasound might show impaired wall motion, but that doesn’t tell doctors if the heart will spontaneously recover, if edema (excess accumulation of fluid) will subside—hallmarks of takotsubo syndrome—or if a patient in fact has an myocardial infarction.
That is why Sörensson, and most other clinical cardiologists, favor CMR imaging for the diagnosis of broken heart syndrome and other types of MINOCA conditions. Results of the SMINC-2 study demonstrated that CMR can diagnose the focal, apical, and basal types of takotsubo syndrome.
SMINC-2 also reflects recent improvements to CMR techniques, notably better pulse sequences, says Sörensson. “We can detect edema easier than we could before.” But researchers believe the increased rate of diagnosis relative to SMINC-1 has more to do with use of CMR earlier in diagnostic workups.
The main hold-ups in broader adoption of CMR is cost—both the magnetic resonance camera and the exams themselves are expensive—and lack of portability, Sörensson says. In contrast, echocardiography machines are transportable, and many hospitals already have catheterization labs with angiography capabilities.
But at bigger hospitals, CMR is becoming commonplace. CMR is also routinely done to diagnose strokes and orthopedic conditions.
Ideally, every hospital emergency department would have an MRI scanner so cardiac exams could be done even sooner than in the SMINC-2 study—potentially, even before the patient leaves the emergency department to reveal the potentially correct diagnose even sooner, says Sörensson.
Expanded clinical applications for CMR could make that a reality sooner rather than later. Researchers elsewhere are already investigating whether the imaging modality might be used to identify and map molecular markers of broken heart syndrome, he notes, including cardiac alfa- and beta-receptors.