Misdiagnosed as a panic attack or a heart attack, takotsubo is finally starting to get the attention it deserves.
By Abigail Abrams
Photographs by Florence Sullivan
IN DECEMBER OF 2022, Linda Zoslocki, a then-69-year-old retired high school counselor in Modesto, California, had a deep cough that wouldn't go away. She was tired, and her legs had been swollen for weeks. When her daughter called on a Saturday to see if Zoslocki wanted to come make pizza with her family, her mother told her she wasn't feeling well and wanted to stay home. Her daughter figured she was struggling with a run-of-the-mill yet stubborn respiratory infection—bronchitis, perhaps.
When her coughing continued all weekend, Zoslocki's husband finally convinced her to go to urgent care. The nurse on duty, a friend, told her she needed to go to the emergency room for a scan. Her problem, it turned out, wasn't bronchitis or any kind of respiratory issue at all. Instead, it was her heart: The left ventricle—the main pumping chamber—had stopped working properly, and her heart had swollen up like a balloon. "I was just really surprised," Zoslocki says. She never, for even a second, considered that she might be dealing with a cardiovascular problem.
Zoslocki's condition, known as takotsubo syndrome or stress cardiomyopathy, is often serious and can be fatal. Up to 8 percent of people who experience takotsubo die from it, and 4 to 10 percent of patients will have another episode within five years. Survivors also have a higher risk of death, heart attacks, strokes, and heart failure.
Takotsubo's prime target? Postmenopausal women like Zoslocki. In fact, 80 to 90 percent of cases occur in women, and the average age is 69, per a recent study in the Journal of the American College of Cardiology. The syndrome is often triggered by major emotional events, such as the death of a spouse or a divorce, which is why it's colloquially called "broken heart syndrome." But happy stressors (like a surprise party or winning the lottery) and, increasingly, physical stressors (like a car crash or major surgery) seem to trigger it too.
In Zoslocki's case, the extreme emotional trigger was likely a big family argument, per her doctors. In the months before she was diagnosed with takotsubo, Zoslocki says, her sister was accusing her of trying to take control of their dying mother's estate. "I was so stressed out, I didn't know what to do with my emotions," she says. "I wanted to run into the street and scream."
Still, in as many as one in three cases, doctors aren't able to identify a single trigger. And even though takotsubo often presents like a heart attack at first—usually starting with the classic symptoms of chest pain and shortness of breath—the syndrome occurs without the arteries being blocked and often without any heart risk factors either. Instead, the heart's left ventricle suddenly stops pumping properly (doctors don't yet understand the biological mechanism that causes this disruption), then part of the heart swells up so it looks like a takotsubo, a Japanese pot used to catch an octopus.
It's taken decades for doctors to begin understanding the condition. Initially, many dismissed takotsubo as a panic attack or misdiagnosed it as an actual heart attack (which resulted in patients taking meds to treat a condition they didn't have). "Some clinicians were not even convinced that it actually existed," says Dana Dawson, MD, a professor of cardiovascular medicine at the University of Aberdeen in Scotland and a leading takotsubo researcher. "It was brushed under the rug, and people were labeled with acute myocardial infarction [heart attack], treated as such, patted on the back, and let go with the wrong medications."
Being misdiagnosed is not a new phenomenon when it comes to women and heart problems. Despite heart disease consistently ranking as a leading cause of death for women around the world—and the number one killer of women in the U.S.—research shows that heart symptoms in women are more likely to be misdiagnosed or missed altogether than they are in men, with often devastating repercussions.
Currently, with no single official diagnostic test for takotsubo syndrome, doctors rely on a process of elimination, often performing multiple tests and completing advanced heart imaging to rule out a heart attack and other common heart issues first. Patients who experience more subtle symptoms (think general fatigue, nausea, or simply a vague ill feeling) may put off seeking care, says David Newby, MD, the British Heart Foundation Duke of Edinburgh Chair of Cardiology at the University of Edinburgh.
Takotsubo syndrome was first scientifically described in Japan in 1990 but didn't become widely recognized by doctors until 15 years later, when a group of physicians published a study in The New England Journal of Medicine looking at 19 patients who presented with dysfunction in their left heart ventricle after "sudden emotional stress." And in the two decades since then, researchers have established major centers around the world devoted to studying takotsubo. Patient registries now exist on several continents, collecting data in Europe, the United Kingdom, Japan, New York, and California, among other places.
The syndrome is quite rare: Studies estimate it accounts for only about 2 to 3 percent of all acute coronary syndrome patients and up to 6 percent of female patients who seek help for suspected heart attacks. But cases have steadily increased since 2006, with a particular rise among postmenopausal women, according to data published in the Journal of the American Heart Association. (The proportion of men with takotsubo syndrome has also grown, from about 10 percent to 15 percent, per data from the International Takotsubo Registry, or InterTAK.) Researchers say this is likely the result of doctors getting better at recognizing it in a clinical setting and increased daily stressors in our modern lifestyles.
At this point, any sort of data is crucial, Dr. Dawson says, because it will help us understand big questions such as why postmenopausal women are most susceptible, what the long-term health impacts are, and most crucially, which treatments actually work. So far, there are no approved methods for treating takotsubo directly, so doctors do what they can to provide "supportive care" for patients, which involves minimizing stress and giving medications that can help address specific heart-related symptoms.
But a targeted treatment for takotsubo is necessary, says Dr. Dawson, as research has largely shown that even if existing medications can help with some symptoms, they do not reduce patients' chances of having another takotsubo episode or dying from heart-related causes.
And while there's a clear stress connection with takotsubo, experts also think menopause could be a factor in its development, since the syndrome overwhelmingly affects women. Estrogen protects a woman's heart by relaxing blood vessels and increasing "good" cholesterol while decreasing "bad" cholesterol. As women approach and go through menopause, estrogen levels begin to fluctuate and eventually drop. So researchers believe that having less of that protective estrogen may leave older women more susceptible to developing takotsubo. Indeed, women's risk for high blood pressure and heart disease increases during menopause.
The different biological mechanisms that women and men use to control their blood pressure may provide another clue, says C. Noel Bairey Merz, MD, director of the Barbra Streisand Women's Heart Center at Cedars-Sinai Medical Center in Los Angeles. Men are more dependent on their sympathetic nervous system—which uses stress hormones to communicate with other parts of the body—to regulate blood pressure. Women, by contrast, have alternate biological means of regulating blood pressure, including other aspects of their autonomic nervous system and, possibly, estrogen. (Spoiler: Scientists don't fully understand women's alternate mechanisms yet.) But this could mean that women going through menopause are more vulnerable to heart injury since they have less routine exposure to these stress hormone surges and are then experiencing them with less protective estrogen.
Examining how the heart relates to other parts of the body—especially the brain, with which it has a long-recognized but complex connection—could also help crack the condition's complex code.
Many studies have found high rates of depression, anxiety, and other psychological disorders among patients with takotsubo—a link that also exists in general cases of cardiovascular disease. But one study shows this connection is stronger for takotsubo patients than for traditional heart attack patients and may be critical to understanding takotsubo, says Jelena Templin-Ghadri, MD, one of the researchers and a cardiologist affiliated with the University of Zurich's Center for Molecular Cardiology and the University Medicine Greifswald in Germany.
Doctors now believe that a rush of stress hormones—including adrenaline and dopamine—damages the heart. In fact, Dr. Templin-Ghadri and other scientists working on the InterTAK Registry found that patients with the syndrome often have abnormalities in their limbic system, a part of the brain that regulates emotional and stress responses. Their findings suggest that heightened activity in those brain areas during emotional or physical stress can trigger the autonomic nervous system to send a rush of stress hormones through the body that may cause the heart to weaken. (But why those hormone surges hurt the heart, especially in women, is still not totally clear.)
At Northwell Health in New York, cardiologists connect the brain-heart dots during treatment and regularly refer patients (not just those with broken heart syndrome!) to a clinical health psychologist with expertise in women's health and behavioral cardiology. Lead psychologist Bella Grossman, PhD, works with heart patients at Northwell Health's Katz Institute for Women's Health using cognitive behavioral therapy to help them with anxiety, depression, sleep concerns, and stress management, all aimed at helping patients manage their particular cardiovascular diagnoses.
Many unanswered questions exist, but the thinking is that "studying this more severe form of heart disease might be able to help us understand other common forms of heart disease," says Nisha Parikh, MD, MPH, system director of the Women's Heart Program for Northwell Health.
Understanding takotsubo isn't just about unpacking how our bodies biologically handle stress. It's also about recognizing how a complex set of circumstances creates that stress in the first place. To put it simply, women move through the world differently than men, often facing specific social stressors in mid- to late life that men can more easily avoid.
"Women tend to experience a lot more stress around child-rearing. They have particularly high stress around job strain," says Dr. Parikh. "And then even the stress of caregiving, loss of a spouse—all of that, we know, can affect women."
As the U.S. population ages, research shows that women make up the majority of unpaid caregivers and often bear the responsibility of caring for senior family members, even as they themselves age. Women also live longer than men on average, which means those in heterosexual relationships often outlive their partners, have more years to experience stressful life-changing events on their own, and can face a high risk of social isolation.
Grossman's female heart patients at the Katz Institute often tell her they aren't used to thinking about their own health because they're so used to taking care of others. "For women, it can take a big toll when they're reminded that they can't do everything, that they need to slow down, they need to take care of themselves," Grossman says.
The good news about takotsubo, initially, is that it's considered a temporary condition—most people start to feel better within a few weeks, and the majority recover after a few months. But more recent research shows a substantial risk of both complications and death over the short and long term.
When Dr. Dawson began studying the syndrome around 2010 in Scotland, she found that even after the heart regained its normal, unswollen shape, some patients continued to have symptoms. "They were still fatigued. They were still getting chest pains. They were breathless, they had palpitations, they weren't quite themselves," she says.
So she started conducting clinical trials with people who'd experienced takotsubo at least one year prior. Not only were some still suffering symptoms, but their maximum exercise capability was worse than that of a control group matched to their age, sex, and other health conditions. Patients also showed slightly abnormal biomarkers—metrics that tell physicians whether an organ is functioning properly—which led Dr. Dawson to find inflammation in the heart during takotsubo incidents as well as chronic, low-grade inflammation afterward.
Perhaps most striking, the death rate for takotsubo survivors is consistently similar to that of heart attack survivors, and just last year, researchers confirmed that patients whose original incident was triggered by a physical stressor often have worse health outcomes over time.
Patients are eager for more of this information. Sheree, a 77-year-old physician in New Jersey who asked that Women's Health use only her first name, experienced takotsubo syndrome nearly two years ago. Despite working in health care, she didn't know much about it before she developed it herself. But when she told her daughter, a nurse, about her symptoms, her daughter guessed it was takotsubo right away—in part because Sheree was in the midst of an intense family conflict at the time.
"FOR WOMEN, IT CAN TAKE A BIG TOLL WHEN THEY'RE REMINDED THAT THEY NEED TO SLOW DOWN."
—Bella Grossman, PhD
Now Sheree is back to hiking regularly, which makes her happy, but she's still anxious for answers. And while Sheree has tried to read up on the condition to prepare herself for any potential future health challenges, there isn't a lot out there. "I don't know the long term," she says. "What happens in the future?"
Similarly, Corinne—a 73-year-old retired nurse anesthetist in Montana who experienced takotsubo syndrome about eight years ago during a period of stress when she and her husband were packing up their longtime home in Minnesota to move to Montana—is still not sure how it might affect her in the years to come. She has been able to go back to her normal routines, walking two to three miles outside each day, but also worries about possible effects later on.
"They weren't terribly specific about anything I should be doing," she says of her doctors.
On Reddit, Corinne and many other women are turning to each other for advice about ongoing symptoms. Multiple Facebook groups dedicated to takotsubo syndrome have thousands of members who discuss the condition and its mysteries. And while they provide reassurance that takotsubo survivors are not alone, concrete information is limited.
Researchers say they're unlikely to discover a one-size-fits-all treatment, but with so many medical groups focusing their efforts on takotsubo, there has been slow yet steady progress.
Fourteen years ago, researchers in Switzerland launched the InterTAK Registry to study patient medical data from hospitals around the world and piece together a broader understanding of the condition. Thanks to their hard work, InterTAK now has info on more than 4,000 patients at 60 research centers in 19 countries. Smaller registries exist in the United States, including one at Cedars-Sinai, run by Dr. Bairey Merz, and another at NYU Langone Health.
In addition, Dr. Dawson has started the Scottish Takotsubo Registry, which she says is the first complete countrywide database of takotsubo patients, using Scotland's national electronic health records to include every case diagnosed there going back to 2010. All these databases have significantly helped researchers paint a clearer picture of the syndrome.
Using their growing pool of data, InterTAK researchers have developed a machine-learning model designed to help doctors differentiate takotsubo from other acute coronary syndromes and properly diagnose it. The researchers are still validating it for routine clinical use, and the model would likely need to get FDA approval in the U.S., but Dr. Templin-Ghadri hopes that it can one day help doctors diagnose takotsubo faster and more accurately.
This past January, Dr. Dawson launched the world's first randomized clinical trial testing a class of medications to see if they can prevent some post-takotsubo complications, including heart attacks, strokes, heart failure, repeat takotsubo episodes, and death. The drugs—renin-angiotensin system inhibitors—relax blood vessels and are widely used to treat heart failure. They were the one treatment that had a slight association with reduced death in Dr. Dawson's prior research, and she plans to start recruiting patients for the new trial this summer.
"IT WAS BRUSHED UNDER THE RUG, AND PEOPLE WERE LABELED WITH ACUTE MYOCARDIAL INFARCTION [HEART ATTACK], TREATED AS SUCH, PATTED ON THE BACK, AND LET GO WITH THE WRONG MEDICATIONS."
—Dana Dawson, MD
"We're starting with a known entity to see whether repurposing something that we've already got might give us the first step of help for these patients who are orphaned of any medication in their recovery," Dr. Dawson says. She's also working on studies that look at whether a prescribed exercise regimen or cognitive behavioral therapy could help people recovering from takotsubo. At the same time, researchers at NYU are testing the effectiveness of deep breathing for reducing stress and potentially lowering the risk of future heart problems in takotsubo patients.
Of course, doctors are fighting an uphill battle if they can't properly pinpoint what causes takotsubo in the first place. So Dr. Bairey Merz and her team at Cedars-Sinai are using their patient registry to try to find answers to this key question by mapping the biological, demographic, psychosocial, and clinical characteristics of those who have experienced takotsubo syndrome.
Just as people with lighter skin and eyes are more likely to get a sunburn, Dr. Bairey Merz says people who experience takotsubo syndrome seem to have certain protein patterns (the sequence of amino acids within protein molecules) that may make them more susceptible to these stress hormones. The research is still very new: Her team just published a study last fall that found two abnormality patterns in the way patients' heart muscles worked during their initial takotsubo incident, which were associated with some increased risk of recurrence. More studies are in the works to explore these patterns further.
"The pie in the sky would be that someday we would be able to recognize anyone at risk for a takotsubo," says Dr. Bairey Merz. "I don't know that we're going to be able to prevent all takotsubos. But once someone's had one, how do we prevent recurrence? That's the goal."
Two years after her diagnosis, Zoslocki mostly feels better, but she's still adjusting to life post-takotsubo and hoping scientists find more information soon. She's made up with her sister and has been dutifully undergoing an echocardiogram twice a year as her doctor recommended. But at an appointment in February, the echo showed that her heart's left ventricle still wasn't quite back to its normal strength.
Zoslocki tells all her friends about her experience so they know what to watch for. "You have to be very vigilant," she says. She wishes she had more answers and actionable steps to protect her heart. The medical advice on how to keep her stress low (don't watch the news, for example) is tough to follow. "I wish I knew more," she says.
Hopefully, thanks to the hard work of doctors and researchers across the globe, Zoslocki won't have to wait too long.
These four steps are key for recurrence prevention.
Your best protection? Taking whatever meds your physician recommends and returning for all scheduled checkups. Follow-up appointments are particularly important so that the doctor can monitor your progress after the first phase of recovery and catch any complications on the early side.
Managing your stress level can help with recovery and potentially reduce the risk of future heart problems, doctors say. Therapists can help you avoid internalizing stressful situations. Other techniques, such as spending time in nature and deep-breathing exercises, have been shown to offer physiological benefits.
You may have low energy levels or difficulty exercising for several months after takotsubo, which can be frustrating and isolating. Cardiologists recommend support groups focused on takotsubo or on heart conditions more broadly, which can connect people with similar experiences and help them learn relaxation strategies.
Patients who want to help researchers find out more about the syndrome can enroll in one of the many patient registries that now exist and share their symptoms—or even sign up to be part of a future study.