Takotsubo cardiomyopathy: Healing a ‘broken heart’ still a puzzle to be solved

“He first deceased; she for a little tried; To live without him; liked it not, and died.”— Sir Henry Wotton, 1651As the incidence of takotsubo cardiomyopathy, or broken heart syndrome, rises, recent studies show that long-term outcomes for patients are not as positive as once thought, while successful treatments remain elusive.Takotsubo cardiomyopathy (TTC) as the above Wotton quote suggests, usually follows an emotional stressor, such as the death of a loved one or other major life event, and can also follow a physical stressor, like a sudden illness. It has traditionally been understood to be a self-limiting disease, spontaneously resolving over a few days. But newer studies indicate it leaves patients with greater mortality risk over time.TTC (also called stress cardiomyopathy) is a rare disorder, with 1%-to-3% of patients who seek treatment for myocardial infarctions (MI) actually having the condition. Its symptoms mimic those of MI, but are not due to a blockage but a sudden ballooning of the lower left ventricle. This bulging ventricle resembles a trap used to catch octopus—a takotsubo in Japanese. A study published in the Journal of the American Heart Association in October 2021 found a steady annual increase in TTC among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older, stating that it may reflect the aging population, the rising prevalence of modern life stressors and the greater awareness and detection of the condition. An article published in JAMA in 2020 reported that the incidence had risen five-fold during the pandemic, which the authors suggested was associated with increased psychological, social and economic stressors.“For the longest time, we thought takotsubo cardiomyopathy was a benign condition,” said cardiologist Dr. Ian Paterson, director of the Canadian Centre for Rare Cardiac Conditions at the University of Ottawa Heart Institute, in an interview with the Medical Post, noting that the condition most affects perimenopausal women.“We said, ‘Oh, the heart recovers. We don't need to worry about these patients.’ But there are more and more data and studies, including the recent one, which suggest that the outcomes for these patients, especially men with takotsubo, actually do have quite high mortality if you follow these patients over time.”That recent study, published in the Journal of American College of Cardiology: Advances in January 2024, comes from researchers at Scotland’s University of Aberdeen Cardiology and Cardiovascular Research Unit. They looked at 620 TTC patients from 2010 to 2017, as well as 620 patients with MI, and 2,480 in the general population. Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years followup. This exceeded mortality rates in the general population for cardiovascular and non-cardiovascular deaths, with cardiovascular and pulmonary causes accounting for a major proportion of deaths after TTC. Mortality rates were just slightly lower for patients with TTC than those with MI, which was attributable to lower rates of cardiovascular deaths. Despite comparable medications used, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction—but not in those with TTC. “This is an administrative health database review, which can have some limitations, but overall, it is quite good,” said Dr. Paterson. “Because this is a rare disorder, having 620 patients with takotsubo makes it quite a significant-sized study. So it’s impactful in that respect, and also the duration of followup, five-and-a-half years was quite good. Often we don't have as long a follow-up on these types of studies, so having such a large group and large followup really increases the power of the study.”Read: 'Significantly higher' than previous estimates: New analysis of out-of-hospital cardiac arrests adds tens of thousands to yearly totalOne of the most interesting findings, said Dr. Paterson, was what it revealed about medication use: No cardiovascular therapy remained associated with improved survival in patients with TTC. “For patients with myocardial infarction, the heart pills were associated with better outcomes. But the same medications given to takotsubo patients did not seem to have an impact on improving their outcomes. In fact, some medications were potentially associated with worse outcomes, like anti-inflammatory and diuretics.”Dr. Paterson said how best to treat TTC is one of many unknowns. “This drives home the point for me that there is still a lot about takotsubo syndrome that we don’t know. First, we don't fully understand the mechanism behind why people get it. We know it seems to be related to stress, but what are the specific hormones or processes in the body that are driving takotsubo syndrome? And we don't have any specific therapies for takotsubo syndrome that have an impact on the longer-term risk of death.”Dr. Paterson said that it also remains unclear why there is an association between TTC and non-cardiovascular mortality. “There is in general an association between people who develop heart disease and people who develop cancer. And again, we don't fully understand all of the reasons behind that. Some of it is because there are shared risk factors. There could be some of that going on in takotsubo as well. Overall, there is still a lot to learn.”Read: Using identical twins: Study tests whether vegan or omnivorous diet is better for cardiometabolic health

Takotsubo cardiomyopathy: Healing a ‘broken heart’ still a puzzle to be solved

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