‘Classic’ Takotsubo? Not So Fast: Different Presentations Could Spell Diverse Prognoses

Patients with Takotsubo cardiomyopathy have similar long-term outcomes to patients with ACS, but despite what has been previously assumed about this rare condition, so-called broken-heart syndrome can be triggered by a wide variety of known and unknown stressors, according to new data. As such, the investigators suggest a new categorization system for more definitively diagnosing the syndrome.

“Given the heterogenous character of triggers, Takotsubo syndrome encompasses a wide spectrum ranging from a benign to fatal condition,” write lead author Jelena Ghadri, MD (University Hospital Zurich, Switzerland), and colleagues, describing the syndrome as “much more multifaceted” than previous studies might have suggested.

“The old woman with an emotional triggering event and apical ballooning, ‘the classic Takotsubo syndrome patient,’ indeed has a good short- and long-term prognosis, whereas patients with Takotsubo syndrome secondary to neurologic disorders and Takotsubo syndrome secondary to physical activities, medical conditions, or procedures reveal an unfavorable outcome,” they add.

For their study, published in the August 21, 2018, issue of the Journal of the American College of Cardiology, the researchers looked at 1,613 patients from the International Takotsubo (InterTAK) Registry between 2011 and 2014. Emotional triggers were identified in 30% of the population, and 39% were found to have a physical trigger (including 6% with an active neurological disorder). The remaining one-third of patients had no identifiable triggering factor.

In an age- and sex-matched cohort analysis of 455 each Takotsubo and ACS patients, long-term mortality was similar (P = 0.49).

Takotsubo syndrome due to physical stress—whether physical activities, medical conditions, or procedures—was associated with higher long-term mortality compared with ACS, but those with emotionally triggered Takotsubo syndrome were more likely to survive. Neurologic conditions spurred the worst short-term mortality outcomes.

In lieu of their findings, Ghadri et al propose that the following new classification system be used for Takotsubo syndrome, as related to the following:

• Class I: Emotional Stress
• Class II: Physical Stress (Class IIa: physical activities, medical conditions, or procedures; Class IIb: neurologic disorders)
• Class III: No Identifiable Triggering Factor

“As medicine approaches delivery of personalized medicine and our knowledge about Takotsubo syndrome grows, it is crucial to consider the ‘individual patient’ to perhaps improve prognosis,” the authors conclude. “Thus, the new InterTAK Classification based on the type of triggering event might be a useful clinical tool for risk stratification.”

The Nitty Gritty of Takotsubo Syndrome

In an accompanying editorial, Scott Sharkey, MD (Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, MD), and Barry Maron, MD (Tufts Medical Center, Boston, MA), write that this large study provides “new and/or confirmatory information for clinicians charged with managing Takotsubo syndrome patients. As a consequence of all these efforts, lasting > 20 years, a more comprehensive understanding has emerged regarding the clinical spectrum and natural history of Takotsubo syndrome.”

Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), commenting on the study for TCTMD, observed that the results match what he sees in clinical practice, but said “it's important because they've got a lot more patients in their registry than any individual physician is going to see even in a lifetime of practice. And it's useful because I think sometimes when physicians see things relatively infrequently, they might form an impression based on the cases they've seen, but not the larger universe of cases.”

There is still much to understand about this disease, especially as more of it is being identified, he said. “With the widespread availability of cath labs being mobilized when there's ST-elevation and almost ubiquitous echocardiography, I think we're just picking up a lot more of this. I don't know that it's necessarily new in any way or more prevalent, it's just that the diagnosis is being made more often. I think some of these folks were just labeled with other diagnoses in the past.”

Bhatt stressed that “it's important to realize that these patients can have a wide variety of prognoses and it's best not to assume anything.”

While most interventional cardiologists have at least heard about Takotsubo syndrome if not treated a few cases by this point, education is still needed, he said. “There's probably value in just the broader cardiology community understanding that this is a syndrome that's out there and to be on the lookout for it.”

Moreover, there needs to be greater awareness of the wide variety of presentations this condition can take. “You can't just assume because it's a man, it's not Takotsubo, much like you can't assume it is Takotsubo because it is a woman either,” according to Bhatt. “Another important message is to treat these patients seriously. They do have a flavor of acute coronary syndrome even though it's not due to plaque rupture and even though it's not going to be treated with a stent, but that doesn't mean that they don't need careful observation and follow-up.”

You can't just assume because it's a man, it's not Takotsubo, much like you can't assume it is Takotsubo because it is a woman either. Deepak Bhatt

Sharkey and Maron conclude that while “remarkable” progress has been made in understanding Takotsubo syndrome in the last two decades, “the fundamental mechanisms by which stressful events cause acute regional myocardial injury remain incompletely resolved, representing the next generation of investigation.”

Bhatt said this is a “great area for future research, and hopefully this report will spur more people to put together their own Takotsubo registries, so that we really have large numbers of patients and get a better handle of what's going on with this disease.”