Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

Trisha Singh, BM; Hilal Khan, MB BCh BAO, MRCP; David T. Gamble, MPharm, MBBS; Caroline Scally, MBChB; David E. Newby, DM, PhD; Dana Dawson, MD, DPhil


Circulation. 2022;145(13):1002-1019. 

In This Article

Natural History

Takotsubo syndrome had previously been viewed as an interesting anomaly that ran a benign course. As such, patients were often given reassurances that they were fortunate not to have had a heart attack, and that their heart would recover completely back to normal with an excellent prognosis. However, we now know this is not the case. Despite the recovery of the left ventricular ejection fraction and the absence of major coronary artery disease, patients with takotsubo syndrome have outcomes that are considerably worse than the general population.[8–13] Takotsubo syndrome has an in-hospital mortality that is comparable to acute ST-segment–elevation myocardial infarction.[9–11,13] Beyond the acute event, patients with takotsubo syndrome have a rate of all-cause death of 5.6% per patient-year and a rate of major adverse cardiac and cerebrovascular events of 9.9% per patient-year.[9]

As many as 1 in 8 patients will experience a repeat acute takotsubo syndrome episode within 5 years of the index event,[24,25] often precipitated by a further (and often different) stressful event, although no known clinical or psychological factors can predict the likelihood of recurrence. Moreover, many patients report substantial morbidity after takotsubo syndrome. Symptoms of dyspnea, lethargy, palpitations, and fleeting chest pains can persist for ≥2 years after the index event despite the normalization of the left ventricular ejection fraction. Thus, there is a substantial burden of long-term morbidity and mortality associated with takotsubo syndrome.