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

Long-term Management

As with in-hospital management, no therapeutic interventions have been shown to reduce recurrences or any other major cardiovascular events in patients with takotsubo syndrome. The focus is therefore to ensure the treatment of associated risk factors and concomitant disease.

Concomitant Disease

Patients with concomitant coronary artery disease (bystander disease) should continue to receive preventative therapies including antiplatelet, statin, and angiotensin-converting enzyme inhibitor therapies. Furthermore, those who have dual pathology (concurrent acute myocardial infarction) may require dual antiplatelet therapy, and treatment should be tailored to individual patients (Daghem et al, A tear and a broken heart. 2022). Where patients demonstrate a degree of persistent left ventricular systolic dysfunction, they should be managed and treated for left ventricular systolic dysfunction according to established guidelines.[63] However, in the vast majority of patients who have normalization of their left ventricular ejection fraction, there is no clear evidence that β-blocker therapy improves long-term survival benefit or reduces the recurrence of takotsubo syndrome.[9,65,68] Likewise, the evidence for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy is contradictory and uncertain.[9,65,69] Randomized controlled trial evidence is urgently needed. In the meantime, each clinician should continue to apply their best judgment, but conservative medical management appears to be the most appropriate approach in the absence of treatable risk factors or comorbidities.

Risk Factors

Psychiatric disorders, usually anxiety or depression, are common in patients with takotsubo syndrome, suggesting that some patients might benefit from a combined psychocardiological rehabilitation. Cognitive-behavioral therapy alongside cardiac rehabilitation can improve mental health and reduce negative thinking compared with cardiac rehabilitation alone.[70] Studies are currently underway to establish whether structured exercise training and mental well-being programs can improve cardiac energetics and attenuate cardiac limitation on exercise after takotsubo syndrome (PLEASE study [Physical Exercise and Mental Wellbeing Rehabilitation for Acute Stress-induced Takotsubo Cardiomyopathy: The PLEASE Study]; NCT04425785). Whether antidepressant or other psychiatric therapies might provide clinical benefit in such patients is controversial and has not been investigated.