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

In-hospital Management

With no robust or clinical trial evidence available for the treatment of this condition, extrapolation of therapies known to be effective after myocardial infarction, such as β-blocker and angiotensin-converting enzyme inhibitor therapies, have been adopted by some clinicians. In the acute setting, the focus of management relates to supportive care and treatment of complications and is predominantly based on clinical experience and expert consensus (Table 2).[25,63]

Heart Failure

In the unusual situation where patients present with pulmonary edema, they should be treated with intravenous diuretic and nitrate therapies. Patients who sustain left ventricular outflow tract obstruction may benefit from sequential small doses of short-acting β-blocker therapy,[64] and small boluses of intravenous fluid, under careful monitoring in a high-dependency care environment, as well.

The management of shock is challenging in both theory and practice. Most inotropic agents can potentially aggravate systolic dysfunction because excess catecholamines may be involved in the underlying pathogenesis and pathophysiology of the condition. As such, expert consensus recommends mechanical approaches to provide hemodynamic support, such as intra-aortic balloon counterpulsation, temporary left ventricular assist devices, and extracorporeal membrane oxygenation.[25,63] However, identification of left ventricular outflow obstruction is important because hemodynamic status may be worsened by intra-aortic balloon counterpulsation in such cases. When mechanical support is not available, low-dose levosimendan is licensed in some countries as a catecholamine-sparing positive inotrope (Table 2).[65,66]


The management of ventricular arrhythmias depends on the clinical picture and mirrors the general principles of acute arrhythmia management. It is important to avoid QT segment–prolonging medications because these may worsen the likelihood of developing ventricular arrhythmias because of the high risk of further QTc prolongation. In clinical practice, electric pacing of torsade de pointes has proven successful to bridge the patient and allow recovery from the acute phase. Although uncommon, if high-degree atrioventricular block is present, inotropes and permanent devices should be avoided, semipermanent (active fixation lead connected to an externalized pulse generator) or temporary right ventricular pacing may be considered if there is hemodynamic instability.[25,67] Patients who present with life-threatening ventricular arrhythmias and takotsubo syndrome should be considered for an implantable cardiac defibrillator. However, there is no specific evidence base to support this approach and there are no long-term outcome data of device discharge rates in patients with takotsubo syndrome.[25]


Patients who have a confirmed left ventricular thrombus should be treated with anticoagulants for at least 3 months or until resolution. Although no guidelines currently exist for the treatment of takotsubo syndrome, the relatively high rates of systemic thromboembolism would suggest that better identification of thrombus on cardiac imaging is needed before discharge and should be considered in high-risk patients, such as those with severe left ventricular dysfunction (ejection fraction <30%) and apical ballooning.