The Broken Heart Study II (BHS-II)

Heterogeneity and Predictors of Stress Reactivity in Takotsubo Syndrome

The goals of this study are as follows:

1. To rigorously establish and characterize heterogeneity in the pathophysiology of Takotsubo Syndrome (TS).
2. To rigorously test the contribution of TS triggering events and mental stress responsiveness to 1-year prognosis after TS event.

Newly admitted patients with a validated diagnosis of Takotsubo Syndrome (TS; n=106) will be enrolled from 3 large medical centers in the Providence, Rhode Island area. Between 2 and 4 weeks after discharge, clinically stable patients will undergo an in-person comprehensive interview to identify the events proximal to the onset of TS symptoms, complete a battery of psychosocial questionnaires and undergo a validated laboratory stress protocol. Baseline and reactive changes in measures of autonomic nervous system activity (epinephrine and norepinephrine - primary outcome), and in the secondary outcomes of cardiac vagal control and left ventricular function (ejection fraction; regional and global longitudinal strain assessed with speckle tracking echocardiography) will be assessed. Echocardiographic evaluations will be repeated 12 months thereafter together with information on major adverse cerebrovascular events.

Inclusion Criteria:

• Age >=18
• A new diagnosis of takotsubo syndrome fulfilling Mayo Clinic criteria
• Ability to understand and speak English

Exclusion Criteria:

• Inability or unwillingness to give informed consent
• Severe cognitive impairment
• Uncontrolled hypertension
• Acute psychosis
• High suicidal risk
• Pregnancy
• Poor echocardiographic window
• Conditions that would interfere with adherence to study requirements (e.g., ongoing alcohol or substance abuse)
• If the participant is clinically unstable