The primary objective of this prospective, observational study is to compare muscle sympathetic nerve activity at rest and during stress between female patients with Takotsubo syndrome and healthy, matched volunteers.

• Do Takotsubo patients have an increased sympathetic nerve activity compared to controls?
• Do Takotsubo patients have an exaggerated sympathetic nerve activity response to stress?
• Does the sympathetic nerve activity response to stress in Takotsubo change after receiving the beta blocking agent metoprolol?

Participants will be examined with muscle sympathetic nerve activity recording in the peroneal nerve at rest and during cold pressor test. After intravenous injection with beta blocking agent (metoprolol) or placebo (saline) in a 1:1 randomized fashion, muscle sympathetic nerve recording at rest and during stress will be repeated.

Female Takotsubo patients included in the SAFT (sympathetic and vascular function in Takotsubo syndrome) study will be invited to undergo microneurography recording of muscle sympathetic nerve activity (MSNA) at rest and during stress one week to two month after study inclusion. Responses to stress with and without the commonly used betablocking agent metoprolol will be compares.

Microneurography will be performed in the morning after a light caffeine-free breakfast with the subject supine and awake. Any medication with a beta blocking agent will be discontinued 24 hours prior to examination. MSNA will be recorded by inserting a tungsten electrode into the sympathetic nerve fibres of the peroneal nerve, with simultaneous blood pressure and heart rate monitoring.

MSNA recording will then continue during stress induced by placing one of the subjects hand in ice-cold water for 90 seconds (cold pressor test).

After intravenous injection with beta blocking agent (metoprolol) or placebo (saline) in a 1:1 randomized fashion, MSNA recording at rest and during stress will be repeated.

Age- and gender-matched healthy volunteers will be recruited as controls and examined similarly with microneurography at rest and during stress.

MSNA recordings will be amplified, computerized and saved for further analyses. MSNA will be quantified as burst incidence (burst per 100 heartbeats), burst frequence (bursts per minute) and relative median burst amplitude (%). MSNA activity will be compared between Takotsubo patients and controls and before and after betablockade in Takotsubo patients.

Inclusion Criteria:

For patients:

• Diagnosis of Takotsubo cardiomyopathy

For Controls:

• Matching age with Takotsubo patients
• Signed informed consent

Exclusion Criteria:

• Coronary anathomy precluding intracoronary investigations
• Severe obstructive pulmonary disease
• Kidney failure with estimated glomerular filtration rate < 30 ml/min/m2
• Active malignancy
• Pericarditis

Needs approval according to GDPR but PI positive to requests

Intervention single blinded to participant. Intervention blinded to person analyzing the MSNA.