Sympathetic and Vascular Function in Takotsubo Syndrome
Condition: Takotsubo Cardiomyopathy
MeSH terms: Cardiomyopathies; Takotsubo Cardiomyopathy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Metoprolol Injection; Saline
Intervention type(s): Drug; Drug
Intervention description(s): If heart rate below 60, give 5 mg IV. If heart rate above 60, give 5 mg IV and repeat until heart rate below 65 or 20 mg given in total or systolic blood pressure below 110 mmHg.; 5 ml given IV
Intervention MeSH terms: Metoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Control group for primary outcome
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science