Sympathetic and Vascular Function in Takotsubo Syndrome

Study Overview
=================
Brief 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.

Official Title
-----------------
Vacular Structure, Function and Sympathetic Activity in Takotsubo Syndrome

Conditions
-----------------
Takotsubo Cardiomyopathy

Intervention / Treatment
-----------------
* Drug: Metoprolol Injection
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Control group for primary outcome
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Takotsubo Control<br>Patients with Takotsubo receiving betablockade | Drug: Metoprolol Injection<br>* 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.<br>|
| Placebo Comparator: Takotsubo Intervention<br>Patients with Takotsubo receiving placebo | Drug: Saline<br>* 5 ml given IV<br>|
| No Intervention: Control<br>Control subjects | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting MSNA | Muscle sympathetic nerve activity during rest | During 5 minutes rest | 
| MSNA increase during CPT | Muscle sympathetic nerve activity increase during cold pressor test | During the last 60 seconds of the CPT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSNA increase during CPT after intervention | Muscle sympathetic nerve activity increase during cold pressor test after betablockade | During the last 60 seconds of the CPT | 
| Hemodynamic changes during CPT | Change in blood pressure | During the last 60 seconds of the CPT |