Sympathetic and Vascular Function in Takotsubo Syndrome

NCT ID: NCT05768542

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-12
• Study Completion Date: 2023-01-23

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.

Conditions

Takotsubo Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Takotsubo Control

Patients with Takotsubo receiving betablockade

Group Type: ACTIVE_COMPARATOR

Metoprolol Injection

Intervention Type: DRUG

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.

Takotsubo Intervention

Patients with Takotsubo receiving placebo

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

5 ml given IV

Control

Control subjects

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metoprolol Injection

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.

Intervention Type: DRUG

Saline

5 ml given IV

Intervention Type: DRUG

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Danderyd Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonas 9, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Danderyd University Hospital and karolinska Institutet

Other Identifiers

SAFT

Identifier Type: -

Identifier Source: org_study_id