Sympathetic and Vascular Function in Takotsubo Syndrome (SAFT)

Vacular Structure, Function and Sympathetic Activity in Takotsubo Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Takotsubo Cardiomyopathy
• Intervention / Treatment: Drug: Metoprolol Injection; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Takotsubo Control; Patients with Takotsubo receiving betablockade	Drug: 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.
Placebo Comparator: Takotsubo Intervention; Patients with Takotsubo receiving placebo	Drug: Saline; 5 ml given IV
No Intervention: Control; 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

Collaborators and Investigators

• Sponsor: Danderyd Hospital
• Investigators: Principal Investigator: Jonas 9, MD, PhD, Danderyd University Hospital and karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2016
• Primary Completion (Actual): March 23, 2022
• Study Completion (Actual): January 23, 2023

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Cardiomyopathies; Takotsubo Cardiomyopathy; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: SAFT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Needs approval according to GDPR but PI positive to requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No