Pathogenesis of Acute Stress Induced (Tako-tsubo) Cardiomyopathy: Energy Shut-Down or Intense Inflammation? (TERRIFIC)

May 7, 2019 updated by: University of Aberdeen

Pathogenesis of Acute Stress Induced (Tako-tsubo) Cardiomyopathy: Energy Shut-Down or Intense Inflammation? The TERRIFIC Study

Tako Tsubo Cardiomyopathy (TTC), also known as "Broken Heart Syndrome", is a disorder of the heart that occurs most commonly in women (although it occasionally occurs in men) and is usually related to a stressful event. Symptoms are often similar to a heart attack, and include chest pain and shortness of breath. Although Tako Tsubo Cardiomyopathy is not a new medical condition, it has not been widely recognised until the last decade. Currently the investigators don't have an exact understanding of how or why the heart is affected in this way, and so the investigators are conducting a study to help understand what causes Tako Tsubo Cardiomyopathy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators aim to study the reciprocal modulation of fatty acids and glucose metabolism in the Tako Tsubo Cardiomyopathy physiology, in both humans and an animal model, and to investigate which metabolic pathway is preferentially adopted by acute Tako Tsubo Cardiomyopathy myocytes during this severe functional shut down with largely preserved variability. The human model will be used to determine the preferential stimulated uptake of glucose/fatty acids under optimal metabolic conditions for each (hyperinsulineamic euglycemic clamp for 18F-Fludeoxyglucose (18F-FDG) and fasting for 14Fluorine-18Fluoro-6-Thia-Heptadecanoic Acid (18F-FTHA cardiac Positron Emission Tomography)). In the rat model the investigators will examine both the metabolic tracer uptake (using micro Positron Emission Tomography-Computed Tomography) as well as the downstream modulation of the two metabolic pathways (transcriptional regulators, mitochondrial respiration, expression of the uncoupling proteins, levels of Adenosine Triphosphate generation and reactive oxygen species production).

The investigators aim to test the hypothesis that inflammation plays a pivotal role in the pathophysiology of this condition by further exploring: 1) In the rat model define time course, extent and subtypes of cellular infiltrate, 2) In the rat model of Tako Tsubo Cardiomyopathy, demonstrate the presence of inflammatory macrophages using in-vivo Ultrasmall Superparamagnetic Iron Oxide-cardiac magnetic resonance imaging and whether this relates to numbers and types of macrophages present as determined by immunohistochemical analysis, 3) In clinical patients, define the time course of specific peripheral blood monocyte subsets and the serum levels of inflammatory cytokines versus matched controls and 4) In clinical patients, establish the compartmentalisation of tissue macrophages in the left ventricle its time course resolution using Ultrasmall Superparamagnetic Iron Oxide-enhanced cardiac magnetic resonance.

The investigators will assess the psycho-emotional factors involved in Tako Tsubo Cardiomyopathy given that in the majority of cases intense emotional trauma is immediately preceding onset.

Study Type

Observational

Enrollment (Actual)

77

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Aberdeenshire
      • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZD
        • Cardiac Research Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients who have been diagnosed with Tako-tsubo Cardiomyopathy Healthy volunteers

Description

Inclusion Criteria:

  • All patients diagnosed with TTC in the past 12 days, able to give consent and who have not lost capacity of consent between the time of diagnosis (usually made at coronary catheterisation, for which they are consented clinically) and time of being approached for inclusion in the study.
  • Age and gender matched healthy controls willing to participate and able to give consent.

Exclusion Criteria:

  • Unwillingness to participate
  • Patients with contraindications to MR scanning
  • Pregnant or breast-feeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
TTC Patients
Patients diagnosed with Tako-tsubo cardiomyopathy.
Procedure: Magnetic resonance imaging
Cardiac MRI and short MRI following USPIO infusion
Biological: Acute Inflammatory Activation study
Blood sampling for exploration of type and level of inflammatory response
Radiation: PET CT
PET study for metabolic pathway study
Behavioral: Psychological assessment
Assessment by a psychologist
Health Volunteers
Participants who have normal hearts.
Procedure: Magnetic resonance imaging
Cardiac MRI and short MRI following USPIO infusion
Biological: Acute Inflammatory Activation study
Blood sampling for exploration of type and level of inflammatory response
Radiation: PET CT
PET study for metabolic pathway study
Behavioral: Psychological assessment
Assessment by a psychologist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac Inflammation as measured by Cardiac Magnetic Resonance Imaging
Time Frame: Three years
As measured by cardiac MRI
Three years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evidence of psycho-emotional factors following intense physical or emotional stress as measured by Hospital Anxiety and Depression Scale
Time Frame: Three years
As measured by psychiatric interview
Three years
Evidence of alterations of the metabolism of myocardium by Cardiac Positron Emission Tomography
Time Frame: Three years
As measured by PET CT
Three years
Systemic Inflammation as measured by inflammatory markers
Time Frame: Three years
As measured by inflammatory markers
Three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aberdeen

Collaborators

NHS Grampian

Investigators

  • Principal Investigator: Dana Dawson, MD, MRCP, University of Aberdeen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2015

Primary Completion (Actual)

March 1, 2019

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

March 24, 2016

First Submitted That Met QC Criteria

September 7, 2016

First Posted (Estimate)

September 13, 2016

Study Record Updates

Last Update Posted (Actual)

May 8, 2019

Last Update Submitted That Met QC Criteria

May 7, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14/NS/1068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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