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Completed

NCT Number: NCT02897739

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

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.

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Key information

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Cardiac Research Office

Aberdeen, Aberdeenshire, AB25 2ZD, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Magnetic Resonance Imaging

Procedure

Cardiac MRI and short MRI following USPIO infusion

Acute Inflammatory Activation study

Biological

Blood sampling for exploration of type and level of inflammatory response

PET CT

Radiation

PET study for metabolic pathway study

psychological assessment

Behavioral

Assessment by a psychologist

Primary outcomes

  1. Cardiac Inflammation as measured by Cardiac Magnetic Resonance Imaging

    Time frame: Three years

    As measured by cardiac MRI

Secondary outcomes

  1. 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

  2. Evidence of alterations of the metabolism of myocardium by Cardiac Positron Emission Tomography

    Time frame: Three years

    As measured by PET CT

  3. Systemic Inflammation as measured by inflammatory markers

    Time frame: Three years

    As measured by inflammatory markers

Sponsors and collaborators

Lead sponsor

University of Aberdeen

Other

Collaborators

  • NHS Grampian

Registry information

Official study title

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

Acronym: TERRIFIC

Important dates

Study start
2015
Primary completion
2019
Study completion
2019
First posted
Sep 13, 2016
Registry last updated
May 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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