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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

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

Brief Summary: 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.

Detailed Summary:

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 c
Sponsor: University of Aberdeen

Current Primary Outcome: Cardiac Inflammation as measured by Cardiac Magnetic Resonance Imaging [ Time Frame: Three years ]

As measured by cardiac MRI


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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
  • Evidence of alterations of the metabolism of myocardium by Cardiac Positron Emission Tomography [ Time Frame: Three years ]
    As measured by PET CT
  • Systemic Inflammation as measured by inflammatory markers [ Time Frame: Three years ]
    As measured by inflammatory markers


Original Secondary Outcome: Same as current

Information By: University of Aberdeen

Dates:
Date Received: March 24, 2016
Date Started: August 2015
Date Completion: July 2017
Last Updated: September 7, 2016
Last Verified: September 2016