Pathogenesis of Acute Stress Induced (Tako-tsubo) Cardiomyopathy: Energy Shut-Down or Intense Inflammation?
Condition: Tako-tsubo Cardiomyopathy
MeSH terms: Cardiomyopathies; Takotsubo Cardiomyopathy; Inflammation
Study type: Observational [Patient Registry]

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 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.
    

Intervention name(s): Magnetic resonance imaging; Acute Inflammatory Activation study; PET CT; Psychological assessment
Intervention type(s): Procedure; Biological; Radiation; Behavioral
Intervention description(s): Cardiac MRI and short MRI following USPIO infusion; Blood sampling for exploration of type and level of inflammatory response; PET study for metabolic pathway study; Assessment by a psychologist
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who have been diagnosed with Tako-tsubo Cardiomyopathy Healthy volunteers
      
Biospecimen description: 
      EDTA blood samples, EDTA Plasma and Serum to be retained.