Tako-tsubo Cardiomyopathy Clinical Trial
Official title:
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.
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.
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