Ischemia-mediated diastolic dysfunction in women with coronary microvascular dysfunction
Description: Ischemic Heart Disease in the absence of obstructive coronary artery disease (CAD) is prevalent in women, causes a decline in functional status, and contributes to increased risk for major adverse cardiovascular events, including myocardial infarction, stroke, and new onset heart failure. Coronary microvascular dysfunction (CMD) plays a major role in the development of ischemia in the absence of obstructive CAD, and women with CMD often develop diastolic dysfunction. The exact mechanism by which CMD contributes to diastolic dysfunction, however, remains to be elucidated. We hypothesize that dysregulation of coronary microvessels triggers functional myocardial ischemia and impairs energy-dependent relaxation of the heart. To address this hypothesis, we will recruit symptomatic women with objective evidence of CMD (cases) and healthy reference controls. Left ventricular diastolic function will be assessed using sensitive magnetic resonance imaging (MRI) techniques, and myocardial ischemia will be measured using phosphorus-31 MR spectroscopy. First, we will establish the relationship between functional myocardial ischemia and diastolic dysfunction, by challenging the balance between oxygen supply and demand with cardiovascular stress. Then, we will determine whether alleviating functional myocardial ischemia, with a proven pharmacologic therapy (i.e., phosphodiesterase type 5 inhibition), will improve diastolic function in women with CMD. Results from this application will provide new mechanistic insight into the relationship between CMD and diastolic dysfunction and facilitate paradigm-changing diagnosis and treatment approaches to reduce the burden of ischemic heart disease in women.
Funder: American Heart Association
Amount: $53,690
Funding type: training
Funder scheme: Predoctoral Fellowship
Start date: 2018-07-01
End date: 2020-06-30
Investigators: T Jake Samuel, T Jake Samuel
Institution: The University of Texas at Arlington
Funded outputs count: 8
Funder award ID: 18PRE33960358
OpenAlex ID: G4191431663