A Single Center Diagnostic, Cross-sectional Study of Coronary Microvascular Dysfunction

Study Overview
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Brief Summary
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Among patients with stable ischemic heart disease who are referred for coronary angiography, a substantial proportion have non-obstructive coronary artery disease (CAD). Ischemia based on symptoms or stress testing may be due to coronary microvascular dysfunction in up to 40% of these patients. However, the mechanisms and optimal treatment of coronary microvascular dysfunction are unknown. Aberrant platelet activity and inflammation have been hypothesized as mechanisms of microvascular dysfunction. Investigators plan to evaluate association between platelet activity, inflammation, and coronary microvascular dysfunction in stable women referred for coronary angiography, and to identify non-invasive correlates of coronary microvascular dysfunction in these patients.

Detailed Description
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The objectives of this study are to Investigate platelet activity and inflammation in patients with and without coronary microvascular disease who are referred for coronary angiography for the evaluation of stable ischemic heart disease and are found to have non-obstructuve epicardial CAD To identify correlates of coronary microvascular dysfunction in non coronary microvascular beds that can be characterized in vivo.

Official Title
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A Single Center Diagnostic, Cross-sectional Study of Coronary Microvascular Dysfunction

Conditions
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Coronary Microvascular Disease, Ischemic Heart Disease, Myocardial Ischemia

Intervention / Treatment
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* Drug: Bivalirudin
* Drug: Adenosine
* Drug: Heparin
* Device: Pressure-Temperature Sensor Guidewire
* Device: Guiding Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women age ≥18 years referred for coronary angiography Stable ischemic heart disease, defined by ischemic symptoms and/or myocardial ischemia by stress testing Administration of aspirin therapy prior to cardiac catheterization Exclusion Criteria: Pre-Cath Exclusion criteria: Active bleeding and/or bleeding diathesis Anemia (hemoglobin <9 mg/dl) Known thrombocytosis (platelet count >500,000) Know thrombocytopenia (platelet count <100,000) NSAIDs (e.g., ibuprofen, naproxen) within 3 days Platelet antagonists other than aspirin and thienopyridines, within 7 days Prior percutaneous coronary intervention or coronary artery bypass grafting Acute myocardial infarction within 3 months Severe valvular heart disease Cardiogenic shock or mechanical circulatory support New York Heart Association (NYHA) Functional Class III or IV heart failure Ejection Fraction <40% Hypertrophic obstructive cardiomyopathy or severe left ventricular hypertrophy Pregnancy Contraindication to intravenous infusion of adenosine during coronary angiography, due to known hypersensitivity to adenosine, known or suspected bronchoconstrictive or bronchospastic lung disease (severe asthma), second- or third-degree AV block (except in patients with a functioning artificial pacemaker), or sinus node disease, such as sick sinus syndrome or symptomatic bradycardia, Angiographic Exclusion criteria: Obstructive CAD (≥50% luminal obstruction in ≥1 major epicardial coronary arteries by invasive coronary angiography) Unfavorable coronary artery anatomy for guidewire positioning (as determined by the angiographer or PI)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 125 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Obstructive CAD<br>After diagnostic coronary angiography, invasive measures of coronary microvascular physiology will be obtained. Blood will be collected for platelet activity, inflammation and isolation of coronary endothelial cells. | Drug: Bivalirudin<br>* After diagnostic catheterization, intravenous bivalirudin (Angiomax) will be administered as part of the research procedure, and a 6F-guiding catheter without side holes will be used to engage the ostium of the coronary artery.<br>* Other names: Angiomax;Drug: Adenosine<br>* An intravenous infusion of adenosine (140 μg/kg/min) will be administered via a large peripheral or central vein to induce steady-state maximal hyperemia.<br>* Other names: Adenoscan;Drug: Heparin<br>* Heparin may be used as an alternative to bivalirudin at the discretion of the interventional cardiologist.<br>Device: Pressure-Temperature Sensor Guidewire<br>* Abbott's Pressure Wire X will be used to measure fractional flow reserve (FFR), cardiac magnetic resonance (CMR) and Index of Microcirculatory Resistance (IMR) in the Left Anterior Descending (LAD) Artery and major epicardial coronary vessels associated with myocardial ischemia.<br>* Other names: Pressure Wire X;Device: Guiding Catheter<br>* Medtronic's 6F Launcher Guide Catheter will be used to engage the left main coronary artery.<br>* Other names: 6F Launcher Guide Catheter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Activity measured by the Index of Microcirculatory Resistance (IMR) |  | 12 Months | 
| Measure of Inflammation measured by the Index of Microcirculatory Resistance (IMR) |  | 12 Months |