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Coronary Flow Reserve to Assess Cardiovascular Inflammation (CIRT-CFR)

冠状动脉血流储备评估心血管炎症 (CIRT-CFR)

基本信息

批准号：
9232196
负责人：
Marcelo F DI CARLI
金额：
$ 63.24万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9232196
关键词：
Affect Anatomy Anti-Inflammatory Agents Anti-inflammatory Atherosclerosis Blood Vessels Blood flow Cardiac Cardiovascular system Cicatrix Clinical Clinical Markers Clinical Trials Coronary Coronary Arteriosclerosis Coronary Circulation Diabetes Mellitus Diffuse Dipyridamole Dose Echocardiography Endothelium Enrollment Event Functional Imaging Funding Heart Heart failure Image Imaging Techniques Impairment Inflammation Injury Investigation Ischemia Left Left Ventricular Function Link Measures Mechanics Mediator of activation protein Metabolic syndrome Methotrexate Microvascular Dysfunction Morphology Myocardial Myocardial Ischemia Myocardial tissue Oral Outcome Parents Patient risk Patient-Centered Care Patients Perfusion Physiological Placebos Positioning Attribute Positron-Emission Tomography Principal Investigator Program Development Quality of life Relaxation Reproducibility Rest Risk Factors Safety Stress Symptoms Systemic Therapy Testing Tissues Translational Research Vascular Diseases Vasodilation Ventricular cardiovascular risk factor circulating biomarkers clinical care clinical translation diabetes risk diabetic diabetic patient disorder risk drug development experience functional improvement hemodynamics high risk imaging biomarker improved non-invasive imaging novel therapeutics outcome forecast patient population precision medicine prognostic programs public health relevance response

项目摘要

DESCRIPTION (provided by applicant): Coronary flow reserve (CFR, calculated as the ratio of hyperemic to rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. It provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease, diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities and affects the entire coronary vasculature. The recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in high-risk patients. a In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular (LV) deformation and, ultimately, symptoms and prognosis. Accordingly, 2 specific aims are proposed: (1) To test the hypothesis that LDM at a target dose of 15 to 20 mg orally weekly for 12 months will, compared to placebo, result in improved CFR and myocardial tissue perfusion, as assessed by quantitative PET imaging, in stable coronary artery disease patients with diabetes or metabolic syndrome. (2) To test the hypothesis that LDM at a target dose of 15 to 20 mg orally weekly for 12 months will, compared to placebo, result in improved LV myocardial mechanics, as assessed by transthoracic echocardiography, and that this functional improvement will be correlated with the change in CFR after 12 months of treatment. Additional exploratory analyses will assess the relationship of changes in CFR and LV function with quality of life scores, circulating biomarkers of inflammation and cardiac injury, and clinica outcomes. The use of physiologic imaging techniques integrated into clinical care to investigate mechanisms linking inflammation to cardiovascular complications will facilitate needed clinical translation.