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.

描述（由适用提供）：冠状动脉流动储备（CFR，计算为HyperMIC与静止心肌血流的比率）正在成为临床心血管风险的强大定量预后成像标记。它提供了对心外膜冠状动脉疾病，弥漫性动脉粥样硬化和微血管功能障碍对心肌组织灌注的综合血液动力学作用的稳健临床测量。炎症是该异常星座的关键介体，并影响整个冠状动脉脉管系统。最近发起的心血管炎症减少试验（CIRT）为机械投资提供了抗炎疗法对CFR变化的影响的独特机会，这可能是冠状动脉血管功能障碍的反映，这可能是在临床结果之前，尤其是在高危患者中。在这样做时，冠状动脉血管反应性，内皮功能和组织灌注的改善可能对心肌力学，左心室（LV）变形以及最终症状和提示具有有益的影响。彼此之间，提出了2个具体目的：（1）测试以下假设：与安慰剂相比，在稳定的冠状动脉疾病患者中，通过定量宠物进行定量宠物评估，将15至20 mg口服的目标剂量每周口服12个月，持续12个月，可以改善CFR和心肌组织灌注。（2）与安慰剂相比，在目标剂量为15至20 mg的目标剂量为15至20 mg的靶剂量与安慰剂相比，LDM将导致LV心肌力学的改善，这将改善LV心肌力学，并且通过经胸脑超声心动图评估，并且该功能改善将与治疗12个月后CFR的变化相关。其他探索性分析将评估CFR和LV功能的变化与生活质量评分，感染和心脏损伤的生物标志物以及临床结局的关系。整合到临床护理中的生理成像技术的使用将感染与心血管并发症联系起来的机制将有助于促进所需的临床翻译。