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)

• 批准号: 9082786
• 负责人: Marcelo F DI CARLI
• 金额: $ 66.94万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9082786
• 关键词: Affect; Anatomy; Anti-Inflammatory Agents; Anti-inflammatory; Atherosclerosis; Blood Vessels; Blood flow; Cardiovascular system; Cicatrix; Clinical; 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; 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; Myocarditis; Outcome; Parents; Patient-Centered Care; Patients; Perfusion; Physiological; Placebos; Positioning Attribute; Positron-Emission Tomography; Principal Investigator; Quality of life; Relaxation; Rest; Risk Factors; Safety; Stress; Symptoms; Systemic Therapy; Testing; Tissues; Translational Research; Translations; Vascular Diseases; Vasodilation; Ventricular; cardiovascular risk factor; circulating biomarkers; clinical care; 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

 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（由申请人提供）：冠状动脉血流储备（CFR，计算为充血心肌血流与静息心肌血流的比值）正在成为临床心血管风险的有力定量预后成像标志物。它为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流动力学影响提供了一种可靠且可重复的临床测量方法。炎症是这一系列异常的关键介质，并影响整个冠状动脉血管系统。最近启动的心血管炎症减少试验（CIRT）为抗炎治疗对CFR变化的影响的机制研究提供了一个独特的机会，CFR变化反映了冠状动脉血管功能障碍，可能先于临床结局，特别是在高危患者中。a在此过程中，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）变形以及最终的症状和预后产生有益影响。因此，提出了2个具体目的：（1）检验以下假设：与安慰剂相比，LDM以15 - 20 mg的目标剂量每周口服12个月，将导致患有糖尿病或代谢综合征的稳定型冠状动脉疾病患者的CFR和心肌组织灌注改善（通过定量PET成像评估）。(2)检验以下假设：与安慰剂相比，LDM目标剂量15 - 20 mg每周一次口服，持续12个月，通过经胸超声心动图评估，可改善LV心肌力学，并且这种功能改善与治疗12个月后CFR的变化相关。其他探索性分析将评估CFR和LV功能变化与生活质量评分、炎症和心脏损伤的循环生物标志物以及临床结局的关系。将生理成像技术整合到临床护理中，以研究将炎症与心血管并发症联系起来的机制，将有助于所需的临床翻译。