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

 描述(由申请人提供)：冠状动脉血流储备(CFR，以充血心肌血流量与静息心肌血流量之比计算)正在成为临床心血管风险的一个强有力的定量预测成像标志。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血流灌注的综合血流动力学效应提供了一种可靠和可重复性的临床测量方法。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轻试验(CIRT)提供了一个独特的机会，可以从机制上研究抗炎治疗对CFR变化的影响，作为冠状动脉血管功能障碍的反映，这可能会先于临床结果，特别是在高危患者中。通过这样做，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、左室(LV)变形以及最终的症状和预后产生有益的影响。因此，我们提出了两个具体目标：(1)验证这样一种假设，即与安慰剂相比，每周口服15-20毫克LDM的目标剂量将改善患有糖尿病或代谢综合征的稳定性冠状动脉疾病患者的CFR和心肌组织灌注量。(2)验证这样一种假设：与安慰剂相比，每周口服目标剂量15-20毫克的LDM将导致经胸超声心动图评估的左室心肌力学改善，并且这种功能改善将与治疗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、炎症和心脏损伤的循环生物标志物以及临床结果的关系。将生理成像技术整合到临床护理中，以研究炎症与心血管并发症之间的联系机制，将有助于必要的临床翻译。

 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.