Prognostic Utility of Absolute Coronary Microvascular Function by PET/CT

描述（由申请人提供）：本提案的目的是促进候选人的科学发展和研究技能，以便她可以成为一名独立的临床研究者。布里格姆妇女医院的无创心血管成像中心提供了理想的环境，候选人将在哈佛大学公共卫生学院攻读公共卫生硕士学位的同时，研究冠状动脉微血管功能的预后价值。通过与临床导师和经验丰富的科学顾问的合作，候选人将为独立学术生涯的发展奠定基础。心肌缺血、硬膜外冠状动脉疾病（CAD）与生存之间的联系已得到充分证实。最近，冠状动脉微血管功能障碍在一些临床综合征如高血压心脏病、心肌病和X综合征中被报道，在没有梗阻性心膜外CAD的受试者中。初步证据表明微血管功能障碍与较差的预后相关。直到最近，冠状动脉微血管功能的评估一直受到方法限制的阻碍，因此，其性质和机制仍然是推测性的。正电子发射断层扫描（PET）是评估冠状动脉微血管功能的一种非常有效的工具。本研究的中心目标是确定使用rubldl82 PET检测冠状动脉微血管功能的预后价值。候选人已经证明了相对铷-82 PET的预后价值，反映了心外膜CAD的严重程度。在具体目标1-3中，候选人将研究冠状动脉微血管功能在预测猝死等主要心脏不良事件、左心室重构/心力衰竭风险以及进展为阻塞性心包外膜CAD风险方面的价值。我们期望在这里提出的研究将提供冠状动脉微血管功能障碍和心脏事件之间的重要机制联系。这些研究的结果将作为设计针对改善冠状动脉微血管功能和临床结果的特异性治疗的未来研究的基础。相关性（见说明）：大冠状动脉在表面上为心脏供血，通过染色注射（血管造影术）可以看到，但进入心肌的血管非常小，在血管造影术上看不到。这些微血管在血液流向心脏的过程中起着重要作用，尤其是在活动期间。本研究的目的是发现微循环异常是否可以预测未来心脏病不良后果的风险。（摘要结束）

DESCRIPTION (provided by applicant): The purpose of this proposal is to promote scientific development and investigative skills of the candidate in order that she may become an independent clinical investigator. The noninvasive cardiovascular imaging center at the Brigham and Women's Hospital provides the Ideal setting in which the candidate will study the prognostic value of coronary microvascular function, while enrolled in a Masters degree in Public Health at the Harvard School of Public Health. Through the collaboration with the clinical mentor, and highly experienced scientific advisors, the candidate will obtain a foundation for the development of an independent academic career. The link between myocardial ischemia, epicardlal coronary artery disease (CAD) and survival Is well established. More recently, coronary microvascular dysfunction has been reported in several clinical syndromes such as hypertensive heart disease, cardiomyopathy and syndrome X, In subjects without obstructive epicardlal CAD. Preliminary evidence suggests that microvascular dysfunction is associated with worse outcomes. Until recently, evaluation of coronary microvascular function has been impeded by methodological limitations, and hence, its nature and mechanisms remain speculative. Positron emission tomography (PET) represents an extremely powerful tool to assess coronary microvascular function. The central goal of this study is to determine the prognostic value of coronary microvascular function using Rubldlum-82 PET. The candidate has demonstrated the prognostic value of relative Rubldium-82 PET, reflecting severity of epicardlal CAD. In specific Aims 1-3, the candidate will study the value of coronary microvascular function to predict major adverse cardiac events of sudden death, risk of left ventricular remodeling/heart failure, and risks from progression to obstructive epicardlal CAD. We anticipate that the proposed studies outlined here will provide important mechanistic links between coronary microvascular dysfunction and cardiac events. The results of these studies will serve as a foundation to design future studies of specific therapies directed at improving coronary microvascular function and clinical outcomes. RELEVANCE (See instructions): The big coronary arteries supplying blood to the heart course on the surface and are visible by dye injection (angiography), but the vessels entering the heart muscle are very small and not seen on angiography. These microvessels play a major role in blood flow to the heart, especially during activity. The purpose of this study is to find out If microcirculatory abnormalities can predict risk of future adverse outcomes from heart disease. (End of Abstract)