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调查技能，以便她成为独立的临床研究者。布里格姆妇女医院的非侵入性心血管成像中心提供了理想的环境，候选人将在哈佛公共卫生学院攻读公共卫生硕士学位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，候选人将获得独立学术生涯发展的基础。心肌缺血、心外膜冠状动脉疾病（CAD）和生存率之间的联系已得到充分证实。最近，在一些临床综合征如高血压性心脏病、心肌病和X综合征中，在无阻塞性心外膜CAD的受试者中报告了冠状动脉微血管功能障碍。初步证据表明，微血管功能障碍与不良结局相关。直到最近，冠状动脉微血管功能的评价一直受到方法学限制的阻碍，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）是一个非常强大的工具，以评估冠状动脉微血管功能。本研究的中心目标是使用Rubldlum-82 PET确定冠状动脉微血管功能的预后价值。候选人已证明相对铷-82 PET的预后价值，反映心外膜CAD的严重程度。在特定目标1-3中，候选人将研究冠状动脉微血管功能的价值，以预测猝死的主要不良心脏事件、左心室重塑/心力衰竭风险以及进展为阻塞性心外膜CAD的风险。我们预计，这里概述的拟议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未来针对改善冠状动脉微血管功能和临床结局的特定治疗研究的基础。相关性（参见说明）：向心脏供血的大冠状动脉在表面上行进，并且通过染料注射（血管造影术）可见，但是进入心肌的血管非常小，并且在血管造影术上看不到。这些微血管在流向心脏的血液中起着重要作用，特别是在活动期间。这项研究的目的是找出微循环异常是否可以预测心脏病未来不良后果的风险。 (End摘要）

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)