Assessment of Perfusion Reserve and Effects of Exercise in Microvascular Angina

描述(由申请人提供)：项目摘要：本建议的目的是促进Jamieson Bourque，M.D.，M.H.S.的临床研究技能和科学发展，以促进他向独立临床研究员的过渡。Bourque博士的培训目标I是接受足够的临床研究培训，以成功地获得由研究人员发起的R01资金。弗吉尼亚大学是进行创新研究的理想场所，该研究涉及微血管功能障碍的非侵入性评估以及运动疗法在这一疾病过程中的应用，这是因为CMR和运动疗法方面的教职员工拥有强大的研究和临床专业知识，以及机构对Bourque博士的坚定承诺。他的主要导师，医学博士克里斯托弗·克莱默，是一位在应用心脏磁共振成像评估微血管功能方面受到国际尊敬的思想领袖。他有着长期被证明是导师的记录。重要的是，Bourque博士的职业发展计划包括血管生物学、高级运动生理学、图像采集和处理、生物统计学和研究伦理学方面的高级课程，这些课程将增强他实现其长期目标的能力，即发展微血管功能障碍的非侵入性评估的专业化，并将运动疗法和以患者为中心的结果临床研究应用于这一病态疾病过程。布尔克博士的研究问题对公共卫生至关重要。心绞痛是一种高度发病率的疾病，但阻塞性冠状动脉疾病(CAD)在50%的病例中可见。这些患者可能有微血管功能障碍，这可以通过心脏磁共振成像(CMR)进行无创性评估。对这种病态种群的最佳治疗方法还没有得到充分的研究。在这一高度流行的患者群体中，多种药物和治疗性运动可能会改善微血管功能、有氧能力和结果，包括心绞痛症状、生活质量和心脏事件。Bourque博士建议的具体目标是：1)确定心绞痛和非梗阻性CAD患者心肌灌注储备减少和以患者为中心的结果的预测因素；2)比较心绞痛和非梗阻性CAD患者在强化药物治疗和强化药物治疗加运动之间心肌灌注储备、有氧能力和以患者为中心的结果的变化。为了实现这些目标，布尔克博士将对冠脉造影术中有心绞痛症状且无梗阻疾病的患者进行前瞻性研究，这些患者将接受临床评估，然后进行CMR灌注成像。那些灌注储备减少的患者将被随机分为药物治疗和药物治疗+锻炼两组，并将评估灌注储备、有氧能力和以患者为中心的结果的变化。来自该研究项目的宝贵培训、强有力的指导和教学计划将极大地帮助Bourque博士实现他成为一名独立临床研究员的目标。

DESCRIPTION (provided by applicant): Project Summary: The purpose of this proposal is to foster the clinical research skills and scientific development of Jamieson Bourque, M.D., M.H.S., to facilitate his transition to an independent clinical investigator. Dr. Bourque's training goal i to receive sufficient clinical research training to successfully pursue investigator-initiated R01 funding. The University of Virginia is an ideal venue to perform innovative research involving the noninvasive assessment of microvascular dysfunction and the application of exercise therapy to this disease process due to the strong research and clinical expertise of faculty in both CMR and exercise therapy and the strong institutional commitment to Dr. Bourque. His primary mentor, Christopher Kramer, M.D., is an internationally- respected thought leader in the application of cardiac magnetic resonance imaging to assess microvascular function. He has a long proven mentorship track record. Importantly, Dr. Bourque's career development plan includes advanced classes in vascular biology, advanced exercise physiology, image acquisition and processing, biostatistics, and research ethics that will strengthen his ability to pursue his long-term goal of developing a specialization in the noninvasive assessment of microvascular dysfunction and the application of exercise therapy and patient-centered outcomes clinical research to this morbid disease process. Dr. Bourque's research question is of paramount public health importance. Angina is a highly morbid condition but obstructive coronary artery disease (CAD) is seen in <50% of cases. These patients may have microvascular dysfunction, which can be assessed noninvasively by cardiac magnetic resonance imaging (CMR). The optimal treatment of this morbid population has not been sufficiently studied. Multiple medications and therapeutic exercise may improve microvascular function, aerobic capacity, and outcomes including anginal symptoms, quality of life, and cardiac events in this highly prevalent patient population. The specific aims of Dr. Bourque's proposal are: 1) to determine the predictors of reduced myocardial perfusion reserve and patient- centered outcomes in patients with angina and no obstructive CAD; and 2) to compare changes in myocardial perfusion reserve, aerobic capacity, and patient centered outcomes between intensive medical therapy and intensive medical therapy plus exercise in patients with angina and no obstructive CAD. To address these aims, Dr. Bourque will perform a prospective study of patients with anginal symptoms and no obstructive disease on coronary angiography, who will undergo a clinical assessment followed by CMR perfusion imaging. Those with reduced perfusion reserve will be randomized to medical therapy versus medical therapy + exercise and changes in perfusion reserve, aerobic capacity, and patient-centered outcomes will be assessed. The invaluable training from this research project, robust mentorship, and didactic program will greatly assist Dr. Bourque in fulfilling his goal of becoming an independent clinical investigator.