Mass General Brigham HeartShare Clinical Center

项目摘要 心力衰竭伴保留射血分数(HFpEF)约占所有心衰的一半，是一种高度 病态的状况。有效治疗射血分数降低的心力衰竭的药物疗法有更多 对HFpEF的影响不大，如果有任何有益的影响，可能是由于HFpEF的不同定义和有限 了解HFpEF中靶向的最佳途径。我们的调查团队在以下方面拥有丰富的经验 HFpEF人体受试者研究。互补的呼吸困难和心力衰竭评估计划吸引了 将HFpEF患者和没有HFpEF的呼吸困难控制患者转诊到马萨诸塞州综合医院 医院和布里格姆妇女医院(MASH General Brigham，MGB)。此外，我们的团队高度重视 通过强有力的临床试验计划，参与评估HFpEF的治疗干预措施。MGB HeartShare团队的PI负责HFpEF临床试验的概念化、设计、实施和 通过在超声心动图、心肺运动试验、 先进的心血管成像，所有这些都可以用来支持心脏共享。我们的团队也有专业知识 在使用基于MGB的电子健康记录数据、人口研究数据和临床试验时， 我们对HFpEF的理解。我们小组使用了综合心肺运动试验(CPET)来 同时定量有创血流动力学、血气、心功能、动脉血压计和气体 具有传统定义的HFpEF的个体在运动过程中的交换模式。我们已经开始描绘 心、肺、血管和外周肌肉骨骼储备能力受损的贡献 休息时不明显。我们的单中心HFpEF表型研究已经包括了700名HFpEF患者 接受统一的表型鉴定(超声心动图、NT-proBNP、静息和 锻炼和全面的CPET)。在目标1中，我们将组建一个协作的多学科调查小组 能够在心跳共享计划中招募、表型确定和保留≥250HFpEF患者的团队 也借鉴了核心实验室监督的经验，电子病历方面的生物信息学专业知识 与HFpEF相关的网络、人群队列和临床试验研究的研究和领导。在AIM 2 我们将通过全面的临床评估来完善HFpEF的诊断和分类，包括 心脏结构和功能的多模式成像，运动试验探测多器官 系统生理储备与脆弱性纵向远程生理监测与评估 认知力。我们还将扩展我们在创建基于组学的病理生理签名方面的经验 在HFpEF中的状态，并对派生数据采用无监督机器学习方法。红心分享会 加深对HFpEF的了解，我们的团队准备将对HFpEF的更好理解转化为 亚型进入HFpEF的新的治疗干预试验。

Project Summary Heart failure with preserved ejection fraction (HFpEF) comprises approximately half of all HF and is a highly morbid condition. Pharmacotherapies that are effective in treating HF with reduced ejection fraction have more modest if any beneficial impacts on HFpEF, potentially owing to heterogeneous definitions of HFpEF and limited understanding of optimal pathways to target in HFpEF. Our team of investigators has extensive experience in HFpEF human subjects research. Complementary Dyspnea and Heart Failure Evaluation Programs attract referral of HFpEF patients as well as dyspneic control patients without HFpEF to the Massachusetts General Hospital and Brigham and Women’s Hospital (“Mass General Brigham, MGB”). In addition, our team is highly engaged in assessing therapeutic interventions for HFpEF through robust clinical trials programs. The MGB HeartShare Team’s PIs are responsible for HFpEF clinical trial conceptualization, design, implementation, and endpoint adjudication via established core laboratories in echocardiography, cardiopulmonary exercise testing, advanced cardiovascular imaging, all of which could be used to support HeartShare. Our team also has expertise in working with MGB-based electronic health record data, population study data, and clinical trials that inform our understanding of HFpEF. Our group has used comprehensive cardiopulmonary exercise testing (CPET) to simultaneously quantitate invasive hemodynamics, blood gases, cardiac function, arterial tonometry and gas exchange patterns during exercise in individuals with conventionally defined HFpEF. We have begun to delineate contributions of impaired cardiac, pulmonary, vascular, and peripheral musculoskeletal reserve capacity that are not evident at rest. Our single-center HFpEF phenotyping study already consists of >700 patients with HFpEF subjected to uniform phenotyping (echocardiography, NT-proBNP, multi-site blood sampling at rest and with exercise and comprehensive CPET). In Aim 1 we will assemble a collaborative multidisciplinary investigative team capable of recruiting, phenotyping, and retaining ≥250 HFpEF patients in the HeartShare Program while also drawing from experience with core lab oversight, bioinformatic expertise in electronic medical record research, and leadership of network, population cohort, and clinical trial research relevant to HFpEF. In Aim 2 we will refine the diagnosis and subclassification of HFpEF through comprehensive clinical assessment including multi-modality imaging of cardiac structure and function, perturbational testing with exercise to probe multi-organ system physiologic reserve and longitudinal remote physiologic monitoring and assessment of frailty and cognition. We will also expand on our experience with creation of omics-based signatures of pathophysiologic states in HFpEF and deploy unsupervised machine learning approaches to the derived data. HeartShare will enhance understanding of HFpEF and our team is poised to translate improved understanding of HFpEF subtypes into new therapeutic intervention trials in HFpEF.