Mass General Brigham HeartShare Clinical Center

项目摘要 射血分数正常的心力衰竭（HFpEF）约占所有HF的一半，是一种高度危险的疾病。 病态有效治疗射血分数降低的HF的药物疗法具有更多的 对HFpEF的有益影响（如果有的话）不大，可能是由于HFpEF的定义不同， 了解HFpEF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人类受试者研究。补充呼吸困难和心力衰竭评估计划吸引 将HFpEF患者以及无HFpEF的呼吸困难控制患者转诊至马萨诸塞州总医院 布里格姆妇女医院（Mass General Brigham，MGB）此外，我们的团队高度 通过强大的临床试验项目评估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 通过已建立的超声心动图、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HeartShare。我们的团队也有专业知识 在使用基于MG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。我们的团队使用了全面的心肺运动测试（CPET）， 同时定量侵入性血流动力学、血气、心脏功能、动脉张力和气体 传统定义的HFpEF个体在运动过程中的交换模式。我们已经开始描绘 受损的心脏、肺、血管和外周肌肉骨骼储备能力的贡献， 静止时不明显。我们的单中心HFpEF表型研究已经包括了>700例HFpEF患者 接受统一的表型分型（超声心动图、NT-proBNP、静息时多部位采血和 综合CPET）。在目标1中，我们将组建一个多学科合作调查小组， 团队能够招募、分型和保留≥250名HFpEF患者参与HeartShare计划，同时 还借鉴了核心实验室监督的经验，电子病历的生物信息学专业知识， 研究，并领导网络，人群队列和HFpEF相关的临床试验研究。在目标2中 我们将通过全面的临床评估来完善HFpEF的诊断和亚分类，包括 心脏结构和功能的多模态成像，运动扰动测试以探测多器官 系统生理储备和纵向远程生理监测和虚弱评估， 认知.我们还将扩大我们的经验与创造组学为基础的签名的病理生理 HFpEF中的状态，并对导出的数据部署无监督机器学习方法。HeartShare将 提高对HFpEF的理解，我们的团队准备将对HFpEF的更好理解转化为 在HFpEF中进行新的治疗干预试验。

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.