Wake Forest Atrium HeartShare Clinical Center

项目摘要 射血分数保留性心力衰竭（HFpEF）是美国最常见的HF形式， 与高发病率和死亡率相关。然而，其病理生理学尚未完全了解， 大多数试验都是中立的，因此几乎没有基于证据的治疗方法。作为回应，NIH召集了2 由Kitzman博士（PI）共同领导的研讨会。最高优先级的研究建议是协调努力 建立一个HFpEF患者和对照的大型队列，并进行全面、深入的表型分析。这 成为HeartShare的基础，其最终目标是发现新的HFpEF机制，亚型， 和治疗靶点。我们的维克森林-Atrium HFpEF团队具备作为临床中心的高素质 并为HeartShare提供强大的超额捐款。Kitzman博士是国际公认的 HFpEF的思想领袖，在开发HFpEF新概念方面有着持续的记录 发病机制，机制和结果，并设计和进行创新的研究来测试它们。他 团队在HeartShare计划的所有关键方面都有丰富的经验，特别是在招聘方面， 保留HFpEF患者和对照的不同人群，并对其进行表型分型，通常显著超过 种族和性别多样性。我们的机构每年约有15，000次HFpEF临床访视。总之，我们的 该团队已经领导或帮助领导了69项研究的招募和表型分析，其中大部分是NIH赞助的， 参与者，证明我们有能力实现HeartShare招募和表型分析目标。数据从这些 研究将被贡献给HeartShare的队列阶段。我们将为HeartShare做出巨大贡献 通过实现4个具体目标：目标1）与HeartShare Steering合作，提供“思想领导力” 委员会;目标2）从我们的HeartShare贡献数据，图像和储存的样本队列阶段 对HFpEF和对照的大量研究，并从HFpEF患者和对照中鉴定和表型。 使用强大的生物信息学工具的电子健康记录;目标3）招募、同意、登记和随访至少 250例HFpEF患者加对照组（类型和数量由共识确定）;目的4） 使用协作确定的协议进行最先进的深度表型检查。我们的表型分析方案是 具有高度创新性，先进的回波多普勒和心脏磁共振成像，CPET，物理 活动监测，远程和人工智能心电图，骨骼肌，脂肪， 血液、微生物组、线粒体能量学和大脑结构/功能。我们多样化的，交叉的- 学科团队拥有全方位的互补专业知识，并可获得两个强大的资源 大型的、紧密联系的卫生系统，以确保实现所有HeartShare的目标。我们将帮助加快 并利用我们的洞察力、创造力和持续的合作记录来优化项目的成功， 创新和传播。

Project Summary Heart Failure with Preserved Ejection Fraction (HFpEF) is the most common form of HF in the US and is associated with high morbidity and mortality. However, its pathophysiology is incompletely understood, and most trials have been neutral such that few evidence-based treatments exist. In response, NIH convened 2 workshops co-led by Dr. Kitzman (PI). The highest priority research recommendation was a coordinated effort to create a large cohort of HFpEF patients and controls and perform comprehensive, deep phenotyping. This became the basis for HeartShare, whose ultimate goals are to discover novel HFpEF mechanisms, subtypes, and therapeutic targets. Our Wake Forest - Atrium HFpEF team is highly qualified to serve as a Clinical Center and make robust, over-arching contributions to HeartShare. Dr. Kitzman is internationally recognized as a thought-leader in HFpEF with a sustained track record of developing novel concepts regarding HFpEF pathogenesis, mechanisms, and outcomes and designing and conducting innovative studies to test them. His team has extensive experience in all key aspects of the HeartShare program, particularly in recruiting, retaining, and phenotyping diverse populations of HFpEF patients and controls, often significantly exceeding goals for racial and gender diversity. Our institutions have ~15,000 HFpEF clinical visits annually. In all, our team has led or helped lead recruitment and phenotyping for 69 studies, mostly NIH-sponsored, with 15,354 participants, demonstrating our ability to fulfill HeartShare recruitment and phenotyping goals. Data from these studies will be contributed to the Cohort phase of HeartShare. We will make robust contributions to HeartShare by achieving 4 Specific Aims: Aim 1) Provide ‘thought leadership’ in collaboration with the HeartShare Steering Committee; Aim 2) Contribute data, images, and stored specimens cohort phase of HeartShare from our numerous studies of HFpEF and controls, and identify and phenotype HFpEF patients and controls from the electronic health record using robust bioinformatics tools; Aim 3) Recruit, consent, enroll and follow at least 250 HFpEF patients plus controls (type and number to be determined by consensus); Aim 4) Conduct state-of- the-art deep phenotyping exams using a collaboratively determined protocol. Our phenotyping proposal is highly innovative, with advanced echo-Doppler and cardiac magnetic resonance imaging, CPET, physical activity monitoring, remote and artificial intelligence electrocardiography, sampling of skeletal muscle, adipose, blood, and microbiome, and mitochondrial energetics, and brain structure/function. Our diverse, cross- disciplinary team has the full range of complementary expertise and access to the robust resources of two large, closely affiliated health systems to ensure fulfillment of all HeartShare’s goals. We will help accelerate and optimize the program’s success with our insight, creativity, and sustained track record of collaboration, innovation, and dissemination.