Wake Forest Atrium HeartShare Clinical Center

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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.