HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets - Clinical Centers

项目总结 心力衰竭(HF)是一个严重的公共卫生问题，影响着500多万美国成年人，并迫使 巨大的临床、社会和经济负担。超过一半的心力衰竭患者心力衰竭患者射血功能保持不变。 分数(HFpEF)。此外，HFpEF是高度异质性的，不同的病理机制起作用。 在几个不同的疾病亚组中，与症状和不良结局有关。尽管有几个大的规模 已经进行了随机试验，还没有确定可以改善的药物疗法 HFpEF患者的症状或临床结局。我们的团队和其他人已经确认了那本小说 对HFpEF患者进行深入表型鉴定的方法可以确定HFpEF患者的亚群 有可能从靶向治疗中受益。 当前提案的首要目标是建立一大批表型较深的患者。 使用HF，重点是HFpEF患者。我们建议建立一个1000名患者的队列，涵盖所有4个 宾夕法尼亚大学临床中心：700名HFpEF患者，200名HFrEF患者(包括100名中级患者 LV EF，40%-50%)和100名非心力衰竭高血压患者(这是一个合适的控制人群，因为大多数 HFpEF患者有高血压病史)。我们将纳入全面的临床数据， 社会经济数据(特别是当它们与健康的社会决定因素有关时)、以患者为中心的数据(例如 生活质量和功能状态)、心脏和心外表型的结构和机械性(包括 实验室内表征和创新的非常规数据收集方法)和多组学方法。 表型数据将得到当代生物信息学方法的补充，以增强我们的 对人类HFpEF的理解。 我们的表型鉴定方案将提供与其他 以上群体，应用群体内聚类方法，以及建立全面的 描述了大量经过严格判定的HFpEF患者的前瞻性队列，以进行前瞻性随访 艰难的结果。在这些患者中，我们将评估详细的心脏和心外表型、电子健康 记录数据、患者报告的结果、对运动的有氧适应以及血浆和尿蛋白组学 代谢组学和微型RNA。我们还将评估关键的流动表型，包括创新 家庭血压监测、体力活动、睡眠时间和质量的方法，以及重要的社交活动 健康的决定因素。心力衰竭的结果将被前瞻性地判定，包括与心力衰竭相关的 住院、死亡、心肌梗塞和中风。我们的分析方法将包括基于假设的 研究以及无偏见的发现方法，将利用当代生物信息学工具，但将 接受指导委员会成员、其他临床研究小组成员的专家解释 中心，以及整个科学界。

PROJECT SUMMARY Heart failure (HF) is a critical public health issue that affects over 5 million US adults and imposes an enormous clinical, social, and economic burden. Over half of individuals with HF have HF with preserved ejection fraction (HFpEF). Furthermore, HFpEF is highly heterogeneous, and different pathologic mechanisms contribute to symptoms and poor outcomes in several different subgroups of the disease. Although several largescale randomized trials have been performed, no pharmacological therapies have been identified that improve symptoms or clinical outcomes in patients with HFpEF. Our group and others have identified that novel approaches to deeply phenotyping patients with HFpEF can identify subgroups of patients with HFpEF that are likely to benefit from targeted therapy. The overarching goal of the current proposal is to establish a large cohort of deeply phenotyped patients with HF with a focus on patients with HFpEF. We propose establishing a cohort of 1000 patients across all 4 Penn clinical centers: 700 patients with HFpEF, 200 patients with HFrEF (including 100 patients with mid-range LV EF, 40-50%) and 100 non-HF patients with hypertension (a suitable control population, given that most patients with HFpEF have a history of hypertension). We will incorporate comprehensive clinical data, socioeconomic data (particularly as they relate to social determinants of health), patient-centered data (such as quality of life and functional status), structural and mechanistic cardiac and extracardiac phenotypes (including in-lab characterization and innovative ambulatory approaches to data collection) and multi-omics approaches. The phenotypic data will be complemented by contemporary bioinformatic approaches to enhance our understanding of human HFpEF. Our phenotyping protocol will provide the opportunity for cross-sectional comparisons against other groups above, application of within-group clustering approaches, as well as establishing a comprehensively characterized large prospective cohort of patients with strictly adjudicated HFpEF for prospective follow-up of hard outcomes. In these patients, we will assess detailed cardiac and extracardiac phenotypes, electronic health record data, patient-reported outcomes, aerobic adaptations to exercise, and plasma and urinary proteomics and metabolomics and micro RNAs. We will also assess key ambulatory phenotypes including innovative approaches to home blood pressure monitoring, physical activity, sleep duration and quality, and important social determinants of health. Heart failure outcomes will be prospectively adjudicated, including heart-failure related hospitalization, death, myocardial infarction and stroke. Our analytic approach will include hypothesis-based research as well as unbiased discovery approaches that will leverage contemporary bioinformatics tools but will be subject to expert interpretation by members of the Steering Committee, investigator teams at the other Clinical Centers, and scientific community at large.