CHIcago Center for Accelerating nextGen Omics, deep phenotyping, and data science in Heart Failure (CHICAGO-HF)

摘要 这项申请建议芝加哥中心加速下一代Omics，深度表型，和 心力衰竭的数据科学(芝加哥-HF)是对RFA的回应：心跳共享：下一代 定义心力衰竭亚型和治疗目标的表型组学--临床中心。心力衰竭伴 保留射血分数(HFpEF)与显著的发病率和死亡率有关，并在 流行率。对于HFpEF患者，目前还没有有效的疾病修正疗法，这主要是由于 目前采用“一刀切”治疗的HFpEF患者存在显著的异质性 范式正在失灵。一项大规模、多中心的观察性研究，旨在对慢性粒细胞白血病患者进行深入的表型鉴定 HFpEF是促进我们对HFpEF病理生理学的理解并将我们的临床和 HFpEF中的研究范式走向精准医学方法。我们提出了三个核心要素， 对于全面解决HFpEF频谱中的表型患者至关重要。第一，直接 使用磁共振成像(MRI)和心内膜心肌等工具对心肌进行表型鉴定 活检对于阐明HFpEF的内在心肌生物学是必要的。第二，详细的表型分析 心脏外并发症的复杂相互作用需要更好地理解心脏外并发症的系统性。 HFpEF。第三，具有代表性的HFpEF患者样本，不同性别、种族/民族、地域、 社会经济地位需要包括在表型工作中，以防止有充分记录的 HFpEF的差异。由西北大学领导的拟议的临床中心芝加哥-HF是唯一有资格的 参与心脏分享网络的所有方面，并大大加强该网络的目标。在我们的 应用，我们展示了关键的先前经验，其中包括：(1)开发世界上第一个 HFpEF的专门临床方案；(2)将大量HFpEF患者招募到多中心 观察性研究和试验；以及(3)作为NHLBI资助队列的现场中心参与。我们的井- 资源丰富的多学科调查团队在流行病学、信息学、深度表型鉴定方面拥有专业知识， 和人工智能。我们将利用我们强大的电子健康记录的经验 高效收集、协调和共享大量回顾和预期数据的基础设施 不同的HFpEF患者和年龄和性别匹配的对照组(EF降低和中等范围的HF和 健康对照)。我们将在与社区的研究时间表内前瞻性地招募至少250名患者 芝加哥各地的合作伙伴(例如联邦合格的医疗中心)。此外，我们在这方面的独特专长 创新的MRI技术和数据分析可以加强网络，并将支持测试重要的 和创新假设，以定义独特的表型，阐明代表潜在的不同内型 病理生物学，并确定新的靶向治疗HFpEF。芝加哥-高频非常适合作为 并为该网络公平改善HFpEF结果的长期使命做出贡献。

ABSTRACT This application proposing the CHIcago Center for Accelerating nextGen Omics, deep phenotyping, and data science in Heart Failure (CHICAGO-HF) is in response to the RFA “HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets-Clinical Centers.” Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality and is increasing in prevalence. No effective disease-modifying therapies exist for patients with HFpEF, largely due to the substantial heterogeneity among patients with HFpEF for whom the current “one-size-fits-all” treatment paradigm is failing. A large-scale, multicenter observational study to conduct deep phenotyping in patients with HFpEF is a critical next step to advance our understanding of HFpEF pathophysiology and shift our clinical and research paradigm in HFpEF towards a precision medicine approach. We propose three central elements that are critical to address to comprehensively phenotype patients across the spectrum of HFpEF. First, direct phenotyping of the myocardium, using tools such as magnetic resonance imaging (MRI) and endomyocardial biopsy, is necessary to elucidate the intrinsic myocardial biology of HFpEF. Second, detailed phenotyping of the complex interplay of extra-cardiac comorbidities is needed to better understand the systemic nature of HFpEF. Third, a representative sample of HFpEF patients with diversity across sex, race/ethnicity, geography, and socioeconomic status needs to be included in phenotyping efforts to prevent widening of well-documented disparities in HFpEF. The proposed Clinical Center, CHICAGO-HF, led by Northwestern, is uniquely qualified to participate in all aspects of the HeartShare Network and to substantially enhance the Network’s goals. In our application, we demonstrate key prior experiences, which include: (1) development of the world’s first dedicated clinical program in HFpEF; (2) recruitment of large numbers of patients with HFpEF into multicenter observational studies and trials; and (3) participation as a Field Center for NHLBI-funded cohorts. Our well- resourced multi-disciplinary investigative team has expertise in epidemiology, informatics, deep phenotyping, and artificial intelligence. We will leverage our experiences with our robust electronic health record infrastructure to efficiently collect, harmonize and share retrospective and prospective data on a large number of diverse patients with HFpEF and age- and sex-matched controls (HF with reduced and mid-range EF and healthy controls). We will prospectively recruit at least 250 patients within the study timeline with community partners across Chicago (e.g. Federally Qualified Health Centers). In addition, our unique expertise in innovative MRI techniques and data analytics can strengthen the Network and will enable testing of significant and innovative hypotheses to define unique phenotypes, elucidate distinct endotypes that represent underlying pathobiology, and identify novel targeted therapeutics for HFpEF. CHICAGO-HF is ideally suited to serve as a Clinical Center and contribute to the Network’s long-term mission to equitably improve HFpEF outcomes.