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

摘要 该申请提出了加速下一代组学、深度表型分析和 心力衰竭数据科学（芝加哥-HF）是对RFA“HeartShare：下一代 表型组学定义心力衰竭亚型和治疗靶点-临床中心。心力衰竭 射血分数保留（HFpEF）与显著的发病率和死亡率相关， 普遍性。HFpEF患者尚无有效的疾病改善疗法，主要是由于 目前“一刀切”治疗的HFpEF患者存在显著异质性 范式失败了。一项大规模、多中心、观察性研究，在患有 HFpEF是推进我们对HFpEF病理生理学的理解并改变我们的临床和病理学的关键下一步。 HFpEF的研究范式走向精准医疗方法。我们提出三个核心要素， 对于解决HFpEF谱中的综合表型患者至关重要。一是直接 使用磁共振成像（MRI）和肌内膜活检等工具对心肌进行表型分析 活组织检查是阐明HFpEF内在心肌生物学的必要条件。第二，详细的表型分析 需要心外共病的复杂相互作用，以更好地了解 HFpEF。第三，HFpEF患者的代表性样本在性别、种族/民族、地理、 和社会经济地位需要包括在表型的努力，以防止扩大有据可查的 HFpEF的差异。拟议的临床中心，芝加哥-HF，由西北大学领导，是唯一合格的 参与HeartShare网络的各个方面，并大大提高网络的目标。在我们 应用，我们展示了关键的经验，其中包括：（1）开发世界上第一个 HFpEF的专门临床项目;（2）招募大量HFpEF患者进入多中心 观察性研究和试验;（3）作为NHLBI资助的队列的现场中心参与。我们的井- 资源丰富的多学科调查小组拥有流行病学，信息学，深层表型分析， 和人工智能我们将利用我们强大的电子健康记录的经验 基础设施，以有效地收集，协调和共享大量的回顾性和前瞻性数据 不同的HFpEF患者和年龄和性别匹配的对照组（HF伴EF降低和中等范围， 健康对照）。我们将在研究时间轴内前瞻性招募至少250例患者， 芝加哥的合作伙伴（例如联邦合格的健康中心）。此外，我们在以下方面的独特专业知识 创新的MRI技术和数据分析可以加强网络，并将使测试的重要 和创新的假设，以定义独特的表型，阐明不同的内在型，代表潜在的 病理生物学，并确定HFpEF的新的靶向治疗。芝加哥-HF非常适合作为 临床中心，并有助于网络的长期使命，公平地改善HFpEF的结果。

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.