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

芝加哥加速心力衰竭下一代组学、深度表型分析和数据科学中心 (CHICAGO-HF)

• 批准号: 10327554
• 负责人: Sadiya Sana Khan
• 金额: $ 28.24万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10327554
• 关键词: Abdomen; Address; Adult; Affect; Age; Artificial Intelligence; Biology; Biopsy; Cardiac; Chicago; Clinical; Clinical Research; Collaborations; Communities; Complex; Data; Data Analytics; Data Science; Development; Disease; EFRAC; Echocardiography; Electronic Health Record; Elements; Environment; Epidemiology; Ethnic Origin; Exercise; Failure; Federally Qualified Health Center; Four-dimensional; Functional disorder; Funding; Genomics; Geography; Goals; Health Expenditures; Heart failure; Heterogeneity; Illinois; Imaging Techniques; Informatics; Infrastructure; Knowledge; Lead; Magnetic Resonance Imaging; Mission; Morbidity - disease rate; Multimodal Imaging; Myocardial; Myocardial perfusion; Myocardium; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; Nature; Network-based; Observational Study; Outcome; Patient-Focused Outcomes; Patients; Phase; Phenotype; Population Heterogeneity; Positioning Attribute; Precision Medicine Initiative; Prevalence; Prospective cohort; Protocols documentation; Public Health; Public Health Informatics; Race; Randomized Controlled Trials; Resources; Retrospective cohort; Sampling; Science; Site; Skeletal Muscle; Socioeconomic Status; Sodium; Syndrome; Testing; TimeLine; Tissues; Trans-Omics for Precision Medicine; Translating; United States National Institutes of Health; Woman; Work; base; body system; clinical center; cohort; comorbidity; data warehouse; effective therapy; ethnic minority population; experience; improved; improved outcome; innovation; insight; mortality; multidisciplinary; new therapeutic target; next generation; patient population; phenomics; phenotypic data; precision medicine; preservation; prevent; programs; prospective; racial and ethnic; recruit; response; sex; success; support network; targeted treatment; therapeutic target; tool

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.

抽象的 该申请提出了芝加哥中心加速下一代组学、深度表型分析和 心力衰竭数据科学 (CHICAGO-HF) 是对 RFA“HeartShare：下一代 定义心力衰竭亚型和治疗目标的表型组学——心力衰竭临床中心。” 射血分数保留（HFpEF）与显着的发病率和死亡率相关，并且在 对于 HFpEF 患者，目前尚无有效的疾病缓解疗法，这主要是由于 目前“一刀切”治疗的 HFpEF 患者存在显着异质性 一项对患者进行深度表型分析的大规模、多中心观察性研究正在失败。 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治疗的关键下一步。 我们提出了 HFpEF 精准医学方法的三个核心要素。 对于全面解决 HFpEF 患者的表型问题至关重要。首先，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分析 活检对于阐明 HFpEF 的内在心肌生物学是必要的。 其次，详细的表型分析。 为了更好地理解心脏外合并症的系统性质，需要了解心脏外合并症之间复杂的相互作用。 第三，HFpEF 患者的代表性样本，具有跨性别、种族/民族、地域的多样性。 和社会经济地位需要纳入表型分析工作，以防止有据可查的范围扩大 由西北大学领导的拟议临床中心 CHICAGO-HF 具有独特的资质。 参与 HeartShare 网络的各个方面并大幅提高网络的目标。 应用中，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 (2) 多中心招募大量HFpEF患者 观察性研究和试验；(3) 作为 NHLBI 资助的研究中心参与。 资源丰富的多学科调查团队拥有流行病学、信息学、深度表型分析等方面的专业知识， 我们将利用我们强大的电子健康记录的经验。 有效收集、协调和共享大量回顾性和前瞻性数据的基础设施 不同 HFpEF 患者以及年龄和性别匹配的对照组（EF 降低和中等范围的 HF 我们将在研究时间表内与社区前瞻性地招募至少 250 名患者。 芝加哥各地的合作伙伴（例如联邦合格的健康中心）。此外，我们在以下方面拥有独特的专业知识。 创新的 MRI 技术和数据分析可以增强网络，并能够测试重要的 和创新的假设来定义独特的表型，阐明代表潜在的不同内型 病理生物学，并确定 HFpEF 的新型靶向治疗方法，CHICAGO-HF 非常适合作为一种治疗方法。 临床中心并为网络的长期使命做出贡献，以公平地改善 HFpEF 结果。