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

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.