HeartShare DeCODE-HF: Data translation center to Combine Omics, Deep phenotyping, and Electronic health records for Heart Failure subtypes and treatment targets

Heart failure (HF) with preserved ejection fraction (HFpEF) is the greatest unmet need in cardiovascular medicine today because of its growing prevalence and lack of effective treatments. In 2017, the NHLBI convened a working group on research priorities in HFpEF, chaired by Sanjiv Shah, MD (contact PI), to address the lack of progress in identifying effective treatments in HFpEF. A key conclusion of that meeting was the need to develop a network of collaborative centers to accelerate translational and clinical research of pathobiological mechanisms underlying specific HFpEF subtypes (a concept that was pioneered by our group at Northwestern). Our working group envisioned that this resource would facilitate comprehensive, deep phenotyping of a multicenter HFpEF patient cohort with standardized protocols and a robust biorepository. This opportunity has now been crystalized by the NHLBI as the HeartShare Program. Although HeartShare presents an immense and novel opportunity to advance the field of HFpEF, doing so will require a comprehensive, integrative, and experienced Data Translation Center (DTC). Here we show the expertise, depth, and breadth of the proposed Northwestern University DTC team, which has unique strengths in each of the key DTC areas of investigation and administration: HFpEF (Shah, contact PI), multicenter study management (Denise Scholtens, PhD, MPI; Abel Kho, MD, MPI; Shah), data integration/harmonization (Scholtens; Kho; Yuan Luo, PhD, MPI; Firas Wehbe, MD, PhD, core PI), clinical informatics, bioinformatics, and electronic health records (EHRs) (Kho, Luo, Wehbe), machine learning and data science (Luo, Shah, Kho, Wehbe), statistics (Scholtens; Lauren Balmert, PhD, core PI), and omics (Scholtens, Luo, Shah). The Overarching Aim of the Northwestern HeartShare DTC is to provide overall management and oversight for HeartShare, including coordination and communication across all subsections and cores of the program, and with the 4 HeartShare Clinical Centers (CCs). The DTC will need to ensure timely completion of the retrospective (first 2 years) and prospective (all 5 years) components of HeartShare. In the enclosed application, we demonstrate the ability and prior experience of our multi-PI team and core leaders in the conduct of and leadership of large-scale, multi-center studies, particularly in the realms of HFpEF, EHR-based investigation, deep phenotyping, and biorepositories. We also highlight our experience as liaisons/translators among clinical researchers, clinicians, and bioinformaticians; expertise in phenotype ontology and harmonization; and collaboration with the University of Vermont biorepository (Russ Tracy, co-I) who is PI of the central biorepository for all of the NHLBI HF Network trials and multiple NHLBI cohort studies. For both the retrospective and prospective HeartShare components, the Northwestern DTC will leverage its considerable experience in: (1) cohorts and trials that have data on adjudicated HFpEF patients, and (2) its leadership and track record as the top enroller in HFpEF trials/studies to ensure optimal recruitment by the HeartShare CCs. The overall contact PI of the proposal (Shah) is a leading HFpEF clinical trialist and has served as overall PI, steering committee member, and/or national leader for > 25 international, multi-center HFpEF trials and observational studies. He is also PI of ancillary studies of multiple NHLBI cohorts, including the Cardiovascular Health Study (CHS), HyperGEN, and the Multi-Ethnic Study of Atherosclerosis (MESA; in which he oversaw deep cardia