PROJECT SUMMARY/ ABSTRACT: ALONSO PROJECT Heart failure (HF) is a global health crisis that impacts 26 million adults worldwide. Ejection fraction (EF) remains the predominant measure used to categorize patients with HF. Approximately half of those with HF have an EF that is reduced to <50% (HFrEF) and half have an EF ≥50%, known as HF with preserved ejection fraction (HFpEF). Patients with HFrEF have benefited from the numerous advances in HF treatment over the last decade. These advances have failed to achieve similar results for patients with HFpEF in part because HFpEF is a heterogeneous syndrome, and we have limited understanding of the HFpEF pathophysiology or consensus on subphenotypes. Therefore, the objective of this proposal is to refine the subphenotypes of heart failure (HF) with preserved ejection fraction (HFpEF) by assessing patient-reported outcomes, cardiovascular (CV) variables, and cytokine profiles leading to personalized diagnostics and treatment strategies for these patients. To achieve this objective, we will address the following specific aims: 1. Quantify patient-reported outcomes and CV variables, 2. Evaluate and link patient-reported outcomes to cytokine profiles, and 3. Examine stress-induced patterns in cytokine profiles. We will recruit 150 patients with HFpEF from Nebraska Medicine to complete instruments measuring patient-reported symptoms and quality of life, undergo cardiopulmonary exercise testing, provide plasma samples for cytokine profiling pre- and post- cardiopulmonary exercise testing, and consent to access to their medical records for demographic, clinical, and echocardiographic data extraction. By gaining a comprehensive understanding of HFpEF, we will be poised to substantially contribute to HF research. This training and research project will provide preliminary data and skills to allow the project leader to submit a competitive R01 to validate project findings and further evaluate the longitudinal patterns in HFpEF subphenotypes. The long-term goals of this project are to provide the project leader with a strong foundation in interdisciplinary team science, to develop knowledge in connecting biology with clinical research, and identify objective measures reflective of patient-reported outcomes and inflammatory biomarkers of HFpEF at rest and during provocative testing.