PROJECT SUMMARY/ABSTRACT Heart failure with preserved ejection fraction (HFpEF) is one of the most urgent prevention and treatment challenges in public health today given its increasing prevalence, limited therapeutic options, and substantial burden on global health care systems. Exercise-based prevention and treatment strategies for HFpEF have historically focused on the promotion of aerobic exercise. However, given the coinciding epidemics of physical inactivity and obesity in the U.S., and the compromised aerobic capacity and exercise intolerance in patients with HFpEF, long-term adherence to aerobic exercise is generally poor and thus, the prevention and treatment of HFpEF remains a major public health challenge. Thus, aligned with NHLBI research priorities for HFpEF, research is critically needed to: (1) identify optimal strategies for improving adherence to exercise in the prevention and treatment of HFpEF; and (2) examine biological pathways linking exercise to HFpEF. In the proposed project, Dr. McDonough, an exercise science and public health researcher, will examine the isolated role of resistance exercise in the prevention and treatment of HFpEF with examination of potential biological intermediates. With the exceptional mentorship team he has assembled, comprised of prolific epidemiologists, physician scientists, and methodologists, and the resources available to him through the University of Minnesota, this Postdoctoral Career Transition Award to Promote Diversity will support Dr. McDonough in filling critical training gaps and conducting the research necessary to launch his career as an independent investigator utilizing cohort studies to inform his future clinical trials in the treatment and secondary prevention of HFpEF. To prepare him for this role, a multifaceted training plan including coursework, mentorship, and research is proposed in: (1) the analysis of longitudinal data from cohort studies using a variety of multivariable regression modeling approaches; (2) the pathophysiology and epidemiology of HFpEF and how to safely implement exercise training in patients with HFpEF; (3) advanced clinical trial methods and statistical analyses; and (4) advanced epidemiologic statistical modeling of pathways and mediators. The expertise Dr. McDonough develops through this training plan will be essential for conducting the proposed research. During the mentored K99 phase, he will leverage NHLBI cohort studies to elucidate the independent role of resistance exercise in HFpEF primary and secondary prevention (Aims 1-3). In the independent R00 phase, Dr. McDonough will conduct an independent feasibility clinical trial examining the effect of resistance exercise on liver fat and subsequent functional capacity, quality of life, and intervention adherence in HFpEF patients (Aim 4). Findings from this project will provide the requisite preliminary data to support an NIH R01 grant proposal examining novel exercise therapies for improving hospita...