Project Summary Heart Failure with Preserved Ejection Fraction (HFpEF) is the most common form of heart failure, is associated with high morbidity and mortality, with increasing prevalence and worsening prognosis. Quality-of-life in HFpEF is as poor or worse than heart failure with reduced ejection fraction, in large part because of severe exercise intolerance; the primary manifestation of this bourgeoning condition. Per funding announcement PAR-20-078 which supports the use of existing human datasets for well-focused secondary analyses to investigate new methods that have the potential for significant impact on NHLBI relevant biomedical or biobehavioral research, we will leverage an existing database of cardiac magnetic resonance images in a cohort of well-phenotyped patients with HFpEF and age- and sex-matched healthy controls to comprehensively identify and characterize pathophysiologic mechanisms driving HFpEF. We will use a novel Single Image Multi-endPoint anaLysis (SIMPL) approach to compare four chamber cardiac function (right atrium, right ventricle, left atrium, left ventricle), aortic distensibility, and pericardial fat burden between HFpEF and healthy controls, and to determine their independent and combined association with exercise tolerance and quality of life.