Shah RV, Schoenike MW, de la Hoz MAA, et al. - This study sought to define and evaluate the metabolic cost of initiating exercise in individuals with and without heart failure with preserved ejection fraction (HFpEF) and its functional consequences. Researchers conducted a prospective cohort study including individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS) between April 2016 and November 2020. Among 3,231 individuals, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. The data demonstrate that internal work, a new body mass index–related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is correlated with steep, early increases in cardiac filling pressures. These outcomes indicate the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.