Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that affects half of all patients with HF. It is rising in prevalence, is associated with high morbidity and mortality, and has very few effective treatments. HFpEF is currently understood as a heterogeneous syndrome originating from the interplay of cardiac and extracardiac abnormalities. The most important pathophysiology in patients with HFpEF is diastolic dysfunction, which presents with impairments in relaxation or increases in chamber stiffness that lead to an increase in left ventricular filling pressures at rest or during exercise that causes dyspnea.