ImportanceHeart failure with preserved ejection fraction (HFpEF), defined as HF with an EF of 50% or higher at diagnosis, affects approximately 3 million people in the US and up to 32 million people worldwide. Patients with HFpEF are hospitalized approximately 1.4 times per year and have an annual mortality rate of approximately 15%.ObservationsRisk factors for HFpEF include older age, hypertension, diabetes, dyslipidemia, and obesity. Approximately 65% of patients with HFpEF present with dyspnea and physical examination, chest radiographic, echocardiographic, or invasive hemodynamic evidence of HF with overt congestion (volume overload) at rest. Approximately 35% of patients with HFpEF present with “unexplained” dyspnea on exertion, meaning they do not have clear physical, radiographic, or echocardiographic signs of HF. These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. In unselected patients presenting with unexplained dyspnea, the H2FPEF score incorporating clinical (age, hypertension, obesity, atrial fibrillation status) and resting Doppler echocardiographic (estimated pulmonary artery systolic pressure or left atrial pressure) variables can assist with diagnosis (H2FPEF score range, 0-9; score >5 indicates more than 95% probability of HFpEF). Specific causes of the clinical syndrome of HF with normal EF other than HFpEF should be identified and treated, such as valvular, infiltrative, or pericardial disease. First-line pharmacologic therapy consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials. Compared with usual care, exercise training and diet-induced weight loss produced clinically meaningful increases in functional capacity and quality of life in randomized clinical trials. Diuretics (typically loop diuretics, such as furosemide or torsemide) should be prescribed to patients with overt congestion to improve symptoms. Education in HF self-care (eg, adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation.Conclusions and RelevanceApproximately 3 million people in the US have HFpEF. First-line therapy consists of sodium-glucose cotransporter type 2 inhibitors, exercise, HF self-care, loop diuretics as needed to maintain euvolemia, and weight loss for patients with obesity and HFpEF.