Mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF)

Exercise intolerance is a well-established symptom of heart failure with preserved ejection fraction (HFpEF) and is associated with impaired quality of life and worse clinical outcomes. Historically attributed to diastolic dysfunction of the left ventricle, exercise intolerance in HFpEF is now known to result not only from diastolic dysfunction, but also from impairments in left ventricular systolic function, left atrial pathology, right ventricular dysfunction, and valvular disease. Disorders of heart rate and rhythm such as chronotropic incompetence and atrial fibrillation have also been implicated in exercise intolerance in this population. Pathologic changes to extra-cardiac organ systems including the respiratory, vascular, hormonal, and skeletal muscle systems are also thought to play a role in exercise impairment. Finally, comorbidities such as obesity, inflammation, and anemia are common and likely contributory in many cases. The role of each of these factors is discussed in this review of exercise intolerance in patients with HFpEF.