Table 3.

Additional clinical entities useful in improving phenotypic characterization of HFpEF.

Variable	Abnormality	Functional correlate
Endothelial dysfunction	Increased circulating levels of IL-6 and TNF-α. Increased endothelial production of ROS.	Increased myocyte stiffness.
Reduced microvascular density	Microvascular rarefaction.	Increased myocardial fibrosis.
Peripheral vascular dysfunction	Increased central arterial stiffness and increased magnitude of arterial wave reflections.	Increased afterload. Increased LVH.
Impaired skeletal muscle vasodilatory reserve during exercise	Results in a blunted exercise-induced reduction in systemic vascular resistance and presumed abnormal skeletal muscle oxygen delivery.	Exercise intolerance.
Pulmonary hypertension	Due to pulmonary vascular remodeling secondary to sustained pulmonary venous pressure elevation, primary abnormalities in pulmonary arterial function, and abnormal right ventricle RV–PA coupling.	Exercise intolerance and dyspnea on exertion.
Lung disease	Airflow limitation	Exercise intolerance.
Obstructive sleep apnea	Impairs LV diastole	Begets LVH and may hasten HFpEF progression.
Chronic kidney disease	Adverse outcomes CKD is associated with worse outcomes in HFpEF rather in HFrEF	RV/LV remodeling and LV longitudinal systolic dysfunction. Poor diuretic response.
Atrial fibrillation	Increased LA stiffness and greater LA pulsatility	Associated with aging and results in more hospitalizations and poor prognosis independent of stroke risk
Frailty	Increased with unhealthy aging.	More comorbidities and associated with greater ED visits and hospitalizations.

Legend: IL=interleukin; TNF-α=tumor necrosis factor-alpha; ROS=reactive oxygen species; LVH=left ventricular hypertrophy; RV–PA=right ventricle-pulmonary artery; CKD=chronic kidney disease; and ED=emergency department.