Approximately half of patients with heart failure have a preserved left ventricular ejection fraction. The prevalence of heart failure with a preserved ejection fraction (HFpEF) is steadily increasing and is expected to exceed that of heart failure with reduced ejection fraction (HFrEF).

As the population ages and these risk factors become more common, the prevalence of HFpEF is rising. Multiple comorbidities cause a systemic pro-inflammatory state that alters cell-signaling pathways, leading to cardiac structural and functional alterations. Similar pathologic changes may occur in other organs such as skeletal muscle and the kidney. This underlying inflammatory state ultimately leads to abnormalities in multiple domains that limit cardiac output and/or cause symptoms.

Considering this extensive list, patients with HFpEF may differ in regards to which mechanisms are contributing most to their symptoms. This may explain why clinical trials have not yet identified treatments that broadly reduce death and hospitalization in HFpEF. Many experts now advocate “phenotyping” of patients with HFpEF to design an appropriate treatment plan.