Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management

It is estimated that half of all patients with heart failure (HF) have HF with preserved ejection fraction (HFpEF). Yet this form of HF remains a diagnostic and therapeutic challenge. Differentiating HFpEF from other causes of dyspnoea may require advanced diagnostic methods, such as exercise echocardiography, invasive haemodynamics and investigations for 'HFpEF mimickers'. While the classification of HF has relied heavily on cut-points in left ventricular ejection fraction (LVEF), recent evidence points towards a gradual shift in underlying mechanisms, phenotypes and response to therapies as LVEF increases. For example, among patients with HF, the proportion of hospitalisations and deaths due to cardiac causes decreases as LVEF increases. Medication classes that are efficacious in HF with reduced ejection fraction (HFrEF) have been less so at higher LVEF ranges, decreasing the risk of HF hospitalisation but not cardiovascular or all-cause death in HFpEF. These observations reflect the burden of non-cardiac comorbidities as LVEF increases and highlight the complex pathophysiological mechanisms, both cardiac and non-cardiac, underpinning HFpEF. Treatment with sodium-glucose cotransporter 2 inhibitors reduces the risk of composite cardiovascular events, driven by a reduction in HF hospitalisations; renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalisations among patients with HFpEF. Comprehensive management of HFpEF includes exercise as well as treatment of risk factors and comorbidities. Classification based on phenotypes may facilitate a more targeted approach to treatment than LVEF categorisation, which sets arbitrary cut-points when LVEF is a continuum. This narrative review summarises the pathophysiology, diagnosis, classification and management of patients with HFpEF.

Automated summary

It is estimated that half of heart failure patients have heart failure with preserved ejection fraction (HFpEF), which presents a diagnostic and therapeutic challenge. Recent evidence suggests that the mechanisms, phenotypes, and response to therapies of heart failure gradually change as left ventricular ejection fraction (LVEF) increases. HF hospitalizations and deaths due to cardiac causes decrease as LVEF increases. Medications effective for heart failure with reduced ejection fraction (HFrEF) have less impact on HFpEF patients with higher LVEF. HFpEF is also influenced by non-cardiac comorbidities. Sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular events by reducing HF hospitalizations, while renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors have smaller effects on HF hospitalizations in HFpEF patients.