Heart Failure With Preserved Ejection Fraction in the Elderly Population: Basic Mechanisms and Clinical Considerations

Heart failure with preserved ejection fraction (HFpEF) refers to a clinical condition in which the signs of heart failure, such as pulmonary congestion, peripheral edema, and increased natriuretic peptide levels, are present despite normal ejection fractions and the absence of other causes (eg, pericardial disease). The ejection fraction cutoff for the definition of HFpEF has varied in the past, but recent society guidelines have settled on a consensus of 50%. HFpEF is particularly common in the elderly population. The aim of this narrative review is to summarize the available literature regarding HFpEF in elderly patients in terms of evidence for the age dependence, specific clinical features, and underlying mechanisms. In the clinical arena, we review the epidemiology, discuss distinct clinical phenotypes typically seen in elderly patients, the importance of frailty, the role of biomarkers, and the role of medical therapies (including sodium-glucose cotransport protein 2 inhibitors, renin-angiotensin-aldosterone system blockers, angiotensin receptor/neprilysin inhibitors, diuretics, and β-adrenergic receptor blockers). We then go on to discuss the basic mechanisms implicated in HFpEF, including cellular senescence, fibrosis, inflammation, mitochondrial dysfunction, enhanced production of reactive oxygen species, abnormal cellular calcium handling, changes in microRNA signalling, insulin resistance, and sex hormone changes. Finally, we review knowledge gaps and promising areas of future investigation. Improved understanding of the specific clinical manifestations of HFpEF in elderly individuals and of the fundamental mechanisms that contribute to the age-related risk of HFpEF promises to lead to novel diagnostic and treatment approaches that will improve outcomes for this common cardiac disorder in a vulnerable population.