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

Robert A Rose, Jonathan Howlett, George Heckman, Stanley Nattel, Susan E Howlett, Kimia Gharagozloo, Mozhdeh Mehdizadeh

Journal: The Canadian journal of cardiology 2024;40(8):1424-1444

PMID: 38604339

Abstract

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.

Copyright © 2024. Published by Elsevier Inc.

Address: Montreal Heart Institute Research Center and Université de Montréal, Montréal, Quebec, Canada; McGill University Departments of Pharmacology and Therapeutics, Montréal, Quebec, Canada.; Schlegel Research Institute for Aging and University of Waterloo, Waterloo, Ontario, Canada.; Department of Cardiac Sciences, Department of Physiology and Pharmacology, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.; Libin Cardiovascular Institute and Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Departments of Pharmacology and Medicine (Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada.; Montreal Heart Institute Research Center and Université de Montréal, Montréal, Quebec, Canada; McGill University Departments of Pharmacology and Therapeutics, Montréal, Quebec, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany. Electronic address: [email protected].
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