State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age

Abstract Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co‐morbidities contributing to its presentation. Establishing the dia...

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Main Authors: Roy Rasalam, Andrew Sindone, Gary Deed, Ralph G. Audehm, John J. Atherton
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.15205
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author Roy Rasalam
Andrew Sindone
Gary Deed
Ralph G. Audehm
John J. Atherton
author_facet Roy Rasalam
Andrew Sindone
Gary Deed
Ralph G. Audehm
John J. Atherton
author_sort Roy Rasalam
collection DOAJ
description Abstract Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co‐morbidities contributing to its presentation. Establishing the diagnosis of HFpEF can be challenging. Two algorithms, the ‘Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elderly age >60, elevated Filling pressures’ (H2FPEF) and the ‘Heart Failure Association Pre‐test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology’ (HFA‐PEFF), can help to determine the likelihood of HFpEF in individuals with symptoms of HF. Phenotype clusters defined largely by the total number and types of co‐morbidities may delineate groups of patients with HFpEF with different management needs. It is important to recognize alternative diagnoses or HFpEF mimics such as infiltrative cardiomyopathies, coronary artery disease, lung disease, anxiety, depression, anaemia, severe obesity, and physical deconditioning, among others. Treatment with sodium‐glucose co‐transporter 2 inhibitors (dapagliflozin and empagliflozin) is recommended for all patients with HFpEF unless contraindicated. Future research should consider alternative approaches to guide the initial diagnosis and treatment of HFpEF, including phenotype clustering models and artificial intelligence, and consider whether LVEF is the most useful distinguishing feature for categorizing HF. Ongoing clinical trials are evaluating novel pharmacological and device‐based approaches to address the pathophysiological consequences of HFpEF.
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spelling doaj-art-16f57d7eb6a6419cabaf020d7b61380c2025-08-20T03:53:16ZengWileyESC Heart Failure2055-58222025-06-011231544155710.1002/ehf2.15205State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic ageRoy Rasalam0Andrew Sindone1Gary Deed2Ralph G. Audehm3John J. Atherton4Endocrinology and Diabetes Department Alfred Health Melbourne Victoria AustraliaConcord Hospital University of Sydney Sydney New South Wales AustraliaHealthCarePlus Medical Centre Carindale Queensland AustraliaFaculty of Medicine University of Melbourne Melbourne Victoria AustraliaFaculty of Medicine, Royal Brisbane and Women's Hospital University of Queensland Herston Queensland AustraliaAbstract Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co‐morbidities contributing to its presentation. Establishing the diagnosis of HFpEF can be challenging. Two algorithms, the ‘Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elderly age >60, elevated Filling pressures’ (H2FPEF) and the ‘Heart Failure Association Pre‐test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology’ (HFA‐PEFF), can help to determine the likelihood of HFpEF in individuals with symptoms of HF. Phenotype clusters defined largely by the total number and types of co‐morbidities may delineate groups of patients with HFpEF with different management needs. It is important to recognize alternative diagnoses or HFpEF mimics such as infiltrative cardiomyopathies, coronary artery disease, lung disease, anxiety, depression, anaemia, severe obesity, and physical deconditioning, among others. Treatment with sodium‐glucose co‐transporter 2 inhibitors (dapagliflozin and empagliflozin) is recommended for all patients with HFpEF unless contraindicated. Future research should consider alternative approaches to guide the initial diagnosis and treatment of HFpEF, including phenotype clustering models and artificial intelligence, and consider whether LVEF is the most useful distinguishing feature for categorizing HF. Ongoing clinical trials are evaluating novel pharmacological and device‐based approaches to address the pathophysiological consequences of HFpEF.https://doi.org/10.1002/ehf2.15205Clinical algorithmsDiagnosisManagementHeart failure with preserved ejection fractionPhenotypesPrecision medicine
spellingShingle Roy Rasalam
Andrew Sindone
Gary Deed
Ralph G. Audehm
John J. Atherton
State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
ESC Heart Failure
Clinical algorithms
Diagnosis
Management
Heart failure with preserved ejection fraction
Phenotypes
Precision medicine
title State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
title_full State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
title_fullStr State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
title_full_unstemmed State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
title_short State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
title_sort state of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age
topic Clinical algorithms
Diagnosis
Management
Heart failure with preserved ejection fraction
Phenotypes
Precision medicine
url https://doi.org/10.1002/ehf2.15205
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