Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment

Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment

Abstract Heart failure with preserved ejection fraction (HFpEF) represents nearly half of all heart failure cases globally. The increased prevalence of cardiometabolic disease, driven by unhealthy lifestyles, has led to a growing population of people developing the so called “cardiometabolic HFpEF (...

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Main Authors: Era Gorica, Martin A. Geiger, Ludovica Di Venanzio, Natalia Atzemian, Jan Alphard Kleeberger, Dominique Grigorian, Alessia Mongelli, Besa Emini Veseli, Shafeeq A. Mohammed, Frank Ruschitzka, Andreas J. Flammer, David Niederseer, Sarah Costantino, Francesco Paneni
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cardiovascular Diabetology
Subjects:
Obesity
HFpEF
Inflammation
Epigenetics
Metabolism
Online Access:https://doi.org/10.1186/s12933-025-02774-w
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Summary:Abstract Heart failure with preserved ejection fraction (HFpEF) represents nearly half of all heart failure cases globally. The increased prevalence of cardiometabolic disease, driven by unhealthy lifestyles, has led to a growing population of people developing the so called “cardiometabolic HFpEF (cmHFpEF)” phenotype. This condition represents an end stage cardiometabolic phenotype which results from the clustering of metabolic stress (obesity), hemodynamic stress (hypertension), immune activation, and systemic inflammation. This form of HFpEF is preceded by a “metabolic cardiomyopathy” phenotype, characterized by myocardial metabolic remodeling, rewiring of lipid metabolism, and inflammation eventually fostering left ventricular hypertrophy, diastolic dysfunction and atrial dilatation. Recent work over the last years has unveiled the molecular cues underpinning cmHFpEF pathogenesis thus contributing to the identification of novel therapeutic approaches to treat this complex syndrome. The present review provides an overview of recent advances in cmHFpEF biology and pathophysiology with particular emphasis on the following aspects: (i) metabolic alterations associated with cmHFpEF; (ii) changes of the immune landscape; (iii) microvascular dysfunction; (iv) inflammation; (v) chromatin remodeling. Additionally, we will discuss potential mechanisms-based therapeutic strategies to tackle this growing health concern.
ISSN:1475-2840

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