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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| Format: | Article |
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BMC
2025-07-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02774-w |
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| author | 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 |
| author_facet | 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 |
| author_sort | Era Gorica |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cf652e484c15452a851b2324e851aebc |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-cf652e484c15452a851b2324e851aebc2025-08-20T03:45:22ZengBMCCardiovascular Diabetology1475-28402025-07-0124111710.1186/s12933-025-02774-wCardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatmentEra Gorica0Martin A. Geiger1Ludovica Di Venanzio2Natalia Atzemian3Jan Alphard Kleeberger4Dominique Grigorian5Alessia Mongelli6Besa Emini Veseli7Shafeeq A. Mohammed8Frank Ruschitzka9Andreas J. Flammer10David Niederseer11Sarah Costantino12Francesco Paneni13Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of ZurichAbstract 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.https://doi.org/10.1186/s12933-025-02774-wObesityHFpEFInflammationEpigeneticsMetabolism |
| spellingShingle | 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 Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment Cardiovascular Diabetology Obesity HFpEF Inflammation Epigenetics Metabolism |
| title | Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment |
| title_full | Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment |
| title_fullStr | Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment |
| title_full_unstemmed | Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment |
| title_short | Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment |
| title_sort | cardiometabolic heart failure with preserved ejection fraction from molecular signatures to personalized treatment |
| topic | Obesity HFpEF Inflammation Epigenetics Metabolism |
| url | https://doi.org/10.1186/s12933-025-02774-w |
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