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REVIEW article

Front. Med.

Sec. Rheumatology

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1557312

This article is part of the Research TopicCardiovascular Comorbidities in Inflammatory Rheumatic DiseasesView all 13 articles

Autoimmune inflammation as a key risk factor for heart failure with preserved ejection fraction (HFpEF). The different types of inflammation driving to HFpEF

Provisionally accepted
  • 1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
  • 2Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
  • 3Rheumatology Unit, DiMePRE-J, University of Bari, Bari, Italy
  • 4Department of Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Gemelli IRCCS, Rome, Italy

The final, formatted version of the article will be published soon.

Importance. Heart failure with preserved ejection fraction (HFpEF), defined by an ejection fraction > 50%, has emerged as the most prevalent form of heart failure at the community level. Multiple comorbidities, including diabetes, hypertension, obesity, atrial fibrillation, renal diseases, and autoimmune conditions, have been linked to its development. These conditions share common pathways involving oxidative stress, metabolic dysregulation, ischemia, and a chronic inflammatory milieu.Observations. Patients with autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) exhibit an increased risk of developing HFpEF, often through mechanisms involving chronic inflammation and endothelial dysfunction, which precede the the clinical manifestation of HFpEF.Clinical studies have demonstrated that the risk of developoing HFpEF exists independently of traditional cardiovascular risk factors, underscoring the pivotal role of chronic inflammation and autoimmunity as key contributors to its pathogenesis.The translational implication is that the distinct inflammatory pathways driving these autoimmune diseases (e.g., myeloid-T cells and T-B cell-mediated inflammation in RA, and B cell-driven inflammation in SLE and SSc) should become personalized therapeutic targets to prevent HFpEF progression.Early intervention with novel therapies, such as sodium-glucose cotransporter type 2 (SGLT2) inhibitors, could be crucial in managing these patients during the early disease stages. Additionally, the H2FPEF score should be routinely employed to facilitate early diagnosis and risk stratification, providing a robust framework for personalized management strategies.

Keywords: Inflammation, Autoimmunity, endothelial dysfunction, diastolic dysfunction, heart failure with preserved ejection fraction

Received: 08 Jan 2025; Accepted: 28 Jul 2025.

Copyright: © 2025 Gremese, Bruno, Perniola and Ferraccioli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Elisa Gremese, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

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