{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:25:53Z","timestamp":1793831153752,"version":"4.6.1"},"reference-count":95,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Heart failure (HF), a prevalent global health issue characterized by the heart\u2019s impaired ability to pump or fill blood, affects millions worldwide and continues to pose significant challenges despite advancements in treatment. This review delves into the critical and increasingly recognized role of inflammation in the development and progression of this complex syndrome. While the incidence of HF has seen a decline in some regions due to improved cardiac care, its overall prevalence is rising, particularly among younger adults and those with heart failure with a preserved ejection fraction (HFpEF). Given the persistently high rates of hospitalization and mortality associated with HF, understanding the underlying mechanisms, including the contribution of inflammation, is crucial for identifying novel therapeutic strategies. Inflammation in heart failure is a multifaceted process involving the activation of the immune system, both innate and adaptive, and encompasses various mechanisms such as the release of pro-inflammatory mediators, endothelial dysfunction, and neurohormonal activation. Myocardial damage triggers the innate immune response, while humoral immunity and chronic systemic inflammation, often linked to cardiovascular risk factors and autoimmune diseases, also play significant roles. Notably, heart failure and inflammation have a reciprocal relationship, with HF itself contributing to inflammatory processes within the cardiac tissue and systemically. Understanding these intricate pathways, including the involvement of specific immune cells and molecular mediators, is essential for comprehending the pathogenesis of heart failure and exploring potential therapeutic interventions. The review further examines various inflammatory biomarkers that have been implicated in heart failure, such as cytokines (including TNF-\u03b1 and IL-1) and C-reactive protein (CRP). While these markers often correlate with the severity and prognosis of HF, clinical trials targeting specific inflammatory mediators have largely yielded disappointing results, highlighting the complexity of the inflammatory response in this context. The exploration of these biomarkers and the challenges encountered in translating anti-inflammatory strategies into effective treatments underscore the need for continued research to unravel the precise role of inflammation across different HF subtypes and to develop more targeted and effective anti-inflammatory therapies.<\/jats:p>","DOI":"10.3390\/cells14141117","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:56:14Z","timestamp":1753084574000},"page":"1117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The Role of Inflammation in the Pathophysiology of Heart Failure"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8524-3579","authenticated-orcid":false,"given":"Marwan","family":"Amara","sequence":"first","affiliation":[{"name":"The Kittner-Davidai Division of Cardiovascular Medicine, Tzafon Medical Center, Tiberias 1520801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Stoler","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan 5290002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-7794","authenticated-orcid":false,"given":"Edo Y.","family":"Birati","sequence":"additional","affiliation":[{"name":"The Kittner-Davidai Division of Cardiovascular Medicine, Tzafon Medical Center, Tiberias 1520801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.cardfail.2023.07.006","article-title":"Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America","volume":"29","author":"Bozkurt","year":"2023","journal-title":"J. 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