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the heart to adequately meet systemic metabolic requirements. While ventricular dysfunction has traditionally been the primary focus in both conceptual and clinical frameworks of HF, emerging evidence highlights atrial myopathy\u2014covering structural, functional, electrical, metabolic, and neurohormonal remodeling\u2014as a central yet often overlooked contributor to disease progression across the HF spectrum. This review offers a comprehensive overview of the molecular and cellular mechanisms underlying atrial remodeling, with a focus on inflammation and innate immune activation as key pathogenic mediators. Among pattern recognition receptors, Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play crucial roles in translating myocardial stress into pro-inflammatory, profibrotic, and pro-arrhythmic signals that exacerbate HF. By combining experimental and clinical evidence, we emphasize atrial myopathy as both a biomarker and an active driver of HF deterioration, advocating for the inclusion of atrial-targeted diagnostics and immunomodulatory therapies in future HF treatment approaches. Such a paradigm shift holds significant potential for improved risk stratification, arrhythmia prevention, attenuation of structural remodeling, and ultimately, better prognosis and clinical outcomes in this increasingly common syndrome.<\/jats:p>","DOI":"10.3390\/ijms26178210","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"8210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Atrial Myopathy and Heart Failure: Immunomolecular Mechanisms and Clinical Implications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-202X","authenticated-orcid":false,"given":"Marta","family":"Gil Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Clinical and Invasive Cardiology Research Group (ICCI-PAZ), Hospital La Paz Institute for Health Research (IdiPAZ), 28046 Madrid, 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