{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:04:14Z","timestamp":1784714654626,"version":"3.55.0"},"reference-count":253,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>Cardiomyopathies have traditionally been regarded as disorders driven primarily by cardiomyocyte injury resulting from genetic defects, infection, metabolic stress, or toxic exposure. This paradigm has substantially advanced diagnosis and treatment. Still, it does not fully account for the marked heterogeneity in disease progression, persistent fibrosis, or variable therapeutic responses among patients with similar phenotypes. Increasing evidence indicates that immune remodeling is not merely a secondary consequence of myocardial injury but a dynamic process that actively shapes disease evolution. In this review, we integrate recent advances in cardiovascular immunology, single-cell and spatial transcriptomics, immunometabolism, and systems biology to propose a unified framework of immunological reprogramming in cardiomyopathies. We discuss how danger-associated molecular patterns, inflammasome activation, trained immunity, the cGAS\u2013STING pathway, fibroblast\u2013immune interactions, and the cardio\u2013bone marrow axis converge to establish chronic inflammatory circuits that promote fibrosis, electrical remodeling, and progressive ventricular dysfunction. We further examine the emerging concept of immunotypes, emphasizing that distinct immune programs may underlie the biological heterogeneity of cardiomyopathies beyond conventional phenotypic or genetic classification. Finally, we discuss the translational potential of immune profiling, advancing a shift toward viewing cardiomyopathies as disorders of a dysregulated cardiac immune ecosystem. We propose that immune ecosystem organization constitutes an additional biological dimension that complements traditional phenotypic and genetic classifications of cardiomyopathies.<\/jats:p>","DOI":"10.3390\/cells15141308","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:20:39Z","timestamp":1784712039000},"page":"1308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunological Reprogramming in Cardiomyopathies: From Cardiomyocyte Injury to Disease of the Cardiac Immune Ecosystem"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-2764","authenticated-orcid":false,"given":"Tomasz","family":"Urbanowicz","sequence":"first","affiliation":[{"name":"Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, \u00bd D\u0142uga, 61-848 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6563-0877","authenticated-orcid":false,"given":"Krzysztof J.","family":"Filipiak","sequence":"additional","affiliation":[{"name":"The Centre of Postgraduate Medical Education, 99\/103 Marymoncka Street, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1161\/CIRCRESAHA.117.309711","article-title":"Classification, Epidemiology, and Global Burden of Cardiomyopathies","volume":"121","author":"McKenna","year":"2017","journal-title":"Circ. 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