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Emerging data implicate inflammasome signaling-particularly NOD-like receptor pyrin domain-containing protein 3 (NLRP3), caspase-1 activation, interleukin (IL)-1\u03b2\/IL-18 maturation, and gasdermin-mediated pyroptosis-as a proximal driver of profibrotic programs. This narrative review synthesizes mechanistic and translational evidence linking pyroinflammation to myofibroblast transition, transforming growth factor \u03b2 (TGF-\u03b2)\/small mother against decapentaplegic (SMAD) and Yes-associated protein (YAP)\/transcriptional coactivator with PDZ-binding motif (TAZ) activation, matrix deposition and cross-linking, and resultant electrical and mechanical heterogeneity. We emphasize multicellular crosstalk among immune cells, fibroblasts, cardiomyocytes, endothelium\/pericytes, and epicardial adipose tissue, and outline organ-axis amplification from kidney and liver disease. We appraise candidate biomarkers and imaging readouts for enrichment, response assessment, and surrogate endpoint potential. The therapeutic landscape spans direct inflammasome inhibitors and IL-1\/IL-18 blockade, modulators of upstream metabolic stress, and antifibrotic strategies. Finally, we propose trial frameworks integrating molecular and imaging phenotyping with rhythm and remodeling outcomes, and highlight priorities including assay standardization for pyroptosis and patient selection. By consolidating the inflammasome-fibrosis axis across cardiometabolic conditions, this review defines actionable diagnostic and therapeutic nodes to inform mechanism-guided clinical studies.<\/jats:p>","DOI":"10.31083\/fbl48667","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":2,"title":["Inflammasome-Driven Cardiac Fibrosis in Cardiometabolic Disease and Arrhythmias: Mechanisms, Biomarkers, and Therapeutic Targets"],"prefix":"10.31083","volume":"31","author":[{"given":"Konstantinos","family":"Grigoriou","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Athens, 11527 Goudi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Lamprou","sequence":"additional","affiliation":[{"name":"Manchester Heart Centre, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, M13 9WL Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios P","family":"Antoniadis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Theofilis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Iliakis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Ktenopoulos","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Apostolos","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Cardiology, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, Harefield Hospital, UB9 6JH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Nasoufidou","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Fyntanidou","sequence":"additional","affiliation":[{"name":"Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstratios","family":"Karagiannidis","sequence":"additional","affiliation":[{"name":"Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Fragakis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Patoulias","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3561-5713","authenticated-orcid":true,"given":"Paschalis","family":"Karakasis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Karakasis P, Theofilis P, Vlachakis PK, Korantzopoulos P, Patoulias D, Antoniadis AP, et al. 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