{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:03Z","timestamp":1787026323287,"version":"build-2736575974"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"The Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Sarcoidosis is a systemic disorder driven by genetic predisposition, environmental exposures, and immune dysregulation, resulting in the formation of noncaseating granulomas across multiple organs. In cardiac sarcoidosis (CS), immune cell infiltration of the myocardium, epicardium, and endocardium may lead to conduction disturbances, ventricular arrhythmias, and heart failure. While overt cardiac involvement was historically considered rare, affecting only 5% of sarcoidosis patients, the wider availability and improved sensitivity of contemporary cardiac imaging have revealed a substantially higher burden, with cardiac involvement reaching up to 55% in selected, systematically screened populations. Current diagnostic approaches for CS, including endomyocardial biopsy (EMB), cardiovascular magnetic resonance (CMR), and fluorine-18 fluorodeoxyglucose\u2013positron emission tomography (FDG-PET), offer valuable insights but are restricted by high costs, invasiveness, and limited sensitivity and specificity. These challenges, together with the disproportionate contribution of cardiac involvement to sarcoidosis-related mortality, underscore the need for innovative, non-invasive, and widely accessible diagnostic strategies. Emerging evidence suggests that novel serum biomarkers and genomic studies hold promise for transforming the diagnostic landscape of CS. Biomarkers may provide accessible, cost-effective tools to complement established diagnostic methods, while genetic insights could identify individuals at higher risk for cardiac involvement and stratify patients based on disease phenotype. This review examines current evidence on serum biomarkers and genetic studies in CS diagnosis, identifies critical knowledge gaps, and proposes future directions aimed at advancing diagnostic precision and improving clinical outcomes.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1754375","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T07:11:40Z","timestamp":1772435500000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomarkers and genetic determinants of cardiac sarcoidosis: current status, the unmet needs and future perspectives"],"prefix":"10.3389","volume":"13","author":[{"given":"Tine","family":"Bajec","sequence":"first","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, Department of Cardiology, University Medical Centre Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matev\u017e","family":"Harlander","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University Medical Centre Ljubljana","place":["Ljubljana, Slovenia"]},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Pucelj Koren","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University Medical Centre Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahwash","family":"Kassi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Poglajen","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, Department of Cardiology, University Medical Centre Ljubljana","place":["Ljubljana, Slovenia"]},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1093\/eurheartj\/ehad067","article-title":"Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis","volume":"44","author":"Lehtonen","year":"2023","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1156474","DOI":"10.3389\/fcvm.2023.1156474","article-title":"Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies","volume":"10","author":"Shah","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1197","DOI":"10.1161\/CIR.0000000000001240","article-title":"Diagnosis and management of cardiac sarcoidosis: a scientific statement from the American Heart Association","volume":"149","author":"Cheng","year":"2024","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.hrthm.2014.03.043","article-title":"HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis","volume":"11","author":"Birnie","year":"2014","journal-title":"Heart Rhythm"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1253\/circj.CJ-19-0508","article-title":"JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis - digest version","volume":"83","author":"Terasaki","year":"2019","journal-title":"Circ J"},{"key":"B6","first-page":"19","article-title":"The WASOG sarcoidosis organ assessment instrument: an update of a previous clinical tool","volume":"31","author":"Judson","year":"2014","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.3390\/jcm9082633","article-title":"Current insights in genetics of sarcoidosis: functional and clinical impacts","volume":"9","author":"Calender","year":"2020","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8565423","DOI":"10.1155\/2019\/8565423","article-title":"Prognostic biomarkers of sarcoidosis: a comparative study of serum chitotriosidase, ACE, lysozyme, and KL-6","volume":"2019","author":"Bergantini","year":"2019","journal-title":"Dis Markers"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1378\/chest.102.4.1128","article-title":"Soluble interleukin 2 receptors in patients with sarcoidosis","volume":"102","author":"Ina","year":"1992","journal-title":"Possible Origin. 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