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As it is fundamentally a diagnosis of exclusion, iCS diagnosis relies on the absence of extracardiac sarcoid and the integration of multimodality imaging, endomyocardial biopsy, and molecular testing, each with inherent limitations. Cardiac magnetic resonance and positron emission tomography provide complementary assessment of inflammation, fibrosis, and ventricular function, enhancing diagnostic confidence. Electroanatomic mapping-guided biopsy may improve histologic yield, whereas genetic testing helps exclude phenocopies such as arrhythmogenic, hypertrophic, or dilated cardiomyopathies. Circulating biomarkers remain non-specific but may complement imaging-based algorithms. Future research should focus on harmonized imaging protocols, non-FDG radiotracers, and molecular tissue profiling to refine activity assessment and guide therapy. Multimodal, probability-based frameworks represent the most promising approach for earlier, more accurate diagnosis and risk stratification in iCS.<\/jats:p>","DOI":"10.1093\/eschf\/xvag159","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:30:04Z","timestamp":1780399804000},"source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic challenges in isolated cardiac sarcoidosis"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-1777","authenticated-orcid":false,"given":"Gregorio","family":"Tersalvi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina A","family":"Rossi","sequence":"additional","affiliation":[{"name":"University Heart Center, University Hospital of Zurich , Zurich 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