CARDIAC SARCOIDOSIS: FROM CLINICAL MANIFESTATIONS TO HEART TRANSPLANTATION

Anna Starshinova^1,2*Petr Fedotov²Musaeva Bulgun²Igor Vladimirovich Kudryavtsev^2,3Artem Rubinstein³Arthur D. Aquino²Dmitry Kudlay^4,5Evgeny Shlyakhto²

• ¹Saint Petersburg State University, Saint Petersburg, Russia
• ²FGBU Nacional'nyj medicinskij issledovatel'skij centr imeni V A Almazova, Saint Petersburg, Russia
• ³Experimental Institute in Medicine, St.-Petersburg, Russia
• ⁴Moskovskij gosudarstvennyj universitet imeni M V Lomonosova Dopolnitel'noe obrazovanie, Moscow, Russia
• ⁵Pervyj Moskovskij gosudarstvennyj medicinskij universitet imeni I M Secenova, Moscow, Russia

Background: Cardiac sarcoidosis (CS) represents one of the most severe and prognostically unfavourable manifestations of systemic sarcoidosis. Its diagnosis is often delayed due to non-specific symptoms and the patchy myocardial distribution of granulomatous inflammation. Objectives: To summarise the current understanding of epidemiology, diagnostic strategies, immunopathology, and therapeutic advances in CS, and to propose recommendations for future research and clinical management. Methods / Scope: We analyse epidemiological data, autopsy series, and clinical cohorts to estimate the true prevalence and spectrum of CS. We review diagnostic algorithms combining electrocardiographic, echocardiographic, cardiac MRI, and ^18F-FDG PET imaging with histopathological methods. Immunopathological mechanisms are discussed, with particular focus on Th17.1 cells, M2 macrophage polarisation, and inflammasome activation. Therapeutic modalities — including corticosteroids, immunosuppressants, biologics (e.g. TNF inhibitors, IL-1/IL-18 blockers), and mechanical support (LVAD, transplantation) — are critically appraised based on existing clinical and registry evidence. Results: Morphological evidence suggests cardiac involvement in 20–30 % of sarcoidosis cases, yet clinically manifest CS is diagnosed in only ~5 %. Advanced imaging has increased detection of subclinical disease. Th17.1 cells and M2 macrophages appear central in granuloma formation and fibrotic progression, while activation of the NLRP3 inflammasome represents a promising therapeutic target. Corticosteroids remain the first-line therapy; steroid-sparing immunosuppression and biological therapies are under investigation. Heart transplantation yields favourable long-term outcomes in CS, with low rates of rejection and recurrence when accompanied by appropriate surveillance. Conclusions: A multifaceted diagnostic and therapeutic approach is essential for CS. Prospective trials are urgently needed to validate biomarkers, optimise immunomodulatory regimens, and test targeted interventions (e.g. IL-1/IL-18 blockade, NLRP3 inhibition). In advanced disease, transplantation remains a viable and effective option. Concerted efforts in mechanistic research, biomarker discovery and multicentre clinical trials will be critical to improving prognosis in cardiac sarcoidosis.