Work

Cardiac sarcoidosis: from clinical manifestations to heart transplantation

Year: 2026

Type: article

Abstract: Background: Cardiac sarcoidosis (CS) represents one of the most severe and prognostically unfavorable manifestations of systemic sarcoidosis. Its diagnosis is often delayed due to non-specific symptoms and the patchy myocardial distribution of granulomatous inflammation. Objectives: To summarize 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 analyze 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 polarization, 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 favorable long-term outcomes in CS, with low rates of rejection and recurrence when accompanied by appropriate surveillance. Conclusion: A multifaceted diagnostic and therapeutic approach is essential for CS. Prospective trials are urgently needed to validate biomarkers, optimize 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 multicenter clinical trials will be critical to improving prognosis in cardiac sarcoidosis.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1723644