Cardiac sarcoidosis: from clinical manifestations to heart transplantation

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.

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.

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.

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.

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.