Granulomas in the Heart: Pathophysiology, Diagnosis, Management, and Outcomes in Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is a rare but potentially fatal manifestation of systemic sarcoidosis, characterized by granulomatous myocardial inflammation that disrupts both cardiac structure and electrical conduction. This narrative review synthesizes current understanding of CS pathophysiology, including immune dysregulation, CD4⁺ T-cell and macrophage activity, cytokine signaling, and fibrosis. Genetic susceptibility and environmental triggers further contribute to disease risk and variability. Clinical presentations span a broad spectrum, ranging from silent conduction abnormalities to ventricular arrhythmias, heart failure, and sudden cardiac death. Diagnostic evaluation integrates electrocardiography, echocardiography, cardiac MRI (CMR), fluorodeoxyglucose positron emission tomography (FDG-PET), and endomyocardial biopsy, supported by the Heart Rhythm Society (HRS), Japanese Ministry of Health and Welfare (JMHW), and World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria. Management involves immunosuppression with corticosteroids, steroid-sparing agents, and biologics; arrhythmia control through medications, catheter ablation, and device therapy; and guideline-directed heart-failure care, including mechanical support or transplantation when needed. Outcomes remain heterogeneous and depend on ventricular function, fibrosis burden, and timely treatment. Early recognition and coordinated multidisciplinary care are critical to improving survival.