Key Concepts
Introduction
Cardiac sarcoidosis (CS) is a potentially life-threatening manifestation of systemic sarcoidosis, a multisystem inflammatory disease of unknown etiology characterized by the formation of non-caseating granulomas in affected organs. Sarcoidosis has a worldwide distribution with highest incidence in Northern European and African American populations. While pulmonary involvement is the most common manifestation of sarcoidosis (present in >90% of patients), cardiac involvement is clinically evident in approximately 5-10% of sarcoidosis patients during life, though autopsy studies reveal subclinical cardiac granulomas in 20-30% of sarcoidosis patients, suggesting significant underdiagnosis. Cardiac sarcoidosis is responsible for 13-25% of sarcoidosis-related deaths and is the leading cause of death from sarcoidosis in Japan. The pathogenesis of sarcoidosis involves an exaggerated CD4+ T helper cell (Th1) immune response to an unidentified antigen (suspected triggers include Mycobacterium tuberculosis-related antigens, Propionibacterium acnes, and environmental exposures such as insecticides, mold, and beryllium). The activated Th1 cells accumulate at sites of disease activity and produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha), which recruit and activate macrophages. These macrophages differentiate into epithelioid cells and multinucleated giant cells, forming the characteristic...