Giant cell myocarditis: from immune pathogenesis to contemporary management

Giant cell myocarditis (GCM) is a rare but devastating inflammatory cardiac disease characterized by rapid hemodynamic deterioration, malignant arrhythmias, and high rates of death or heart transplantation. Without immunosuppressive treatment, median transplant-free survival is approximately three months. Current evidence identifies GCM as a predominantly T cell-mediated autoimmune disorder driven by a breakdown of immune tolerance, with contributions from macrophage-derived multinucleated giant cells and neutrophil extracellular trap formation. Viral infections and environmental factors have been implicated as potential triggers. GCM typically affects middle-aged adults, with concomitant non-cardiac autoimmune diseases present in approximately 20% of cases. Early diagnosis remains challenging, as clinical presentation and imaging findings are nonspecific and overlap considerably with cardiac sarcoidosis. Endomyocardial biopsy continues to represent the diagnostic gold standard, with a sensitivity of 85%, while cardiac biomarkers including cardiac troponins and NT-proBNP provide important prognostic information. Cardiac magnetic resonance imaging and FDG-PET contribute to the diagnostic workup but cannot reliably differentiate GCM from cardiac sarcoidosis. Management requires prompt initiation of combination immunosuppressive therapy-typically corticosteroids combined with T cell-targeted agents such as cyclosporine and azathioprine or tacrolimus and mycophenolate mofetil, which has substantially improved survival in contemporary registries. Mechanical circulatory support and heart transplantation are frequently required for refractory cases. Given the high arrhythmic burden, systematic evaluation for implantable cardioverter-defibrillator placement is recommended. This review provides a comprehensive overview of the pathogenesis, diagnosis, and current management of GCM and highlights priorities for future research, including noninvasive diagnostic tools and standardized treatment protocols.