Current Challenges and Emerging Therapeutic Strategies in Acute Myocarditis

Acute myocarditis encompasses a heterogeneous group of inflammatory myocardial disorders with clinical presentations ranging from self-limited chest pain to fulminant cardiogenic shock. Despite advances in cardiac magnetic resonance imaging and molecular diagnostics, substantial uncertainty persists regarding early diagnosis, etiologic classification, and optimal therapeutic strategies. Current management relies largely on supportive care, as robust randomized evidence guiding immunomodulatory therapy remains limited and confined to selected virus-negative or autoimmune phenotypes. This review synthesizes contemporary evidence on the pathophysiology, diagnostic challenges, and treatment paradigms of acute myocarditis, with a particular focus on the critical distinction between virus-positive and virus-negative disease. We discuss established supportive and guideline-directed therapies, emerging immunomodulatory approaches-including corticosteroids, biologics targeting interleukin-1, complement, and mammalian target of rapamycin pathways-and the evolving role of mechanical circulatory support in fulminant myocarditis. COVID-19 vaccination-related myocarditis is highlighted as a modern example of immune-triggered, predominantly virus-negative myocarditis, illustrating both the generally favorable prognosis and the potential for severe clinical courses. Finally, this review outlines future directions toward precision immunocardiology, emphasizing the integration of endomyocardial biopsy, molecular virology, multi-omics profiling, and artificial intelligence-guided phenotyping to enable mechanism-driven, individualized therapy. Advancing from empirical management to precision-based intervention will be essential to improving outcomes in acute myocarditis.