Immune checkpoint inhibitor-associated myocarditis: current insights into pathogenesis, diagnosis, and treatment Artykuł przeglądowy

Abstrakt

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing T-cell-mediated antitumor immunity through blockade of cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1 pathways. Despite their clinical efficacy across multiple solid tumors and select hematologic malignancies, ICIs can disrupt peripheral immune tolerance, triggering immune-related adverse events, among which myocarditis is rare but potentially fatal. Immune checkpoint inhibitor-associated myocarditis (ICI-M) typically emerges early after therapy initiation and is characterized by dense myocardial infiltration of activated T lymphocytes, particularly clonally expanded CD8+ cells. Mechanisms involve autoreactive responses against cardiac antigens, such as α-myosin heavy chain, and molecular mimicry with tumor or skeletal muscle proteins. Clinical presentations are highly heterogeneous, ranging from isolated biomarker elevation to fulminant myocarditis with cardiogenic shock, malignant arrhythmias, or conduction disturbances. Concomitant myositis or myasthenia gravis-like syndromes are common, reflecting shared antigenic targets. Diagnosis requires integrated evaluation using clinical assessment, cardiac biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance, with endomyocardial biopsy remaining definitive. Early recognition and prompt initiation of high-dose corticosteroids are critical to mitigate morbidity and mortality, while second-line immunosuppressive strategies are increasingly explored in refractory cases. Despite its low incidence, ICI-M carries substantial risk, underscoring the need for vigilance and multidisciplinary management.