Andrea Bottardi, Gabriele Busin, Lam Nguyen, Paolo Del Fiore, Giorgia Alberti, Andrea Danese, Michele Nori, Raimondo Pittorru, Fortunato Cassalia
Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of advanced melanoma, significantly improving long-term survival. Nevertheless, these therapies may induce immune-related cardiovascular adverse events, which are uncommon but potentially life-threatening. Myocarditis is the best-characterized and most severe manifestation, although a broad spectrum of cardiovascular complications-including pericardial disease, arrhythmias, conduction abnormalities, heart failure, Takotsubo syndrome, and vascular events-has increasingly been recognized. Emerging evidence suggests that melanoma itself and dual immune checkpoint blockade may confer a higher risk of cardiotoxicity than other malignancies or single-agent immunotherapy. This narrative review summarizes current evidence regarding the epidemiology, pathophysiological mechanisms, clinical presentation, diagnostic evaluation, cardiovascular surveillance, and management of ICI-associated cardiotoxicity in patients with melanoma. Diagnosis relies on integrating clinical findings with electrocardiography, cardiac biomarkers, echocardiography, cardiac magnetic resonance imaging, and, in selected cases, endomyocardial biopsy. Prompt interruption of ICI therapy, early administration of high-dose corticosteroids, and escalation to additional immunosuppressive therapies in refractory cases remain the cornerstone of treatment. As the use of ICIs continues to expand, improving cardiovascular risk stratification and implementing evidence-based surveillance strategies will become increasingly important. A multidisciplinary cardio-oncology approach is essential to ensure early diagnosis, optimize cardiovascular outcomes, and preserve the anticancer efficacy of immunotherapy.