Immune checkpoint inhibitor-associated myocarditis: clinical characteristics, management, and outcomes from a tertiary cardio-oncology unit

Abstract Introduction and Objectives Myocarditis induced by immune checkpoint inhibitors (ICIs) is a rare but life-threatening immune-related adverse event (irAE) with high morbidity and mortality. The aim of this study is to describe the clinical characteristics, treatment strategies, and outcomes of patients diagnosed with ICI-related myocarditis at our center. Methods We conducted a descriptive analysis of patients hospitalized with ICI-induced myocarditis at our center between 2020 and 2024. We assessed clinical presentation, cardiac investigations, treatment approaches, and both in-hospital and post-discharge outcomes. Results A total of 13 patients with ICI-related myocarditis were included (85% male, mean age 72 years). The most frequent underlying malignancy was lung cancer. Only one patient had pre-existing structural heart disease. The most commonly used ICIs were pembrolizumab (38%) and nivolumab (38%), with three cases of combination therapy. Myocarditis typically developed after three treatment cycles, with an earlier onset in patients receiving combination therapy. Presenting symptoms varied, including fatigue and myalgias (54%), heart failure symptoms (23%), and neurological manifestations (31%). Additionally, 69% of patients had concurrent myositis, and 54% developed a myasthenia-like syndrome. New-onset conduction abnormalities in the electrocardiogram (ECG) were observed in 46% of cases. All patients had elevated cardiac biomarkers at diagnosis (mean baseline creatine kinase 3426 U/L, peak troponin T 1048 ng/L). Left ventricular ejection fraction (LVEF) was preserved in 92% of cases. Cardiac magnetic resonance imaging (CMR) was performed in 10 out of 13 patients, revealing myocarditis-related findings in 7 (70%) cases. All patients received corticosteroids, with additional immunosuppressive therapy in some cases (52% immunoglobulins, 38% mycophenolate mofetil). In-hospital mortality was 31% (4 patients), primarily due to severe immune-related toxicity. During post-discharge follow-up (mean 10 months), an additional 3 patients (23%) died due to oncological disease progression. Conclusions ICI-induced myocarditis presents with a broad spectrum of clinical manifestations, often with preserved LVEF and frequent extracardiac involvement, including myositis and neuromuscular syndromes. Despite prompt initiation of immunosuppressive therapy, mortality remains high, highlighting the need for early detection and optimized management strategies. Multimodal cardiac imaging, particularly cardiac MRI, plays a crucial role in diagnosis. Future research should focus on refining risk stratification and therapeutic interventions to improve patient outcomes.