Non-Bacterial Thrombotic Endocarditis and Intraventricular Small Vessel Thromboembolic Occlusion Mimicking ICI Myocarditis in a Patient Treated with Pembrolizumab: A Case Report

Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and are increasingly associated with cardiovascular toxicities, including myocarditis and accelerated atherosclerosis. While ICI-myocarditis has received substantial attention, thrombotic complications remain underrecognized and may be difficult to distinguish from immune-mediated cardiac inflammation and cancer-related hypercoagulable state. We present a case of non-bacterial thrombotic endocarditis (NBTE) and myocardial microthrombi mimicking ICI-myocarditis. Case Summary A 76-year-old woman with metastatic adenosquamous lung carcinoma presented with progressive dyspnea three weeks after initiating pembrolizumab. Pulmonary arterial and coronary imaging were unremarkable, but cardiac MRI showed late gadolinium enhancement and myocardial edema suggestive of ICI-myocarditis. Chest CT revealed inflammatory lung changes, and empirical corticosteroids were initiated with initial clinical improvement. One week later, brain MRI showed multifocal infarcts, and Doppler ultrasound identified bilateral lower extremity deep vein thromboses. Transesophageal echocardiography showed thickened mitral and aortic valves with moderate regurgitation. NBTE with embolic phenomena was suspected. Anticoagulation was escalated from apixaban to therapeutic enoxaparin, followed by warfarin. Despite initial stabilization, the patient died two months later. Post-mortem examination revealed fibrin-rich valvular vegetations consistent with NBTE, widespread intramyocardial thrombi, and no histopathologic evidence of myocarditis. Discussion This case underscores how microthrombotic complications of ICI therapy may closely mimic myocarditis on imaging. Nonspecific cardiac MRI findings such as LGE and T2 signal elevation can result from thrombotic or ischemic injury alike. Histopathologic confirmation may be required for accurate diagnosis, as misclassification can lead to suboptimal treatment.