Fulminant Myocarditis Associated with Immune Checkpoint Inhibition

Abstract

Immune checkpoint inhibitors (ICIs) have improved survival in advanced malignancies, including metastatic renal cell carcinoma (RCC), but are associated with immune-related adverse events affecting multiple organs. ICI-associated myocarditis is rare but carries high morbidity and mortality and often presents with nonspecific symptoms, making early diagnosis challenging.

A 77-year-old man with metastatic clear cell renal cell carcinoma (RCC) receiving pembrolizumab and axitinib developed acute dyspnea and fatigue approximately 61 days after initiation of therapy and 19 days after his third pembrolizumab dose. He developed hypoxemic respiratory failure requiring non-invasive ventilatory support. Investigations revealed markedly elevated cardiac biomarkers (troponin and NT-proBNP), new ST-segment changes on electrocardiography, and global left ventricular hypokinesia with a reduction in left ventricular ejection fraction (LVEF) from 60% at baseline to 36% on echocardiography. Infectious etiologies were not identified, and ischemic heart disease was considered less likely based on the overall clinical and echocardiographic findings. Based on contemporary ESC/IC-OS diagnostic criteria, a diagnosis of ICI-associated myocarditis was established.

The patient was treated with high-dose intravenous methylprednisolone followed by an oral taper, resulting in clinical improvement and reduction in cardiac biomarkers. Although left ventricular dysfunction persisted at 8-week follow-up, repeat echocardiography demonstrated gradual recovery of ventricular function, with LVEF improving to 50% at 6 months and 52% at 10 months. During follow-up, the patient also developed immune-related hypothyroidism requiring levothyroxine replacement therapy.

This case highlights the diagnostic challenge of ICI-associated myocarditis in hemodynamically unstable patients in whom definitive investigations are not feasible. Delayed recovery of ventricular function despite early improvement in clinical status and cardiac biomarkers underscores the need for prolonged cardiac surveillance and follow-up in patients recovering from ICI-associated myocarditis.