Acute Cardiac Tamponade Following Enfortumab Vedotin Initiation in Metastatic Urothelial Carcinoma: Successful Rescue by Pericardial Fenestration

Introduction Enfortumab vedotin is a Nectin‐4‐directed antibody–drug conjugate approved for metastatic urothelial carcinoma. Cardiac adverse events such as pericardial effusion or tamponade associated with enfortumab vedotin are extremely rare. Case Presentation A 50‐year‐old man with metastatic UC developed chest pain and dyspnea 3 days after the first EV infusion, followed by rapid progression to cardiac tamponade on Day 9. Emergency pericardiocentesis and thoracoscopic pericardial fenestration drained 2400 mL of pericardial and pleural fluid. Pericardial cytology revealed inflammatory cells without malignancy, while pleural nodules confirmed urothelial carcinoma. Infectious causes were excluded, and an acute EV‐related inflammatory reaction was suspected. EV was safely resumed on postoperative Day 20, achieving a sustained partial response for 8 months without recurrence of pericardial effusion. Conclusion This rare case highlights the potential for acute, enfortumab vedotin‐related inflammatory pericardial effusion and emphasizes the importance of early recognition and prompt surgical intervention.