Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment over the past decade; however, it is crucial to recognize their rare but clinically significant cardiotoxicities. These agents are often combined with other chemotherapeutics carrying distinct cardiotoxic profiles. CASE SUMMARY: A 37-year-old man presented with cardiogenic shock shortly after initiating ICI and fluorouracil (5FU) therapy. He was treated concurrently for suspected ICI myocarditis and 5FU cardiotoxicity with rapid improvement. Given higher suspicion for 5FU as the culprit, he was rechallenged successfully with nivolumab. DISCUSSION: Distinguishing between overlapping cardiotoxicities and establishing causality can be challenging in patients receiving combination therapy. Diagnostic tests alone may be insufficient to confirm a diagnosis and should be complemented by a thorough assessment of risk factors and clinical presentation. TAKE-HOME MESSAGE: This case highlights the importance of prompt and accurate identification of a causative agent for cardiotoxicity with consequential impact on future therapeutics and cancer prognosis.