Myocarditis Mimicking Takotsubo Cardiomyopathy With First Dose of Neoadjuvant Nivolumab-Relatlimab.

Neoadjuvant use of immune checkpoint inhibitors (ICIs) is the new standard of care in patients with clinical stage III melanoma. However, it is associated with immune-related adverse events (irAEs). Nivolumab-relatlimab in the neoadjuvant setting is an NCCN-recommended treatment for patients with clinical stage III melanoma. Anti-LAG3 molecule comes with an increased risk of cardiac irAE, especially myocarditis. Takotsubo cardiomyopathy (TTC), a reversible decline in heart function driven by catecholamine overload, is reported as a cardiac irAE in the literature. However, the mechanism of TTC being an irAE is elusive. It is known that myocarditis and TTC share a lot of common features, although the presence of cardiac inflammation essentially rules out TTC. Here, we report the case of an elderly patient with a history of heart failure with midrange ejection fraction, diagnosed with clinical stage III melanoma, who developed shortness of breath with the first dose of neoadjuvant nivolumab-relatlimab. Cardiac magnetic resonance (CMR) imaging demonstrated a severe apical hypokinesis and no myocardial edema, suggestive of TTC. However, since myocarditis could not be ruled out, the patient was started on high-dose methylprednisolone followed by a 9-week taper of prednisone. The CMR changes reverted to baseline 44 days later, with the patient experiencing complete recovery. He underwent wide local excision of the primary melanoma and complete lymph node dissection, which showed a major pathologic response. Postoperatively, he remains on surveillance with no evidence of recurrence. This report emphasizes early recognition of cardiac irAEs and initiation of corticosteroids, which could help prevent morbid long-term complications.