Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate

BACKGROUND: Nivolumab is a human IgG4 anti-programmed cell death protein-1 (PD-1) monoclonal antibody that works by augmenting the immune response against tumour cells. It has the potential of causing multiple autoimmune-related events, including cardiac. However, the real incidence and diagnosis of cardiac complications remains unclear. CASE SUMMARY: A 47-year-old woman with a history of carotid artery dissection and metastatic melanoma presented with acute heart failure. One year prior to presentation, she had received one cycle only of checkpoint inhibitor therapy with both ipilimumab and nivolumab, and nivolumab only was restarted 4 months prior to presentation. On admission, she was hypotensive, tachycardic due to atrial tachycardia and with pulmonary oedema. An echocardiogram revealed a left ventricular ejection fraction of 26%. Cardiovascular magnetic resonance (CMR) demonstrated a non-ischaemic pattern of late gadolinium enhancement (LGE), most consistent with myocarditis. The diagnosis of immunotherapy-mediated cardiac toxicity was highly considered and immunosuppressive therapy was initiated. However, she went into refractory cardiogenic shock and did not survive. An autopsy performed with samples from areas of myocardium with and without LGE on the CMR, found correlation. DISCUSSION: According to the literature, cardiac complications develop in less than 1% of patients treated with checkpoint inhibitors, with a 0.06% incidence reported in nivolumab specifically. However, it may be higher, given the lack of cardiac monitoring during treatment. We present the first case demonstrating direct histological correlation of T-lymphocytic infiltration with areas of LGE on CMR. Future investigation using CMR for early detection of inflammation and left ventricular dysfunction may help to diagnosis disease earlier.