A Case of Immune Checkpoint Inhibitor (ICI) Related Myocarditis

Description of Clinical Presentation: A 77-year-old man with anaplastic thyroid carcinoma being treated with a dual immune checkpoint inhibitor (ICI) therapy (nivolumab/pembrolizumab) presented in March 2025 with polyarticular pain, lethargy, productive cough, light-headedness and myalgias. The patient was hypotensive with markedly elevated serum troponin levels, peaking at 24,000pg/mL. ECG demonstrated ST elevation, and echocardiography revealed a left ventricular function ejection fraction of 34%. A CMR was subsequently performed given suspected myocarditis. On the basis of history, clinical status, labs and MR he was diagnosed with fulminant myocarditis, likely resulting from his ICI. Autopsy revealed myocardium with acute and subacute ischemic changes, patchy T-cell vasculitis, and associated thrombi. Despite escalation of care, he developed refractory cardiogenic shock and widespread cardioembolic infarcts. His course was further complicated by hypotension and arrhythmias. The patient ultimately died due to cardiac necrosis secondary to ischemia, in the setting of ICI therapy.

Diagnostic Techniques and Their Most Important Findings: Following admission, a cardiac MR was performed to evaluate for myocarditis. This confirmed a severely reduced LV function with an ejection fraction of 37%. On postcontrast sequences, there was extensive patchy subepicardial and mid-myocardial delayed gadolinium enhancement involving multiple segments, most notable in the basal to apical mid and lateral walls. Of note, T2 values were normal, ranging from 50-56msec globally. Conversely, T1 values were globally elevated measuring up to 1208 msec. There was a small pericardial effusion, with associated post-contrast enhancement indicative of pericardial inflammation.

Learning Points from this Case: ICI’s enhance T-cell activity against tumors but can cause immune-related adverse events, including myocarditis, which although rare is associated with high fatality rates. Toxicity is thought to result from T-cell cross-reactivity in which tumor antigens resemble cardiac muscle proteins leading to off-target immune injury. Clinical presentation ranges from asymptomatic biomarker elevation to fulminant cardiogenic shock with arrhythmias and multiorgan dysfunction. Early recognition of this complication is crucial, as treatment requires immediate cessation of the agent and prompt initiation of immunosuppression, with steroid-refractory cases often requiring advanced therapies.

CMR is highly sensitive for detecting the tissue changes of myocardial inflammation, including edema, hyperemia and fibrosis, and plays a central role in diagnosis. CMR findings in acute myocarditis is classically associated with mid myocardial delayed gadolinium enhancement, with elevated T1 values and T2 values indicative of myocardial edema. However, our case further reinforces the literature suggesting that T2 values can be normal even in the setting of fulminant ICI-myocarditis, and a normal value should not dissuade the reader from diagnosing myocarditis in clinically suspected cases with other supportive CMR findings.

Figure 1: Delayed gadolinium enhancement pattern in the base (A), mid (B) and apical (C) cardiac segments