Acute Myocarditis by Immune Checkpoint Inhibitor Identified by Quantitative Pixel-Wise Analysis of Native T1 Mapping

A 73-year-old man with intrahepatic bile duct cancer was treated with nivolumab, an immune checkpoint inhibitor (ICI), at a cancer center.Although he was asymptomatic, his serum creatine kinase (CK) level was elevated to 1485 mg/dL, and he was positive for troponin T on routine blood testing.Therefore, this patient was transferred to our hospital for the diagnosis and treatment of ICI myocarditis.In the ECG, ST-segment depression and negative T waves were observed in V2-6 leads (Figure 1).The left ventricular wall motion was normal with an ejection fraction of 65%.At the time of admission, blood test showed a CK level of 715 mg/ dL, CK-MB level of 52 mg/dL, and troponin T level of 0.115 ng/mL.Cardiac magnetic resonance imaging (MRI) was performed to screen for ICI myocarditis.Although there was no hyperenhancement on late gadolinium-enhanced MRI, slight hyperenhancement was suspected in the anteroseptal wall on black-blood T2-weighted MRI, suggesting myocardial edema (Figure 2).On T1 mapping images, native T1 time and extracellular volume fraction (ECV) were elevated in the anteroseptal wall on quantitative pixel-wise analysis using a commercially available software (Ziostation, Ziosoft Inc, Tokyo, Japan; Figure 2).These abnormalities presumably corresponded to myocardial edema, therefore, the definitive diagnosis was of ICI myocarditis.After admission, we started the infusion of corticosteroid (sodium methylprednisolone succinate 500 mg/d).After tapering the amount of corticosteroid, CK and CK-MB were elevated again on day 3, so we increased the amount of corticosteroid again.During the clinical course, native T1 mapping was repeated on day 16.The native T1 time of the anteroseptal wall decreased to normal value on day 16 (Figure 3).ST-segment depression and negative T waves in lead V2-6 improved after steroid therapy.The patient's condition improved, and the patient was transferred to his former hospital to continue the treatment for intrahepatic bile duct cancer.Nivolumab is a novel drug for malignant tumors that promotes the attack of cancer cells by lymphocytes by suppressing the expression of programmed cell death-1 on the cell surface of cancer cells. 1 Treatment with nivolumab is known to cause several immune-related adverse events, including thyroid dysfunction, colitis, pneumonitis, type 1 diabetes, Guillain-Barré syndrome, and myasthenia gravis.However, the frequency of myocarditis is very rare, with an incidence of 0.06%. 2 Although its probability of occurrence is not high, myocarditis cannot be ignored as it can lead to a fatal outcome.Therefore, an accurate and noninvasive diagnostic method would be desirable for the clinical management of patients treated with nivolumab.Cardiac MRI is an established method for diagnosing acute myocarditis.The Lake Louise Criteria, established in 2009, are the recommended cardiac MRI criteria for diagnosing patients with suspected myocarditis. 3Lake Louise Criteria use tissuebased MRI markers consisting of T2-weighted ratio and early and late gadolinium enhancement.However, one of the limitations of these criteria is the need for gadolinium contrast media.Therefore, this method cannot be applied in patients Acute Myocarditis by Immune Checkpoint Inhibitor Identified by Quantitative Pixel-Wise Analysis of Native T1 Mapping CARDIOVASCULAR IMAGES