A 25-Year-Old Man with Refractory Schizophrenia and Clozapine-Induced Myocarditis Diagnosed by Non-Invasive Cardiovascular Magnetic Resonance

Abstract

BACKGROUND Clozapine, a second-generation antipsychotic, is often prescribed for refractory schizophrenia; however, it can cause life-threatening adverse events including agranulocytosis and myocarditis. Making the diagnosis of clozapine-induced myocarditis can be challenging given the non-specific presentation as well as risk involved in obtaining an endomyocardial biopsy. As clozapine-induced myocarditis carries a mortality risk of up to 30%, timely recognition, diagnosis, and management are vital. This report presents a case of clozapine-induced myocarditis in a 25-year-old man with refractory schizophrenia who was diagnosed using non-invasive imaging with cardiovascular magnetic resonance (CMR). CASE REPORT A 25-year-old man with refractory schizophrenia was admitted with severe psychotic symptoms and started on a rapid titration of clozapine. During his hospitalization he developed somnolence, fever, and tachycardia with leukocytosis, elevated inflammatory markers, and cardiac biomarkers concerning for clozapine-induced myocarditis. Alternative etiologies were ruled out and CMR was used to confirm the diagnosis. The patient's symptoms resolved following discontinuation of clozapine and initiation of supportive therapies. CONCLUSIONS Clozapine-induced myocarditis is challenging to diagnose due to a lack of consensus on diagnostic criteria, reliance on voluntary reporting, and non-specific presentation. This report highlights that myocarditis can be associated with clozapine pharmacotherapy in patients with schizophrenia and demonstrates the value of diagnosis using non-invasive CMR. Additional studies are needed to understand the mechanism of clozapine-induced myocarditis and how clozapine titration may affect risk.

Figure 1.

Electrocardiogram (EKG) while the patient experienced tachycardia without chest pain. EKG demonstrated sinus tachycardia with diffuse ST-segment elevations that were most prominent in the anteroseptal leads. These findings were concerning for ischemia versus pericarditis versus myocarditis.

Figure 2.

Cardiovascular magnetic resonance (CMR) demonstrates myocardial changes that reveal the diagnosis. (A) Late gadolinium enhancement CMR revealed acute myocarditis as evidenced by epicardial necrosis and edema of the middle and apical lateral wall (yellow arrowheads), as well as small foci of mid-myocardial necrosis in the apical septum (red arrowheads). (B) Direct T2 quantification confirmed the presence of myocardial edema indicative of acute ischemia in these regions, measuring 84.5±6.3 ms (Region 1), compared with 61.9±4.7 ms in healthy non-ischemic myocardium (Region 2). These findings support the diagnosis of clozapine-induced myocarditis.