1351432 - (Psycho)analyzing Suspected Clozapine-Induced Myocarditis

A 21-year-old male with a past medical history significant for schizophrenia presented to the hospital from a psychiatric facility with a two-day history of progressively worsening pressure-like substernal chest pain. This chest pain occurred at rest and on exertion, was worse with inspiration, and was associated with nausea and diaphoresis. The patient denied having any recent viral prodrome, sick contacts, or gastrointestinal symptoms. There was no known family history of cardiomyopathy or sudden cardiac death, and his social history was negative for smoking, alcohol, and drug use. Further medication review was significant for a recent initiation of Clozapine two weeks before presentation. In the emergency department, his heart rate was 89 bpm, his blood pressure was 117/70 mmHg, and his SaO2 was 99% on room air. Labs were significant for a Troponin T of 898 ng/L, mild eosinophilia, erythrocyte sedimentation rate of 69 mm/hr, C-reactive protein 8.20 mg/dl, and a negative urine toxicology screen. Chest X-ray revealed no acute pathology and an electrocardiogram on presentation showed QTc prolongation. Further transthoracic echocardiogram imaging revealed an ejection fraction of 34% with new onset global hypokinesis without regional variation. Blood cultures, viral panel, COVID -19, HIV testing, Coxsackie antibody panel, enterovirus assay, Lyme IgM, and Lyme DNA RT-PCR were negative. There was a high suspicion for myocarditis secondary to clozapine therapy. With the help of psychiatry colleagues, clozapine was discontinued, and he was initiated on olanzapine.

Diagnostic Techniques and Their Most Important Findings:

Cardiac MRI was pursued which revealed patchy areas of mid myocardial and epicardial enhancement, more prominent along the mid to lateral wall of the left ventricle with the corresponding edema on T2-weighted imaging, consistent with a sequela of myocarditis (images 1,2,3).

Learning Points from this Case:

Given the temporal relationship between initiation of Clozapine, patient’s presentation, and cardiac MRI findings, the leading differential was concluded to be Clozapine-induced myocarditis. Clozapine-induced myocarditis is a rare side-effect associated with clozapine use and is proposed to be a type-1 drug hypersensitivity reaction due to cardiotoxic metabolites of clozapine. Limited case report data shows that over 50% of cases were seen within the first fourteen days of clozapine treatment and 62% of cases were associated with eosinophilia, both of which were seen in this patient. Treatment includes drug discontinuation and initiation of goal-directed medical therapy for heart failure. This case demonstrates the diagnostic utility of cardiac MRI imaging in tissue characterization and identifying myocarditis. As the only non-invasive test that was able to clinch the diagnosis and help identify the etiology of this patient’s acute chest pain presentation, cardiac MRI imaging allowed for prompt pathology recognition and treatment management.