Introduction: Clozapine is the most effective antipsychotic for refractory schizophrenia-spectrum disorders. While it is known for its risk of severe neutropenia, myocarditis is often overlooked. Clozapine-induced myocarditis (CIM) can include a range of symptoms in addition to elevated troponin and C-reactive protein (CRP). Rarely, CIM is associated with acute decompensated heart failure. CIM typically within two months of clozapine initiation and is most commonly reported in young males prescribed high clozapine doses and/or with rapid dose increase. We present a possible severe case of CIM and discuss important diagnostic considerations in CIM.
Description: A 36-year-old male on a stable dose of clozapine 600 mg nightly was admitted after becoming unresponsive on a hike. His family reported he had no complaints during the hike or in the preceding days. On presentation he was in shock and was cardioverted for unstable supraventricular tachycardia. Initial evaluation revealed fever, encephalopathy, thrombocytopenia, AKI, and elevated troponin. Infectious workup including lumbar puncture was negative. On hospital day 2 a TTE showed a dilated right ventricle with reduced systolic function and left ventricular ejection fraction of 25-30% and a clozapine level was obtained (804 ng/mL). Dobutamine was started after identification of biventricular disease. On hospital day 3 his CRP level was 123 mg/L. Over the next 3 days, the patient improved. On hospital day 6 a TTE was repeated with resolution of previous biventricular disease. A cardiac MRI was obtained on hospital day 8 and did not find evidence of myocarditis. Clozapine was held for the whole admission, and a repeat level on day 8 was 62 ng/mL. The patient was flown to his home country via critical care transport and follow-up information is being obtained.
Discussion: This case highlights the complexity of CIM in the setting of critical illness. This patient likely had CIM or stress cardiomyopathy (CM). Aspects supporting CIM include age, sex, high clozapine dose, fever, and high CRP, though high CRP is often seen in stress CM. The severity of illness and late onset of CIM are particularly unique. Precise techniques to assess for myocarditis on cardiac MRI are crucial, and imaging for this case may not have been adequate to identify myocarditis.
