Successful Rechallenge of Clozapine Therapy Following Previous Clozapine-Induced Myocarditis Confirmed on Cardiac MRI

Abstract

[Author Affiliation]Vincent Chow. 1 Department of Cardiology, Concord Repatriation General Hospital and The University of Sydney, Sydney, Australia.Isabelle Feijo. 2 Walker Unit, Concord Centre for Mental Health, Sydney, Australia.Joseph Trieu. 3 Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia.Jean Starling. 2 Walker Unit, Concord Centre for Mental Health, Sydney, Australia.Leonard Kritharides. 1 Department of Cardiology, Concord Repatriation General Hospital and The University of Sydney, Sydney, Australia.Address correspondence to: Vincent Chow, MBBS, Department of Cardiology, Concord Repatriation General Hospital, Level 3 West, Hospital Road, Concord, NSW 2139, Australia, E-mail: vchow@optusnet.com.auTo The Editor:Clozapine is the most effective therapy in patients with treatment refractory schizophrenia (Meltzer et al. 2003). However, clozapine is associated with potentially fatal adverse effects, such as myocarditis and cardiomyopathy.The diagnosis of clozapine-induced myocarditis is challenging, and relies on the combination of clinical, electrocardiographic, echocardiographic, or biochemical changes indicative of myocardial damage and inflammation. In reported cases, myocardial biopsy was rarely performed to confirm the diagnosis of myocarditis. Recently, cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis (Friedrich et al. 2009).We describe the first adolescent case of CMRI-confirmed clozapine-induced myocarditis and subsequent successful clozapine rechallenge without recurrence of myocarditis, as evidenced by serial monitoring over 12 months with biochemistry and imaging modalities. The role of gradual dose escalation in permitting successful rechallenge is discussed.Case ReportWe describe a 15-year-old adolescent who was first diagnosed with schizophrenia in March 2011 after having exhibited increasingly disabling psychotic symptoms over a 3 year period prior to his formal diagnosis. From March 2011 to July 2011, he was trialed on multiple atypical antipsychotic medications with limited effect. He was commenced on clozapine in July 2011, according to a standardized protocol, and soon after starting clozapine, there was a significant improvement in his mental state.Fourteen days after the commencement of clozapine, he developed sinus tachycardia and experienced an episode of chest discomfort at rest, associated with nausea and vomiting. He was afebrile with heart rate of 110 beats per minute, and his electrocardiogram (ECG) revealed sinus rhythm with new T wave inversion in leads V4-V6. Troponin I 3.99 was elevated to nearly 40 times the upper limit of normal (reference range An urgent CMRI was performed, and revealed a focus of late gadolinium enhancement within the basal lateral wall of the left ventricle (LV) in the outer epicardial portion of the myocardium. This enhancement pattern is consistent with myocarditis. LV function remained normal with LV ejection fraction (LVEF) measured at 54% (Fig. 1A). A diagnosis of clozapine-induced myocarditis was made. Clozapine was ceased and Troponin I returned to normal within 48 hours. No further episodes of chest discomfort were noted. Viral serology and eosinophil counts were normal.FIG. 1. (A) Cardiac magnetic resonance imaging (CMRI) confirmed myocarditis with focus of late gadolinium enhancement (white) within the epicardial portion of the left ventricle (arrows). Subsequent CMRI performed prior to clozapine rechallenge (B) and 6 months following treatment rechallenge (D) revealed chronic scarring with no recurrence of myocarditis. (C) Serial biochemical, hemodynamic, electrocardiographic, and echocardiographic measurements confirmed no recurrence of myocarditis at 12 months following clozapine rechallenge. …