Late onset myocarditis with clozapine use

To the Editor

Myocarditis is a serious complication of clozapine therapy with a reported incidence between 0.7% to 1.2% (Layland et al., 2009). The majority of cases occur within two months of commencement (Layland et al., 2009) with occasional reports after long-term therapy (Lang et al., 2008). The exact mechanism underlying clozapine-related myocarditis is unknown. Hypotheses include: IgE-mediated hypersensitivity, increased plasma catecholamine, cytochrome P450 1A2 enzyme deficiency, blockade of calcium-dependent ion channels, increased production of inflammatory cytokines, and low serum selenium levels (Layland et al., 2009).

We report two cases of myocarditis after long-term clozapine therapy identified during routine monitoring.

Mr R, a 62-year-old male nursing home resident, was treated with clozapine (500mg/day) from 1997 for schizophrenia. He has a background of diabetes, hyperlipidaemia and peripheral vascular disease. He presented with lethargy, temperature of 38.3º C, CRP 200mg/L and troponin T 276ng/L. Serial ECG showed T wave inversion with variable broadening of QRS complex. His echocardiogram revealed moderate systolic dysfunction and ejection fraction of 33% with global hypokinesis. A diagnosis of clozapine-induced myocarditis was made after excluding alternative aetiologies. Clozapine was ceased and he was commenced on olanzapine 5mg. He made good clinical recovery and was discharged two weeks later but died seven weeks later due to renal failure.

Mr S, a 52-year-old male with a 24-year history of schizophrenia was treated on 500mg/day of clozapine since 2009. His clozapine levels ranged from 146-910µg/L suggesting long-term partial compliance. His medical history includes hyperlipidaemia and diabetes. He presented with a two-week history of exertional dyspnoea without chest pain. ECG showed new onset atrial flutter 2:1 with sinus tachycardia, troponin T 294ng/L, CRP 25mg/L. Echocardiogram revealed systolic dysfunction with an ejection fraction of 35% and global hypokinesis. He was diagnosed with myocarditis secondary to clozapine. Clozapine was ceased, and olanzapine 10mg was initiated. He was discharged home one week later following clinical recovery. His cardiac condition remains stable four months after discharge.

These cases meet the criteria for clozapine-related myocarditis but occur outside the initial high-risk period following commencement (Ronaldson et al., 2010) suggesting the need for ongoing clinical vigilance for symptoms suggestive of myocarditis for the duration of clozapine treatment. Suspicion should lead to prompt investigation with troponin T, CRP and ECG to facilitate early identification and treatment of myocarditis.