• Shanathan Sritharan, Kindelan Murray, Dominic Lam, Daniel Wittaker, Aaron Sverdlov, Andrew Boyle, Allan Davies, Trent Williams, and Nicholas Collins.
• Cardiology Department, John Hunter Hospital Newcastle, Newcastle, New South Wales, Australia.
• Intern Med J. 2025 Jan 8.

BackgroundClozapine has demonstrated superiority in improving both positive and negative symptoms of treatment-resistant schizophrenia; however, there are associated treatment-limiting side effects, including myocarditis, cardiomyopathy and agranulocytosis.AimThis retrospective cohort study describes the prevalence of myocarditis, left ventricular (LV) dysfunction, cardiovascular risk factors and outcomes in a cohort of patients maintained on clozapine therapy.MethodsData were retrospectively collated from patients who had a diagnosis of schizophrenia, had been managed with clozapine at any stage during their care and undergone at least one echocardiogram.ResultsBetween March 2020 and September 2021 674 patients were identified, 71% were male, with a mean age of 47 years old (interquartile range (IQR) 40-57). The mean duration of clozapine use was 7 years (IQR 4-13). The overall mortality was 5.54% during the follow-up period. Myocarditis was identified in one patient (0.15%) within the first 30 days, and an additional five cases were identified over the follow-up period (0.89%). The combined incidence of heart failure (HF) and myocarditis was 1.6% during the follow-up period. There was no association between LV size and function at baseline or during follow-up and adverse cardiac outcomes (comprising death, myocarditis, HF). Older age at initiation of therapy and baseline E/e' ratio were associated with risk of HF and myocarditis.ConclusionThe overall incidence of myocarditis and HF during follow-up was low, with surveillance echocardiography offering limited predictive value. Patients maintained on clozapine are at risk of significant cardiovascular sequelae, likely reflecting an adverse risk factor profile.© 2025 Royal Australasian College of Physicians.

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