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OBJECTIVE To review the published literature on clozapine associated cardiotoxicity (CACT), summarize diagnostic features, and evaluate monitoring procedures for safe clozapine re-challenge. RESULTS Clozapine-associated Myocarditis (CAM) - Incidence of early myocarditis (≤2 months) is infrequent but serious. Clinical diagnosis is confounded by variability in presentation and non-specificity of symptoms. Re-challenge considerations include clozapine impact on symptomatic severity and associated disability and risk of suicidality. Re-challe