## Clozapine-Induced Myocarditis and Cardiomyopathy **Key Point:** Clozapine carries a risk of myocarditis and dilated cardiomyopathy, particularly in the first 2 weeks of therapy. This is a serious, potentially life-threatening adverse effect that mandates cardiac monitoring. ### Mechanism and Epidemiology Clozapine-induced myocarditis is thought to result from: - Direct toxic metabolite formation - Hypersensitivity reaction - Immune-mediated inflammation Incidence: ~0.7–1.2% of clozapine-treated patients; mortality if untreated can be significant. ### Clinical Presentation and Monitoring | Finding | Timing | Action | |---|---|---| | Chest pain, dyspnea, palpitations | First 2 weeks (peak risk) | **Stop clozapine immediately** | | Elevated troponin, BNP | Early phase | Cardiology consult, echocardiogram | | Cardiomegaly on imaging | Weeks 2–8 | Assess for dilated cardiomyopathy | | Fulminant heart failure | Rare but severe | ICU management; consider LVAD/transplant | **High-Yield:** Clozapine is the only antipsychotic with a black-box warning for myocarditis. Baseline ECG and troponin are recommended before initiation. Weekly troponin monitoring for the first 4 weeks is standard practice in many centers. **Warning:** Do NOT confuse clozapine myocarditis with QT prolongation (seen with haloperidol, risperidone, ziprasidone). Myocarditis is an inflammatory/toxic process; QT prolongation is an electrophysiologic effect. **Clinical Pearl:** Clozapine is still used despite this risk because of its superior efficacy in treatment-resistant schizophrenia and its low EPS profile. The benefit-risk ratio must be carefully weighed, and cardiac monitoring is non-negotiable. **Mnemonic:** **CLOZ-CARDIAC**: **C**lozapine, **L**ife-threatening, **O**ften early, **Z**ero tolerance → **C**ardiac monitoring mandatory, **A**cute troponin rise, **R**apid cessation, **D**ilated cardiomyopathy risk, **I**nflammatory mechanism, **A**void rechallenge, **C**ardiomyopathy surveillance. [cite:Harrison 21e Ch 397]
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