Asymptomatic left ventricular dysfunction with long-term clozapine treatment for schizophrenia: a multicentre
1Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia ; ANZAC Medical Research Institute , Sydney, New South Wales , Australia.
Insights
Long-term clozapine treatment for schizophrenia is linked to subclinical heart muscle impairment. This condition, characterized by reduced left ventricular ejection fraction and global longitudinal strain, is associated with elevated neutrophil counts and low high-density lipoprotein cholesterol.
Area of Science:
- Cardiology
- Psychiatry
- Pharmacology
Background:
- Clozapine is a crucial antipsychotic for schizophrenia but carries risks of myocarditis and cardiomyopathy.
- Subclinical cardiomyopathy prevalence and associations in clozapine-treated patients remain understudied.
Purpose of the Study:
- To investigate the prevalence of subclinical cardiomyopathy in schizophrenia patients on long-term clozapine.
- To identify associations between subclinical cardiomyopathy and clinical/biochemical factors in these patients.
Main Methods:
- Compared 100 clozapine-treated schizophrenia patients (group 1) with controls on non-clozapine antipsychotics (group 2) and healthy controls (group 3).
- Utilized clinical examination, ECG, echocardiography (LVEF, GLS), and biochemical profiling.
- Analyzed associations using univariate and multivariable analyses.
Main Results:
- Clozapine patients showed globally impaired left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) compared to controls.
- Metabolic syndrome features, elevated neutrophil count, and low HDL-C were associated with impaired LV function in clozapine users.
- Elevated neutrophil count and low HDL-C independently predicted impaired GLS in clozapine-treated patients.
Conclusions:
- Asymptomatic, mild left ventricular impairment is common in schizophrenia patients on long-term clozapine.
- This impairment is associated with neutrophilia and low HDL-C, suggesting potential targets for monitoring and intervention.
Objectives:
Patients with schizophrenia treated with clozapine are at risk of acute myocarditis and dilated cardiomyopathy. However, there are no data on the prevalence of subclinical cardiomyopathy or its associations.
Methods:
100 consecutive patients with schizophrenia treated with clozapine for >1 year and without a history of cardiac pathology (group 1), 21 controls with a history of schizophrenia treated with non-clozapine antipsychotics for >1 year (group 2) and 20 controls without schizophrenia (group 3) were studied. Comprehensive evaluation by clinical examination, ECG, transthoracic echocardiography including left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) and biochemical profiles were performed.
Results:
Patients with schizophrenia were of similar age, but had higher body mass index (BMI), rates of smoking and hyperlipidaemia than controls. Patients with schizophrenia had received clozapine or non-clozapine antipsychotics for a mean duration of 6.8±5.3 and 9.7±6.1 years, respectively. Patients taking clozapine demonstrated globally impaired LVEF (58.3%: group 1 vs 62.2%: group 2 vs 64.8%: group 3, p<0.001) and GLS (-16.7%: group 1 vs -18.6%: group 2 vs -20.2%: group 3, p<0.001). Moreover, LVEF was <50% in 9/100 (9%) patients receiving clozapine and in non-clozapine schizophrenia patients or healthy controls, but this was not statistically significantly different (analysis of covariance, p=0.19). Univariate analysis in patients taking clozapine found that impaired LV was not predicted by high-sensitivity troponin T, but was associated with features of the metabolic syndrome (including increased triglycerides, low high-density lipoprotein cholesterol (HDL-C), high-sensitivity C reactive protein and BMI), elevated neutrophil count, elevated heart rate, smoking and N-terminal probrain natriuretic peptide. In patients taking clozapine, multivariable analysis identified elevated neutrophil count and low HDL-C as the only independent predictors of impaired GLS.
Conclusions:
Asymptomatic mild LV impairment is common in patients with schizophrenia receiving long-term clozapine treatment and is associated with neutrophilia and low HDL-C.
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