title: Asymptomatic left ventricular dysfunction with long-term clozapine treatment for schizophrenia: a multicentre cross-sectional cohort study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Asymptomatic mild LV impairment is common in patients with schizophrenia receiving long-term clozapine treatment and is associated with neutrophilia and low HDL-C.
authors.affiliation: Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia ; ANZAC Medical Research Institute , Sydney, New South Wales , Australia.
authors.forename: V
authors.initials: V
authors.lastname: Chow
authors.affiliation: Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia ; Department of Cardiology , Canterbury Hospital, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: T
authors.initials: T
authors.lastname: Yeoh
authors.affiliation: Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: A C C
authors.initials: AC
authors.lastname: Ng
authors.affiliation: Department of Psychiatry , Croydon Health Centre , Sydney, New South Wales , Australia.
authors.forename: T
authors.initials: T
authors.lastname: Pasqualon
authors.affiliation: School of Medicine, Notre Dame University, Sydney, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Scott
authors.affiliation: Department of Psychiatry , Croydon Health Centre , Sydney, New South Wales , Australia.
authors.forename: J
authors.initials: J
authors.lastname: Plater
authors.affiliation: National Youth Mental Health Foundation, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: B
authors.initials: B
authors.lastname: Whitwell
authors.affiliation: Department of Cardiology , Canterbury Hospital, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: D
authors.initials: D
authors.lastname: Hanzek
authors.affiliation: Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: T
authors.initials: T
authors.lastname: Chung
authors.affiliation: Department of Cardiology , Liverpool Hospital, University of New South Wales , Sydney, New South Wales , Australia.
authors.forename: L
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Cardiology , Royal Prince Alfred Hospital, The University of Sydney , Sydney, New South Wales , Australia.
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
authors.affiliation: Department of Cardiology , Concord Hospital, The University of Sydney , Sydney, New South Wales , Australia ; ANZAC Medical Research Institute , Sydney, New South Wales , Australia.
authors.forename: L
authors.initials: L
authors.lastname: Kritharides