Does A Subclinical Cardiotoxic Effect of Clozapine Exist? Results from a Follow-up Pilot Study

Carlo      Rostagno; Sandro      Domenichetti; Gian      Franco Gensini

Abstract

Aim: The aim of the present study was to investigate by serial echocardiography and dosage of NT-pro-BNP, whether, in previously healthy subjects, long term therapy with clozapine may lead to subclinical cardiac toxicity.

Methods and Results: 38 patients (24 males, 14 females, mean age 38.4 years) suffering from a severe personality disorder were enrolled. At inclusion duration of clozapine treatment averaged 66 months at a mean daily dose of 296 mg. Clinical evaluation, NT-pro-BNP dosage and echocardiography were performed at baseline, 3 and 12 months.

At first visit 15 patients showed depression of left ventricular function (12 had LVEF between 50 and 55%, 2<50% and 1<30%). Biventricular dysfunction was observed in 10. NT-pro-BNP showed a significant inverse relation with LVEF (r2= -0.4619, p <0.0001). At 1 year the whole group did not show significant changes in clinical, ECG and echocardiographic measurement, however a LVEF decrease > 5% was found in 33% of patients with baseline normal LVEF while LVEF remained below 55% in 70% of group B patients. LVEF and NT-pro-BNP values were still significantly different in the two groups at the term of follow-up.

Conclusions: subclinical heart dysfunction, frequently biventricular, occurs in 1/3 of young, previously healthy, clozapine treated patients. NT-pro-BNP values relate inversely with LVEF. At 1 year follow –up a LVEF decrease >5% occurred in 1/3 of patients with baseline normal left ventricular function.

Keywords: Adverse effects, cardiomyopathy, clozapine, diastolic function, echocardiography, metabolic syndrome, NT-pro- BNP, QT interval, refractory schizophrenia, right ventricular function