Impairment of left ventricular function early in treatment with clozapine: a preliminary study

This preliminary prospective study evaluated cardiac status in 15 treatment-resistant schizophrenia patients (aged 18-55 years) without evidence of cardiovascular disease. Patients underwent clinical assessment, blood tests, ECG, and echocardiography before and during clozapine treatment for 4 weeks as doses increased from 25 to 100 mg/day. Serum concentrations of high-sensitivity C-reactive protein, troponin-I, brain natriuretic peptide, and clozapine+norclozapine were assayed at week 3; ECG and echocardiography were repeated at week 4. At moderate serum drug concentrations (124 ng/ml), the heart rate increased by 10% and high-sensitivity C-reactive protein levels were slightly elevated, but troponin-I and brain natriuretic peptide levels were not elevated. Echocardiographic indices indicated declining left ventricular (LV) diastolic and systolic function in 60-80% of participants, with an increase in systolic pulmonary artery pressure, A-wave velocity, and LV myocardial performance index by 16-24% in 60-80% of participants and a decrease in the E/A ratio by 29% in 73% of participants - all uncorrelated with drug concentrations. Early treatment with moderate doses of clozapine was associated with subclinical but substantial decreases in LV functioning in surprisingly high proportions of participants. Studies with more participants, higher drug doses, and long-term follow-up are needed to confirm and determine the course of the observed abnormalities and to evaluate their relationship with rare clinical cardiotoxicity associated with clozapine.