title: Does a subclinical cardiotoxic effect of clozapine exist? Results from a follow-up pilot study.
abstract: OBJECTIVE
  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.
  
  
  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 < 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.
authors.affiliation: Dipartimento Area Critica, Università di Firenze, Firenze, Italy. c.rostagno@katamail.com
authors.forename: Carlo
authors.initials: C
authors.lastname: Rostagno
authors.forename: Sandro
authors.initials: S
authors.lastname: Domenichetti
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010554:Personality Disorders / Q000188:drug therapy; D010865:Pilot Projects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000175:diagnosis; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced* / Q000175:diagnosis; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine