clozapine and Ventricular-Dysfunction--Left

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.. 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.. 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.

Topics: Adult; Antipsychotic Agents; Clozapine; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Personality Disorders; Pilot Projects; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right

Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment.. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion.. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment.. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

Topics: Adult; Antipsychotic Agents; Cardiotoxicity; Clozapine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Schizophrenia; Ventricular Dysfunction, Left

Clozapine is considered as a strong psychopharmaceutic agent in symptom control of psychotic disturbances. However, possible side effects to hematologic, metabolic and cardiologic systems are still entailing a defensive application in psychiatric praxis.. A patient suffering from schizoaffective disorder clinically developed symptoms of cardial disturbances under the psychopharmacotherapy of Clozapine. Specific laboratory analysis and technical procedures were applied, clarifying the background of this serious event.. ECG and specific myocardial enzymes (CK, Troponine-I) requesting an acute myocardial infarction were negative. Specific laboratory analysis revealed positive inflammation markers with elevated C-reactive protein and interleukin-6. Additionally, there was increasing of TNF-alpha and C3 as well as an eosinophilia at differential blood cell count. Echocardiography found an unspecific dyskinesia of the left ventricle, but contrast-enhanced cardial MRI showed structural intramyocardial inhomogeneities suggesting a myocarditis.. In spite of the striking psycho-pharmacotherapeutic benefit, Clozapine may be associated with serious cardial events. We discuss these cardiological problems in association to a Clozapine therapy in regard to its clinical relevance in treatment of psychotic disturbances.

Topics: Adult; Antipsychotic Agents; Clozapine; Crisis Intervention; Dangerous Behavior; Delusions; Dose-Response Relationship, Drug; Humans; Male; Myocarditis; Patient Admission; Psychotic Disorders; Ventricular Dysfunction, Left

Available information regarding clozapine-related cardiomyopathy is limited to reports of severe left ventricular dysfunction not rarely with fatal clinical evolution. A subclinical cardiotoxic effect might be diagnosed using echocardiography and N-terminal pro-B-type natriuretic peptide assay.. Thirty-eight patients with psychotic disorder in chronic therapy with clozapine (24 male and 14 female subjects; mean age, 38.4 years) were enrolled. Left ventricular ejection fraction (LVEF) was measured by area-length method (average of 5 measurements).. Twelve patients showed a mild depression of left ventricular function (LVEF between 50% and 55%), 2 LVEF less than 50% and 1 less than 30%. The area under the receiver operating characteristic curve for N-terminal pro-B-type natriuretic peptide as a predictor of left ventricular dysfunction was 0.87.. A subclinical left ventricular dysfunction was found in 3 of 38 patients, whereas a mild impairment of the left ventricular systolic function occurred in 1 of 3 of young, previously healthy, clozapine-treated patients A prospective study in clozapine-naive patients may be useful to better understand cardiotoxic effects of clozapine.

Topics: Adult; Antipsychotic Agents; Biomarkers; Cardiomyopathies; Clozapine; Female; Humans; Male; Mental Disorders; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ultrasonography; Ventricular Dysfunction, Left