title: Valvular heart disease associated with benfluorex therapy: results from the French multicentre registry.
abstract: OBJECTIVE
  The aim of this paper is to report clinical characteristics, consequences, echocardiographic features, and pathological findings encountered in patients suffering from valvular disease associated with benfluorex exposure in a multicentre French registry.
  
  
  RESULTS
  Forty patients suffering from unexplained restrictive valvular disease with a previous exposition to benfluorex, a fenfluramine derivative, were identified from eight French university hospitals. Patients were mostly women (87.5%) with a mean age of 57 ± 9 years and high body mass index of 30 ± 7 kg/m²; 37.5% of them presented with severe heart failure symptoms (NYHA class III and IV). Benfluorex mean daily dose was 415 ± 131 mg with total therapy duration of 72 ± 53 months. Resulting cumulative dose was 910 ± 675 g. Common echocardiographic findings were leaflets and sub-valvular apparatus thickening and retraction. Aortic and mitral valve regurgitations resulting from leaflets loss of coaptation were the most frequent findings (87.5 and 82.5%) and were severe in 29 patients (72.5%). Multiple valve involvements were present in 31 cases (77.5%). Pulmonary arterial hypertension was identified in 20 cases (50%). Histopathological examination demonstrated abundant extra cellular matrix encasing the leaflets without modification of valve architecture. Fifteen patients (37.5%) underwent valvular surgery.
  
  
  CONCLUSIONS
  Benfluorex-related valvulopathy shares numerous characteristics with other drug-induced valvular disease. Clinical consequences may be serious with severe heart failure symptoms that may lead to surgical treatment.
authors.affiliation: Department of Cardiology, University Hospital Brest, Brest, France. florent.le.ven@free.fr
authors.forename: Florent
authors.initials: F
authors.lastname: Le Ven
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
authors.forename: Gilbert
authors.initials: G
authors.lastname: Habib
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gueffet
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Maréchaux
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eicher
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Blanchard-Lemoine
authors.forename: Juliette
authors.initials: J
authors.lastname: Rousseau
authors.forename: Pierre
authors.initials: P
authors.lastname: Hénon
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jobic
authors.forename: Yves
authors.initials: Y
authors.lastname: Etienne
mesh_terms: D001067:Appetite Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D015992:Body Mass Index; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D017548:Echocardiography, Transesophageal; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005602:France / Q000453:epidemiology; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000601:surgery; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001067:Appetite Depressants; D005277:Fenfluramine; C001584:benfluorex