Valvular heart disease associated with benfluorex therapy: results from the French multicentre registry

Eur J Echocardiogr. 2011 Apr;12(4):265-71. doi: 10.1093/ejechocard/jeq172. Epub 2010 Dec 30.

Abstract

Aims: 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.

Methods and 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.

Conclusion: 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.

Publication types

  • Multicenter Study

MeSH terms

  • Appetite Depressants / administration & dosage
  • Appetite Depressants / adverse effects*
  • Body Mass Index
  • Comorbidity
  • Dose-Response Relationship, Drug
  • Echocardiography, Transesophageal
  • Female
  • Fenfluramine / administration & dosage
  • Fenfluramine / adverse effects
  • Fenfluramine / analogs & derivatives*
  • France / epidemiology
  • Heart Valve Diseases / chemically induced*
  • Heart Valve Diseases / diagnostic imaging*
  • Heart Valve Diseases / epidemiology
  • Heart Valve Diseases / surgery
  • Humans
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / epidemiology
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome

Substances

  • Appetite Depressants
  • Fenfluramine
  • benfluorex