title: Drug-induced aortic valve stenosis: An under recognized entity.
abstract: BACKGROUND
  We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS.
  
  
  METHODS
  Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria.
  
  
  RESULTS
  Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD.
  
  
  CONCLUSIONS
  The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Centre Hospitalier Universitaire de Grenoble, France. Electronic address: ennezat@yahoo.com.
authors.forename: Pierre-Vladimir
authors.initials: PV
authors.lastname: Ennezat
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris-Descartes University, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Institut Mutualiste Montsouris, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Czitrom
authors.affiliation: Department of Cardiology and Vascular Diseases, Institut du Thorax, Centre Hospitalo Universitaire de Nantes, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gueffet
authors.affiliation: Department of Cardiology and Vascular Diseases, Institut du Thorax, Centre Hospitalo Universitaire de Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Piriou
authors.affiliation: Department of Cardiology and Vascular Diseases, Institut du Thorax, Centre Hospitalo Universitaire de Nantes, France.
authors.forename: Jean Noël
authors.initials: JN
authors.lastname: Trochu
authors.affiliation: Nouvelles Cliniques Nantaises, Nantes, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Patra
authors.affiliation: Baron Cardiology Office, Orléans, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Blanchard-Lemoine
authors.affiliation: Baron Cardiology Office, Orléans, France.
authors.forename: Xavier Halna
authors.initials: XH
authors.lastname: du Fretay
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire de Reims, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Nazeyrollas
authors.affiliation: Department of Cardiology, Clinique Pasteur, Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Assoun
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire de Brest, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jobic
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire Bichat, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Brochet
authors.affiliation: Echocardiography laboratory, Clinique Saint-Augustin, Bordeaux, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bogino
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire de Bordeaux, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Roudaut
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Centre Hospitalier Universitaire de Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Augier
authors.affiliation: Department of Cardiology, Centre Hospitalier Victor Provo de Roubaix, France.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Greffe
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire de Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Petit-Eisenmann
authors.affiliation: Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Dambrin
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Centre Hospitalier Universitaire de Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chavanon
authors.affiliation: Department of Cardiovascular Surgery, Clinique Saint Martin, Caen, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Guillou
authors.affiliation: Department of Cardiovasculaire Surgery, Centre Hospitalier Universitaire La Timone, Marseille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Grisoli
authors.affiliation: Department of Cardiovasculaire Surgery, Centre Hospitalier Universitaire La Timone, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Morera
authors.affiliation: Division of Cardiovascular Surgery, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Banfi
authors.affiliation: Department of Cardiovascular Surgery, Centre Hospitalier Universitaire d'Amiens, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remadi
authors.affiliation: GCS-Artois Cardiovascular surgery, Hôpital privé de Bois Bernard, Centre Hospitalier de Lens, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fabre
authors.affiliation: Department of Cardiovascular Surgery, Centre Hospitalier Régional Universitaire de Lille, France.
authors.forename: André
authors.initials: A
authors.lastname: Vincentelli
authors.affiliation: Department of Biopathology-MESOPATH, Centre de Lutte Contre le Cancer Léon Bérard, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lantuejoul
authors.affiliation: Department of Pathology, Centre Hospitalier Universitaire d'Amiens, France.
authors.forename: Jean-Fortuné
authors.initials: JF
authors.lastname: Ikoli
authors.affiliation: Department of Pathology, Université de Lille, CHU de Lille, Faculté de Médecine, F-59000 Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, Institut Mutualiste Montsouris, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Malergue
authors.affiliation: Department of Cardiology, Groupement des Hôpitaux de l'Institut Catholique de Lille, Faculté libre de médecine / Université Catholique de Lille, France and INSERM U 1088, Amiens, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Maréchaux
authors.affiliation: Department of Cardiology, Centre Hospitalier Universitaire d'Amiens and INSERM U 1088, Amiens, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects* / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008784:Methysergide / Q000009:adverse effects*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D005277:Fenfluramine; C001584:benfluorex; D008784:Methysergide
keywords: Aortic stenosis; Benfluorex; Drug induced-valvular heart disease; Fenfluramin derivatives