title: Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.
abstract: OBJECTIVE
  The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD.
  
  
  RESULTS
  This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001).
  
  
  CONCLUSIONS
  FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves.
authors.affiliation: INSERM U 1088, Université de Picardie, Amiens, France Université Lille Nord de France, GCS-Groupement des Hôpitaux de l'Institut Catholique de Lille/Faculté de médecine et de maïeutique, Université Catholique de Lille, Lille 59000, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Maréchaux
authors.affiliation: Pôle cardiovasculaire et thoracique, Centre Hospitalier Universitaire Amiens, Amiens, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Rusinaru
authors.affiliation: Département de Cardiologie, Hôpital de la Cavale Blanche, Brest 29609, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jobic
authors.affiliation: Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris VI, Service de Cardiologie, Paris 75012, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ederhy
authors.affiliation: Service de Cardiologie et Maladies Vasculaires et CIC-IT 804, LTSI INSERM U 642, Centre Hospitalier Universitaire Rennes, Hôpital Pontchaillou, Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Donal
authors.affiliation: Hôpital Cardiologique Haut - Lévêque, Centre Hospitalier Universitaire de Bordeaux, CIC0005, Pessac 33604, France Université Bordeaux 2, Bordeaux 33000, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Réant
authors.affiliation: Service de Médecine Interne et Cardiologie, Centre Hospitalier de Beauvais, Beauvais 60021, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Arnalsteen
authors.affiliation: Centre Hospitalier de Compiègne, Service de Cardiologie, Compiègne 60200, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Boulanger
authors.affiliation: Hôpital Universitaire G et R Laennec, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Garban
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Hôpital cardiologique, Lille 59037, France.
authors.forename: Pierre-Vladimir
authors.initials: PV
authors.lastname: Ennezat
authors.affiliation: Pôle cardiovasculaire et thoracique, Centre Hospitalier Universitaire Amiens, Amiens, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Jeu
authors.affiliation: INSERM U 1088, Université de Picardie, Amiens, France Pôle cardiovasculaire et thoracique, Centre Hospitalier Universitaire Amiens, Amiens, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Szymanski
authors.affiliation: INSERM U 1088, Université de Picardie, Amiens, France Pôle cardiovasculaire et thoracique, Centre Hospitalier Universitaire Amiens, Amiens, France tribouilloy.christophe@chu-amiens.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
mesh_terms: D000368:Aged; D001067:Appetite Depressants / Q000009:adverse effects*; D016022:Case-Control Studies; D015150:Echocardiography, Doppler / Q000379:methods*; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000031:analogs & derivatives*; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000145:classification / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001067:Appetite Depressants; D005277:Fenfluramine; C001584:benfluorex
keywords: Drugs; Echocardiography; Valvular heart disease