Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study

Sylvestre Maréchaux (1, 2) , Dan Rusinaru (3) , Yannick Jobic (4) , Stephane Ederhy (5) , Erwan Donal (6, 7) , Patricia Réant (8) , Elise Arnalsteen (9) , Jacques Boulanger (10) , Thierry Garban (11) , Pierre-Vladimir Ennezat (12) , Antoine Jeu (3) , Catherine Szymanski (3, 2) , Christophe Tribouilloy (2)

1 Groupement Hospitalier de l'Institut Catholique de Lille
2 Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux
3 Pôle cardiovasculaire et thoracique
4 CHRU - Cardio - Département de Cardiologie
5 Service de Cardiologie [CHU Saint-Antoine]
6 Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes]
7 LTSI - Laboratoire Traitement du Signal et de l'Image
8 Département de cardiologie
9 Service de Médecine Interne et Cardiologie
10 Service de Cardiologie
11 Hôpital Universitaire G et R Laennec
12 Service de cardiologie

Aims 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. Methods and 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

Keywords: Drugs; Echocardiography; Valvular heart disease

Domains: Life Sciences [q-bio]; Bioengineering

Sylvestre Maréchaux, Dan Rusinaru, Yannick Jobic, Stephane Ederhy, Erwan Donal, et al.. Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study. European Heart Journal - Cardiovascular Imaging, 2015, 16 (2), pp.158--165. ⟨10.1093/ehjci/jeu212⟩. ⟨hal-01260660⟩