Benfluorex and Unexplained Valvular Heart Disease: A Case-Control Study

BACKGROUND: Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. METHODS: We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. RESULTS: Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. CONCLUSION: The use of benfluorex is associated with unexplained mitral regurgitation

Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.

International audienceBACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. METHODS AND RESULTS: This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation. CONCLUSIONS: Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research

Contemporary Management of Severe Symptomatic Aortic Stenosis

There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS).This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey.Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention.A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age-adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001).A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians

Evaluation par Color Kinesis des conséquences d'un bloc de branche gauche complet sur la cinétique ventriculaire gauche en systole et en diastole

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'échographie cardiaque peut-elle remplacer le cathétérisme cardiaque droit dans l'évaluation des résistances vasculaires pulmonaires ?

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Communication inter auriculaire ostium secundum : comparaison entre la fermeture percutanée et la chirurgie

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Comparaison par Color Kinesis de la cinétique ventriculaire gauche avant et après stimulation gauche

Le bloc de branche gauche (BBG) entraîne une désynchronisation inter ventriculaire et intra ventriculaire gauche (VG) susceptible d'être délétère chez les patients porteurs d'une cardiomyopathie dilatée (CMD). La resynchronisation ventriculaire par la stimulation gauche permet d'améliorer l'état fonctionnel de ces patients. Notre étude utilise le Color Kinesis (CK), technique d'imagerie échographique validée, pour analyser l'amplitude et la chronologie du déplacement de l'endocarde avant et après la stimulation gauche. 12 patients d'âge moyen 68.6+-2.8 ans porteurs d'une CMD avec BBG en stade III et IV de la NYHA ont bénéficié d'un CK avant stimulation gauche et un mois après, en systole et en diastole, en coupe apicale 4 cavités. Nous avons étudié des paramètres de fonction globale (fraction de raccourcissement de surface, temps moyen d'éjection et de remplissage, pic de vitesse, temps au pic) et de fonction régionale (fraction de raccourcissement de surface segmentaire, temps moyen d'éjection et de remplissage segmentaire, pourcentage d'éjection et de remplissage segmentaire). Nous avons défini quatre index par les rapports des mesures CK de la paroi septale sur la paroi latérale : index d'amplitude et de déplacement, index de temps moyen, index d'asynchronisme d 'éjection ou de remplissage, écart-type de la moyenne du pourcentage d'éjection ou de remplissage des six segments à 25% et à 50% de la systole ou de la diastole. Le CK objective des modifications significatives de la cinétique globale et segmentaire du VG après stimulation gauche, notamment une amélioration de ces paramètres en systoleAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

[Letter on the article: "benfluorex and valvular heart disease"].

International audienc

Mitral and aortic valvular disease associated with benfluorex use.

International audienceFenfluramine has been associated with an increased risk of pulmonary hypertension and valvular disease. Benfluorex is a fenfluramine derivative approved for the treatment of metabolic syndrome and type 2 diabetes mellitus. To date, only three isolated clinical cases of valvular disease and two recent case-control studies have been reported in patients exposed to benfluorex. Herein, the case is described of a patient with mitral and aortic valvular disease, with both echocardiographic and histopathological findings, who had been receiving benfluorex for several years, without any other etiology of valvular disease. The case is suggestive of toxic valvular lesions, similar to those observed previously during treatment with fenfluramine, pergolide, and cabergolide