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International audienceBACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions.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

Caractéristiques et pronostic des patients présentant une endocardite infectieuse associée à une spondylodiscite

Introduction : L association d une endocardite infectieuse à une spondylodiscite peut se rencontrer en pratique courante. Toutefois, les caractéristiques et le pronostic de ces patients restent peu décrits dans la littérature. Objectifs : Déterminer les caractéristiques cliniques et paracliniques de l endocardite infectieuse associée à une spondylodiscite et en évaluer son pronostic. Déterminer des facteurs prédictifs de survenue d une spondylodiscite en cas d endocardite infectieuse. Méthode : Etude de cohorte sur 418 patients consécutifs atteints d une endocardite infectieuse, inclus entre janvier 1990 et avril 2009 au CHU d Amiens. Résultats : Les patients présentant une endocardite associée à une spondylodiscite ont une tendance à être plus âgé (67+-11 ans vs 62+-15 ans ; p=0,084). Ils ne semblent pas présenter un surcroît de complications de l endocardite en dehors d une tendance à plus d embolies spléniques (32% vs 16% ; p=0,07). En revanche, la durée moyenne d hospitalisation est significativement allongée (45+-29 jours vs 34+-22 jours ; p=0,029). Les germes retrouvés chez les patients présentant une endocardite infectieuse associée à une spondylodiscite étaient : streptocoque bovis (59%), streptocoque milleri (5%), staphylocoque doré (9%), staphylocoque à coagulase négative (9%), entérocoque (18%). Aucune rechute de spondylodiscite n a été observée. Le recours à une chirurgie précoce de l endocardite tend à être moins fréquent en présence d une spondylodiscite mais de façon non significative (18% versus 35%; p=0,11). Les facteurs prédictifs indépendants de survenue d une spondylodiscite au cours de l endocardite infectieuse sont la présence d un streptocoque bovis (OR 8,17 ; IC 95% 3,2 20,8 ; p<0,001) et la durée plus longue des symptômes avant le diagnostic de l endocardite (OR 1,006 ; IC 95% 1,001 1,012 ; p=0,024). La mortalité hospitalière des endocardites associées à une spondylodiscite est comparable à celle des endocardites sans spondylodiscite (13,6% vs 18,8% ; p=0,78). La survie à un an de l endocardite infectieuse compliquée ou non de spondylodiscite est également comparable (72,4% vs 69,3 % ; p=0,76). Conclusion : Une spondylodiscite est associée à l endocardite infectieuse dans 5% des cas. La survenue d une spondylodiscite au cours de l endocardite infectieuse est indépendamment associée la présence d un streptocoque bovis et à un retard diagnostic. Le pronostic de l endocardite infectieuse n est pas aggravé par la survenue d une spondylodiscite. La spondylodiscite semblant plutôt être une métastase septique de l endocardite, il faut envisager la réalisation systématique d un bilan échocardiographique devant toute découverte de spondylodiscite surtout si le germe identifié est un streptocoque (et plus particulièrement un streptocoque bovis), un entérocoque, ou un staphylocoque (et plus particulièrement un staphylocoque à coagulase négative). Il ne faut néanmoins pas méconnaître que de façon moins fréquente, la spondylodiscite peut être la source d une endocardite infectieuse.Background: Association between spondylodiscitis and infective endocarditis (IE) has been low described. To our knowledge, only two studies, with small effective, comparing patients with spondylodiscitis and infective endocarditis and patients with infective endocarditis alone have been published. Characteristics and prognosis of patients with infective endocarditis and spondylodiscitis is still unknown. Objectives: To analyse clinical, echocardiographic and microbiological characteristics and prognosis of IE associated with spondylodiscitis. To determine predictive factors of finding spondylodiscitis in patients with IE. Methods and results: 418 patients with definite IE according to the Duke criteria were prospectively enrolled in our database. Spondylodiscitis was found in 22 patients (5,3 %). We compared two groups of patients: 396 patients with IE alone, and 22 patients with IE and spondylodiscitis. Compared to patients without spondylodiscitis (n=396), aortic valve IE, Streptococcus IE, Streptococcus bovis IE, splenic embolism were more frequently observed in patients with spondylodiscitis (n=22). Prosthetic valve IE and history of renal failure were less frequent in patients with spondylodiscitis. Mean duration of symptoms ( delay between the onset of symptoms and the diagnosis) and mean time hospitalization length were significantly longer in patients with IE and spondylodiscitis. No recidive of spondylodiscitis was noted. Microbiological characteristics of patients with IE and spondylodiscitis were: Streptococcus bovis ( 59%), Enterococcus (18%). Streptococcus milleri (5%), Staphylococcus aureus (9%), Staphylococcus coagulase negative (9%). Tow independent predictive factors of association between spondylodiscitis and IE were found: Streptococcus bovis IE (OR 8,17 [3,2-20,8]; p<0,001), long duration of symptoms (0R 1,006 [1,001-1,012]; p=0,024). In hospital mortality and 1-year mortality were similar in our two groups. The 1-year mortality was also evaluated after a propensity score matching and no significant difference was found between our two matched groups. Conclusion: Spondylodiscitis was found in 5 % of endocarditis. Spondylodiscitis was more frequently found in case of Streptococcus IE and especially in case of Streptococcus bovis IE. The occurence of spondylodiscitis doesn t affect the prognosis of endocarditis. In hospital mortality and 1-year mortality were similar in our two groups. Spondylodiscitis, when associated with IE, seems to be a septic metastatis of the endocarditis. We suggest that an echocardiography should be performed in all cases of spondylodiscitis when blood cultures shown a Streptococcus (especially Streptococcus bovis), a Staphylococcus (especially Staphylococcus coagulase negative), or an Enterococcus . However, we should not forget that in few cases, endocarditis could occur after spondylodiscitis.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study.

International audienceAIMS: The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue. METHODS AND RESULTS: This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD (+) for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD (-) for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD (+), 733 (87.8%) patients were classified as DI-VHD (-), and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001). CONCLUSIONS: About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions

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

International audienceAims 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 valve

Infective Endocarditis in Patients on Chronic Hemodialysis

International audienceInfective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD)

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes