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International audienceBACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions.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

Comparaison de deux méthodes de sélection classique avec l'haplodiploïdisation pour la résistance à la mouche de Hesse chez le blé tendre (Triticum aestivum)

L'efficacité des méthodes classiques et alternatives d'amélioration génétique repose sur l'évolution de la variabilité génétique des populations ségrégatives sous sélection. L'objectif de cette étude est de comparer l'évolution de la fréquence des gènes de résistance à la mouche de Hesse (Mayetiola destructor) sous deux méthodes classiques de sélection en comparaison avec la méthode de l'haplodiploïdisation. Les distributions et les proportions observées du caractère "résistance à la mouche de Hesse" ont été évaluées pour des lignées produites par la méthode de filiation unipare (FUP), la méthode " bulk " et l'haplodiploïdisation (DH) de quatre populations hybrides de blé tendre (Triticum aestivum). Ces populations sont issues des croisements entre des parents résistants à la mouche de Hesse marocaine et des parents sensibles mais adaptés aux conditions marocaines. Les résultats ont montré un effet marqué de la méthode d'amélioration génétique. En effet, malgré leur avancement à la génération F6, les lignées produites par les méthodes FUP et " bulk " présentent toujours un taux non négligeable d'hétérozygotie pour ce caractère alors que la méthode DH a abouti à une homozygotie parfaite. Les proportions de résistance observées chez les lignées FUP et haploïdes doublées sont approximativement les mêmes que celles théoriquement attendues. Cependant, la méthode " bulk " a permis une sélection naturelle au champ qui a favorisé le caractère résistant de manière significativeThe relative usefulness of conventional and alternative breeding methods relies on the evolution of genetic variability in segregating populations undergoing selection. The objective of this study was to compare the frequencies of genetic resistance to Hessian fly (Mayetiola destructor) in populations generated by two conventional breeding methods in comparison with lines advanced through doubled haploid method. Distribution and proportions of Hessian fly resistance were evaluated in four populations of bread wheat lines advanced through 'Single Seed Descent' (SSD), 'Bulk', and doubled-haploid (DH) methods. These populations were all derived from crosses involving resistant parents and susceptible lines adapted to Moroccan conditions. The results of this study have shown a clear effect of the breeding method. The Bulk and SSD (F6) derived lines have shown a substantial residual heterozygocity while DH method has produced completely homozygous material. The observed proportions of resistance did not deviate from expected in the populations of lines derived through SSD and DH methods while evidence of natural selection for resistance was significant in the lines derived through the Bulk method

Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets results from a large international multicenter study

Background-Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. Methods and Results-The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA<55 mm, those with LA â¥55 mm had lower 8-year overall survival (P<0.001). LA â¥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA â¥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA â¥55 mm was observed in asymptomatic and symptomatic patients (P for interaction, 0.77). In patients who underwent mitral surgery, LA â¥55 mm had no impact on postoperative outcome (P<0.20). Mitral surgery was associated with greater survival benefit in patients with LA â¥55 mm compared with LA <55 mm (P for interaction, 0.008). Conclusions-In MR caused by flail leaflets, LA diameter â¥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction. © 2011 American Heart Association, Inc

Diagnosis of paradoxical low-flow/low-gradient aortic stenosis: A complex process!

International audienc

Diagnosis of paradoxical low-flow/low-gradient aortic stenosis: A complex process! (vol 110, pg 135, 2017)

International audienc

Risk Stratification of Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction Using Peak Aortic Jet Velocity An Outcome Study

International audienceBackground-Current guidelines consider aortic valve replacement reasonable in asymptomatic patients with very severe aortic stenosis (AS); however, the definition of very severe AS based on peak aortic jet velocity (Vmax) remains unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines. Because approximate to 20% of patients with severe AS and preserved left ventricular ejection fraction have Vmax in this range, we aimed to assess the relationship between Vmax and mortality and determine the best threshold to define very severe AS. Methods and Results-A total of 1140 patients with severe AS (aortic valve area = 4 m/s) and preserved left ventricular ejection fraction were included. The population was divided into 4 groups according to Vmax (4-4.49, 4.5-4.99, 5-5.49, and >= 5.5 m/s). After adjustment for covariates (including surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49 m/s and Vmax 4.5 to 4.99 m/s (P=0.64). Both Vmax 5 to 5.49 m/s and Vmax >= 5.5 m/s exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted hazard ratio=1.34 [1.18-1.52]; P= 5.5 m/s (P=0.93). Compared with Vmax = 5 m/s had greater mortality risk (adjusted hazard ratio=1.86 [1.55-2.54]; P= 5 m/s at the time of AS diagnosis identifies patients with very severe AS at high risk of death

Impact of Preoperative Left Atrial Dimension on Outcome in Patients in Sinus Rhythm Undergoing Surgical Valve Repair for Severe Mitral Regurgitation due to Mitral Valve Prolapse

International audienceBackground: Left atrial (LA) enlargement has been previously identified as a predictor of mortality in patients with medically managed mitral regurgitation (MR) due to mitral valve prolapse (MVP). No study has specifically assessed the prognostic value of LA size in patients undergoing mitral valve repair (MVRp). Objective: We aimed to investigate the relationship between LA area and mortality in patients in sinus rhythm (SR) undergoing MVRp for MVP. Methods: We included 305 patients in SR who underwent MVRp for MVP. Median follow-up time was 7.9 years. Patients were divided into 3 groups: LA area 30 cm(2). Results: Compared with patients with an LA area 30 cm(2) had a lower 10-year survival (98 +/- 2 vs. 86 +/- 4%; p = 0.037). In multivariate analysis, after adjustment for established outcome predictors including age, symptoms, EuroSCORE, and left ventricular size and function, LA enlargement >30 cm(2) was associated with increased mortality (adjusted HR = 2.20, 95% CI 1.03-4.90; p = 0.042), whereas LA enlargement between 26 and 30 cm(2) was not (adjusted HR = 1.37, 95% CI 0.56-3.56; p = 0.52). Conclusion: LA enlargement is independently predictive of long-term mortality after MVRp in patients in SR with severe MR due to MVP. Our findings suggest that MVRp should be considered before the LA area exceeds 30 cm(2)

Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction

International audienceAims In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi) 35 mL/m(2) or SV > 70 mL; (ii) SVi 30-35 mL/m(2) or SV 55-70 mL; and (iii) SVi 35 mL/m(2) [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV 70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m(2) vs. > 35 mL/m(2) [adjusted HR 1.05(0.78-1.41)], and for SV 55-70 mL vs. > 70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m(2) and SV < 55mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS. Conclusion Low flow defined as SVi < 30 mL/m(2) or SV < 55mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making