Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus

OBJECTIVES: REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. METHODS: Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. RESULTS: At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30 ± 0.80 to 7.77 ± 1.31 versus pioglitazone: from 8.30 ± 0.80 to 7.45 ± 1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. CONCLUSION: After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug

Apport de la TEMP couplée à l'ECG au Tc-99m-sestamibi sous perfusion de dobutamine dans la prediction du remodelage du ventricule gauche chez des patients traités par angioplastie à la phase aiguë d'un primo-infarctus du myocarde

Le remodelage ventriculaire gauche après infarctus du myocarde est fréquent et entraîne une augmentation du risque d'insuffisance cardiaque et de la mortalité. Sa détection précoce permettait d'adapter le traitement et la surveillance des patients à risque. Le but de cette étude prospective était d'évaluer la capacité de la TEMP couplée à l'ECG au Tc-99m-sestamibi, à l'état basal et sous faible dose de dobutamine, réalisée au 6e jour après infarctus du myocarde, à détecter une évolution vers le remodelage ventriculaire au 6e mois. Notre travail a mis en évidence que l'analyse combinée de la fixation moyenne du traceur dans le territoire de l'artère responsable de l'infarctus et de l'épaississement pariétal systolique de ce même territoire, à l'état basal, permet de prédire un remodelage ventriculaire gauche au 6e mois avec une sensibilité de 70%, une spécificité de 86,7%, une exactitude de 90%, une VPP de 63,7% et une VPN de 89,7%. L'analyse de ces mêmes paramètres sous dobutamine, en démasquant une viabilité myocardique résiduelle, permet d'augmenter la sensibilité à 90%, la spécificité à 96,7%, l'exactitude du test à 95%, la VPP à 90,9% et la VPN à 96%.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The role of hyperglycaemia in the development of diabetic cardiomyopathy

International audienceAbstract The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance

Systolic Myocardial Dysfunction in Patients with Type 2 Diabetes Mellitus: Identification at MR Imaging with Cine Displacement Encoding with Stimulated Echoes

International audienc

Moderate hypoxia but not warming conditions at larval stage induces adverse carry-over effects on hypoxia tolerance of European sea bass ( Dicentrarchus labrax ) juveniles

Environmental conditions, to which organisms are exposed during all their life, may cause possible adaptive responses with consequences in their subsequent life-history trajectory. The objective of this study was to investigate whether ecologically relevant combinations of hypoxia (40% and 100% air saturation) and temperature (15° and 20 °C), occurring during the larval period of European sea bass larvae (Dicentrarchus labrax), could have long-lasting impacts on the physiology of resulting juveniles. Hypoxic challenge tests were performed over one year to give an integrative evaluation of physiological performance. We revealed that juvenile performance was negatively impacted by hypoxia but not by the thermal conditions experienced at larval stage. This impact was related to the prevalence of opercular abnormalities. The present study indicates that exposure to a moderate hypoxia event during larval stage may have adverse carry-over effects, which could compromise fitness and population recruitment success

Decreased Radial Function is Associated With Subtle Left Ventricular Remodeling in Type 2 Diabetes Mellitus

Background: Previous studies have suggested that reduced longitudinal myocardial function might be compensated by increased radial contractility in patients with type 2 diabetes mellitus (DM). Aim: To evaluate left ventricular (LV) remodeling in type 2 DM according to radial function assessed by STI. Methods: 234 asymptomatic type 2 DM patients with no sign or history of heart disease and normal conventional echo parameters were included. Mean radial strain (SR) was assessed by STI from short-axis view at the midventricular level. Mean longitudinal strain (SL) was calculated from the apical 2- and 4-chamber views. The population was divided into 3 groups according to SR value: group I = SR 60% (n = 57). Differences between groups were tested by ANOVA. Results: Clinical, biological and echographic data are shown in table. Age, body mass index (BMI), duration and severity of DM, systolic (sBP) and diastolic (dBP) blood pressure and LV mass index (LVMi) were similar between groups. Conventional systolic parameters (LVEF: LV ejection fraction and FS: fractional shortening) were also similar. However, a lower SR was associated with a significant increase in LV end-diastolic (LVEDD) and end-systolic (LVESD) diameters and a decreased SL. Conclusion: These data suggest that an altered radial function might be an indicator of more advanced diabetic cardiomyopathy with altered systolic function and beginning of eccentric LV remodelling

Diastolic function deterioration in type 2 diabetes mellitus: predictive factors over a 3-year follow-up

International audienceAims Diastolic dysfunction is frequent in patients with type 2 diabetes mellitus (DM2) and associated with a poor prognosis. This study aimed to describe diastolic function changes over time in DM2 patients and to identify predictive factors of diastolic function deterioration. Methods and results Diastolic function was assessed by echocardiography according to the EACVI/ASE recommendations at baseline and 3-year follow-up in a prospective cohort of 310 DM2 patients without overt heart disease. Predictors of diastolic function deterioration were identified using logistic regression analysis. During the 3-year follow-up, prevalence of diastolic dysfunction increased from 49% to 67% (P = 0.001). Only 32% of the patients had a normal diastolic function both at baseline and 3 years and 27% of the patients presented diastolic function deterioration. At multivariable analysis, age (OR = 1.05 [1.01-1.09], P \textless 0.01), retinopathy (OR = 2.00 [1.10-3.63], P = 0.02), and increase in systolic blood pressure during follow-up (OR = 1.03 [1.01-1.04], P \textless 0.01) were predictive of diastolic function deterioration. Conclusion Age, retinopathy, and increase in blood pressure over time are associated with an increased risk of diastolic function deterioration in DM2 patients. The presence of these co-factors might help to early identify patients at risk of heart failure