Clinical experience of dabigatran and rivaroxaban in electrical cardioversion of atrial fibrillation

Patients scheduled for atrial fibrillation (AF) cardioversion were excluded from clinical trials of novel oral anticoagulants (NOACs). We evaluated efficacy and safety of NOACs in patients undergoing electrical cardioversion for AF. We performed a monocentric study of all patients on NOACs who underwent elective electrical cardioversion for non-valvular AF between January 2012 and December 2014. We analyzed incidence of stroke and bleeding at 30 days. Fifty patients were included, 28 receiving dabigatran, 22 rivaroxaban. Mean age was 65 ± 12 years. Mean CHADS2-VA2SC and HASBLED scores were 3 ± 1.8 and 2.2 ± 1.1 respectively. Transoesophageal echocardiography was performed in 41 (79%) patients, revealing a thrombus in 2 (5%). No clinical evidence of stroke occurred in the 30 days, 1 major gastrointestinal bleeding (2%) in patient on rivaroxaban (led to premature discontinuation) and 3 minor bleedings. NOACs seem to be safe in daily practice of electrical cardioversion in our population

Intestinal permeability and appetite regulating peptides-reactive immunoglobulins in severely malnourished women with anorexia nervosa

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Evaluation of a Supervised Adapted Physical Activity Program Associated or Not with Oral Supplementation with Arginine and Leucine in Subjects with Obesity and Metabolic Syndrome: A Randomized Controlled Trial

International audienceBackground: In patients with obesity and metabolic syndrome (MetS), lifestyle interventions combining diet, in particular, and physical exercise are recommended as the first line treatment. Previous studies have suggested that leucine or arginine supplementation may have beneficial effects on the body composition or insulin sensitivity and endothelial function, respectively. We thus conducted a randomized controlled study to evaluate the effects of a supervised adapted physical activity program associated or not with oral supplementation with leucine and arginine in MetS-complicated patients with obesity. Methods: Seventy-nine patients with obesity and MetS were randomized in four groups: patients receiving arginine and leucine supplementation (ALs group, n = 20), patients on a supervised adapted physical activity program (APA group, n = 20), patients combining ALs and APA (ALs+APA group, n = 20), and a control group (n = 19). After the baseline evaluation (m0), patients received ALs and/or followed the APA program for 6 months (m6). Body composition, MetS parameters, lipid and glucose metabolism markers, inflammatory markers, and a cardiopulmonary exercise test (CPET) were assessed at m0, m6, and after a 3-month wash-out period (m9). Results: After 6 months of intervention, we did not observe variable changes in body weight, body composition, lipid and glucose metabolism markers, inflammatory parameters, or quality of life scores between the four groups. However, during the CPET, the maximal power (Pmax and Ppeak), power, and O2 consumption at the ventilatory threshold (P(VT) and O2(VT)) were improved in the APA and ALs+APA groups (p < 0.05), as well as the forced vital capacity (FVC). Between m6 and m9, a gain in fat mass was only observed in patients in the APA and ALs+APA groups. Conclusion: In our randomized controlled trial, arginine and leucine supplementation failed to improve MetS in patients with obesity, as did the supervised adapted physical activity program and the combination of both. Only the cardiorespiratory parameters were improved by exercise training

Cardiac overexpression of PDE4B blunts β-adrenergic response and maladaptive remodeling in heart failure

International audienceBackground The cAMP-hydrolyzing phosphodiesterase 4B (PDE4B) is a key negative regulator of cardiac β-adrenergic (β-AR) stimulation. PDE4B deficiency leads to abnormal Ca2+ handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure (HF). Methods: We measured PDE4B expression in human cardiac tissues, developed two transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B (PDE4B-TG), and an adeno-associated virus serotype 9 encoding PDE4B (AAV9-PDE4B). Myocardial structure and function were evaluated by echocardiography, ECG, and in Langendorff-perfused hearts. Cyclic AMP and PKA activity were monitored by Förster resonance energy transfer, ICa,L by whole cell patch-clamp, and cardiomyocyte shortening and Ca2+ transients with an Ionoptix® system. HF was induced by 2 weeks infusion of isoproterenol (Iso) or transverse aortic constriction (TAC). Cardiac remodeling was evaluated by serial echocardiography, morphometric analysis and histology. Results: PDE4B protein was decreased in human failing hearts. The first PDE4B-TG mouse line (TG15) had a ~15-fold increase in cardiac cAMP-PDE activity and a ~30% decrease in cAMP content and fractional shortening associated with a mild cardiac hypertrophy that resorbed with age. Basal ex vivo myocardial function was unchanged, but β-AR stimulation of cardiac inotropy, cAMP, PKA, ICa,L, Ca2+ transients and cell contraction were blunted. Endurance capacity and life expectancy were normal. Moreover, these mice were protected from systolic dysfunction, hypertrophy, lung congestion and fibrosis induced by chronic Iso treatment. In the second transgenic mouse line (TG50), markedly higher PDE4B overexpression, resulting in a ~50-fold increase in cardiac cAMP-PDE activity caused a ~50% decrease in fractional shortening, hypertrophy, dilatation and premature death. In contrast, mice injected with AAV9-PDE4B (1012 viral particles/mouse) had a ~50% increase in cardiac cAMP-PDE activity which did not modify basal cardiac function but efficiently prevented systolic dysfunction, apoptosis and fibrosis, while attenuating hypertrophy induced by chronic Iso infusion. Similarly, AAV9-PDE4B slowed contractile deterioration, attenuated hypertrophy and lung congestion and prevented apoptosis and fibrotic remodeling in TAC. Conclusions: Our results indicate that a moderate increase in PDE4B is cardioprotective and suggest that cardiac gene therapy with PDE4B might constitute a new promising approach to treat HF