Nlle. Hollande, Baie des Chiens-marins, Presqu'ile Peron, entrevue avec les sauvages [picture] /

Pl. no. 12 of: Voyage autour du monde. Atlas historique / Louis de Freycinet.; S7233

The 26RFa (QRFP)/GPR103 neuropeptidergic system in mice relays insulin signalling into the brain to regulate glucose homeostasis

International audienceAIMS/HYPOTHESIS: 26RFa (pyroglutamilated RFamide peptide [QRFP]) is a biologically active peptide that regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity at the periphery. 26RFa is also produced by a neuronal population localised in the hypothalamus. In this study we investigated whether 26RFa neurons are involved in the hypothalamic regulation of glucose homeostasis. METHODS: 26Rfa(+/+), 26Rfa(-/-) and insulin-deficient male C57Bl/6J mice were used in this study. Mice received an acute intracerebroventricular (i.c.v.) injection of 26RFa, insulin or the 26RFa receptor (GPR103) antagonist 25e and were subjected to IPGTTs, insulin tolerance tests, acute glucose-stimulated insulin secretion tests and pyruvate tolerance tests (PTTs). Secretion of 26RFa by hypothalamic explants after incubation with glucose, leptin or insulin was assessed. Expression and quantification of the genes encoding 26RFa, agouti-related protein, the insulin receptor and GPR103 were evaluated by quantitative reverse transcription PCR and RNAscope in situ hybridisation. RESULTS: Our data indicate that i.c.v.-injected 26RFa induces a robust antihyperglycaemic effect associated with an increase in insulin production by the pancreatic islets. In addition, we found that insulin strongly stimulates 26Rfa expression and secretion by the hypothalamus. RNAscope experiments revealed that neurons expressing 26Rfa are mainly localised in the lateral hypothalamic area, that they co-express the gene encoding the insulin receptor and that insulin induces the expression of 26Rfa in these neurons. Concurrently, the central antihyperglycaemic effect of insulin is abolished in the presence of a GPR103 antagonist and in 26RFa-deficient mice. Finally, our data indicate that the hypothalamic 26RFa neurons are not involved in the central inhibitory effect of insulin on hepatic glucose production, but mediate the central effects of the hormone on its own peripheral production. CONCLUSION/INTERPRETATION: We have identified a novel mechanism in the hypothalamic regulation of glucose homeostasis, the 26RFa/GPR103 system, and we provide evidence that this neuronal peptidergic system is a key relay for the central regulation of glucose metabolism by insulin

0379: Premature ventricular beat-induced cardiomyopathy. Characteristics and prognosis factor for recovery after radio-frequency ablation

IntroductionFrequent premature ventricular beats (PVB) may induce cardiomyopathy (CM). Characteristics and prognosis factor for recovery after RF ablation remain debated.Methods93 patients (74% men, 58±14 yo) with dilated CM associated with frequent isolated PVB were included. A group of 75 pts undergoing ablation for symptomatic PVB without significant cardiac disease serves as the control group.ResultsEF was 38±10% and left ventricular end diastolic diameter (LVEDD) was 63±8mm. One third have various associated cardiomyopathy.PVB burden was 27±12%. PVB arose from the left ventricle in 96 pts (LVOT 61, mitral 16, apex 7, septal 12) and from the right ventricle in 61 pts (RVOT 58) and multiple in 11. Epicardial ablation in the CS was needed in 25.In multivariate analysis, lack of palpitations (OR 9.09 [3.45-33.33]), VPB number > 20000 (OR 5.40 [1.98-14.70]), left ventricular origin (OR 4.12 [1.53-11.11]), epicardial location (OR 11.00 [1.92-62.50]), VPB right inferior axis (OR 2.31 [0.85-6.27]), baseline QRS width > 100ms (OR 3.66 [1.2810.43]), VPB coupling interval > 500ms (OR 3.11 [1.14-8.55]) and polymorphic VPB (OR 10.40 [1.05-103.05]) were independantly associated with CM compared to controls (p<0.05).Over a mean follow-up of 22±20 months, 79% presented with a significant decrease of VPB (> 80% reduction). In these, EF increased (36±9 to 51±12%, p<0.0001) and LVEDD decreased (62±7 to 56±7mm, p<0.0001). Reversal of CM was defined by > 10% increase in EF. Only a VPB > 2mV (OR 19.2 [1.84-200.00], p=0.01) was independanlty associated with reversal of CM in multivariate analysis.ConclusionMechanisms leading to PVB-induced CM may involve lack of palpitations, a high VPB number, a left ventricular origin, an epicardial location, a VPB right inferior axis, a large baseline QRS duration, a long VPB coupling interval and polymorphic VPB. Reversal of CM after RF ablation may associate a high VPB amplitude and a shorter VPB coupling interval. This may help in selecting patients for RF ablation of suspected VPB-induced CM

Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome

International audienceRisk stratification in Brugada syndrome (BS) remains controversial. The time interval between the peak and the end of the T wave (Tpe interval), a marker of transmural dispersion of repolarization, has been linked to malignant ventricular arrhythmias in various settings but leads to discordant results in BS

Relation of outcomes to ABC (Atrial Fibrillation Better Care) pathway adherent care in European patients with atrial fibrillation: an analysis from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) Registry

International audienceAbstract Aims There has been an increasing focus on integrated, multidisciplinary, and holistic care in the treatment of atrial fibrillation (AF). The ‘Atrial Fibrillation Better Care’ (ABC) pathway has been proposed to streamline integrated care in AF. We evaluated the impact on outcomes of an ABC adherent management in a contemporary real-life European-wide AF cohort. Methods and results Patients enrolled in the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry with baseline data to evaluate ABC criteria and available follow-up data were considered for this analysis. Among the original 11 096 AF patients enrolled, 6646 (59.9%) were included in this analysis, of which 1996 (30.0%) managed as ABC adherent. Patients adherent to ABC care had lower CHA2DS2-VASc and HAS-BLED scores (mean ± SD, 2.68 ± 1.57 vs. 3.07 ± 1.90 and 1.26 ± 0.93 vs. 1.58 ± 1.12, respectively; P &lt; 0.001). At 1-year follow-up, patients managed adherent to ABC pathway compared to non-adherent ones had a lower rate of any thromboembolic event (TE)/acute coronary syndrome (ACS)/cardiovascular (CV) death (3.8% vs. 7.6%), CV death (1.9% vs. 4.8%), and all-cause death (3.0% vs. 6.4%) (all P &lt; 0.0001). On Cox multivariable regression analysis, ABC adherent care showed an association with a lower risk of any TE/ACS/CV death [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.44–0.79], CV death (HR: 0.52, 95% CI: 0.35–0.78), and all-cause death (HR: 0.57, 95% CI: 0.43–0.78). Conclusion In a large contemporary cohort of European AF patients, a clinical management adherent to ABC pathway for integrated care is associated with a significant lower risk for cardiovascular events, CV death, and all-cause death