Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Critères de choix du site de stimulation ventriculaire gauche dans la resynchronisation cardiaque (écart inter-électrodes ou paroi la plus retardée)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Suivi à long terme de l'ablation par radiofréquence des flutters auriculaires

MONTPELLIER-BU Médecine (341722104) / SudocMONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude d'évaluation du coroscanner dans le diagnostic de la resténose intrastent

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

La FA méconnue (intérêt d'un questionnaire basé sur les symptomes dans le dépistage de la fibrillation atriale méconnue à haut risque)

Le dépistage systématique de la fibriIIation atriale (FA) par prise du pouls des sujets de plus de 65 ans est recommandé depuis 2012 (ESC). La FA méconnue est responsable d'environ 20% des accidents vasculaires cérébraux (AVC). Si elle peut être silencieuse, détectée par la prise du pouls ou par d'autres techniques, la FA peut être mécounue car les signes cliniques n'y sont pas attribués. Objectif: Le dépistage d'une FA chez les patients de plus de 65 ans consultant en médecine générale. Méthodes: Pendant une semaine tous les patients de plus de 65 ans consultant chez un médecin généraliste ont rempli un questionnaire basé sur des symptômes inexpliqués (palpitations, douleur thoracique, malaise, dyspnée). Si un des symptômes était présent une consultation cardiologique était recommandée. Résultats: 457 patients ont été inclus par 41 médecins généralistes (âge moyen: 76,8 ans, sexe masculin: 63%, HTA: 60%, diabète: 22.8%, antécédents AVC: 14.1%). Les scores CHADS2 et CHA2DS2.VASC moyens étaient de 1,8+-1,4 et 3.4+-1.6. La FA était connue chez 72 patients (16%) de 81,8 ans d'âge moyen, 67% d'hommes, 78% d'hypertendus, 37,5% de diabétiques et 43% avec antécédent d'AVC. Les scores de CHADS2 et CHA2,DS2.VASC étaient de 3,0+-1,6 et 4,6+-1,8. La FA était silencieuse chez 16/72 patients (22%). La FA était suspectée chez 85 patients (19%), avec soit des palpitations (n=25), malaise (n=28), douleur thoracique (n=14), ou dyspnée (n=33). 8 patients avaient un pouls irrégulier. L'âge moyen des patients était de 76,6 ans, 56% étaient des hommes, 59% hypertendus, 20,8% diabétiques et 17.6% avaient un antécédent d'AVC. Les scores de CHADS2 et CHA2DS2.VASC étaient de 2,0+-1,3 et 3,7+-1,5. Une consultation car diologique était proposée et une FA a été diagnostiquée pour 31 patients (36%). 7% des patients de plus de 65 ans en FA vus en médecine de ville peuvent être dépistés par notre questionnaire. Conclusion: L'utilisation d'un questionnaire adapté basé sur les symptômes semble détecter un nombre significatif de FA chez les patients à haut risque. Une amélioration de la prise en charge de la FA peut être attendueMONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Depletion of proBNP1-108 in patients with heart failure prevents cross-reactivity with natriuretic peptides.

BACKGROUND: After synthesis by cardiomyocytes, precursor proBNP1-108 is cleaved into NT-proBNP and BNP. Recently, cross-reactivity between these assays was discussed. The aim of this study was to characterize the cross-reactivities, through a new biochemical innovative approach consisting in the total depletion of the circulating proBNP1-108 in patients with heart failure (HF). METHODS: This prospective study included 180 patients with chronic HF. BNP and NT-proBNP were dosed with commercial kits. ProBNP1-108 was determined using an ELISA research assay specific to the precursor. ProBNP1-108 depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP1-108 hinge region. ProBNP1-108, BNP and NT-proBNP levels were determined before and after depletion using this process in HF patients. RESULTS: Mean age was 74.34 +/-12.5 y, and 69% of patients were males. NYHA classes II and III were the most frequent (32% and 45% respectively). Before depletion, ProBNP1-108, NT-proBNP and BNP levels were 316.8+/-265.9 pg/ml; 6,054.0+/-11,539 pg/ml and 684.3+/-82.1 pg/ml respectively, and were closely correlated with NHYA classes. After immuno-depletion, proBNP1-108 was decreased in mean by 96% (p<0.0001), BNP by 53% (p<0.0001) and NT-proBNP by 5%. The relationship between BNP or NT-proBNP and NHYA classes remained unchanged. CONCLUSION: Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP1-108 with our immunodepletion process, we are now able to assess the remaining "true" BNP and NT-proBNP molecules and further evaluate their clinical relevance

325: Ivabradine and dobutamine associated as a pure inotropic drug in cardiogenic shock?

IntroductionDobutamine remains gold-standard treatment in cardiogenic shock. However, it exacerbates tachycardia, worsening heart failure. Ivabradine, a specific inhibitor of If channel, could reduce this deleterious effect in association with dobutamine in patients with cardiogenic shock.We report the case of a 41-year-old woman admitted in intensive care unit for a severe heart failure with hemodynamic shock. She had no medical history.She suffered from thoracic and epigastric pain and cholecystis was initially diagnosed with an indication of sphincterotomy. However, her clinical status progressively worsened with severe dyspnea and global heart failure requiring appropriate treatment. ECG showed inverted T waves in the lateral leads and echocardiography showed a dilated cardiomyopathy with severe systolic alteration (LVEF: 35%). Coronary angiogram was strictly normal. Finally, no evidence was found on cardiac MRI for ischemic process or myocarditis. She progressively worsened with renal and hepatic dysfunction. Troponin and inflammation markers remained negative. It was necessary to introduce dobutamine and intravenous diuretics but we noticed an initial increase in heart rate concomitantly with blood pressure. We added ivabradine in order to reduce heart rate without effect on blood pressure (fig). Her clinical status improved and dobutamine could be stopped after 5 days and beta-blockers were then introduced.DiscussionHeart rate is a well-known marker of prognosis and tachycardia worsened by dobutamine could be deleterious to evolution of patient with cardiogenic shock. Ivabradine could be helpful in reducing heart rate without effect on blood pressure. However, this drug is indicated in stable heart failure but, to this day, hemodynamic instability is excluded. New prospective studies seem necessary to evaluate this benefit.ConclusionIn cardiogenic shock, association of dobutamine and ivabradine could be interesting to create a pure inotropic drug

Predicting One-Year Mortality after Discharge Using Acute Heart Failure Score (AHFS)

Background: Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods: This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results: During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76–0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59–0.77). Conclusions: The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis