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 NaV1.5, 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 NaV1.5 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

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

Strategies to improve AV synchrony in patients with a Micra AV leadless pacemaker.

The second generation of transcatheter pacing systems, called Micra AV, can provide atrio-ventricular (AV) synchronous pacing via a new pacing algorithm relying on sensing mechanical atrial contraction. Several novel programming parameters were introduced to enable AV synchronous pacing, including an A3 and A4 window as well as a conduction and an activity mode switch. In addition to several automated features, manual programming optimization of some of the novel parameters is key to improving AV synchrony. A solid knowledge of the features and their programming is essential for electrophysiologists implanting or following patients with Micra AV devices. Differences in programming optimization might partially explain the high variability of AV synchrony published in real-world data reports. This article reviews the key programming parameters of Micra AV. Subsequently, optimal programming recommendations for defined patient profiles are presented. Those were established by consensus within an Experts Panel comprised of 11 European electrophysiologists from high-volume Micra AV centers. The patient profiles were 1) high degree AV block and slow sinus rhythm; 2) high degree AV block and fast sinus rhythm; and 3) intermittent AV block. The panel recommended to evaluate the mechanical atrial activity on transthoracic echocardiography prior to implant. It was also agreed that Auto A3 Threshold and Tracking Check should be turned off in all patients, AV Conduction Mode Switch should be turned off in all patients with high degree AV block, and the lower rate should be programmed to 50 bpm with exceptions based on individual clinical assessment. Future studies will be useful to evaluate the strength of those recommendations to improve the AV synchrony

Quand implanter un stimulateur cardiaque dans la maladie de Steinert ?

International audienc

Utility of the lateral fluoroscopic view for subxiphoid pericardial access.

Journal Articleinfo:eu-repo/semantics/publishe

Catheter ablation of persistent and permanent atrial fibrillation: Bordeaux experience.

The seminal observation that ectopics from the pulmonary veins may initiate paroxysmal atrial fibrillation (AF) heralded an era of potentially curative catheter ablation therapy for AF. In recent years, catheter ablation has been performed for not only paroxysmal but also persistent and permanent AF. It is anticipated that the number of procedures will continue to increase and the indication for catheter ablation will expand. This article details our experience with catheter ablation therapy for patients with persistent and chronic AF.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Focal arrhythmia confined within the coronary sinus and maintaining atrial fibrillation.

The coronary sinus (CS) is a complex structure comprising a mesh of circumferential muscular fibers with oblique connections to both atria. We describe further evidence for the clinical importance of CS arrhythmogenicity in maintaining atrial fibrillation (AF) in humans.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

Radiofrequency puncture of the fossa ovalis for resistant transseptal access.

Transseptal puncture with a conventional mechanical technique can fail because of a resistant interatrial septum. We evaluated the efficacy and safety of a new method to cross-resistant septae by transmitting radiofrequency (RF) energy through the transseptal needle.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Impact of a patent foramen ovale on paroxysmal atrial fibrillation ablation

info:eu-repo/semantics/publishe