Loss of cardiac splicing regulator RBM20 is associated with early-onset atrial fibrillation

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified altered sarcomere and mitochondrial structure on electron microscopy imaging and found compromised mitochondrial function. Finally, we demonstrated that 3 novel LOF variants in RBM20, identified in patients with atrial fibrillation, lead to significantly reduced splicing activity. Our results implicate alternative splicing as a novel proarrhythmic mechanism in the atria

Effect of cancellation on triggered averaging used to determine synchronization between motor unit discharge in separate muscles

Synchronization between single motor unit (SMU) discharges in separate muscles has been estimated from peaks in averaged electromyographic (EMG) recordings from one muscle triggered from SMU discharge in another. This study evaluated the effect of EMG signal cancellation on this measure of synchronization. SMU activity was recorded with 8 fine-wire electrodes in vastus medialis obliquus (VMO) and vastus lateralis (VL) during gentle isometric knee extension in 7 subjects. Data from 5 VL recordings were summed then rectified, or rectified then summed, to produce multi-unit recordings with and without cancellation, respectively. Averages of summed VL data were triggered from VMO SMUs. Synchronization, defined as a peak >3 SD above the triggered average mean, occurred in 73.68% and 78.95% of recordings with and without cancellation, respectively. To further investigate the effect of cancellation on synchronization, 250 "virtual" EMG recordings were created from VL data. VL SMUs were sorted and modified with respect to discharge rate, amplitude and polarity to create a collection of possible SMU discharge patterns. Virtual recordings were added one-by-one to VL recordings that showed synchronization. Virtual channels were rectified then added or added then rectified, to create data with and without cancellation. Identification of synchronization decreased similarly in both conditions with addition of virtual data. Our data show estimation of synchronization from triggered averages is more likely to detect synchronization in recordings with fewer SMUs, but cancellation has little effect. Synchronization must be interpreted with caution if number of SMUs changes between condition

Current strategy for treatment of patients with Wolff-Parkinson-White syndrome and asymptomatic preexcitation in Europe: European Heart Rhythm Association survey

The aims of this survey was to provide insight into treatment activity, the strategy of treatment, and risk stratification of patients with asymptomatic and symptomatic ventricular pre-excitation across Europe. Fifty-eight centres, members of the European Heart Rhythm Association EP research network, covering 20 countries answered the survey questions. All centres were high-volume ablation centres. A younger person with asymptomatic Wolff-Parkinson-White (WPW) pattern has a higher likelihood of being risk-stratified or receiving ablation therapy compared with an older subject. Two-thirds of centres report that they have observed a decline in the number of patients ablated for an accessory pathway during the last 10 years. Pre-excited atrial fibrillation is rarely seen. Discontinuation of a scheduled WPW ablation due to close vicinity of the accessory pathway to the AV node happens very rarely. Patients with a first episode of pre-excited atrial fibrillation would immediately be referred for catheter ablation to be performed within weeks by 80.4% of the centres. A significant proportion of responders (50.9%) would use electrical cardioversion to restore sinus rhythm in a patient with pre-excited atrial fibrillation. With respect to the choice of antiarrhythmic medication for a patient with pre-excited AF, the majority (80.0%) would choose class 1C antiarrhytmic drugs while waiting for a catheter ablation. A patient seen in the emergency room with a second episode of orthodromic atrioventricular reentry tachycardia would be referred for immediate ablation by 79.2-90.6% of centres depending on the presence of pre-excitation. The volume of paediatric ablations performed on children younger than 12 years was low (46.4%: 0 patients per year; 46.4%: 1-9 patients per year). The majority of responding centres (61-69%) report that their country lack national guidelines dealing with clinical strategies related to WPW. There is a need for national guidelines dealing with clinical strategy in patients with WPW syndrome. Older individuals with asymptomatic WPW pattern have a higher risk of not receiving risk stratification or curative therapy with ablation compared with younger patients, despite the higher risk of developing atrial fibrillation. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved

Approach to cardiac resyncronization therapy

AimsThe purpose of this EP Wire is to compare indications, techniques, implant strategy, and follow-up regarding cardiac resynchronization therapy (CRT) in several countries across Europe. Methods and resultsForty-one centres, members of the EHRA-EP Research Network, responded to this survey and completed the questions. Thirty-two per cent of the responding centres always use CRT in heart failure (HF) patients with New York Heart Association functional class II and QRS width >120 ms, and 55 of the responding centres demand additional criteria when indicating CRT, most often QRS width >150 ms (49) and echocardiographic criteria of asynchrony (34). Only 10 of centres indicate CRT in all HF patients with QRS >120 ms and right bundle branch block, and 51 demand additional criteria, most frequently echocardiographic asynchrony parameters. The vast majority of centres also indicate CRT in patients with atrial fibrillation and standard criteria for CRT. In 24 of the centres, biventricular pacemaker (CRT-P) is implanted in all situations, unless there is an indication for secondary prevention of sudden cardiac death, while 10 always choose to implant a biventricular defibrillator (CRT-D). There are no clear evidence-based recommendations concerning the implant procedure and follow-up in patients treated with CRT; therefore, the chosen strategies vary widely from one centre to another. ConclusionThis EP Wire survey shows a wide variation not only as far as CRT indications are concerned, but especially in techniques, implant strategy, and follow-up across the European countries. © The 2012 Author