Mutations in RBM20 encoding the RNA-binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine-rich domain (RS domain). Here, we investigated in several cardiomyopathy patients, the previously described RBM20-mutation p.Pro638Leu localized within the RS domain. In addition, we identified in a patient the novel mutation p.Val914Ala localized in the (glutamaterich) Glu-rich domain of RBM20 encoded by exon 11. Its impact on the disease was investigated with a novel TTN-and RYR2-splicing assay based on the patients' cardiac messenger RNA. Furthermore, we showed in cell culture and in human cardiac tissue that mutant RBM20-p.Pro638Leu is not localized in the nuclei but causes an abnormal cytoplasmic localization of the protein. In contrast the splicing deficient RBM20-p.Val914Ala has no influence on the intracellular localization. These results indicate that disease-associated variants in RBM20 lead to aberrant splicing through different pathomechanisms dependent on the localization of the mutation. This might have an impact on the future development of therapeutic strategies for the treatment of RBM20-induced cardiomyopathies.

Aims Pacing the specific conduction system like the Bundle of His (HB) can lead to more physiologic activation patterns compared to traditional right ventricular apical pacing. The aim of this study was to estimate the feasibility and value of electroanatomical mapping (EAM) for HB pacing during the learning curve and its impact on procedural outcome. Methods and results Fifteen consecutive patients were treated using EAM of the His bundle region before implantation. Voltage and activation maps of HB potentials were performed. The activation time from His potential to R wave (ECG-reference) was measured and correlated to the HV interval. The atrial and ventricular potentials were blended so the active window could only see the His potential. After completing the activation map, it was transformed into a peak-to-peak voltage map of the HB. With reversed black and white colour scale, the exact point of the maximal His signal amplitude was visualized. Procedural data for the implantation were analysed using this innovative approach. The average total procedural time and fluoroscopy time was 88.2 ± 19.1 min and 10.9 ± 4.5 min, respectively. The 3D mapping time was 18.4 ± 5.1 min. The 13.9 ± 5.1 His potential points were needed in average to complete the map. No periprocedural complications were seen in this cohort. In 86.7% of cases, His bundle pacing was successful. The average threshold for the His bundle stimulation and the R-wave amplitude was 1.62 ± 1 V (@1.0 ms) and 4.8 ± 3.2 mV, respectively. The pacing impedance was 513.5 ± 102.8 Ω. Average paced QRS complex width was 116.9 ± 20.3ms. On average 2.6 ± 1.6 lead positions were targeted to find the optimal pacing site. Conclusion Electroanatomical mapping-guided implantation of His-bundle leads can facilitate the identification of optimal pacing sites and allow to minimize procedure and fluoroscopy times even during the phase of the learning curve.

Background:The non-fluoroscopy approach with the use of a three-dimensional (3D) navigation system is increasingly recognized as a future technology in the treatment of arrhythmias. However, there are a limited number of articles published concerning transseptal puncture without the use of fluoroscopy.Methods: Presented in this paper is the first series of patients (n = 10) that have undergone transseptal puncture without the use of fluoroscopy under transesophageal echocardiography control using a radiofrequency transseptal needle and a 3D navigation system. Results:All patients were treated without complications. In six patients, re-pulmonary vein isolation was performed. In 5 cases, linear ablation of the left atrium for treatment of left atrial macro re-entry tachycardia was provided. In 2 patients, focal atrial tachycardia was treated, 1 patient underwent cavo tricuspidal isthmus (CTI) ablation and one patient, re-CTI ablation.The ablation of complex fragmented atrial electrograms was done in 2 patients. In 1 case, right atrial macro re-entry tachycardia was treated. Conclusions:Transseptal puncture without using fluoroscopy is safe and effective when using a radiofrequency needle, a 3D navigation system and transesophageal echocardiography.