SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction

Electroanatomical Mapping Systems. An Epochal Change in Cardiac Electrophysiology

In the last two decades new mathematical and computational models and systems have been applied to the clinical cardiology, which continue to be developed particularly to quantify and simplify anatomy, physio-pathological mechanisms and treatment of many patients with cardiac arrhythmias. The Authors report our large experience on electroanatomical mapping systems and techniques that are currently used to quantify and analyze both anatomy and electrophysiology of the heart. In the last 15 years the Authors have performed more than 15,000 invasive catheter ablation procedures using different non-fluoroscopic three-dimensional (3D) electroanatomical mapping and ablation systems (CARTO, Ensite) to safely and accurately treat many patients with different cardiac arrhythmias particularly those with atrial fibrillation with a median age of 60 years (IQR, 55-64). The Authors have also developed and proposed for the first time a new robotic magnetic system to map and ablate cardiac arrhythmias without use of fluoroscopy (Stereotaxis) in >500 patients. Very recently, epicardial mapping and ablation by electroanatomical systems have been successfully performed to treat Brugada syndrome at risk of sudden death in a series of patients with a median age of 39 years (IQR, 30-42). Our experience indicates that electroanatomic mapping systems integrate several important functionalities. (1) Non-fluoroscopic localization of electrophysiological catheters in three-dimensional space; (2) Analysis and 3D display of cardiac activation sequences computed from local or calculated electrograms, and 3D display of electrogram voltage; (3) Integration of ‘electroanatomic’ data with non-invasive images of the heart, such as computed tomography or magnetic resonance images. The widespread use of such 3D systems is associated with higher success rates, shorter fluoroscopy and procedure times, and accurate visualization of complex cardiac and extra-cardiac anatomical structures needing to be protected during the procedure

New Imaging and Computational Technology as a Guide for Catheter Ablation of Incessant Tachyarrhythmias

Computational technology in the era of catheter ablation (RFA) has made it possible to experience relief from incessant atrial tachyarrhythmias (AT) by 3D electroanatomical mapping (EAM) systems. The Authors report the results of such technology in > 500 consecutive patients (57% males, mean age 56.9 years) with incessant refractory post-ablation left AT (mean cycle length 256 ms). Patients underwent electroanatomical-mapping systems, which combine electrophysiological and spatial information allowing accurate reconstruction of the whole atria with real-time activation sequence guiding RFA for continuous transmural linear lesions. Color-coded voltage and/or activation maps were successfully performed in all patients. Mapping distinguished clearly and rapidly between micro-macro-reentrant (>80%) and focal mechanisms. Acute success was obtained without major complications, with repeated procedures in about 5% of patients. EAM technology allows determining both mechanism and location of arrhythmia, ensuring successful elimination of complex arrhythmogenic substrates

Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome

Background— There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. Methods and Results— A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome–related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 ( P =0.007). AES increased after ajmaline in both groups ( P <0.001) and was larger in men ( P =0.008). The increase of type-1 ST-segment elevation correlated with AES expansion ( r =0.682, P <0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF. Conclusions— In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02641431