High prevalence and distinctive clinical features of LMNA-associated atrioventricular block in young patients.

BACKGROUND AND AIMS: Atrioventricular block (AVB) is a degenerative disease and more commonly encountered in elderly patients, but unusual and often of unknown etiology in young patients. This study aimed to investigate the potential contributions of genetic variations to AVB of unknown reasons in young patients. METHODS: We enrolled 41 patients aged <55 years with high-degree AVB of unknown etiology whose clinical and genetic data were collected. RESULTS: Genetic variants were identified in 20 (20/41, 48.8%) patients, 11 (11/20, 55%) of whom had LMNA variants including 3 pathogenic (c.961C > T, c.936+1G > T and c.646C > T), 4 likely pathogenic (c.1489-1G > C, c.265C > A, c.1609-2A > G and c.1129C > T) and 3 of uncertain significance (c.1158-3C > G, c.776A > G and c.674G > T). Compared to those without LMNA variants, patients with LMNA variants demonstrated a later age at onset of AVB (41.45 ± 9.89 years vs 32.93 ± 12.07 years, P = .043), had more prevalent family history of cardiac events (81.8% vs 16.7%, P < .000), suffered more frequently atrial (81.8% vs 10.0%, P < .000) and ventricular (72.7% vs 10.0%, P < .000) arrhythmias, and were more significantly associated with enlargement of left atrium (39.91 ± 7.83 mm vs 34.30 ± 7.54 mm, P = .043) and left ventricle (53.27 ± 8.53 mm vs 47.77 ± 6.66 mm, P = .036). CONCLUSIONS: Our findings provide insights into the genetic etiology of AVB in young patients. LMNA variants are predominant in genotype positive patients and relevant to distinctive phenotypic properties.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

Comparison of strategies for catheter ablation of left posterior fascicular ventricular tachycardia.

AIMS: Traditional ablation strategies including targeting the earliest Purkinje potential (PP) during left posterior fascicular (LPF) ventricular tachycardia (VT) or linear ablation at the middle segment of LPF during sinus rhythm are commonly used for the treatment of LPF-VT. Catheter ablation for LPF-VT targeting fragmented antegrade Purkinje (FAP) potential during sinus rhythm is a novel approach. We aimed to compare safety and efficacy of different ablation strategies (FAP ablation vs. traditional ablation) for the treatment of LPF-VT. METHODS AND RESULTS: Consecutive patients with electrocardiographically documented LPF-VT referred for catheter ablation received either FAP ablation approach or traditional ablation approach. Electrophysiological characteristics, procedural complications, and long-term clinical outcome were assessed. A total of 189 consecutive patients who underwent catheter ablation for LPF-VT were included. Fragmented antegrade Purkinje ablation was attempted in 95 patients, and traditional ablation was attempted in 94 patients. Acute ablation success with elimination of LPF-VT was achieved in all patients. Left posterior fascicular block occurred in 11 of 95 (11.6%) patients in the FAP group compared with 75 of 94 (79.8%) patients in the traditional group (P < 0.001). Fragmented antegrade Purkinje ablation was associated with significant shorter procedure time (94 ± 26 vs. 117 ± 23 min, P = 0.03) and fewer radiofrequency energy applications (4.1 ± 2.4 vs. 6.3 ± 3.5, P = 0.003) compared with the traditional group. One complete atrioventricular block and one left bundle branch block were seen in the traditional group. Over mean follow-up of 65 months, 89 (93.7%) patients in the FAP group and 81 (86.2%) patients in the traditional group remained free of recurrent VT off antiarrhythmic drugs (P = 0.157). CONCLUSION: Left posterior fascicular-ventricular tachycardia ablation utilizing FAP and traditional ablation approaches resulted in similar acute and long-term procedural outcomes. Serious His-Purkinje injury did occur infrequently during traditional ablation. The use of FAP ablation approach was associated with shorter procedure time and fewer radiofrequency energy applications, especially for non-inducible patients.

Prevalence of congenital heart disease among school children in Qinghai Province.

OBJECTIVES: This study aimed to investigate the prevalence of congenital heart disease (CHD) among school children in Qinghai province, a high-altitude region in China. METHODS: A cross-sectional study was conducted among school-aged children in 2019. All subjects completed a survey with a structure questionnaire and underwent CHD screening. CHD was screened by standard physical examination and further confirmed by echocardiography. Multivariate logistic regression were used to estimate the association of CHD prevalence with gender, nationality, and altitude. RESULTS: A total of 43,562 children aged 3-19 years participated in the study. The mean (SD) age was 11.2 (3.3) years. 49.7% were boys, and 80.0% were of Tibetan. CHD was identified in 293 children, with an overall prevalence of 6.73 ‰. Among them, 239 were unrecognized CHD, yielding a prevalence of 5.49 ‰. Atrial septal defect accounted for 51.9% of the CHD, followed by patent ductus arteriosus (31.1%), ventricular septal defect (9.9%). The CHD prevalence was significantly higher in female (8 ‰), Han race (18 ‰), children lived in Qumalai county (13 ‰), and children lived in a higher altitude (13 ‰). Female had greater prevalence of total CHD, atrial septal defect, and patent ductus arteriosus, but insignificant difference was observed in ventricular septal defect prvalence than male. In multivariable logistic regression analyses, female (OR, 1.48; 95% CI, 1.17-1.87, P = 0.001), Han population (OR, 3.28; 95% CI, 1.67-6.42, P = 0.001), and higher altitudes (OR, 2.28; 95% CI, 1.74-3.00, P < 0.001) were shown to be independently association with CHD prevalence. CONCLUSIONS: The prevalence of CHD in Qinghai province was 6.73 ‰. Altitude elevation, female, and Han population were independently association with CHD prevalence.

Inability to capture with increasing current strength: Is this near-field or far-field?

We present a case of wide-complex tachycardia in which the clinical electrophysiological diagnosis was considered to be bundle branch re-entry ventricular tachycardia. A series of ventricular entrainment attempts were performed from the left and right ventricular septum to confirm the diagnosis. Entrainment pacing with a general current output (10 mA) was performed from the right ventricular septum with manifest fusion and a post-pacing interval similar to tachycardia cycle length. Thereafter, another entrainment attempt with a greater current output (20 mA) was performed from the same site. Paradoxically, concealed fusion was demonstrated by selective RB capture only, though there was no clear "RB" potential seen. In this case, we attempt to explain and illustrate the mechanism of paradoxical near-field inability to capture with increasing current strength.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

Genetic Variants on SCN5A, KCNQ1, and KCNH2 in Patients with Ventricular Arrhythmias during Acute Myocardial Infarction in a Chinese Population.

OBJECTIVE: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. About half of sudden deaths from AMI are mainly because of malignant ventricular arrhythmias (VA) after AMI. The sodium channel gene SCN5A and potassium channel genes KCNQ1 and KCNH2 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS). A few studies reported the association of SCN5A variant with ventricular tachycardia (VT)/ventricular fibrillation (VF) complicating AMI. However, little is known about the role of KCNQ1 and KCNH2 in AMI with VA (AMI_VA). This study focuses on investigating the potential variants on SCN5A, KCNQ1, and KCNH2 contributing to AMI with VA in a Chinese population. MATERIALS AND METHODS: In total, 139 patients with AMI_VA, and 337 patients with AMI only, were included. Thirty exonic sites were selected to be screened. Sanger sequencing was used to detect variants. A subsequent association study was also performed between AMI_VA and AMI. RESULTS: Twelve variants [5 on KCNH2(NM_000238.3), 3 on KCNQ1(NM_000218.2), and 4 on SCN5A(NM_198056.2)] were identified in AMI_VA patients. Only 5 (KCNH2: c.2690A>C; KCNQ1: c.1927G>A, c.1343delC; SCN5A: c.1673A>G, c.3578G>A) of them are missense variants. Two (KCNQ1: c.1343delC and SCN5A: c.3578G>A) of the missense variants were predicted to be clinically pathogenic. All these variants were further genotyped in an AMI without VA group. The association study identified a statistically significant difference in genotype frequency of KCNH2: c.1539C>T and KCNH2: c.1467C>T between the AMI and AMI_VA groups. Moreover, 2 rare variants (KCNQ1: c.1944C>T and SCN5A: c.3621C>T) showed an elevated allelic frequency (more than 1.5-fold) in the AMI_VA group when compared to the AMI group. CONCLUSION: Twelve variants (predicting from benign/VUS to pathogenic) were identified on KCNH2, KCNQ1, and SCN5A in patients with AMI_VA. Genotype frequency comparison between AMI_VA and AMI identified 2 significant common variants on KCNH2. Meanwhile, the allelic frequency of 2 rare variants on KCNQ1 and SCN5A, respectively, were identified to be enriched in AMI_VA, although there was no statistical significance. The present study suggests that the ion-channel genes KCNH2, KCNQ1, and SCN5A may contribute to the pathogenesis of VA during AMI.

Inadvertent transseptal puncture into the aortic root: the narrow edge between luck and catastrophe in interventional cardiology.

AIMS: Inadvertent puncture of the aortic root (AR) is a well-known complication of transseptal puncture (TSP). Strategies for handling of this potentially lethal complication have not been identified yet. In this study, we present typical anatomical locations and clinical management of aortic root puncture (ARP) due to TSP. METHODS AND RESULTS: All patients with ARP were retrospectively collected from seven hospitals. Aortic root puncture was identified and classified regarding angiographical and intraoperative findings in cardiac surgery: (i) TSP from the right atrium (RA) to the non-coronary sinus (NCS), (ii) TSP from RA to the non-coronary sinutubular junction (STJ), and (iii) TSP from RA to the ascending aorta (AA). A total of 24 patients with inadvertent ARP were identified. In 19 patients, penetration of the aorta was accomplished by the inner dilator, in 5 patients by the complete sheath. Previous cardiac surgery had been performed in six patients. There were 13 RA-to-NCS punctures, 2 RA-to-STJ punctures, and 9 RA-to-AA punctures. No cardiac tamponade (CT) occurred in patients with RA-to-NCS and RA-to-STJ punctures. In 8 of 9 patients with RA-to-AA puncture, CT occurred immediately requiring urgent pericardiocentesis and surgical repair. Two patients died after surgical repair. In the 16 patients without surgical therapy, no shunt from the AR to the RA was observed 3 months after the procedure. CONCLUSION: Aortic root puncture due to mislead TSP via NCS or STJ is usually not associated with a severe clinical course while ARP into the AA via the epicardial space generally leads to CT requiring surgical repair.

Unique electrocardiographic pattern "w" wave in lead I of idiopathic ventricular arrhythmias arising from the distal great cardiac vein.

BACKGROUND: The ECG characteristics of the distal coronary venous system ventricular arrhythmias (VAs) share common features with VAs arising from the aortic cusps or the endocardial left ventricular outflow tract (LVOT) beneath the cusps. The purpose of this study was to identify specific electrocardiographic and electrophysiological characteristics of VAs originating from the distal great cardiac vein (GCV). METHODS: Based on the successful ablation site, patients with idiopathic VAs from the distal GCV, left coronary cusp (LCC) or the subvalvular left ventricular outflow tract (LVOT) area were included in the present study. RESULTS: The final population consisted of 39 patients (35 males, mean age 51 ± 23 years). All VAs displayed a right bundle branch block (RBBB) morphology with inferior axis. Among these patients, 15 were successfully ablated at the GCV, 15 at the LCC and 9 at the subvalvular region. A "w" pattern in lead I was present in 12 out of 15 (80%) VAs originating from the distal GCV compared to none of VAs arising from the other two sites (p < 0.01). VAs with a GCV origin exhibited more commonly increased intrinsicoid deflection time, higher maximum deflection index and wider QRS duration compared to LCC and subvalvular sites (p < 0.05). Acceptable pace mapping at the successful ablation site was achieved in 10 patients. After an average of 36 ± 24 months follow up, 14 (93.3%) patients were free from VAs recurrence. CONCLUSION: A "w" pattern in lead I may distinguish distal GCV VAs from VAs arising from the LCC or the subvalvular region.

Association between elevated blood glucose level and non-valvular atrial fibrillation: a report from the Guangzhou heart study.

BACKGROUND: To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China. METHODS: The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence. RESULTS: The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40-2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14-2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12-2.91, P = 0.016). CONCLUSIONS: In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.

Mid-term outcomes of concomitant left atrial appendage closure and catheter ablation for non-valvular atrial fibrillation: a multicenter registry.

To investigate the safety and midterm outcome of concomitant left atrial appendage (LAA) closure and catheter ablation (CA) as a one-stage hybrid procedure for non-valvular atrial fibrillation (AF) in a multicenter registry. A total of 50 consecutive patients with symptomatic drug-resistant non-valvular AF with CHA2DS2-VASc score ≥ 2 and contraindications for antithrombotic therapy were included in the prospectively established LAA closure registry, and underwent concomitant LAA closure (48 for WATCHMAN and 2 for ACP) and CA procedure (40 for radiofrequency and 10 for cryoballoon CA). Two cardiac tamponades, one peripheral vascular complications and one mild air embolism were observed during perioperative period. After mean follow-up of 20.2 ± 11.5 months, 18 (36%) patients presented with atrial arrhythmia relapse and 45 (91.8%) patients presented with complete sealing; furthermore, there were two transient ischemic attacks and one ischemic stroke under an off-oral anticoagulant situation, respectively. Concomitant CA and LAA closure as a one-stage hybrid procedure might be feasible and potentially decrease costs in patients with symptomatic non-valvular AF with high stroke risk and contraindication to antithrombotic treatment, and as safe as LAA closure procedure only during the perioperative period. However, it was necessary to further validate the mid-term safety.

Characteristics, Mechanism and Long-Term Ablation Outcome of Atrial Tachycardias After Mitral Valvular Surgery and Concomitant Cox-MAZE IV Procedure.

The incidence of atrial tachycardia (AT) after rheumatic mitral valvular (RMV) surgery has been well described. However, there have been few reports on the characteristics, mechanism, and long-term ablation outcome of ATs after RMV surgery and concomitant Cox-MAZE IV procedure.The present study reviewed consecutive patients who underwent AT ablation between May 2008 and July 2013. All patients were refractory to antiarrhythmic drugs (AADs) and had a history of RMV surgery and Cox-MAZE IV procedure. A total of 34 patients underwent AT ablation after RMV surgery and concomitant Cox-MAZE IV procedure, and presented 57 mappable and 2 unmappable ATs. The 57 mappable ATs included 14 focal-ATs and 43 reentry-ATs. Ten of the 14 focal-like ATs were located at the pulmonary vein (PV) antrum and border of a box lesion. Of the 43 reentry-ATs, 16 were marco-reentrant around the mitral annulus (MA) and 16 around the tricuspid annulus. There were 41 atypical ATs (non-cavotricuspid isthmus related) including 16 ATs related to the box lesion and 21 ATs related to other Cox-MAZE IV lesions. The AT were successfully terminated in 33 (97.1%) patients. After mean follow-up of 46.9 ± 15.7 months, 25 (73.5%) patients maintained sinus rhythm without AADs after a single procedure and 28 (82.4%) patients after repeated procedures.The recurrent ATs after RMV surgery and concomitant Cox-MAZE IV were mainly reentry mechanism, and largely related to LA. An incomplete lesion or re-conductive gaps in a prior lesion might be the predominant mechanisms for these ATs. Catheter-based mapping and ablation of these ATs seems to be effective and safe during a long-term follow-up.

Case report of familial sudden cardiac death caused by a DSG2 p.F531C mutation as genetic background when carrying with heterozygous KCNE5 p.D92E/E93X mutation.

BACKGROUND: Sudden cardiac death (SCD) induced by malignant ventricular tachycardia (MVT) among young adults with right ventricular cardiomyopathy/dysplasia (ARVC/D) is a devastating event. Parts of ARVC/D patients have a mutation in genes encoding components of cardiac desmosomes, such as desmoglein-2 (DSG2), plakophilin-2 and desmoplakin. CASE PRESENTATION: Here we report a potentially pathogenic mutation in the DSG2 gene, which was identified in a family with ARVC/D using Whole Exome Sequencing (WES) and Sanger Sequencing. In all, Patient III:1 with ARVC/D carried the compound heterozygous mutations of DSG2 p.F531C and KCNE5 p.D92E/E93X, which were both inherited from her mother (II:2), who died of SCD. Carriers of DSG2p.F531C showed various phenotypes, such as ARVC/D, SCD, MVT and dilated cardiomyopathy. For III:1, there were significant low-voltage regions in the inferior-apical, inferior-lateral wall of the right ventricular epicardium and outflow tracts of the right ventricle. Under the guidance of a three-dimensional mapping system, MVT was successfully ablated with an epicardial-endocardial approach targeting for late, double or fragmental potentials after implantable cardioverter-defibrillator (ICD) electrical storms. No VT recurrence was observed during the one year of follow-up. CONCLUSIONS: When coexisting with heterozygous KCNE5 p.D92E/E93X, heterozygous DSG2 p.F531C as a genetic background was found to predispose to ARVC/D, SCD and MVT, which were successfully ablated using an epicardial-endocardial approach.

Association of Thromboembolic Risk Score with Left Atrial Thrombus and Spontaneous Echocardiographic Contrast in Non-Anticoagulated Nonvalvular Atrial Fibrillation Patients.

OBJECTIVES: The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. METHODS: Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. RESULTS: Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, p = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). CONCLUSIONS: CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients.

Using the MB-LATER score for predicting arrhythmia outcome after catheter ablation for atrial fibrillation: The Guangzhou atrial fibrillation project.

INTRODUCTION: Several clinical scoring systems have been derived to predict the arrhythmia outcome of catheter ablation (CA) for atrial fibrillation (AF) but which is better is not clear. Simple clinical risk scores (that any clinician can use in the everyday clinic) can help assess the likelihood of recurrence of AF following CA and the simple MB-LATER score has recently been described. We compare the predictive ability of seven existing clinical scoring systems (HATCH, CHADS2 , CHA2 DS2 -VASc, BASE-AF2 , APPLE, CAAP-AF, and MB-LATER) in a Chinese cohort of AF patients undergoing CA. METHODS AND RESULTS: 1410 patients (mean age 57.2 ± 11.6 years; 68% male) with AF undergoing CA during 2011-2015 were enrolled in final analysis. Symptoms, 12 lead ECG and Holter ECGs were recorded before discharge, and at 1, 3, 6 months, and every 6 months thereafter to detect the arrhythmia relapse. During a mean 20.7 ± 8.8-month follow-up, recurrence occurred in 365 patients(25.9%). All tested scores were predictors of AF recurrence with areas under the curve (AUCs) of 0.58, 0.57, 0.57, 0.75, 0.74, 0.71, and 0.73 respectively (all P < 0.01). Compared to all other scores, the MB-LATER score showed improved reclassification (NRI range 30%-82.6%, P < 0.01) and discrimination indexes (IDI range 2.6%-18.6%, all P < 0.01) in predicting AF recurrence. CONCLUSION: Based on net reclassification and discrimination analysis, the MB-LATER score performed best for predicting AF recurrent postablation, in a large "all comers" Chinese cohort. This simple clinical risk score (that any clinician can use in the everyday clinic) can help assess the likelihood of recurrence of AF following catheter ablation.

Whole Genome Sequence Identified a Rare Homozygous Pathogenic Mutation of the DSG2 Gene in a Familial Arrhythmogenic Cardiomyopathy Involving Both Ventricles.

BACKGROUND: This study was designed to identify the pathogenic mutation in a Chinese family with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using whole genome sequencing (WGS). METHODS AND RESULTS: Probands II:1 and II:2 underwent routine examinations for diagnosis. Genomic DNA was extracted from the peripheral blood of family members and analyzed using WGS. A total of 60,285 single-nucleotide polymorphisms (SNP) and 13,918 insertions/deletions (InDel) occurring in the exonic regions of genes and predisposing to cardiomyopathies and arrhythmias were identified. When filtered using the 1000 Genomes Project (2014 version), NHLBI ESP6500, and ExAC databases, 12 missense SNP and 2 InDel in exonic regions remained, the allele frequencies of which were <0.01 or unknown. The potentially pathogenic mutations that occurred in the genes DSG2, PKP4, PRKAG2, FOXD4, CTTN, and DMD, which were identified by SIFT or PolyPhen-2 software as "damaging," were validated using Sanger sequencing. Probands II:1 and II:2 shared an extremely rare homozygous mutation in the DSG2 (p.F531C) gene, which was also demonstrated using intersection analysis of WGS data from probands II:1 and II:2. Electron microscopy and histological staining of myocardial biopsies showed widened and destroyed intercalated discs, and interrupted, atrophic, and disarranged myocardial fibers, and hyperplastic interstitial fibers, collagen fibers, and adipocytes were infiltrated and invaded. CONCLUSIONS: A homozygous mutation of DSG2 p.F531C was identified as the pathogenic mutation in patients with ARVC/D involving both ventricles, as a result of widened and impaired intercalated discs, interrupted myocardial fibers, and abnormally hyperplastic interstitial fibers, collagen fibers, and adipocytes.

Incidence and outcomes of cerebrovascular events complicating catheter ablation for atrial fibrillation.

AIMS: Cerebrovascular complications are relatively uncommon, but severe adverse events are associated with catheter ablation of atrial fibrillation (AF). This study aimed to investigate the incidence, risk factors, and hospital outcomes of cerebrovascular events complicating AF ablation. METHODS AND RESULTS: Cerebrovascular complications occurring during the procedure or hospitalization after AF ablation were assessed. Cerebrovascular events occurred in 9 of 1946 consecutive procedures (0.46%). Seven patients (0.36% per procedure) were diagnosed with ischaemic stroke and two patients (0.1% per procedure) with intracranial haemorrhage (ICH). Six events (6/9, 66.7%) occurred during the ablation and the remainders within 24 h after the ablation. Multivariable analysis revealed that previous ischaemic stroke [odds ratio (OR) 10.549; 95% confidence interval (CI) 2.551-43.625, P = 0.001] and mechanical valve replacement (OR 3.261; 95% CI 1.337-7.953, P = 0.009) were independent predictors. In a separate model, CHA2DS2-VASc score ≥3 (OR 7.992; 95% CI 2.046-31.215, P = 0.003) and mechanical valve replacement (OR 4.104; 95% CI 1.644-10.245, P = 0.002) were significantly associated with cerebrovascular complications. All patients survived to discharge except the two cases with ICH. CONCLUSION: Cerebrovascular complications related to catheter ablation of AF are relatively infrequent and typically occur early either during the procedure or within the first 24 h after AF ablation. Previous ischaemic stroke, mechanical valve replacement, and CHA2DS2-VASc score ≥3 are independent predictors of such complications. The majority of these events are ischaemic stroke with a benign clinical outcome, while ICH may correlate with poor prognosis.

Features of accessory pathways in adult Ebstein's anomaly.

AIMS: The aim of the study was to describe the complex electrophysiological features of accessory pathways (APs) in adult Ebstein's anomaly (EA). METHODS AND RESULTS: We performed a retrospective study of 17 consecutive adult EA cases with APs who underwent electrophysiological study and radiofrequency catheter ablation (RFCA) from November 2011 to May 2013. There were a total of 24 atrioventricular reentrant tachycardias (AVRTs) due to 23 APs, including 20 (87.0%) non-decremental conducting, 2 (8.7%) decremental conducting, and 1 (4.3%) nodofascicular bundle. Six (6/17 = 35.3%) patients had two APs while others had only one. Twenty-one APs (91.3%) in 15 patients were manifested and 2 APs (8.7%) in 2 patients were concealed. Six APs (26.1%) were broad, while 17 APs (73.9%) were narrow in width. Two patients suffered from duodromic tachycardias mediated by two APs. Accessory pathways were mainly located on the posterior, posteroseptal, and posterolateral tricuspid annulus (TA). Right ventriculography confirmed that all APs were located on the anatomic TA. All the patients remained free from tachycardias during 11.9 ± 6.8 months of follow-up after RFCA. For the 15 patients with manifest APs, 10 patients' electrocardiograms (ECGs) after RFCA demonstrated morphologies of right bundle branch block, while 5 patients' ECGs were normal. CONCLUSIONS: Accessory pathways in EA are predominantly right-sided, manifest and localize to the lower half of the anatomic TA. A number of APs in EA have broad widths. The incidence of multiple APs is high in these patients and RFCA is effective.

Combined approach improves the outcomes of catheter ablation of idiopathic ventricular arrhythmias originating from the vicinity of tricuspid annulus.

BACKGROUND: Ablation of idiopathic ventricular arrhythmias (VAs) originating from the vicinity of tricuspid annulus (TA) is often unsuccessful via inferior approach. We report the initial experience with catheter ablation of VAs arising from the vicinity of the TA via superior approach. METHODS: We retrospectively studied 36 patients with VAs arising from the vicinity of TA who underwent ablation via transfemoral vein approach first. If patients had a failed prior ablation or VAs recurred during follow-up, they were referred for repeat ablation via transsubclavian vein approach. RESULTS: Among 36 patients, 11 (30.6%) patients (five failed during the index procedure and six recurred during the follow-up) were assigned to perform repeat ablation via the transsubclavian vein approach. After the final procedure two patients recurred again, and success rate increased from 69.5% (25/36) to 94.4% (34/36). Amplitudes of the atrial electrograms of all successful ablation sites via the transsubclavian vein approach was <0.036 mV. CONCLUSIONS: The transsubclavian vein approach plus transfemoral vein approach improve the outcomes of catheter ablation of idiopathic VAs originating from the vicinity of TA. The transsubclavian vein approach is a feasible alternative for VAs, which has been refractory to ablation via the inferior approach.