Identification of rare variants in cardiac sodium channel ß4-subunit gene SCN4B associated with ventricular tachycardia.

Ventricular tachycardia (VT) causes sudden cardiac death, however, the majority of risk genes for VT remain unknown. SCN4B encodes a ß-subunit, Navß4, for the voltage-gated cardiac sodium channel complex involved in generation and conduction of the cardiac action potential. We hypothesized that genomic variants in SCN4B increase the risk of VT. We used high-resolution melt analysis followed by Sanger sequencing to screen 199 VT patients to identify nonsynonymous variants in SCN4B. Two nonsynonymous heterozygous variants in SCN4B were identified in VT patients, including p.Gly8Ser in four VT patients and p.Ala145Ser in one VT patient. Case-control association studies were used to assess the association between variant p.Gly8Ser and VT in two independent populations for VT (299 VT cases vs. 981 controls in population 1 and 270 VT patients vs. 639 controls in population 2). Significant association was identified between p.Gly8Ser and VT in population 1 (P = 1.21 × 10-4, odds ratio or OR = 11.04), and the finding was confirmed in population 2 (P = 0.03, OR = 3.62). The association remained highly significant in the combined population (P = 3.09 × 10-5, OR = 6.17). Significant association was also identified between p.Gly8Ser and idiopathic VT (P = 1.89 × 10-5, OR = 7.27). Functional analysis with Western blotting showed that both p.Gly8Ser and p.Ala145Ser variants significantly reduced the expression level of Navß4. Based on 2015 ACMG Standards and Guidelines, p.Gly8Ser and p.Ala145Ser can be classified as the pathogenic and likely pathogenic variant, respectively. Our data suggest that SCN4B is a susceptibility gene for common VT and idiopathic VT and link rare SCN4B variants with large effects (OR = 6.17-7.27) to common VT.

Phenotype and Functional Analyses in a Transgenic Mouse Model of Left Ventricular Noncompaction Caused by a DTNA Mutation.

DTNA encoding dystrobrevin-α (α-DB) is a putative causal gene associated with left ventricular noncompaction cardiomyopathy (LVNC). The aim of the study was to investigate the causal role of DTNA in LVNC using a transgenic mouse model.A missense mutation (c.146A > G, p.N49S) of DTNA was identified in a patient with LVNC by Sanger sequencing. Six independent lines of transgenic mice expressing the mutant DTNA under a myosin heavy chain 6 (Myh6) promoter were generated (Myh6:DtnaN49S). Phenotypic characteristics of DTNA-p.N49S mutations were evaluated by echocardiography, histological observation, and immunoblotting. Multiple trabeculation and a higher ratio of non-compacted to compact myocardial layer were found in the Myh6:DtnaN49S mice compared to the controls. The transgenic mice also showed left ventricular (LV) dilation and cardiac systolic dysfunction. In conclusion, overexpression of the DTNA-p.N49S mutation in a mouse heart can be responsible for the phenotype of deep trabeculation, dilated cardiomyopathy, and cardiac dysfunction, which resembles the phenotype of LVNC.

A novel lamin A/C gene missense mutation (445 V > E) in immunoglobulin-like fold associated with left ventricular non-compaction.

AIMS: Two LMNA mutations (R644C and R190W) have been associated with familial and sporadic left ventricular non-compaction (LVNC). However, the mechanisms underlying these associations have not been elucidated. METHODS AND RESULTS: Genomic DNA was isolated from peripheral blood leucocytes and analysed by direct sequencing. Human embryonic kidney 293 cells were transfected with either wild type or mutant LMNA and SCN5A for whole-cell patch-clamp experiment and fluorescence microscopy. Point mutation modeling for mutant LMNA was also performed. One novel LVNC-associated mutation (V445E) in ß2 sheet of immunoglobulin (Ig)-like fold was found in the proband and his father. We also found that the peak current of sodium channel was markedly reduced in mutant LMNA compared with WT while the activation, inactivation, and recovery curves were not significantly altered. The mutant lamin A/C were aggregated into multiple highlighted particles. Three ß sheets and multiple side chains in Ig-like fold were altered due to the replacement of a valine by glutamic acid. CONCLUSION: Our data associated a novel lamin A/C mutation (V445E) with a sudden death form of familial LVNC. The reduced sodium current in mutant LMNA may account for the advent of malignant ventricular arrhythmias. The altered structures of three ß sheets and side chains may partially explain the aggregation of lamin A/C protein subjacent to the nuclear envelope.

Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction.

OBJECTIVES: Genetic testing, a gold standard for long QT syndrome (LQTS) diagnosis, is time-consuming and costly when all the 15 candidate genes are screened. Since genotype-specific ECG patterns are present in most LQT1-3 mutation carriers, we tested the utility of ECG-guided genotyping in a large cohort of Chinese LQTS patients. METHODS AND RESULTS: We enrolled 230 patients (26 ± 17 years, 66% female) with a clinical diagnosis of LQTS. Genotypes were predicted as LQT1-3 based on the presence of ECG patterns typical for each genotype in 200 patients (85 LQT1, 110 LQT2 and 5 LQT3). Family-based genotype prediction was also conducted if gene-specific ECG patterns were found in other affected family members. Mutational screening identified 104 mutations (44% novel), i.e. 46 KCNQ1, 54 KCNH2 and 4 SCN5A mutations. The overall predictive accuracy of ECG-guided genotyping was 79% (157/200) and 79% (67/85), 78% (86/110) and 80% (4/5) for LQT1, LQT2 and LQT3, respectively. The predictive accuracy was 98% (42/43) when family-based ECG assessment was performed. CONCLUSIONS: From this large-scale genotyping study, we found that LQT2 is the most common genotype among the Chinese. Family-based ECG-guided genotyping is highly accurate. ECG-guided genotyping is time- and cost-effective. We therefore recommend it as an optimal approach for the genetic diagnosis of LQTS.

Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA2DS2-VASc score of ≤1 and without anticoagulant therapy.

Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6-14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0-5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1-1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients.

Comparison of cardiovascular magnetic resonance characteristics and clinical consequences in children and adolescents with isolated left ventricular non-compaction with and without late gadolinium enhancement.

BACKGROUND: Although cardiovascular magnetic resonance (CMR) is showing increasingly diagnostic potential in left ventricular non-compaction (LVNC), relatively little research relevant to CMR is conducted in children with LVNC. This study was performed to characterize and compare CMR features and clinical outcomes in children with LVNC with and without late gadolinium enhancement (LGE). METHODS: A cohort of 40 consecutive children (age, 13.7 ± 3.3 years; 29 boys and 11 girls) with isolated LVNC underwent a baseline CMR scan with subsequent clinical follow-up. Short-axis cine images were used to calculate left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), myocardial mass, ratio of non-compacted-to-compacted myocardial thickness (NC/C ratio), and number of non-compacted segments. The LGE images were analyzed to assess visually presence and patterns of LGE. The primary end point was a composite of cardiac death and heart transplantation. RESULTS: The LGE was present in 10 (25%) children, and 46 (27%) segments were involved, including 23 non-compacted segments and 23 normal segments. Compared with LGE- cohort, LGE+ cohort had significantly lower LVEF (23.8 ± 10.7% vs. 42.9 ± 16.7%, p < 0.001) and greater LVEDV (169.2 ± 65.1 vs. 118.2 ± 48.9 mL/m2, p = 0.010), LVESV (131.3 ± 55.5 vs. 73.3 ± 46.7 mL/m2, p = 0.002), and sphericity indices (0.75 ± 0.19 vs. 0.60 ± 0.20, p = 0.045). There were no differences in terms of number and distribution of non-compacted segments, NC/C ratio, and myocardial mass index between LGE+ and LGE- cohort. In the LGE+ cohort, adverse events occurred in 6 patients compared to 2 events in the LGE- cohort. Kaplan-Meier analysis showed a significant difference in outcome between LGE+ and LGE- cohort for cardiac death and heart transplantation (p = 0.011). CONCLUSIONS: The LGE was present in up to one-fourth of children with LVNC, and the LGE+ children exhibited a more maladaptive LV remodeling and a higher incidence of cardiovascular death and heart transplantation.

The role of variability in night-time mean heart rate on the prediction of ventricular arrhythmias and all-cause mortality in implantable cardioverter defibrillator patients.

AIMS: This study was to use implantable cardioverter defibrillator (ICD) home monitoring (HM) feature to evaluate the role of mean night-time heart rate (MNHR) in the occurrence of ventricular arrhythmias (VAs) and mortality. METHODS AND RESULTS: This study retrospectively analysed clinical and ICD device data in 318 ICD patients. Data of the first 30-day MNHR (recorded 02:00-06:00 am) by HM were collected. The average and standard deviation of 30-day MNHR (AVHR and SDHR, respectively) were then determined in each patient. The primary endpoint was appropriate ICD treatment of VAs. The secondary endpoint was all-cause mortality. During a mean follow-up period of 32 ± 10 months, 179 of the 318 patients (56.3%) experienced VAs, 123 patients (38.7%) were treated by ICD shocks, and 37 patients (11.6%) died. The overall SDHR in this study cohort was 4.5 ± 3.0 bpm. Based on the receiver operating characteristic curve, the cut-off value of SDHR = 3.685 bpm was identified to predict VAs. In the Kaplan-Meier survival, SDHR ≥ 3.685 bpm was associated with increased VAs [hazard ratio (HR) = 1.885; 95% confidence interval (CI) = 1.362-2.609; P < 0.001], shock events (HR = 1.637; 95% CI = 1.11-2.414; P = 0.013), all-cause mortality (HR = 2.42; 95% CI = 1.266-4.627; P = 0.008), and the combined endpoints (HR = 1.872; 95% CI = 1.365-2.567; P < 0.001). In univariate and multivariate Cox models (adjusting for clinical factors), SDHR ≥ 3.685 bpm was still an independent predictor for all endpoints. CONCLUSION: In ICD population, SDHR ≥ 3.685 bpm was an independent predictor for VAs and all-cause mortality.

A common NOS1AP genetic polymorphism, rs12567209 G>A, is associated with sudden cardiac death in patients with chronic heart failure in the Chinese Han population.

BACKGROUND: Variants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated. METHODS AND RESULTS: A total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rs12567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124-1.698 [P = .002], and HR 1.645, 95% CI 1.184-2.287 [P = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054-1.624 [P = .015], and HR 1.601, 95% CI 1.129-2.271 [P = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population (P = .026). CONCLUSIONS: The A allele of rs12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population.

Electrocardiographic difference between ventricular arrhythmias from the right ventricular outflow tract and idiopathic right ventricular arrhythmias.

BACKGROUND: Ventricular arrhythmias (VA) arising from arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT-VA) share the pattern of left bundle branch block (LBBB)/inferior axis. The existence of QRS notching showed a discriminating effect of the two conditions in recent research; however, there are little data regarding the difference in the distribution of QRS notching. The aim of this study was to compare the VA morphology between the two conditions, especially evaluating the diagnostic role of QRS notching. METHODS: Electrocardiographic (ECG) recordings of VA episode with LBBB/inferior axis of 16 ARVD/C and 45 idiopathic RVOT-VA patients (30 originated from the septum, 15 from the free-wall) were gathered and compared. RESULTS: ARVD/C had longer mean QRS duration in all 12 leads, and significant differences existed in leads Ⅰ,Ⅱ,Ⅲ, aVL, aVF, and V1 (P < 0.05). Lead Ⅰ had the largest mean difference of 25.1 ± 5.8 ms. In addition, ARVD/C had more R-wave transition in lead V5 or later (37.5% vs 8.9%, P < 0.01).The presence of QRS notching (15/16 [93.8%] vs 36/45 [80.0%], P = 0.20) and the total number of leads expressing notching (2.88 ± 2.0 vs 2.80 ± 2.0, P = 0.90) were not different between ARVD/C and idiopathic RVOT-VA. However, QRS notching existing simultaneously in leads I and aVL was more common in ARVD/C (43.8% vs13.3%, P = 0.011). CONCLUSION: Longer QRS duration, later precordial R/S transition, and QRS notching in lateral leads (leads Ⅰ and aVL) are useful in discriminating ARVD/C from idiopathic RVOT-VA.

The autopsy study of 553 cases of sudden cardiac death in Chinese adults.

Despite a recent epidemiological study reporting a lower incidence of sudden cardiac death (SCD) in China as compared with that in Western countries, the exact causes of SCD are still unknown. Using a uniform review protocol and diagnostic criteria, a retrospective autopsy study identified 553 cases of SCD in 14,487 consecutive autopsies from eight regions in China representing different geographic and population features. Their ages ranged from 18 to 80 years (median 43.0 years) with a ratio of 4.3/1.0 for male/female. Out-of-hospital deaths and unwitnessed cases accounted for 74.3 and 22.6 %, respectively. The main causes of death were coronary atherosclerotic disease (CAD 50.3 %), myocarditis (14.8 %), and hypertrophic cardiomyopathy (4.5 %), with unexplained sudden death accounting for 12.1 % of the cases. CAD had a proportion of 10.4 % in victims <35 years, lower as compared with 59.0 and 83.0 % in victims aged 35-54 and in victims ≥55 years. On the other hand, myocarditis and unexplained sudden death were major causes and accounted for 34.7 and 22.5 % in victims <35 years. In order to differentiate the degree of the cause-effect relationship between autopsy findings and sudden death, a grading method was used in this series and characterized 24.3 % of findings as certain, 52.9 % as highly probable, and 22.8 % as uncertain. Our data indicated that there most likely are less CAD but more myocarditis and unexplained sudden death in Chinese youth with SCD than in populations from Western countries. Molecular genetic testing should be conducted in those cases with uncertain findings and unexplained sudden death in routine autopsy.

The electrophysiological characteristics of isolated diastolic potentials in idiopathic ventricular arrhythmias arising from the right ventricular outflow tract.

OBJECTIVE: The significance of isolated diastolic potentials (IDPs) in patients with idiopathic ventricular arrhythmias (IVAs) arising from right ventricular outflow tract (RVOT) is currently unknown. The objective of this study was to clarify the characteristics of IDPs and its role in guiding ablation in RVOT-IVAs. METHODS AND RESULTS: Twenty-five consecutive patients with RVOT-IVAs and ten control subjects were studied. Electro-anatomical mapping was performed in RVOT during sinus rhythm. The electrophysiological characteristics of IDPs and its relation to successful ablation site were evaluated. Successful ablation was achieved during IVAs in 22 patients and during sinus rhythm in the remaining three. IDPs were recorded in all patients in the vicinity of successful ablation sites during sinus rhythm before ablation, with the area of 1.44 /- 0.28 cm2, maximal amplitude of 0.32 +/- 0.06 mV and the distance to pulmonary valve of 1.39 +/- 0.25 cm. IDPs could still be recorded after ablation except one. Moreover, IDPs were characterized by decremental and/or automatic property by studying intervals between ventricular activation and IDPs (V-IDPs) during sinus rhythm. And V-IDPs intervals during sinus rhythm were longerthan those during IVAs (P = 0.012). However, IDPs were only recorded in one patient in the control group and the incidence of IDPs was remarkably lower than that in the RVOT-IVAs group (1/10 vs. 25/25, P < 0.001). CONCLUSIONS: IDPs were present in patients with RVOT-IVAs. IDPs area and/or border region might be the successful ablation site and their precise mechanism remains to be clarified.

Clinical characteristics and long-term prognosis in patients with chronic heart failure and reduced ejection fraction in China.

AIMS: Chronic heart failure with reduced ejection fraction (CHF-REF) remains a major public health problem with high morbidity and mortality, but the data on current treatment status and long-term prognosis in China were still missing. METHODS: Among prospectively recruited 2368 patients with CHF-REF in 10 hospitals, 2154 patients provided complete followed data. Two aetiology subgroups (dilated cardiomyopathy, DCM and ischaemic cardiomyopathy, ICM) were classified. Clinical data and long-term prognosis were analysed. RESULTS: After a median follow-up of 52 months, 850 (39.46%) patients died, of whom 302 (35.53%) were sudden cardiac death (SCD). Unadjusted rates of all-cause mortality and SCD were higher in DCM than those in ICM (p<0.001 for both modes of death), but mortalities were comparable after adjustment for co-variables (p=0.387 and p=0.483 respectively). ACEIs/ARBs, aldosterone receptor antagonists, ß-blockers and diuretics were dominant prescribed drugs with the prescription rates of 65.97%, 74.61%, 68.29% and 74.37% respectively. Multivariable analysis identified co-morbidities (eg, hypertension), NHYA class, ventricular tachycardia/fibrillation (VT/VF), QRS duration, left ventricular EF and creatinine as independent predictors of mortalities, whereas ACEIs/ARB, ß-blockers and statins were associated with better prognosis. Survived from sustained VT/VF episodes had the highest predictive value for SCD (HR, 4.230; 95% CI, 2.500-7.157; p<0.001). The predictors for mortalities in DCM and ICM were different. CONCLUSIONS: Patients with CHF-REF had a poor prognosis in China despite being under current standard therapies, especially patients with DCM. Predictors for all-cause mortality and SCD might be identified for evaluating the prognosis of these patients.

Digenic inheritance novel mutations in SCN5a and SNTA1 increase late I(Na) contributing to LQT syndrome.

SCN5A and SNTA1 are reported susceptible genes for long QT syndrome (LQTS). This study was designed to elucidate a plausible pathogenic arrhythmia mechanism for the combined novel mutations R800L-SCN5A and A261V-SNTA1 on cardiac sodium channels. A Caucasian family with syncope and marginally prolonged QT interval was screened for LQTS-susceptibility genes and found to harbor the R800L mutation in SCN5A and A261V mutation in SNTA1, and those with both mutations had the strongest clinical phenotype. The mutations were engineered into the most common splice variant of human SCN5A and SNTA1 cDNA, respectively, and sodium current (INa) was characterized in human embryonic kidney 293 cells cotransfected with neuronal nitric oxide synthase (nNOS) and the cardiac isoform of the plasma membrane Ca-ATPase (PMCA4b). Peak INa densities were unchanged for wild-type (WT) and for mutant channels containing R800L-SCN5A, A261V-SNTA1, or R800L-SCN5A plus A261V-SNTA1. However, late INa for either single mutant was moderately increased two- to threefold compared with WT. The combined mutations of R800L-SCN5A plus A261V-SNTA1 significantly enhanced the INa late/peak ratio by 5.6-fold compared with WT. The time constants of current decay of combined mutant channel were markedly increased. The gain-of-function effect could be blocked by the N(G)-monomethyl-l-arginine, a nNOS inhibitor. We conclude that novel mutations in SCN5A and SNTA1 jointly exert a nNOS-dependent gain-of-function on SCN5A channels, which may consequently prolong the action potential duration and lead to LQTS phenotype.

[Retrospective analysis on the clinical features and management of acute and subacute right ventricular perforation by pacemaker lead].

OBJECTIVE: To describe the clinical characteristics and management of the acute and subacute cardiac perforation by pacing leads. METHODS: We retrospectively analyzed clinical data of patients with acute and subacute right ventricular perforation by pacemaker lead occurred in our hospital between 2006 and 2011. RESULTS: Seven cases of confirmed acute and subacute right ventricular perforation by pacemaker lead were enrolled. The perforation rate was 0.15%, 2 cases of perforation occurred during the procedure. The main manifestation was low blood pressure and pericardial effusion. These two patients with cardiac tamponade underwent urgent percutaneous pericardiocentesis and patients recovered without complication. The remaining 5 cases of perforation occurred within 4-16 days after the pacemaker implantation. The main symptoms were diaphragm stimulation and chest pain. Signs of leads dysfunction were observed in all 5 patients. The diagnosis of cardiac perforation was confirmed by chest X-ray, echocardiography, or computed tomography. In all these 5 patients, the leads were removed by simple traction under fluoroscopic guidance with surgical backup support, no complication was observed. CONCLUSION: Acute and subacute right ventricular perforation is a rare but serious complication of pacemaker implantation. In most patients, the leads can be safely removed under fluoroscopic guidance with surgical backup support and close monitoring.

[Radiofrequency catheter ablation of the premature ventricular contractions originating from His bundle region].

OBJECTIVE: To explore the electrocardiogram and 3-dimensional electroanatomic mapping features and radiofrequency catheter ablation efficacy of patients with premature ventricular contractions (PVCs ) originating from His bundle region. METHODS: Between February 2009 and February 2011, 10 consecutive patients ( 4 male, aged from 19 to 59 years) who underwent ablation for frequent PVCs originating close to His bundle region in our department were included. Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm-tip ablation catheter. RESULTS: Among these 10 patients with PVCs originating from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC. Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and 1 patient with PVCs originated from NCC showed RBBB morphology. At the successful ablation sites, local ventricular activation v wave was detected 22-52 (32.6 ± 10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance between target and His bundle was 5.0-8.4(7.0 ± 1.1)mm. Ablation was successful in all 10 patients without complications (PVCs < 500 beats/24 h post ablation). CONCLUSION: PVCs originating near the His bundle have similar electrocardiographic and electrophysiological characteristics for PVSc originated from the RVOT or ASC. Because of the close anatomical relationship between RVOT and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the site of PVCs origin and to guild successful ablation.

[Value of identifying the slow conduction zone of idiopathic left ventricular tachycardia by electroanatomic mapping].

OBJECTIVE: To explore the value of identifying slow conduction zone(SCZ) of idiopathic left ventricular tachycardia(ILVT) by electroanatomic mapping. METHODS: Twelve patients with ILVT were mapped by a 3-dimensional electroanatomic (EA) mapping system. Left posterior fascicular potential (PP) and the SCZ with diastolic potential (DP) in LV during sinus rhythm (SR) and ventricular tachycardia (VT) were mapped after a three-dimensional endocardial geometry of the left ventricular was established. Then we investigated the electrophysiological and anatomic characteristics of SCZ. RESULTS: EA mapping was successfully performed in 9 patients during SR and VT, and in 3 patients during VT. The SCZ with DP was located at the inferoposterior septum, and the length of the SCZ was (25.1 ± 2.2) mm with a conduction velocity of (0.08 ± 0.01) m/s. There was no difference in these parameters between patients during SR and VT (P > 0.05). There was one area with PP located at the posterior septum. The areas with both DP and PP were found in 9 patients during SR and VT. In addition, this area was coincided with such area during VT during SR and radiofrequency ablation targeting the site within the area abolished VT in all patients. CONCLUSIONS: The ILVT substrate within the junction area of the SCZ and the posterior fascicular can be identified by EA mapping and used to guide the ablation of ILVT.

[Preferential conduction to right ventricular outflow track leads to left bundle-branch block morphology in patient with premature ventricular contraction originating from the aortic sinus cusp].

OBJECTIVE: The purpose of this study was to explore the relationship between originate and breakout and radiofrequency catheter ablation strategy in patients undergoing radiofrequency ablation for premature ventricular contractions originating from the aortic sinus cusp (ASC) using 3-dimensional electro anatomic mapping. METHODS: This study included 21 consecutive patients (10 male) underwent ablation for frequent PVCs originating from ASC in our hospital between May 2009 and February 2012. Electro anatomic mapping and ablation of right ventricular outflow track (RVOT) and left ventricular outflow track (LVOT) were performed with the 7F 4-mm-tip ablation catheter from right femoral vein and artery. Activation mapping and pacing mapping were performed in all patients. RESULTS: Ablation was successful in all 21 patients successful ablation target in left coronary sinus cusp (LCC, n = 17), in right coronary sinus cusp (RCC, n = 2) and in noncoronary sinus cusp (NCC, n = 2). Seven patients showed a RBBB morphology (group A) and 14 patients showed a LBBB morphology (group B). In group A, earliest ventricular activation (EVA) was recorded 22 - 34 (27.4 ± 4.6) ms earlier before QRS at the site of catheter ablation in ASC. In group B, EVA was later in RVOT than that in ASC in 5 patients and EVA at the site of catheter ablation in RVOT and ASC was 22 - 28 (25.2 ± 2.7) ms and 26 - 40 (32.8 ± 5.2) ms, respectively (t = -3.6, P = 0.024) while EVA was earlier in the remaining 9 patients and EVA recorded in RVOT and ASC was 22 - 38 (28.7 ± 5.9) ms and 18 - 28 (22.7 ± 3.6) ms, respectively (t = 3.8, P = 0.005). CONCLUSION: Patients with premature ventricular contractions originating from the ASC often show preferential conduction to the RVOT, which may explain the LBBB morphology of ECG in these patients.

Novel SCN5A frame­shift mutation underlying in patient with idiopathic ventricular fibrillation manifested with J wave in inferior lead and prolonged S­wave in precordial lead.

Mutations in the SCN5A gene has been recognized as resulting in a series of life-threatening arrhythmias. However, it also causes idiopathic ventricular fibrillation (IVF) with J wave in inferior leads and prolonged S-wave upstroke in precordial leads, which has not been previously reported. The present study aimed to study the mechanisms of a patient with IVF manifested with J wave in inferior leads and prolonged S-wave upstroke in precordial leads. The electrocardiograms (ECG) of the proband were recorded and genetic testing was conducted. Patch-clamp and immunocytochemical studies were performed in heterologously transfected 293 cells. The VF attacks was documented in a 55-year-old male proband with syncope episodes. 12-lead ECG shown the transient J wave in the inferior leads and prolonged S-wave upstroke in precordial V1-V3 leads in the same timeframe. Genetic analysis revealed a novel 1 base deletion (G) at position 839 in exon 2 in SCN5A gene (C280S*fs61), which causes a severe truncation of the sodium channel. The functional study revealed that in 293 cells transfected with mutant channel, no sodium current could be recorded even though the immunocytochemical experiment confirmed the truncated sodium channel existed in cytosol. The kinetics of the wild-type (WT) channel were not altered when co-transfected with C280S*fs61 mutant which suggested a haploinsufficiency effect of sodium channel in the cells. The present study identified a novel C280Sfs*61 mutation that caused the 'loss of function' of the sodium channel by haploinsufficiency mechanism. The reduced sodium channel function in the heart may cause conduction delay that may underlie the manifestation of J wave and prolonged S-wave upstroke associated with IVF.

Identification of the slow conduction zone in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia using electroanatomic mapping.

BACKGROUND: Although idiopathic left ventricular tachycardia (ILVT) has been shown to possess a slow conduction zone (SCZ), the details of the electrophysiological and anatomic aspects are still not well understood. OBJECTIVE: We hypothesized that the SCZ can be identified using a 3-dimensional electroanatomic (EA) mapping system. METHODS: Ten patients with ILVT were mapped using a 3-dimensional electroanatomic (EA) mapping system. After a 3-dimensional endocardial geometry of the left ventricular was created, the conduction system with left Purkinje potential (PP) and the SCZ with diastolic potential (DP) in LV were mapped during sinus rhythm (SR) and ventricular tachycardia (VT) and were tagged as special landmarks in the geometry. The electrophysiological and anatomic aspects of it were investigated. RESULTS: EA mapping during SR and VT was successfully performed in 7 patients, during VT in 3 patients. The SCZ with DPs located at the inferoposterior septum was found in 7 patients during SR and all patients during VT. The length of the SCZ was 25.2 ± 2.3 mm with conduction velocity 0.08 ± 0.01 m/s. No differences in these parameters were found between patients during SR and VT (P > 0.05). An area with PP was found within the posterior septum. A crossover junction area with DP and PP was found in 7 patients during SR and VT. This area with DP and PP during SR coincided or were in proximity to such area during VT and radiofrequency ablation targeting the site within the area abolished VT in all patients. CONCLUSION: The ILVT substrate within the junction area of the SCZ and the posterior fascicular can be identified and can be used to guide the ablation of ILVT.

The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure.

AIMS: To investigate the relationship between electrocardiogram (ECG) parameters [J wave, fragmented QRS (fQRS), QTc, the peak-to-end interval of T wave (Tp-Te)], and sudden cardiac death (SCD) in chronic heart failure (CHF). METHODS AND RESULTS: The ECGs of 1570 CHF patients, 572 cases with dilated cardiomyopathy (DCM) and 998 cases with ischaemic cardiomyopathy (ICM) were analysed with the endpoint being an SCD or non-SCD (NSCD). During a median follow-up period of 36 months (0.40-65 months), 438 (27.89%) patients died, of which 158 (35.84%) were SCD. Overall, the occurrence of J wave, fQRS, and long Tp-Te were greater in SCD patients than that of NSCD patients (all P< 0.01). For DCM cases, more SCD patients had J waves observed in the inferior leads than that in the NSCD group (26.78 vs. 13.07%, P<0.001). However, ICM cases with SCD did have more fQRS in the inferior leads than that with NSCD (42.16 vs. 26.67%, P= 0.01). After adjusting for other risk factors, Cox regression analysis revealed that presence of J wave or fQRS in the inferior leads predicted a higher risk for SCD in DCM [hazard ratio (HR), 4.095; 95% confidence interval (CI), 2.132-7.863] and ICM (HR, 2.714; 95% CI, 1.809-4.072) patients. A left ventricular ejection fraction ≤ 30% also predicted SCD and NSCD in DCM and ICM patients. In contrast, the predictive value of QTc and Tp-Te for SCD was not significant. CONCLUSIONS: Presence of J wave or fQRS in the inferior leads predicted higher risk of SCD in DCM and ICM patients and might serve as independent predictors for SCD in patients with CHF.