Functional analysis of a novel SCN5A mutation G1712C identified in Brugada syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To elucidate the molecular and electrophysiological mechanisms of Brugada syndrome through functional analysis of a novel SCN5A gene mutation G1712C.</p><p><b>METHODS</b>A recombinant plasmid pRc<CMV-hH1 containing the mutant human cardiac sodium channel α subunit (hH1) cDNA was constructed using in vitro PCR-based site-directed mutagenesis technique. LipofectamineTM 3000 was used to transfect the plasmid DNA into HEK293 cell line to induce stable expression of Nachannel β1-subunit, and the positive colonies were selected by screening with G418.The standard liposome method was used to transiently transfect HEK293 cells with either the wild-type or mutant Nachannel subunits (hH1 and mhH1, respectively), and the macroscopic Nacurrents were recorded using whole-cell patch-clamp technique. Data acquisition and analysis, generation of voltage commands and curve fitting were accomplished with EPC-10, PatchMaster and IGOR Pro 6.0.</p><p><b>RESULTS</b>An HEK293 cell line that stably expressed Nachannel β1-subunit was successfully established. After transient transfection with the WT subunit, large Nacurrents were recorded from the stable β1-cell line. Transient transfection with the G1712C subunit, however, did not elicit a Nacurrent in the cells.</p><p><b>CONCLUSION</b>Compared with normal Nachannel, the wild-type channel exhibits a similar sodium current. The characteristic kinetics of sodium channel of WT-hH1 was identical to that in normal cardiac muscle cell, and the missense mutation (G1712C) in the P-loop region of the domain IV may have caused the failure of sodium channel expression.</p>

Zero-fluoroscopy catheter ablation for idiopathic premature ventricular contractions from the aortic sinus cusp / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the safety, feasibility, and efficacy of a completely nonfluoroscopic approach to radiofrequency catheter ablation (RFCA) using CARTO3 and ablation with conventional fluoroscopic guidance for treatment of idiopathic premature ventricular contractions from the aortic sinus cusp (ASC-PVCs).</p><p><b>METHODS</b>From April 2013 to October 2015, we prospectively enrolled 52 consecutive patients with ASC-PVCs scheduled for either CARTO3 mapping-guided zero-fluoroscopy ablation (group A, n=23) or conventional fluoroscopic ablation (group B, n=29). The success rates, rates of complications, rates of recurrences, number of radiofrequency applications, procedure time, mapping time and fluoroscopy time were compared between the 2 groups.</p><p><b>RESULTS</b>s No significant differences were found in the success rates between the 2 groups [22/23 (96%) vs 24/29 (83%), P=0.21]. No major complications occurred during the procedures in either group. There was no significant difference with regard to the procedure time between the two groups (79.6∓8.8 vs 77.4∓7.2 min, P=0.332). The procedure was completed without any fluoroscopy use in group A, while the mean fluoroscopy time in group B was 23.1∓6.0 min. Group A showed a shorter mapping time than group B (4.3∓1.7 vs 7.8∓2.6 min, P<0.01) with significantly fewer radiofrequency applications (4.8∓1.1 vs 7.9∓3.2, P<0.01). The recurrence rates were comparable between the two groups over a follow-up period of 5 to 20 months.</p><p><b>CONCLUSION</b>Compared with the conventional fluoroscopic technique, the zero-fluoroscopy approach can shorten the total procedure time and the ablation time with significantly reduced RF applications to eliminate ionizing radiation exposure in RFCA. RFCA guided by CARTO3 system without fluoroscopy is feasible, safe, and effective for treatment of ASC-PVCs.</p>

Correlation of Tp-e interval and Tp-e/Q-T ratio with malignant ventricular arrhythmia in patients with implantable cardioverter-defibrillator for primary prevention / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether Tpeak-Tend interval (Tp-e) and Tp-e/QT ratio are associated with malignant ventricular arrhythmia in patients with implantable cardioverter-defibrillator (ICD) for primary prevention.</p><p><b>METHODS</b>A cohort of 68 consecutive patients with chronic heart failure undergoing standard ICD for primary prevention indications (NYHA function class II-III, left ventricular ejection fraction ≤35%, systolic cardiomyopathy without prior malignant ventricular arrhythmia) were enrolled in this study. The patients were followed up for 18-48 months and were divided into high-risk group and low-risk group according to the occurrence of the endpoint events of sudden cardiac death (SCD), ventricular tachycardia (VT), or ventricular fibrillation (VF). Electrocardiographic and echocardiographic characteristics, Tp-e, and Tp-e/QT ratio were analyzed in all cases before ICD implantation.</p><p><b>RESULTS</b>During the follow-up, ICD shock for sustained ventricular tachycardia or ventricular fibrillation occurred in 11 patients; nonsustained ventricular tachycardia (NSVT) that did not require therapy was detected by ICD in 7 patients (high-risk group, 18 cases). ICD did not detect ventricular tachycardia or ventricular fibrillation in 50 patients (low-rsk group). Compared with the low-rsik group, the high-risk group had an increased Tp-e/QT ratio (0.27±0.04 vs 0.22±0.05 P<0.01) and an increased Tp-e (105±15 vs 90±17 ms P<0.01). ROC analysis revealed that a Tp-e/QT ratio ≥0.255 had a sensitivity of 72.2% and a specificity of 65.9%, and a Tp-e ≥103 ms had a sensitivity of 66.7% and a specificity of 67.9% for predicting VT and VF in these patients.</p><p><b>CONCLUSION</b>Increased Tp-e and Tp-e/QT ratio are associated with increased risks of ventricular arrhythmias in patients with ICD for primary prevention.</p>

Early repolarization syndrome and recurrent syncope in two Chinese pedigrees / 中华心血管病杂志

<p><b>OBJECTIVE</b>to investigate the clinical characteristics in two families with early repolarization syndrome (ERS) and recurrent syncope.</p><p><b>METHOD</b>all family members including the probands were screened with routine clinical examination, electrocardiography, echocardiography, Holter recording, chest x-ray, head-up tilt test and blood biochemistry.</p><p><b>RESULTS</b>there was no clinical evidence of organic heart disease in all members from the two families. Proband 1 showed recurrent syncope, ERS and repeated torsade de pointes ventricular tachycardia and ventricular fibrillation were documented with resting ECG. ERS was detected in one brother, one nephew and one son from him and all were free of cardiac events including syncope, cardiac arrest and sudden cardiac death. Proband 2 showed recurrent syncope, ERS and ST segment arched upward elevation in V(1)-V(3) were documented by ECG. His father suffered sudden cardiac death at the age of 65 and asymptomatic ERS was detected in one of his nephew.</p><p><b>CONCLUSIONS</b>ERS is not always linked with benign clinical course and can sometimes lead to repeated syncope, torsade de pointes ventricular tachycardia and ventricular fibrillation. Pedigree research is of importance for ERS.</p>

Therapeutic effect of recombinant human brain natriuretic peptide for treatment of decompensated heart failure: comparison with nitroglycerin / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic effect of recombinant human brain natriuretic peptide (rhBNP) and nitroglycerin on acute decompensated heart failure (ADHF).</p><p><b>METHODS</b>Fifty ADHF patients were randomly divided into rhBNP group and nitroglycerin group. In all the patients, dyspnea and global clinical status were assessed before and at 30 min, 6 h and 24 h after drug administration, and the volume of fluid intake and urine along with hemodynamic parameters was recorded 24 h after drug administration. In the nitroglycerin group, the patients received an initial nitroglycerin dose of 5 microg/min, with subsequent dose increment of 5 microg/min every 3 to 5 min; the dose was adjusted individually according to the hemodynamics of the patients. The patients in rhBNP group were given rhBNP at the initial dose of 1.5 microg/kg by with an intravenous bolus injection followed by infusion at the rate of 0.0075 microg.kg(-1).min(-1) for 72 h.</p><p><b>RESULTS</b>At 30 min and 6 h after drug administration, the patients in the rhBNP group showed significant greater improvement of dyspnea (P=0.042 and 0.019) and global clinical status (P=0.018 and 0.044) than those in the nitroglycerin group, but 24 h after drug administration, no significant difference was noted between the two groups (P=0.192 and 0.179). Twenty-four hours after drug administration, the mean urine volume was significantly greater in rhBNP group than in nitroglycerin group (1513.8-/+242.9 vs 1341.2-/+239.7 ml, P=0.015), and the ejection fraction increased and pulmonary arterial pressure and systolic blood pressure decreased at greater amplitude in the former group (P=0.001,0.000 and 0.002, respectively). At 72 h, the numbers of premature ventricular contraction and couplets premature beats and onset of paroxysmal ventricular tachycardia were significantly reduced in rhBNP group as compared with the nitroglycerin group (P=0, 0.001 and 0.002, respectively).</p><p><b>CONCLUSION</b>RhBNP promotes urine excretion, decreases pulmonary arterial pressure and increases left ventricular ejection fraction to improve dyspnea and global clinical status and reduce the onset of ventricular arrhythmia in ADHF patients.</p>

Clinical features of idiopathic ventricular tachycardia of various types and their radiofrequency ablation therapy / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the clinical features idiopathic ventricular tachycardia (IVT) and evaluate the effect of radiofrequency ablation therapy for their management.</p><p><b>METHODS</b>An retrospective analysis was conducted in 165 IVT patients who received radiofrequency ablation therapy. IVT was classified into 3 types according to the site of origin, namely the right ventricular outflow tract (RVOT-IVT, 86 cases), left ventricular septum (LV-IVT, 75 cases), and left Valsalva sinus (4 cases).</p><p><b>RESULTS AND CONCLUSION</b>RVOT-IVT was more frequent in female patients than in male patients (60 vs 26, M/F ratio of 0.43). In LV-IVT, male patients prevailed (54 vs 21, M/F ratio of 2.57), suggesting a gender difference in the incidence of IVT. IVT occurred mainly in young and middle-age patients. Most RVOT-IVT occurred in the third to fourth decade of life (mean 36-/+12 years), and LV-IVT occurred at a younger age than did RVOT-IVT (mean 26-/+15 years, P<0.01). Twelve-lead ECGs revealed left bundle branch block morphology in RVOT-IVT, and most of them presented with frequent premature ventricular contraction and/or non-sustained ventricular tachycardia. All the RVOT-IVT patients were successfully ablated by radiofrequency energy in pace mapping. LV-IVT patients with right bundle branch block morphology presented sustained ventricular tachycardia for most of the time, and 97% of the patients were successfully managed with radiofrequency ablation in activation mapping. Four IVT patients were characterized by atypical bundle branch block, an inferior axis, and an R/S ratio >1 in lead V3 or V2, and their tachycardia was ablated successfully in the left sinus of Valsalva using pace mapping. Radiofrequency ablation is currently an effective procedure for IVT management.</p>