Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

VEGF gene rs3025039C/T and rs833052C/A variants are associated with bladder cancer risk in Asian descendants.

INTRODUCTION: Polymorphisms of vascular endothelial growth factor (VEGF) gene were evaluated in a number of studies to evaluate bladder cancer (BCa) susceptibility but with controversial conclusions. MATERIAL AND METHODS: We performed a pooled analysis and used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to investigate the correlation between VEGF gene rs3025039C/T and rs833052C/A variants and risk of BCa. Furthermore, we utilized in silico tools to demonstrate the relationship of VEGF expression correlated with BCa susceptibility and survival time. RESULTS: A total of eight studies including 4359 BCa patients and 5417 control subjects were enrolled in our study. For VEGF rs3025039C/T, a significant association was indicated between this variant and BCa risk in homozygote comparison (OR = 1.51; 95% CI = 1.13-2.02; P heterogeneity = 0.815) and recessive genetic model (OR = 1.49; 95% CI = 1.12-1.99; P heterogeneity = 0.874), in particular in an Asian population subgroup. For VEGF rs833052C/A, we observed a positive association between this variant and BCa susceptibility in Asian descendants. Results from in silico tool showed evidence that VEGF expression in bladder carcinoma tissue is higher than that in normal counterpart (transcripts per kilobase million = 7.21 vs 6.85; P < 0.05). CONCLUSIONS: The VEGF gene rs3025039C/T and rs833052C/A variants may contribute to the risk of developing BCa, especially in Asian descendants. Future larger sample studies should be continued to focus on this issue in more detail.

[Catheter ablation of epicardial accessory pathway associated with coronary sinus musculature].

OBJECTIVE: To report the single-center clinical experience of catheter ablation of epicardial accessory pathway associated with coronary sinus musculature. METHODS: The data of 721 cases of left sided accessory pathway ablation were retrospectively analyzed. Ablation in the coronary sinus was performed in 17 (2.4 %) cases [11 males, mean age (37 ± 11) years]. RESULTS: Among the 17 cases, the accessory pathway was successfully ablated in middle cardiac vein and posterior lateral coronary sinus in 11 and 6 cases, respectively. Deverticulum of middle cardiac vein was seen in 2 cases. Mean time required to block the accessory pathway was (4.7 ± 2.7) s. An accessory pathway potential could be recorded at the target site in 10 out of 17 patients (59%). During a mean (21 ± 16) months follow up, only one patient experienced recurrence who was successfully cured by a second ablation session. No procedure related complication was reported. CONCLUSION: About 2.4% of left accessory pathway may have epicardial connection locating at middle cardiac vein or lateral part of the coronary sinus and require epicardial ablation. The epicardial ablation is safe and effective, warrants an excellent long-term results.

Downregulation of quinone reductase 2 attenuates vascular smooth muscle cells proliferation and neointimal formation in balloon injured rat carotid artery.

BACKGROUND/AIMS: Quinone reductase 2 (NQO2) is a flavoprotein that catalyzes the metabolic reduction of quinines, but its biological mechanism in vascular smooth muscle cells (VSMCs) is unclear. The aim of this study was to evaluate the role of NQO2 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery. METHODS: Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 50 µL solution of NQO2-siRNA-GFP lentiviral vectors, NC-siRNA-GFP lentiviral vectors or PBS for 1 h. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with NQO2-siRNA-GFP or NC-siRNA-GFP lentiviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. In order to detect the vascular or intracellular ROS level, the lentiviral vectors without GFP were used to transfect the injured common carotid arteries and the cultured rat VSMCs. RESULTS: Lentiviral vectors bearing NQO2 siRNA could reduce NQO2 protein level and suppress NQO2 mRNA expression in balloon injured artery walls and cultured rat VSMCs. Downregulation of NQO2 significantly suppressed VSMCs proliferation and intimal formation. NQO2 siRNA treatment could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs. CONCLUSION: Our study suggests that downregulation of NQO2 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury.

Update analysis of studies on the MMP-9 -1562 C>T polymorphism and cancer risk.

Polymorphisms in the matrix metalloproteinase (MMP) gene have been hypothesized to be functional and may contribute to genetic susceptibility to cancers. The common sequence variation in MMP-9 -1562 C>T (rs3918242), has been involved in cancer risk. However, results of the related published studies were somewhat controversial and underpowered in general. To clarify the role of MMP-9 -1562 C>T genotype in global cancer, we performed a meta-analysis of all the available published studies involving 4,124 cancer patients and 4,728 control subjects. The overall results indicated that there was no major association of the variant on cancer risk. However, stratified analysis by cancer type showed that the MMP-9 -1562 C>T polymorphism has a lower risk in colorectal cancer (OR = 0.80, 95%CI = 0.66-0.96, P (heterogeneity) = 0.391) and lung cancer (OR = 0.70, 95%CI = 0.51-0.96, P (heterogeneity) = 0.959) by allelic contrast. Furthermore, association of the MMP-9 -1562 C>T polymorphism and cancer risk was also observed in hospital-based studies under the dominant genetic model (OR = 0.87, 95%CI = 0.78-0.97, P (heterogeneity) = 0.355), allelic contrast (OR = 0.85, 95%CI = 0.75-0.96, P (heterogeneity) = 0.271) and heterozygote comparison (OR = 0.89, 95%CI = 0.79-0.99, P (heterogeneity) = 0.402). This pooled analysis showed evidence that the MMP-9 -1562 C>T polymorphism may decrease both the colorectal and lung cancer risk. Further prospective studies with larger numbers of participants worldwide are required to evaluate the association in more detail.

[Catheter ablation of focal atrial tachycardia:the topographic distribution and long-term outcome].

OBJECTIVE: To explore the topographic distribution and long-term outcome of catheter ablation for focal atrial tachycardia (AT). METHOD: The data of 207 patients who underwent electrophysiologic study for AT were retrospectively analyzed. RESULTS: A total of 200 AT were identified in 185 patients. The most common site for AT was ostium of the coronary sinus (23.8%), followed by crista terminalis (20.5%), perinodal area (20.0%), cava vena (17.8%), annulus (13.0%), and appendage (10.3%). Eighty percent AT originated from the right atrium, 17.8% originated from the left atrium. AT originated from the left atrium was more common in male than in female (25.0% vs. 13.3%, P = 0.042), while AT originated from the right atrium was more common in female than in male (69.4% vs. 86.7%, P = 0.004). Among the 185 patients, acute success ablation rate was 93.5% (n = 173). The acute success rate in the conventional mapping group was lower than that in the three-dimensional mapping group (79.3% vs. 96.5%, P < 0.01). During a median of 36 months follow up, the AT recurred in 20 patients (success ablation rate 88.4%). Success ablation rate was similar between the conventional mapping group and the three-dimensional mapping group (P > 0.05). CONCLUSIONS: Focal AT commonly originates from ostium of coronary sinus, crystal terminalis, perinodal area, and cava veins. There is a gender related difference in the distribution of focal AT. The radiofrequency catheter ablation yields a satisfying success rate and very low complication rate and could be the first line choice for treating ATs in experienced electrophysiological center.

An algorithm to predict the site of origin of focal atrial tachycardia.

BACKGROUND: Only a few algorithms for predicting the site of origin of focal atrial tachycardia (AT) have been reported. We aimed to develop a new and more effective algorithm. METHODS: Surface 12-lead electrocardiograms were collected during tachycardia and sinus rhythm in 61 patients who received successful radiofrequency ablation. P-wave polarities, durations, and amplitudes were analyzed. Predictive values of the most significant parameters were determined. An algorithm was then developed and prospectively evaluated in 30 new consecutive AT patients. RESULTS: Thirty-six percent (22/61) of the foci were located at the ostium of coronary sinus (CS). Other common foci included pulmonary veins (PVs, n = 15), right atrial appendage (RAA, n = 7), parahisian area (n = 7), and crista terminalis (CT, n = 3). Positive P waves in inferior leads (II, III, and aVF) and a negative P wave in lead aVR indicated high atrial origins (high CT, superior PVs, and RAA, defined as Area A), with a sensitivity of 95% and a specificity of 90%. Negative P waves in inferior leads and a positive P wave in lead aVR suggested right low septal origins (CS ostium and inferior tricuspid annulus, defined as Area B), with good sensitivity and specificity (88% and 89%, respectively). This new P-wave diagnostic algorithm correctly identified the site of origin in 90% of AT cases. CONCLUSION: Combination of data from multiple leads and regrouping of sites of origin provides a better predictive value.

[Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation].

OBJECTIVE: To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs). METHODS: Data from patients with ICD implantation between Jan, 2003 and Jun, 2006 in our hospital were retrospectively analyzed. ES was defined as either ≥ 3 times of ventricular tachyarrhythmias (VTAs) resulting in ICD therapy or VTAs lasting more than 30 s detected by ICD without any therapy within 24 hours. RESULTS: During a follow-up period of (27.5 ± 21.2) months, ES was recorded in 39 cases [34 males, average age (52.0 ± 13.1) years] out of 119 patients (32.8%) and 9 patients died after ES. During the period of storm attack, ES was successfully controlled in 25/30 patients by various interventions, including predisposing factors corrected in 5 cases, ICD reprogramming and antiarrhythmic drugs therapy optimized in 16 cases (one received intravenous injection of metoprolol), and VTAs eliminated by catheter ablation in 4 cases. ES was spontaneously resolved in the remaining 5 cases. In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26.8 ± 13.9) mg/d to (88.9 ± 53.5) mg/d without any adverse effects (9 patients received also oral amiodarone 200 mg/d). Post dosage adjustment, the total VTA episodes [(1.9 ± 1.7) times/month vs. (0.8 ± 0.6) times/month, P = 0.004], incidence of antitachycardia pacing therapies [(4.2 ± 3.8) runs/month vs. (2.3 ± 2.0) runs/month, P = 0.003], as well as electrical cardioversion or defibrillation [(1.1 ± 0.9) times/month vs. (0.4 ± 0.2) times/month, P = 0.001] were significantly decreased. ES was not controlled until a extremely high dosage [225 - 300 (255.3 ± 41.7) mg/d] of metoprolol was reached in the remaining 5 patients. CONCLUSIONS: Metoprolol use is essential and its dosage should be individualized in the majority of ICD recipients with ES. In approximately 1/6 patients, the dosage of metoprolol should be higher than 200 mg/d.

[Clinical characteristics of congenital ventricular aneurysm and diverticula in inland China].

OBJECTIVE: To summarize the clinical characteristics of congenital ventricular aneurysm and diverticula in inland China. METHODS: To identify the literature of congenital aneurysm and diverticula from Wanfang, China National Knowledge Infrastructure (CNKI) and PubMed databases, and to analyze the clinical characteristics of congenital aneurysm and diverticula from January of 2001 to December of 2009. RESULTS: A total of 116 patients [78 men, 1 - 80 (33.5 ± 21.3) years old] with congenital aneurysm or diverticula were included in 109 articles. Twenty-five patients (13 men) were congenital ventricular aneurysm, including a family of 4 patients. Ninety-one patients (65 men) were congenital ventricular diverticula. One hundred patients were detected by echocardiography during medical examination, 34 patients combined with other cardiac anomalies, 4 of which with extracardiac structures. There were 8 patients with ventricular arrhythmia, 8 patients with thrombosis, 2 patients died of cardiac rupture, 4 patients died of sudden death, surgical operation was performed in 46 patients and 3 patients received ablation procedure. All patient did not receive implantable cardioverter defibrillator (ICD) implantation. CONCLUSIONS: Congenital ventricular aneurysm or diverticulum is a rare cardiac malformation. Most congenital left ventricular aneurysms and diverticula are asymptomatic and detected by echocardiography. Congenital ventricular aneurysm or diverticulum may cause ventricular tachycardia, ventricular wall rupture, systemic embolization or sudden death, which had to be treated individually.

Right-sided free wall accessory pathway refractory to conventional catheter ablation: lessons from 3-dimensional electroanatomic mapping.

INTRODUCTION: the aim of this study was to delineate the electroanatomic substrates of right-sided free wall (RFW) accessory pathways (APs) that were refractory to conventional catheter ablation utilizing 3-dimensional (3-D) mapping. METHODS AND RESULTS: eleven patients with RFW APs that failed initial conventional catheter ablation(s) by a mean of 1.9 ± 0.5 attempts were enrolled in the study. Electroanatomic mapping of the right atrium was performed during orthodromic reciprocating tachycardia in 3 patients and right ventricular pacing in 8 patients. The earliest atrial activation site, which represented the atrial insertion of the AP, was separated from the tricuspid annulus by an average of 14.3 ± 3.9 mm, and the local activation time was 27.8 ± 17.0 ms earlier than that of the corresponding annular point. One patient exhibited an AP with wide branching on the atrial side. RF ablation with an irrigated catheter successfully interrupted AP conduction in all patients without complications. CONCLUSIONS: RFW APs resistant to conventional catheter ablation might be due to unique anatomic AP features such as more epicardial course at the annulus level with atrial insertion distant from the tricuspid annulus. Electroanatomic mapping is helpful to accurately localize the atrial insertion sites of these APs and facilitates catheter ablation.

Antidigoxin antiserum prevents endogenous digitalis-like compound-mediated reperfusion injury via modulating sodium pump isoform gene expression.

Endogenous digitalis-like compound (EDLC) is an endogenous ligand of the digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Antidigoxin antiserum (ADA), a selective EDLC antagonist, may lessen myocardial reperfusion injury; however, the molecular mechanisms underlying the effect remain unclear. Therefore, this study investigated whether ADA may prevent myocardial reperfusion injury and modulate gene expression of sodium pump alpha isoforms. Cardiac function was examined in isolated rat hearts subjected to ischemia and reperfusion (I/R). The infarct size, EDLC level, Na+/K+-ATPase activity, and the levels of mRNA for sodium pump alpha isoforms were measured in vivo I/R rat hearts in the presence or absence of ADA. It was found that ADA significantly improved the recovery of cardiac function, decreased infarct size, decreased EDLC level, and recovered Na+/K+-ATPase activity in I/R hearts. Further studies showed that sodium pump alpha1, alpha2, and alpha3 isoform mRNA levels were significantly reduced in I/R hearts, and pretreatment with ADA induced a large increase in the mRNA levels. These results indicate that EDLC may participate in depressing Na+/K+-ATPase activity and sodium pump alpha isoform gene expression in I/R heart. It is suggested that treatment with ADA may prevent EDLC-mediated reperfusion injury via modulating sodium pump isoform gene expression.

Clinical characteristics and long-term prognosis of ischemic and non-ischemic cardiomyopathy.

OBJECTIVES: The different etiology of HF has different prognostic risk factors. Prognosis assessment of ICM and NICM has important clinical value. This study is aimed to explore the predicting factors for ICM and NICM. METHODS: 1082 HFrEF patients were retrospectively enrolled from Jan. 01, 2016 to Dec. 31, 2017. On Jan. 31, 2019, 873 patients were enrolled for analysis excluding incomplete, unfollowed, and unexplained data. The patients were divided into ischemic and non-ischemic group. The differences in clinical characteristics and long-term prognosis between the two groups were analyzed, and multivariate Cox analysis was used to predict the respective all-cause mortality, SCD and rehospitalization of CHF. RESULTS: 873 patients aged 64(53,73) were divided into two groups: ICM (403, 46.16%) and NICM. At the end, 203 died (111 in ICM, 54.68%), of whom 87 had SCD (53 in ICM, 60.92%) and 269 had rehospitalization for HF(134 in ICM, 49.81%). Independent risk factors affecting all-cause mortality in ICM: DM, previous hospitalization of HF, age, eGFR, LVEF; for SCD: PVB, eGFR, Hb, revascularization; for readmission of HF: low T3 syndrome, PVB, DM, previous hospitalization of HF, eGFR. Otherwise; factors affecting all-cause mortality in NICM: NYHA III-IV, paroxysmal AF/AFL, previous hospitalization of HF, ß-blocker; for SCD: low T3 syndrome, PVB, nitrates, sodium, ß-blocker; for rehospitalization of HF: paroxysmal AF/AFL, previous admission of HF, LVEF. CONCLUSIONS: Both all-cause mortality and SCD in ICM is higher than that in NICM. Different etiologies of CHF have different risk factors affecting the prognosis.

Cardiac electrical and mechanical synchrony of super-responders to cardiac resynchronization therapy.

BACKGROUND: Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs. METHODS: We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging. RESULTS: Seventeen SRs were included with LV ejection fraction increased from 33.0 ±â€Š4.6% to 59.3 ±â€Š6.3%. The intrinsic QRS duration after super-response was 148.8 ±â€Š30.0 ms, significantly shorter than baseline (174.8 ±â€Š11.9 ms, P = 0.004, t = -3.379) but longer than BIV-paced level (135.5 ±â€Š16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ±â€Š16.5° vs. 19.8 ±â€Š8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ±â€Š64.2° vs. 60.5 ±â€Š22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ±â€Š8.1° vs. 15.2 ±â€Š6.4°, P = 0.005, t = 3.414; PHB, 60.5 ±â€Š22.9° vs. 46.0 ±â€Š16.3°, P = 0.009, t = 3.136). CONCLUSIONS: SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

Premature ventricular contractions originating from the right ventricular outflow tract: three-dimensional distribution of the target sites and their electrocardiographic characteristics.

1. The purpose of the present study was to explore the relationship between electrocardiogram (ECG) patterns of right ventricular outflow tract (RVOT) premature ventricular contractions and the three-dimensional distribution of the target sites. 2. Thirty-three consecutive patients were included in the study. The target sites were identified by non-contact mapping and confirmed by successful ablation. The distribution of the target sites in the three-dimensional reconstructed geometry of the RVOT was classified in three directions: (i) anterior (A)/posterior (P); (ii) free wall (F)/septal (Se); and (iii) superior (Su)/inferior (I). The ECG characteristics were then analysed according to the three-dimensional distribution of the target sites. 3. The following indices were helpful to identify the position of the target site: (i) QRS duration (> or = 150 msec = F; < 150 msec = Se; P < 0.05); (ii) the R wave pattern in the inferior leads (RR' or Rr' = F; R = Se; P < 0.05); (iii) the R wave amplitude in the inferior leads (high = Se; low = F; P < 0.05); (iv) the initial r wave width in lead V(1) (wide = F; narrow = Se; P < 0.05); (v) the QS wave amplitude in aVR and aVL (if aVR < aVL, A; if aVR > or = aVL, P; P < 0.05); and (vi) the initial r wave amplitude in lead V(1) and V(2) (if V(1) > or = 0.15 mV and V(2) > or = 0.3 mV, Su; if V(1) < 0.15 mV or V(2) < 0.3 mV, I; P < 0.05). 4. In conclusion, the ECG characteristics were associated with target site locations in all three directions.

[Prevalence of Epsilon wave in patients with arrhythmogenic right ventricular cardiomyopathy].

OBJECTIVE: To investigate the prevalence of Epsilon wave in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: The epsilon wave was detected in 32 patients [24 men, mean age (42.3 +/- 13.3) years] with ARVC using three different electrocardiography (ECG) recording methods: standard twelve leads ECG (S-ECG), right precordial leads ECG (R-ECG) and Fontaine bipolar precordial leads ECG (F-ECG). The Epsilon wave was defined as wiggler, small spike wave and smooth potential between the end of the QRS complex and the beginning of the ST segment. RESULTS: Epsilon wave was detected in 37.5%, 37.5% and 50.0% patients with ARVC by S-ECG, R-ECG and F-ECG respectively. The detection rates derived from the three recording methods were similar (P > 0.05). The Epsilon wave was only detectable by S-ECG in one case, by R-ECG in three cases, and by F-ECG in five cases. The detection rate of Epsilon wave was 50.0% by combined use of S-ECG and R-ECG (SR-ECG), 56.3% by combined use of S-ECG and F-ECG (SF-ECG), and 65.6% by combined use of the three recording methods (SRF-ECG). The detection rate was significantly higher by SF-ECG (56.3%) and SRF-ECG (65.6%) than by S-ECG alone (37.5%, all P < 0.05). Most Epsilon waves detected by the S-ECG, R-ECG and F-ECG were small spiked waves. CONCLUSION: Combined use of S-ECG, F-ECG and R-ECG could increase the detection rate of Epsilon wave in patients with ARVC.

Microvolt T-wave alternans complemented with electrophysiologic study for prediction of ventricular tachyarrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: a long-term follow-up study.

BACKGROUND: The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC. METHODS: All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or anti-tachycardia pacing. RESULTS: Thirty-five patients with ARVC (age 38.6 ±â€Š11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0-27.0) µV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ±â€Š7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 µV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33-26.8; P = 0.01) independently predicted positive events in patients with ARVC. CONCLUSIONS: MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

Negative regulation of quinone reductase 2 by resveratrol in cultured vascular smooth muscle cells.

1. Resveratrol, a polyphenol in red wine, has a cardioprotective effect. Resveratrol-targeting protein (RTP) has been purified using a resveratrol affinity column (RAC) and has been identified as quinone reductase type 2 (NQO2). We hypothesize that NQO2 is the target protein of resveratrol in vascular smooth muscle cells (VSMC) and that resveratrol inhibits proliferation of VSMC through its action on NQO2. In the present study, we investigated the correlation between NQO2 regulation and cell proliferation in VSMC in response to resveratrol treatment. 2. The RTP was purified using RAC and was detected with a NQO2 polyclonal antibody. The VSMC were incubated with resveratrol (1, 10 and 50 micromol/L) for 24, 48 and 72 h. Cell proliferation was detected by cell counting and bromodeoxyuridine (BrdU) assay. A lentiviral vector incorporating NQO2 short interference (si) RNA of short hairpin design was constructed and transduced into VSMC. Real-time quantitative polymerase chain reaction was used to measure NQO2 mRNA levels; NQO2 expression was determined by western blot analysis. 3. Using RAC, we extracted a 26 kDa protein from aortic smooth muscle, which was referred to as RTP-26. Proliferation of VSMC was inhibited by resveratrol in a concentration- and time-dependent manner. The mRNA and protein expression of NQO2 was also repressed by resveratrol in a concentration- and time-dependent manner. A similar pattern of inhibition was observed for cells treated with resveratrol (25 micromol/L) as for cells transduced with a lentiviral vector containing siRNA sequences against NQO2. 4. Collectively, these data indicate that the suppression of VSMC proliferation mediated by resveratrol correlates with NQO2 downregulation.

[Detection of gene mutations of SCN5A in 7 patients with Brugada syndrome].

OBJECTIVE: Brugada syndrome is linked to sodium channel mutations and could induce arrhythmias that even lead to sudden death. The purpose of this study was to detect if there was gene mutation of SCN5A in 7 patients with Brugada syndrome and explore the molecular genetic characteristics of this disease. METHOD: Genomic DNA was extracted from peripheral blood of all 7 patients with Brugada syndrome and 41 pairs of PCR primers were designed to amplify all the 28 exons of SCN5A. RESULT: There was no novel mutation in exons of Gene SCN5A in these patients with Brugada syndrome. CONCLUSION: Brugada syndrome might associated gene mutation or other mechanisms independent of SCN5A gene mutation.

Pathway-based analysis of genome-wide association study of circadian phenotypes.

Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms (SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies (GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime, totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.

Association between three genetic variants in kallikrein 3 and prostate cancer risk.

BACKGROUND: Epidemiological studies have assessed the association between kallikrein 3 (KLK3) polymorphisms and prostate cancer (PCa) susceptibility. However, published data on this association are somewhat inconclusive. METHODS: Articles investigating the association between three KLK3 (rs1058205, rs2735839, and rs266882) variants and PCa susceptibility were searched from online databases, which included 35,838 patients and 36,369 control participants. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to demonstrate the strength of the association. We also utilized ELISA to detect serum expression of KLK3. In addition, in silico tools were adopted to evaluate the relationship of KLK3 expression and PCa survival time. RESULTS: The overall results indicated that polymorphism T>C of rs1058205 was associated with decreased risk of PCa (allele contrast: OR = 0.75, 95% CI = 0.64-0.88, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.42-0.81, Pheterogeneity < 0.001), particularly in Caucasian population (allele contrast: OR = 0.77, 95% CI = 0.65-0.91, Pheterogeneity < 0.001; homozygote comparison: OR = 0.58, 95% CI = 0.41-0.82, Pheterogeneity < 0.001). No association was observed between the polymorphism A>G of rs2735839 and risk of PCa. In addition, no association was observed between polymorphism A>G of rs266882 and risk of PCa. Serum KLK3 levels in PCa patients carrying CC/CT genotypes were statistically lower than those carrying TT genotypes. Conclusion: This meta-analysis suggests that rs1058205 polymorphism of KLK3 is a risk factor for PCa development, polymorphism T>C of rs1058205 is associated with decreased susceptibility to PCa particularly in Caucasian population.