Jihong Guo

Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Aim. To systematically review trials concerning the effects of omega-3 fatty acids on sudden cardiac death (SCD), cardiac death, and all-cause mortality in coronary heart disease (CHD) patients. Methods. PubMed, Embase, and the Cochrane database (1966–2007) were searched. We identified randomized controlled trials that compared dietary or supplementary intake of omega-3 fatty acids with control diet or placebo in CHD patients. Eligible studies had at least 6 months of follow-up data, and cited SCD as an end-point. Two reviewers independently assessed methodological quality. Meta-analysis of relative risk was carried out using the random effect model. Results. Eight trials were identified, comprising 20,997 patients. In patients with prior myocardial infarction (MI), omega-3 fatty acids reduced relative risk (RR) of SCD (RR = 0.43; 95% CI: 0.20–0.91). In patients with angina, omega-3 fatty acids increased RR of SCD (RR = 1.39; 95% CI: 1.01–1.92). Overall, RR for cardiac death and all-cause mortality were 0.71 (95% CI: 0.50–1.00) and 0.77 (95% CI: 0.58–1.01), respectively. Conclusions. Dietary supplementation with omega-3 fatty acids reduces the incidence of sudden cardiac death in patients with MI, but may have adverse effects in angina patients.

A novel mutation in the KCNH2 gene associated with short QT syndrome

A gain of function mutation N588K in the KCNH2 gene that encodes HERG channels has been shown to underlie the SQT1 form of short QT syndrome (SQTS). We describe a different mutation in the KCNH2 gene in a Chinese family with clinical evidence of SQTS. A Chinese family with a markedly short QT interval (QTc=316 ± 9 ms, n=4) and a strong family history of sudden death was investigated. Analysis of candidate genes contributing to ventricular repolarization identified a C1853T mutation in the KCNH2 gene coding for the HERG channel, resulting in an amino acid change (T618I) that was found to 100% co-segregate with the SQTS phenotype (n=4). Whole cell voltage clamp studies of the T618I mutation in HEK-cells demonstrated a 6-fold increase in maximum steady state current (146.1 ± 16.7 vs 23.8 ± 5.5 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -78.6 ± 6.8 vs T618I -29.3 ± 1.7 mV). Kinetic analysis revealed slower inactivation rates of T618I but faster rates of recovery from inactivation. Quinidine (5 μM) and sotalol (500 μM) had similar inhibitory effects on steady currents measured at +20 mV in WT and T618I but were less effective in inhibiting tail currents of mutant channels. The altered function of T618I-HERG channels suggests that this mutation in the KCNH2 gene is responsible for the SQTS phenotype in this family. Both quinidine and sotalol may be therapeutic options for patients with the T618I HERG mutation.

Efficacy and safety of telmisartan vs. losartan in control of mild-to-moderate hypertension: a multicentre, randomised, double-blind study

This multicentre, randomised, double‐blind, double‐dummy, parallel‐group study compared the efficacy and safety of telmisartan with those of losartan after 8u2003weeks treatment. In total, 330 patients with mild‐to‐moderate hypertension (systolic blood pressure [SBP] <180u2003mmHg; diastolic blood pressure [DBP] 95–109u2003mmHg) were randomly assigned to receive once‐daily treatment with telmisartan 40u2003mg (nu2003=u2003164) or losartan 50u2003mg (nu2003=u2003166). After 4u2003weeks treatment, if a patients DBP was ≥90u2003mmHg, the dose was increased to telmisartan 80u2003mg or losartan 100u2003mg, respectively. The results show that mean trough seated blood pressure was reduced significantly more in the telmisartan group than that in the losartan group (SBP 12.5u2003mmHg vs. 9.4u2003mmHg, pu2003=u20030.037; DBP 10.9u2003mmHg vs. 9.3u2003mmHg, pu2003=u20030.030). The overall DBP response rate (reduction from baseline in mean seated DBP≥ 10u2003mmHg and/or a mean seated DBPu2003<90u2003mmHg) at the end of the study in the telmisartan group was higher than that in losartan group (70.1% vs. 58.7%, pu2003= 0.020). At both the low and high doses, the DBP response rates for telmisartan were significantly higher than those for losartan (telmisartan 40u2003mg vs. losartan 50u2003mg: 46.3% vs. 32.5%, pu2003=u20030.010; telmisartan 80u2003mg vs. losartan 100u2003mg: 79.3% vs. 65.3%, pu2003=u20030.008). Adverse events with the two treatments were comparable (telmisartan vs. losartan 23.2% vs. 22.9%, pu2003=u20030.952). Most events were mild in intensity and abated within 72u2003h. Thus, telmisartan 40u2003mg or 80u2003mg administered once daily can reduce SBP and DBP effectively and safely.

The surface electrocardiographic changes after radiofrequency catheter ablation in patients with idiopathic left ventricular tachycardia

Surface electrocardiographic changes after radiofrequency (RF) catheter ablation (RFCA) were observed in patients with idiopathic left ventricular tachycardia (ILVT), and the possible mechanisms were analysed. In 41 cases with ILVT who underwent the RFCA, the surface electrocardiograms (ECGs) before and after RFCA were recorded and the serum cardiac troponin I (cTnI) were measured before, immediately after, 4u2003h after and 24u2003h after RFCA. Seven patients developed different models and degrees of fascicular block after successful RFCA. The configurations of fascicular block had no dynamic alteration during the follow‐up periods. No significant difference in the duration of the RF energy delivered, the numbers of RF lesion and the serum levels of cTnI between the patients with or without the electrocardiographic alteration was observed. Thus, the RFCA can cause the fascicular block in some of the patients with ILVT. The different distribution models of the left bundle branch, but not the damage degree to the endocardium induced by RF current, is the primary factor to the changes of ECG.

A novel nonsense mutation Y652X in the S6/pore region of human ether-go-go gene found in a long QT syndrome family

Objectives. To investigate the gene mutation and its possible mechanism in a long QT family. Design. Using DNA samples obtained from the proband and his family members, we sequenced all the exons and flanking intron regions of human ether-go-go gene (HERG) gene using polymerase chain reaction (PCR) and direct sequencing. We also investigated the mRNA expression of the HERG gene in mutation carriers. Results. We found a novel nonsense mutation (Y652X) in the HERG gene. There were six mutation carriers in the family The Y652X mutation located in the S6/pore region and subjected to the mechanism of nonsense-mediated decay (NMD) according to the proposed NMD rules. The mRNA level of the HERG gene was significantly lower in Y652X carriers than in non-carriers. The mRNA expressed from the normal alleles was about 54% of that expressed in the non-carriers. Conclusions. A novel nonsense mutation was found in a LQTS family. The mutated transcript was subjected to NMD mechanism according to the NMD rule. NMD might contribute to the mild phenotype presented in the pore surrounding mutation carriers.

Elderly Patients and Coronary Heart Disease on Response to Treadmill Exercise Test

To study the response of the cardiovascular system, to exercise tolerance in-patients over 75xa0years old with coronary heart disease (CHD), and to evaluate the significance of the parameters of the treadmill exercise test (TET). 110 patients received TET and coronary artery angiography. They were divided into two groups: the elderly patients group included 50 patients over 75xa0years old, and the control group included 60 patients under 60xa0years old. (1) With aging, there were much more CHD patients in the positive TET (Pxa0<xa00.05) than in the negative TET (Pxa0>xa00.05). (2) The parameters of TET for the elderly CHD patients group, included exercise time, peak heart rate, and the onset of ST depression, were lower than the control group (Pxa0<xa00.05). There was no statistical significance between the two groups in the extent and duration of ST depression (Pxa0<xa00.05). (1) In TET, the elderly patients had the higher diagnostic value on CHD. (2) The elderly patients with CHD had the lower endurance to exercise test.

Effects of Ibutilide on Inhibiting Heart Rate and Rapidly Terminating Atrial Flutter in Canine

Ibutilide is a newer class-III antiarrhythmic agent approved for clinical use. We sought to investigate its electrophysiological effects in canines and also the underlying mechanism of conversion of atrial flutter (AFL). For this purpose, 15 male mongrel dogs were anesthetized, intubated with tracheal tube, and heart was exposed and connected to electrodes. Electrophysiologic variables were measured with and without ibutilide (10-min infusion-dose: 0.10xa0mg/kg; 30-min later, maintaining dose: 0.01xa0mg/min) which included heart rate, conduction of intra- and inter-atrium, conduction ratio of isthmus, and ERP. Ibutilide had a significant inhibitory effect on sinus atrial node, peak response time was 20–30xa0min, and heart rate returned to the baseline after 2xa0h. One canine had 5xa0s sinus pause, and the other had 2:1 atrioventricular conduction post-administration. Atrial, ventricular, and pulmonary vein ERP was significantly prolonged (Pxa0<xa00.05). No significant differences were observed regarding conduction of intra-atrium, inter-atrium, and isthmus. It was, therefore, concluded that ibutilide had suppressive effect on sinus atrial and atrioventricular nodes. Ibutilide rapidly terminated AFL due to the reentrant wave front’s inability to proceed as the refractory period was protracted and hence caused the whole excitable gap of the reentrant circuit to be affected by refractoriness.

Experimental research on the in vitro antitumor effects of Crataegus sanguinea.

Crataegus sanguinea is a wild plant, which has been widely grown in the north and south of the Tianshan mountains in Xinjiang. In order to explore their anti-cancer properties, edible wild plants from Xinjiang have been tested for their antitumor properties. We used Ames tests, mouse bone marrow polychromatic erythrocytes micronucleus tests, and tumor cells cultured in vitro to study the anti-mutagenic and anti-tumor effects of C. sanguinea extract. We have shown that C. sanguinea has anti-mutagenic effect, but no mutagenicity. Cell culture in vitro experiments show that there is no inhibition of growth or increase in cell death on normal mouse fibroblasts, but a stronger inhibition of cell growth and an increase in cell death of Hep-2 and MGC-803 tumor cells. The results of this study illustrate that C. sanguinea extract has both anti-mutagenic and anti-tumor effects.

Effects of Ibutilide on Canine Cardiac Pacing Threshold and on Induction Rates of Atrial Fibrillation

This study aims to observe the effects of ibutilide on canine cardiac pacing threshold and on induction rates of atrial fibrillation. Eighteen mongrel dogs were anesthetized and administrated with ibutilide. The pacing thresholds and induction rates of atrial fibrillation were measured with and without ibutilide (10-min infusion dose was 0.10xa0mgxa0kg−1, followed by a maintaining dose of 0.01xa0mgxa0min−1 30xa0min later). This study found that ibutilide increases pacing thresholds in dogs. Moreover, there were significant differences between pacing thresholds with and without ibutilide (Pxa0<xa00.05). Further, ibutilide significantly reduces the induction rates of atrial fibrillation (Pxa0<xa00.05). Our findings indicate that pacing voltage changes should be closely monitored in patients taking anti-arrhythmic drugs, who are treated with cardiac stimulation or have undergone pacemaker implantation. We also found that ibutilide is an effective drug in preventing or controlling atrial fibrillation.

T Wave Safety Margin during the Process of ICD Implantation As a Novel Predictor of T Wave Oversensing

Introduction: T wave oversensing (TWOS) is a major drawback of implantable cardioverter defibrillator (ICD) and data on predictors of TWOS in ICD is limited. We aimed to calculate a novel index of T wave safety margin (TWSM) and assess its potential for evaluating TWOS during the procedure of ICD implantation. Methods and Results: Thirty-two consecutive patients with ICD implantation were enrolled. During each procedure of ICD implantation, different ICD generators were connected to implanted sensing lead through active-fixation leads and bridging cables. R and T wave amplitudes were measured on ICD printouts according to the gain. The ICDs were programed to the most sensitive settings to reveal possible TWOS. A novel index TWSM was calculated according to the corresponding sensing algorithm of ICD. There was discrepancy of R wave amplitudes measured by different ICDs (P < 0.01). In Fortify and Teligen ICDs, T wave amplitudes showed no difference (P > 0.05) and TWSMs were sufficiently high (post sensing: 13.0 ± 7.6 and 28.3 ± 16.5, respectively, post pacing: 5.0 ± 2.2 and 4.6 ± 0.9, respectively). In nine patients with 10 TWOS episodes detected during the procedure of ICD implantation, generators with the highest TWSM were chosen. Only one TWOS episode during pacing was recorded during the 25 ± 7 mo follow-up period. Conclusions: We first propose the index of TWSM during ICD implantation as a potentially efficient predictor for TWOS. Evaluation of TWSM might help to reduce TWOS episodes in patients with high risk of TWOS. Prospective studies are warranted to validate this index and its potential to reduce TWOS episodes.