The RAISE Trial: A Novel Device and First-in-Man Trial.

BACKGROUND: Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation-based interatrial shunting for HFpEF with a novel atrial septostomy device. METHODS: A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study. RESULTS: Percutaneous radiofrequency ablation-based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0-6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0-4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204-3301] P=0.028), with 6-minute walk distance increased by 88 m ([95% CI, 50-249] P=0.008) and with New York Heart Association class improved in 8 patients at 6 months. CONCLUSIONS: The present results showed that percutaneous radiofrequency ablation-based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900027664.

Ginkgolide A alleviates cardiac remodeling in mice with myocardial infarction via binding to matrix metalloproteinase-9 to attenuate inflammation.

Ginkgolides are terpenoids peculiar to Ginkgo biloba, which have protective properties against cardiac diseases. This study aims to explore whether ginkgolide A (GA) could improve cardiac dysfunction of MI mice, and whether it could alleviate cardiac remodeling via binding to matrix metalloproteinase-9 (MMP9) to attenuate inflammation. Cardiac remodeling in mice induced by left coronary artery ligation were used in the in vivo model, and angiotensin (Ang) II-induced cardiac fibroblasts (NRCFs) and cardiomyocytes (NRCMs) isolated from neonatal rats were used in in vitro fibrosis and hypertrophy models, respectively. Cardiac dysfunction and fibrosis in MI mice were alleviated by GA treatment. Upregulations of collagen I (Col I), collagen III (Col III) and fibronectin in NRCFs, and enhanced levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (ß-MHC) in NRCMs were inhibited by GA treatment. A total of 100 potential targets were found in 5 databases (TCMSP, BATMAN-TCM, PharmMapper, ETCM and SWISS Target). According to Protein Data Bank database GA could form hydrogen bonds between LYS65, GLU157, ASN17, ARG109, ARG106 of MMP9 protein, a target of GA. The regulatory role of GA in downregulating Col I, Col III, fibronectin in NRCFs, and enhancing levels of ANP, BNP and ß-MHC in NRCMs were reversed by MMP9 overexpression, so as the downregulation of IL-1ß, IL-6 and TNF-α in Ang II-induced NRCFs and NRCMs. GA could alleviate cardiac dysfunction and remodeling via binding to MMP9 to attenuate inflammation. Therefore, GA is a potential drug for cardiac remodeling therapy.

Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats.

Alamandine (Ala) is a novel member of the renin-angiotensin-system (RAS) family. The present study aimed to explore the effects of Ala on hypertension and renal damage of Dahl salt-sensitive (SS) rats high-salt diet-induced, and the mechanisms of Ala on renal-damage alleviation. Dahl rats were fed with high-salt diets to induce hypertension and renal damage in vivo, and HK-2 cells were treated with sodium chloride (NaCl) to induce renal injury in vitro. Ala administration alleviated the high-salt diet-induced hypertension, renal dysfunction, and renal fibrosis and apoptosis in Dahl SS rats. The HK-2 cells' damage, and the increases in the levels of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl were inhibited by Ala. Ala attenuated the NaCl-induced oxidative stress in the kidney and HK-2 cells. DETC, an inhibitor of SOD, reversed the inhibitory effect of Ala on the apoptosis of HK-2 cells induced by NaCl. The NaCl-induced increase in the PKC level was suppressed by Ala in HK-2 cells. Notably, PKC overexpression reversed the moderating effects of Ala on the NaCl-induced apoptosis of HK-2 cells. These results show that Ala alleviates high-salt diet-induced hypertension and renal dysfunction. Ala attenuates the renal damage via inhibiting the PKC/reactive oxygen species (ROS) signaling pathway, thereby suppressing the apoptosis in renal tubular cells.

A novel parametric method-based nomogram of left ventricular internal diameters in normal Chinese adults.

BACKGROUND: Current echocardiographic normal reference values and nomograms in healthy adults are commonly normalized by body surface area (BSA) with simple linear or isometric corrections. However, various lines of evidence suggest this method might be flawed. In this study, we established the normative data of left ventricular internal diameter (LViD) by BSA-correlated regression equations with the calculation of Z-scores in healthy Han Chinese adults. METHODS: A total of 577 healthy Han Chinese adults were enrolled (age 44.4±13.0 years, 43% male and 57% female). LViD was acquired from two-dimensional-guided M-mode echocardiography on all participants from the parasternal long-axis view. Linear and nonlinear regression models were built to correlate LViD with BSA in different sexes and age groups. The best-fit models and nomograms are presented with the Z-scores calculated by the models. Residual analysis and reproducibility were evaluated in each best-fit model for reliability. RESULTS: Body surface area showed polynomial (quadric) correlations with left ventricular end-diastolic diameter (LVDd, R2=0.615, P<0.001) and left ventricular end-systolic diameter (LVDs, R2=0.540, P<0.001). Corresponding regression equations and nomograms for computing the Z-scores of the overall LViD and BSA/sex-specific and BSA/age-specific reference values are presented. Reproducibility, residual distribution, autocorrelation and heteroscedasticity were confirmed in each model. CONCLUSIONS: This study proposes a comprehensive approach for normal reference values of left ventricular internal diameters with echocardiographic nomograms in healthy Han Chinese adults, which may offer a more precise way to diagnose cardiovascular disease in clinical practice.

Left ventricular energy loss and wall shear stress assessed by vector flow mapping in patients with hypertrophic cardiomyopathy.

The aim of this study was to assess left ventricular (LV) summation of energy loss (EL-SUM), average energy loss (EL-AVE) and wall shear stress (WSS) using vector flow mapping (VFM) in patients with hypertrophic cardiomyopathy (HCM). Forty HCM patients, and 40 controls were evaluated by transthoracic echocardiography. Conventional echocardiographic parameters, summation and average of energy loss (EL-total, EL-base, EL-mid and EL-apex), and WSS in each segment were calculated at different phases. Compared with controls, conventional diastolic measurements were impaired in HCM patients. HCM patients also showed increased EL-SUM-total and EL-AVE-total at the peak of LV rapid ejection period as well as decreased EL-SUM-total and EL-AVE-total at the end of early diastole. In controls, EL-SUM and EL-AVE showed a gradual decrease from the basal segment to the apex, this regularity was not observed in HCM patients. Compared with controls, HCM patients showed increased WSS at the peak of the LV rapid ejection period and the atrial contraction period as well as decreased WSS at the end of early diastole (all p < 0.05). WSS was increased slightly at the peak of the LV rapid filling period in HCM patients (p = 0.055). EL and WSS values derived from VFM are novel flow dynamic parameters that can effectively evaluate systolic and diastolic hemodynamic function in HCM patients.

Diosgenin glucoside protects against myocardial injury in diabetic mice by inhibiting RIP140 signaling.

Myocardial injury is often observed during diabetes, but the nature physiological association is unclear. Here, we investigated the protective effective of diosgenin glucoside (DG), a pharmacologically active saponin extracted from Tritulus terrestris L., against myocardial injury in type 2 diabetic (db/db) mice and its molecular mechanism of action. Levels of serum and myocardial tissues, blood glucose and inflammatory cytokines, as well as cardiac function indicators, of db/db mice were measured, and DG's mechanism of action was evaluated by immunohistochemistry and Western blotting. We found that long-term DG treatment improved glucose tolerance and lipid profiles, reduced production of IL-1ß, IL-6, and TNF-α, and decreased serum levels of the cardiac injury indicators creatine kinase and lactate dehydrogenase. Interestingly, DG also inhibited RIP140 signaling, which normally regulates transcription of estrogen receptor genes and influences expression of proinflammatory cytokines. Our study revealed a novel mechanism of DG's anti-inflammatory effect against myocardial injury via RIP140 signaling modulation in diabetic mice.

Predictive value of plasma copeptin level for the risk and mortality of heart failure: a meta-analysis.

Epidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta-analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random-effects model was used to combine study-specific risk estimates. A total of 13 studies were included in the meta-analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90-2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02-1.33). For all-cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33-2.33). Our dose-response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all-cause mortality (HR, 1.03; 95% CI, 1.01-1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all-cause mortality in patients with HF.

Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia.

The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.

A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.

Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy.

Updating the evidence for the effect of radiofrequency catheter ablation on left atrial volume and function in patients with atrial fibrillation: a meta-analysis.

OBJECTIVES: To systematically review the effects of radiofrequency catheter ablation (RFCA) on left atrial (LA) size, volumes and function in patients with atrial fibrillation (AF). METHODS: We searched MEDLINE, EMBASE, ScienceDirect, Highwire, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the reference lists of retrieved reports in July 2012. SETTING: China. PARTICIPANTS: Twenty-six studies (enrolling 1821 patients) were included in the final analysis. MAIN OUTCOME MEASURES: Changes of LA size or volumes and/or function in patients with AF after RFCA. RESULTS: Compared to pre-ablation values, there were significant decreases in LA diameter and LA volumes at post-ablation follow-up. However, compared to pre-ablation values, there were no significant differences in LA ejection fraction/LA active emptying fraction and LA strain at post-ablation follow-up. Decreases in LA diameter and LA volumes remained significant in those without AF recurrence but not in those with AF recurrence. LA ejection fraction/LA active emptying fraction did not decrease in patients without AF recurrence, whereas they decreased in patients with AF recurrence. As for LA strain, it seems that LA strain increases in patients without AF recurrence, with less fibrosis and with more LA volumes decrease, but the differences were not significant. CONCLUSIONS: Successful RFCA in patients with AF significantly decreases LA size and volumes and does not seem to adversely affect LA function.

Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.

BACKGROUND: Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. METHODS: Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. RESULTS: In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. CONCLUSIONS: Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function.

Catheter-based intramyocardial delivery (NavX) of adenovirus achieves safe and accurate gene transfer in pigs.

BACKGROUND: Hepatocyte growth factor (HGF) is one of the major angiogenic factors being studied for the treatment of ischemic heart diseases. Our previous study demonstrated adenovirus-HGF was effective in myocardial ischemia models. The first clinical safety study showed a positive effect in patients with severe and diffused triple coronary disease. METHODS: 12 Pigs were randomized (1:1) to receive HGF, which was administered as five injections into the infarcted myocardium, or saline (control group). The injections were guided by EnSite NavX left ventricular electroanatomical mapping. RESULTS: The catheter-based injections caused no pericardial effusion, malignant arrhythmia or death. During mapping and injection, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine and creatine kinase-MB levels have no significant increase as compared to those before and after the injection in HGF group(P>0.05). HGF group has high HGF expression with Western blot, less myocardial infarct sizes by electroanatomical mapping (HGF group versus after saline group, 5.28 ± 0.55 cm(2) versus 9.06 ± 1.06 cm(2), P<0.01), better cardiac function with Gated-Single Photon Emission Computed Tomography compared with those in saline group. Histological, strongly increased lectin-positive microvessels and microvessel density were found in the myocardial ischemic regions in HGF group. CONCLUSION: Intramyocardial injection guided by NavX system provides a method of feasible and safe percutaneous gene transfer to myocardial infarct regions.

Circumferential myocardial contraction patterns in patients with idiopathic frequent premature ventricular complexes from the right ventricular outflow tract.

BACKGROUND: The pathogenesis of frequent premature ventricular complexes (PVCs) in patients without overt cardiovascular disease is considered idiopathic. Idiopathic PVCs are predominantly from the right ventricular outflow tract (RVOT) and considered a reversible cause of left ventricular (LV) dysfunction. OBJECTIVES: We investigated whether alternations in LV contraction patterns exist in patients with idiopathic frequent PVCs originating from the RVOT. METHODS: Segmental myocardial circumferential strain (CS)-time curves were acquired from 29 patients with idiopathic frequent RVOT-PVCs and 30 healthy subjects. Peak CS and the time to peak CS (TPcs) of each segment were analyzed, with the standard deviation of TPcs for 18 LV segments (SDtpcs) calculated. All values of patients with RVOT-PVCs were recorded during both sinus beats (PVC-S) and ventricular extrasystoles (PVC-V), respectively. RESULTS: The distribution of peak CS and TPcs in the PVC-V was opposite that of the healthy subjects. The distribution of TPcs of PVC-S within the different layers differed from that of healthy subjects. These patients had significantly greater dyssynchrony compared with the healthy subjects assessed by SDtpcs (healthy subjects: 6.7%±1.9%, PVC-S: 8.1%±3.1%, PVC-V: 9.7%±3.4%, healthy subjects vs. PVC-S p=0.04; healthy subjects vs. PVC-V p=0.001). Furthermore, a positive correlation was observed between PVC frequency and SDtpcs of PVC-S (r=0.44, p=0.02). CONCLUSIONS: Idiopathic frequent RVOT-PVCs can induce alterations in the LV myocardial contractile pattern during both sinus beats and ventricular extrasystoles. Circumferential contraction dyssynchrony of patients during sinus beats relates to PVC frequency. Therefore, attention should be paid to patients with frequent RVOT-PVCs, especially those with a high prevalence of PVCs.

Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction.

Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnormal remodeling are observed following induction of myocardial infarction. Here we explored the therapeutic potential of sustained synd4 over-expression in the context of myocardial infarction. Adenovirus containing the synd4 gene (Ad-synd4), or corresponding control adenovirus (Ad-null), was administered intramyocardially in rats immediately after induction of myocardial infarction. Cardiac function was ascertained by echocardiography, hemodynamic assessment and brain natriuretic peptide level 28 days post-intervention. Hearts were excised for molecular and histological analyses at predetermined time points. We observed reduced mortality and improved cardiac function post-myocardial infarction in the Ad-synd4 as compared to the Ad-null group, with associated attenuation of cardiac remodeling, less myocyte loss and reduced fibrosis. Additionally, the Ad-synd4 group exhibited endothelial cell activation and increased angiogenesis and arteriogenesis in the myocardium. The Ad-synd4 group also showed evidence of reduced myocardial inflammation as compared with the Ad-null group, with reduced inflammatory cell (CD45+) and myofibroblast (α-SMA+) infiltration as well as suppressed collagen III deposition and iNOS expression. Our results suggest that sustained synd4 over-expression in the myocardium is of therapeutic benefit following experimental myocardial infarction, through inducing neovascularization, suppressing tissue inflammation and fibrosis, with resultant improvements in cardiac function and remodeling.

Risk factors and outcomes of post-procedure heart blocks after transcatheter device closure of perimembranous ventricular septal defect.

OBJECTIVES: The aim of this study was to analyze the risk factors and mid-term outcomes associated with post-procedure heart blocks (PPHBs) after transcatheter closure of perimembranous ventricular septal defect (pmVSD). BACKGROUND: The development of heart blocks remains a major challenge for transcatheter closure of pmVSD. METHODS: Transcatheter closure of pmVSD was carried out in 228 patients. Electrocardiography and 24-h Holter monitoring were performed before the procedure, within 1 week after the procedure, then 1, 3, 6, and 12 months, and every year thereafter. RESULTS: Thirty-three patients (14.5%) who received transcatheter closure of pmVSD developed PPHBs. PPHBs included right bundle branch block (57.6%), left bundle branch block (24.2%), and atrioventricular block (18.2%). High-degree atrioventricular blocks occurred in 4 patients and recovered to normal conduction after intravenous administration of hydrocortisone. PPHBs recovered to normal conduction in 21 patients by the time of hospital discharge. Compared with the patients without PPHBs, the patients suffering PPHBs were characterized by a significantly longer distance between the aortic valve and the defect (DAVD), a shorter distance from the lower rim of the defect to the septal leaflet of the tricuspid valve (DLRD-SLTV), and a larger diameter difference between the occluder and ventricular septal defect (DDOV). The earlier the PPHBs developed after the procedure, the more difficult the recovery to normal conduction. CONCLUSIONS: The outcome of PPHBs after transcatheter closure of pmVSD was satisfactory, as most patients recovered to normal conduction. Measurements of DLRD-SLTV, DAVD, and DDOV may be useful in predicting the incidence of PPHBs.

Evaluation of global and regional left ventricular systolic function in patients with frequent isolated premature ventricular complexes from the right ventricular outflow tract.

BACKGROUND: Frequent premature ventricular complexes from the right ventricular outflow tract (RVOT-PVCs) are associated with left ventricular dysfunction. This study adopted two-dimensional speckle tracking imaging to evaluate global and regional left ventricular myocardial function in patients with frequent RVOT-PVCs. METHODS: This study included 30 patients with frequent RVOT-PVCs and 30 healthy subjects. Aortic systolic velocity-time integral (AoVTI) and myocardium strain in circumferential (CS), radial (RS) and longitudinal (LS) directions were evaluated by conventional echocardiography and speckle tracking imaging. All values of patients with RVOT-PVCs were recorded during sinus (PVC-S) and PVC beats (PVC-V). RESULTS: Significant differences were demonstrated in global CS, RS and LS between the control subjects and the PVC-V (CS: (17.46 ± 2.48)% vs. (11.52 ± 3.28)%, RS: (48.26 ± 10.20)% vs. (20.92 ± 9.78)%, LS: (19.89 ± 2.62)% vs. (11.79 ± 3.66)%, P < 0.01), and in segmental RS and LS of nearly all the left ventricular segments. Statistical differences in segmental CS between the PVC-V and the control subjects were only observed in anterior, anteroseptal and septal segments (only seen in anteroseptal and septal segments at apex). Furthermore, V/S AoVTI (AoVTI during the PVC beat divided by AoVTI during the sinus beat, then multiplied by 100%) correlated with coupling interval (r = 0.67, P < 0.001) and global strain (CS: r = 0.48, P = 0.007; RS: r = 0.65, P < 0.001; LS: r = 0.65, P < 0.001). CONCLUSIONS: Frequent RVOT-PVCs can induce global and regional left ventricular systolic dysfunction. The reduction of hemodynamic parameters relates to the coupling interval and the global systolic function.

Late recurrent high degree atrioventricular block after percutaneous closure of a perimembranous ventricular septal defect.

High degree atrioventricular block (HDAVB) is a serious complication of transcatheter closure of a perimembranous ventricular septal defect (PMVSD). We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure.

Regulation of angiotensin-(1-7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure.

AIM: To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats, and to explore the changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression of angiotensin II type 1/2 receptors (AT(1)R / AT(2)R) and Mas receptor caused by the two drugs. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: the control group, ADR-treated heart failure group (ADR-HF), telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR). ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily), respectively, for 6 weeks. The plasma level of Ang-(1-7) was determined using ELISA. The mRNA and protein expression of myocardial Mas receptor, AT(1)R and AT(2)R were measured using RT-PCR and Western blotting, respectively. RESULTS: ADR significantly reduced the plasma level of Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT(2)R, while significantly increased the expression of myocardial AT(1)R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT(1)R expression, but did not influence the expression of Mas receptor and AT(2)R. CONCLUSION: The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT(1)R expression.

Transcatheter closure of perimembranous ventricular septal defect in children: safety and efficiency with symmetric and asymmetric occluders.

OBJECTIVES: This study was designed to determine the safety and efficiency of asymmetric and symmetric ventricular septal occluders (AVSDOs and SVSDOs, respectively) for closure perimembranous ventricular septal defect (PMVSD) in children. METHODS: Between January 2003 and December 2007, 142 children with PMVSD were treated with occluders (64 with AVSDOs and 78 with SVSDOs). RESULTS: The defect diameter was 5.3 ± 1.1 mm in the AVSDO group and 5.4 ± 1.3 mm in the SVSDO group (P > 0.05). The success rates were similar between two groups [93.8% (AVSDO) vs. 94.9% (SVSDO), P > 0.05]. Two patients in the AVSDO group were switched to the SVSDO group due to residual shunts, and one patient in the SVSDO group was switched due to aortic regurgitation after deployment of the occluder. After procedure, 17 patients [seven with AVSDOs and nine with SVSDOs (P > 0.05)] developed various types of heart block (HB). Among them, 13 patients converted to the normal sinus rhythm. The remaining four cases had not recovered at the end of the study. CONCLUSIONS: Transcatheter closure of PMVSD using both AVSDO and SVSDO was safe and effective. Development of HB was the main complication for both devices.

Acute mechanical effect of right ventricular pacing at different sites using velocity vector imaging.

OBJECTIVE: Velocity vector imaging (VVI) allows noninvasive measurement of left ventricular (LV) strain and rotation angle-independently. We investigated strain, rotation and myocardial synchrony when pacing at different sites in the right ventricle to determine which site yields the most physiological pacing, as determined with VVI imaging. METHOD: Thirty-one patients with normal LV function referred for elective electrophysiology exam were used in this study. Catheters (6F quadripolar) were positioned in the right atrium, right ventricular apex, right ventricular outflow tract, and His bundle after electrophysiology exam was done. Regional and global LV circumferential strain (CS), radial strain (RS), and LV rotation of LV short-axis measurements were obtained. Two dyssynchrony parameters (AS-P delay and SDt(6S)) of CS and RS were obtained. Compare these values among each pacing, respectively. RESULT: CS, RS, and twist, which represent the LV systolic function, were significantly reduced in RVOT pacing and RVA pacing than RA pacing. Two dyssynchrony parameters (AS-P delay and SDt(6S)) were significantly longer in response to RVOT or RVA pacing compared to RA pacing. No significant differences were found between RVOT pacing and RVA pacing. CS and RS were obviously reduced in the regions surrounding the pacing site. There was no significant difference in CS, RS, twist, and mechanical dyssynchrony parameters when comparing His and RA pacing. CONCLUSION: Among these alternate right ventricular pacing locations, His bundle pacing is most like physiological pacing. Both RVOT pacing and RVA pacing worsen the normal LV systolic function with regard to strain, twist, and mechanical dyssynchrony along the LV short axis.