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Aims Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as ‘initial therapy’ for AF is to be determined. Methods and results Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27–0.48, P Conclusions Catheter ablation as ‘initial therapy’ was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.

Aims Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group. Methods and results This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients’ data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P Conclusions VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild–moderate liver disease.

Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, resulting in an increased risk of morbidity and longer hospital stay. Pharmacologic prophylaxis has been recommended to improve the outcome in patients at high risk of developing POAF after cardiac surgery. Several studies have applied the CHA2DS2-VASc (Congestive heart failure, Hypertension Age [≥65 = 1 point, ≥75 = 2 points], Diabetes, and Stroke/transient ischemic attack (2 points)–vascular disease [peripheral arterial disease, previous myocardial infarction, aortic atheroma]) score in the risk stratification of POAF but yielded contradicting results. This study aims to determine the association between CHA2DS2-VASc score and POAF and further to explore its discriminative ability for the prediction of POAF. Methods We systematically searched the Medline, Embase, Cochrane library, and other data sources with key terms “CHA2DS2-VASc,” “atrial fibrillation,” and “cardiac surgery.” Studies designed for CHA2DS2-VASc score in stratifying the risks of POAF in patients undergoing cardiac surgery were included. Statistical analyses were performed with R 3.5.1 and STATA 13.0. Results Seven hundred twenty-one studies were identified, of which 12 studies with 18,086 patients were finally included in our analysis. The CHA2DS2-VASc score was found to be an independent predictor of POAF after cardiac surgery (odds ratio, 1.46; 95% confidence interval [CI], 1.25-1.72) and exhibited a relatively strong specificity (0.70; 95% CI, 0.61-0.78) and sensitivity (0.72; 95% CI, 0.54-0.85) for predicting POAF. The bivariate model-based pooled area under the receiver operating curve was estimated to be 0.76 (95% CI, 0.72-0.79). Conclusions The CHA2DS2-VASc score has relatively good performance in predicting POAF after cardiac surgery and may help identify the patients at high risk of POAF.

Ultrasound can promote the drug release from drug-loaded substances and alter the tumor local microenvironment to facilitate the transport of drug carriers into the tumor tissues. Based on the altered tumor microenvironment, nanobubbles (NBs) as drug carriers with surfaces functionalized with targeting ligands can reach the tumor sites, thereby increasing the efficacy of chemotherapy. Herein, paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) NBs are prepared as drug carriers with covalently conjugated herceptin (anti-HER2 monoclonal antibody) on the surface to guide the target. The effect of ultrasound on the drug release and targeting of the herceptin-conjugated drug-loaded nanobubbles (PTX-NBs-HER) on the cancerous cells is determined. The use of ultrasound significantly improves the cell targeting capability in vitro, and efficiency of enhanced permeability and retention in vivo. The combination of PTX-NBs-HER and ultrasound facilitates the release of PTX, as well as the uptake and cell apoptosis in vitro. The in vivo application of both PTX-NBs-HER and ultrasound enhances the PTX targeting and accumulation in breast cancers while reducing the transmission and distribution of PTX in healthy organs. The combination of ultrasound with PTX-NBs-HER as contrast agents and drug carriers affords an image-guided drug delivery system for the precise targeted therapy of tumors.

Aims The optimal treatment for patients with atrial fibrillation (AF) and heart failure (HF) has been a subject of debate for years. We aimed to evaluate the efficacy and safety of rhythm control strategy in patients with AF complicated with HF regarding hard clinical endpoints. Methods and results Up-to-date randomized data comparing rhythm control using antiarrhythmic drugs (AADs) vs. rate control (Subset A) or rhythm control using catheter ablation vs. medical therapy (Subset B) in AF and HF patients were pooled. The primary outcomes were all-cause mortality, re-hospitalization, stroke, and thromboembolic events. A total of 11 studies involving 3598 patients were enrolled (Subset A: 2486; Subset B: 1112). As compared with medical rate control, the AADs rhythm control was associated with similar all-cause mortality [odds ratio (OR): 0.96, P = 0.65], significantly higher rate of re-hospitalization (OR: 1.25, P = 0.01), and similar rate of stroke and thromboembolic events (OR: 0.91, P = 0.76,); however, as compared with medical therapy, catheter ablation rhythm control was associated with significantly lower all-cause mortality (OR: 0.51, P = 0.0003), reduced re-hospitalization rate (OR: 0.44, P = 0.003), similar rate of stroke events (OR: 0.59, P = 0.27), greater improvement in left ventricular ejection fraction [weighted mean difference (WMD): 6.8%, P = 0.0004], lower arrhythmia recurrence (29.6% vs. 80.1%, OR: 0.04, P Conclusion Catheter ablation as rhythm control strategy substantially improves survival rate, reduces re-hospitalization, increases the maintenance rate of sinus rhythm, contributes to preserve cardiac function, and improves quality of life for AF patients complicated with HF.

Objective This study was performed to observe the effect of radiofrequency catheter ablation (RFCA) in patients with paroxysmal atrial fibrillation (PAF) and to explore the risk factors for late recurrence of atrial fibrillation (LRAF) after a single RFCA session. Methods In this retrospective study, 243 patients with PAF underwent RFCA and were followed up regularly. Results At a median follow-up of 37 months after a single procedure, 60.5% of patients maintained sinus rhythm (SR), and at a median follow-up of 42 months after multiple procedures, 74.9% of patients maintained SR. The statistically significant risk factors for LRAF after a single RFCA session were the left atrial diameter (LAD), left inferior pulmonary vein superior–inferior diameter (LIPV SID), PV number variation, circumferential pulmonary vein isolation (CPVI) combined with additional ablation, and early recurrence of atrial fibrillation (ERAF). The best cut-off value for LAD was 35.5 mm. Conclusions During a 3-year follow-up, about 70% of the patients with PAF maintained SR. LRAF after a single procedure was associated with the LAD, LIPV SID, PV number variation, CPVI combined with additional ablation, and ERAF.

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs, however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding, however, more randomized controlled trials are warranted.

Background Recurrence rate after radiofrequency catheter ablation (RFCA) remains high, and further investigation on predictors of recurrence is needed. Objects To identify risk factors of atrial fibrillation (AF) recurrence in patients undergoing RFCA. Methods We retrospectively studied 257 patients with AF who underwent RFCA preceded by transthoracic echocardiographic and pulmonary vein CT examination from 2016 to 2019. Electrocardiogram examination was performed at baseline, 1, 3, 6 months, and 1 year after RFCA. We divided patients into two groups based on AF recurrence including recurrence group (n = 79) and nonrecurrence group (n = 178). The crude and independent association between clinical variables and AF recurrence was evaluated with logistic regression analysis. Specificity and positive predictive value of relevant factors for AF recurrence were performed by ROC curve. Results Of these AF patients, 174 (68%) was paroxysmal AF and 83 (32%) was persistent AF. The multivariate logistic regression demonstrated that AF duration (OR = 1.008, 95% CI 1.002-1.013, p = .008), pulmonary arterial hypertension (PAH; OR = 2.313, 95% CI 1.031-5.192, p = .042), and low-density lipoprotein cholesterol (LDL-C; OR = 1.646, 95% CI 1.129-2.398, p = .010) were independently correlated with recurrence of AF. For predicting AF recurrence, the specificity and sensitivity of AF duration were 30.1% and 87.3%, and for LDL-C, the specificity and sensitivity of AF duration were 60.6% and 60.5%, respectively. Conclusions Atrial fibrillation duration, PAH, and LDL-C might be independent risk factors for the recurrence of AF after RFCA.

At present, MRI is the primary choice of examination for the diagnosis of thoracic extramedullary hemopoiesis. When thoracic extramedullary hemopoiesis presents as posterior mediastinum masses in specific clinical contexts, the diagnosis is not challenging. Other radiological presentations may be more difficult for diagnosis and require biopsy. Needle biopsy is typically preferred for the diagnosis of extramedullary hemopoiesis however, the high vascularization of tissues is one of the complications of this method thus, it is avoided. The aim of the present study was to compare the diagnostic parameters of CT with MRI for the diagnosis of thoracic extramedullary hemopoiesis in patients with leukemia, with an open lung biopsy as a reference standard. Chest CT, chest MRI and open lung biopsy data from a total of 912 patients with leukemia with a sign(s) and symptoms of suspected paravertebral and/or pulmonary extramedullary hemopoiesis were reviewed. In the present study, thoracic extramedullary hemopoiesis was defined as diffusivity of both lung fields being increased compared with the blood pool and no other abnormal focal of lungs being increased compared with the blood pool. The beneficial score was calculated for CT and MRI and plotted for the decision making of irradiation. With respect to open lung biopsy, MRI had a higher sensitivity compared with CT (0.865 vs. 0.809; P

Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson's trichrome staining and the expression of transforming growth factor-β1 (TGF-β1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin-angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.

Background Renin-angiotensin-system inhibitors (RASIs) have been suggested as an upstream therapy for selected AF patients; however, the evidence in surgical setting is limited. Objective We aimed to evaluate the role of preoperative RASIs in prevention of postoperative atrial fibrillation (POAF) and adverse events for patients undergoing cardiac surgery. Methods In this collaborative pooled-analysis, both randomized and nonrandomized controlled trials comparing preoperative RASIs with no preoperative RASIs treatment on the incidence of POAF were identified. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall-effect, and meta-regression to explore the potential risk of bias. The primary outcome was POAF, and the secondary outcomes includes rate of stroke, mortality and duration of hospitalization. Results Eleven trials involving 27885 patients (male 74%, median age 65yrs) were included. As compared to the control group, preoperative RASIs did not significantly reduce the risk of POAF (OR: 1.04, 95% CI: 0.91–1.19), stroke (OR: 0.86, 95% CI: 0.62–1.19), death (OR: 1.07, 95% CI: 0.85–1.35), composite adverse cardiac events (OR: 1.04, 95% CI: 0.91–1.18), and hospital stay (WMD: −0.04, 95% CI: −1.05 to 0.98). Pooled-analysis of randomized trials showed consistent results. The primary overall-effect was maintained in sensitivity and subgroup analyses. Meta-regression showed that male-gender was a significant risk-factor of POAF and use of Beta-blockers was associated with a significantly reduced risk in developing POAF. Conclusion and relevance This study demonstrates that preoperative RASIs do not offer additional benefit in reducing the risk of postoperative AF, stroke, death and hospitalization in the setting of cardiac surgery. The results provide no support for use of RASIs for the prevention of POAF and adverse events in patients undergoing cardiac surgery.

Myocardial fibrosis plays an important role in the development of heart failure and malignant arrhythmia, which potentially increases the incidence of sudden cardiac death. Therefore, early detection of myocardial fibrosis is of great significance for evaluating the prognosis of patients and formulating appropriate treatment strategies. Late gadolinium enhanced magnetic resonance imaging is considered as the currently effective strategy for noninvasive detection of myocardial fibrosis, but it still suffers from some critical issues. In this work, multifunctional CNA35-labeled perfluoropentane nanoparticles (CNA35-PFP NPs) have been elaborately designed and constructed for molecular imaging of fibrotic myocardium based on ultrasound imaging. These as-constructed CNA35-PFP NPs are intravenously infused into rabbit circulation with an animal model of myocardial infarction. Especially, these targeted CNA35-PFP NPs with nanoscale size could efficiently pass through the endothelial cell gap and adhere to the surface of fibroblasts in the fibrotic myocardium. Importantly, followed by low-intensity focused ultrasound irradiation on the myocardium, these intriguing CNA35-PFP NPs could transform from liquid into gaseous microbubbles, which further significantly enhanced the ultrasound contrast in the fibrotic area, facilitating the detection by diagnostic ultrasound imaging. Therefore, this work provides a desirable noninvasive, economical, and real-time imaging technique for the assessment of cardiac fibrosis with diagnostic ultrasound based on the rational design of liquid-to-gas phase-changeable nanoplatforms.

Objective To assess efficacy and safety of renal denervation (RDN) for heart failure (HF). Background RDN has been demonstrated to be an effective method in lowing overactive sympathetic nerve. However, it's feasibility and efficacy for HF is unclear. Methods In this randomized, controlled pilot study, patients with HF were randomly assigned in 1:1 ratio to undergo RDN plus optimal medical therapy (RDN group) or only optimal medical therapy (control group). Before randomization, patients received optimal medical therapy at least half a year. Primary efficacy end point was the change in LVEF over six months; secondary efficacy end points were the change in six-minute walk distance and SF-36 Health Survey scores over six months. Results Up to Apr 2015, sixty symptomatic HF patients were successfully enrolled into study. Thirty patients were randomly assigned to RDN group and 30 patients were randomly assigned to control group. All patients completed six months follow up. During follow up, no severe adverse events were observed. Blood pressure was stable in both groups. Patients in RDN group had shown a significant improvement in LVEF (P

Background Cell metabolic pathways are highly conserved among species and change rapidly in response to drug stimulation. Therefore, we explore the effects of angiotensin-(1-7) in a primary cell model of cardiac fibrosis established in angiotensin II-stimulated cardiac fibroblasts via metabolomics analysis and further clarify the potential protective mechanism of angiotensin-(1-7). Methods and Results After exposing cardiac fibroblasts to angiotensin II and/or angiotensin-(1-7), 172 metabolites in these cells were quantified and identified by gas chromatography-mass spectrometry. The data were subsequently analyzed by orthogonal partial least squares discriminant analysis to shortlist biochemically significant metabolites associated with the antifibrotic action of angiotensin-(1-7). Seven significant metabolites were identified: 10,13-dimethyltetradecanoic acid, arachidonic acid, aspartic acid, docosahexaenoic acid (DHA), glutathione, palmitelaidic acid, and pyroglutamic acid. By metabolic network analysis, we found that these metabolites were involved in six metabolic pathways, including arachidonic acid metabolism, leukotriene metabolism, and the γ-glutamyl cycle. Since these metabolic pathways are related to calcium balance and oxidative stress, we further verified that angiotensin-(1-7) suppressed the abnormal extracellular calcium influx and excessive accumulation of intracellular reactive oxygen species (ROS) in angiotensin II-stimulated cardiac fibroblasts. Furthermore, we found that angiotensin-(1-7) suppressed the abnormal calcium- and ROS-dependent activation of calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ), the increased expression of CaMKIIδ-related proteins (NADPH oxidase 4 (Nox4), cellular communication network factor 2 (CTGF), and p-ERK1/2), and excessive collagen deposition in vitro and in vivo. Conclusions Angiotensin-(1-7) can ameliorate the angiotensin II-stimulated metabolic perturbations associated with cardiac fibroblast activation. These metabolic changes indicate that modulation of calcium- and ROS-dependent activation of CaMKIIδ mediates the activity of angiotensin-(1-7) against cardiac fibrosis. Moreover, pyroglutamic acid and arachidonic acid may be potential biomarkers for monitoring the antifibrotic action of angiotensin-(1-7).

Background: The effect of catheter ablation (CA) versus drug therapy on cardiac function improvement is not clear for patients with persistent atrial fibrillation and heart failure. To compare the short-term therapeutic effects between CA and conventional drug therapy, we conducted a meta-analysis of the current randomized controlled trials (RCTs). Objective and method: The analyses systematically collected PubMed, Embase, and the Cochrane Library for RCTs comparing catheter ablation with medical therapy in patients with persistent atrial fibrillation and heart failure. In order to reduce the impact of other factors on cardiac function, we limited the maximum follow-up time to two years. The primary outcome is changes in left ventricular ejection fraction (LEVF), second outcomes are changes in 6-minute walk test (6MWT), Minnesota Living with Heart Failure Score (MLHFQ), B-type natriuretic peptide (BNP). SMD was used for the results measured by different methods. Random-effects model or fixed-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results: A total of six randomized controlled trials included 775 patients included in the final analysis, compared with drug therapy, catheter ablation has a better improvement in left ventricular ejection fraction (SMD, 0.57; 95% CI [0.40, 0.94], p

Background: The present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation. Methods and results: A total of 397 patients with nonvalvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to ablation. LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF50%), LA ≥ 40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate coumadin therapy, CHADS2 score of ≥ 2 and CHA2DS2VASC score of ≥ 2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥ 2 (p=0.02) and previous stroke or TIA (p=0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus. Conclusion: Both CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. It seemed safe to perform AF ablation or cardio version in AF patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy.

Importance Postoperative atrial fibrillation (POAF) is a well-known complication after cardiac surgery. Renin-angiotensin system inhibitors (RASIs) have been suggested as an upstream therapy for selected patients with AF; however, evidence in the surgical setting is limited. Objective To evaluate the role of preoperative RASIs in prevention of POAF and adverse events for patients undergoing cardiac surgery. Data Sources The PubMed database and the Cochrane Library from inception until December 31, 2018, were searched by using the keywordsrenin-angiotensin system inhibitorsORangiotensin-converting enzyme inhibitorsORangiotensin receptor blockerORaldosterone antagonistANDcardiac surgery. ClinicalTrials.gov was searched from inception until December 31, 2018, by using the keywordspostoperative atrial fibrillation. Study Selection Randomized clinical trials (RCTs) and observational studies comparing the association between preoperative RASI treatment vs no preoperative RASI treatment (control group) and the incidence of POAF were identified. Eleven unique studies met the selection criteria. Data Extraction and Synthesis Pooled analysis was performed using a random-effects model. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall effect. Metaregression was conducted to explore potential risk of bias. Main Outcomes and Measures The primary outcome was POAF, and the secondary outcomes included rates of stroke and mortality and duration of hospitalization. Results Eleven unique studies involving 27 885 unique patients (74.4% male; median age, 65 years [range, 58.5-74.5 years]) were included. Compared with the control group, the RASI group did not have a significantly reduced risk of POAF (odds ratio [OR], 1.04; 95% CI, 0.91-1.19;P = .55;z = 0.60), stroke (OR, 0.86; 95% CI, 0.62-1.19;P = .37;z = 0.90; without significant heterogeneity,P = .11), death (OR, 1.07; 95% CI, 0.85-1.35;P = .56;z = 0.59; without significant heterogeneity,P = .12), composite adverse cardiac events (OR, 1.04; 95% CI, 0.91-1.18;P = .58;z = 0.56), or a reduced hospital stay (weighted mean difference, −0.04; 95% CI, −1.05 to 0.98;P = .94;z = 0.07) using a random-effects model. Pooled analysis focusing on RCTs showed consistent results. The primary overall effect was maintained in sensitivity and subgroup analyses. Metaregression showed that male sex was significantly associated with POAF (τ2 = 0.0065;z = 3.47;Q = 12.047;P Conclusions and Relevance The findings from this study suggest that preoperative RASI treatment does not offer additional benefit in reducing the risk of POAF, stroke, death, and hospitalization in the setting of cardiac surgery. The results provide no support for conventional use of RASIs for the possible prevention of POAF and adverse events in patients undergoing cardiac surgery; further randomized data, particularly among those patients with heart failure, are needed.

The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p

Whether ZES can further improve angiographic and clinical outcomes compared to SES still remains uncertain.The aim of this study was to assess the efficacy and safety of zotarolimus-eluting stents (ZES) compared with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary interventions (PCI).Major electronic information sources were explored for randomized controlled trials comparing ZES with SES among patients undergoing PCI during at least 9 months follow-up. The primary efficacy outcomes were target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE); safety outcomes were stent thrombosis (ST), myocardial infarction (MI), and cardiac death.Seven comparative studies were identified (a total of 5983 patients). When compared with ZES at 12-month follow-up, SES significantly reduced risk of MACE (relative risk [RR]: 0.74, 95% confidence interval [CI]: 0.61 to 0.89, p=0.002), and TLR (RR:0.39; 95% CI: 0.29 to 0.52; p0.00001), without significant differences in terms of TVR (RR:0.68, 95% CI: 0.38 to 1.20; p=0.18), ST (RR:0.71; 95% CI: 0.39 to 1.31; p=0.28), cardiac death (RR:0.83; 95% CI: 0.49-1.42, p=0.50) or MI (RR:1.08; 95%CI: 0.80 to 1.45; p=0.62).At 12-month follow-up, SES are superior to ZES in reducing the incidences of TLR and MACE in patients undergoing PCI, without significant differences in terms of TVR, ST, cardiac death, and MI.

Objective Current literature shows there is widespread controversy regarding the indications and outcomes of using an intra-aortic balloon pump (IABP); furthermore, little is known about the late effects of IABP use. Design To determine whether IABP use can have beneficial effects for patients undergoing high risk reperfusion therapies, by conducting a meta-analysis of randomised trials. Setting Databases of Pubmed, Cochrane Library, and Clinicaltrials.gov were searched up to 15 June 2013. Patients Patients undergoing high risk reperfusion therapies. Interventions Randomised clinical trials comparing IABP with no IABP were considered eligible for this meta-analysis. Main outcome measures Primary outcomes were early (30-day) and long term (≥6-month) mortality. Results Among the 1079 articles retrieved, 10 randomised studies with 2037 high risk patients were included in the quantitative analysis. Meta-analysis revealed that early mortality rate did not differ between the IABP group and the non-IABP group (OR 0.79, 95% CI 0.48 to 1.29). However, long term mortality was significantly reduced in the IABP group (OR 0.63, 95% CI 0.45 to 0.9), and this effect seemed more pronounced in the subset of patients treated with contemporary percutaneous coronary intervention (OR 0.55, 95% CI 0.38 to 0.80). Further analysis found that IABP use was associated with a reduced risk of 30-day re-ischaemia rate (OR 0.62, 95% CI 0.42 to 0.91) and the composite outcome of re-ischaemia and heart failure events (OR 0.75, 95% CI 0.58 to 0.98). No significant heterogeneity was observed. Conclusions This meta-analysis suggests that adjunctive IABP use in high risk reperfusion therapy can improve long term survival.

It is controversial whether angiotensin II receptor blockers provide better protection than calcium antagonists against atrial fibrillation (AF) recurrence in hypertensive patients. This study was designed to compare the effect of nifedipine- and telmisartan-based antihypertensive treatments for preventing AF recurrence in hypertensive patients with paroxysmal AF. A total of 149 hypertensive patients with paroxysmal AF were randomized to nifedipine- or telmisartan-based antihypertensive treatment groups. The target blood pressure (BP) was P =0.742), and Kaplan–Meier analysis showed no significant difference in the freedom from AF recurrence (log-rank test; P =0.48). However, the rate of developing persistent AF in telmisartan group was lower than that in nifedipine group (5.4% versus 16.0%; P =0.035). Patients in telmisartan group had lower values of left atrial diameter, left atrial volume index, and left ventricular mass index at the end of follow-up. The effects of telmisartan in preventing AF recurrences in hypertensive patients with paroxysmal AF after intensive lowering BP is similar to that of nifedipine, but telmisartan has more potent effects on preventing progression to persistent AF.

To predict the recurrence of atrial fibrillation is important for selecting patients who will be undergoing catheter ablation, several studies respectively evaluated the risk factor of the recurrence of atrial fibrillation post-ablation.To investigate the factors predicting the recurrence of atrial fibrillation (AF) after catheter ablation.186 patients (55.12 ± 12.06 years, 123 male) including 161 paroxysmal AF and 25 non-paroxysmal AF who underwent catheter ablation were studied. Clinical datum before and during ablation were recorded, and systematic follow-up was conducted after ablation. Univariate and multivariate analyses were carried out to determine the factors predicting late recurrence of AF (LRAF) which means AF recurrence after 3 months.There were 47(25.27%) patients who experienced LRAF. Multivariate Logistic regression analysis was carried out to the parameters that P0.10 in the univariate analysis, which includes overweight/obesity, metabolic syndrome (MetS), AF categories, duration of AF history, left atrial diameter (LAD), diabetes mellitus, ablation strategies, procedural failure and early recurrence of AF after ablation (ERAF). Ultimately, the results demonstrated that overweight/obesity (OR=4.71, 95% CI 1.71-12.98, P=0.003), MetS (OR=4.41, 95% CI 1.56-12.46, P=0.005), procedural failure (OR=58.34, 95% CI 6.83-498.34, P0.001), and ERAF (OR=3.18, 95% CI 1.07-9.44, P=0.037) were independent predictors of AF recurrence after ablation.Overweight/obesity, metabolic syndrome, procedural failure and ERAF are independent predictors of late recurrence of atrial fibrillation in this group of patients.

Aims The purpose of this study was to evaluate the efficacy and safety of cardiac resynchronization plus implantable cardioverter defibrillator (CRT-D) therapy and implantable cardioverter defibrillator (ICD) therapy in treating heart failure by systematically reviewing randomized controlled trials. Methods and results Databases of Medline, Embase, and Cochrane Library were searched for published studies up to 31 May 2012. Clinicaltrials.gov and US Food and Drug Administration websites were searched as well. Only randomized controlled trials comparing the efficacy of CRT-D therapy with ICD therapy were enrolled in meta-analysis. Eight randomized controlled trials characterizing 5674 patients were finally included. Meta-analysis found that CRT-D therapy was associated with significant improvement in clinical conditions [odds ratio (OR): 1.66; 95% confidence interval (CI):1.33-2.07] and a reduction in hospitalization (OR: 0.7; 95% CI: 0.6-0.81) and all-cause mortality (OR: 0.8; 95% CI: 0.67-0.95). Although advantages of CRT-D therapy over ICD therapy were obvious, the peri-implantation adverse events of CRT-D therapy remained to be concerns. Conclusion Compared with ICD therapy, patients receiving CRT-D therapy have favourable outcomes regarding improvement in clinical conditions, hospitalization rate, and overall survival, but at a significantly higher risk of peri-implantation adverse events. Future studies are warranted to optimize the clinical application of CRT-D.

BACKGROUND:The efficacy of short-term antiarrhythmic drugs (AADs) use compared with no-AADs prescription after catheter ablation of atrial fibrillation (AF) in preventing atrial arrhythmia recurrence is uncertain. METHODS:We searched PubMed, Embase, and the Cochrane Library through December 2015 to identify randomized controlled trials (RCTs) which evaluated the efficacy of short-term AADs use compared with no-AADs prescription after AF ablation in preventing atrial arrhythmia recurrence. The primary outcome was labeled as early atrial arrhythmia recurrence within 3 months after ablation. Secondary outcome was defined as late recurrence after 3 months of ablation. Random-effects model or fixed-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). RESULTS:Six RCTs with 2,667 patients were included into this meta-analysis. Compared with no-AADs administration after AF ablation, short-term AADs use was associated with significant reduction of early atrial arrhythmia recurrence (RR, 0.68; 95% CI, 0.52-0.87; p = 0.003). Trial sequential analysis (TSA) showed that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, establishing sufficient and conclusive evidence. However, compared with no-AADs prescription, short-term AADs use after AF ablation didn't significantly reduce the risk of late atrial arrhythmia recurrence (RR, 0.92; 95% CI, 0.83-1.03; p = 0.15). TSA supported this result; meanwhile the estimated required information size (1,486 patients) was also met. CONCLUSION:Short-term use of AADs after AF ablation can significantly decrease the risk of early atrial arrhythmia recurrence but not lead to corresponding reduction in risk of late atrial arrhythmia recurrence.

Background: More widespread use of drug-eluting stents (DES) to treat coronary heart disease (CHD) has recently generated more attention to thrombosis, which was relative to the polymer. Polymer-free and biodegradable polymer-based stents are more frequently studied, but their efficacy on preventing detrimental clinical events is unclear. Methods and Results: To assess whether polymer-free paclitaxel-eluting stent (YINYI stent) was noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents (EXCEL stent) in preventing detrimental clinical cardiovascular events, a total of 167 consecutive CHD patients requiring DES implantation were randomly divided into the YINYI group (n = 82) and the EXCEL group (n = 85). The primary end-point was major adverse cardiac events (MACE). The secondary end-points included stent thrombosis events, all-cause mortality, and rehospitalization. The study was designed to test the noninferiority or equivalence of the YINYI stent compared with the EXCEL stent with respect to one-year MACE according to a noninferiority or equivalence margin of 0.1. One-year MACE was 6.10% in the YINYI group versus 5.88% in the EXCEL group. The lower limit of the one-sided 95% confidence interval was −0.0582 (P = 0.002 from the test for noninferiority). The 95% confidence interval for the equivalence test was [−0.0698, 0.0742] (P1=0.004 and P2=0.007 from 2 times the 1-sided test for equivalence). There was no statistically significant difference in thrombosis events, all-cause death, and rehospitalization (all P > 0.05). Conclusions: In this small randomized trial, polymer-free paclitaxel-eluting stents appear to be noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents. (J Interven Cardiol 2012;25:604–610)

The purpose of this study was to compare the efficacy of focused ultrasound circumferential pulmonary vein ablation (CPVa) and BOX ablation (BOXa) in an acute atrial fibrillation (AF) model. Twenty mongrel dogs were divided into either CPVa or BOXa groups. CPV or BOX focused ultrasonic ablation was conducted in each group after successful establishment of the AF model. Before-and-after ablation left atrial effective refractory period (LAERP), AF inducibility, and induced AF lasting time were measured in both groups. The LAERP after AF model establishment was significantly shorter than that before establishment (102 ± 10 vs. 140 ± 10 ms, p

In recent years, ultrasound-targeted microbubble destruction (UTMD) has been utilised for the targeted delivery of stem cells. We tested the effects of the myocardial micro-environment changes induced by UTMD on promoting the homing of mesenchymal stem cells (MSCs) to the ischemic myocardium. Dogs were randomly divided into two groups and treated with or without UTMD after the establishment of myocardial infarction models. 4,6-diamino-2-phenyl indole (DAPI) labelled MSCs were transplanted via coronary injections 2 weeks after myocardial infarction in both groups. The results from real-time PCR and western blot analyses indicated that the expression of various cytokines in UTMD-treated dogs was much higher than that observed in non-treated dogs. Histopathological findings demonstrate that ultrasound at a frequency of 1MHz and an intensity of 1.0W/cm(2) provoked inflammatory reactions with mild myocardial damage. Myocardial microenvironment changes caused by UTMD may promote the homing of MSCs to the ischemic myocardium. This non-invasive technique may be a promising method for cardiac cell transplantation therapy.

The purpose of this study is to evaluate the relationship between plasma high-sensitivity C-reactive protein (hs-CRP), atrial natriuretic peptides (ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, and the risk and recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF).Plasma ANP, NT-proBNP, and hs-CRP levels were measured before and 3 months after PVI in 33 patients with PAF and 30 control participants.(1) NT-proBNP levels at baseline were significantly elevated in subjects with PAF compared with control subjects (296.8 ± 272.1 vs. 80.8 ± 69.1 pg/ml), but ANP and hs-CRP levels were normal; NT-proBNP levels normalized 3 months after PVI, but ANP and hs-CRP levels did not change significantly; NT-proBNP levels at baseline in the recurrent group were markedly higher than those in the nonrecurrent AF group (572.7 ± 234.2 vs. 176.8 ± 188.7 pg/ml). (2) Cox stepwise multivariate analysis demonstrated that only elevated NT-proBNP level at baseline was an independent predictor of AF recurrence (p 0.001) after PVI among 13 variables, such as echocardiographic parameters, plasma ANP, NT-proBNP, and hs-CRP levels. A cutoff value of NT-proBNP ≥ 423.2 pg/ml was a significant risk factor for AF recurrence (p = 0.002).Elevated NT-proBNP level at baseline, but not ANP and hs-CRP, is a sensitive biomarker for early predicting AF recurrence in patients with PAF.

The effect of different treatment strategies of atrial fibrillation on left atrial (LA) size has not been compared in lone paroxysmal atrial fibrillation. The objective of the present study was to evaluate the evolution of LA size over time in patients who underwent different treatment interventions. Two hundred forty patients with lone paroxysmal atrial fibrillation were assigned to four groups. The circumferential pulmonary vein ablation (CPVA) group (n = 60) was treated with CPVA, segmental pulmonary vein isolation (SPVI) group (n = 60) with SPVI, AMIO group (n = 60) with amiodarone alone, and AMIO + LO group (n = 60) with amiodarone plus losartan. LA diameter was measured with transthoracic echocardiogram at baseline, 3, 6, 9, and 12 months after the interventions. In the CPVA group, LA size at third, sixth, ninth, and 12th month had a significant decrease than that at baseline and in the other three groups. LA size in patients with atrial fibrillation recurrence in the four groups was significant higher than that in patients with no atrial fibrillation recurrence (P = 0.002–0.001). The results suggested that a shortened LA size is not consistent with improved sinus rhythm maintenance. Although maintenance of sinus rhythm is not the only factor in determining shrinking or enlargement of the left atrium, inhibiting or eliminating activity of the pulmonary vein is very important for paroxysmal atrial fibrillation. Atrial fibrillation recurrence is a main factor contributing to enlargement of the LA.

Background Previous studies have shown that contrast-enhanced multidetector computed tomography (CE-MDCT) could identify ventricular fibrosis after myocardial infarction. However, whether CE-MDCT can characterize atrial low-voltage regions remains unknown. Objective The purpose of this study was to examine the association of CE-MDCT image attenuation with left atrial (LA) low bipolar voltage regions in patients undergoing repeat ablation for atrial fibrillation recurrence. Methods We enrolled 20 patients undergoing repeat ablation for atrial fibrillation recurrence. All patients underwent preprocedural 3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the LA during the ablation procedure. Epicardial and endocardial contours were manually drawn around LA myocardium on multiplanar CE-MDCT axial images. Segmented 3-dimensional images of the LA myocardium were reconstructed. Electroanatomic map points were retrospectively registered to the corresponding CE-MDCT images. Results A total of 2028 electroanatomic map points obtained in sinus rhythm from the LA endocardium were registered to the segmented LA wall CE-MDCT images. In a linear mixed model, each unit increase in the local image attenuation ratio was associated with 25.2% increase in log bipolar voltage (P = .046) after adjusting for age, sex, body mass index, and LA volume, as well as clustering of data by patient and LA regions. Conclusion We demonstrate that the image attenuation ratio derived from CE-MDCT is associated with LA bipolar voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful alternative in patients with contraindications to magnetic resonance imaging.

The purpose of this trial was to compare the long-term efficacy of low-dose amiodarone with losartan and perindopril (both combined with low-dose amiodarone) for the prevention of atrial fibrillation (AF) recurrence in patients with lone paroxysmal AF.One-hundred and seventy-seven patients with lone paroxysmal AF were randomly assigned to three treatment groups: group 1 received low-dose amiodarone alone, group 2 received low-dose amiodarone plus losartan, and group 3 received low-dose amiodarone plus perindopril. Left atrial diameter was measured with transthoracic echocardiogram at baseline and 6, 12, 18, and 24 months after randomization. The primary endpoint was the incidence of AF documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. The primary endpoint was reached in 24 patients (41%) in group 1, 11 (19%) in group 2, and 14 (24%) in group 3 (P = 0.02). The Kaplan-Meier survival analysis demonstrated a significant reduction in AF recurrence in group 2 (P = 0.006, log-rank test) as well as in group 3 (P = 0.04, log-rank test) when compared with group 1. No difference in the AF recurrence-free survival was found between group 2 and group 3. After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36 +/- 2.3 and 35 +/- 2.4 vs. 38 +/- 2.4 mm, P0.001 for both comparisons).The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.

The efficacy of short-term antiarrhythmic drugs (AADs) use compared with no-AADs prescription after catheter ablation of atrial fibrillation (AF) in preventing atrial arrhythmia recurrence is uncertain. We searched PubMed, Embase, and the Cochrane Library through December 2015 to identify

Background The effectiveness of catheter-based renal denervation (RDN) remains controversial. Although the reasons for this have not yet been elucidated, ineffective denervation appears to be an important factor. The present study aimed to investigate the difference in RDN between a saline-irrigated catheter (SIC) and a temperature-controlled catheter (TCC). Methods Dogs (n = 6) from the Kunming province in Chinese were ablated; the SIC was introduced into the right renal artery, while the TCC was introduced into the left renal artery. After 6 months, histopathology and renal angiography were performed, and the change in neural density was evaluated using morphometric software. The average values of heart rate (HR), blood pressure (BP), and catecholamine metabolites were assessed at baseline and follow-up. Results Histopathology showed nerve demyelination and denaturation, as well as interstitial hyperplasia, although these changes were more pronounced when the SIC was used. The change in neural density was greater and ablation was deeper when the SIC was used. Intimal hyperplasia was greater when the TCC was used, whereas medial hyperplasia was greater when the SIC was used. A trend toward a decrease in HR, BP, metanephrine, and normetanephrine between baseline and follow-up was observed. Conclusions Our findings suggest that SIC ablation results in more extensive neural degeneration, deeper penetration, and less extensive intimal hyperplasia than TCC ablation for RDN.

Background: The study was to evaluate the value of CHADS2 and CHADS2VASC scores on predicting left atrial (LA) thrombus in the patients with atrial fibrillation (AF). Methods and Results: All the non-valvular AF patients undergoing AF ablation from June 2010 to June 2012 were included and divided into two groups: patients without anticoagulation and with Coumadin anticoagulation for at least 4 weeks. The relationship between CHADS2 and CHADS2VASC scores and LA thrombus as identified on transesophageal echocardiography (TEE) was analyzed prior to ablation. A total of 397 patients underwent pre-ablation TEE: 212 patients without anticoagulation, and 185 with anticoagulation. There were no differences in the CHADS2 and CHADS2VASC scores in the two groups. LA thrombus was present in 15.6% and 5.9% for the patients without anticoagulation and for those with anticoagulation, respectively (p = 0.002). There was a strong association between CHADS2 and LA thrombus, and between CHADS2VASC and LA thrombus in the two groups. No thrombus was identified in patients with CHADS2VASC score of 0 in both groups. However, thrombus was detected in 3.5% of patients with CHADS2 score of 0 in the group without anticoagulation, while no thrombus was present in the ones with anticoagulation. CHADS2VASC score of ≥1 (r=2.03, p = 0.04) was the only factor independently associated with LA thrombus in patients without anticoagulation, while both CHADS2VASC score of ≥2 (r=2.61, p=0.02) and CHADS2 score of ≥2 (r=2.73, p=0.01) were independently associated with LA thrombus. Further analyses showed that CHADS2VASC score was a better predictor for LA thrombus than CHADS2 score in patients without anticoagulation. However, there was no difference between the two scoring systems in predicting LA thrombus in patients with anticoagulation. Conclusions: LA thrombus was associated with CHADS2VASC and CHADS2 scores in non-valvular AF patients without anticoagulation. CHADS2VASC score was a better predictor than CHADS2 score for LA thrombus in patients without anticoagulation. The data suggested that it might be unnecessary to undergo a TEE evaluation for LA thrombus in low risk patients identified by CHADS2VASC score regardless anticoagulation therapy prior to cardioversion or ablation.

The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1–7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin–angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF. Electronic supplementary material The online version of this article (doi:10.1007/s00395-015-0499-0) contains supplementary material, which is available to authorized users.

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

Over the past decade, catheter ablation has emerged as an important therapeutic option for ventricular tachycardia (VT) in both patients with and without structural heart disease. In patients without structural heart disease, catheter ablation serves as sole therapy for the treatment of VT. For those with structural heart disease, VT ablation has generally been reserved for patients who experience ICD therapies, and particularly those who fail antiarrhythmic agents. With the growing number of patients with implantable devices as well as improvements in heart failure therapy resulting in improved survival among ICD patients, the overall number of patients needing therapy for VT continues to increase. The past years have witnessed significant advances in our understanding of the arrhythmic substrate in various cardiomyopathies, resulting in substrate-based approaches for targeted VT ablation. Further, the growth in better technologies and techniques for VT ablation, such as the use of percutaneous epicardial ablation, the innovation of multielectrode catheters for rapid mapping, the use of intracardiac echocardiography (ICE) for mapping unusual sites, and activation and entrainment mapping of previously unmappable VTs assisted by mechanical circulatory support devices, has overcome the limitations and greatly improved the success rates of catheter ablation. This review summarizes recent advances and novel approaches in both technology and techniques for catheter ablation of ventricular tachycardia.

Aims The aim of this study was to investigate the predictive ability of paced QRS duration (pQRSd) for heart failure events among patients receiving right ventricular apical pacing (RVAP). Methods and results A total of 194 patients with complete atrioventricular block receiving pacemaker treatment were enrolled and stratified to group 1, pQRSd < 160 ms, n = 53; group 2, 160 ≤ pQRSd < 190 ms, n = 97; and group 3, pQRSd ≥ 190 ms, n = 44. Study outcomes were heart failure events, changes in pQRSd, and changes in left ventricular ejection fraction (LVEF). During the 3-year follow-up, the incidence of heart failure events was 9.4, 27.8, and 56.8% in groups 1, 2, and 3, respectively (P < 0.001). Among the patients without heart failure events, the pQRSd at 3 years remained longer than that at baseline (162.1 ± 22.6 vs. 160.9 ± 22.1 ms, P < 0.05), whereas among patients who experienced heart failure events, the prolonged pQRSd at 3 years seemed more pronounced as compared with baseline (184.1 ± 21.1 vs. 179.8 ± 21 ms, P < 0.001). Linear regression demonstrated that a decrease in LVEF was positively correlated with pQRSd over time (relative risk 0.423; P < 0.05). The receiver operating charactersitic curve showed that the cut-off value of pQRSd was 165 ms with a sensitivity of 0.789. Conclusion A prolonged pQRSd has a detrimental effect on long-term cardiac function during RVAP in patients with complete atrioventricular block. pQRSd could be a useful predictor to identify patients who are at risk for heart failure events during RVAP.

Importance The timing and selection of patients with Kawasaki disease for corticosteroid use to prevent coronary artery complications remain controversial. Objective To evaluate the effect of corticosteroid therapy in KD. Data Sources Databases of Medline, The Cochrane Library, and the Clinicaltrials.gov website until July 2015. We used the key words [“Kawasaki disease”] and [“steroid” OR “corticosteroid”] to retrieve potentially relevant studies in the databases of Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2015. Both English and non-English literature was identified. Titles and abstracts were reviewed by 2 authors (S.C. and Y.D.) to determine suitability for inclusion. Relevant articles were reassessed by reviewing the full text. Discrepancies in study inclusion were resolved by consensus (M.G.K.). Study Selection Clinical studies that compared corticosteroids plus intravenous immunoglobulin (IVIG) therapy with IVIG therapy alone in treating patients with KD. Studies either using corticosteroids as initial therapy or as rescue therapy were included. Data Extraction and Synthesis Investigators independently extracted the data information. Data were quantitatively synthesized using random-effects analysis. Main Outcomes and Measures Rate of coronary artery abnormalities. Results Sixteen comparative studies characterizing 2746 patients were analyzed. The duration of illness before corticosteroids therapy was significantly shorter in the initial corticosteroids subset than in the rescue corticosteroids subset. The rate of coronary artery abnormalities was significantly lower in adjunctive corticosteroids therapy than in IVIG therapy (odds ratio [OR], 0.424; 95% CI, 0.270-0.665). Meta-regression based on known variables demonstrated that the overall efficacy was negatively correlated with the duration of illness before corticosteroid therapy ( P Conclusions and Relevance This study highlights the importance of timing to prevent coronary artery complication in treating KD. High-risk patients with KD benefit greatly from a timely and potent adjunctive corticosteroid therapy strategy.

The aim of the present study was to explore whether ultrasound microbubble destruction augments site-targeted engraftment of bone marrow mesenchymal stem cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of mercuric chloride (HgCl₂). Forty Sprague-Dawley (SD) rats were randomly divided into the following groups after the establishment of rat models of AKI (n = 10): (1) Model group alone (control group); (2) 1.0 W/cm² ultrasound (US) + microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm² US+MB + MSCs group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI) labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase chain reaction (RT-PCR) and Western blotting and histological examination were performed 7 days after MSCs transplantation. It was observed via fluorescence microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB + MSCs group was significantly more than the MSCs group (p < 0.05). The results from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic acid (mRNA) compared with the control group and the MSCs group (p < 0.05). Western blot analysis showed that the expression of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly increased compared with the all other groups (p < 0.01). The extent of tubular necrosis and dilation was significantly milder in the US/MB + MSCs group (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm² with a 5s pause, totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by 1.0 W/cm² ultrasound can promote both the homing of BM-MSCs to kidney tissue and the recovery of the kidney in AKI in rats.

antiplatelet therapy after coronary stenting: a randomizedmulticenter trial. Circulation Apr 24 2012;125(16):2015–26. [6] Campo G, Tebaldi M, Vranckx P, et al. Short vs. long term duration of dual antiplatelet therapy in patients treated for in-stent restenosis. A PRODIGY trial substudy. J Am Coll Cardiol 2014;63(6):506–12. [7] Valgimigli M, Tebaldi M, Borghesi M, et al. Two-year outcomes after firstor secondgeneration drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the PRODIGY study. JACC Cardiovasc Interv 2014;7(1):20–8.

Background Thrombolysis in myocardial infarction (TIMI) flow grade (TFG) was a gold standard for comparison of the various methods of evaluating the efficacy of reperfusion, and risk score was a pragmatic method of risk stratification and evaluation of prognosis for acute coronary syndrome (ACS). However, it is uncertain whether or not the prognostic value of combining risk score and TFG on outcome of acute coronary syndrome could be improved. Materials and Methods A total of 279 consecutive patients with ACS (mean age 67.57 ± 9.88 years, 69.2% male) admitted to our hospital were enrolled. Clinical risk score, TFG, and combined risk score were calculated. The primary endpoint of this study included cardiac death and noncardiac death; the secondary endpoint included nonfatal stroke, reinfarction, heart failure, and recurrent angina. Results During the follow-up of 11.41 ± 5.33 months, 11 patients reached the primary endpoint, and 23 patients reached the secondary endpoint. The prognostic values evaluated by composite endpoint, primary endpoint, and secondary endpoint were 0.722, 0.685, and 0.721, respectively, for clinical risk score they were 0.774, 0.798, and 0.737, respectively, for TFG they were 0.805, 0.808, and 0.776, respectively, for combined risk score. In pair-wise comparisons of prognostic values, there were no significant differences among these methods, except that the combined risk score can more accurately predict the composite endpoint than the others. Conclusion The results suggest that the combined risk score is a simple and efficient method of prediction of composite endpoint. Copyright © 2009 Wiley Periodicals, Inc.

Background Although amiodarone plus angiotensin II receptor blockers (ARBs) and catheter ablation may improve sinus rhythm maintenance of paroxysmal atrial fibrillation (AF), their clinical efficacies have not been compared. This prospective cohort study was designed to compare clinical efficacy of catheter ablation and amiodarone plus losartan on sinus rhythm maintenance in patients with paroxysmal AF. Materials and methods A total of 240 patients with paroxysmal AF were assigned to four groups. CPVA group (n = 60) was treated with circumferential pulmonary vein ablation (CPVA), SPVI group (n = 60) with segmental pulmonary vein isolation, AMIO group (n = 60) with amiodarone and AMIO + LO group (n = 60) with amiodarone plus losartan. The endpoint was documented recurrence of AF > 30 s by Holter or conventional 12-lead ECG in the 1-year follow-up period. Results During 12 months of follow-up, the primary end point was reached in 28 patients in CPVA group, 14 patients in SPVI group, 25 patients in AMIO group and 13 patients in AMIO + LO group, respectively. The sinus rhythm in SPVI and AMIO + LO group were significant higher than that in CPVA and AMIO group (P

Background Inflammation plays a role in the pathogenesis of coronary atherosclerosis. Materials and methods Six hundred twenty-three patients with acute coronary syndrome (ACS) referred for coronary angiography for the first time in our hospital were enrolled in this study. White blood cell and its subtypes were measured on admission. The study population was divided into three groups based on total white blood cell count and followed up. Clinical end points were major adverse cardiac events (MACEs), including cardiogenic death, stroke, heart failure, non-fatal myocardial infarction, rehospitalization for angina pectoris. Results The median age was 68 years (range 31–92) and 64·2% of the patients were men. The median white blood cell count was 6·48 × 109 L−1 (range 2·34–27·10 × 109 L−1). The median follow-up duration was 21 months (range 1–116) and MACEs occurred in 167 patients. The multivariable Cox proportional hazards regression model revealed that neutrophil count [Relative risk = 1·098, 95% Confidence interval (CI): 1·010–1·193, P = 0·029) was a risk factor for MACEs. The logistic regression model revealed that lymphocyte count [Odds ratio (OR) = 1·075, 95% CI: 1·012–1·142, P = 0·018] and monocyte count (OR = 8·578, 95% CI: 2·687–27·381, P

Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with increased risk for stroke, heart failure, and all-cause mortality [(1–3)][1]. The mortality rate of patients with AF is about double that of patients in normal sinus rhythm, and data from the Framingham Heart

Objectives The transplantation of bone-marrow derived mesenchymal stem cells (MSCs) to ischaemic myocardium is considered to be a useful therapeutic approach to ischaemic heart disease, but the MSCs delivery efficacy still can9t meet the needs for therapy. Recently, ultrasound-targeted microbubble destruction (UTMD) has been utilised in the targeted delivery of stem cells. In this study, we tested the effects of myocardial micro-environment changes induced by ultrasound target microbubble destruction on promoting the MSCs homing to the ischaemic myocardium. Methods In order to optimise the ultrasonic parameters and to explore the biological effects of different intensities of ultrasound mediated microbubble destruction to the myocardium of canine, 9 mongrel dogs were randomly divided into three groups. Three groups were treated with frequency of 1 MHz ultrasonic irradiation, but the intensity of ultrasonic irradiation was different in each group. Group 1 was treated with intensity of 0.5 W/cm 2 , group 2 was treated with intensity of 1.0 W/cm 2 and group 3 was treated with intensity of 1.5 W/cm 2 . The myocardium was harvested for hematoxylcne & eosin (HE) staining and Transmission electron microscope (TEM) detection to observe the tissue microstructures. The ultrasound parameters were optimised according to the results of TEM and HE staining results. Then, ultrasound with optimised parameters was used to investigate the cardiac micro-environment change induced by ultrasound mediated microbubble destruction. Twenty mongrel dogs were randomly divided into a treatment group and a control group after the establishment of animal models of myocardial infarction. One-week later, dogs in treatment group were treated by ultrasonic microbubble destruction for three times in 1 week, no treatment for the dogs in the control group. Vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), vascular cell adhesion molecule-1 (VCAM-1) and interleckin-1β (IL-1β) levels of the myocardium were measured by Real time PCR and western blot analyses in half of the dogs in each group after 2 weeks. The other half of the remaining dogs (n=10) in each group were transplanted with 5 ml DAPI labelled MSCs (2.45×10 7 cells/ml) with via coronary ostium by intervention technique under digital subtraction arteriography (DSA) monitor. Five-days later, the myocardium was harvested from the margin of the infarcted area. Laser scanning confocal microscope (LSCM) was used to observe the distribution of the stem cells. Results The 1 MHz ultrasound at the intensity of 1.0 W/cm 2 provoked pertinent inflammatory reaction with mild myocardial damage. Real time PCR and western blot analyses showed that the expression of VEGF, SDF-1, VCAM-1 and IL-1β in the treatment group were much higher than that in the control group. By laser scanning confocal microscope, we found that the distribution of MSCs in pretreatment myocardium was significantly wider than that in the control group. Conclusions Ultrasound targeted microbubble destruction improved myocardial microenviroment changes might promote MSCs homing to the ischaemic myocardium. This noninvasive technique might be a promising method for the cardiac cell transplantation therapy.