The association between paced left ventricular activation time and cardiac reverse remodeling in heart failure patients with left bundle branch block.

INTRODUCTION: The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow-up. METHODS: Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT-proBNP and echocardiographic parameters were recorded during routine follow-up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow-up were analyzed. RESULTS: Eighty-three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT-proBNP 1057[513-3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p < .001) and median paced LVAT was 80[72-88] ms. After a median follow-up of 12[9-29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT-proBNP decreased to 215[73-532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p < .001; LVEFbaseline: p = .001). The difference in LVEF6M was statistically significant among groups (p < .001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p = .090). There was no significant correlation between ΔLVEF6M-baseline, ΔLVEF1Y-6M and LVAT respectively (ΔLVEF6M-baseline: p = .261, r = -.126; ΔLVEF1Y-6M: p = .085, r = .218). CONCLUSION: Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover.

Left Bundle Branch Pacing for Bradycardia in Non-obstructive Hypertrophic Cardiomyopathy Patients: Feasibility, Safety, and Effect.

PURPOSE: Left bundle branch pacing (LBBP) is as an innovative physiological pacing approach. The research on LBBP in non-obstructive hypertrophic cardiomyopathy (NOHCM) patients is scarce. This study aimed to assess the feasibility, safety, and effect of LBBP in bradycardia NOHCM patients with permanent pacemaker (PPM) implantation indication. METHODS: Thirteen consecutive patients with NOHCM who received LBBP were retrospectively enrolled as a hypertrophic cardiomyopathy (HCM) group. Following 1:3 matching, 39 patients without HCM were randomly matched as a control group. Echocardiographic index and pacing parameters were collected. RESULTS: The successful LBBP was achieved in 96.2% of all cases (50/52), and the success rate of the HCM group was 92.3% (12/13). In the HCM group, the paced QRS duration (from the pacing stimulus to QRS end) was 145.6±20.8 ms. The stimulus to left ventricular activation time (s-LVAT) was 87.4±15.2 ms. In the control group, the paced QRS duration was 139.4±17.2 ms, and the s-LVAT was 79.9±14.1 ms. During the implantation, R-wave sensing and the pacing threshold of the HCM group were significantly higher than the control group (20.2±10.5 vs 12.5±5.9 mV, P < 0.05; 0.8±0.3 vs 0.6±0.2V/0.4 ms, P < 0.05). In addition, the fluoroscopic duration and procedural duration were longer in the HCM group (14.8±8.3 vs 10.3±6.6min, P = 0.07; 131.8±50.5 vs 101.4±41.6 min, P < 0.05). The lead insertion depth was 15±2 mm in the HCM group, and no procedure-related complications occurred. During the 12-month follow-up, pacing parameters remained stable and were of no significance in the two groups. The cardiac function did not deteriorate, and the left ventricular outflow tract gradient (LVOTG) did not increase in the follow-up. CONCLUSION: LBBP might be feasible and safe for NOHCM patients with conventional bradycardia pacing indication, and there is no deterioration in cardiac function and LVOTG of patients with NOHCM.

Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression.

This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 µmol/gprot vs. DCM 22.89 ± 5.90 µmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.

Discussion of LBBP synchronization effects in HF patients with LBBB and comparison with BiV-CRT.

Left bundle branch block (LBBB) is common in heart failure patients, and could induce dyssynchrony of ventricular contraction, deterioration of cardiac function, and increased mortality. Cardiac resynchronization therapy (CRT) with biventricular pacing reduces ventricular dyssynchrony, heart failure hospitalization, and all-cause mortality in heart failure patients with LBBB. However, there are approximately 30% nonresponders and 10% of patients remain untreated owing to an unsuitable coronary sinus vein. His bundle pacing (HBP) is a more physiological pacing modality which has showed inspiring outcomes in heart failure patients with LBBB, but is limited by implantation challenges, lower success rates, and high pacing capture threshold. Recently, left bundle branch pacing (LBBP), defined as the capture of left bundle branch via transventricular septal approach, has emerged as a newly physiological pacing modality, which is implanted slightly distal to the His bundle. Early clinical studies have demonstrated the procedural feasibility of LBBP with rare complications and high success rate. Recent studies have indicated its potential to be an alternative for CRT. Synchronization effect and the current status of LBBP in the field of CRT are summarized in this paper.

Beneficial Effects of Sacubitril/Valsartan at Low Doses in an Asian Real-World Heart Failure Population.

This study aimed at analyzing the clinical profile of real-world patients with heart failure with reduced ejection fraction (HFrEF) and evaluating the safety and efficacy of sacubitril/valsartan among Asian patients in daily practice. We conducted a single-center prospective observational cohort study of HFrEF patients treated with sacubitril/valsartan from September 2017 to September 2018 with a follow-up of 6 months. The mean (SD) age of the 110 patients enrolled was 59.7 ± 13.3, 85 (77.3%) were men and 41 (37.3%) had ischemic cardiomyopathy. Thirty-one (27.2%) patients with low systolic blood pressure initiated sacubitril/valsartan on a tiny dose of 12/13 mg. Despite the low mean daily dose achieved in real world mainly because of hypotension, left ventricular ejection fraction increased significantly from 35.4 ± 8.9% at baseline to 43.0 ± 12.2% after 6-month follow-up (P < 0.001). We also observed a significant improvement in a 6-minute walk test (6-MWT) distance and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration reduction. No severe adverse event was recorded. Low dose sacubitril/valsartan induces beneficial cardiac reverse remodeling and improves clinical functional performance in real-world HFrEF patients without severe adverse effect. A tiny initial dose may enhance tolerability and reduce discontinuation rate by minimizing hypotension events in patients with low systolic blood pressure. These data further support using low-dose sacubitril/valsartan among eligible patients with HFrEF in Asia.

Typical BBB morphology and implantation depth of 3830 electrode predict QRS correction by left bundle branch area pacing.

AIM: Strict criteria of typical left bundle branch block (LBBB) can help with the prediction for cardiac resynchronization therapy response. The aim of this study is to determine whether the use of strict criteria for both LBBB and right bundle branch block (RBBB) predicts successful QRS correction (≤130 ms) by left bundle branch area pacing (LBBAP). METHODS: Consecutive patients with pacemaker indications according to the present guideline who also underwent LBBAP implantation were retrospectively assessed. Inclusion criteria were patients with BBB and the baseline QRSd > 130 ms. Baseline characteristics and pacing parameters were compared between typical and atypical BBB groups. Multivariate logistic regression was used to adjust for covariates that were found in univariate analyses for successful QRS correction by LBBAP. RESULTS: Seventy-three patients were enrolled. Among them, 10 (13.6%) had atypical BBB (5 LBBB and 5 RBBB) and 63 (86.4%) had typical BBB (30 LBBB and 33 RBBB). The rate of successful QRS correction was higher in typical-BBB patients (52/63; 82.5%) than that in atypical-BBB patients (3/10; 30%), P < .001. Paced QRSd was obviously narrower in patients with typical BBB than that in patients with atypical-BBB (118 ± 14 vs 133 ± 14 ms, P = .003). In multivariate logistic regression, only typical BBB morphology and the implantation depth of 3830 pacing electrode in the ventricular septum were independent predictors for successful QRS correction. CONCLUSION: This study demonstrates that patients with typical-BBB morphology benefit more from LBBAP for QRS correction. Typical BBB morphology together with deep penetration of 3830 ventricular electrode in the interventricular septum predicts the success of QRS correction by LBBAP.

Reversion of cardiac memory during left bundle branch pacing.

Cardiac memory (CM) is identified as an altered T wave when normal ventricular activation resumes after an abnormal myocardial activation period. We present a case who initially underwent temporary right ventricular apex (RVA) pacing for one week which induced typical pseudo-primary T wave changes. The T wave inversion was observed after the end of RVA pacing when left bundle branch pacing (LBBP) was initiated, and the abnormal T waves gradually return to almost normal repolarization during LBBP 40 days later.

Quantification of Acute Myocardial Damage Secondary to Implantation of Electrodes for the Left Bundle Branch Area Pacing.

BACKGROUND: Different from the traditional right ventricular pacing, the left bundle branch area pacing (LBBAP) is accomplished with deeper lead implantation and more attempts. However, myocardial damage is unclear in LBBAP. OBJECTIVE: The objective of the study was to observe the change of troponin T and explore possible factors associated with greater myocardial damage in LBBAP. METHODS: Patients with an indication for pacemaker implantation underwent attempts for LBBAP by transventricular septal method. Levels of troponin T were determined before operation, 12 h and 1 week after the operation. Parameters of intraoperation and follow-up were recorded and analyzed. RESULTS: In total, successful LBBAP was achieved in 126 patients. The levels of troponin T increased significantly at 12 h after the operation compared with those before operation (96.45 ± 11.07 [69.06] vs. 16.59 ± 1.84 [11.92] ng/L, p < 0.001), while there were no significant differences between pre- and post-operative levels at 1 week. Correlation and regression analysis showed that only the number of attempts was an independent factor related to the change of troponin T. During 1 year of follow-up, LBBAP was safe and feasible with few complications. CONCLUSIONS: Myocardial damage of LBBAP was clinically significant. The number of attempts was an independent factor related to the myocardial damage.

Identification of biomarkers correlated with hypertrophic cardiomyopathy with co-expression analysis.

Hypertrophic cardiomyopathy (HCM) is reported to be the most common genetic heart disease. To identify key module and candidate biomarkers correlated with clinical prognosis of patients with HCM, we carried out this study with co-expression analysis. To construct a co-expression network of hub genes correlated with HCM, the Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network analysis of central genes was performed to recognize the interactions of central genes. Gene set enrichment analyses were carried out to discover the possible mechanisms involved in the pathways promoted by hub genes. To validate the hub genes, quantitative real-time polymerase chain reaction (RT-PCR) was performed. Based on the results of topological overlap measure based clustering, 2,351 differentially expressed genes (DEGs) were identified. Those genes were included in six different modules. Of these modules, the yellow and the blue modules showed a pivotal correlation with HCM. DEGs were enriched in immune system procedure associated GO terms and KEGG pathways. We identified nine hub genes (TYROBP, STAT3, CSF1R, ITGAM, SYK, ITGB2, LILRB2, LYN, and HCK) affected the immune system significantly. Among the genes we validated with RT-PCR, TYROBP, CSF1R, and SYK showed significant increasing expression levels in model HCM rats. In conclusion, we identified two modules and nine hub genes, which were prominently associated with HCM. We found that immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.

Effects of Angiotensin Receptor Neprilysin Inhibitors on Inducibility of Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy.

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy.

BACKGROUND/AIMS: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. METHODS: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague-Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson's trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. RESULTS: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-ß1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). CONCLUSIONS: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.

Clinical outcomes with biventricular versus right ventricular pacing in patients with atrioventricular conduction defects.

There have been increasing concerns about the unexpected effects of right ventricular (RV) pacing. We aimed to systematically evaluate the effect of biventricular (BiV) versus RV pacing on clinical events in patients with impaired AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies comparing BiV pacing with RV pacing in patients with AV block, through April 2017. We selected randomized controlled trials (RCTs) reporting data on mortality, hospitalization for heart failure (HF), and/or 6-min walk distance (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that BiV pacing was associated with a significantly reduced all-cause mortality in contrast to RV pacing (risk ratio (RR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, I2 = 9.6%). BiV pacing, compared with RV pacing, significantly reduced the rate of HF hospitalization (RR = 0.74, 95% CI 0.59 to 0.93, I2 = 10.1%). Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV pacing still had a lower mortality and non-significant reduced HF hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow-up (mean difference = 4.99 m, 95% CI - 11.34 to 21.33 m, I2 = 0%). Meta-regression analysis showed that the effect size of all-cause mortality or HF hospitalization was not significantly associated with mean LVEF value at baseline. In patients with impaired AV conduction that need frequent ventricular pacing, BiV pacing was associated with reduced mortality and hospitalization for HF, compared with traditional RV pacing mode.

Influence of Renal Sympathetic Denervation in Patients with Early-Stage Heart Failure Versus Late-Stage Heart Failure.

Renal sympathetic denervation (RDN) is currently being investigated in multiple studies of heart failure (HF). Our aim was to assess the safety and effectiveness of RDN in patients with HF, and determine which patients could achieve more beneficial effects of RDN. A total of 17 consecutive patients with HF were enrolled in the study. Clinical symptoms, office blood pressure, and laboratory results were obtained and echocardiography was performed before and 12 months after RDN. Changes from baseline to 12 months were analyzed for all patients and for two subgroups based on HF duration (group 1: HF duration ≤ 3 years, n = 9; group 2: HF duration > 3 years, n = 8). The RDN procedure was successful in all patients and no procedure-related complications were documented. In comparison to baseline, there was a significant increase in left ventricular ejection fraction (LVEF) in all patients and group 1 (P < 0.05 for both), which did not happen in group 2. LAD, LVDs, and RVD also showed a significant reduction in group 1 (P < 0.05 for both). At 12 months, the reductions in TNF-α and CRP were significant for all patients and for patients in group 1 separately. No obvious changes in echocardiographic parameters, 6-minute walking distance, TNF-α, or CRP were recorded in group 2. No changes in BNP in either group were observed at the 12th month of follow-up. RDN could improve cardiac function and led to a significant drop in inflammatory markers in patients with HF. We also found that patients in early-stage HF could benefit more from RDN.

Renal Denervation for Ventricular Arrhythmia in Patients with Implantable Cardioverter Defibrillators.

To investigate the efficacy of renal denervation (RDN) on the recurrence of ventricular arrhythmia (VA) in Asian patients with implantable cardioverter defibrillators (ICDs).Eight ICD patients with recurrent VA episodes underwent RDN using an off-the-shelf saline-irrigated catheter. The pre- and postprocedural VA episodes were counted via ICD interrogation. All patients underwent successful RDN without any complications related to radiofrequency catheter ablation. The median follow-up was 15 months (range 6-30), and the median VA episodes per month were significantly reduced from 3.17 (range 0.33-15.33) to 0.10 (range 0-5.83) after RDN (P < 0.05).RDN is an effective suppressor of VA in Asian patients with ICDs.

Preliminary effects of renal denervation with saline irrigated catheter on cardiac systolic function in patients with heart failure: A Prospective, Randomized, Controlled, Pilot Study.

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 < 0.001), SMWD (P = 0.043), NYHA class (P < 0.001), NT-proBNP (P < 0.001) and office heart rate (P = 0.008). Compared with control group, RDN patients were associated with significant improvement in all domains of SF-36 but bodily pain (P = 0.74). No significant change in estimate glomerular filtration nor complication of renal artery stenosis were observed. CONCLUSIONS: Results imply that RDN could be safely applied to treatment of HF and probably improve cardiac systolic function and patients' quality of life. © 2016 Wiley Periodicals, Inc.

Low-Dose Quinidine Effectively Reduced Shocks in Brugada Syndrome Patients with an Implantable Cardioverter Defibrillator: A Chinese Case Series Report.

BACKGROUND: Only implantable cardioverter defibrillators (ICD) have been proven to prevent sudden cardiac death (SCD) in patients with Brugada syndrome (BrS). However, ICD discharge, whether appropriate or inappropriate, leads to impaired quality of life and even increases rehospitalization. Quinidine might prevent the recurrence of ventricular arrhythmia (VA); however, the effect of low-dose quinidine for preventing spontaneous arrhythmias remains less clear. METHODS: In our cardiology center, 10 confirmed patients with BrS (all men, mean age 38.7 ± 6.72 years) who underwent appropriate ICD shocks due to recurrent VAs were treated with quinidine (≤200 mg/day) and followed regularly. RESULTS: All the patients underwent ICD shocks due to ventricular tachycardia (VT)/ventricular fibrillation (VF) before taking quinidine. A 24-hour distribution of VT/VF demonstrated that most of the events occurred in the sleeping time from 22:00 to 8:00. Quinidine prevented recurrence of VAs in nine patients. The other one patient took quinidine discontinuously because of anxiety suffered from less episodes of VA, and after psychological guidance, he took quinidine 200 mg/day and experienced no VA episodes from then on. In our series, only one patient suffered leukopenia related to quinidine. No other side effect was observed. CONCLUSIONS: Quinidine with a very low dose (≤200 mg/day) well controlled VT/VF recurrence for a long-term period in Chinese patients with BrS. Administration (at 21:00) according to the circadian distribution of VT/VF episodes might increase the efficiency and improve the patient's tolerance.

Renal Denervation Attenuates Multi-Organ Fibrosis and Improves Vascular Remodeling in Rats with Transverse Aortic Constriction Induced Cardiomyopathy.

BACKGROUND/AIMS: To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy. METHODS: Thirty-six male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1) RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten weeks after TAC, samples were collected. RESULTS: TAC rats showed an increased diastolic interventricular septal thickness at week 5. At 10 weeks, Masson staining showed that left ventricular and renal glomerular fibrosis were significantly reduced in RDN compared with Sham group. In comparison to Sham group, hepatic perivascular fibrosis was attenuated in both RDN and Carvedilol group, so were the media thickness and the media/lumen of aorta. The plasma levels of B-type natriuretic peptide (BNP), Cystatin C (Cys-C), Alanine Transaminase, angiotensin II (Ang II), transforming growth factor beta 1 (TGF-ß1), and malondialdehyde increased, and total superoxide dismutase (T-SOD) decreased in Sham but not in RDN group, compared with Control group. Both RDN and Carvedilol reduced the Cys-C and TGF-ß1 levels, and restored T-SOD concentration, compared with Sham group. While only RDN lowered the plasma levels of BNP and Ang II. No significant effects of RDN on blood pressure (BP) and heart rate (HR) were oberved. CONCLUSIONS: RDN can attenuate multi-organ fibrosis and improve vascular remodeling independent of BP and HR change in TAC-induced cardiomyopathy. These effects of RDN may be associated with the direct inhibition of renin-angiotensin-aldosterone system and oxidative stress.

Meta-Analysis of Efficacy and Safety of Apixaban in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

BACKGROUND: The efficacy and safety of apixaban in patients undergoing catheter ablation (CA) for atrial fibrillation (AF) are little investigated. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE were searched up to September 2015. Four literatures comparing apixaban with vitamin K antagonists (VKAs) were included. Data were pooled in Review Manager Software, using Mantel-Haenszel methods with a fixed-effects model. The funnel plots and Egger's test were used to examine publication bias. Heterogeneity was assessed using the I(2) test. Risk ratios (RR) and 95% confidence intervals (CI) of each study were calculated and pooled. RESULTS: No significant differences were observed in rates of total bleeding (RR = 0.91, 95% CI [0.57, 1.46], I(2) = 0.0%), thromboembolic complications (RR = 0.75, 95% CI [0.03, 18.22], I(2) = 0.0%), or total events (RR = 0.90, 95% CI [0.56, 1.44], I(2) = 0.0%) between apixaban and VKAs group. The frequency of major bleeding was similar between apixaban and VKAs group (RR = 1.34, 95% CI [0.34, 5.30], I(2) = 0.0%). CONCLUSION: Apixaban was as effective and safe as VKAs in the periprocedural period of CA.

Renal sympathetic denervation improves rate control in patients with symptomatic persistent atrial fibrillation and hypertension.

AIM: The aim of this study was to investigate whether renal sympathetic denervation (RSD) improves ventricular heart rate (HR) control in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: Twenty-one patients (aged 57.5 ± 10.2 years, 76.2% male) with persistent AF and hypertension underwent RSD and completed 7-days follow-up evaluations, including 24-hour Holter monitoring (Holter), blood pressure (BP), 24-hour ambulatory BP monitoring (ABPM). Patients were grouped into tertiles of average HR at baseline Holter recording for evaluation of RSD effects on atrioventricular (AV) node (group 1: HR ≧ 90 bpm; group 2: 80 bpm ≦ HR < 90 bpm; group 3: HR < 80 bpm). RESULTS: All patients successfully underwent RSD without any complications. The clinical and procedural characteristics were similar in all groups of patients. No significant changes in BP were observed in the three groups before and after RSD. Compared with baseline, the average HR (Holter) of patients in group 1, 2 and 3 had a reduction of 22.6 ± 13.2 bpm (83.3 ± 4.9 vs 106.0 ± 14.6, P = 0.004), 9.7 ± 7.8 bpm (75.7 ± 7.6 vs 85.4 ± 3.7, P = 0.017) and 2.3 ± 2.9 bpm (71.4 ± 4.0 vs 73.7 ± 4.7, P = 0.089) at 7 days after RSD, respectively. CONCLUSIONS: RSD could improve ventricular HR control in patients with persistent AF. RSD slowed AV node conduction in baseline HR-dependent manner. RSD may become an alternative non-pharmaceutical tool for rate control in patients with persistent AF.

[Effects of renal denervation on left atrial fibrosis in rats with isoproterenol induced chronic heart failure].

OBJECTIVE: To investigate the effects of renal denervation (RDN) on left atrial fibrosis in rats with chronic heart failure. METHODS: Sixty healthy male Sprague Dawley rats were randomly assigned to control group (n=10, intraperitoneal injection with 5 mg/kg normal saline daily for 3 consecutive weeks), sham group (n=25) and RDN group (n=25). Rats in sham and RDN group were intraperitoneally injected with 5 mg/kg isoproterenol daily for 3 consecutive weeks. RDN and sham RDN procedure was implemented at week 5. The renal arteries and veins were not isolated and the nerves were left intact in sham group. The experiment ended at week 10. Cardiac function, diastolic interventricular septal thickness (IVSD) and left atrial dimension (LAD) were evaluated by echocardiography at baseline, week 5 and 10. The rats of all three groups were sacrificed at week 10 and the left atrial tissue was used for following analysis: fibrosis was detected by Masson staining, plasma BNP was measured by ELISA kit, the protein expression of AngII, TGF-ß1, MMP2 and collagen I was determined by Western blot. RESULTS: (1) Cardiac function: compared with control group, LVEF decreased (P<0.01), IVSD (P<0.01) and LAD (P<0.01) increased significantly in the sham and RDN group at week 5. Compared with sham group at week 10, LVEF and IVSD significantly improved (P<0.05) and LAD tended to be smaller (P>0.05) in RDN group. (2) The degree of left atrial tissue fibrosis: Masson staining (collagen volume fraction, CVF) showed significantly decreased fibrosis of left atrial tissue in RDN group compared with that in sham group (P<0.01). (3) Plasma BNP level: ELISA assay revealed that plasma BNP in sham group was significantly increased compared with that in control group (P<0.05) and was similar between RND group and control group at week 10. (4) Protein expression of AngII, TGF-ß1, MMP2 and collagen I in rats left atrial: Western blot analysis demonstrated that the expression of AngII, TGF-ß1, MMP2 and collagen I was significantly down-regulated in RDN group compared to sham group (all P<0.05) but still significantly higher than in control group (all P<0.05). CONCLUSIONS: RDN can effectively attenuate the left atrial fibrosis in rats with isoproterenol induced chronic heart failure. The attenuation of left atrial fibrosis by RDN in these rats may be attributed to improved cardiac function and downregulated pro-fibrogenic factors (AngII, TGF-ß1, MMP2 and collagen I).