Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study.

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

Emergency catheter ablation: A feasible option for acute treatments of patients with unstable pre-excited atrial fibrillation.

BACKGROUND: Pre-excited atrial fibrillation (AF) is associated with increased risk of life-threatening events. However, at times, patients with pre-excited AF still repetitively suffer from hemodynamic disturbance, with resistance to acute treatments of antiarrhythmic therapy and cardioversion. METHODS: To evaluate the feasibility in correcting hemodynamic disturbance, patients with pre-excited AF who underwent catheter ablation of accessory pathway as an emergency procedure, were retrospectively collected from two centers of China. The medical records of patients were analyzed and summarized in this case series. RESULTS: Five patients with pre-excited AF who received emergency catheter ablation of accessory pathway, were collected from two contributor centers and reported in this case series. All collected patients still repetitively suffered from hemodynamic disturbance induced by rapid anterograde conduction of AF via pathway, even guideline recommended acute interventions of intravenous antiarrhythmic therapy and cardioversion had been performed. Finally, as an emergency procedure, catheter ablation of accessory pathway was performed in collected patients. Correspondingly, the hemodynamic unstable status was greatly relieved. Meanwhile, all collected patients with high risk of pre-excited AF were combined with left-sided accessory pathway, with shortest RR interval of widened pre-excited QRS complex less than 250 ms. Thus, combination with left-sided pathway is proposed as an indicator for the increased risk of life-threatening events in patients with high risk of pre-excited AF. CONCLUSIONS: Emergency catheter ablation of accessory pathway is an effective option for the acute managements of patients with high risk of pre-excited AF in unstable hemodynamics, which is resistant to antiarrhythmic therapy and cardioversion.

Using ensemble of ensemble machine learning methods to predict outcomes of cardiac resynchronization.

INTRODUCTION: The efficacy of cardiac resynchronization therapy (CRT) has been widely studied in the medical literature; however, about 30% of candidates fail to respond to this treatment strategy. Smart computational approaches based on clinical data can help expose hidden patterns useful for identifying CRT responders. METHODS: We retrospectively analyzed the electronic health records of 1664 patients who underwent CRT procedures from January 1, 2002 to December 31, 2017. An ensemble of ensemble (EoE) machine learning (ML) system composed of a supervised and an unsupervised ML layers was developed to generate a prediction model for CRT response. RESULTS: We compared the performance of EoE against traditional ML methods and the state-of-the-art convolutional neural network (CNN) model trained on raw electrocardiographic (ECG) waveforms. We observed that the models exhibited improvement in performance as more features were incrementally used for training. Using the most comprehensive set of predictors, the performance of the EoE model in terms of the area under the receiver operating characteristic curve and F1-score were 0.76 and 0.73, respectively. Direct application of the CNN model on the raw ECG waveforms did not generate promising results. CONCLUSION: The proposed CRT risk calculator effectively discriminates which heart failure (HF) patient is likely to respond to CRT significantly better than using clinical guidelines and traditional ML methods, thus suggesting that the tool can enhanced care management of HF patients by helping to identify high-risk patients.

Catheter ablation of premature ventricular contractions originating from periprosthetic aortic valve regions.

BACKGROUND: Little is known about the ablation outcomes of premature ventricular contractions (PVCs) that originate from the periprosthetic aortic valve (PPAV) regions of patients with aortic valve replacement (AVR). METHODS AND RESULTS: Our study had 11 patients who underwent catheter ablation for PVCs arising from the PPAV regions (bioprosthetic aortic valve, n = 5; mechanical aortic valve, n = 6). The PVC characteristics, procedure characteristics, and efficacy of ablation were compared with the control group (n = 33). At baseline, the PPAV group had a lower left ventricular ejection fraction (mean [SD], 41% [12%] vs. 51% [8%]; p = .002). The rate of acute ablation success was 90.9% in the PPAV group. Ablation sites were identified above the left coronary cusp (LCC) and right coronary cusp commissure (LRCC) in one PVC, below the prosthetic valve in eight PVCs (four below LCC and four below LRCC), and within the distal coronary sinus in two PVCs. The mean procedure time, fluoroscopy time, and radiation in the PPAV group were all significantly greater than those in the control group (all p < .05). However, the number of radiofrequency ablation energy deliveries was not different. The PPAV group had a long-term success rate compared with the control group (72.7% vs. 87.9%, p = .48) and an increase of left ventricular ejection fraction from 43% to 49% after successful PVC ablation at follow-up (p < .001). Echocardiography showed no significant change in valve regurgitation after ablation. No new atrioventricular block occurred. CONCLUSION: PVCs arising from PPAV regions can be successfully ablated in patients with prior AVR, without damaging the prosthetic aortic valve and atrioventricular conduction.

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.

The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

BACKGROUND: Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT). METHODS: Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group). RESULTS: Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P < 0.001) and the left renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P < 0.001), with significantly shorter RF delivery time (P < 0.001), but higher RF power (P = 0.011). Baseline office BPs was 179.4 ± 13.7/102.8 ± 9.4 mm Hg in the full-length group and 181.9 ± 12.8/103.5 ± 8.9 mm Hg in the proximal group (P > 0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P < 0.001), -42.0 ± 11.6/-21.4 ± 7.9 mm Hg at 6 months and -40.9 ± 10.3/-22.1 ± 5.6 mm Hg at 12 months in the proximal group (P < 0.001), and progressive BP reductions were observed over the 6 months (P < 0.001) in both groups. The drop in ambulatory 24-hr SBP and DBP were significantly less than the drop in office BP (P < 0.001). No renovascular or other adverse complications were observed. CONCLUSIONS: The results indicate that proximal RDN has a similar efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN. © 2016 Wiley Periodicals, Inc.

Explainable machine learning models for predicting 30-day readmission in pediatric pulmonary hypertension: A multicenter, retrospective study.

Background: Short-term readmission for pediatric pulmonary hypertension (PH) is associated with a substantial social and personal burden. However, tools to predict individualized readmission risk are lacking. This study aimed to develop machine learning models to predict 30-day unplanned readmission in children with PH. Methods: This study collected data on pediatric inpatients with PH from the Chongqing Medical University Medical Data Platform from January 2012 to January 2019. Key clinical variables were selected by the least absolute shrinkage and the selection operator. Prediction models were selected from 15 machine learning algorithms with excellent performance, which was evaluated by area under the operating characteristic curve (AUC). The outcome of the predictive model was interpreted by SHapley Additive exPlanations (SHAP). Results: A total of 5,913 pediatric patients with PH were included in the final cohort. The CatBoost model was selected as the predictive model with the greatest AUC for 0.81 (95% CI: 0.77-0.86), high accuracy for 0.74 (95% CI: 0.72-0.76), sensitivity 0.78 (95% CI: 0.69-0.87), and specificity 0.74 (95% CI: 0.72-0.76). Age, length of stay (LOS), congenital heart surgery, and nonmedical order discharge showed the greatest impact on 30-day readmission in pediatric PH, according to SHAP results. Conclusions: This study developed a CatBoost model to predict the risk of unplanned 30-day readmission in pediatric patients with PH, which showed more significant performance compared with traditional logistic regression. We found that age, LOS, congenital heart surgery, and nonmedical order discharge were important factors for 30-day readmission in pediatric PH.

Tailored Target Ablation Index Guided Pulmonary Vein Isolation in Treating Paroxysmal Atrial Fibrillation: A Single Center Randomized Study in Asian Population (AI-Asian-I).

Objective: To evaluate the efficacy and safety of lower ablation indexes (AI) guided pulmonary vein isolation (PVI) in treating paroxysmal atrial fibrillation (AF). Methods: Ninety patients with paroxysmal AF scheduled for radiofrequency ablation were randomly divided into three groups. The AI targets for PVI were as follows: In group A/B/C, 550/500/450 for roof and anterior wall, and 400/350/300 for posterior/inferior wall. The first-pass PVI rate, ablation time, complications and recurrence of atrial tachyarrhythmia (ATa) were compared. Results: The mean age was 62.5 years (male: 63.0%), mean body mass index (BMI): 24.35 ± 3.66 kg/m2. The baseline characteristics were comparable. There was no significant difference in the first-pass PVI rate among the three groups (left-sided-PV: 66.7% vs. 80% vs. 73.3%, P = 0.51; right-sided-PV: 70% vs. 83.3% vs. 73.3%, P = 0.64), also with similar gap rate during the procedural waiting time. At 1-year follow-up there was no significant difference in the recurrence rate of ATa among the three groups (10% vs. 13.3% vs. 13.3%, P = 1.00). The ablation time in the Group C was significantly less than that in the other two groups (47.8 min. vs. 47.0 min. vs. 36.6 min, P < 0.001). Higher AI seemed to link a non-significant trend toward higher rate of pericardial effusion (group A + B vs. group C:6.7% vs. 0%, P = 0.30), although the rate of overall complications was not different among the three groups. Conclusion: This randomized study shows that, a relatively lower target AI guided ablation may be similarly effective to achieve PVI with significantly reduced ablation time and obtain similar clinical outcome in treating paroxysmal AF in Asian population. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT:04549714].

Extracardiac Vagal Stimulation-Assisted Cardioneuroablation: Dynamically Evaluating the Impact of Sequential Ganglionated Plexus Ablation on Vagal Control of SAN and AVN in Patients with Sinoatrial Node Dysfunction.

Cardioneuroablation (CNA) is proposed as a promising therapy for patients with sinoatrial node dysfunction (SND) that is mediated by excessive vagal tone. However, a series of urgent questions about CNA remain unanswered. From December 2020 to March 2022, six patients with symptomatic SND who underwent CNA were summarized in this report. Sequential CNA targeting Ao-SVC GP, PMLGP, RAGP, and LSGP was performed in patients, guided by fractionated intracardiac electrograms and dynamically evaluated by extracardiac vagal stimulation (ECVS). The results showed that Ao-SVC GP ablation led to a significant increase in heart rate (HR) and the elimination of sinus arrest evoked by ECVS, while the vagal responses of atrial ventricular block were eliminated by the ablation of PMLGP and LSGP. Post-procedure HR increased up to 64-86% of the maximum HR of an atropine test at baseline. The median HR from Holter monitoring increased from 52.8 ± 2.1 bpm at baseline to 73.0 ± 10.4 bpm after the procedure (p = 0.012) and to 71.3 ± 10.1 bpm at the six-month follow-up (p = 0.011). Bradycardia-related symptoms disappeared in all patients at the six-month follow-up. This case series reveals the feasibility of using the ECVS-assisted sequential CNA technique and indicates the critical role of ECVS in dynamically evaluating the impact of sequential CNA on the vagal control of SAN and AVN.

Better CRT Response in Patients Who Underwent Atrioventricular Node Ablation or Upgrade From Pacemaker: A Nomogram to Predict CRT Response.

Background: Response rates for cardiac resynchronization therapy (CRT) in patients without intrinsic left bundle-branch block (LBBB) morphology are poor. Objective: We sought to develop a nomogram model to predict response to CRT in patients without intrinsic LBBB. Methods: We searched electronic health records for patients without intrinsic LBBB who underwent CRT at Mayo Clinic. Logistic regression and Cox proportional hazards regression analysis were performed for the odds of response to CRT and risk of death, respectively. Results were used to develop the nomogram model. Results: 761 patients without intrinsic LBBB were identified. Six months after CRT, 47.8% of patients demonstrated improvement of left ventricular ejection fraction by more than 5%. The 1-, 3-, and 5-year survival rates were 95.9, 82.4, and 66.70%, respectively. Patients with CRT upgrade from pacemaker [odds ratio (OR), 1.67 (95% CI, 1.05-2.66)] or atrioventricular node (AVN) ablation [OR, 1.69 (95% CI, 1.09-2.64)] had a greater odds of CRT response than those patients who had new implant, or who did not undergo AVN ablation. Patients with right bundle-branch block had a low response rate (39.2%). Patients undergoing AVN ablation had a lower mortality rate than those without ablation [hazard ratio, 0.65 (95% CI, 0.46-0.91)]. Eight clinical variables were automatically selected to build a nomogram model and predict CRT response. The model had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.63-0.78). Conclusions: Among patients without intrinsic LBBB undergoing CRT, upgrade from pacemaker and AVN ablation were favorable factors in achieving CRT response and better long-term outcomes.

Renin-angiotensin system-related gene polymorphisms are associated with risk of atrial fibrillation.

BACKGROUND: Renin-angiotensin system (RAS) plays an important role in atrial fibrillation (AF). Recently, many publications have studied the associations between RAS-related gene polymorphisms and AF risk, with inconsistent results. To further evaluate these associations, we carried out a meta-analysis of all the published studies. METHODS: Electronic searches were used to identify published studies evaluating RAS-related gene polymorphisms and AF risk before April 2009. We extracted data sets and performed meta-analysis with standardized methods. RESULTS: A meta-analysis of 12 publications on association between angiotensin-converting enzyme (ACE insertion/deletion) and AF risk was performed. The pooled relative risk (RR) of allele D versus I was 1.19 (95% CI, 1.07-1.32, P < .01), pooled RR of DD and DI versus II was 1.31(95% CI, 1.09-1.58, P < .01) and 1.06 (95% CI, 0.97-1.16, P = .22) respectively. In subgroup analysis, a stronger association was found in hypertensive population, Western ethnic, lone AF, and patients aged > or = 65 years, with pooled RR of DD versus II was 1.74 (95% CI, 1.39-2.18, P < .01), 1.27 (95% CI, 1.01-1.59, P = .04), 1.53 (95% CI, 1.31-1.78, P < .01) and 1.38 (95% CI, 1.10-1.73, P < .01), respectively. CONCLUSION: The results suggested an association between ACE insertion/deletion and AF risk. More large-scale studies are warranted to document the conclusive evidence of the effects of the RAS genes on AF risk.

Notch3 Modulates Cardiac Fibroblast Proliferation, Apoptosis, and Fibroblast to Myofibroblast Transition via Negative Regulation of the RhoA/ROCK/Hif1α Axis.

Cardiac fibrosis is a common pathological process in multiple cardiovascular diseases, including myocardial infarction (MI). Abnormal cardiac fibroblast (CF) activity is a key event in cardiac fibrosis. Although the Notch signaling pathway has been reported to play a vital role in protection from cardiac fibrosis, the exact mechanisms underlying cardiac fibrosis and protection from it have not yet been elucidated. Similarly, Hif1α and the RhoA/ROCK signaling pathway have been shown to participate in cardiac fibrosis. The RhoA/ROCK signaling pathway has been reported to be an upstream pathway of Hif1α in several pathophysiological processes. In the present study, we aimed to determine the effects of notch3 on CF activity and its relationship with the RhoA/ROCK/Hif1α signaling pathway. Using in vitro experiments, we demonstrated that notch3 inhibited CF proliferation and fibroblast to myofibroblast transition (FMT) and promoted CF apoptosis. A knockdown of notch3 using siRNAs had the exact opposite effect. Next, we found that notch3 regulated CF activity by negative regulation of the RhoA/ROCK/Hif1α signaling pathway. Extending CF-based studies to an in vivo rat MI model, we showed that overexpression of notch3 by the Ad-N3ICD injection attenuated the increase of RhoA, ROCK1, ROCK2, and Hif1α levels following MI and further prevented MI-induced cardiac fibrosis. On the basis of these results, we conclude that notch3 is involved in the regulation of several aspects of CF activity, including proliferation, FMT, and apoptosis, by inhibiting the RhoA/ROCK/Hif1α signaling pathway. These findings are significant to further our understanding of the pathogenesis of cardiac fibrosis and to ultimately identify new therapeutic targets for cardiac fibrosis, potentially based on the RhoA/ROCK/Hif1α signaling pathway.

Anatomy Versus Physiology-Guided Ablation for Persistent Atrial Fibrillation.

BACKGROUND: Pulmonary vein isolation remains the cornerstone of atrial fibrillation (AF) ablation. However, due to high recurrence rates, especially in patients with persistent AF, PV antral isolation, complemented by linear ablation, autonomic modulation, and ablation of complex fractionated electrograms, have been attempted to increase the odds of success. However, the optimum approach for a complementary strategy in addition to PVI for persistent AF is unknown. METHODS: We performed a prospective randomized trial by assigning 92 patients with persistent AF in 1:1 ratio to pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity (45 patients), or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus (47 patients). The duration of follow-up was five years. The primary endpoint was freedom from any documented recurrence of atrial fibrillation after a single ablation procedure. RESULTS: At a 12-month follow-up, 9 (23%) patients had AF recurrence in the linear ablation and 8 (21%) patients in the CFAE groups. At a mean follow-up duration of 59±36 months, 48.3% of patients in the linear ablation group and 44.6% of patients in the CFAE group were free from AF (p=0.403). There were no significant differences between the two groups for independent predictors of freedom from AF. The overall procedure time and radiation exposure were higher in the PVI+linear ablation group. There were five adverse events noted, two in the linear group (pericardial effusion not requiring drain) and 3 in the CFAE group (1 pseudoaneurysm, one effusion requiring pericardiocentesis and one effusion nor requiring drain). CONCLUSIONS: Among patients with persistent atrial fibrillation, we found no difference in maintenance of sinus rhythm in either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary vein isolation in short- and long-term follow-up.

Left cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome.

BACKGROUND: Although left cardiac sympathetic denervation (LCSD) is an effective antiarrhythmic therapy for patients with long QT syndrome (LQTS), direct evidence of reduced sympathetic activity after LCSD in humans is limited. OBJECTIVE: The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD. METHODS: We prospectively enrolled 17 patients with LQTS who underwent LCSD between 2017 and 2019. SKNA recordings from the left arm (L-SKNA) and chest (C-SKNA) leads were performed before and after LCSD. Mean SKNA, burst activity, and nonburst activity of L-SKNA and C-SKNA were analyzed. RESULTS: The mean patient age was 21 ± 9 years (8 men 47%). The longest baseline corrected QT value was 497 ± 55 ms at rest and 531 ± 38 ms on exercise stress testing. Five patients (29.4%) had previous LQTS-triggered cardiac events including syncope, documented torsades de pointes, and ventricular fibrillation. In the 24 hours after LCSD, mean L-SKNA decreased from 1.25 ± 0.64 to 0.85 ± 0.33 µV (P = .005) and mean C-SKNA from 1.36 ± 0.67 to 1.05 ± 0.49 µV (P = .11). The frequency of episodes of SKNA bursts recorded from the left-arm lead (2.87 ± 1.61 bursts per minute vs 1.13 ± 0.99 bursts per minute; P < .001) and mean L-SKNA during burst (1.82 ± 0.79 µV vs 1.15 ± 0.44 µV; P < .001) and nonburst (1.09 ± 0.60 µV vs 0.75 ± 0.32 µV; P = .03) periods significantly decreased after LCSD, while the frequency of episodes of SKNA bursts recorded from the chest lead (P = .57) and mean C-SKNA during burst (P = .44) and nonburst (P = .10) periods did not change significantly. No arrhythmic events were documented after 11.9 months (range 3.0-22.2 months) of follow-up. CONCLUSION: LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA.

Experimental Study on the Effect of a Weifufang on Human Gastric Adenocarcinoma Cell Line BGC-823 Xenografts and PTEN Gene Expression in Nude Mice.

Background: This study aims at investigating the effect of the Weifufang, an effective prescription for the treatment of gastric cancer developed by the Traditional Chinese Medicine (TCM)/Combination of TCM and Western Medicine Department of the Hunan Cancer Hospital, on gastric cancer xenografts in nude mice and its effect on the PTEN gene; it also aims at exploring the possible tumor suppression mechanism. Methods: Nude mice with xenografts were treated with different concentrations of the Weifufang for 2 weeks, and changes in tumor volume were observed. The histopathology of the tumor was detected by hematoxylin and eosin staining; PTEN gene expression in tumor tissues was detected by immunohistochemistry (IHC) and western blot. Results: After 2 weeks of treatment, tumor inhibition rates in the 5-flourouracil (5-FU) group, and in the Weifufang low-, middle-, and high-dose groups were 30.67%, 19%, 49.52%, and 29.36%, respectively. The IOD of the PTEN gene was detected by IHC. The values in the water group, the 5-FU group, and the Weifufang low-, middle-, and high-dose groups were 0.013 ± 0.004, 0.085 ± 0.062, 0.041 ± 0.024, 0.128 ± 0.032, and 0.061 ± 0.052, respectively. Except for the 5-FU group, the differences between the gastric compound middle dose-group and the other groups were statistically significant (p < 0.05). Results of PTEN expression detection by western blot: The expression levels in the water group, 5-FU group, and the Weifufang low-, middle-, and high-dose groups were 0.2240 ± 0.0172, 0.4200 ± 0.0228, 0.2760 ± 0.0163, 0.3840 ± 0.0133, and 0.3040 ± 0.0211, respectively. Except for the 5-FU group, differences between the Weifufang middle-dose group and the other groups were statistically significant (p < 0.05). Conclusion: The Weifufang may inhibit the growth of gastric cancer xenografts by upregulating PTEN gene expression. The middle-dose group had the best effect.

Cardiac resynchronization therapy modulates peripheral sympathetic activity.

BACKGROUND: Heightened sympathetic nerve activity has been associated with poorer prognosis in patients with reduced left ventricular systolic function (ie, heart failure with reduced ejection fraction [HFrEF]). OBJECTIVE: The purpose of this study was to investigate the effects of cardiac resynchronization therapy (CRT) on sympathetic nerve activity, measured by average skin sympathetic nerve activity (aSKNA). METHODS: This prospective study enrolled 36 patients with HFrEF who received CRT. Ten patients who received an implantable cardioverter-defibrillator for primary prevention served as controls. Patient clinical data, echocardiographic variables, and aSKNA at baseline and 3-month follow-up were collected. RESULTS: CRT patients who exhibited wider QRS duration had higher aSKNA (1.52 ± 0.65 µV vs 0.97 ± 0.49 µV; P = .027) compared to the control group at baseline. In the CRT group, patients with QRS duration ≥150 ms had higher aSKNA than those with QRS duration <150 ms (1.67 ± 0.63 µV vs 1.19 ± 0.51 µV; P =.039). After CRT, left ventricular ejection fraction (LVEF) improved from 29.6% to 35.4% (P = .001). aSKNA decreased significantly (1.52 ± 0.65 µV vs 1.31 ± 0.63 µV; P = .018). Seventeen of the 36 CRT patients were CRT responders, with LVEF improvement ≥5% at 3-month follow-up. aSKNA significantly decreased from 1.47 to 1.15 µV (P = .003) in CRT responders but was unchanged in nonresponders (1.44 ± 0.69 to 1.37 ± 0.70; P = .61). After CRT, a significant reduction in aSKNA was associated with improvement in LVEF (r = 0.638; P = .001). CONCLUSION: CRT reduces elevated sympathetic activity in HFrEF patients, accompanied by improvement in systolic function at short-term follow-up. The reduction of sympathetic activity is mainly seen in CRT responders.

Associations of leptin and leptin receptor genetic variants with coronary artery disease: a meta-analysis.

Background: Some pilot studies already tried to investigate potential associations of leptin (LEP) and LEP receptor (LEPR) variants with coronary artery disease (CAD). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between LEP/LEPR variants and CAD in a larger pooled population.Methods: Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible case-control studies on associations between LEP/LEPR variants and CAD. The initial search was conducted in September 2018 and the latest update was performed in December 2018. Q test and I2 statistic were employed to assess between-study heterogeneities. If probability value(P-value) of Q test was less than 0.1 or I2 was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses.Results: A total of ten studies published between 2006 and 2018 were eligible for analyses (1989 cases and 2601 controls). Pooled analyses suggested that LEP rs7799039 variant was significantly associated with CAD under over-dominant model (P=0.0007, odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14-1.63, I2 = 41%, FEM) in overall population, and this significant finding was further confirmed in East Asians in subsequent subgroup analyses. However, no positive findings were observed for LEPR rs1137100 and rs1137101 variants in overall and subgroup analyses.Conclusions: Our meta-analysis suggested that LEP rs7799039 variant might affect individual susceptibility to CAD.

Radiofrequency catheter ablation for paroxysmal atrial fibrillation: outcomes during a 3-year follow-up period.

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.

Selective Renal Denervation Guided by Renal Nerve Stimulation in Canine.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P<0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P<0.001 and R=0.927, P<0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.

Utility of 30-Day Continuous Ambulatory Monitoring to Identify Patients With Delayed Occurrence of Atrioventricular Block After Transcatheter Aortic Valve Replacement.

BACKGROUND: Mechanical injury in the conduction system requiring permanent pacemaker (PPM) associated with transcatheter aortic valve replacement (TAVR) procedure is a common complication. The objective of this study was to use ambulatory monitor BodyGuardian to assess late occurrence of atrioventricular block (AVB) after TAVR. METHODS: This prospective study evaluated 365 patients who underwent TAVR at Mayo Clinic, Rochester, Minnesota between June 2016 and August 2017. Patients who received PPM for bradycardia after TAVR before discharge were considered as the PPM group. Those not requiring PPM received a BodyGuardian system (BodyGuardian group) for 30 days of continuous monitoring. Primary end point was Mobitz II or third-degree atrioventricular block (II/III AVB) at 30-day follow-up. RESULTS: Of 365 patients, 74 who had a PPM or an implantable cardioverter-defibrillator before TAVR and 94 who were enrolled in other studies were excluded. Of 197 patients enrolled in the study, 70 (35.5%) received PPM and 127 had BodyGuardian before the hospital dismissal. Eleven of 127 (8.6%) BodyGuardian group required PPM within 30 days after TAVR for late occurrence of symptomatic bradycardia. In total, 33 of 197 (16.7%) patients developed II/III AVB (24 before and 9 after discharge). Thirty-four patients had preexisting right bundle branch block. Of them, 16 (47%) developed II/III AVB. Of 53 patients who developed new left bundle branch block after TAVR, 14% progressed to II/III AVB within 30 days. CONCLUSIONS: In patients without a standard post-TAVR pacing indication, yet a potential risk to develop AVB, a strategy of 30-day monitoring identifies additional patients who require permanent pacing.