Percutaneous left atrial appendage closure with SeaLA device in non-valvular atrial fibrillation.

OBJECTIVES: The clinical efficacy and safety of a novel left atrial appendage (LAA) occluder of the SeaLA closure system in patients with nonvalvular atrial fibrillation (NVAF) were reported. BACKGROUND: Patients with NVAF are at a higher risk of stroke compared to healthy individuals. Left atrial appendage closure (LAAC) has emerged as a prominent strategy for reducing the risk of thrombosis in individuals with NVAF. METHODS: A prospective, multicenter study was conducted in NVAF patients with a high risk of stroke. RESULTS: The LAAC was successfully performed in 163 patients. The mean age was 66.93 ± 7.92 years, with a mean preoperative CHA2DS2-VASc score of 4.17 ± 1.48. One patient with residual flow >3 mm was observed at the 6-month follow-up, confirmed by TEE. During the follow-up, 2 severe pericardiac effusions were noted, and 2 ischemic strokes were observed. Four device-related thromboses were resolved after anticoagulation treatment. There was no device embolism. CONCLUSIONS: The LAAC with the SeaLA device demonstrates encouraging feasibility, safety, and efficacy outcomes.

CLOSE protocol versus lower ablation index value for paroxysmal atrial fibrillation: A randomized noninferior clinical trial.

INTRODUCTION: The optimized ablation index (AI) value for catheter ablation of atrial fibrillation (AF) remains to be defined. We aimed to compare the efficacy and safety of CLOSE protocol and lower AI protocol in paroxysmal AF. METHODS AND RESULTS: Patients with symptomatic, drug-resistant paroxysmal AF for first ablation were prospectively enrolled from September 2020 to January 2022. The patients were randomly divided into CLOSE group (AI ≥ 550 for anterior/roof segments and ≥400 for posterior/inferior segments) and lower AI group (AI ≥ 450 for anterior/roof segments and ≥350 for posterior/inferior segments). First-pass isolation, acute pulmonary vein (PV) reconnections, 1-year arrhythmia recurrence, and major complications were assessed. Of the 270 enrolled patients, 238 completed 1-year follow-up (118 in CLOSE group and 120 in lower AI group). First-pass isolation in left PVs was higher in CLOSE group (71.2% vs. 53.3%, p = .005). Acute PV reconnections were comparable between groups (9.3% vs. 14.2%, p = .246). At 1 year, 86.4% in CLOSE group versus 81.7% in lower AI group were free from atrial arrhythmia (log rank p = .334). The proportion difference was -4.8% (95% CI: -14.1% to 4.6%), and p = .475 for noninferiority. Stroke occurred in four patients of lower AI group, and no cardiac tamponade, atrioesophageal fistula, major bleeding or death occurred post procedure. CONCLUSION: For patients with paroxysmal AF and treated by AI-guided PV ablation, lower AI is not noninferior to CLOSE protocol.

The Safety and Feasibility of Pulsed-Field Ablation in Atrioventricular Nodal Re-Entrant Tachycardia: First-in-Human Pilot Trial.

BACKGROUND: The incidence of atrioventricular conduction system damage during the catheter ablation procedure has long been a safety concern in patients with atrioventricular nodal re-entrant tachycardia (AVNRT). Pulsed-field ablation (PFA) with high tissue selectivity is a promising technique to address this problem in patients with AVNRT. OBJECTIVES: This study aimed to evaluate the safety and feasibility of PFA in patients with AVNRT. METHODS: This was an investigator-initiated, single-center, single-arm, prospective study performed in West China Hospital, Sichuan University. Patients diagnosed with AVNRT by electrophysiological examination were included and treated using PFA. The primary outcome was the ability to achieve acute ablation success. The secondary outcomes were ablation success after 6 months and safety incidents reported. RESULTS: A total of 30 patients with AVNRT with a mean age of 47.9 ± 13.9 years were included and underwent PFA. Acute ablation success was achieved in all patients. The skin-to-skin procedure time was 109.1 ± 32.1 minutes, and fluoroscopy time was 4.1 ± 0.9 minutes. A median of 8 (range: 6.5 to 11.0) PFA applications were delivered. The average distance of the closest ablation site to the His bundle was 6.5 ± 2.5 mm, with a minimum distance of 2.0 mm. All patients maintained sinus rhythm after 6 months. No adverse events occurred in any patient during the ablation or the 6-month follow-up. CONCLUSIONS: PFA showed favorable feasibility and safety in patients with AVNRT in this pilot study. Further study with larger population and longer follow-up time is warranted to verify the results.

First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Investigation of the Cellular Pharmacological Mechanism and Clinical Evidence of the Multi-Herbal Antiarrhythmic Chinese Medicine Xin Su Ning.

Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.

Simultaneous Endocardial and Epicardial Delineation of 3D Reentrant Ventricular Tachycardia.

BACKGROUND: Mechanisms of scar-related ventricular tachycardia (VT) are largely based on computational and animal models that portray a 2-dimensional view. OBJECTIVES: The authors sought to delineate the human VT circuit with a 3-dimensional perspective from recordings obtained by simultaneous endocardial and epicardial mapping. METHODS: High-resolution mapping was performed during 97 procedures in 89 patients with structural heart disease. Circuits were characterized by systematic isochronal analysis to estimate the dimensions of the isthmus and extent of the exit region recorded on both myocardial surfaces. RESULTS: A total of 151 VT morphologies were mapped, of which 83 underwent simultaneous endocardial and epicardial mapping; 17% of circuits activated in a 2-dimensional plane, restricted to 1 myocardial surface. Three-dimensional activation patterns with nonuniform transmural propagation were observed in 61% of circuits with only 4% showing transmurally uniform activation, and 18% exhibiting focal activation patterns consistent with mid-myocardial reentry. The dimensions of the central isthmus were 17 mm (12 to 28 mm) × 10 mm (9 to 19 mm) with 55% exhibiting a minimal dimension of <1.5 cm. QRS activation was transmural in 63% and located 43 mm (34 to 52 mm) from the central isthmus. On the basis of 6 proposed definitions for epicardial VT, the prevalence of an epicardial circuit ranged from 21% to 80% in ischemic cardiomyopathy and 28% to 77% in nonischemic cardiomyopathy. CONCLUSIONS: A 2D perspective oversimplifies the electrophysiological circuit responsible for reentrant human VT and simultaneous endocardial and epicardial mapping facilitates inferences about mid-myocardial activation. Intricate activation patterns are frequently observed on both myocardial surfaces, and the epicardium is functionally involved in the majority of circuits. Human reentry may exist within isthmus dimensions smaller than 1 cm, whereas QRS activation is often transmural and remote from the critical isthmus target. A 3-dimensional perspective of the VT circuit may enhance the precision of ablative therapy and may support a greater role for adjunctive strategies and technology to address arrhythmogenic tissue harbored in the mid-myocardium and subepicardium.

Pan-Asia United States PrEvention of Sudden Cardiac Death Catheter Ablation Trial (PAUSE-SCD): rationale and study design.

BACKGROUND: The role of catheter ablation as an adjunct and alternative to ICD implantation is not known in patients at risk for recurrent ventricular tachycardia (VT) and sudden cardiac death (SCD) across Asia. Patients with nonischemic etiologies of cardiomyopathy, which are highly prevalent in Asia, have not been previously enrolled in randomized trials of VT ablation. OBJECTIVE: To evaluate whether preemptive catheter ablation in patients with monomorphic VT and an indication for ICD implantation results in improved clinical outcomes compared to ICD implantation with standard medical therapy alone. To examine the natural history of ablation outcomes in the absence of background ICD therapy in patients that refuse randomization. METHODS: The PAUSE-SCD study (NCT02848781) is a prospective, multi-center, randomized controlled trial enrolling patients with structural heart disease (EF < 50%) with an indication for ICD implantation. Patients are randomized in a 1:1 fashion to two treatment arms: ICD with ablation and ICD with standard medical therapy alone. A prospective registry cohort was designed to follow the outcomes of patients who refuse ICD and randomization but elect to receive catheter ablation as primary therapy. The primary endpoint is defined as a composite of recurrent VT, cardiovascular rehospitalization, and death. Pre-specified secondary endpoints include each of the individual components of the primary endpoint in addition to comparison between randomized and registry patients. CONCLUSION: The PAUSE-SCD study is a prospective, multi-center, randomized, and controlled trial examining the impact of preemptive catheter ablation on cardiovascular outcomes in patients with an indication for ICD at risk for recurrent VT and SCD. It represents the first multi-center VT ablation study in Asia, with a design intended to provide insights into the role of both ICD and ablation therapy in a predominantly nonischemic population.

Efficacy and safety of catheter ablation combined with left atrial appendage occlusion for nonvalvular atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) is currently the most prevalent arrhythmia in clinical practice, with stroke being one of its major complications. Combining catheter ablation and percutaneous left atrial appendage occlusion (LAAO) into a "one-stop" intervention could reduce stroke incidence in selected high-risk patients and, at the same time, relieve AF symptoms in a single procedure. This meta-analysis analyzed the efficacy and safety of catheter ablation combined with LAAO for nonvalvular AF. PubMed, EMBASE, and the Cochrane Library were searched from inception to April 2019 to identify relevant citations. Efficacy indexes were procedural success, AF recurrence, stroke/transient ischemic attacks (TIA), and device-related thrombus (DRT). Safety indexes were all-cause death, major hemorrhagic complications, and pericardial effusion/cardiac tamponade. The incidence rate of events (ratio of events to patients) and 95% confidence interval (CI) were calculated as summary results. A forest plot was constructed to present pooled rates. Eighteen studies (two randomized controlled trials and 16 observational studies) were included. The results showed that one-stop intervention has significant efficacy and safety, with procedural success of .98 (95% CI, .97-1.00), AF recurrence of .24 (95% CI, .15-.35), stroke/TIA of .01 (95% CI, .00-.01), DRT of .00 (95% CI, .00-.01), all-cause mortality of .00 (95% CI, .00-.00), cardiac/neurological mortality of .00 (95% CI, .00-.00), major hemorrhagic complications of .01 (95% CI, .00-.02), and pericardial effusion/cardiac tamponade of .01 (95% CI, .00-.01). A single procedure with catheter ablation and LAAO in AF is a feasible strategy with significant efficacy and safety.

Is ablation to atrial fibrillation termination of persistent atrial fibrillation the end point?: A systematic review and meta-analysis.

BACKGROUND: The ideal ablation strategy and end point for persistent atrial fibrillation (AF) have not been well founded. Defining periprocedural AF termination as the end point of catheter ablation is still controversial. This meta-analysis aimed to analyze the differences between periprocedural AF termination and non-termination in the long-term AF recurrence rate and postoperative complications. METHODS: Randomized controlled trials (RCTs) were identified by a systematic search of electronic databases including PubMed, EMBASE, and Cochrane library from January 2008 to August 2019. The primary outcome was freedom from AF or any atrial arrhythmia without antiarrhythmic drugs at the long-term (≥12 months) follow-up. The secondary outcome was overall postoperative complication rates. The risk ratio (RR) with 95% confidence interval (CI) was pooled for these outcomes. A forest plot, fixed-effects model or random-effect model, Q test, I statistic, and Egger funnel plot were used in the statistical analysis. RESULTS: Fourteen RCTs were included in this meta-analysis. Overall, no significant difference was found in freedom from AF at the long-term follow-up between patients in whom AF termination was achieved and not achieved (RR = 0.93, 95% CI = 0.78-1.09, P = .36, I = 69%). Patients with AF non-termination had a lower complication occurrence rate than those with AF termination (RR = 1.74, 95% CI = 1.11-2.73, P = .02, I = 0%). CONCLUSION: Our meta-analysis suggests that AF termination is not a reliable procedural end point during ablation of persistent AF.

Safety and efficacy analysis of one-stop intervention for treating nonvalvular atrial fibrillation.

BACKGROUND: Nonvalvular atrial fibrillation (AF) is a common arrhythmia. The treatment strategy for AF mainly includes controlling symptoms and decreasing the rate of complications. Our study aimed to evaluate the safety and efficacy of combination treatment of catheter ablation and left atrial appendage (LAA) closure (one-stop intervention) in patients with nonvalvular AF. METHODS AND RESULTS: Thirty-four patients with symptomatic AF (mean CHA2 DS2 -VASc score 4.1 ± 1.3, mean HAS-BLED score 3.8 ± 1.2) were included. Patients first received radiofrequency-based left atrial ablation, and then the Watchman device (Boston Scientific, Natick, MA, USA) or AMPLATZER Cardiac Plug (ACP) (St. Jude Medical, Inc., St. Paul, MN, USA) was implanted for LAA closure. Follow-up was performed at 45 days and 3 months after LAA closure to assess for recurrence of AF and prevent stroke. Radiofrequency ablation and LAA closure were successful in 100% of patients without evidence of residual flow at the final transesophageal echocardiography evaluation. A Watchman device was implanted in 29 (85.3%) patients, and an ACP was implanted in five (14.7%) patients. No device-related thrombus formation or embolization was identified at the 45-day or 3-month follow-up. Serious complications, including death, transient ischemic attack, ischemic or hemorrhagic stroke, or major bleeding, were also not identified during the follow-ups. CONCLUSION: For symptomatic patients with nonvalvular AF and a high risk of stroke, the one-stop intervention is feasible, safe, and efficacious.