Key PointsQuestionDoes left atrial appendage ligation improve catheter ablation treatment of nonparoxysmal atrial fibrillation? FindingsIn this randomized clinical trial of 610 adults, primary effectiveness was based on freedom from atrial arrhythmias at 12 months and was not statistically different between those receiving percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation and pulmonary vein isolation alone (64.3% vs 59.9%; difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]). Primary safety was met, with a 30-day serious adverse event rate of 3.4%. At 12 months after pulmonary vein isolation, there was complete closure in 84% of patients who underwent left atrial appendage, and 99% had less than or equal to 5 mm of residual communication with the left atrium. MeaningPercutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation met prespecified safety criteria, but did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone. ImportanceLeft atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. ObjectiveTo assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and ParticipantsThis multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. InterventionsLeft atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and MeasuresA bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. ResultsOverall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and RelevancePercutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial RegistrationClinicalTrials.gov Identifier: NCT02513797 This multicenter randomized clinical trial examines the effectiveness and safety of left atrial appendage ligation plus pulmonary vein isolation for nonparoxysmal atrial fibrillation treatment.

BACKGROUND:Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking. METHODS:We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHA2DS2-VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation. Patients were randomly assigned in a 1:1 ratio to undergo left atrial appendage closure or receive oral anticoagulation. The primary safety end point, tested for superiority, was non-procedure-related major bleeding or clinically relevant nonmajor bleeding. The primary efficacy end point, tested for noninferiority, was a composite of death from any cause, stroke, or systemic embolism at 36 months. The secondary end point, tested for noninferiority, was major bleeding, including procedure-related bleeding, through 36 months. RESULTS:A total of 803 patients were assigned to undergo left atrial appendage closure, and 797 to receive anticoagulant therapy. The mean (±SD) age of the patients was 69.6±7.7 years, 34.1% of the patients were women, and the mean CHA2DS2-VASc score was 3.5±1.3. At 36 months, a primary safety end-point event had occurred in 65 patients (8.5%) in the left atrial appendage closure group (device group) and in 137 patients (18.1%) in the anticoagulation group (P<0.001 for superiority); a primary efficacy end-point event had occurred in 41 patients (5.3%) and 44 patients (5.8%), respectively (P<0.001 for noninferiority); and a secondary end-point event had occurred in 3.9% and 5.0% (P<0.001 for noninferiority). Complications related to the appendage closure device or procedure occurred in 23 patients. CONCLUSIONS:Among patients who underwent catheter-based atrial fibrillation ablation, left atrial appendage closure was associated with a lower risk of non-procedure-related major or clinically relevant nonmajor bleeding than oral anticoagulation and was noninferior to oral anticoagulation with respect to a composite of death from any cause, stroke, or systemic embolism at 36 months. (Funded by Boston Scientific; OPTION ClinicalTrials.gov number, NCT03795298.).

BACKGROUND:Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study. METHODS:The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I or IIa indication for a single-chamber implantable cardioverter defibrillator per guidelines were enrolled. Freedom from major system- or procedure-related complications and appropriate and inappropriate therapy rates were assessed through 3 years with the Kaplan-Meier method. ATP success was calculated from simple proportions. RESULTS:An implantation was attempted in 316 patients (25.3% female; 53.8±13.1 years of age; 81.6% primary prevention; left ventricular ejection fraction, 38.9±15.4%). Of 299 patients with a successful implantation, 24 experienced 82 spontaneous arrhythmic episodes that were appropriately treated with ATP only (38, 46.3%), shock only (34, 41.5%), or both (10, 12.2%) for a Kaplan-Meier-estimated rate of first any appropriate therapy of 9.2% at 3 years. ATP was successful in 77.1% (37/48) of episodes, and ATP use significantly increased from discharge to last follow-up visit (P<0.0001). Shock therapy was successful in 100% (27/27) of discrete, spontaneous ventricular arrhythmias. The inappropriate shock rates at 1 and 3 years were 9.8% and 17.5%, respectively, with P-wave oversensing the predominant cause. No major intraprocedural complications were reported, and the estimated freedom from system- or procedure-related major complications was 91.9% at 1 year and 89.0% at 3 years. The most common major complications were lead dislodgement (10 events; n=9 patients, 2.8%), postoperative wound or device pocket infection (n=8, 2.5%), and device inappropriate shock delivery (n=4, 1.3%). Twenty-four system revisions were performed as a result of major complications related to the EV ICD system or procedure. CONCLUSIONS:From implantation to study completion, the EV ICD Pivotal study demonstrated that a single integrated system with an extravascular lead placed in the substernal space maintains high ATP success, effective defibrillation, and a consistent safety profile. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04060680.

BACKGROUND:The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known.METHODS:We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%.RESULTS:A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period.CONCLUSIONS:In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

Ivabradine is a unique antiarrhythmic drug that was designed to affect chronotropy with no effect on inotropy or lusitropy. It was first approved by the European Medicines Agency in 2005 for stable angina treatment, and then in 2009 the indication was expanded to include uncontrolled angina with heart rates ≥60 beats per minute (bpm) on optimal beta-blocker therapy.1 Based on the SHIFT – HF trial in 2011, it got accepted for use in patients with systolic heart failure with heart rate greater than 70 bpm on maximally tolerated beta-blocker therapy or who have contraindication(s) to beta-blockers.

Background Impella CP support during Posterior Vein Isolation/Posterior Wall Isolation (PVI/PWI) in the setting of persistent cardiogenic shock from refractory atrial fibrillation with rapid ventricular response (AF/RVR), has not been reported in the literature to the best of our knowledge. Case A 61-year-old male truck driver was admitted with acute HFrEF with AF/RVR 130 - 150. His EF was 20% with global hypokinesis. He was diuresed and cardioverted to sinus rhythm and had QTc of 532. He reverted to AF/RVR in less than 24 hours, requiring amiodarone drip. Shortly, amiodarone was discontinued because of intense anorexia, nausea, and vomiting. Class III and Class 1c agents were contraindicated due to prolonged QTc and cardiomyopathy. He developed cardiogenic shock, worsening cardiorenal syndrome, and shock liver requiring continuous renal replacement therapy (CRRT). Inotropes and vasopressors were contraindicated. AVN ablation was refused because he wanted to return to truck driving. EF dropped to 10%, and moderate RV dysfunction ensued. Right heart catheterization showed PASP 53, PADP 38, and PCWP 37 with RAP 28mmHg. Coronary angiogram was normal. An Impella device was inserted, and support was set to P6 with 3.4 L/min cardiac output. PVI with cryoablation, PWI, and anterior mitral isthmus ablation was successful. The adequacy of isolation was verified by demonstrating a complete exit block 30 mins after ablation. Normal sinus rhythm was restored after cardioversion. Echo 48 hours later revealed improvement in EF from 10% to 40% in sinus rhythm. Impella and CRRT were weaned. He was discharged on GDMT. Conclusion There are no recommendations regarding PVI for AF/RVR on mechanical circulatory support (MCS). MCS assisted PVI/PWI may be the only resort to restore hemodynamic stability in cases where a pacemaker is not desirable. PVI/PWI is a lengthy procedure; the use of the Impella support for PVI/PWI in cardiogenic shock allows adequate time for exit block testing and PWI. The operator can do thorough mapping and ablation, knowing that the patient is receiving adjustable support based on hemodynamic demands. We had a good outcome; nevertheless, the potential pitfalls are unknown.