Background ADVANTAGE AF examined the safety and efficacy of pulsed field ablation (PFA) to treat persistent atrial fibrillation (AF). During AF ablation, typical atrial flutter (AFL) is commonly treated with cavotricuspid isthmus (CTI) ablation. Objectives Adjunctive CTI ablation in ADVANTAGE AF was performed with radiofrequency ablation (RFA; phase 1) or bipolar linear PFA (phase 2). Here, we compared lesion characteristics, CTI ablation efficacy, and safety between the ablation modalities. Methods A preclinical study assessed lesion dimensions with a novel 2.0 kV bipolar linear PFA catheter. In ADVANTAGE AF, after AF ablation with a pentaspline PFA catheter, CTI ablation was performed: in phase 1 with irrigated RFA, and in phase 2 with the linear PFA catheter (Farapoint). Before PFA CTI ablation ,patients were treated with a vasopressor bolus followed by high-dose intravenous nitroglycerin. Results Preclinical assessment showed lesion depth increasing at higher field strength and plateauing after 2 applications. In ADVANTAGE AF, 50 and 141 patients received CTI ablation with RFA and PFA, respectively. Patient characteristics across the 2 cohorts were similar (RFA vs PFA). Acute CTI conduction block was similar between techniques (50 of 50 RFA [100%] vs 139 of 141 PFA [98.6%]; P = 1.00). PFA was associated with a shorter CTI ablation time (median: RFA 5 min [Q1-Q3: 4-8 min] vs 14 min [Q1-Q3: 9-19 min]; P = 0.001). RFA and PFA had similar safety event rates (RFA 2.0% vs PFA 2.1%; P = 0.96). With the use of nitroglycerin pretreatment, there was no clinical manifestation of coronary artery spasm with PFA. Conclusions This subanalysis of ADVANTAGE AF extends the primary results by allowing comparison of bipolar linear PFA and RF ablation for CTI, integrating preclinical lesion modeling with clinical dosing, and establishing a standardized reliable coronary safety protocol. Although not randomized comparisons, these findings suggest that CTI ablation with a linear PFA catheter is associated with safety and efficacy similar to RF ablation and greater efficiency. (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation [ADVANTAGE AF; NCT05443594])

Importance Left atrial appendage occlusion (LAAO) is used in patients with contraindications to oral anticoagulation, who are at increased risk for major bleeding (MB). Objective To evaluate the incidence, predictors, management, and clinical outcomes of MB after LAAO in the Amulet IDE trial. Design, Setting, and Participants The randomized clinical Amulet IDE trial enrolled patients from 2016 through 2019 with 5-year follow-up. Procedures were performed at specialized LAAO centers. Of 1878 randomized patients (1:1 Amulet vs Watchman), 1833 underwent attempted LAAO implantation. These data were analyzed from May 2025 through November 2025. Main Outcomes and Measures Pooled (Amulet and Watchman) patients with vs without MB (Bleeding Academic Research Consortium [BARC] score ≥3: overt bleeding with transfusion and ≥3 g/dL hemoglobin drop) were compared. Results This study included a total of 1833 patients (57.7% male and 42.3% female; mean [SD] age, 75.8 [7.5] years). MB occurred in 331 patients (18.1%) over 5 years (annualized rate 5.9% per year). Patients with MB were older (76.8 vs 74.7 years) and had higher CHA 2 DS 2 -VASc (4.8 vs 4.6) and HAS-BLED (3.4 vs 3.2) scores, as well as greater prevalence of diabetes (38.7% vs 34.1%), prior MB (45.3% vs 28.0%), and kidney disease (9.4% vs 4.5%). MB risk was highest in the first 6 months after LAAO (20.5% per year), then decreased to 3.9% per year through 5 years. Most MB events were nonprocedural (88.8%) with gastrointestinal bleeding accounting for 252 of 438 events. Independent predictors of MB included increasing age (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06), female sex (HR, 1.25; 95% CI, 1.01-1.56), diabetes (HR, 1.26; 95% CI, 1.01-1.58), prior MB (HR, 1.93; 95% CI, 1.55-2.40), and kidney disease (HR, 2.15; 95% CI, 1.48, 3.12). At first MB event, 47.1% of patients were not receiving antithrombotic therapy and 92 patients had recurrent events. Patients with MB had significantly higher rates of the composite of stroke, systemic embolism, or cardiovascular death (32.5% vs 18.0%; P < .001), driven by higher stroke (14.7% vs 6.6%) and cardiovascular death (24.4% vs 12.9%) rates. All-cause mortality was also higher (49.2% vs 25.4%; P < .001). MB was fatal (BARC score of 5) in 25 patients (1.4%). Conclusions and Relevance In this study, MB was common in this high-risk population and largely related to underlying patient factors. Early MB risk was highest 6 months post-LAAO, then dropped considerably. Most events were gastrointestinal and occurred even in patients on minimal or no antithrombotic therapy. MB after LAAO was strongly associated with increased stroke and mortality. Trial Registration ClinicalTrials.gov Identifier: NCT02879448

Background:Permanent junctional reciprocating tachycardia (PJRT) is a rare form of orthodromic atrioventricular reciprocating tachycardia involving a slowly conducting, decremental concealed accessory pathway. Its incessant nature may result in tachycardia-induced cardiomyopathy, which is reversible with timely rhythm control. Case summary:A 41-year-old patient presented with progressive exertional dyspnoea and reduced exercise capacity. Continuous electrocardiogram monitoring revealed an incessant long RP narrow QRS tachycardia (heart rate 135 b.p.m.). Echocardiography demonstrated severe LV systolic dysfunction (LVEF 14%) and LV dilatation (LVEDD 63 mm). Coronary angiography and cardiac MRI excluded relevant structural or infiltrative cardiomyopathy. Electrophysiological study confirmed PJRT using a posteroseptal concealed accessory pathway. Catheter ablation at the site of earliest atrial activation resulted in immediate termination of tachycardia and loss of accessory pathway conduction. Post-ablation echocardiography showed early improvement in LVEF to 26%. The patient was discharged on guideline-directed medical therapy for heart failure. At 6-month follow-up, he remained asymptomatic, with no arrhythmia recurrence and recovery of LVEF to 50% with normalization of LV dimensions. Discussion:This case highlights the reversibility of severe cardiomyopathy secondary to incessant PJRT. Even in cases with severe LV dysfunction, timely identification and ablation of the accessory pathway can achieve recovery of LV function. Careful electrophysiologic evaluation is essential to differentiate PJRT from other long RP tachycardias and guide curative therapy.

AIMS:Atrial fibrillation (AF) ablation by pulmonary vein isolation (PVI) and left atrial appendage closure (LAAC) are increasingly performed as standalone procedures. Given that PVI and LAAC share the same access route, a combined approach of pulsed field ablation (PFA)-based PVI and LAAC might be beneficial. The COCONUT study focused on safety, efficacy, and outcomes combining PVI by PFA with LAAC in one procedure. METHODS:This is a retrospective, multinational registry study. The primary endpoints were the following: (1) primary safety endpoint: serious adverse events; and (2) primary efficacy endpoint: success of PVI and LAA closure defined as the ability to isolate all pulmonary veins and the successful closure of the LAA. For secondary endpoints, peri-procedural data and follow-up data were collected. RESULTS:A total of 155 patients from 22 centres of nine European countries were treated by concomitant pentaspline catheter PFA-based PVI and LAAC. The mean CHA2DS2-VA score was 3.1 ± 1.4. The primary efficacy endpoint was achieved at 97.4% with successful PVI at 100% and successful LAAC in 151/155 patients (97.4%). The primary safety endpoint was observed in 3/155 patients (1.9%). Transoesophageal echocardiography and/or CCTA 67 ± 26 days after the procedure showed no device embolization and no device-related thrombus, 24/151 (15.9%) patients showed peri-device gaps of <5 mm while gaps of >5 mm have been observed in 3/151 (2.0%). Among 137/155 patients with available arrhythmia, a follow-up >6 months at 78.1% showed sinus rhythm. CONCLUSION:In this large multicentre study, concomitant PFA-based AF ablation and LAA closure proved to be feasible, effective, and safe and overall procedure duration was short.

Importance:Left atrial appendage occlusion (LAAO) is used in patients with contraindications to oral anticoagulation, who are at increased risk for major bleeding (MB). Objective:To evaluate the incidence, predictors, management, and clinical outcomes of MB after LAAO in the Amulet IDE trial. Design, Setting, and Participants:The randomized clinical Amulet IDE trial enrolled patients from 2016 through 2019 with 5-year follow-up. Procedures were performed at specialized LAAO centers. Of 1878 randomized patients (1:1 Amulet vs Watchman), 1833 underwent attempted LAAO implantation. These data were analyzed from May 2025 through November 2025. Main Outcomes and Measures:Pooled (Amulet and Watchman) patients with vs without MB (Bleeding Academic Research Consortium [BARC] score ≥3: overt bleeding with transfusion and ≥3 g/dL hemoglobin drop) were compared. Results:This study included a total of 1833 patients (57.7% male and 42.3% female; mean [SD] age, 75.8 [7.5] years). MB occurred in 331 patients (18.1%) over 5 years (annualized rate 5.9% per year). Patients with MB were older (76.8 vs 74.7 years) and had higher CHA2DS2-VASc (4.8 vs 4.6) and HAS-BLED (3.4 vs 3.2) scores, as well as greater prevalence of diabetes (38.7% vs 34.1%), prior MB (45.3% vs 28.0%), and kidney disease (9.4% vs 4.5%). MB risk was highest in the first 6 months after LAAO (20.5% per year), then decreased to 3.9% per year through 5 years. Most MB events were nonprocedural (88.8%) with gastrointestinal bleeding accounting for 252 of 438 events. Independent predictors of MB included increasing age (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06), female sex (HR, 1.25; 95% CI, 1.01-1.56), diabetes (HR, 1.26; 95% CI, 1.01-1.58), prior MB (HR, 1.93; 95% CI, 1.55-2.40), and kidney disease (HR, 2.15; 95% CI, 1.48, 3.12). At first MB event, 47.1% of patients were not receiving antithrombotic therapy and 92 patients had recurrent events. Patients with MB had significantly higher rates of the composite of stroke, systemic embolism, or cardiovascular death (32.5% vs 18.0%; P < .001), driven by higher stroke (14.7% vs 6.6%) and cardiovascular death (24.4% vs 12.9%) rates. All-cause mortality was also higher (49.2% vs 25.4%; P < .001). MB was fatal (BARC score of 5) in 25 patients (1.4%). Conclusions and Relevance:In this study, MB was common in this high-risk population and largely related to underlying patient factors. Early MB risk was highest 6 months post-LAAO, then dropped considerably. Most events were gastrointestinal and occurred even in patients on minimal or no antithrombotic therapy. MB after LAAO was strongly associated with increased stroke and mortality. Trial Registration:ClinicalTrials.gov Identifier: NCT02879448.

Since its introduction in 2002, left atrial appendage closure (LAAC) has rapidly expanded as an alternative to anticoagulation in patients with atrial fibrillation at high risk of stroke. Harmonized processes for data collection, analysis, and reporting in LAAC trials are essential to enhance research quality and improve clinical practice. The Left Atrial Appendage Academic Research Consortium (LAARC) initiative is an independent collaboration of academic research organizations, cardiology and neurology experts, clinical trialists, and regulatory authorities from the USA, Europe, and Asia. The consortium engaged clinical experts, regulators-including the US Food and Drug Administration (FDA), European Notified Bodies, and Japan's Pharmaceuticals and Medical Devices Agency (PMDA)-and industry leaders to define standardized study elements and endpoints for LAAC trials. Key considerations included alignment with prior Academic Research Consortium initiatives, procedural and mechanistic insights, and clinical relevance. Consensus definitions were proposed for mortality, stroke, bleeding, and device performance, along with composite endpoints for safety and effectiveness. The proposed LAARC consensus definitions aim to standardize endpoint reporting, improve comparability across studies, and support regulatory and clinical trial applications for this evolving therapy through broad dissemination in the peer-reviewed literature.

A significant proportion of patients with atrial fibrillation (AF) who need thromboembolic protection are not treated with or discontinue oral anticoagulation after its initiation. Undertreatment in clinical practice has not improved sufficiently despite the availability of direct oral anticoagulants, which are associated with less intracranial bleeding than vitamin K antagonists. Multiple reasons account for this phenomenon, including bleeding events or ischemic strokes while on anticoagulation, poor treatment adherence despite best educational attempts, or aversion to drug therapy. Percutaneous left atrial appendage (LAA) closure was introduced as an alternative to pharmacological therapy in AF patients in the early 2000s. Due to significant improvements in procedural safety over the years, left atrial appendage closure (LAAC), predominantly achieved through a percutaneous catheter-based device implantation approach, is increasingly favoured for preventing thromboembolic events in patients who cannot achieve effective anticoagulation or have a high hemorrhagic risk. This focused summary and update of a recently published practical guide, developed within guideline/guidance boundaries, provides a perspective of current evidence of potential indications, benefits, complications and limitations of LAAC for neurologists and stroke physicians who may consider this increasingly utilised therapy.

INTRODUCTION:Both percutaneous left atrial appendage occlusion (LAAO) and nonvitamin K antagonist oral anticoagulants (NOACs) are noninferior to warfarin for stroke prevention in high-risk patients with atrial fibrillation (AF). However, there is limited data comparing LAAO with NOACs. The CATALYST trial compares a dual-seal LAAO device (Amplatzer™ Amulet™) to NOACs in AF patients indicated for thromboprophylaxis. METHOD:CATALYST is a prospective, multicenter, randomized controlled, open-label trial with an adaptive statistical design. Up to 2,650 AF patients with CHA2DS2-VASc score ≥2 (men) or ≥3 (women) will be randomly assigned to LAAO or NOAC at 123 global sites. Patients randomized to NOACs take the appropriate labeled dose with compliance monitored at each visit, while LAAO patients receive dual antiplatelet therapy followed by aspirin monotherapy for ≥12 months postimplant. Patients are followed through 5 years, with postimplant cardiac imaging at 3- and 12-months. There are three co-primary endpoints: (1) ischemic stroke, systemic embolism, or cardiovascular death through 2 years, tested for noninferiority; (2) major or clinically relevant nonmajor bleeding through 2 years, tested for superiority; and (3) ischemic stroke or systemic embolism through 3 years, tested for noninferiority. The following secondary endpoints will be tested if the primary endpoints are met: (1) all-bleeding, tested for noninferiority; (2) followed by testing for superiority; (3) disabling or fatal strokes, tested for superiority; all through 2 years. CONCLUSIONS:CATALYST is evaluating the safety and effectiveness of a dual seal LAAO device compared to NOACs in patients with AF at increased risk of stroke. CLINICAL TRIAL REGISTRATION:URL https://clinicaltrials.gov; Unique Identifier NCT04226547.

BACKGROUND:Patients with atrial fibrillation (AF) and kidney failure are at particularly high risk of both thromboembolic and bleeding complications. The safety and efficacy of oral anticoagulation in this population remain uncertain, as pivotal direct oral anticoagulant (DOAC) trials excluded patients with kidney failure and warfarin has been associated with excess bleeding risk. Left atrial appendage (LAA) closure may provide an alternative strategy in stroke prevention, but has not been tested in randomized trials in dialysis-dependent patients. METHODS/DESIGN:The LAA-KIDNEY trial is a prospective, multicenter, randomized controlled clinical trial comparing percutaneous LAA closure with best medical care (including DOAC therapy whenever considered feasable) in patients with non-valvular AF and kidney failure at high risk of both, ischemic stroke and bleeding. A total of 272 patients will be randomized 1:1 across ∼35 centers in Germany, Belgium and the Czech Republic. The primary efficacy endpoint is net clinical benefit defined as time to a composite of first stroke (including ischemic or hemorrhagic strokes), systemic embolism, cardiovascular or unexplained death or major bleeding (BARC 3-5). Secondary endpoints include individual components of the composite outcome, myocardial infarction, cardiovascular hospitalization, cognitive function, quality of life, and device-related complications. Analysis will be performed in the intention-to-treat population. CONCLUSION:LAA-KIDNEY is the first randomized trial to evaluate LAA closure versus best medical care in AF patients with kidney failure. This trial will address a major evidence gap and is expected to inform clinical practice and guideline recommendations for stroke prevention in this high risk population. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT05204212.

Female sex is an established, non-modifiable risk factor for adverse outcomes in atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) has been shown to be a generally safe and effective alternative to oral anticoagulation (OAC) for stroke prevention in patients with AF. However, there is limited data on sex-based outcomes with LAAC associated with catheter ablation. The OPTION trial compared the strategy of LAAC to oral anticoagulation for reducing the risk of thromboembolism in patients who had a catheter ablation for atrial fibrillation. Evaluation of outcome in women vs men was prespecified. OPTION was a randomized controlled trial enrolling catheter ablation patients. The ablation procedure could have occurred 90 to 180 days prior to or within 10 days of randomization. Groups were randomized 1:1 to either ablation+LAAC or ablation+OAC (~95% DOAC). The primary safety endpoint was 36-month non-procedural bleeding defined as International Society on Thrombosis and Haemostasis [ISTH] major bleeding or clinically relevant non-major bleeding. The primary efficacy endpoint was 36-month all-cause death, stroke, or systemic embolism. The secondary endpoint was 36-month ISTH major bleeding, including procedural bleeding. Additional endpoints included ablation and LAAC procedural characteristics, medication adherence, and arrythmia recurrence. A total of 1600 patients were randomized in OPTION (803 patients to catheter ablation+LAAC and 797 to ablation+OAC); one-third were women. The rate of the primary efficacy endpoint was similar in ablation+LAAC and ablation+OAC-treated men and women (Table). The primary safety endpoint was significantly lower in the ablation+LAAC treated men compared to ablation+OAC-treated men. The difference in ablation+LAAC vs ablation+OAC-treated women was directionally similar. At 3 years, no differences in rates of mortality, ischemic stroke, and systemic embolism were found between treatment arms in women or in men. The reduction in post-operative bleeding was higher in men as compared to women. OPTION demonstrated that LAAC reduced non-procedural bleeding compared to OAC without increasing the risk of thromboembolic events. Women exhibited higher rates of major bleeding compared to men; however, a beneficial reduction in bleeding was still observed with LAAC although conclusions may be impacted by the smaller sample size.

Die chronische Nierenkrankheit (CKD) ist einer der wichtigsten Risikofaktoren für Herz-Kreislauf-Erkrankungen (CVD; manifestiert durch koronare Herzkrankheit, Herzinsuffizienz, Arrhythmien und plötzlichen Herztod), und das gleichzeitige Vorliegen sowohl von CVD und CKD hat einen erheblichen Einfluss auf die Prognose der Patienten. Die diagnostischen und therapeutischen Möglichkeiten kardiovaskulärer Erkrankungen sind bei fortgeschrittener CKD häufig eingeschränkt, und für viele interventionelle und medikamentöse Therapien besteht wenig oder keine Evidenz aus großen klinischen Studien. Das vorliegende Konsensuspapier gibt einen Überblick über die Besonderheiten kardiovaskulärer Erkrankungen bei CKD und fasst die aktuelle Evidenz und Empfehlungen zur Therapie von Patienten mit CVD und CKD zusammen.