Citations

Abstract 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.

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: Bilateral cardiac sympathetic denervation (BCSD) has shown promise in treating patients with nonischemic cardiomyopathy (NICM) suffering from refractory multifocal premature ventricular contractions (PVCs) and ventricular tachycardia (VT). Despite its growing use, the effectiveness of BCSD across different NICM etiologies has not been extensively studied. Research Question: How effective is BCSD across a variety of NICM etiologies? Goals: To evaluate the effectiveness of BCSD on left ventricular ejection fraction (LVEF) and PVC burden in patients with NICM. Methods: We conducted a subset analysis on a previous retrospective, observational study of NICM patients who underwent BCSD. Eight NICM etiologies were assessed. Results: 43 NICM patients underwent BCSD (mean age 52.3±14.7 years; 30% females). Overall, LVEF significantly improved (38.7±7.9% to 46.2±9.6%, p <0.001), and PVC burden (PVCb) significantly decreased (23.7±9.9% to 1.3±1%, p <0.001). A similar phenomenon was seen in idiopathic/dilated cardiomyopathy (CM) (LVEF: +8.7%, p <0.001; PVCb: -20.6%, p <0.001), post-viral CM (LVEF: +4.8%, p =0.2; PVCb: -24.2%, p <0.001), familial CM (LVEF: +10%; PVCb: +23.3%), giant cell CM (LVEF: +10%; PVCb: + 30.5%), and arrhythmogenic right ventricular CM (LVEF: +12.5%, p=0.09; PVCb -30.6%, p =0.001). Catecholaminergic polymorphic VT had a non-significant increase in LVEF (+5%, p=0.5) but a significant decrease in PVCb (-21.8%, p=0.02), whereas sarcoidosis had the opposite effect with significant increase in LVEF (LVEF: +13.4%, p=0.3) but non-significant decrease in PVCb (-16.1%, p=0.02). Lastly, hypertrophic CM remained unchanged in LVEF (30%) but PVCb decreased (-8%). Conclusion: BCSD demonstrates efficacy in improving LVEF and reducing PVCb across almost all NICM with refractory VT. However, a case-by-case evaluation is still needed for its use.

AbstractIntroductionCatheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.BackgroundStudies on catheter ablation of AF may benefit from well‐described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost‐effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects.MethodsA panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials.ResultsA comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm‐related and other endpoints.ConclusionThis expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology.CONDENSED ABSTRACTRecent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

BACKGROUND: The National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry (LAAO) includes the vast majority of transcatheter LAAO procedures performed in the United States. The objective of this study was to develop a model predicting adverse events among patients undergoing LAAO with Watchman FLX. METHODS: Data from 41 001 LAAO procedures with Watchman FLX from July 2020 to September 2021 were used to develop and validate a model predicting in-hospital major adverse events. Randomly selected development (70%, n=28 530) and validation (30%, n=12 471) cohorts were analyzed with 1000 bootstrapped samples, using forward stepwise logistic regression to create the final model. A simplified bedside risk score was also developed using this model. RESULTS: Increased age, female sex, low preprocedure hemoglobin, no prior attempt at atrial fibrillation termination, and increased fall risk most strongly predicted in-hospital major adverse events and were included in the final model along with other clinically relevant variables. The median in-hospital risk-standardized adverse event rate was 1.50% (range, 1.03%–2.84%; interquartile range, 1.42%–1.64%). The model demonstrated moderate discrimination (development C-index, 0.67 [95% CI, 0.65–0.70] and validation C-index, 0.66 [95% CI, 0.62–0.70]) with good calibration. The simplified risk score was well calibrated with risk of in-hospital major adverse events ranging from 0.26% to 3.90% for a score of 0 to 8, respectively. CONCLUSIONS: A transcatheter LAAO risk model using National Cardiovascular Data Registry and LAAO Registry data can predict in-hospital major adverse events, demonstrated consistency across hospitals and can be used for quality improvement efforts. A simple bedside risk score was similarly predictive and may inform shared decision-making.

Introduction: Incident cardiac arrhythmias are common in hospitalized COVID-19 patients, but the impact of a second incident cardiac arrhythmia during hospitalization on clinical outcomes remain unclear. Hypothesis: The aim of this study was to assess the frequency and prognostic implications of a second incident arrhythmia in hospitalized COVID-19 patients over the pandemic course till vaccine availability. Methods: The multicenter COVID-RHYTHM Registry enrolled hospitalized COVID-19 patients from 3/8/2020 to 1/24/2021. Cardiac arrhythmia included documented atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), severe sinus bradycardia (<40 bpm) or AV block. Outcomes were compared between patients with single vs. more than one incident arrhythmias adjusting for baseline variables. Results: Of 6299 hospitalized COVID-19 patients, 4398 had an had an incident cardiac arrhythmia during hospitalization, of which 822 (19%) had a second incident arrhythmia. Those with >1 incident arrhythmia had a higher baseline prevalence of heart failure, chronic kidney disease, coronary artery disease and sleep apnea (Table). Those with >1 incident arrhythmia had higher in-hospital mortality, need for ICU admission and need for rehab upon discharge. Length of stay was similar between the groups. Conclusions: In hospitalized COVID-19 patients with incident cardiac arrhythmias, a second incident arrhythmia during hospitalization was seen in 19%. Having >1 incident arrhythmia was associated with increased need for ICU admission and reduced survival.

Introduction: Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear. Hypothesis: This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients. Methods: Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival. Results: Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48). Conclusions: In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.

Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.

Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.