Redefining the blanking period after pulsed-field ablation in patients with atrial fibrillation.

BACKGROUND: Recurrence during the 3-month blanking period after radiofrequency ablation of atrial fibrillation (AF) is typically not considered as a predictor for late recurrence. OBJECTIVE: We investigated the significance of early recurrence as a risk factor for late recurrence in patients with AF receiving pulsed-field ablation (PFA). METHODS: Consecutive patients undergoing PFA were prospectively followed up for 1 year. All patients received isolation of pulmonary veins. Additional ablation procedures were performed per operator's discretion. After the procedure, all remained on their previously ineffective antiarrhythmic drugs (AADs) during the 2-month blanking period after which the AADs were discontinued. Early recurrence was defined as atrial arrhythmia of >30-second duration during the 3-month blanking period, and any recurrence beyond 3 months was considered as late recurrence. RESULTS: A total of 337 patients undergoing PFA for AF were included. Early recurrence was recorded in 53 patients (15.7%): 10 in the first month, 12 in the second month, and 31 in the third month. Of the 10 patients having recurrence during the first month, 7 (70%) remained in sinus rhythm after cardioversion whereas 3 (30%) underwent a redo procedure because of late recurrence. At 1 year, all patients with recurrence in the second and third months experienced late recurrence; among these patients, 10 (83.3%) of 12 and 27 (87%) of 31 underwent a redo procedure and the remaining 6 patients were in sinus rhythm on AADs. CONCLUSION: In this consecutive series of patients with AF, early recurrence in the second or third month after the PFA procedure was associated with a high risk of late recurrence. Thus, blanking period could be redefined as 1 month after PFA.

Anticoagulation Alone vs Anticoagulation Plus Aspirin or DAPT Following Left Atrial Appendage Occlusion.

BACKGROUND: The prevalence of and outcomes associated with different antithrombotic strategies after left atrial appendage occlusion (LAAO) are not well described. OBJECTIVES: This study sought to evaluate patterns of antithrombotic medication strategies at discharge following LAAO with the Watchman FLX device in real-world practice and to compare the risk of adverse events among the different antithrombotic regimens. METHODS: The authors evaluated patients in the NCDR (National Cardiovascular Data Registry) LAAO Registry who underwent LAAO with the second-generation LAA closure device between 2020 and 2022. They grouped patients by mutually exclusive discharge antithrombotic strategies and compared the rates of adverse events at 45 days and 6 months using multivariable Cox proportional hazards regression. RESULTS: Among 53,878 patients undergoing successful LAAO with the second-generation LAA closure device, the most common antithrombotic discharge regimens were direct oral anticoagulant (DOAC) plus aspirin (48.3%), DOAC alone (22.6%), dual antiplatelet therapy (8.1%), warfarin plus aspirin (7.7%), and DOAC plus P2Y12 inhibitor (4.9%). In multivariate analysis, DOAC alone had a lower rate of major adverse events and major bleeding at 45 days of follow-up compared with DOAC plus aspirin (major adverse events: HR: 0.78; 95% CI: 0.68-0.91; major bleeding: HR: 0.69; 95% CI: 0.60-0.80). These differences persisted at 6 months. Warfarin without aspirin also showed lower rates of major bleeding at both time points. No differences were seen in stroke/transient ischemic attack or device-related thrombus. CONCLUSIONS: In real-world U.S. practice, discharge on DOAC alone or warfarin alone was associated with a lower rate of adverse events compared with DOAC plus aspirin.

VARIPULSE: A step-by-step guide to pulmonary vein isolation.

INTRODUCTION: The VARIPULSE™ variable-loop circular catheter (VLCC) is a bidirectional, multielectrode catheter that can perform electrophysiological mapping and deliver pulsed field energy through the TRUPULSE™ Generator for the treatment of atrial fibrillation. This ablation system, including the CARTO 3™ three-dimensional electroanatomical mapping system, represents a fully integrated system. METHODS: Pulsed field ablation (PFA) is a novel, primarily cardiac tissue-selective ablation technology with a minimal thermal effect, potentially eliminating the collateral tissue damage associated with radiofrequency ablation or cryoablation. Integration of a mapping system may lead to shorter fluoroscopy times and improve the usability of the system, allowing tracking of energy density and placement to confirm no areas around the vein are left untreated. RESULTS: This step-by-step review covers patient selection, mapping, the step-by-step ablation workflow, details on catheter repositioning and ensuring contact, considerations for ablation of specific anatomical variations, and discussion of ablation without fluoroscopy based on our initial clinical experience. CONCLUSIONS: The VLCC is part of the fully integrated PFA system designed for pulmonary vein isolation, using mapping to guide catheter placement and lesion set creation. The current workflow, which is based on our initial clinical experience, may be further refined as the PFA system is used in real-world settings.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

Outcomes With the WATCHMAN FLX in Everyday Clinical Practice From the NCDR Left Atrial Appendage Occlusion Registry.

BACKGROUND: PINNACLE FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the WATCHMAN FLX LAA Closure Technology) demonstrated improved outcomes and low incidence of adverse events with the WATCHMAN FLX device in a controlled setting. The National Cardiovascular Disease Registry's Left Atrial Appendage Occlusion Registry was utilized to assess the safety and effectiveness of WATCHMAN FLX in contemporary clinical practice in the United States. METHODS: The WATCHMAN FLX Device Surveillance Post Approval Analysis Plan used data from the Left Atrial Appendage Occlusion registry to identify patients undergoing WATCHMAN FLX implantation between August 2020 and September 2022. The key safety end point was defined as all-cause death, ischemic stroke, systemic embolism, or device or procedure-related events requiring open cardiac surgery or major endovascular intervention between device implantation and hospital discharge. Major adverse events were reported at hospital discharge, 45 days, and 1 year. RESULTS: Among 97 185 patients in the Left Atrial Appendage Occlusion registry undergoing WATCHMAN FLX, successful implantation occurred in 97.5% (n=94 784) of patients. The key safety end point occurred in 0.45% of patients. At 45 days post-procedure, all-cause death occurred in 0.81% patients, ischemic stroke in 0.23%, major bleeding in 3.1%, pericardial effusion requiring intervention in 0.50%, device-related thrombus in 0.44%, and device embolism in 0.04% patients. No peri-device leak was observed in 83.1% of patients at 45 days. At 1 year, the rate of all-cause death was 8.2%, the rate of any stroke was 1.5% (ischemic stroke, 1.2%), and major bleeding occurred in 6.4% of patients. CONCLUSIONS: In a large contemporary cohort of patients with the WATCHMAN FLX device, the rates of implant success and clinical outcomes through 1 year were comparable with the PINNACLE FLX study, demonstrating that favorable outcomes achieved in the pivotal approval study can be replicated in routine clinical practice.

Micra Extraction Out To 4.5 Years.

Leadless pacemaker systems (LPs) were developed as an alternative to traditional transvenous permanent pacemakers (TV-PPM) due to increasing rates of device and procedural related complications, leading to a high-cost burden to our health-care system. LPs were initially indicated for single-chamber ventricular pacing; however, recent developments have allowed for dual-chamber pacing too. These systems have demonstrated highly successful implant rates with stable pacing performance. This article describes the retrieval techniques of the Micra LPs and ways to mitigate challenges encountered during the retrieval process.

A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Dual-energy lattice-tip ablation system for persistent atrial fibrillation: a randomized trial.

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year and included freedom from acute procedural failure and repeat ablation at any time, plus arrhythmia recurrence, drug initiation or escalation or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from a composite of serious procedure-related or device-related adverse events. The primary effectiveness endpoint was observed for 73.8% and 65.8% of patients in the investigational and control arms, respectively (P < 0.0001 for non-inferiority). Major procedural or device-related complications occurred in three patients in the investigational arm and in two patients in the control arm (P < 0.0001 for non-inferiority). In a secondary analysis, procedural times were shorter in the investigational arm as compared to the control arm (P < 0.0001). These results demonstrate non-inferior safety and effectiveness of the dual-energy catheter for the treatment of persistent AF. Future large-scale studies are needed to gather real-world evidence on the impact of the focal dual-energy lattice catheter on the broader population of patients with AF. ClinicalTrials.gov identifier: NCT05120193 .

Early real-world implant experience with a helix-fixation ventricular leadless pacemaker.

BACKGROUND: Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1 year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release. METHODS: In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated. RESULTS: A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70 years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5 min [20.0, 35.0] and 5.7 min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8 V [0.5, 1.3], 9.0 mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events. CONCLUSIONS: The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications.

DAPT Is Comparable to OAC Following LAAC With WATCHMAN FLX: A National Registry Analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is an approved alternative for stroke prevention in atrial fibrillation for patients with an "appropriate rationale" to avoid long-term oral anticoagulation (OAC). Many patients undergoing LAAO are at high risk of bleeding. OBJECTIVES: This study sought to investigate whether dual antiplatelet therapy (DAPT) is a safe alternative to OAC (direct oral anticoagulation [DOAC] or warfarin) with aspirin after LAAO. METHODS: Using National Cardiovascular Data Registry LAAO registry data, patients undergoing Watchman FLX (Boston Scientific) implantation (August 5, 2020-September 30, 2021) were included in 1:1 propensity-matched analyses comparing discharge medication regimens (DAPT, DOAC/aspirin, or warfarin/aspirin). A composite endpoint (death, stroke, major bleeding, and systemic embolism), its components, and device-related thrombus between discharge and 45 days were evaluated. RESULTS: In 49,968 patients implanted with the Watchman FLX during the study period, the mean age was 77 years, and 40% were women. Postimplant DOAC/aspirin was prescribed in 24,497 patients, warfarin/aspirin in 3,913, and DAPT in 4,155. DAPT patients had more comorbid conditions than patients receiving OAC/aspirin. After propensity score matching, the 45-day composite endpoint rates were similar among the groups (DAPT = 3.44% vs DOAC/aspirin: 4.06%; P = 0.13 and DAPT = 3.23% vs warfarin/aspirin: 3.08%; P = 0.75). Death, stroke, and device-related thrombus were also similar; major bleeding was slightly increased in DOAC/aspirin patients (DAPT = 2.48% vs DOAC/aspirin = 3.25%; P = 0.04 and DAPT = 2.25% vs warfarin/aspirin = 2.22%; P = 0.93). CONCLUSIONS: In a large registry, DAPT had a similar safety profile compared with current Food and Drug Administration-approved postimplant drug regimens of OAC with aspirin following LAAO with the Watchman FLX. Shared decision making for nonpharmacologic stroke prevention should include a discussion of postprocedure medical therapy options.

Intracardiac vs Transesophageal Echocardiography for Left Atrial Appendage Occlusion With Watchman FLX in the U.S.

BACKGROUND: Intraprocedural imaging is critical for device delivery in transcatheter left atrial appendage occlusion (LAAO). Although pivotal trials of LAAO devices were conducted using transesophageal echocardiography (TEE), intracardiac echocardiography (ICE) is an emerging imaging modality. OBJECTIVES: This study compared outcomes after ICE- and TEE-guided Watchman FLX implantation in the SURPASS (SURveillance Post Approval AnalySiS Plan) nationwide LAAO registry. METHODS: Baseline characteristics were compared using chi-square and t-tests. Outcomes were reported in unadjusted and adjusted comparisons via propensity weighting. RESULTS: Between August 2020 and September 2021, LAAO was attempted in 39,759 patients at 698 sites, including 2,272 cases (5.7%) with ICE and 31,835 (80.0%) with TEE. ICE and TEE patients had similar baseline characteristics and mean procedural times (ICE 82 minutes vs TEE 78 minutes). ICE patients were less likely to receive general anesthesia (54% vs 98%, P < 0.01). Successful device implantation (98.3% vs 97.6%) and complete seal rates at 45 days were similar (n = 25,280; 83% vs 82%). Most adverse event rates were similar; unadjusted mortality rates at 45 days were 1.1% for ICE vs 0.8% for TEE (P = 0.14), and 1.0% vs 0.7% (P = 0.27) in adjusted analyses. Even after adjustment, pericardial effusion rates requiring intervention were significantly higher with ICE at 45 days (1.0% vs 0.5%; P = 0.02). This rate decreased as operators performed more ICE-guided procedures, although 82% of operators had performed <10 ICE-guided procedures overall. CONCLUSIONS: In the largest comparison to date, ICE use was infrequent. ICE and TEE both achieved high rates of complete LAAO. ICE was associated with significantly higher rates of pericardial effusion requiring intervention.

Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model.

BACKGROUND: The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated. METHODS: Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes. RESULTS: At a median of 1.9 years postimplant (range, 1.8-2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5-36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy. CONCLUSIONS: This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

BACKGROUND: The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or LV electrical delay durations) are associated with patients who benefit from AVO. METHODS: This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. RESULTS: A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). CONCLUSIONS: Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03089281.

Two-Year Outcomes With a Next-Generation Left Atrial Appendage Device: Final Results of the PINNACLE FLX Trial.

Background The PINNACLE FLX (Protection Against Embolism for Non-valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next-generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2-year outcomes with this next-generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA2DS2-VASc, 4.2±1.5), the secondary efficacy end point of 2-year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1-sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two-year rates of adverse events were as follows: 9.3% all-cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device-related thrombi after 1 year. Conclusions The secondary end point of 2-year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next-generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Multiparameter diagnostic sensor measurements during clinically stable periods and worsening heart failure in ambulatory patients.

AIMS: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. METHODS AND RESULTS: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment. CONCLUSIONS: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable.