Thromboembolism after electrical isolation of the left atrial appendage: a new indication for interventional closure?

AIMS: Left atrial appendage electrical isolation (LAAI) may improve the rhythm outcome in selected patients with atrial fibrillation (AF). Controversy exists if LAAI is associated with an increased rate of thromboembolic complications. We sought to assess the feasibility, efficacy, and safety of interventional left atrial appendage closure (LAAC) in comparison to oral anticoagulation (OAC) after electrical LAAI. METHODS AND RESULTS: Weeks after index LAAI using the cryoballoon or a linear maze like ablation strategy patients' left atrial appendage was invasively remapped. In case of persistent LAAI, LAAC was performed. Patients who refused invasive remapping continued OAC. The primary endpoint was composed of any stroke or systemic embolism (SE) and the occurrence of intracardiac thrombus. Secondary endpoints included stroke/SE, major bleeding, and all-cause death. Of 166 patients (51% female; mean age 70 ± 8 years; mean CHAD2S2VASc score 3.4 ± 1.8) after LAAI, 94 patients received LAAC (LAAC group) and 72 continued OAC (no LAAC). After LAAC, 83% of patients received dual antiplatelet therapy for 6 weeks and aspirin thereafter. During a mean follow-up of 778 ± 630 days, 5 and 11 primary endpoint events were observed in the LAAC and no LAAC group, respectively [hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.75; P = 0.010]. The calculated annual thromboembolic event rates were 6.9% (no LAAC) and 2.3% (LAAC), respectively. Left atrial appendage closure significantly reduced the incidence of stroke and SE (HR 0.31, CI 0.1-0.98; P = 0.04). CONCLUSION: After electrical LAAI for rhythm control in AF patients, interventional LAAC was associated with fewer thromboembolic complications when compared with OAC.

Left atrial appendage occlusion using LAmbre Amulet and Watchman in atrial fibrillation.

BACKGROUND: Left atrial appendage closure (LAAC) has been suggested as an alternative to anticoagulation in non-valvular atrial fibrillation (AF). The present study aimed to compare a LAmbre LAA occluder system [Lifetech Scientific (Shenzhen) Co. Ltd., Shenzhen, China] with the most investigated Amulet (St. Jude Medical Inc., St. Paul, MN, USA) and Watchman (Boston Scientific, Plymouth, MN, USA) devices in terms of peri-procedural and short-term outcomes. METHODS: This is a prospective observational study. RESULTS: Overall, 140 patients (50 female, mean age 76.2±8.4 years) were consecutively enrolled. Mean CHA2DS2-VASc score was 3.8±1.5, and mean HAS-BLED score was 3.9±1.1. Baseline clinical characteristics were comparable between the three groups (LAmbre, n=30; Amulet, n=74; Watchman, n=36); the LAmbre group had significantly more patients with complicated LAA morphology (p=0.006). The implant success rate was 100% in LAmbre, 99% in Amulet, and 100% in Watchman group (p=0.638). The number of device repositions was not significantly different between groups (0.7±1.1 in LAmbre, 1.0±2.0 in Amulet, and 1.4±1.8 in Watchman group, p=0.345). Fluoroscopic and procedural times were similar between groups. Major peri-procedural adverse events did not differ between groups (0% vs. 0% vs. 2.8%, p=0.233). Six months' follow-up showed good device stability and patients' clinical condition in all groups. CONCLUSION: LAmbre, Amulet, and Watchman exhibit remarkable implant success rate, low risk of peri-procedural adverse events, and good clinical outcomes.

Antithrombotic strategies after interventional left atrial appendage closure: an update.

INTRODUCTION: Interventional left atrial appendage occlusion (LAAO) has emerged as a valid alternative to oral anticoagulation (OAC) therapy for the prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). Areas covered: Antithrombotic therapy following interventional LAAO is critical in balancing the risk of thromboembolism and bleeding during the endothelialization of the implanted devices. In this article, the most recent clinical trials are reviewed and the current real-world antithrombotic strategies following LAAO device implantation are discussed. Expert commentary: For patients eligible for OAC and receiving a Watchman device, the most solid scientific evidence exists for warfarin plus aspirin for 45 days followed by dual antiplatelet therapy (DAPT) for 6 months and a lifelong aspirin therapy. In real-world most patients are being treated with DAPT for 3-6 months. Alternatively, the Watchman was approved for 3 months of novel OAC (NOAC) therapy in conjunction with aspirin. For all other devices, DAPT for 1-6 months has been used in the vast majority of cases. Considering major bleeding as the predominant complication following LAAO, evidence suggests that short-term DAPT (6 weeks) or single antiplatelet therapy using aspirin may be a viable option.

Low Risk of Pulmonary Vein Stenosis After Contemporary Atrial Fibrillation Ablation　- Lessons From Repeat Procedures After Radiofrequency Current, Cryoballoon, and Laser Balloon.

BACKGROUND: The incidence of pulmonary vein stenosis (PVS) after AF ablation following contemporary procedures remains unclear. We compared the incidence of PVS/narrowing (PVS/N) after PV isolation (PVI) for (1) 3-D mapping-guided wide-area encircling irrigated radiofrequency current (RFC) ablation; (2) first-third-generation big cryoballoon (CB1-3) ablation; and (3) laser balloon (LB) ablation.Methods and Results:All patients undergoing a second procedure between January 2012 and November 2016 were subgrouped according to index ablation (PVI): RFC; CB; or LB. PVS/N was classified using PV diameter ratio (second/index procedure) on selective PV angiogram performed before ablation: mild, 25-49%; moderate, 50-74%; or severe, ≥75%. A total of 344 patients (1,362 PV) were analyzed (RFC, n=211; 840 PV; CB1, n=21; 82 PV; CB2,3, n=64; 250 PV; LB, n=48; 190 PV). In the LB group, 45 patients (94%) were treated with dose ≥8.5 W. Second procedures were performed on average 14.9±14.1 months after the index procedure. Mild PVS/N was observed in 18.4%, 9.5% and 3.6% of PV in the LB, RFC and CB groups, respectively (P<0.01). Moderate PVS was recognized in 2 PV (0.1%; RFC, LB). Severe PVS was never observed, and no PV intervention/surgery was required. CONCLUSIONS: The risk for significant PVS is low after RFC/CB. The incidence of mild PVS/N was highest after standard-dose LB ablation and lowest after high-dose CB ablation.

Short-term dual antiplatelet therapy after interventional left atrial appendage closure with different devices.

AIMS: We aimed to assess the feasibility, efficacy and safety of short-term dual antiplatelet therapy (DAPT) for six weeks after left atrial appendage closure (LAAC). METHODS AND RESULTS: Data of the Cardioangiologisches Centrum Bethanien-LAAC registry were analysed. DAPT (aspirin 100 mg plus clopidogrel 75 mg) was administered until transoesophageal echocardiography (TEE) evaluation six weeks after LAAC. In the absence of significant peri-device flow or device-related thrombus (DRT), the medication was decreased to single antiplatelet therapy (SAPT). Outpatient visits were timed at six-month intervals. The incidences of major bleeding (BARC ≥3) and of thromboembolic events were investigated. A total of 298 patients (76±8 years; 62% male; CHA2DS2-VASc 4.3±1.5; HAS-BLED 3.5±1.0; 61% with history of bleeding) with successful LAAC were included. TEE revealed DRT in 7/298 (2.3%) patients (five at six-week follow-up [FU] 45±10 days after implant, two during a median long-term FU of 731 days). Non-procedure-related bleeding events occurred in 25/298 (8.4%) patients and non-procedure-related thromboembolic events in 11/298 (3.7%) patients. This translated into 3.9 bleeding events/100 patient-years and 1.7 thromboembolic events/100 patient-years, respectively. Procedure-related events consisted of major bleeding in 7/298 (2.3%) patients and stroke in 2/298 (0.7%) patients. Age ≥75 years (OR 3.2; CI: 1.2-8.0; p=0.015) and renal impairment (OR 2.5; CI: 1.1-5.7; p=0.027) were identified as independent predictors for major bleeding after LAAC. CONCLUSIONS: Short-term DAPT for six weeks appears to be a viable alternative for patients after LAAC. Age ≥75 years and renal impairment increase major bleeding events threefold.

Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo.

The submembrane cytoskeletal meshwork of the axon contains the scaffolding protein betaIV-spectrin. It provides mechanical support for the axon and anchors membrane proteins. Quivering (qv(3j)) mice lack functional betaIV-spectrin and have reduced voltage-gated sodium channel (VGSC) immunoreactivity at the axon initial segment and nodes of Ranvier. Because VGSCs are critically involved in action potential generation and conduction, we hypothesized that qv(3j) mice should also show functional deficits at the network level. To test this hypothesis, we investigated granule cell function in the dentate gyrus of anesthetized qv(3j) mice after electrical stimulation of the perforant path in vivo. This revealed an impaired input-output relationship between stimulus intensity and granule cell population spikes and an enhanced paired-pulse inhibition of population spikes, indicating a reduced ability of granule cells to generate action potentials and decreased network excitability. In contrast, the input-output curve for evoked field excitatory postsynaptic potentials (fEPSPs) and paired-pulse facilitation of fEPSPs were unchanged, suggesting normal excitatory synaptic transmission at perforant path-granule cell synapses in qv(3j) mutants. To corroborate our findings, we analyzed the influence of VGSC density reduction on dentate network activity using an established computational model of the dentate gyrus network. This in silico approach confirmed that the loss of VGSCs is sufficient to explain the electrophysiological changes observed in qv(3j) mice. Taken together, our findings demonstrate that betaIV-spectrin is required for normal granule cell firing and for physiological levels of network excitability in the mouse dentate gyrus in vivo.