WATCHMAN Left Atrial Appendage System Research Articles

Performing transcatheter left atrial appendage closure: Techniques and challenges.

The left atrial appendage (LAA) has been demonstrated to be the major source of thromboemboli in patients with atrial fibrillation.1 The rationale of LAA closure is based on eliminating LAA continuity with the left atrium (LA), thereby reducing stroke risk. Indeed, left atrial appendage occlusion (LAAO) procedures play an important role in anticoagulation-intolerant patients who are at risk for atrial fibrillation–related stroke. Based on the PROTECT AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation)2 and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation [AF] Versus Long Term Warfarin Therapy)3 studies, the Food and Drug Administration (FDA) approved use of the Watchman (Boston Scientific, Marlborough, MA) device in 2015, with an updated generation of device subsequently ratified in 2020 following the PINNACLE-FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) study.

Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure

BackgroundIn the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA “closure.” However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized. ObjectivesWe sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device. MethodsUsing combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5. ResultsThe cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHA2DS2-VASc 4.1 ± 1.4. TEE imaging at 45 days revealed 634 patients (60.2%) without and 404 (38.3%) with PDL≤5, and 1-year TEE revealed 704 patients (71.6%) without and 272 (27.7%) with PDL≤5. The presence of PDL≤5 at 1 year, but not at 45 days, was associated with an increased 5-year risk of ischemic stroke or systemic embolism (adjusted HR: 1.94; 95% CI: 1.15-3.29; P = 0.014), largely driven by an increase in nondisabling stroke (HR: 1.97; 95% CI: 1.03-3.78; P = 0.04), while disabling or fatal stroke rates were similar (HR: 0.69; 95% CI: 0.19-2.46; P = 0.56). PDL≤5 was not associated with an increased risk of cardiovascular or unexplained death (HR: 1.20; P = 0.45) or all-cause death (HR: 0.87; P = 0.42). ConclusionsPDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291])

Patient-Level Analysis of Watchman Left Atrial Appendage Occlusion in Practice Versus Clinical Trials.

The aim of this study was to compare outcomes among patients from the PROTECT-AF (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the WATCHMAN Left Atrial Appendage [LAA] Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) left atrial appendage occlusion (LAAO) trials with matched patients from the National Cardiovascular Data Registry LAAO Registry using patient-level data. Patients undergoing LAAO in clinical practice generally have more comorbidities than trial participants. Propensity-matched analyses, with up to 3 registry patients matched to each trial patient, were performed using Cox proportional hazards and Fine-Gray models. A total of 1,904 registry patients were matched to 667 trial LAAO patients; 1,010 registry patients were matched to 348 warfarin patients. Compared with registry patients, trial LAAO patients experienced more pericardial effusion requiring intervention (3.8% vs 0.6%, P< 0.001), periprocedural ischemic stroke (0.9% vs 0.2%, P=0.005), and failed device implantation (7.5% vs 3.6%, P< 0.001). The 425-day risk of ischemic stroke in trial LAAO patients was higher than in registry patients (2.70% vs 1.21%; HR: 1.951; P=0.03); warfarin patients had comparable rates of ischemic stroke compared with registry patients (1.15% vs 1.29%; HR: 0.728; P=0.57). Hemorrhagic stroke risk was similar among trial LAAO and registry patients (P=0.88). Hemorrhagic stroke risk was greater among warfarin patients versus registry patients (1.44% vs 0.20%; HR: 5.871, P=0.03). Mortality was lower in trial LAAO patients than in registry patients (2.92% vs 6.23%; HR: 0.477; P=0.004), a difference attributable to noncardiovascular deaths. Mortality was similar (P=0.44) among trial warfarin (4.48%) and registry (5.86%) patients. In clinical practice, patients who meet trial criteria and undergo LAAO experience a lower risk of ischemic stroke, a similar risk of hemorrhagic stroke, and a higher risk of death after implant versus LAAO trial patients. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation [PROTECT-AF], NCT00129545; Evaluation of the WATCHMAN Left Atrial Appendage [LAA] Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL], NCT01182441).

Percutaneous left atrial appendage occlusion: A South African experience

Background. Atrial fibrillation (AF) is associated with all-cause mortality, heart failure and non-fatal stroke, and thromboprophylaxis is traditionally provided with oral anticoagulants (OACs). Percutaneous left atrial appendage occlusion (LAAO) with a dedicated device is an alternative approach to thromboprophylaxis in patients with AF who are: (i) intolerant to OACs (e.g. life-threatening haemorrhage); (ii) non-adherent to OACs; or (iii) at a high bleeding risk with OACs. Non-inferiority of LAAO compared with OACs was demonstrated in e.g. the WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) trial. Only very limited data are available on percutaneous LAAO in South Africa (SA), and no local outcome data have been reported. Objectives. To compare the safety and efficacy outcomes of an SA percutaneous LAAO programme with larger international series. Methods. All patients undergoing percutaneous LAAO from 2013 to 2020 at a single centre (SAEndovascular, Kuils River Netcare Hospital, SA) were included from an ongoing registry. Survival analysis was performed with the Kaplan-Meier method. Results. Of 101 LAAO recipients (mean (standard deviation) age 77 (10) years, 64% male) analysed, 90 (90%) had permanent AF, 1 (1%) persistent AF and 9 (9%) paroxysmal AF. The most common indication for LAAO was previous severe bleeding (n=23; 23%). The mean device size was 23 (3) mm and the procedural success rate was 98%. After a median (interquartile range) follow-up of 21 (5 - 41) months, 6 patients (6%) experienced stroke or all-cause mortality. Four patients (4%) had a life-threatening procedural complication (tamponade n=2 (2%) and device embolisation n=2 (2%)). These outcomes are comparable to large international series, e.g. PROTECT AF. Conclusions. The safety and efficacy outcomes of an SA percutaneous LAAO programme were comparable to large international series. A successful percutaneous LAAO programme is feasible in a southern African context

Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries

BackgroundLong-term data on the safety and efficacy of left atrial appendage closure (LAAC) for stroke prevention in patients with nonvalvular atrial fibrillation remain limited. ObjectivesThe purpose of this study was to evaluate 4.5- to 5-year data in 2 U.S. Food and Drug Association LAAC mandated registries (CAP [Continued Access to PROTECT-AF] and CAP2 [Continued Access to PREVAIL]) for safety and efficacy. MethodsTwo registries of patients implanted with LAAC devices provide the largest source of follow-up data. Both accompanied their respective randomized clinical trials, PROTECT-AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation versus Long Term Warfarin Therapy), which used the same endpoints (primary efficacy of composite of stroke, systemic embolism, cardiovascular/unexplained death, and safety). ResultsCAP included 566 patients with an average follow-up of 50.1 months (2,293 patient-years), and CAP2 included 578 patients with an average follow-up of 50.3 months (2,227 patient-years). CAP2 patients were significantly older and had higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores (4.51 vs. 3.88; p < 0.001). Procedural success was similar in both (94%). The primary composite endpoint occurred at a rate of 3.05 per 100 patient-years in CAP and 4.80 per 100 patient-years in CAP2; events contributing to this endpoint were most commonly cardiovascular/unexplained death (1.69 per 100 patient-years for CAP and 2.92 per 100 patient-years for CAP2). Hemorrhagic stroke was significantly less than ischemic stroke (0.17 per 100 patient-years in CAP and 0.09 per 100 patient-years in CAP2), and total stroke rates were significantly less than predicted by CHA2DS2-VASc score (78% reduction with CAP, 69% reduction with CAP2). ConclusionsThese registries, which contain the longest and largest follow-up data of patients with the Watchman device, support LAAC as a safe and effective therapy for long-term anticoagulation in patients with nonvalvular atrial fibrillation, and document the lowest rate of hemorrhagic stroke identified in this population.

Cost-Effectiveness of Left Atrial Appendage Closure for Stroke Reduction in Atrial Fibrillation: Analysis of Pooled, 5-Year, Long-Term Data.

BackgroundRecent publications reached conflicting conclusions about the cost‐effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost‐effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long‐term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long‐Term Warfarin) trials.Methods and ResultsA Markov model was constructed from a US payer perspective with a lifetime (20‐year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5‐year data. Warfarin and NOAC inputs were derived from published meta‐analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost‐effective relative to warfarin by year 7 ($48 674/quality‐adjusted life‐year) and dominant (more effective and less costly) by year 10. LAAC became cost‐effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality‐adjusted life‐years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost‐effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively.ConclusionsUsing pooled, 5‐year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost‐effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Propensity-Matched Comparison of Oral Anticoagulation Versus Antiplatelet Therapy After Left Atrial Appendage Closure With WATCHMAN

ObjectivesIn this propensity-matched analysis of post–left atrial appendage closure antithrombotic therapy, the safety and effectiveness of oral anticoagulation (OAC) and antiplatelet therapy (APT) were compared. BackgroundLeft atrial appendage closure with the WATCHMAN device is an alternative to OAC in patients with nonvalvular atrial fibrillation, who are at high bleeding risk. Initial trials included 45 days of post-implantation OAC, but registry data suggest that APT may suffice. MethodsPatients from the PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), CAP (Continued Access to PROTECT-AF), CAP2 (Continued Access to PREVAIL), ASAP (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology), and EWOLUTION (Registry on WATCHMAN Outcomes in Real-Life Utilization) trials receiving either OAC or APT post-implantation were matched and compared for nonprocedural bleeding and stroke or systemic thromboembolism over 6 months following implantation. Each patient on APT was matched with 2 patients on OAC, with propensity scores derived from age, sex, congestive heart failure, hypertension, diabetes, prior transient ischemic attack or stroke, peripheral vascular disease, left ventricular ejection fraction, renal impairment, and different atrial fibrillation subtypes. ResultsThe cohort on OAC (n = 1,018; 95% receiving warfarin and 5% receiving nonwarfarin OAC) was prescribed 45-day OAC post-implantation (92% also received single APT), followed by 6-month single or dual APT. The cohort on APT (n = 509; 91% receiving dual APT and 9% receiving single APT) received APT for variable durations. Six-month freedom from nonprocedural major bleeding was similar (OAC, 95.7%; APT, 95.5%; p = 0.775) despite more early bleeds with OAC. Freedom from thromboembolism beyond 7 days was similar between groups (OAC, 98.8%; APT, 99.4%; p = 0.089). However, device-related thrombosis was more frequent with APT (OAC, 1.4%; APT, 3.1%; p = 0.018). ConclusionsAfter left atrial appendage closure with the WATCHMAN, although device-related thrombosis was more common with APT, both APT and OAC strategies resulted in similar safety and efficacy endpoints.

Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

In patients with atrial fibrillation, left atrial appendage closure with the Watchman device prevents thromboembolism from the left atrial appendage; however, thrombus may form on the left atrial face of the device, and then potentially embolize. Herein, we studied the incidence, predictors, and clinical outcome of device-related thrombus (DRT) using a large series of clinical trial cohorts of patients undergoing Watchman implantation. We studied the device arms of 4 prospective Food and Drug Administration trials: PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) (n=463); PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) (n=269); CAP (Continued Access to PROTECT AF registry) (n=566); and CAP2 (Continued Access to PREVAIL registry) (n=578). Surveillance transesophageal echocardiographs were performed at 45 days and 12 months in all patients, and also at 6 months in the randomized control trials. We assessed both the incidence of DRT during these transesophageal echocardiographs (and other unscheduled transesophageal echocardiographs), and clinical outcomes of postprocedure stroke or systemic embolism (SSE) and adjusted for CHA2DS2-VASC and HAS-BLED scores. Of 1739 patients who received an implant (7159 patient-years follow-up; CHA2DS2-VASc=4.0), DRT was seen in 65 patients (3.74%). The rates of SSE with and without DRT were 7.46 and 1.78 per 100 patient-years (adjusted rate ratio, 3.55; 95% confidence interval [CI], 2.18-5.79; P<0.001), and ischemic SSE rates were 6.28 and 1.65 per 100 patient-years (adjusted rate ratio, 3.22; 95% CI, 1.90-5.45, P<0.001). On multivariable modeling analysis, the predictors of DRT were as follows: history of transient ischemic attack or stroke (odds ratio [OR], 2.31; 95% CI, 1.26-4.25; P=0.007), permanent atrial fibrillation (OR, 2.24; 95% CI, 1.19-4.20; P=0.012); vascular disease (OR, 2.06; 95% CI, 1.08-3.91; P=0.028); left atrial appendage diameter (OR, 1.06 per mm increase; 95% CI, 1.01-1.12; P=0.019); left ventricular ejection fraction (OR, 0.96 per 1% increase; 95% CI, 0.94-0.99; P=0.009). DRT and SSE both occurred in 17 of 65 patients (26.2%). Of the 19 SSE events in these patients with DRT, 9 of 19 (47.4%) and 12 of 19 (63.2%) occurred within 1 and 6 months of DRT detection. Conversely, after left atrial appendage closure, most SSEs (123/142, 86.62%) occurred in patients without DRT. After left atrial appendage closure with Watchman, DRT (≈3.7%) is not frequent but, when present, is associated with a higher rate of stroke and systemic embolism.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials

BackgroundThe PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. ObjectivesThe final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. MethodsPREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. ResultsFor the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). ConclusionsThese 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441)

Efficacy and Safety of the WATCHMAN Left Atrial Appendage System for Stroke Prevention in Chinese Patients with Nonvalvular Atrial Fibrillation: A Single-center, Prospective, Observational Study.

Background:In patients with nonvalvular atrial fibrillation (NVAF), embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. The WATCHMAN LAA Occlusion Device has been shown to be noninferior to conventional oral anticoagulation with warfarin for stroke prevention in patients with NVAF. This study aimed to evaluate the procedural feasibility, safety and 12-month outcomes of the WATCHMAN LAA Occlusion Device in NVAF patients with high risk for stroke in China.Methods:The clinical data of 106 NVAF patients, who were consecutively underwent LAA closure with the WATCHMAN Device between April 2014 and May 2015, were collected. Patients were followed up at 1, 3, 6, and 12 months after discharge. A transesophageal echocardiograph was performed at 45 days after implantation and repeated in case of an unexpected event during the follow-up period.Results:This study included 106 NVAF patients with a mean age of 64.2 ± 8.6 years (ranging from 50 to 88 years), and the mean CHA2DS2-VASc score of all patients was 3.6 ± 1.6 (ranging from 2 to 9). Among those 106 NVAF patients, 100 (94.3%) patients were implanted with the device successfully. The procedural success rate was 94.3% (100/106), and the occlusion rate was 100.0% (100/100). There were one tamponade, one ischemic stroke, and eight minor pericardial effusions during hospitalization. During 12-month follow-up period, two patients developed a thrombus layer on the device that resolved with additional anticoagulation: one with visible device-thrombus experienced transient ischemic stroke, and one had a hemorrhagic stroke. There were no deaths in this study. The overall survival rate was 100.0%, and nonmajor adverse event rate was 95.0% (95/100). In this study, the expected annual rate of ischemic stroke risk in these patients according to the CHA2DS2-VASc score was 4.0%, while the observed ischemic stroke rate was 2.0% per year.Conclusions:LAA closure with the WATCHMAN Device was feasible, efficient, and safe for NVAF to prevent the accidence of stroke in Chinese patients. During the 12-month follow-up period, the observed ischemic stroke rate (2.0% per year) in our study was lower than the predicted annual stroke risk (4.0%) using the CHA2DS2-VASc score.

Left atrial appendage closure: therapeutic option or solution?

Atrial fibrillation (AF) is the most common type of arrhythmia. AF increases the risk of thromboembolic complications including stroke. Stroke in patients with AF is more severe compared with patients with sinus rhythm. Long-term oral anticoagulant therapy (OAT) is widely used in a large population of patients with AF to prevent arterial thromboembolic events, such as stroke and systemic embolism. However, it is well established that OAT significantly increases the risk of bleeding. Percutaneous left atrial appendage closure (LAAC) is an option for stroke prophylaxis in patients with nonvalvular AF and high risk of bleeding. This paper provides an overview of recent studies that address the effectiveness and safety of LAAC using the Amplatzer Cardiac Plaque and Watchman Left Atrial Appendage System. LAAC provides a superior choice of treatment in patients with absolute contraindication of systemic OAT, in cases of refusal of systemic OAT by a patient, and as a complementary treatment to anticoagulation in patients with embolic events despite adequate OAT. LAAC should be also considered as a therapeutic option for patients with high thromboembolic risk and very high bleeding risk on the basis of individual risk/benefit evaluation for OAT vs. alternative methods of treatment. In general, LAAC becomes more attractive with increasing thromboembolic risk. There is a need for further studies to address the question of whether LAAC is actually the best method for preventing thromboembolism for patients with moderate/high thromboembolic risk and relatively low bleeding risk, to determine the optimum antithrombotic or antiplatelet therapy in patients who underwent LAAC, as well as to conduct direct comparative analysis of LAAC and the use of new oral anticoagulant drugs (NOAC).

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial)

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.

Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF: Warfarin Versus NOACs Versus LAA Closure

BackgroundLeft atrial appendage closure (LAAC) and nonwarfarin oral anticoagulants (NOACs) have emerged as safe and effective alternatives to warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF). ObjectivesThis analysis assessed the cost-effectiveness of warfarin, NOACs, and LAAC with the Watchman device (Boston Scientific, Marlborough, Massachusetts) for stroke risk reduction in patients with nonvalvular AF at multiple time points over a lifetime horizon. MethodsA Markov model was developed to assess the cost-effectiveness of LAAC, NOACs, and warfarin from the perspective of the Centers for Medicare & Medicaid Services over a lifetime (20-year) horizon. Patients were 70 years of age and at moderate risk for stroke and bleeding. Clinical event rates, stroke outcomes, and quality of life information were drawn predominantly from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) 4-year data and meta-analyses of warfarin and NOACs. Costs for stroke risk reduction therapies, treatment of associated acute events, and long-term care following disabling stroke were presented in 2015 U.S. dollars. ResultsRelative to warfarin, LAAC was cost-effective at 7 years ($42,994/quality-adjusted life-years [QALY]), and NOACs were cost-effective at 16 years ($48,446/QALY). LAAC was dominant over NOACs by year 5 and warfarin by year 10. At 10 years, LAAC provided more QALYs than warfarin and NOACs (5.855 vs. 5.601 vs. 5.751, respectively). In sensitivity analyses, LAAC remained cost-effective relative to warfarin ($41,470/QALY at 11 years) and NOACs ($21,964/QALY at 10 years), even if procedure costs were doubled. ConclusionsBoth NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs. The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF.

Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation: A Patient-Level Meta-Analysis

BackgroundThe risk-benefit ratio of left atrial appendage closure (LAAC) versus systemic therapy (warfarin) for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation (NVAF) requires continued evaluation. ObjectivesThis study sought to assess composite data regarding left atrial appendage closure (LAAC) in 2 randomized trials compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in patients with nonvalvular AF. MethodsOur meta-analysis included 2,406 patients with 5,931 patient-years (PY) of follow-up from the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device In Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials, and their respective registries (Continued Access to PROTECT AF registry and Continued Access to PREVAIL registry). ResultsWith mean follow-up of 2.69 years, patients receiving LAAC with the Watchman device had significantly fewer hemorrhagic strokes (0.15 vs. 0.96 events/100 patient-years [PY]; hazard ratio [HR]: 0.22; p = 0.004), cardiovascular/unexplained death (1.1 vs. 2.3 events/100 PY; HR: 0.48; p = 0.006), and nonprocedural bleeding (6.0% vs. 11.3%; HR: 0.51; p = 0.006) compared with warfarin. All-cause stroke or systemic embolism was similar between both strategies (1.75 vs. 1.87 events/100 PY; HR: 1.02; 95% CI: 0.62 to 1.7; p = 0.94). There were more ischemic strokes in the device group (1.6 vs. 0.9 and 0.2 vs. 1.0 events/100 PY; HR: 1.95 and 0.22, respectively; p = 0.05 and 0.004, respectively). Both trials and registries identified similar event rates and consistent device effect in multiple subsets. ConclusionsIn patients with NVAF at increased risk for stroke or bleeding who are candidates for chronic anticoagulation, LAAC resulted in improved rates of hemorrhagic stroke, cardiovascular/unexplained death, and nonprocedural bleeding compared to warfarin.

How Could Pre-Procedural Imaging Guide Successful Left Atrial Appendage Closure?

REFER TO THE PAGE 211-218 Atrial fibrillation (AF) is the most common sustained arrhythmia and strongly associated with ischemic stroke.1) In patients with AF, the main site of thrombus formation is the left atrial appendage (LAA).2) Autopsy and surgical data have suggested that about 90% of atrial thrombi in AF patients originate from the LAA.3) There are two reasonable ways to prevent ischemic stroke events in patients with AF. The first is maintenance of anticoagulation. The second is to isolate the LAA as a major embolic source from the systemic circulation. Multiple randomized, controlled trials have suggested that oral anticoagulation (OAC) decrease the risk of stroke in patients with AF.4) However, long-term OAC is contraindicated in 14% to 44% of AF patients with risk of stroke.5) Because there are various barriers against maintenance of long-term OAC such as the risk of bleeding, inconvenience of dose adjustments, drug interactions, and restrictions on diet.6) Other novel anticoagulants are also limited by the side effects, and the risk of bleeding from systemic administration of these agents.7) Because the LAA is a separate anatomic structure, it may be relatively easily isolated from systemic circulation by excision or ligation. Recently, less invasive technique using percutaneous transcatheter have been introduced for LAA isolation by occlusion of this anatomical structure with implantable devices.8) The PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) trial was planned to determine whether systemic anticoagulation with warfarin, the most commonly used anticoagulant, could be replaced by LAA closure with a percutaneously positioned device. This final results of the PROTECT AF trial followed up for an accumulated exposure of 1588 patient-years revealed LAA closure with the Watchman device to be non-inferior to systemic anticoagulation with warfarin regarding prevention of stroke, systemic embolism, and cardiovascular death.9) On the basis of these data, LAA closure has been decided a class IIb recommendation in the 2014 ACC/ASA guideline as an alternative strategy to prevent stroke. For this procedure to be accepted as an alternative, there must be a high success rate. Although success rate of the LAA closure is generally high, peri-device leakage of LAA persists due to incomplete closure.9),10) During percutaneous LAA closure for stroke prophylaxis, the geometric variability of the LAA ostium may result in an incomplete seal of the LAA. To understand the technical limitations of LAA closure, it is important to consider the anatomical variations of the LA and LAA geometry. The geometry of LA and LAA, a detailed knowledge of its anatomical characteristics and relationship might be very useful when planning the procedure. As LA and LAA geometry is complex, there are limited available data about the predictors of successful procedure. The anatomical relationship of LAA and interatrial septum (IAS) may affects the success rate of device implantation.11) In this issue, Chung et al.12) introduced 3-dimensional anatomical relation of IAS and LAA orifice as a predictor of peri-device leakage after LAA closure. One of the novel and interesting aspects of this study is that they use new novel analysis program for accurate measurement of 3-dimensional relationship between IAS and LAA orifice and found that 3-dimensional angulation between IAS and LAA significantly associated with development of peri-device leakage after LAA occlusion. In this study, the angle between the IAS plane and the line linking the LAA orifice midline and foramen ovale was measured using 3-dimensional geometric cardiac CT analysis. Measurement of this new parameter can provide more detail geometric information and predict success of the procedure. In addition, it might be helpful to select catheter and to decide the direction of IAS puncture site. This study is the first study that anatomical relationship of IAS and LAA orifice might affect peri-device leakage. However, clinical implication of peri-device leakage after LAA occlusion is unclear. Despite some previous studies suggested that the incomplete LAA occlusion was not associated with cardioembolic stroke event,10) understanding the clinical impact of peri-device leakage would be critical. As the authors commented in the limitation, larger sample size, prospective and long-term follow up data are needed to determine the clinical implication of peri-device leak after LAA occlusion. Despite some limitations, this study results suggested that novel anatomical parameter could be measured by their new software and this parameter is useful to predict peri-device leakage after LAA device closure.

Watchman LAA Closure Device in Patients with AF

This article presents the results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation trial [PROTECT AF; NCT00129545] that compared the Watchman left atrial appendage device with warfarin therapy for patients with atrial fibrillation.

Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection In Patients With Atrial Fibrillation) trial

Background: The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation. Methods and results: Patients (n = 707) with nonvalvular atrial fibrillation and at least 1 risk factor (age >75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n = 463) or continued warfarin (n = 244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy endpoint included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3 ± 1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%–1.30% per year), which met the criteria for noninferiority (probability of noninferiority >0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%–7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%–5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95–2.70). Conclusions: The “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation.

Left Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral Anticoagulation: The ASAP Study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology)

The purpose of this study was to assess the safety and efficacy of left atrial appendage (LAA) closure in nonvalvular atrial fibrillation (AF) patients ineligible for warfarin therapy.The PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that LAA closure with the Watchman device (Boston Scientific, Natick, Massachusetts) was noninferior to warfarin therapy. However, the PROTECT AF trial only included patients who were candidates for warfarin, and even patients randomly assigned to the LAA closure arm received concomitant warfarin for 6 weeks after Watchman implantation.A multicenter, prospective, nonrandomized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥1, who were considered ineligible for warfarin. The primary efficacy endpoint was the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death.The mean CHADS₂ score and CHA₂DS₂-VASc (CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease, age 65 to 74 years, or female sex) score were 2.8 ± 1.2 and 4.4 ± 1.7, respectively. History of hemorrhagic/bleeding tendencies (93%) was the most common reason for warfarin ineligibility. Mean duration of follow-up was 14.4 ± 8.6 months. Serious procedure- or device-related safety events occurred in 8.7% of patients (13 of 150 patients). All-cause stroke or systemic embolism occurred in 4 patients (2.3% per year): ischemic stroke in 3 patients (1.7% per year) and hemorrhagic stroke in 1 patient (0.6% per year). This ischemic stroke rate was less than that expected (7.3% per year) based on the CHADS₂ scores of the patient cohort.LAA closure with the Watchman device can be safely performed without a warfarin transition, and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation. (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ASAP]; NCT00851578).

Quality of Life Assessment in the Randomized PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) Trial of Patients at Risk for Stroke With Nonvalvular Atrial Fibrillation

This study sought to assess quality of life parameters in a subset of patients enrolled in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial. The PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) and CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke, transient ischemic attack, or thromboembolism) score ≥1, a left atrial appendage closure device is noninferior to long-term warfarin for stroke prevention. Given this equivalency, quality of life (QOL) indicators are an important metric for evaluating these 2 different strategies. QOL using the Short-Form 12 Health Survey, version 2, measurement tool was obtained at baseline and 12 months in a subset of 547 patients in the PROTECT AF trial (361 device and 186 warfarin patients). The analysis cohort consisted of patients for whom either paired quality of life data were available after 12 months of follow-up or for patients who died. With the device, the total physical score improved in 34.9% and was unchanged in 29.9% versus warfarin in whom 24.7% were improved and 31.7% were unchanged (p = 0.01). Mental health improvement occurred in 33.0% of the device group versus 22.6% in the warfarin group (p = 0.06). There was a significant improvement in QOL in patients randomized to device for total physical score, physical function, and in physical role limitation compared to control. There were significant differences in the change in total physical score among warfarin naive and not-warfarin naive subgroups in the device group compared to control, but larger gains were seen with the warfarin naive subgroup with a 12-month change of 1.3 ± 8.8 versus -3.6 ± 6.7 (p = 0.0004) device compared to warfarin. Patients with nonvalvular AF at risk for stroke treated with left atrial appendage closure have favorable QOL changes at 12 months versus patients treated with warfarin. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [WATCHMAN PROTECT]; NCT00129545).

Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial Fibrillation

Background— The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation. Methods and Results— Patients (n=707) with nonvalvular atrial fibrillation and at least 1 risk factor (age &gt;75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n=463) or continued warfarin (n=244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy end point included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%–1.30% per year), which met the criteria for noninferiority (probability of noninferiority &gt;0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%–7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%–5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95–2.70). Conclusions— The “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation. Clinical Trial Registration:— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00129545.