Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation

Purpose of Review

Anticoagulant therapy effectively reduces the incidence of stroke in patients with atrial fibrillation (AF) but is underutilized and frequently contraindicated. The left atrial appendage (LAA) is the primary site of thrombus formation in AF patients. Surgical and percutaneous appendage closure has been evaluated as a site-specific therapy to reduce systemic thromboembolism.

Recent Findings

We will review LAA closure techniques, examine recent outcome data, and discuss the indications for, and potential complications of, each approach.

Summary

Randomized data examining surgical LAA closure and epicardial closure with the LARIAT device are lacking. High quality, randomized data supports the efficacy of the WATCHMAN device for stroke prevention in patients with AF.

     

Percutaneous Left Atrial Appendage Ligation for Stroke Prevention in Atrial Fibrillation

Prevention of thromboembolic complications in atrial fibrillation remains a tremendous clinical challenge. Knowledge that the left atrial appendage (LAA) is the most common anatomical origin of cardioembolic strokes1 has been the main motivation to develop clinical and procedural strategies to exclude the LAA from the circulation, either surgically or percutaneously. This review discusses the rationale behind these strategies, their relative merits, and future prospects for LAA exclusion strategies.     

Percutaneous Left Atrial Appendage Closure With the Watchman Device: Long-Term Results Up to 5 Years

ObjectivesThe aim of this study was to evaluate long-term outcomes in patients with atrial fibrillation undergoing percutaneous left atrial appendage (LAA) closure with the Watchman device.BackgroundAtrial fibrillation is one of the most common arrhythmias and is associated with a high risk for cardioembolic ischemic events, most notably stroke. Percutaneous LAA closure is an alternative to oral anticoagulation, because most thrombi originate from the LAA.MethodsAll consecutive patients with minimum CHADS₂ or CHA₂DS₂-VASc scores of 1 who underwent LAA closure with the Watchman device between June 2006 and August 2010 were eligible. Follow-up examinations were performed after 45 days to 3 months, 6 months, and 1 year and thereafter annually. Afterward, alternating office visits and telephone follow-up were performed every 6 months.ResultsA total of 102 patients were included. The mean age was 71.6 ± 8.8 years, and 37.3% were women. The mean CHADS₂ and CHA₂DS₂-VASc scores were 2.7 ± 1.3 and 4.3 ± 1.7, respectively. Procedural success was achieved in 96.1% of patients. During a mean follow-up period of 3.0 ± 1.6 years, the annual rates of transient ischemic attack, stroke, intracranial hemorrhage, and death were 0.7%, 0.7%, 1.1%, and 3.5%, respectively.ConclusionsLAA closure with the Watchman device is safe and feasible for stroke protection in patients with atrial fibrillation. Low ischemic events rates demonstrate its effectiveness during long-term follow-up.     

Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)–related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown.ObjectivesThis study sought to compare DOACs with LAAC in high-risk patients with AF.MethodsLeft Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHA₂DS₂-VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat.ResultsA high-risk patient cohort (CHA₂DS₂-VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients.ConclusionsAmong patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944)     

Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy : The PREVAIL Trial

Background

In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified.

Objectives

The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy.

Methods

This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS₂ (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed.

Results

At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days’ postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: –0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small.

Conclusions

In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days’ post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.     

The clinical impact of incomplete left atrial appendage closure with the watchman device in patients with atrial fibrillation A PROTECT AF (percutaneous closure of the left Atrial appendage versus warfarin therapy for prevention of stroke in patients with

Objectives The purpose of this study was to investigate the frequency and clinical impact of incomplete left atrial appendage (LAA) sealing and consequent peri-device residual blood flow in patients undergoing percutaneous LAA closure with the Watchman device (Atritech,Inc.,Plymouth,Minnesota).Background During percutaneous LAA closure for stroke prophylaxis,the geometric variability of the LAA ostium may result in an incomplete seal of the LAA.On the one hand,this could enhance thrombus formation and embolization of thrombi around the device into the circulation;on the other hand,the relatively small size of these leaks may preclude clinically relevant embolizations.Methods Patients randomly assigned to device implantation in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial were analyzed.Transesophageal echocardiography was performed at 45 days,6 months,and 12 months.Per the study protocol,patients discontinued warfarin therapy if the 45-day Transesophageal echocardiogram revealed either minimal or no peri-device flow (jet 5 mm width).The impact of peri-device flow severity,defined as minor,moderate,or major (< 1 mm,1 mm to 3 mm,> 3 mm,respectively) on the composite primary efficacy endpoint (stroke,systemic embolism,and cardiovascular death) is expressed as hazard ratio (HR) with 95 % confidence interval (CI).Results Transesophageal echocardiography follow-up revealed that 32.0% of implanted patients had at least some degree of peri-device flow at 12 months.The HR of the primary efficacy endpoint per 1 mm larger per-device flow was 0.84 (95% CI:0.62 to 1.14;P=0.256).Compared to patients with no peri-device flow,the HRs were 0.85 (95 % CI:0.11 to 6.40),0.83 (95 % CI:0.33 to 2.09),and 0.48 (95 % CI:0.11 to 2.09) for minor,moderate,and major peri-device flow,respectively (P=0.798).Compared to patients with no peri-device flow who discontinued warfarin,the HR for patients with any peri-device flow and continuing warfarin was 0.63 (95 % CI:0.14 to 2.71;P=0.530).Conclusions These data indicate that residual peri-device flow into the LAA after percutaneous closure with the Watchman device was common,and is not associated with an increased risk of thromboembolism.This finding should be interpreted with caution as the low event rate decreases the confidence of this conclusion.     

Percutaneous Left Atrial Appendage Closure in a Patient with Diffuse Alveolar Hemorrhaging Associated with Anticoagulant Therapy and Atrial Fibrillation

Diffuse alveolar hemorrhaging (DAH) due to oral anticoagulation (OAC) is a life-threatening condition that leads to severe respiratory failure. There is a clinical dilemma in that OAC-induced DAH often forces the discontinuation of OAC therapy and the administration of high-dose corticosteroids, which increases the risk of stroke and cardiovascular events. We herein report the first case of OAC-induced DAH and atrial fibrillation (AF) in a patient who completely discontinued OAC therapy and high-dose corticosteroids after experiencing percutaneous left atrial appendage (LAA) occlusion. This case suggests that percutaneous LAA closure may aid in the management of OAC-induced DAH and AF.