Left atrial appendage closure: An emerging option in atrial fibrillation when oral anticoagulants are not tolerated
ABSTRACTAtrial fibrillation is associated with a risk of stroke, primarily from embolization of clots that form in the left atrial appendage. This structure has been targeted to reduce stroke risk in patients who have contraindications to oral anticoagulation. This article appraises the current literature describing surgical and percutaneous isolation of the left atrial appendage.
KEY POINTS
- Few well-designed studies of surgical closure have been done.
- The Watchman percutaneous device was shown to be noninferior to warfarin in certain patients. Other closure devices demonstrate similar success, though trials have not compared them with warfarin.
- Occlusion of the left atrial appendage is an emerging option for general internists to be aware of when treating those with atrial fibrillation who cannot tolerate oral anticoagulation.
SURGICAL CLOSURE AS AN ADD-ON TO OTHER PROCEDURES
If the patient is undergoing cardiac surgery for another reason, the surgeon can excise, suture, staple, or clip the left atrial appendage shut at the same time. Closure is recommended as part of valve replacement.8 In a 2008 retrospective study, left atrial appendage closure was successfully performed in 40% of those undergoing the procedure during cardiac surgery, and complete closure occurred more often with excision than with suture exclusion and stapler exclusion.23 A study of patients who underwent ligation of the left atrial appendage during mitral value replacement found that 35% demonstrated incomplete closure as determined by transesophageal echocardiography.24
Newer devices have shown more success. The AtriClip (AtriCure Inc., West Chester, OH) is a self-closing, implantable clip applied epicardially by either an open surgical or a minimally invasive technique.25 Successful closure was confirmed in 60 of 61 patients at 90 days as determined by computed tomography or transesophageal echocardiography, and there were no adverse events related to implantation of the device.25 The TigerPaw system (Terumo Cardiovascular Systems, Ann Arbor, MI)26 is a fastener delivered surgically around the base of the ostium of the left atrial appendage. In an initial trial, 90 days after the procedure, transesophageal echocardiography showed no leaks in any of those who were examined (54 of 60 patients).
Amputation of the left atrial appendage is also considered part of the maze procedure for atrial fibrillation, in which the operator creates multiple small scars in the atria to prevent irregular impulses from being conducted.27
Results of these surgical approaches have been mixed, as incomplete closure or clipping actually increases the risk of left atrial thrombus formation and embolization.28 Moreover, these invasive surgical techniques are associated with significant periprocedural morbidity.29 Because of the high risk of surgical complications, cardiac specialists have sought less invasive percutaneous procedures to manage stroke risk in patients with atrial fibrillation.
PERCUTANEOUS OCCLUSION
One option for closing the left atrial appendage is a percutaneous transseptal approach in which a plug is placed in the opening connecting the appendage to the rest of the atrium.
The PLAATO device
The Percutaneous LAA Transcatheter Occlusion (PLAATO) device (Appriva Medical Inc., Sunnyvale, CA) contains an expandable nitinol-covered cage designed to be placed in the orifice of the left atrial appendage. Over time, tissue grows into the device, entirely isolating the appendage from the rest of the atrium.
In 2002, Sievert et al30 reported using this device in 15 patients. Subsequently, in a nonrandomized trial in patients with contraindications to lifelong anticoagulation, total occlusion was achieved in 108 of 111 patients, with no thrombosis or migration of the device at 6 months. The annual risk of stroke was 2.2%, a reduction in relative risk of 65% based on the CHADS2 score.31
But despite this apparent success, the PLAATO device was discontinued for unspecified commercial reasons.
Amplatzer cardiac plug
Modeled after an atrial septal occluder, the Amplatzer cardiac plug (St. Jude Medical, St. Paul, MN) consists of a lobe and a disk connected by a central waist.
In 2011, Park et al32 published their initial experience implanting this device in patients who either could not tolerate or did not desire long-term anticoagulation. They reported a 96% closure rate (137 of 143 patients), but there were serious complications in 10 patients: 3 with ischemic stroke, 2 with device embolism, and 5 with pericardial effusions.
Urena et al33 reported similar results in 52 patients with absolute contraindications to warfarin, with a 98.1% implantation rate. Patients were then maintained on either single or dual antiplatelet therapy at the discretion of the operator. At 20-month follow-up, there had been one stroke, one transient ischemic attack, and one major bleeding event. The leakage rate was 16.2% as determined by transesophageal echocardiography.
While initial results were promising, a clinical trial comparing this device and optimal medical treatment is currently on hold. Thus, there are no clear data comparing the Amplatzer device with oral anticoagulation.34
The Watchman device
The Watchman device (Boston Scientific, Marlborough, MA), an evolution of the PLAATO device, is a self-expanding nitinol structure with fixation barbs and a polyethylene membrane to protect the atrium-facing side of the device (Figure 1).
A pilot trial reported successful implantation in 66 of 75 patients, though the device was found to migrate after placement in 5 of the first 16 patients using the original device and delivery system. The device was modified, and no further embolization of the device occurred.35
The PROTECT-AF trial (Protection in Patients With Atrial Fibrillation)36 was the first completed and published randomized controlled trial evaluating left atrial appendage closure using a device vs long-term warfarin therapy. This study randomized 707 people with nonvalvular atrial fibrillation from 59 centers worldwide to receive the Watchman device or a control treatment. The study included patients age 18 or older with nonvalvular atrial fibrillation who were able to tolerate warfarin therapy. Patients in the control group received warfarin for the duration of the study and were monitored every 2 weeks for a goal INR of 2 to 3, achieving a therapeutic INR 66% of the time. The device group was also treated with warfarin for 45 days to allow device endothelialization. Warfarin was discontinued if transesophageal echocardiography showed complete closure or significantly decreased flow around the device. Patients in the device group were then treated with aspirin and clopidogrel for 6 months, and then with aspirin indefinitely.
At 1,065 patient-years of follow-up, PROTECT-AF showed that in patients with atrial fibrillation who were candidates for warfarin therapy, percutaneous left atrial appendage closure using the Watchman device reduced the rate of hemorrhagic stroke compared with warfarin and was noninferior to warfarin in terms of all-cause mortality and stroke. A 4-year follow-up to the PROTECT-AF trial found that receiving the Watchman was better than taking warfarin in terms of risk of cardiovascular death, stroke and other systemic embolization, and all-cause mortality. The adverse event rates were 2.3% in the device group and 3.8% in the control group, a 40% relative risk reduction in the Watchman group.37
The PREVAIL trial (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation vs Long-Term Warfarin Therapy) aimed to confirm the safety and efficacy of the Watchman device compared with long-term warfarin therapy.38 The event rate (defined as 7-day occurrence of death, ischemic stroke, systemic embolism, and procedure- or device-related complications requiring major cardiovascular or endovascular intervention) was 2.2%. But the PREVAIL trial was unable to show that the device was noninferior to warfarin in terms of its second primary end point of stroke, systemic embolism, and cardiovascular or unexplained death at 18 months. When performed by physicians who were new to the procedure, the procedure was successful (ie, the device was successfully implanted) in 93.2%; the rate was slightly higher (96.3%) when performed by experienced implanters.
Safety data gathered in PREVAIL in conjunction with demonstrated efficacy from PROTECT-AF suggest that the Watchman device may be a safe and effective alternative to long-term oral anticoagulation in patients with nonvalvular atrial fibrillation.
