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.
In patients with contraindications to warfarin
Most of the published data have been about the efficacy of occlusion devices compared with long-term warfarin therapy. Unfortunately, the population that has not been studied extensively is patients who have contraindications to long-term oral anticoagulation, who would benefit the most from an occlusive device.
The ASA Plavix Feasibility Study (ASAP) focused on this population, specifically those who had a CHADS2 score of 1 or higher and who were considered ineligible for warfarin, to determine whether closure using the Watchman device could be safely performed without a transition period with warfarin.39 After device implantation, trial participants were given clopidogrel for 6 months and aspirin indefinitely. The trial enrolled 150 patients and followed them for a mean of 14.4 (± 8.6) months. In that time, there were four strokes, five pericardial effusions, and six instances of device-related thrombus by transesophageal echocardiography. Three of the strokes were ischemic (1.7% per year), which is a 77% reduction from the expected rate of 7.3% based on the CHADS2 scores of the patient cohort.
These data suggest that implantation of the Watchman device may be appropriate for those who cannot tolerate warfarin even in the short term.
The Lariat system
The Lariat suture delivery device (SentreHeart, Inc., Redwood City, CA) is approved by the US Food and Drug Administration (FDA) for soft-tissue closure and has been used for percutaneous left atrial appendage closure. It uses a magnet-tipped wire that is passed to the epicardial side of the left atrial appendage via pericardial access to meet a second magnet-tipped wire introduced into the appendage via transseptal access. A “lasso” is then advanced over the epicardial guide wire and tightened down around the ostium of the left atrial appendage. This tool facilitates deployment of a nonabsorbable polyester suture, which effectively ligates off the appendage from the rest of the left atrium (Figure 2).40 In theory, the Lariat’s epicardial approach could eliminate the need for short- and long-term anticoagulation, as there would be no foreign body left within the heart.
In an initial cohort of 89 patients in Poland,41 the investigators reported a 96% closure rate as determined by transesophageal echocardiography immediately after the procedure. At 1-year follow-up, there was 98% complete closure, including cases of incomplete closure detected earlier.41 Adverse events were limited, with only two cases of severe pericarditis, two strokes, and one pericardial effusion. These results were replicated in the United States in a cohort of 25 patients, with a 100% closure rate and no stroke events.42
There have been three published case reports of left atrial clot formation after successful left atrial appendage ligation using the Lariat device.43–45 These experiences further emphasize that closure does not necessarily confer instant stroke prevention, and there remains a need to investigate the need for routine imaging and possibly periprocedural anticoagulation after ligation.
More recently, Pillai et al46 published their initial experience following 71 patients with echocardiograms 3 months after left atrial appendage closure using the Lariat device. They reported leaks in 6 of the 71 patients; five of the leaks were successfully closed using the Amplatzer Septal Occluder, and one was closed with a repeat Lariat procedure.
Although the Lariat system has been used in more than 2,000 patients worldwide (SentreHeart, personal communication), there has been no published systematic comparison between it and oral anticoagulation to date.
AN EMERGING OPTION
Established guidelines help determine which patients with atrial fibrillation should receive oral anticoagulant therapy. For patients who have absolute contraindications to oral anticoagulants or who are undergoing cardiac surgery, surgical ligation of the left atrial appendage is an option. But for those with contraindications to oral anticoagulation in both the short term and the long term, there is a growing body of evidence suggesting that a percutaneous intervention is at least noninferior to—and in some cases is superior to—warfarin. Figure 3 shows our recommendations for the steps to determine which patients would be most appropriate to consider for left atrial appendage closure.
Holmes et al47 propose that we may now have enough evidence to support an expedited regulatory approval process of these occlusion devices. But there are still a number of areas in which further investigation is clearly needed before left atrial appendage occlusion devices can be widely adopted.
The trials discussed above had specific inclusion and exclusion criteria, and therefore, although they support percutaneous intervention, the generalizability of their results remains in question. Indeed, the patients in PROTECT-AF36 had an average CHADS2 score of only 2.2. This study also included only patients who were able to tolerate both aspirin and clopidogrel simultaneously for a significant amount of time. Hence, one cannot assume the results would be the same in patients who have strict contraindications to warfarin or any target-specific oral anticoagulant. Concern regarding the generalizability of the conclusions from PROTECT-AF and PREVAIL has led to mixed votes (three assessments to date) from the FDA Circulatory Device Panel.48
In an encouraging review of cases, Gafoor et al49 reported safe and efficacious occlusion in octogenarians using the devices mentioned above. These patients often pose the greatest challenge in initiating long-term anticoagulation because of the many drug-drug interactions and the risk of intracranial hemorrhage secondary to falls.
Further, while occlusion devices would clearly be useful for patients in whom traditional oral anticoagulation is not an option, the newer oral anticoagulants might complicate the picture somewhat. As shown by Ruff et al,21 the risk-benefit ratio of these target-specific oral anticoagulants is quite favorable and by some measurements is superior to that of warfarin. Could there be a group of patients who cannot take warfarin but could instead do well on one of the newer anticoagulants, thus alleviating the need for percutaneous intervention? As the newer oral anticoagulants become more commonly used, the cost-benefit analysis of implanting an occlusion device could shift.
Lastly, in this era of high-value medical care, one must consider the cost-effectiveness of these novel interventions. As with any new technology, the up-front cost of implantation is certainly greater than that of warfarin therapy. If device implantation can prevent a hospitalization from a major bleed secondary to warfarin use or prevent a catastrophic stroke due to untreated atrial fibrillation, then the cost-benefit analysis may be tipped in the other direction. As these devices become more widely available and physicians have more experience implanting them, the costs will likely decrease.
As with oral anticoagulation therapy, all interventions, whether surgical or percutaneous, carry a risk of bleeding and stroke. There remains no substitute for frank and clear discussions between the physician and patient regarding the risks and benefits of each approach.
While a growing body of evidence surrounds left atrial appendage occlusion devices, many questions remain. Notably, could these devices be used in patients who can tolerate oral anticoagulants? And if so, which subgroups would benefit most? Does occlusion or ligation of the left atrial appendage affect electrical connections between it and the left atrium, thereby lowering the burden of atrial fibrillation?
We expect that continued investigation of and experience with left atrial appendage closure devices will position them one day as a viable and equal option for preventing stroke in patients with atrial fibrillation.
