The left atrial appendage (LAA) is found in the left wall of the primary atrium, and is formed during the fourth week of embryonic development. It has developmental, structural, and physiological characteristics distinct from the left atrium proper. The LAA lies within the confines of the pericardium in close relation to the free wall of the left ventricle and thus its emptying and filling may be significantly affected by left ventricle function. The physiological properties and anatomical structure of the LAA render it ideally suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. These properties include the position of the LAA high in the body of the left atrium; the increased elasticity of the LAA compared to the left atrium proper; the high concentrations of atrial natriuretic factor (ANF) granules contained within the LAA; and the neuronal configuration of the LAA.
The LAA is the site most commonly associated with thrombus formation, particularly in patients with non-valvar atrial fibrillation. The pathogenesis of LAA thrombus is not fully understood, but the tendency of thrombus formation in the LAA is likely to result from stagnation within the long, blind-ended tissue banded-pouch. LAA dysfunction is also likely to be related in part to a myopathic process that results in atrial fibrillation or that occurs as a result of the atrial fibrillation itself (an atrial fibrillation-induced myopathy). LAA function in patients with atrial flutter is reported to be associated with a regular pattern of LAA emptying and significantly higher peak emptying velocities than in patients with atrial fibrillation, in keeping with the lower incidence of thromboembolism in atrial flutter.
Atrial fibrillation is the most common sustained arrhythmia, increases with age, and presents with a wide spectrum of symptoms and severity. Paroxysmal, persistent, and permanent forms require very individualized approaches to management. New information about electrical and anatomic remodeling emphasizes the importance of time-related thrombogenicity and progressive interference with mechanical function of the atria and ventricles. The most important aspect of diagnosis is risk stratification with respect to risk of thromboembolism.
The occlusion, ablation or surgical removal of the LAA may help to reduce the risk of thromboembolism but this may result in undesirable physiological aftereffects such as increased risk of reduced atrial compliance and a reduced capacity for ANF secretion in response to pressure and volume overload.
Stroke prevention in atrial fibrillation is an important consideration. Treatment with anticoagulant medications is the most common approach to stroke prevention. The majority of embolic strokes originate from the left atrial appendage; therefore, left atrial appendage occlusion devices offer a non-pharmacologic alternative to anticoagulant medications.
Stroke is the most serious complication of atrial fibrillation. The estimated incidence of stroke in non-treated patients with atrial fibrillation is 5% per year. Stroke associated with atrial fibrillation is primarily embolic in nature, tends to be more severe than the typical ischemic stroke, and causes higher rates of mortality and disability. As a result, stroke prevention is one of the main goals of atrial fibrillation treatment.
Stroke occurs primarily as a result of thromboembolism from the left atrium. The lack of atrial contractions in atrial fibrillation leads to blood stasis in the left atrium, and this low flow state increases the risk for thrombosis. The area of the left atrium with the lowest blood flow in atrial fibrillation, and, therefore, the highest risk of thrombosis, is the left-atrial appendage (LAA). It has been estimated that 90% of left-atrial thrombi occur in the LAA.
The main treatment for stroke prevention in atrial fibrillation is anticoagulation, which has proven efficacy. Warfarin is the predominant agent in clinical use. A number of newer anticoagulant medications have recently received U.S. Food and Drug Administration (FDA) approval for this indication and have demonstrated noninferiority to warfarin in clinical trials. While anticoagulation is effective for stroke prevention, there is an increased risk of bleeding. Also, warfarin requires frequent monitoring and adjustments, as well as lifestyle changes. Dabigatran does not require monitoring. However, unlike warfarin, the antithrombotic effects of dabigatran are not reversible with any currently available hemostatic drugs.
Surgical removal, or exclusion, of the LAA is often performed in patients with atrial fibrillation who are undergoing open heart surgery for other reasons. Percutaneous LAA closure devices have been developed as a nonpharmacologic alternative to anticoagulation for stroke prevention in atrial fibrillation. The devices may prevent stroke by occluding the LAA, thus preventing thrombus formation.
Several versions of LAA occlusion devices have been developed. The WATCHMAN® left atrial appendage system (Boston Scientific, Maple Grove, MN) is a self-expanding nickel titanium device. It has a polyester covering and fixation barbs for attachment to the endocardium. Implantation is performed percutaneously through a catheter delivery system, utilizing venous access and transseptal puncture to enter the left atrium. Following implantation, patients are anticoagulated with warfarin or alternate agents for approximately 1-2 months. After this period, patients are maintained on antiplatelet agents (i.e., aspirin and/or clopidogrel) indefinitely. The Lariat® Loop Applicator is a suture delivery device that is intended to close a variety of surgical wounds in addition to left atrial appendage closure. The Cardioblate® closure device developed by Medtronic Corp. is currently being tested in clinical studies. The Amplatzer® cardiac plug (St. Jude Medical, Minneapolis, MN), is FDA-approved for closure of atrial septal defects but has not received FDA approval for LAA closure device. The Percutaneous LAA Transcatheter Occlusion (PLAATO) device (eV3, Plymouth, MN) has also been evaluated in research studies but has not received FDA approval.
There are currently no percutaneous LAA closure devices with FDA approval. The WATCHMAN® device was considered for FDA approval in 2009 based on the results of the Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients with Atrial Fibrillation (PROTECT-AF) randomized controlled trial. While the FDA advisory panel for this topic voted in favor of approval, the FDA did not grant final approval after concluding that further studies of efficacy and safety were necessary.
At least two other devices, referred to earlier, have been studied for left atrial appendage occlusion, but are not approved in the U.S. for percutaneous closure of the left atrial appendage. The Lariat® Loop Applicator device (SentreHEART, Inc, Redwood City, CA) is a suture delivery system that received 510(k) marketing clearance from the FDA in 2006. The intended use is to facilitate suture placement and knot tying in surgical applications where soft tissues are being approximated or ligated with a pre-tied polyester suture. The Amplatzer Amulet® device (St. Jude Medical, Plymouth, MN) has a CE approval in Europe for left atrial appendage closure, but is not currently approved in the U.S. for any indication.