In June 2010, Dr. William Nicholson and colleagues at York Hospital became the first hospital in the country to implant a cardiac plug device. Learn more about this technology below. Atrial fibrillation (AF) is the most common arrhythmia encountered in the general population. The prevalence of AF clearly increases with patient age, occurring in greater than 9% of the United States population over the age of 80.1 In treating patients with AF, the goals are mitigating symptoms and stroke prevention. Regardless of whether the treating physician chooses to adopt a rhythm or rate control strategy, the risk of stroke as a result of AF persists. The annual risk of embolization and stroke increases according to concomitant medical conditions. Several stratification methods are available for calculating risk, with the most common being the CHADS2 score. Patients are given 1 point for the presence of each of the following: history of Congestive heart failure, Hypertension, Age greater than 75, Diabetes mellitus; and 2 points for a previous ischemic Stroke or TIA. While all patients must be individually assessed clinically, it is generally felt that patients with a CHADS2 score of 2 or more benefit from stroke prevention with warfarin therapy.2,3 While warfarin therapy has clearly been shown to be effective in reducing the risk of stroke in patients with AF, the major risk of bleeding often limits its clinical utility. Several risk calculators have been developed to estimate a patient’s likelihood of experiencing a major bleed while on warfarin. Even patients in the lowest risk category have a 1.5% incidence of major bleeding per year, and this incidence rises to 6% and greater than 25% in patients with intermediate and high risk profiles, respectively.4 While the danger of major bleeding with warfarin treatment poses a risk to patients with AF, it is estimated that at least 20% of patients with AF needing stroke prophylaxis have an absolute contraindication precluding the use of anticoagulation.5 When considering the large population of patients placed at risk of major bleeding with warfarin and the risk of stroke in patients who are not candidates for warfarin, alternative methods of stroke prophylaxis are needed. When considering patients with nonvalvular AF, the most common origin for a clot to form and subsequently embolize is the left atrial appendage (LAA). This blind pouch or cul-de-sac creates a stagnant pool of blood in AF and is felt to be the source of clot formation in AF, as exemplified in Figure 1, in greater than 90% of ischemic strokes. Alternatives to anticoagulation treatment for stroke prophylaxis have focused on ligation, amputation and occlusion of the appendage. While surgical ligation would seem to be an effective means of eliminating the LAA as a potential source for thrombus formation, it is fraught with several issues. First, amputation or ligation of the appendage usually requires open surgery, and as such it is usually reserved as an adjunct to an already indicated open-heart operation. Additionally, a recent transesophageal echocardiography (TEE) study from the Cleveland Clinic evaluated the effectiveness of amputation or ligation after surgery. A residual stump of >1 cm, a persistent patent LAA, or continued flow into the LAA were considered to be unsuccessful closures.6 Only 40% of all patients met criteria for successful closure, with excision being the most effective surgical technique with only a 73% rate of effective closure. Less invasive techniques for appendage occlusion have been pursued in place of surgical excision. Two devices, the PLAATO and WATCHMAN systems, have been studied in clinical trials with encouraging results. The PLAATO system (ev3 Endovascular, Inc., Plymouth, MN) was evaluated in a feasibility trial in the United States and Europe with effective rates of closure (98%).7 However, the system is not yet commercially available and thus did not enter the general clinical arena. The WATCHMAN device (Atritech, Inc., Plymouth, MN) is a similar LAA occlusive system delivered via a percutaneous approach. The PROTECT-AF trial evaluated the efficacy of this system as compared to warfarin therapy in patients with a CHADS2 score of 1 or more. Device implantation was successful in 91% of patients, and the device arm did reach the non-inferiority endpoint compared to anticoagulation therapy.8 However, due to some concerns with the trial, including the low number of patients enrolled in the trial, the FDA mandated that another randomized trial be performed to gain approval. As such, there is currently no clinically available LAA occlusion device available in the US. AGA Medical Corporation is in the process of evaluating a new cardiac plug system designed for percutaneous transcatheter occlusion of the LAA. The Amplatzer cardiac plug (AGA Medical Corporation, Plymouth, MN) represents the next generation of left atrial appendage closure devices (Figure 2). The system consists of a lobe designed to conform to the inner wall of the LAA requiring only a 10 mm depth for deployment. The lobe is attached to a disc with an articulating waist that allows the disc to self orient. The disc is designed to cover the orifice of the LAA to provide apposition against the chamber wall under gentle tension from the anchored lobe. The United States feasibility trial was recently commenced. In June 2010, we enrolled and implanted the first US patient at our institution in York, Pennsylvania. The feasibility trial is designed to test the safety and feasibility of device implantation. Depending upon the results of the feasibility phase of the trial, efficacy will be assessed as compared to standard anticoagulation therapy. Patients enrolled in the trial must have nonvalvular AF with a CHADS2 score of 2 or greater. Patients are randomized in a 2:1 fashion to either receive the device or continue on standard anticoagulation therapy. After successful implantation, device recipients are assessed at 45 days post implantation with TEE for effective closure of the LAA. If effective closure is achieved, warfarin therapy is discontinued at that time. Patients randomized to receive device implantation have their warfarin discontinued prior to the procedure and are bridged with enoxaparin until the morning of implantation. Implantation is done under general anesthesia with TEE guidance during the procedure. Femoral venous access is gained and a standard transseptal puncture is performed to gain access to the left atrium. Full anticoagulation with intravenous heparin is given following transseptal puncture. A 5 French (Fr) marker pigtail is used to atraumatically enter the LAA and perform angiography in multiple views to assess the appendage size and preferred landing zone for the lobe. TEE imaging of the appendage is used to validate the angiographic measurements. Following appropriate sizing and device choice, the device is prepped in a sterile air-free fashion. The device’s nitinol structure filled with polyester fabric has an attachment microscrew. This allows the device to be connected to a delivery cable, which is then collapsed and loaded into a delivery sheath ranging from 9-12 Fr in size. The device is delivered similar to AGA’s other device systems such as the atrial septal occluder. After exposing the lobe in the landing zone, the device’s stability is assessed with both TEE and fluoroscopy (Figures 3A and 3B). Stabilizing wires secure the lobe into the LAA wall. The atrial disc is then exposed in the body of the left atrium and covers the orifice of the LAA with gentle pressure exerted toward the wall of the left atrium by the neck attachment to the lobe (Figure 3C). When echocardiographic and fluoroscopic criteria are met for adequate closure and stability, the device is released by counterclockwise rotation of the delivery cable (Figure 4). After implantation, the patient is kept overnight for observation in the hospital. A baseline surface echocardiogram is done the following morning to evaluate the device and confirm the absence of a pericardial effusion. Patients are bridged to warfarin with enoxaparin until a therapeutic INR is reached. As described earlier, the device is assessed 45 days following implantation to allow time for endothelial coverage of the left atrial disc. The patient who received the first US implant at our institution met the occlusion criteria on his day 45 TEE and as per the protocol, his anticoagulation was discontinued. The Amplatzer cardiac plug system represents the latest iteration in devices designed to occlude the LAA with the hopes of someday obviating the need for anticoagulation for AF. Following the initial feasibility phase with a target enrollment of 45 patients, plans are set to begin the efficacy phase of the trial.
1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375. 2. Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: How well do randomized trials translate into clinical practice? JAMA 2003;290:2685-2692. 3. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: Results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-2870. 4. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998;105:91-99. 5. Gottlieb LK, Salem-Schatz S. Anticoagulation in atrial fibrillation. Does efficacy in clinical trials translate into effectiveness in practice? Arch Intern Med 1994;154:1945-1953. 6. Kanderian AS, Gillinov AM, Pettersson GB, et al. Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography. J Am Coll Cardiol 2008;52:924-929. 7. Ostermayer SH, Reisman M, Kramer PH, et al. Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high-risk patients with non-rheumatic atrial fibrillation: results from the international multi-center feasibility trials. J Am Coll Cardiol 2005;46:9-14. 8. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-542.Editor’s Note: This article underwent peer review by one or more members of EP Lab Digest’s editorial board. Disclosure: The author discloses that travel expenses for training were covered or reimbursed by the company mentioned in this article. There are no other disclosures to report.