Amplatzer Cardiac Plug

Left Atrial Appendage Occlusion: (LAAO)

Atrial fibrillation (AF) is the commonest cardiac arrhythmia with a prevalence of 0.9% in the general population, increasing to >13% of people over the age of 80.1 As our population ages, the prevalence of AF will continue to rise with significant clinical and economic implications.2 The most feared and catastrophic complication of AF is stroke, which is increased fivefold over an age-matched population in sinus rhythm. This is independent of other factors and mostly secondary to thromboembolic events.3

Proven therapies to reduce AF-associated stroke include oral anticoagulation with vitamin K antagonists, such as warfarin. However, its narrow therapeutic window and large number of drug, dietary, and metabolic interactions make patient response unpredictable and difficult to manage. This is particularly true in older patients who are at increased bleeding and stroke risk. Newer pharmacological agents such as the direct thrombin inhibitor, dabigatran, are promising and show similar stroke protection to warfarin with less significant bleeding.4 Several ongoing studies are examining the potential role of new orally active anti-factor X agents.

Given the problems with available pharmacological therapies there has been an impetus for the development of a device-based solution for AF-associated stroke. Such strategies have focussed on occlusion of the left atrial appendage (LAA). The reason is that this site is predisposed to in-situ thrombus formation and accounts for the origin of 90% of atrial thrombi in patients with non-valvular atrial fibrillation (NVAF). 5-7The LAA, an embryonic remnant of the original LA, is a multi-lobed, trabeculated structure with considerable anatomical variation attached to the LA cavity. In patients with AF it has been found to be larger and with greater dysfunction, which are markers for increased embolic risk.6, 8-10 Also, previous observations have demonstrated that most embolic phenomena were associated with LAA thrombus in patients with AF.11,12

Interest in LAA removal or occlusion dates back to the 1930s and can be safely performed during cardiac surgery either with sutures or staples.13 This is most often performed during valve surgery or during Maze procedures (the creation of left atrial lesion patterns during open heart surgery to eliminate AF), although isolated LAA exclusion via a thoracoscopic approach has been shown to be feasible and safe.14

An alternative, less invasive means of LAA exclusion using endovascular techniques has been developed. Three different devices have been used to date: percutaneous LAA transcatheter occlusion (PLAATO) system, the WATCHMAN system and the Amplatzer cardiac plug. These devices are delivered to the LAA following a percutaneous femoral transvenous approach and transeptal puncture under fluoroscopic and transoesophageal echocardiographic (TOE) guidance.

The first of these was the PLAATO system (ev3, Inc., Plymouth, Minnesota) (Figure 1) consisting of a self-expanding nitinol implant covered with an occlusive ePTFE (expanded polytetrafluoroethylene) membrane.15 Despite initially encouraging results in patients who had contraindications to warfarin device development was halted for financial considerations in December 2006.16,17

The second percutaneous LAA exclusion device is the Watchman Left Atrial Appendage System (Atritech Inc., Plymouth, Minnesota) (Figure 2). The device is a self-expanding nitinol frame structure with fixation barbs and a permeable polyester fabric that covers the atrial side.18

The pivotal clinical trial evaluating this device was the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial.19 This was a multicentre, prospective, non-inferiority, unblinded study of patients with NVAF who were deemed eligible for warfarin therapy. Patients were enrolled in the trial if they had a CHADS2 risk score of 1 or more (ie, at least one of the following: previous stroke or transient ischaemic attack, congestive cardiac failure, diabetes mellitus, hypertension, or were 75 years or older). 707 eligible patients were randomly assigned in a 2:1 ratio to percutaneous closure of the LAA and short term warfarin (45 days) or to long term warfarin (control group, target international normalised ratio 2.0-3.0). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolisation. At 1065 patients-years of follow-up the efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. The device was successfully implanted in 91% of those in whom implantation was attempted and 86% of these patients (at 45 days of follow-up) were able to stop taking warfarin; followed by initially 6 months of aspirin and clopidogrel after randomisation and then long term aspirin monotherapy. For the control group, a therapeutic INR range (2.0-3.0) was achieved 66% of the time. There was a higher rate of adverse safety events in the interventional group than the control group, predominantly a result of peri-procedural complications such as pericardial effusions. As a result of this trial the WATCHMAN device won the recommendations of a US Food and Drug Administration (FDA) advisory panel in April 2009, but is awaiting a further study with more safety and efficacy data before being granted full approval by the FDA.

The third occlusion device, the Amplatzer Cardiac Plug (ACP), is constructed from a nitinol mesh and Dacron and is currently undergoing clinical testing.20-22 It comprises of the lobe, which conforms to the inner structure of the LAA; the waist, which acts as an articulating, compliant connection; and the disc, which covers the LAA orifice (see figure 3, Images 1 &2). The device is fully recapturable and repositionable if necessary. Unlike the WATCHMAN device patients do not require warfarin therapy, but rather a short period of dual antiplatelet therapy followed by long term aspirin once successful LAA occlusion has been proven by a follow-up TOE.

AF significantly increases the risk of stroke and providing safe and effective anticoagulant therapy can be challenging. Closure of the LAA provides an alternative strategy of stroke prophylaxis in patients with NVAF. Routine implantation, however, does not appear warranted, though LAA occlusion may be an option in selected patients with a high risk of bleeding complications from anticoagulation. It should be noted that these warfarin-ineligible patients were excluded in the PROTECT-AF trial. Further larger, adequately powered studies comparing device deployment to optimal anticoagulation are needed to evaluate the long term safety and efficacy of such occlusion devices. This is especially true in patients with higher CHADS2 scores or with a previous transient ischemic attack or ischaemic stroke.


Figure 1: The PLAATO Device

 

Figure 2: WATCHMAN Device

 

Figure 3: Amplatzer Cardiac Plug

 

Image 1: LAA (90deg on transoesophageal echocardiogram)

Image 1: LAA (90deg on transoesophageal echocardiogram)

 

Image 2: Occlusion of the LAA by an Amplatzer cardiac plug (90deg on the transoesophageal echocardiogram)

Image 2: Occlusion of the LAA by an Amplatzer cardiac plug (90deg on the transoesophageal echocardiogram)

Author:

Dr Tim Gattorna
Cardiology Fellow
Royal Perth Hospital, Perth, Australia

Facebook Comments