J. of Cardiovasc. Trans. Res. (2014) 7:458–464 DOI 10.1007/s12265-014-9565-5
Left Atrial Appendage Devices for Stroke Prevention in Atrial Fibrillation Sarah K. Hussain & Rohit Malhotra & John P. DiMarco
Received: 16 January 2014 / Accepted: 7 April 2014 / Published online: 1 May 2014 # Springer Science+Business Media New York 2014
Abstract Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, and stroke prevention remains an integral part of management of AF. Long-term therapy with oral anticoagulants, though effective, has many limitations, and these limitations have encouraged the search for devicebased alternatives. In patients with non-valvular AF, approximately 90 % of thrombi are thought to arise from the left atrial appendage (LAA). The LAA can be obliterated surgically or percutaneously, and this should reduce the incidence of systemic thromboembolic events in AF, ideally without the need for further anticoagulation. We explore the currently available LAA occlusion devices and the evidence behind these devices. Although additional evidence from randomized trials is required to fully characterize the safety and efficacy of all of these devices, LAA occlusion has the potential to offer an attractive alternative for those at high stroke risk but are underprotected because of contraindications to anticoagulant therapy. Keywords Atrial fibrillation . Stroke prevention . Left atrial appendage occlusion devices
“silent” AF [3]. The risk for stroke among patients with nonvalvular AF is 5 % per year, and when transient ischemic attacks (TIAs) and subclinical strokes detected on brain imaging are included, this risk may exceed 7 % per year [4]. The current strategy for stroke prevention in AF revolves around oral anticoagulant agents. Although vitamin K antagonists are effective in preventing thromboembolic events, their use in clinical practice is made difficult by drug and dietary interactions, genetic variability in metabolism, and a high prevalence of bleeding in the AF population. These factors contribute both to difficulties in maintaining target INR values in the therapeutic range and to a general underuse of vitamin K antagonists in these patients [5, 6]. The newer anticoagulants such as dabigatran, rivaroxaban, and apixaban have been shown to be non-inferior, if not superior, to warfarin [7–10]. They have helped overcome some of the drawbacks of warfarin therapy. However, these agents are still associated with potential bleeding complications, high cost, and unlike warfarin; there are no currently available antagonists. For these reasons, device-based therapies for stroke prevention have received considerable recent attention.
Introduction Anatomy of the Left Atrial Appendage Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice [1]. It is a disease of older individuals, affecting up to 15 % of people aged 80 years and older, and its prevalence is expected to increase with the overall aging of the population worldwide [2]. One in every five strokes is attributable to AF, and there is a concern that even more may be associated with subclinical Associate Editor Angela Taylor oversaw the review of this article S. K. Hussain (*) : R. Malhotra : J. P. DiMarco The University of Virginia, Charlottesville, VA, USA e-mail: [email protected]
The left atrial appendage (LAA) is a trabeculated, and often multi-lobed structure, a vestige of the primitive atrium [11]. It is highly contractile in sinus rhythm, but in AF, ineffective and disorganized contraction and diminished blood-flow velocities have been observed. In patients with non-valvular AF, approximately 90 % of thrombi are thought to arise from the LAA [12]. The LAA can be obliterated surgically or percutaneously, and this should reduce the incidence of systemic thromboembolic events in AF. Once occlusion has been accomplished, long-term oral anticoagulation should not be necessary and the risks of bleeding should be reduced.
J. of Cardiovasc. Trans. Res. (2014) 7:458–464
Currently Available LAA Occlusion Devices The Amplatzer® Cardiac Plug The Amplatzer® (AGA Medical Corporation, Plymouth, MN, USA) Cardiac Plug, which was first approved in Europe in 2008, is made from braided nitinol with a polyester patch and consists of a distal lobe that anchors the device in the LAA body by means of fixation hooks (Fig. 1a). The lobe of the device is connected to a proximal disc meant to cover the LAA orifice and induce endocardial occlusion of the LAA mouth. The device is available in eight different sizes, ranging from 16 to 30 mm. Introduction of the device is performed via a transseptal puncture, following which contrast angiography is used to delineate the LAA to determine device selection. Transesophageal echocardiography (TEE) can also assist with sizing of the appendage. The delivery sheath corresponding to the size of the plug is then introduced over a 0.035-in. stiff wire and directed inside the LAA ostium. The use of the inner core wire enables visualization of the device in a tension-free position before release. Alternatively, a 13-F sheath may be used as a default carrier for all device cases and enables simultaneous delivery of the contrast agent for angiography through the transseptal sheath during device sizing. Unsheathing and slowly pushing forward deploy the device and then further retracting the sheath while still gently pushing on the device deploys the proximal disc. The Amplatzer® is retrievable and can be repositioned before release from its pusher cable. For optimal implantation, upsizing of the device by 3–6 mm over the diameter of the LAA neck is recommended to ensure some compression of the lobe. The proximal disc should be pulled slightly inwards at the center of the LAA orifice to give a concave appearance. The recommended antiplatelet therapy after the Amplatzer® implantation is 100 mg aspirin for at least 3 months, and 75 mg clopidogrel daily for at least 1 month [13]. A follow-up TEE assessment at 1–6 months after device
Fig. 1 Transcatheter mechanical left atrial appendage occlusion devices. a The Amplatzer® (AGA Medical Corp, St. Paul, MN, USA) cardiac plug. b The Watchman® device (Atritech Inc., Plymouth, MA, USA) and c the Lariat suture delivery device (SentreHeart Inc., Redwood City, CA, USA)
459
implantation is recommended to detect any residual shunts or thrombus formation. Although routine post-procedural oral anticoagulation is not recommended, it should be considered if thrombus on the proximal disc surface is detected at a follow-up echocardiographic assessment. A second-generation device, the Amplatzer Amulet® left atrial appendage occluder (St. Jude Medical, Saint Paul, MN, USA), has been developed and is premounted on a modified movable core in diameters of 16–34 mm delivered through 12–14-F sheaths [14]. Advantages of this newer version include deeper lobes in larger devices and an increased number of more evenly distributed fixation hooks, potentially resulting in improved safety of implantation. The Amplatzer® occluder is reportedly easy to use and most can be implanted without even TEE guidance. The main concern with these devices has been of device embolization, which, in one study, was reported as high as 6 % in the acute post-operative period [15]. A randomized trial (NCT01118299) comparing the Amplatzer® Cardiac Plug to oral anticoagulation is now recruiting patients, but results are not expected to be available for several years. In a large multicenter observational European study [16, 17], the largest to date, 204 patients with nonvalvular AF were followed to determine procedural success of device deployment and related adverse events and to assess the learning curve, building on a prior European registry from 2011 [13]. In the study, 58 % of patients were in permanent AF, and the mean CHADS2 score of these patients was 2.6. Additionally, 40 % of these patients had experienced either a prior stroke or transient ischemic attack, and 80 % were intolerant or had a contraindication to therapy with warfarin. Device implantation was successful in 96.5 % of patients, as confirmed by TEE assessment and implant closure, defined as absence of flow or a jet with a diameter of 3 mm or more flowing into the LAA, and these results remained consistent out to a follow-up period of 6 months (98.9 %). Serious adverse events were uncommon: pericardial effusion (1.5 %) and device embolization (1.5 %).
460
J. of Cardiovasc. Trans. Res. (2014) 7:458–464
The Watchman® (Atritech, Inc., Plymouth, MA, USA) occlusion device is a nitinol cage [20–27]; the atrial surface of which is lined with a polyethylene terephthalate membrane, which promotes device endothelialization (Fig. 1b). Fixation barbs project from the circumference of the occluder and secure the device position within the LAA. Implantation requires a 14-F venous access and transseptal puncture. Once the transseptal sheath is positioned in the left atrium and the dilator and needle removed, a pigtail catheter is advanced into the LAA. Angiograms are performed with subsequent exchange of the pigtail catheter for a stiff 0.035-in. guidewire. The access sheath is then positioned over the stiff guidewire into the LAA, and the guidewire is removed. Alternatively, after transseptal puncture, a stiff 0.035-in. J-tipped wire can be positioned into the left upper pulmonary vein and the sheath exchanged for the access sheath. Then, the access sheath is slightly withdrawn from the pulmonary vein, and a pigtail catheter advanced into the LAA followed by advancement of the access sheath over the pigtail catheter. The Watchman® device is premounted on a delivery catheter and advanced within this catheter to the tip of the access sheath. The access sheath has a distal marker that assures alignment of the occluder with the distal sheath tip before deployment, as well as three proximal markers according to device size, which is
currently available in sizes of 21–33 mm. After positioning the device with fluoroscopic and TEE assistance, it is released by gradual pullback of the access sheath and delivery catheter. If positioning in the LAA is suboptimal following deployment, it can be partially recaptured into the sheath and redeployed in a slightly modified position. Finally, when in the optimal position, the device is released from the delivery cable (Fig. 2). A device with a diameter approximately 10–20 % larger than the maximal diameter of the LAA ostium should be used. At the end of the procedure, it is important to confirm adequate device sizing. This is done by measuring the degree of diameter shortening of the deployed device as compared with the undeployed device. The optimal is 8–20 % of the undeployed occluder. In addition, protrusion of the device less than 4.2–6.6 mm beyond the LAA ostium is ideal. Once the transseptal puncture is performed, intraprocedural anticoagulation with intravenous heparin is recommended, with a goal-activated clotting time of >200–250 s [20]. The ideal post-operative anticoagulation regimen after implantation is somewhat controversial. Based on PROTECT-AF [20], patients are kept on oral anticoagulation therapy, mainly with warfarin, in addition to 81 mg of aspirin for 45 days after implantation. Following that, if at follow-up, any residual leakage from the LAA is small (a single jet
Left Atrial Appendage Devices for Stroke Prevention in Atrial Fibrillation Sarah K. Hussain & Rohit Malhotra & John P. DiMarco
Received: 16 January 2014 / Accepted: 7 April 2014 / Published online: 1 May 2014 # Springer Science+Business Media New York 2014
Abstract Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, and stroke prevention remains an integral part of management of AF. Long-term therapy with oral anticoagulants, though effective, has many limitations, and these limitations have encouraged the search for devicebased alternatives. In patients with non-valvular AF, approximately 90 % of thrombi are thought to arise from the left atrial appendage (LAA). The LAA can be obliterated surgically or percutaneously, and this should reduce the incidence of systemic thromboembolic events in AF, ideally without the need for further anticoagulation. We explore the currently available LAA occlusion devices and the evidence behind these devices. Although additional evidence from randomized trials is required to fully characterize the safety and efficacy of all of these devices, LAA occlusion has the potential to offer an attractive alternative for those at high stroke risk but are underprotected because of contraindications to anticoagulant therapy. Keywords Atrial fibrillation . Stroke prevention . Left atrial appendage occlusion devices
“silent” AF [3]. The risk for stroke among patients with nonvalvular AF is 5 % per year, and when transient ischemic attacks (TIAs) and subclinical strokes detected on brain imaging are included, this risk may exceed 7 % per year [4]. The current strategy for stroke prevention in AF revolves around oral anticoagulant agents. Although vitamin K antagonists are effective in preventing thromboembolic events, their use in clinical practice is made difficult by drug and dietary interactions, genetic variability in metabolism, and a high prevalence of bleeding in the AF population. These factors contribute both to difficulties in maintaining target INR values in the therapeutic range and to a general underuse of vitamin K antagonists in these patients [5, 6]. The newer anticoagulants such as dabigatran, rivaroxaban, and apixaban have been shown to be non-inferior, if not superior, to warfarin [7–10]. They have helped overcome some of the drawbacks of warfarin therapy. However, these agents are still associated with potential bleeding complications, high cost, and unlike warfarin; there are no currently available antagonists. For these reasons, device-based therapies for stroke prevention have received considerable recent attention.
Introduction Anatomy of the Left Atrial Appendage Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice [1]. It is a disease of older individuals, affecting up to 15 % of people aged 80 years and older, and its prevalence is expected to increase with the overall aging of the population worldwide [2]. One in every five strokes is attributable to AF, and there is a concern that even more may be associated with subclinical Associate Editor Angela Taylor oversaw the review of this article S. K. Hussain (*) : R. Malhotra : J. P. DiMarco The University of Virginia, Charlottesville, VA, USA e-mail: [email protected]
The left atrial appendage (LAA) is a trabeculated, and often multi-lobed structure, a vestige of the primitive atrium [11]. It is highly contractile in sinus rhythm, but in AF, ineffective and disorganized contraction and diminished blood-flow velocities have been observed. In patients with non-valvular AF, approximately 90 % of thrombi are thought to arise from the LAA [12]. The LAA can be obliterated surgically or percutaneously, and this should reduce the incidence of systemic thromboembolic events in AF. Once occlusion has been accomplished, long-term oral anticoagulation should not be necessary and the risks of bleeding should be reduced.
J. of Cardiovasc. Trans. Res. (2014) 7:458–464
Currently Available LAA Occlusion Devices The Amplatzer® Cardiac Plug The Amplatzer® (AGA Medical Corporation, Plymouth, MN, USA) Cardiac Plug, which was first approved in Europe in 2008, is made from braided nitinol with a polyester patch and consists of a distal lobe that anchors the device in the LAA body by means of fixation hooks (Fig. 1a). The lobe of the device is connected to a proximal disc meant to cover the LAA orifice and induce endocardial occlusion of the LAA mouth. The device is available in eight different sizes, ranging from 16 to 30 mm. Introduction of the device is performed via a transseptal puncture, following which contrast angiography is used to delineate the LAA to determine device selection. Transesophageal echocardiography (TEE) can also assist with sizing of the appendage. The delivery sheath corresponding to the size of the plug is then introduced over a 0.035-in. stiff wire and directed inside the LAA ostium. The use of the inner core wire enables visualization of the device in a tension-free position before release. Alternatively, a 13-F sheath may be used as a default carrier for all device cases and enables simultaneous delivery of the contrast agent for angiography through the transseptal sheath during device sizing. Unsheathing and slowly pushing forward deploy the device and then further retracting the sheath while still gently pushing on the device deploys the proximal disc. The Amplatzer® is retrievable and can be repositioned before release from its pusher cable. For optimal implantation, upsizing of the device by 3–6 mm over the diameter of the LAA neck is recommended to ensure some compression of the lobe. The proximal disc should be pulled slightly inwards at the center of the LAA orifice to give a concave appearance. The recommended antiplatelet therapy after the Amplatzer® implantation is 100 mg aspirin for at least 3 months, and 75 mg clopidogrel daily for at least 1 month [13]. A follow-up TEE assessment at 1–6 months after device
Fig. 1 Transcatheter mechanical left atrial appendage occlusion devices. a The Amplatzer® (AGA Medical Corp, St. Paul, MN, USA) cardiac plug. b The Watchman® device (Atritech Inc., Plymouth, MA, USA) and c the Lariat suture delivery device (SentreHeart Inc., Redwood City, CA, USA)
459
implantation is recommended to detect any residual shunts or thrombus formation. Although routine post-procedural oral anticoagulation is not recommended, it should be considered if thrombus on the proximal disc surface is detected at a follow-up echocardiographic assessment. A second-generation device, the Amplatzer Amulet® left atrial appendage occluder (St. Jude Medical, Saint Paul, MN, USA), has been developed and is premounted on a modified movable core in diameters of 16–34 mm delivered through 12–14-F sheaths [14]. Advantages of this newer version include deeper lobes in larger devices and an increased number of more evenly distributed fixation hooks, potentially resulting in improved safety of implantation. The Amplatzer® occluder is reportedly easy to use and most can be implanted without even TEE guidance. The main concern with these devices has been of device embolization, which, in one study, was reported as high as 6 % in the acute post-operative period [15]. A randomized trial (NCT01118299) comparing the Amplatzer® Cardiac Plug to oral anticoagulation is now recruiting patients, but results are not expected to be available for several years. In a large multicenter observational European study [16, 17], the largest to date, 204 patients with nonvalvular AF were followed to determine procedural success of device deployment and related adverse events and to assess the learning curve, building on a prior European registry from 2011 [13]. In the study, 58 % of patients were in permanent AF, and the mean CHADS2 score of these patients was 2.6. Additionally, 40 % of these patients had experienced either a prior stroke or transient ischemic attack, and 80 % were intolerant or had a contraindication to therapy with warfarin. Device implantation was successful in 96.5 % of patients, as confirmed by TEE assessment and implant closure, defined as absence of flow or a jet with a diameter of 3 mm or more flowing into the LAA, and these results remained consistent out to a follow-up period of 6 months (98.9 %). Serious adverse events were uncommon: pericardial effusion (1.5 %) and device embolization (1.5 %).
460
J. of Cardiovasc. Trans. Res. (2014) 7:458–464
The Watchman® (Atritech, Inc., Plymouth, MA, USA) occlusion device is a nitinol cage [20–27]; the atrial surface of which is lined with a polyethylene terephthalate membrane, which promotes device endothelialization (Fig. 1b). Fixation barbs project from the circumference of the occluder and secure the device position within the LAA. Implantation requires a 14-F venous access and transseptal puncture. Once the transseptal sheath is positioned in the left atrium and the dilator and needle removed, a pigtail catheter is advanced into the LAA. Angiograms are performed with subsequent exchange of the pigtail catheter for a stiff 0.035-in. guidewire. The access sheath is then positioned over the stiff guidewire into the LAA, and the guidewire is removed. Alternatively, after transseptal puncture, a stiff 0.035-in. J-tipped wire can be positioned into the left upper pulmonary vein and the sheath exchanged for the access sheath. Then, the access sheath is slightly withdrawn from the pulmonary vein, and a pigtail catheter advanced into the LAA followed by advancement of the access sheath over the pigtail catheter. The Watchman® device is premounted on a delivery catheter and advanced within this catheter to the tip of the access sheath. The access sheath has a distal marker that assures alignment of the occluder with the distal sheath tip before deployment, as well as three proximal markers according to device size, which is
currently available in sizes of 21–33 mm. After positioning the device with fluoroscopic and TEE assistance, it is released by gradual pullback of the access sheath and delivery catheter. If positioning in the LAA is suboptimal following deployment, it can be partially recaptured into the sheath and redeployed in a slightly modified position. Finally, when in the optimal position, the device is released from the delivery cable (Fig. 2). A device with a diameter approximately 10–20 % larger than the maximal diameter of the LAA ostium should be used. At the end of the procedure, it is important to confirm adequate device sizing. This is done by measuring the degree of diameter shortening of the deployed device as compared with the undeployed device. The optimal is 8–20 % of the undeployed occluder. In addition, protrusion of the device less than 4.2–6.6 mm beyond the LAA ostium is ideal. Once the transseptal puncture is performed, intraprocedural anticoagulation with intravenous heparin is recommended, with a goal-activated clotting time of >200–250 s [20]. The ideal post-operative anticoagulation regimen after implantation is somewhat controversial. Based on PROTECT-AF [20], patients are kept on oral anticoagulation therapy, mainly with warfarin, in addition to 81 mg of aspirin for 45 days after implantation. Following that, if at follow-up, any residual leakage from the LAA is small (a single jet
