- Email: [email protected]
Editorial commentary: Percutaneous left atrial appendage closure for stroke prevention
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Available online at www.sciencedirect.com
www.elsevier.com/locate/tcm
Editorial Commentary
Percutaneous left atrial appendage closure for stroke prevention Jacqueline Saw, MD, FRCPC, FACC, FSCAIn Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
“The left atrial appendage: our most lethal human attachment… Johnson WD et al.” The left atrial appendage (LAA) was recognized as a potential harbinger of thrombus with thromboembolic risks since the 1940s, and the first surgical excision of the LAA was reported by Madden in 1949 [1]. In the setting of atrial fibrillation (AF), the LAA undergoes remodeling resulting in larger luminal surface area, smoother endocardial surface, and higher endocardial fibroelastosis, which together with the Virchow triad of events can contribute to thrombus formation [2,3]. Indeed, transesophageal echocardiography (TEE) studies reported that 91% of thrombi in the setting of non-valvular AF were located in the LAA [4]. These thrombi no doubt were implicated as the etiology for the majority of cardioembolic strokes with AF. The stroke-risk with AF is increased on average by 5-fold, with incremental risks that can be estimated and validated with modern risk-scores like CHADS2 or CHA2DS2-VASc scores. However, despite multinational guidelines that endorse the utility of these scores to recommend oral anticoagulation (OAC), approximately 40% of patients at high stroke-risk remain unanticoagulated because of contraindications or intolerance to OAC [5]. Thus, alternative strategies especially local targeted therapy to exclude/ excise the LAA as a potential thromboembolic source has been explored over half a century ago. LAA closure can be achieved by an open-surgical or percutaneous fashion; and percutaneous LAA closure can be performed via an endovascular or an epicardial approach. The first
dedicated percutaneous LAA closure device, PLAATO, was implanted in humans in 2001, but has been removed from the market for commercial reasons. Several percutaneous devices have been developed since, including 3 devices that have received CE Mark approval [WATCHMAN, Amplatzer Cardiac Plug (ACP)/Amulet, Wavecrest], and several more should be approved in the near future. The 2 current leading devices, WATCHMAN and ACP/Amulet, are currently available in 450 countries, and 410,000 of each device has been implanted worldwide. In the United States, the WATCHMAN device received FDA approval on March 13, 2015, and has rapidly been adopted as a stroke preventative therapy in patients who can tolerate warfarin for 45 days post-implant. In other countries, indications for percutaneous LAA closure varies geographically, although many countries are more conservative due to limitations on reimbursement, and tend to only implant these devices in patients at high stroke-risk and have contraindications to OAC. The article by Romero et al. [6] in this issue of the Journal provides a nice overview of the pre-clinical and clinical data on contemporary percutaneous LAA closure devices that are currently available and a few that are in the pipeline. The authors also explored the peri-procedural risks and long-term complications with these devices. There are several remaining unanswered questions and hypotheses in the field of LAA closure, including the comparative efficacy of percutaneous devices, antithrombotic regimen post-implant, unstudied patient populations, head-to-head comparison to direct OAC, and efficacy of open-surgical LAA occlusion. Although
Disclosures: Dr. Saw is a proctor and consultant for LAA closure devices for St Jude Medical and Boston Scientific. Dr. Saw has also received unrestricted research grant support (from the Canadian Institutes of Health Research, University of British Columbia Division of Cardiology, AstraZeneca, Abbott Vascular, St Jude Medical, Boston Scientific, and Servier), speaker honoraria (AstraZeneca, St Jude Medical, Boston Scientific, Bayer and Sunovion), consultancy and advisory board honoraria (AstraZeneca, St Jude Medical, Boston Scientific, and Abbott Vascular), and proctorship honoraria (St Jude Medical and Boston Scientific). n Tel.: þ1 604 875 5547; fax: þ1 604 875 5563. E-mail address: [email protected] http://dx.doi.org/10.1016/j.tcm.2015.06.006 1050-1738/& 2015 Elsevier Inc. All rights reserved.
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registry observational studies have explored a few of these areas, the limited published randomized trials have only addressed WATCHMAN in patients eligible for warfarin [7,8]. There is an ongoing large phase 3 randomized controlled trial of open-surgical LAA closure (LAAOS III) [9], which is anticipated to provide definitive answers on the safety and efficacy of the surgical approach. Several randomized trials are currently being designed to address the population of patients with contraindications to OAC, and to address comparisons of different percutaneous LAA devices by non-inferiority designs. Future randomized trials that will be of interests to clinicians include comparing the strategy of antiplatelet to anticoagulant regimen following percutaneous LAA closure, and to compare percutaneous LAA closure to a direct OAC. The field of LAA closure has rapidly advanced from a technological, clinical experience, and clinical trial perspective. Overcoming the learning curve with percutaneous LAA closure has improved the safety of this approach, and is expected to further improve efficacy outcomes in future randomized trials. It is not surprising that this technology is being rapidly adopted in countries that have device approval, as the alternative of life-long OAC administration is associated with cumulative risks of major bleeding annually. Nevertheless, many clinicians remain critical and have not fully embraced percutaneous LAA closure as the published randomized trial data is limited. Perhaps the ultimate litmus test with this technology is to prove non-inferiority to a direct OAC, together with cost-effectiveness analyses to address the economic impact of these 2 treatment strategies. This is believed to be achievable and would then fully expand this technology to all high stroke-risk patients with non-valvular AF.
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E D I C I N E
] (2015) ]]]–]]]
re fe r en ces
[1]
[2]
[3] [4]
[5]
[6]
[7]
[8]
[9]
Madden JL. Resection of the left auricular appendix: a prophylaxis for recurrent arterial emboli. J Am Med Assoc 1949;140:769–72. Shirani J, Alaeddini J. Structural remodeling of the left atrial appendage in patients with chronic non-valvular atrial fibrillation: Implications for thrombus formation, systemic embolism, and assessment by transesophageal echocardiography. Cardiovasc Pathol 2000;9:95–101. Ho SY, Cabrera JA, Sanchez-Quintana D. Left atrial anatomy revisited. Circ Arrhythm Electrophysiol 2012;5:220–8. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–9. Kakkar AK, Mueller I, Bassand JP, et al. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PloS One 2013;8:e63479. Romero J, Natale A, Engstrom K, Di Biase L. Left atrial appendage isolation using percutaneous (endocardial/epicardial) devices: pre-clinical and clinical experience. Trends Cardiovasc Med 2015 [in press]. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. J Am Med Assoc 2014;312:1988–98. Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1–12. Whitlock R, Healey J, Vincent J, et al. Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III. Ann Cardiothorac Surg 2014;3:45–54.
E N D S I N
C
A R D I O V A S C U L A R
M
E D I C I N E
] (2015) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/tcm
Editorial Commentary
Percutaneous left atrial appendage closure for stroke prevention Jacqueline Saw, MD, FRCPC, FACC, FSCAIn Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
“The left atrial appendage: our most lethal human attachment… Johnson WD et al.” The left atrial appendage (LAA) was recognized as a potential harbinger of thrombus with thromboembolic risks since the 1940s, and the first surgical excision of the LAA was reported by Madden in 1949 [1]. In the setting of atrial fibrillation (AF), the LAA undergoes remodeling resulting in larger luminal surface area, smoother endocardial surface, and higher endocardial fibroelastosis, which together with the Virchow triad of events can contribute to thrombus formation [2,3]. Indeed, transesophageal echocardiography (TEE) studies reported that 91% of thrombi in the setting of non-valvular AF were located in the LAA [4]. These thrombi no doubt were implicated as the etiology for the majority of cardioembolic strokes with AF. The stroke-risk with AF is increased on average by 5-fold, with incremental risks that can be estimated and validated with modern risk-scores like CHADS2 or CHA2DS2-VASc scores. However, despite multinational guidelines that endorse the utility of these scores to recommend oral anticoagulation (OAC), approximately 40% of patients at high stroke-risk remain unanticoagulated because of contraindications or intolerance to OAC [5]. Thus, alternative strategies especially local targeted therapy to exclude/ excise the LAA as a potential thromboembolic source has been explored over half a century ago. LAA closure can be achieved by an open-surgical or percutaneous fashion; and percutaneous LAA closure can be performed via an endovascular or an epicardial approach. The first
dedicated percutaneous LAA closure device, PLAATO, was implanted in humans in 2001, but has been removed from the market for commercial reasons. Several percutaneous devices have been developed since, including 3 devices that have received CE Mark approval [WATCHMAN, Amplatzer Cardiac Plug (ACP)/Amulet, Wavecrest], and several more should be approved in the near future. The 2 current leading devices, WATCHMAN and ACP/Amulet, are currently available in 450 countries, and 410,000 of each device has been implanted worldwide. In the United States, the WATCHMAN device received FDA approval on March 13, 2015, and has rapidly been adopted as a stroke preventative therapy in patients who can tolerate warfarin for 45 days post-implant. In other countries, indications for percutaneous LAA closure varies geographically, although many countries are more conservative due to limitations on reimbursement, and tend to only implant these devices in patients at high stroke-risk and have contraindications to OAC. The article by Romero et al. [6] in this issue of the Journal provides a nice overview of the pre-clinical and clinical data on contemporary percutaneous LAA closure devices that are currently available and a few that are in the pipeline. The authors also explored the peri-procedural risks and long-term complications with these devices. There are several remaining unanswered questions and hypotheses in the field of LAA closure, including the comparative efficacy of percutaneous devices, antithrombotic regimen post-implant, unstudied patient populations, head-to-head comparison to direct OAC, and efficacy of open-surgical LAA occlusion. Although
Disclosures: Dr. Saw is a proctor and consultant for LAA closure devices for St Jude Medical and Boston Scientific. Dr. Saw has also received unrestricted research grant support (from the Canadian Institutes of Health Research, University of British Columbia Division of Cardiology, AstraZeneca, Abbott Vascular, St Jude Medical, Boston Scientific, and Servier), speaker honoraria (AstraZeneca, St Jude Medical, Boston Scientific, Bayer and Sunovion), consultancy and advisory board honoraria (AstraZeneca, St Jude Medical, Boston Scientific, and Abbott Vascular), and proctorship honoraria (St Jude Medical and Boston Scientific). n Tel.: þ1 604 875 5547; fax: þ1 604 875 5563. E-mail address: [email protected] http://dx.doi.org/10.1016/j.tcm.2015.06.006 1050-1738/& 2015 Elsevier Inc. All rights reserved.
2
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E N D S I N
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registry observational studies have explored a few of these areas, the limited published randomized trials have only addressed WATCHMAN in patients eligible for warfarin [7,8]. There is an ongoing large phase 3 randomized controlled trial of open-surgical LAA closure (LAAOS III) [9], which is anticipated to provide definitive answers on the safety and efficacy of the surgical approach. Several randomized trials are currently being designed to address the population of patients with contraindications to OAC, and to address comparisons of different percutaneous LAA devices by non-inferiority designs. Future randomized trials that will be of interests to clinicians include comparing the strategy of antiplatelet to anticoagulant regimen following percutaneous LAA closure, and to compare percutaneous LAA closure to a direct OAC. The field of LAA closure has rapidly advanced from a technological, clinical experience, and clinical trial perspective. Overcoming the learning curve with percutaneous LAA closure has improved the safety of this approach, and is expected to further improve efficacy outcomes in future randomized trials. It is not surprising that this technology is being rapidly adopted in countries that have device approval, as the alternative of life-long OAC administration is associated with cumulative risks of major bleeding annually. Nevertheless, many clinicians remain critical and have not fully embraced percutaneous LAA closure as the published randomized trial data is limited. Perhaps the ultimate litmus test with this technology is to prove non-inferiority to a direct OAC, together with cost-effectiveness analyses to address the economic impact of these 2 treatment strategies. This is believed to be achievable and would then fully expand this technology to all high stroke-risk patients with non-valvular AF.
M
E D I C I N E
] (2015) ]]]–]]]
re fe r en ces
[1]
[2]
[3] [4]
[5]
[6]
[7]
[8]
[9]
Madden JL. Resection of the left auricular appendix: a prophylaxis for recurrent arterial emboli. J Am Med Assoc 1949;140:769–72. Shirani J, Alaeddini J. Structural remodeling of the left atrial appendage in patients with chronic non-valvular atrial fibrillation: Implications for thrombus formation, systemic embolism, and assessment by transesophageal echocardiography. Cardiovasc Pathol 2000;9:95–101. Ho SY, Cabrera JA, Sanchez-Quintana D. Left atrial anatomy revisited. Circ Arrhythm Electrophysiol 2012;5:220–8. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–9. Kakkar AK, Mueller I, Bassand JP, et al. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PloS One 2013;8:e63479. Romero J, Natale A, Engstrom K, Di Biase L. Left atrial appendage isolation using percutaneous (endocardial/epicardial) devices: pre-clinical and clinical experience. Trends Cardiovasc Med 2015 [in press]. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. J Am Med Assoc 2014;312:1988–98. Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1–12. Whitlock R, Healey J, Vincent J, et al. Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III. Ann Cardiothorac Surg 2014;3:45–54.