Catheterization and Cardiovascular Interventions 85:304–305 (2015)
Editorial Comment At a Crossroads: An Amulet in the Uneasy Left Atrial Appendage Crown Zoltan G. Turi,* MD, MSCAI Division of Cardiovascular Diseases and Hypertension, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
Key Points
This is a small but well-presented series describing a second generation Amplatzer Cardiac Plug device with short-term follow-up. As with the first generation device, a high level evidence base remains lacking. Left atrial appendage occlusion is at a crossroads, exacerbated by years of ad hoc use of a variety of such technologies that, other than the WATCHMAN, have not been subjected to randomized controlled studies.
The fine description of a small registry of AmuletTM deployments with 90-day follow-up is one of the first reports of a series of patients treated with this second generation Amplatzer Cardiac Plug (ACP, St. Jude Medical, Minneapolis, MN). The implanting group, which has pioneered the use of these technologies dating back to the original PLAATO device [1] (percutaneous left atrial appendage transcatheter occluder), has extraordinarily wide experience with LAA occlusion. The high success rate as well as the single pericardial effusion reported are in keeping with the profile of both the ACP as well as the WATCHMAN device [2] (Boston Scientif1ic, Natick, MA). The numbers in the current report are too small for meaningful analysis or comparison, as the authors carefully point out in their thoughtful discussion. The only prior series on the Amulet, by Frexia et al. [3], featured 25 patients with somewhat shorter followup, that report included one incidental observation of device thrombus. Regrettably, the information available on this device (which was CE marked almost 2 years ago) and the first generation ACP (available for many more years) is exceptionally lean: no randomized C 2015 Wiley Periodicals, Inc. V
control trials, no systematic long-term follow-up, no core labs, no clinical events committees, no data safety monitoring boards. This is despite years of widespread availability outside the United States. The device has been promoted as indicated for patients who are deemed “not suitable for anticoagulation,” “with high stroke risk,” arguably the indications where the greatest need exists, but questionable given abject lack of a high level evidence base to support this claim. LAA occlusion is at a crossroads. The third FDA panel hearing occurred on October 8, 2014 to review the WATCHMAN Premarket Approval (PMA) application. The PREVAIL trial [4], primarily intended to address the FDA’s safety concerns raised by the original PROTECT-AF study [2], actually met its safety endpoint without difficulty, demonstrating the benefits of expanded experience and training; unexpectedly however it failed both of its efficacy endpoints. While there are multiple potential explanations for this that leave the interventional cardiology community hopeful that some limited approval may yet follow, the outcome is anything but assured. Outright rejection may well spell doom for LAA occlusion, at least by plugs, for the foreseeable future in the United States. This uncertain future for the intra-cardiac LAA occlusion approach is exacerbated by the lack of data outside the WATCHMAN series (that device has been the subject of extensive randomized controlled trials and registries with some 1,877 patients enrolled and nearly 6,000 patient-years of follow-up). The ACP PMA randomized trial, which was to include several thousand patients, has been aborted for now. The small study in this edition of CCI by Sievert and coworkers is one of relatively few series studying the ACP with systematic follow-up, even though it includes only 17 patients followed for only 3 months. All this leaves the
Conflict of interest: Nothing to report. *Correspondence to: Zoltan G. Turi, M.D., Professor of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 582A, New Brunswick, NJ 08903. E-mail: [email protected] Received 1 December 2014; Revision accepted 6 December 2014 DOI: 10.1002/ccd.25763 Published online 20 January 2015 in Wiley Online Library (wileyonlinelibrary.com)
Left Atrial Appendage
practitioner in limbo, with the unsatisfactory alternative of a single FDA sanctioned device (albeit not approved for LAA occlusion per se), the LARIAT (SentreHEART, Redwood City, CA), which lacks an evidence base even more than the ACP and has a quite uncertain risk/benefit profile. Both interventional cardiologists and electrophysiologists need LAA plugs for patients with atrial fibrillation. In my opinion, the FDA may well mandate a randomized trial of LAA occlusion devices for patients who are not suitable for long-term anticoagulation, not the patients studied in PROTECTAF or PREVAIL, and not the population that the ACP randomized study was going to enroll. While this is a trial that is long overdue, it will engender great practical and some ethical challenges as well at this point. It is time for industry to step up to the plate and sponsor these studies. Until then, those of us who have long awaited left atrial appendage occlusion approval for
305
high risk patients with non-valvular AF continue to have cause to remain uneasy, even as promising technology like the Amulet continues to evolve. REFERENCES 1. Sievert H, Lesh MD, Trepels T, et al. Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in high-risk patients with atrial fibrillation: Early clinical experience. Circulation 2002;105:1887–1889. 2. 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 noninferiority trial. Lancet 2009;374:534–542. 3. Freixa X, Abualsaud A, Chan J, et al. Left atrial appendage occlusion: initial experience with the Amplatzer amulet. Int J Cardiol 2014;174:492–496. 4. 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.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment At a Crossroads: An Amulet in the Uneasy Left Atrial Appendage Crown Zoltan G. Turi,* MD, MSCAI Division of Cardiovascular Diseases and Hypertension, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
Key Points
This is a small but well-presented series describing a second generation Amplatzer Cardiac Plug device with short-term follow-up. As with the first generation device, a high level evidence base remains lacking. Left atrial appendage occlusion is at a crossroads, exacerbated by years of ad hoc use of a variety of such technologies that, other than the WATCHMAN, have not been subjected to randomized controlled studies.
The fine description of a small registry of AmuletTM deployments with 90-day follow-up is one of the first reports of a series of patients treated with this second generation Amplatzer Cardiac Plug (ACP, St. Jude Medical, Minneapolis, MN). The implanting group, which has pioneered the use of these technologies dating back to the original PLAATO device [1] (percutaneous left atrial appendage transcatheter occluder), has extraordinarily wide experience with LAA occlusion. The high success rate as well as the single pericardial effusion reported are in keeping with the profile of both the ACP as well as the WATCHMAN device [2] (Boston Scientif1ic, Natick, MA). The numbers in the current report are too small for meaningful analysis or comparison, as the authors carefully point out in their thoughtful discussion. The only prior series on the Amulet, by Frexia et al. [3], featured 25 patients with somewhat shorter followup, that report included one incidental observation of device thrombus. Regrettably, the information available on this device (which was CE marked almost 2 years ago) and the first generation ACP (available for many more years) is exceptionally lean: no randomized C 2015 Wiley Periodicals, Inc. V
control trials, no systematic long-term follow-up, no core labs, no clinical events committees, no data safety monitoring boards. This is despite years of widespread availability outside the United States. The device has been promoted as indicated for patients who are deemed “not suitable for anticoagulation,” “with high stroke risk,” arguably the indications where the greatest need exists, but questionable given abject lack of a high level evidence base to support this claim. LAA occlusion is at a crossroads. The third FDA panel hearing occurred on October 8, 2014 to review the WATCHMAN Premarket Approval (PMA) application. The PREVAIL trial [4], primarily intended to address the FDA’s safety concerns raised by the original PROTECT-AF study [2], actually met its safety endpoint without difficulty, demonstrating the benefits of expanded experience and training; unexpectedly however it failed both of its efficacy endpoints. While there are multiple potential explanations for this that leave the interventional cardiology community hopeful that some limited approval may yet follow, the outcome is anything but assured. Outright rejection may well spell doom for LAA occlusion, at least by plugs, for the foreseeable future in the United States. This uncertain future for the intra-cardiac LAA occlusion approach is exacerbated by the lack of data outside the WATCHMAN series (that device has been the subject of extensive randomized controlled trials and registries with some 1,877 patients enrolled and nearly 6,000 patient-years of follow-up). The ACP PMA randomized trial, which was to include several thousand patients, has been aborted for now. The small study in this edition of CCI by Sievert and coworkers is one of relatively few series studying the ACP with systematic follow-up, even though it includes only 17 patients followed for only 3 months. All this leaves the
Conflict of interest: Nothing to report. *Correspondence to: Zoltan G. Turi, M.D., Professor of Medicine, Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Place, MEB 582A, New Brunswick, NJ 08903. E-mail: [email protected] Received 1 December 2014; Revision accepted 6 December 2014 DOI: 10.1002/ccd.25763 Published online 20 January 2015 in Wiley Online Library (wileyonlinelibrary.com)
Left Atrial Appendage
practitioner in limbo, with the unsatisfactory alternative of a single FDA sanctioned device (albeit not approved for LAA occlusion per se), the LARIAT (SentreHEART, Redwood City, CA), which lacks an evidence base even more than the ACP and has a quite uncertain risk/benefit profile. Both interventional cardiologists and electrophysiologists need LAA plugs for patients with atrial fibrillation. In my opinion, the FDA may well mandate a randomized trial of LAA occlusion devices for patients who are not suitable for long-term anticoagulation, not the patients studied in PROTECTAF or PREVAIL, and not the population that the ACP randomized study was going to enroll. While this is a trial that is long overdue, it will engender great practical and some ethical challenges as well at this point. It is time for industry to step up to the plate and sponsor these studies. Until then, those of us who have long awaited left atrial appendage occlusion approval for
305
high risk patients with non-valvular AF continue to have cause to remain uneasy, even as promising technology like the Amulet continues to evolve. REFERENCES 1. Sievert H, Lesh MD, Trepels T, et al. Percutaneous left atrial appendage transcatheter occlusion to prevent stroke in high-risk patients with atrial fibrillation: Early clinical experience. Circulation 2002;105:1887–1889. 2. 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 noninferiority trial. Lancet 2009;374:534–542. 3. Freixa X, Abualsaud A, Chan J, et al. Left atrial appendage occlusion: initial experience with the Amplatzer amulet. Int J Cardiol 2014;174:492–496. 4. 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.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
