EDITORIAL COMMENTARY
Catheter ablation for atrial fibrillation in patients with left atrial appendage closure devices David J. Callans, MD, FHRS From the Section of Cardiac Electrophysiology, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
In this issue of HeartRhythm, Heeger et al1 present an interesting observational study of the feasibility of left atrial catheter ablation for the treatment of atrial fibrillation (AF) in patients with previous left atrial appendage (LAA) occlusion devices. As the authors point out, given the proximity of the mechanical device and ablation targets around the left pulmonary veins, ablation may conceivably be less successful and/or unsafe. The data they present are important (particularly because it includes a cautionary tale), well in keeping with this group’s history of excellent clinical research. Describing what we do from day to day is important, as the delivery of care is ever more complex and the combinations of therapies more intricate. Observational research provides a monitoring strategy for unintended consequences, which occur even after robust preclinical and clinical product development. This study involves 8 patients (mean age 69 ⫾ 8 years) with previous implantation of LAA occlusion devices (Watchman in 7 patients and Amplatzer in 1 patient) for standard indications2: a high HAS-BLED score in 4 patients and previous severe anticoagulation associated bleeding (not further described) in 4 patients. All LAA occlusion procedures were performed by the Hamburg investigators and were successful, without implant complications. Standard postprocedure guideline-directed management of anticoagulation was prescribed. At a mean duration of 201 days after LAA occlusion (range 41–756 days), catheter ablation for the treatment of symptomatic drug refractory AF was performed; this represented a repeat procedure for 2 patients. A transesophageal echocardiogram (TEE) was performed in all patients, documenting optimal positioning of the occlusion device before the ablation procedure. Periprocedural anticoagulation was prescribed according to the institution’s usual care (bridging warfarin, reduced-dose target specific oral anticoagulant treatment after ablation, and heparin dosed to activated clotting time (ACT) 4 250 seconds during left Address reprint requests and correspondence: Dr David J. Callans, Section of Cardiac Electrophysiology, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
atrial access). Standard left atrial ablation was performed (dual transseptal access, multipolar circular mapping catheter, electroanatomic mapping, and irrigated radiofrequency ablation) consisting of circumferential antral pulmonary vein isolation with the addition of linear lesions (n ¼ 4) and complex fractionated atrial electrograms (CFAE) ablation (n ¼ 1) in selected patients. Despite the proximity of the device to the anterior aspect of the left pulmonary veins, acute success was noted in all patients without procedural complications. All patients received standard oral anticoagulation for 3 months, followed by aspirin or clopidogrel where feasible. After a mean follow-up of 554 days, 5 of 8 patients remained in sinus rhythm, albeit with minimal monitoring. A repeat TEE was required to assess “procedure-related complications” but obtained an average of 503 days (range 113–1006 days) after the ablation procedure. No incidence of device dislodgment or leakage was detected; however, in 1 patient, a large thrombus attached to the LAA occlusion device was noted 113 days after the ablation procedure despite adherence to oral anticoagulation. The authors propose that this may have been secondary to a relatively short period between device placement and ablation (63 days, although another patient had ablation 41 days after LAA occlusion without detected problems), perhaps related to incomplete endothelialization of the device. It is also conceivable that the relatively low target intraprocedural ACT values contributed to this finding. Using intracardiac echocardiography we have observed that sheath-related thrombus during left atrial ablation procedures is virtually abolished at ACTs 4 350 seconds.3 No thromboembolic complications were noted, and the thrombus resolved with continued full dose anticoagulation after 20 months. The authors concluded that left atrial ablation in patients with preexisting LAA occlusion devices is feasible and that device-related thrombus formation may occur after ablation. I am writing one day after the Food and Drug Administration announced approval of the Watchman as an alternative to long-term warfarin anticoagulation for the treatment of patients with nonvalvular AF at an increased risk of stroke who are suitable for warfarin and have “appropriate rationale” to seek a nonpharmacologic http://dx.doi.org/10.1016/j.hrthm.2015.03.040
Callans
Editorial Commentary
alternative to warfarin. This announcement comes at the end of an impressive dossier of clinical trial and registry evidence.4–7 I confess a typical American jealousy of European colleagues who often receive useful technology for patient care years before we do. I must also admit my naïveté related to the use of LAA occlusion devices, and my discomfort at the tales of woe occasioned by the use of the Lariat device, even in experienced hands8 but so much more so in operators without substantial transseptal and epicardial access experience. I am excited about the future of LAA occlusion in the United States, but concerned about indication creep. This brings me (finally) to my point regarding the present work. What sort of patient is an appropriate candidate for both LAA occlusion and AF ablation? Patients with LAA occlusion devices are typically older and burdened by so many medical conditions that symptoms of AF are the least of their problems. Candidates for AF ablation are usually at a relatively low stroke and bleeding risk, and their AF-related symptoms are the most pressing problem. If patients are at such an extreme risk of bleeding, how does the intense periprocedural anticoagulation required for catheter ablation make sense? Even in patients in whom both strategies make sense, is there an optimal way to incorporate both into a thoughtful plan of care? I understand that clinical care is often messy, but it seems that each procedure was done without any appreciation for prospects of performing the other. I am not necessarily advocating simultaneous AF ablation and LAA occlusion in appropriately selected patients, although the idea has been proposed9 and has an appealing sense of efficiency. As the authors point out, ablation too early after LAA occlusion may cause unnecessary additional risk. Certainly the need for careful and prompt TEE monitoring after the ablation procedure makes sense, at least until we understand this phenomenon more completely. The authors should be congratulated for their careful work in demonstrating the feasibility of ablation in patients with LAA occlusion devices, a clinical circumstance that will undoubtedly increase in prevalence. Importantly, they have also detected a new complication, an unintended
1533 consequence that was not observed despite 46000 patientyears of experience in the Watchman program. Further observational clinical research is vital in many applications of LAA occlusion. Immediate questions to be answered include optimal patient selection in the age of target specific oral anticoagulants and whether LAA occlusion has an independent antifibrillatory effect10. The timing of this work is extraordinary, as we embark on our own US LAA closure adventures.
References 1. Heeger C-H, Rillig A, Lin T, Mathew S, Deiss S, Lemes C, Botros M, Metzner A, Wissner E, Kuck K-H, Ouyang F, Tilz RR. Feasibility and clinical efficacy of left atrial ablation for the treatment of atrial tachyarrhythmias in patients with left atrial appendage closure devices. Heart Rhythm 2015;12:1524–1531. 2. Meier B, Blaauw Y, Khattab AA, Lewalter T, Sievert H, Tondo C, Glikson M. Document Reviewers. EHRA/EAPCI expert consensus statement on catheterbased left atrial appendage occlusion. Europace 2014;16:1397–1416. 3. Ren J-F, Marchlinski FE, Callans DJ, Gerstenfeld EP, Dixit S, Lin D, Nayak HM, Hsia HH. Increased intensity of anticoagulation may reduce risk of thrombus during atrial fibrillation ablation procedures in patients with spontaneous echo contrast. J Cardiovasc Electrophysiol 2005;16:474–477. 4. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation 2011;123:417–424. 5. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D. PROTECT AF Investigators. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year followup of the PROTECT AF (Watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation 2013;127:720–729. 6. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. 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. 7. Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, Huber K, Whisenant B, Kar S, Swarup V, Gordon N, Holmes D. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA 2014;312:1988–1998. 8. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. Transcatheter LAA Ligation Consortium. J Am Coll Cardiol 2014;64:565–572. 9. Swaans MJ, Post MC, Rensing BJ, Boersma LV. Ablation for atrial fibrillation in combination with left atrial appendage closure: first results of a feasibility study. JAHA 2012;1:e002212. 10. Afzal MR, Kanmanthareddy A, Earnest M, et al. Impact of left atrial appendage exclusion using an epicardial ligation system (LARIAT) on atrial fibrillation burden in patients with cardiac implantable electronic devices. Heart Rhythm 2015;12:52–59.
Catheter ablation for atrial fibrillation in patients with left atrial appendage closure devices David J. Callans, MD, FHRS From the Section of Cardiac Electrophysiology, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
In this issue of HeartRhythm, Heeger et al1 present an interesting observational study of the feasibility of left atrial catheter ablation for the treatment of atrial fibrillation (AF) in patients with previous left atrial appendage (LAA) occlusion devices. As the authors point out, given the proximity of the mechanical device and ablation targets around the left pulmonary veins, ablation may conceivably be less successful and/or unsafe. The data they present are important (particularly because it includes a cautionary tale), well in keeping with this group’s history of excellent clinical research. Describing what we do from day to day is important, as the delivery of care is ever more complex and the combinations of therapies more intricate. Observational research provides a monitoring strategy for unintended consequences, which occur even after robust preclinical and clinical product development. This study involves 8 patients (mean age 69 ⫾ 8 years) with previous implantation of LAA occlusion devices (Watchman in 7 patients and Amplatzer in 1 patient) for standard indications2: a high HAS-BLED score in 4 patients and previous severe anticoagulation associated bleeding (not further described) in 4 patients. All LAA occlusion procedures were performed by the Hamburg investigators and were successful, without implant complications. Standard postprocedure guideline-directed management of anticoagulation was prescribed. At a mean duration of 201 days after LAA occlusion (range 41–756 days), catheter ablation for the treatment of symptomatic drug refractory AF was performed; this represented a repeat procedure for 2 patients. A transesophageal echocardiogram (TEE) was performed in all patients, documenting optimal positioning of the occlusion device before the ablation procedure. Periprocedural anticoagulation was prescribed according to the institution’s usual care (bridging warfarin, reduced-dose target specific oral anticoagulant treatment after ablation, and heparin dosed to activated clotting time (ACT) 4 250 seconds during left Address reprint requests and correspondence: Dr David J. Callans, Section of Cardiac Electrophysiology, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
atrial access). Standard left atrial ablation was performed (dual transseptal access, multipolar circular mapping catheter, electroanatomic mapping, and irrigated radiofrequency ablation) consisting of circumferential antral pulmonary vein isolation with the addition of linear lesions (n ¼ 4) and complex fractionated atrial electrograms (CFAE) ablation (n ¼ 1) in selected patients. Despite the proximity of the device to the anterior aspect of the left pulmonary veins, acute success was noted in all patients without procedural complications. All patients received standard oral anticoagulation for 3 months, followed by aspirin or clopidogrel where feasible. After a mean follow-up of 554 days, 5 of 8 patients remained in sinus rhythm, albeit with minimal monitoring. A repeat TEE was required to assess “procedure-related complications” but obtained an average of 503 days (range 113–1006 days) after the ablation procedure. No incidence of device dislodgment or leakage was detected; however, in 1 patient, a large thrombus attached to the LAA occlusion device was noted 113 days after the ablation procedure despite adherence to oral anticoagulation. The authors propose that this may have been secondary to a relatively short period between device placement and ablation (63 days, although another patient had ablation 41 days after LAA occlusion without detected problems), perhaps related to incomplete endothelialization of the device. It is also conceivable that the relatively low target intraprocedural ACT values contributed to this finding. Using intracardiac echocardiography we have observed that sheath-related thrombus during left atrial ablation procedures is virtually abolished at ACTs 4 350 seconds.3 No thromboembolic complications were noted, and the thrombus resolved with continued full dose anticoagulation after 20 months. The authors concluded that left atrial ablation in patients with preexisting LAA occlusion devices is feasible and that device-related thrombus formation may occur after ablation. I am writing one day after the Food and Drug Administration announced approval of the Watchman as an alternative to long-term warfarin anticoagulation for the treatment of patients with nonvalvular AF at an increased risk of stroke who are suitable for warfarin and have “appropriate rationale” to seek a nonpharmacologic http://dx.doi.org/10.1016/j.hrthm.2015.03.040
Callans
Editorial Commentary
alternative to warfarin. This announcement comes at the end of an impressive dossier of clinical trial and registry evidence.4–7 I confess a typical American jealousy of European colleagues who often receive useful technology for patient care years before we do. I must also admit my naïveté related to the use of LAA occlusion devices, and my discomfort at the tales of woe occasioned by the use of the Lariat device, even in experienced hands8 but so much more so in operators without substantial transseptal and epicardial access experience. I am excited about the future of LAA occlusion in the United States, but concerned about indication creep. This brings me (finally) to my point regarding the present work. What sort of patient is an appropriate candidate for both LAA occlusion and AF ablation? Patients with LAA occlusion devices are typically older and burdened by so many medical conditions that symptoms of AF are the least of their problems. Candidates for AF ablation are usually at a relatively low stroke and bleeding risk, and their AF-related symptoms are the most pressing problem. If patients are at such an extreme risk of bleeding, how does the intense periprocedural anticoagulation required for catheter ablation make sense? Even in patients in whom both strategies make sense, is there an optimal way to incorporate both into a thoughtful plan of care? I understand that clinical care is often messy, but it seems that each procedure was done without any appreciation for prospects of performing the other. I am not necessarily advocating simultaneous AF ablation and LAA occlusion in appropriately selected patients, although the idea has been proposed9 and has an appealing sense of efficiency. As the authors point out, ablation too early after LAA occlusion may cause unnecessary additional risk. Certainly the need for careful and prompt TEE monitoring after the ablation procedure makes sense, at least until we understand this phenomenon more completely. The authors should be congratulated for their careful work in demonstrating the feasibility of ablation in patients with LAA occlusion devices, a clinical circumstance that will undoubtedly increase in prevalence. Importantly, they have also detected a new complication, an unintended
1533 consequence that was not observed despite 46000 patientyears of experience in the Watchman program. Further observational clinical research is vital in many applications of LAA occlusion. Immediate questions to be answered include optimal patient selection in the age of target specific oral anticoagulants and whether LAA occlusion has an independent antifibrillatory effect10. The timing of this work is extraordinary, as we embark on our own US LAA closure adventures.
References 1. Heeger C-H, Rillig A, Lin T, Mathew S, Deiss S, Lemes C, Botros M, Metzner A, Wissner E, Kuck K-H, Ouyang F, Tilz RR. Feasibility and clinical efficacy of left atrial ablation for the treatment of atrial tachyarrhythmias in patients with left atrial appendage closure devices. Heart Rhythm 2015;12:1524–1531. 2. Meier B, Blaauw Y, Khattab AA, Lewalter T, Sievert H, Tondo C, Glikson M. Document Reviewers. EHRA/EAPCI expert consensus statement on catheterbased left atrial appendage occlusion. Europace 2014;16:1397–1416. 3. Ren J-F, Marchlinski FE, Callans DJ, Gerstenfeld EP, Dixit S, Lin D, Nayak HM, Hsia HH. Increased intensity of anticoagulation may reduce risk of thrombus during atrial fibrillation ablation procedures in patients with spontaneous echo contrast. J Cardiovasc Electrophysiol 2005;16:474–477. 4. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation 2011;123:417–424. 5. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Halperin JL, Holmes D. PROTECT AF Investigators. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year followup of the PROTECT AF (Watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation 2013;127:720–729. 6. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. 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. 7. Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, Huber K, Whisenant B, Kar S, Swarup V, Gordon N, Holmes D. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA 2014;312:1988–1998. 8. Price MJ, Gibson DN, Yakubov SJ, et al. Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. Transcatheter LAA Ligation Consortium. J Am Coll Cardiol 2014;64:565–572. 9. Swaans MJ, Post MC, Rensing BJ, Boersma LV. Ablation for atrial fibrillation in combination with left atrial appendage closure: first results of a feasibility study. JAHA 2012;1:e002212. 10. Afzal MR, Kanmanthareddy A, Earnest M, et al. Impact of left atrial appendage exclusion using an epicardial ligation system (LARIAT) on atrial fibrillation burden in patients with cardiac implantable electronic devices. Heart Rhythm 2015;12:52–59.
