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The Last Shot for “One Shot” Pulmonary Vein Isolation with Radiofrequency Energy? SUNEET MITTAL, M.D. and JONATHAN S. STEINBERG, M.D. From the Arrhythmia Institute of the Valley Hospital Health System, Ridgewood, New Jersey and New York, New York, USA
catheter ablation, pulmonary vein isolation, radiofrequency energy Editorial Comment Current practice guidelines recommend catheter ablation to maintain sinus rhythm in patients with symptomatic, paroxysmal, atrial fibrillation (AF) who have failed treatment with an antiarrhythmic drug.1 Based on the observation that triggers that initiate AF usually emanate from within the pulmonary veins (PVs), ablation strategies that target the PVs and/or PV antrum to an endpoint of PV isolation (PVI) are considered the cornerstone for most AF ablation procedures.2 Currently, PVI can be achieved by delivery of point-to-point radiofrequency (RF) energy or as a “one shot” technique with a cryoenergy balloon system; both techniques are associated with a similar long-term efficacy.3,4 Virtually all ablation laboratories make use of an 8–20 pole circular mapping catheter positioned at the PV ostium to demonstrate or confirm successful PVI after energy delivery. Potentials from the PVs have distinct characteristics yet must be distinguished from far-field atrial electrical signals originating in neighboring structures. Mapping and catheter manipulation is usually facilitated by integration into a 3dimensional (3-D) electroanatomic mapping system. The use of point-by-point RF requires acquisition of an experiential skill set and procedures can be time consuming. In particular, creating circumferential lesions that are contiguous and transmural is challenging, but is required to achieve durable PVI for most ablation strategies. Thus, there has been a long-standing interest in developing a single catheter capable of both mapping and ablating the PV ostia/antra using RF energy. The PV ablation catheter or PVAC (Medtronic, Inc., Carlsbad, CA, USA), capable of independently delivering nonirrigated, duty-cycled, RF energy in various combinations of unipolar and/or bipolar current, was a multipolar ablation catheter that attempted to achieve these valuable goals. The PVAC isolation technique demonstrated significantly shorter procedure and fluoroscopy times, without the J Cardiovasc Electrophysiol, Vol. 25, pp. 346-348, April 2014. J.S. Steinberg reports: Consultant to Biosense-Webster, Boston-Scientific, and Medtronic; research grant from Biosense-Webster, Boston-Scientific, and Medtronic; honoraria from Bristol Myers Squibb, Pfizer, and Janssen. S. Mittal reports: Consultant to Boston Scientific and Medtronic; research grant from Biosense Webster. Address for correspondence: Suneet Mittal, M.D., Electrophysiology Laboratory, The Valley Hospital, 223 N. Van Dien Avenue, Ridgewood, NJ 07450, USA. Fax: 201-432-7830; E-mail: [email protected] doi: 10.1111/jce.12341
need for a 3-D mapping system, and high acute procedural success.5 Despite favorable early results, enthusiasm was greatly tempered when 2 independent observational studies reported a much higher incidence of asymptomatic cerebral events (ACE) on magnetic resonance imaging (MRI) when using PVAC as compared with conventional irrigated RF delivery or cryoballoon for PVI.6,7 The risk was about 5-fold greater and the PVAC patients had between 1 and 5 new lesions with a wide intracranial distribution, consistent with an embolic source. In an editorial, we opined that it would be difficult to justify the use of PVAC until greater clarification regarding mechanism and long-term consequences of silent cerebral embolism were clarified and addressed, or the findings were refuted.8 Subsequent bench work has suggested that close proximity between the proximal and distal electrodes and lack of tissue contact may have generated microembolic debris and thus created ACE,9 and the PVAC has been redesigned. We had also suggested that testing for ACE be part of the regulatory process8 and new clinical investigatory efforts on the multipolar ablation catheters have reassuringly incorporated these examinations. In this issue of the Journal, Deneke et al. provide the first data on the acute safety and efficacy of another multipolar RF ablation catheter (nMARQTM , Biosense-Webster, Diamond Bar, CA, USA) for PVI.10 This catheter differs from the PVAC by providing saline irrigation at the electrode-tissue interface and by not using phased RF delivery, features that may mitigate the previously described complications. The study’s cohort included 43 patients with either paroxysmal or short duration (median 2 months) persistent AF. Ablation was performed by delivering RF energy via all 10 electrodes in a unipolar mode. Esophageal temperature monitoring was performed in all patients using a multisensor probe (Sensitherm, St. Jude Medical, St. Paul, MN, USA); ablation was terminated if any sensor recorded an esophageal luminal temperature >40.5 ◦ C. In the first 31 patients, 25 Watts (W) was delivered to all poles; in the last 12 patients, power was limited to 20 W on poles overlying the posterior wall of the left atrium. All patients underwent endoscopic evaluation of the esophagus a day postablation to assess for esophageal thermal lesions as well as pre- and postablation cerebral MRIs to assess for ACE. Acute PVI, as defined by the presence of entrance and exit block assessed 30 minutes following the last ablation, could be achieved in 160 (98%) of 163 targeted PVs using the nMARQTM mapping and ablation catheter alone. Approximately 5 separate 60-second applications of RF energy were required to isolate any given PV. Acute PV reconnections were observed in 15 (35%) patients and involved 19 (12%) targeted PVs; repeat ablation reisolated all of these reconnected veins.
Mittal and Steinberg
One of the most feared complications of AF ablation is the development of a left atrial-esophageal fistula (AEF). Despite its low incidence (0.03–0.10%), AEF results in bleeding, septicemia, and stroke related to air embolism and is thus associated with a high mortality rate.11 Thermal injury to the esophageal vasculature, which progresses to an ischemic lesion, is considered the precursor to an AEF. Thus, monitoring of the luminal esophageal temperature during ablation has become a widely accepted method to monitor for potential esophageal thermal injury.12,13 In this study, at least one instance of an esophageal temperature increase to >40.5 ◦ C necessitating premature termination of ablation delivery was observed in 22 (51%) patients. By protocol design, in these instances, the nMARQTM catheter was either repositioned or subsequent ablations delivered at lower power. However, in 12 of these patients, the esophageal temperature rose again during repeat ablation. Postablation endoscopy, which was performed in all patients, demonstrated that esophageal thermal lesions were limited to patients in whom an increase in esophageal temperature was observed. Specifically, 14 (64%) of these 22 patients had endoscopically documented esophageal thermal damage that included mild superficial erythema in 12 patients and a superficial ulcerous lesion in the other 2 patients. Of concern, in 6 (43%) of the 14 patients with evidence of an esophageal thermal lesion, only a single instance of temperature increase had been observed. In addition to the esophageal lesions, ACE were observed in 14 (33%) patients. There were a mean of 1.9 ACE per patient (range: 1–8). Although 23 (88%) of the ACE were ≤3 mm, there were 3 lesions with a diameter between 4 and 9 mm. The anticoagulation protocol appeared to impact the likelihood of developing an ACE. The lowest incidence of ACE was observed in patients undergoing ablation during uninterrupted anticoagulation with warfarin; however, even in this arm, the incidence of ACE was 14%. The clinical significance, if any, of the ACE remains uncertain. However, some evidence suggests that these silent infarcts may not be benign. For example, in population-based studies, the presence of silent brain infarcts has been associated with worse performance on neuropsychological tests, a steeper decline in global cognitive function, and doubling of the risk of developing dementia.14 Although the majority of MRI lesions disappear in weeks on repeat scanning,15 larger lesions do not and there is pathologic evidence that these lesions are permanent despite absence of residual MRI findings.16 It seems eminently prudent that until proven otherwise, the incidence and extent of ACE should be minimized for all ablation techniques. What implications do the data presented have for the “oneshot” mapping and ablation concept for PVI? A fundamental goal of left atrial catheter ablation for management of AF is the ability to achieve durable PVI since failure of AF ablation is almost universally accompanied by recurrence of PV conduction and reisolation of PVs at the time of a repeat procedure results in an important increment in efficacy.17 The ideal system would at the same time be associated with a low risk of collateral damage. Against this standard, the findings presented by Deneke et al. are disconcerting. When ablation was performed with 25 W, PVI could be achieved with a shorter duration of RF delivery, which translated into shorter procedure duration. However, this came at the expense of a 42% incidence of esophageal thermal lesions. When power was reduced to 20 W along the posterior wall,
Editorial Comment
347
the incidence of esophageal thermal lesions was reduced to 20%, still suboptimal. Furthermore, RF delivery and procedure duration increased; additionally, the incidence of acute PV reconnections increased from 29% to 50%; reconnections were observed almost exclusively on the posterior wall, at sites where ablation had been performed at lower power. Although all PVs were successfully reisolated acutely, the durability of PVI with this catheter is yet unknown. Before a final conclusion on the long-term viability of the nMARQTM catheter can be drawn, some additional data are necessary. First, the same authors previously demonstrated that following PVI with the PVAC, endoscopy documented esophageal damage was limited to patients who had undergone esophageal temperature monitoring.18 This suggests that the esophageal temperature probe in itself may pose an inadvertent risk. Thus, a cohort needs to be evaluated who undergoes PVI with the nMARQTM catheter without the use of esophageal temperature monitoring and then undergoes endoscopy to assess for esophageal thermal damage. Second, the relationship between “one shot” RF mapping and ablation catheters and an extremely high incidence of ACE (as previously observed with the PVAC and now being reported with nMARQTM catheter) needs to be better understood. Similar to what has recently been reported,19,20 saline irrigation and even ablation during uninterrupted anticoagulation with warfarin could not reduce the incidence of ACE observed with the nMARQTM catheter to the much lower incidence reported with both point-by-point RF and cryoballoon ablation systems.7,21 It is entirely possible that the concept of simultaneous circular mapping and ablation by a single catheter (e.g., PVAC and nMARQTM ) is flawed because their relatively limited shape and diameter cannot achieve homogenous consistent tissue contact around the unpredictably shaped and sized PV orifices. The absence of “high quality contact” generates a milieu that potentially promotes both poor contact and resultant char or gas bubble formation causing ACE and excessive contact increasing esophageal injury. Unless these concerns can be satisfactorily addressed, this may have been the last shot for “one shot” PVI using RF energy.
Acknowledgment: The authors wish to thank Dr. David E. Haines for thoughtful insight and discussion.
References 1. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NAM 3rd, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM; on behalf of the 2006 ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation Writing Committee: 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;57:223-242. 2. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJG, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, KirchhofP, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Sheim RJ, Tsao HM, Wilber D: 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and
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5.
6.
7.
8. 9.
10.
11.
Journal of Cardiovascular Electrophysiology
Vol. 25, No. 4, April 2014
Follow-up, Definitions, Endpoints, and Research Trial Design. Heart Rhythm 2012;9:632-696. Wilber DJ, Pappone C, Neuzil P, DePaola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; for the ThermoCool AF Trial Investigators: Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation. A randomized controlled trial. JAMA 2010;303:333-340. Packer DL, Kowal RC, Wheelan KR, Irwin JM,Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, Lehmann JW, Ruskin JN; for the STOP AF Cryoballoon Investigators: Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation. First results of the North American Artic Front (STOP AF) pivotal trial. J Am Coll Cardiol 2013;61:1713-1723. Wieczorek M, Hoeltgen R, Akin E, Salili AR, Oral H, Morady F: Results of short-term and long-term pulmonary vein isolation for paroxysmal atrial fibrillation using duty-cycled bipolar and unipolar radiofrequency energy. J Cardiovasc Electrophysiol 2010;21:399-405. Siklody CH, Deneke T, Hocini M, Lehrmann H, Shin DI, Miyazaki S, Henschke S, Fluegel P, Schiebeling-Romer J, Bansmann PM, Bourdias T, Dousset V, Haissaguerre M, Arentz T: Incidence of asymptomatic intracranial embolic events following pulmonary vein isolation: Comparison between different AF ablation technologies in a multicentric study. J Am Coll Cardiol 2011;58:681-688. Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F, Schade A, Froehner S, Ziegler V, Sergi D, Cesarani F, Blandino A: Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: Comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol 2011;22:961-968. Steinberg JS, Mittal S: Intracranial emboli associated with catheter ablation of atrial fibrillation. J Am Coll Cardiol 2011;58:689-691. Haines DE, Stewart MT, Ahlberg S, Barke N, Candle C, Fiedler GR, Kirchhof NA, Halimi F, Deneke T: Microembolism and catheter ablation I. A comparison of irrigated radiofrequency and multi-electrode phased radiofrequency catheter ablation of pulmonary vein ostia. Circ Arrhythm Electrophysiol 2013;6:16-22. Deneke T, Schade A, Muller P, Schmitt R, Christopoulos G, Krug J, Szollosi G, Mugge A, Kerber S, Nentwich K: Acute safety and efficacy of a novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation. J Cardiovasc Electrophysiol 2013;25:339345. Liu E, Shehata M, Liu T, Amorn A, Cingolani E, Kannarkat V, Chugh SS, Wang X: Prevention of esophageal thermal injury during radiofre-
12.
13. 14. 15.
16.
17.
18.
19.
20.
21.
quency ablation for atrial fibrillation. J Interv Card Electrophysiol 2012;35:35-44. Musat D, Aziz EF, Koneru J, Arshad A, Kamath GS, Mittal S, Steinberg JS: Novel computational method to predict esophageal temperature elevations during pulmonary vein isolation. PACE 2010;33:12391248. Musat D, Mittal S: The esophageal temperature probe: Helpful monitoring device or inadvertent amplifier of risk? J Cardiovasc Electrophysiol 2011;22:262-244. Vermeer SE, Prins ND, Heijer TD, Hofman A, Koudstaal PJ, Breteler MMB: Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-1222. Deneke T, Shin DI, Balta O, Bunz K, Fassbender F, Mugge A, Anders H, Horlitz M, Pasler M, KarthikapallilS, Arentz T, Beyer D, Bansmann M: Postablation aymptomatic cerebral lesions: Long-term follow-up using magnetic resonance imaging. Heart Rhythm 2011;8:1705-1711. Haines DE, Steward MT, Barka ND, Kirchhof N, Lentz LR, Reinking NM, Urban JF, Halimi F, Deneke T, Kanal E: Microembolism and catheter ablation II. Effects of microemboli injection in a canine model. Circ Arrhythm Electrophysiol 2013;6:23-30. Shah AN, Mittal S, Sichrovsky TC, Cotiga D, Arshad A, Maleki K, Pierce WJ, Steinberg JS: Long-term outcome following successful pulmonary vein isolation: Patterns and prediction of very late recurrence. J Cardiovasc Electrophysiol 2008;19:661-667. Deneke T, Bunz K, Bastian A, Pasler M, Anders H, Lehmann R, Meuser W, DeGroot JR, Horlitz M, Haberkorn R, Mugge A, Shin DI: Utility of esophageal temperature monitoring during pulmonary vein isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation. J Cardiovasc Electrophysiol 2011;22:255-261. Scaglione M, Blandino A, Raimondo C, Caponi D, DiDonna P, Toso E, Ebrille E, Cesarani F, Ferrarese E, Gaita F: Impact of ablation catheter irrigation design on silent cerebral embolism after radiofrequency catheter ablation of atrial fibrillation: Results from a pilot study. J Cardiovasc Electrophysiol 2012;23:801-805. Martinek M, Sigmund E, Lemes C, Derndofer M, Aichinger J, Winter S, Jauker W, Gschwendtner M, Nesser HJ, Purerfellner H. Asymptomatic cerebral lesions during pulmonary vein isolation under uninterrupted anticoagulation. Europace 2013;15:325-31. Neumann T, Kuniss M, Conrad G, Janin S, Berkowitsch A, Wojcik M, Rixe J, Erkapic D, Zaltsberg S, Rolf A, Bachmann G, Dill T, Hamm CW, Pitschner HF: MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation: Comparison of pulmonary vein isolation using cryoballoon technique vs. radiofrequency energy. Europace 2011;13: 37-44.
The Last Shot for “One Shot” Pulmonary Vein Isolation with Radiofrequency Energy? SUNEET MITTAL, M.D. and JONATHAN S. STEINBERG, M.D. From the Arrhythmia Institute of the Valley Hospital Health System, Ridgewood, New Jersey and New York, New York, USA
catheter ablation, pulmonary vein isolation, radiofrequency energy Editorial Comment Current practice guidelines recommend catheter ablation to maintain sinus rhythm in patients with symptomatic, paroxysmal, atrial fibrillation (AF) who have failed treatment with an antiarrhythmic drug.1 Based on the observation that triggers that initiate AF usually emanate from within the pulmonary veins (PVs), ablation strategies that target the PVs and/or PV antrum to an endpoint of PV isolation (PVI) are considered the cornerstone for most AF ablation procedures.2 Currently, PVI can be achieved by delivery of point-to-point radiofrequency (RF) energy or as a “one shot” technique with a cryoenergy balloon system; both techniques are associated with a similar long-term efficacy.3,4 Virtually all ablation laboratories make use of an 8–20 pole circular mapping catheter positioned at the PV ostium to demonstrate or confirm successful PVI after energy delivery. Potentials from the PVs have distinct characteristics yet must be distinguished from far-field atrial electrical signals originating in neighboring structures. Mapping and catheter manipulation is usually facilitated by integration into a 3dimensional (3-D) electroanatomic mapping system. The use of point-by-point RF requires acquisition of an experiential skill set and procedures can be time consuming. In particular, creating circumferential lesions that are contiguous and transmural is challenging, but is required to achieve durable PVI for most ablation strategies. Thus, there has been a long-standing interest in developing a single catheter capable of both mapping and ablating the PV ostia/antra using RF energy. The PV ablation catheter or PVAC (Medtronic, Inc., Carlsbad, CA, USA), capable of independently delivering nonirrigated, duty-cycled, RF energy in various combinations of unipolar and/or bipolar current, was a multipolar ablation catheter that attempted to achieve these valuable goals. The PVAC isolation technique demonstrated significantly shorter procedure and fluoroscopy times, without the J Cardiovasc Electrophysiol, Vol. 25, pp. 346-348, April 2014. J.S. Steinberg reports: Consultant to Biosense-Webster, Boston-Scientific, and Medtronic; research grant from Biosense-Webster, Boston-Scientific, and Medtronic; honoraria from Bristol Myers Squibb, Pfizer, and Janssen. S. Mittal reports: Consultant to Boston Scientific and Medtronic; research grant from Biosense Webster. Address for correspondence: Suneet Mittal, M.D., Electrophysiology Laboratory, The Valley Hospital, 223 N. Van Dien Avenue, Ridgewood, NJ 07450, USA. Fax: 201-432-7830; E-mail: [email protected] doi: 10.1111/jce.12341
need for a 3-D mapping system, and high acute procedural success.5 Despite favorable early results, enthusiasm was greatly tempered when 2 independent observational studies reported a much higher incidence of asymptomatic cerebral events (ACE) on magnetic resonance imaging (MRI) when using PVAC as compared with conventional irrigated RF delivery or cryoballoon for PVI.6,7 The risk was about 5-fold greater and the PVAC patients had between 1 and 5 new lesions with a wide intracranial distribution, consistent with an embolic source. In an editorial, we opined that it would be difficult to justify the use of PVAC until greater clarification regarding mechanism and long-term consequences of silent cerebral embolism were clarified and addressed, or the findings were refuted.8 Subsequent bench work has suggested that close proximity between the proximal and distal electrodes and lack of tissue contact may have generated microembolic debris and thus created ACE,9 and the PVAC has been redesigned. We had also suggested that testing for ACE be part of the regulatory process8 and new clinical investigatory efforts on the multipolar ablation catheters have reassuringly incorporated these examinations. In this issue of the Journal, Deneke et al. provide the first data on the acute safety and efficacy of another multipolar RF ablation catheter (nMARQTM , Biosense-Webster, Diamond Bar, CA, USA) for PVI.10 This catheter differs from the PVAC by providing saline irrigation at the electrode-tissue interface and by not using phased RF delivery, features that may mitigate the previously described complications. The study’s cohort included 43 patients with either paroxysmal or short duration (median 2 months) persistent AF. Ablation was performed by delivering RF energy via all 10 electrodes in a unipolar mode. Esophageal temperature monitoring was performed in all patients using a multisensor probe (Sensitherm, St. Jude Medical, St. Paul, MN, USA); ablation was terminated if any sensor recorded an esophageal luminal temperature >40.5 ◦ C. In the first 31 patients, 25 Watts (W) was delivered to all poles; in the last 12 patients, power was limited to 20 W on poles overlying the posterior wall of the left atrium. All patients underwent endoscopic evaluation of the esophagus a day postablation to assess for esophageal thermal lesions as well as pre- and postablation cerebral MRIs to assess for ACE. Acute PVI, as defined by the presence of entrance and exit block assessed 30 minutes following the last ablation, could be achieved in 160 (98%) of 163 targeted PVs using the nMARQTM mapping and ablation catheter alone. Approximately 5 separate 60-second applications of RF energy were required to isolate any given PV. Acute PV reconnections were observed in 15 (35%) patients and involved 19 (12%) targeted PVs; repeat ablation reisolated all of these reconnected veins.
Mittal and Steinberg
One of the most feared complications of AF ablation is the development of a left atrial-esophageal fistula (AEF). Despite its low incidence (0.03–0.10%), AEF results in bleeding, septicemia, and stroke related to air embolism and is thus associated with a high mortality rate.11 Thermal injury to the esophageal vasculature, which progresses to an ischemic lesion, is considered the precursor to an AEF. Thus, monitoring of the luminal esophageal temperature during ablation has become a widely accepted method to monitor for potential esophageal thermal injury.12,13 In this study, at least one instance of an esophageal temperature increase to >40.5 ◦ C necessitating premature termination of ablation delivery was observed in 22 (51%) patients. By protocol design, in these instances, the nMARQTM catheter was either repositioned or subsequent ablations delivered at lower power. However, in 12 of these patients, the esophageal temperature rose again during repeat ablation. Postablation endoscopy, which was performed in all patients, demonstrated that esophageal thermal lesions were limited to patients in whom an increase in esophageal temperature was observed. Specifically, 14 (64%) of these 22 patients had endoscopically documented esophageal thermal damage that included mild superficial erythema in 12 patients and a superficial ulcerous lesion in the other 2 patients. Of concern, in 6 (43%) of the 14 patients with evidence of an esophageal thermal lesion, only a single instance of temperature increase had been observed. In addition to the esophageal lesions, ACE were observed in 14 (33%) patients. There were a mean of 1.9 ACE per patient (range: 1–8). Although 23 (88%) of the ACE were ≤3 mm, there were 3 lesions with a diameter between 4 and 9 mm. The anticoagulation protocol appeared to impact the likelihood of developing an ACE. The lowest incidence of ACE was observed in patients undergoing ablation during uninterrupted anticoagulation with warfarin; however, even in this arm, the incidence of ACE was 14%. The clinical significance, if any, of the ACE remains uncertain. However, some evidence suggests that these silent infarcts may not be benign. For example, in population-based studies, the presence of silent brain infarcts has been associated with worse performance on neuropsychological tests, a steeper decline in global cognitive function, and doubling of the risk of developing dementia.14 Although the majority of MRI lesions disappear in weeks on repeat scanning,15 larger lesions do not and there is pathologic evidence that these lesions are permanent despite absence of residual MRI findings.16 It seems eminently prudent that until proven otherwise, the incidence and extent of ACE should be minimized for all ablation techniques. What implications do the data presented have for the “oneshot” mapping and ablation concept for PVI? A fundamental goal of left atrial catheter ablation for management of AF is the ability to achieve durable PVI since failure of AF ablation is almost universally accompanied by recurrence of PV conduction and reisolation of PVs at the time of a repeat procedure results in an important increment in efficacy.17 The ideal system would at the same time be associated with a low risk of collateral damage. Against this standard, the findings presented by Deneke et al. are disconcerting. When ablation was performed with 25 W, PVI could be achieved with a shorter duration of RF delivery, which translated into shorter procedure duration. However, this came at the expense of a 42% incidence of esophageal thermal lesions. When power was reduced to 20 W along the posterior wall,
Editorial Comment
347
the incidence of esophageal thermal lesions was reduced to 20%, still suboptimal. Furthermore, RF delivery and procedure duration increased; additionally, the incidence of acute PV reconnections increased from 29% to 50%; reconnections were observed almost exclusively on the posterior wall, at sites where ablation had been performed at lower power. Although all PVs were successfully reisolated acutely, the durability of PVI with this catheter is yet unknown. Before a final conclusion on the long-term viability of the nMARQTM catheter can be drawn, some additional data are necessary. First, the same authors previously demonstrated that following PVI with the PVAC, endoscopy documented esophageal damage was limited to patients who had undergone esophageal temperature monitoring.18 This suggests that the esophageal temperature probe in itself may pose an inadvertent risk. Thus, a cohort needs to be evaluated who undergoes PVI with the nMARQTM catheter without the use of esophageal temperature monitoring and then undergoes endoscopy to assess for esophageal thermal damage. Second, the relationship between “one shot” RF mapping and ablation catheters and an extremely high incidence of ACE (as previously observed with the PVAC and now being reported with nMARQTM catheter) needs to be better understood. Similar to what has recently been reported,19,20 saline irrigation and even ablation during uninterrupted anticoagulation with warfarin could not reduce the incidence of ACE observed with the nMARQTM catheter to the much lower incidence reported with both point-by-point RF and cryoballoon ablation systems.7,21 It is entirely possible that the concept of simultaneous circular mapping and ablation by a single catheter (e.g., PVAC and nMARQTM ) is flawed because their relatively limited shape and diameter cannot achieve homogenous consistent tissue contact around the unpredictably shaped and sized PV orifices. The absence of “high quality contact” generates a milieu that potentially promotes both poor contact and resultant char or gas bubble formation causing ACE and excessive contact increasing esophageal injury. Unless these concerns can be satisfactorily addressed, this may have been the last shot for “one shot” PVI using RF energy.
Acknowledgment: The authors wish to thank Dr. David E. Haines for thoughtful insight and discussion.
References 1. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NAM 3rd, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM; on behalf of the 2006 ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation Writing Committee: 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;57:223-242. 2. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJG, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, KirchhofP, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Sheim RJ, Tsao HM, Wilber D: 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and
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6.
7.
8. 9.
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11.
Journal of Cardiovascular Electrophysiology
Vol. 25, No. 4, April 2014
Follow-up, Definitions, Endpoints, and Research Trial Design. Heart Rhythm 2012;9:632-696. Wilber DJ, Pappone C, Neuzil P, DePaola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; for the ThermoCool AF Trial Investigators: Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation. A randomized controlled trial. JAMA 2010;303:333-340. Packer DL, Kowal RC, Wheelan KR, Irwin JM,Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, Lehmann JW, Ruskin JN; for the STOP AF Cryoballoon Investigators: Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation. First results of the North American Artic Front (STOP AF) pivotal trial. J Am Coll Cardiol 2013;61:1713-1723. Wieczorek M, Hoeltgen R, Akin E, Salili AR, Oral H, Morady F: Results of short-term and long-term pulmonary vein isolation for paroxysmal atrial fibrillation using duty-cycled bipolar and unipolar radiofrequency energy. J Cardiovasc Electrophysiol 2010;21:399-405. Siklody CH, Deneke T, Hocini M, Lehrmann H, Shin DI, Miyazaki S, Henschke S, Fluegel P, Schiebeling-Romer J, Bansmann PM, Bourdias T, Dousset V, Haissaguerre M, Arentz T: Incidence of asymptomatic intracranial embolic events following pulmonary vein isolation: Comparison between different AF ablation technologies in a multicentric study. J Am Coll Cardiol 2011;58:681-688. Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F, Schade A, Froehner S, Ziegler V, Sergi D, Cesarani F, Blandino A: Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: Comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol 2011;22:961-968. Steinberg JS, Mittal S: Intracranial emboli associated with catheter ablation of atrial fibrillation. J Am Coll Cardiol 2011;58:689-691. Haines DE, Stewart MT, Ahlberg S, Barke N, Candle C, Fiedler GR, Kirchhof NA, Halimi F, Deneke T: Microembolism and catheter ablation I. A comparison of irrigated radiofrequency and multi-electrode phased radiofrequency catheter ablation of pulmonary vein ostia. Circ Arrhythm Electrophysiol 2013;6:16-22. Deneke T, Schade A, Muller P, Schmitt R, Christopoulos G, Krug J, Szollosi G, Mugge A, Kerber S, Nentwich K: Acute safety and efficacy of a novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation. J Cardiovasc Electrophysiol 2013;25:339345. Liu E, Shehata M, Liu T, Amorn A, Cingolani E, Kannarkat V, Chugh SS, Wang X: Prevention of esophageal thermal injury during radiofre-
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13. 14. 15.
16.
17.
18.
19.
20.
21.
quency ablation for atrial fibrillation. J Interv Card Electrophysiol 2012;35:35-44. Musat D, Aziz EF, Koneru J, Arshad A, Kamath GS, Mittal S, Steinberg JS: Novel computational method to predict esophageal temperature elevations during pulmonary vein isolation. PACE 2010;33:12391248. Musat D, Mittal S: The esophageal temperature probe: Helpful monitoring device or inadvertent amplifier of risk? J Cardiovasc Electrophysiol 2011;22:262-244. Vermeer SE, Prins ND, Heijer TD, Hofman A, Koudstaal PJ, Breteler MMB: Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215-1222. Deneke T, Shin DI, Balta O, Bunz K, Fassbender F, Mugge A, Anders H, Horlitz M, Pasler M, KarthikapallilS, Arentz T, Beyer D, Bansmann M: Postablation aymptomatic cerebral lesions: Long-term follow-up using magnetic resonance imaging. Heart Rhythm 2011;8:1705-1711. Haines DE, Steward MT, Barka ND, Kirchhof N, Lentz LR, Reinking NM, Urban JF, Halimi F, Deneke T, Kanal E: Microembolism and catheter ablation II. Effects of microemboli injection in a canine model. Circ Arrhythm Electrophysiol 2013;6:23-30. Shah AN, Mittal S, Sichrovsky TC, Cotiga D, Arshad A, Maleki K, Pierce WJ, Steinberg JS: Long-term outcome following successful pulmonary vein isolation: Patterns and prediction of very late recurrence. J Cardiovasc Electrophysiol 2008;19:661-667. Deneke T, Bunz K, Bastian A, Pasler M, Anders H, Lehmann R, Meuser W, DeGroot JR, Horlitz M, Haberkorn R, Mugge A, Shin DI: Utility of esophageal temperature monitoring during pulmonary vein isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation. J Cardiovasc Electrophysiol 2011;22:255-261. Scaglione M, Blandino A, Raimondo C, Caponi D, DiDonna P, Toso E, Ebrille E, Cesarani F, Ferrarese E, Gaita F: Impact of ablation catheter irrigation design on silent cerebral embolism after radiofrequency catheter ablation of atrial fibrillation: Results from a pilot study. J Cardiovasc Electrophysiol 2012;23:801-805. Martinek M, Sigmund E, Lemes C, Derndofer M, Aichinger J, Winter S, Jauker W, Gschwendtner M, Nesser HJ, Purerfellner H. Asymptomatic cerebral lesions during pulmonary vein isolation under uninterrupted anticoagulation. Europace 2013;15:325-31. Neumann T, Kuniss M, Conrad G, Janin S, Berkowitsch A, Wojcik M, Rixe J, Erkapic D, Zaltsberg S, Rolf A, Bachmann G, Dill T, Hamm CW, Pitschner HF: MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation: Comparison of pulmonary vein isolation using cryoballoon technique vs. radiofrequency energy. Europace 2011;13: 37-44.
