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 Table of Contents  
Year : 2017  |  Volume : 2  |  Issue : 1  |  Page : 13-21

Latest technologies and techniques to improve pulmonary vein isolation

Department of Cardiology, Princess Margaret Hospital, Lai Chi Kok, Kowloon, Hong Kong, China

Date of Web Publication19-Jun-2017

Correspondence Address:
Ho-Chuen Yuen
Princess Margaret Hospital, 2.10 Princess Margaret Hospital Road, Lai Chi Kok, Kowloon, Hong Kong
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2352-4197.208460

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Pulmonary vein isolation (PVI) is the established cornerstone in catheter ablation for atrial fibrillation (AF). The traditional point-to-point ablation by focal radiofrequency (RF) catheter to achieve PVI was technically challenging, and the outcome remained suboptimal despite advancement in three-dimensional electroanatomical mapping systems and steerable sheaths. Different catheter designs including contact force, balloon-based catheters with other energy sources (cryothermal and laser energies), and circular RF catheters have been developed to make the ablation procedure more user-friendly and PVI more durable. Adjunctive techniques including detection of dormant conduction by adenosine triphosphate injection and pace-capture-guided ablation have also been studied to improve the durability of PVI and thus reduce the AF recurrence rate.

Keywords: Atrial fibrillation, latest technologies, pulmonary vein isolation

How to cite this article:
Yuen HC, Chan NY. Latest technologies and techniques to improve pulmonary vein isolation. Int J Heart Rhythm 2017;2:13-21

How to cite this URL:
Yuen HC, Chan NY. Latest technologies and techniques to improve pulmonary vein isolation. Int J Heart Rhythm [serial online] 2017 [cited 2022 Jan 28];2:13-21. Available from: https://www.ijhronline.org/text.asp?2017/2/1/13/208460

  Introduction Top

Thanks to the early work of Haissaguerre, pulmonary vein (PV) was identified as a source of ectopic activity initiating atrial fibrillation (AF).[1] PVs have muscular sleeves which extend into the left atrium, and special cells (P cells, transitional cells, and Purkinje cells) are found in these muscular extensions in histopathological observations. This forms the basis for PV isolation (PVI) as an ablation strategy for AF. Electrical isolation of PVs by catheter ablation significantly reduces the burden of AF as compared to antiarrhythmic drugs.[2] PVI is now the mainstay of catheter-based therapy for paroxysmal AF. For persistent AF, additional ablation is thought to be necessary because of other predisposing substrates in perpetuation of AF in addition to PV trigger. Different ablation strategies have been tried to improve the success rate in persistent AF. However, the recent STAR AF 2 trial showed that PVI alone was as effective as PVI with additional complex electrogram ablation or linear ablation.[3]

In the past, the only available technology for PVI involved a focal radiofrequency (RF) catheter, making circumferential lesions around PV antrum in a point-to-point fashion. It is time-consuming and technically demanding to achieve a truly contiguous lesion set even with the advent of three-dimensional electroanatomical mapping systems and steerable sheaths. Effective lesion formation requires good catheter contact, but catheter contact cannot be accurately assessed by tactile feedback alone even in experienced hands.[4] Contact force (CF)-sensing technology has been developed to give clear guidance for catheter contact and lesion formation. In response to the urge for faster and more user-friendly ablation tools for PVI, balloon-based catheters with the use of other energy sources and circular RF catheters have been developed as a single-shot device to meet this need. Different balloon-based catheters included cryoballoon (CB), laser-based balloon, high-intensity focused ultrasound (HIFU) balloon, and hot balloon. In this paper, we will focus on CB and laser-based balloon because HIFU balloon was withdrawn from the market after several serious complications, and data on hot balloon were limited outside Japan. [Table 1] shows the brief summary of the characteristics and outcomes of different ablation tools.
Table 1: Brief summary of characteristics and outcomes of different ablation tools

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Despite all the advancement of ablation tools, AF still recurs after complete electrical disconnection of the PVs in around 30–50% of cases. Reconnection of the initially isolated PVs and non-PV trigger are thought to be the major causes of recurrence. Studies showed at least one PV was found to be reconnected in 80% of patients with recurrence of AF.[5] The ability to predict the durability of PVI during an ablation procedure might enable additional targeted ablation of veins at high risk of reconnection, and thus prevent arrhythmia recurrence. In this regard, adenosine triphosphate (ATP) injection and pace-capture-guided ablation are the two recently developed methods to improve the durability of PVI.

  Latest Technologies for Pulmonary Vein Isolation Top

Contact force

The occurrence of PV reconnection is considered to be due to failure to create transmural RF lesions. The electrode-tissue contact of the ablation catheter tip has been shown to be an important factor in determining the RF lesion size.[6] CF-sensing technology might be the solution to ensure catheter contact. There are now two commercially available CF-sensing RF catheters in the market: TactiCath (St. Jude Medical Inc., St. Paul, MN, USA) and ThermoCool SmartTouch (Biosense Webster Inc., Diamond Bar, CA, USA) [Figure 1]. The feasibility and efficacy of CF monitoring during AF ablation have been demonstrated in recent clinical trials. The EFFICAS I trial showed minimum CF and minimum force-time integral (FTI) were strong predictors of gap formation.[7] A catheter CF of 20 g with a minimum of 400 g/s FTI should be the optimal CF parameter recommendation. The use of CF with the above recommendation was associated with more durable PVI as shown in EFFICAS II trial.[8] About 85% of PVs remained isolated at 3 months in EFFICAS II in which CF parameter recommendation was used, whereas only 72% of PVs were kept isolated in EFFICAS I in which CF parameter recommendation was not used. TOCCASTAR study, a prospective, multicenter, randomized, controlled trial, randomized 300 patients with paroxysmal AF to RF with either a CF-sensing catheter or a non-CF catheter (control).[9] Effectiveness was similar between two groups with freedom from AF at 12 months being 67.8% in the CF group and 69.4% in the control group (P = 0.0073 for noninferiority). When the CF arm was stratified into optimal CF (≥90% ablations with ≥10 g) and nonoptimal CF groups, freedom from AF at 12 months was achieved in 75.9% versus 58.1%, respectively (P = 0.018). For the safety aspect, similar device-related serious adverse events occurred in the CF and control groups (P = 0.0004 for noninferiority) with 1 cardiac perforation in each group. Achieving optimal CF with a CF-sensing catheter seems to be the way to go to achieve permanent PVI with RF catheter.
Figure 1: Contact force module integrated into EnSite cardiac mapping system. It demonstrated real-time position of contact over catheter tip, contact force, and force-time integral.

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Point-to-point movement of the focal ablation catheter requires high level of manual skills and is time-consuming. Given the approximately circular shape of the PV ostia, more recent ablation platforms have logically been built with circumferential energy delivery. Among all the single-shot PV isolation tools, the CB (Arctic Front, Medtronic Inc., Minneapolis, MN, USA) has achieved widespread use in the recent years. The CB ablation system also allows a circular mapping catheter (Achieve, Medtronic Inc., Minneapolis, MN, USA), which is deployed through the CB catheter guidewire lumen to provide recording of real-time PV potentials during cryoablation [10] [Figure 2]. Cryothermal energy is demonstrated to create more favorable lesions with less thrombus formation and preserved underlying cellular matrix and tensile strength when compared to RF.[11] The novel CB system was first shown to be effective for isolating PVs in dogs in 2005.[12] CB was then tested in humans, and the treatment success of CB was significantly better than antiarrhythmic drugs in patients with paroxysmal AF in STOP AF study, a prospective, multicenter, randomized, controlled trial.[13] In this study, freedom from AF at 12 months was 69.9% in cryoablation patients compared with only 7.3% in patients on antiarrhythmic drugs (P< 0.001). In a meta-analysis of CB ablation including 519 participants with paroxysmal AF in 5 studies, the 1-year freedom from recurrent AF with a 3-month blanking period was 72.83%.[14] In a single center prospective randomized trial, FreezeAF study comparing CB with irrigated-tip RF catheter, CB ablation showed similar efficacy in achieving freedom from AF at 1 year (multiple procedure success, 73.6% in CB group vs. 70.7% in RF group, P < 0.001 for noninferiority).[15] As expected for a single-shot device, CB ablation required shorter procedural time (median 161 min) when compared to RF catheter (median 174 min, P = 0.006).[14] A steep learning curve for CB ablation was demonstrated in different centers with progressively shorter procedural and fluoroscopy time as the number of cases performed increased.[16],[17]
Figure 2: The inner lumen mapping catheter was positioned distal to the cryoballoon in the left superior pulmonary vein to provide recording of real-time pulmonary vein potentials during cryoablation (LAO 40°).

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In the first generation CB, one of the technical limitations is a temperature gradient from the equator to the distal pole of the balloon with less effective cooling around the balloon nose. This area is typically in contact with the lower circumference of the inferior PVs where conduction gaps were preferentially found during repeat procedures.[18] With this design of the first generation CB, the ability to complete PVI without touch-up lesions by focal ablation catheter ranged from 40% to 92%.[13],[19],[20] This limitation has been overcome in the development of second generation CB (Arctic Front Advance, Medtronic Inc., Minneapolis, MN, USA). The second generation CB has a more homogenous cooling of the frontal balloon hemisphere because of repositioning and doubling the number of injection ports and increasing the refrigerant flow in the larger 28 mm balloon. In a high volume Germany center, second generation CB attained a high rate of acute PVI with fewer balloon applications, no requirement of focal touch-up, and shorter procedural time when compared to first generation CB.[21] In the SUPIR study by Reddy et al., a second PV remapping procedure at 3 months after PVI by second generation CB in 21 patients revealed that 91% of veins remained electrically isolated.[22] Nonrandomized outcome studies showed the 1-year treatment success was significantly better in the second generation CB group when compared to the first generation CB group.[23],[24] The rate of freedom from AF without antiarrhythmic drugs at 1 year was higher than 80% in the second generation CB group.[23],[24] The third generation of CB (Arctic Front Advance Short-tip, Medtronic Inc., Minneapolis, MN, USA) has received the US Food and Drug Administration approval recently. It is designed with a 40% shortened tip length compared to the former second generation CB. A shorter tip should permit an improved visualization of real-time recordings of PV potential due to a more proximal positioning of the inner lumen mapping catheter.

To achieve an even lower PV reconnection and AF recurrence rate, predictors for durable PVI were studied in patients undergoing a repeat procedure for AF recurrence after second generation CB ablation.[25] It showed that faster time to isolation and achievement of −40°C within 60s independently predicted durable PVI. In addition, 60s cutoff for time to PVI indicated persistent isolation with 96.4% negative predictive value.

Randomized studies comparing the second generation CB with RF catheter are lacking, but one nonrandomized study showed better efficacy for second generation CB when compared to RF. This multicenter, retrospective, nonrandomized study comparing the clinical outcomes of 1196 patients (76% with paroxysmal AF) undergoing PVI using second generation CB, and open-irrigated, non-CF sensing RF showed that second generation CB had greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic drugs (76.6% in second generation CB vs. 60.4% in RF, P < 0.001).[26] With the advent of CF-sensing RF catheter and evidence of better outcome with optimal CF during procedure, it would be interesting to see if second generation CB could outperform CF-sensing RF catheter. In a recent multicenter nonrandomized study comparing second generation CB and CF-sensing RF catheter, the single procedure freedom from any atrial arrhythmias at 18 months was comparable in both groups (73.3% vs. 76% respectively, P = 0.63).[27]

Recently, the long-awaited FIRE AND ICE trial has been published. In this randomized trial comparing CB to open-irrigated RF in treating patients with symptomatic paroxysmal AF, CB ablation was noninferior to RF ablation with respect to efficacy. The primary efficacy endpoint (mainly recurrence of atrial arrhythmias) occurred in 34.6% in CB group and 35.9% in RF group by 1-year Kaplan–Meier event rate estimates P < 0.001 for noninferiority. There was no significant difference between two methods with regard to overall safety.[28]

One of the major concerns in CB ablation is the higher rate of phrenic nerve injury during right-sided PV ablation when compared to RF. Rate of phrenic nerve palsy was found to be quite high (11.2%) in cryoablation patients in STOP AF trial although most of them resolved within 12 months.[13] Different methods have been developed to minimize the risk of phrenic nerve injury. The most promising one seems to be phrenic nerve monitoring by recording diaphragmatic compound motor action potentials (CMAP) described by Franceschi et al.[29] In this study, cessation of CB ablation when there was 30% reduction of CMAP amplitude could successfully prevent phrenic nerve palsy. Another problem with CB, especially the more powerful second generation CB is the increased incidence of esophageal injury. One study showed esophageal thermal lesions occurred in 12% of patients after second generation CB ablation.[30] Atrioesophageal fistula, a dreadful complication of AF ablation which was previously thought to occur only after RF ablation, was also reported after CB ablation recently.[31] Fürnkranz et al. advocated the use of luminal esophageal temperature (LET) to reduce esophageal injury after CB ablation. In his study, interrupting CB ablation at 15°C LET reduced the incidence of esophageal lesions to 1.5%.[32]

  Visually Guided Laser Balloon Top

Laser balloon is a balloon-based catheter ablation system which emerges to be feasible and safe in achieving PVI for patients with AF. The unique characters in visually guided laser balloon (VGLB) catheter using the endoscopic ablation system (CardioFocus Inc., Marlborough, MA, USA) are its abilities to provide real-time endoscopic visualization and to deliver laser energy at operator-determined locations around PV-left atrial junction. The VGLB catheter is a balloon that is delivered through a deflectable 12-Fr sheath. Within the central shaft of the balloon is a 2-Fr endoscope that provides real-time visualization of the face of the balloon: Both the tissue and blood in contact with the balloon. In addition, within the central shaft is additional lumens for circulating D2O to cool the balloon, and a maneuverable optical fiber that generates an arc of visible diode laser energy (980 nm). The arc of light can be advanced/retracted and rotated to any location on the face of the balloon. Ablation lesions are placed in a contiguous and overlapping manner to achieve electrical isolation of the PV [Figure 3].
Figure 3: Endoscopic view of a left superior pulmonary vein. The shaft of the endoscopic ablation system obstructs the view of the posterior portion of the pulmonary vein. The green light is the aiming beam of the laser. Reproduced from, with permission from John Wiley and Sons. Copyright © 2012, John Wiley and Sons.[38]

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The first generation VGLB catheter was demonstrated to be feasible for AF ablation in canine models and humans in 2009.[33] In this study, the rate of acute PVI was suboptimal (91%). The major limitations in the first generation VGLB catheter are its difficulty in achieving optimal balloon contact due to balloon noncompliance (20, 25, and 30 mm fixed diameter) and the risk of thrombus formation from ablation at areas with overlapping blood due to the large 90–150° ablative arc. The balloon was later redesigned to (1) maximize balloon-tissue contact by making a balloon of adjustable diameter and compliance (9–35 mm diameter) and (2) allow the delivery of spot laser lesions (30° ablative arc). The laser source is titratable and allows energy level from 5.5 W to 12 W with the length of an energy application for 20–30 s depending on operator's choice. This second generation VGLB catheter was first evaluated in 27 patients with paroxysmal AF in 2010.[34] About 100% of PVs were acutely isolated, and 90% of PVs continued to be electrically isolated during remapping at 3 months. In another multicenter PV remapping study including 56 patients with paroxysmal AF, 98% of PVs were acutely isolated and 86% of PVs remained isolated at 3 months.[35]

Concerning the outcome data, the rate of freedom from AF at 1 year ranged from 60.2% to 82.3% according to different publications.[36],[37],[38] In these studies, almost 99% of PVs were acutely isolated without additional catheters for touch-up energy delivery. In the study reporting the relatively high recurrence rate, the author attributed it to possible ostial location of laser lesions which largely excluded areas in the antrum that might be responsible for the initiation and perpetuation of AF.[36] The more ostial ablation in this study was probably operator-dependent rather than related to the VGLB catheter design. The VGLB catheter actually allows delivery of a more antral lesion because the 30° ablative arc can be advanced/retracted and rotated to any location on the face of the balloon. Another possible explanation for the higher recurrence rate could be the unknown optimal energy level for PVI. Two studies tried to examine the clinical efficacy of VGLB catheter on the use of low-energy versus high-energy application.[39],[40] In the study by Metzner et al., ablation was performed using 5.5 and 7.0 W (Group A), 7.0 and 8.5 W (Group B), and 8.5 and 10.0 W (Group C) along the posterior and anterior portion of each PV, respectively.[39] The rate of acute PVI after a single circular lesion set was significantly higher in Group C than in Group A (P = 0.025) and Group B (P = 0.045). Better results in high-dose group were also demonstrated in another study comparing 5.5–8.5 W in the low-dose group and >8.5 W in the high-dose group with acute PVI after a single circular lesion set being 69% and 89%, respectively (P = 0.0004).[40] Esophageal temperature rises and phrenic nerve palsies occurred at a similar rate in both groups in this study.

There is limited data on comparison of the VGLB catheter with other ablation catheters. One single center study in Germany, prospectively randomized 140 patients with paroxysmal AF to the CB and VGLB groups.[41] During 12 months follow-up, the recurrence rate was statistically not different with 37% of patients in the CB group and 27% in the VGLB group experiencing an AF recurrence (P = 0.18). Phrenic nerve palsies occurred in 5.7% of CB patients and 4.2% of VGLB patients. The mean procedural time was also similar in both groups (136 ± 30 min in CB group vs. 144 ± 33 min in VGLB group, P = 0.13). The VGLB catheter was compared to standard irrigated RF ablation in a recent multicenter randomized controlled study involving 353 patients at 19 clinical sites.[42] The 1-year freedom from AF without antiarrhythmic drugs was similar between two groups with 61.1% in the VGLB group and 61.7% in the RF group (P = 0.003 for noninferiority). Diaphragmatic paralysis was higher in the VGLB group (3.5%) when compared to only 0.6% in the RF group (P = 0.05). The mean procedural, ablation, and fluoroscopy times were longer with VGLB compared with RF. Most of the operators in this study had extensive experience with standard RF catheter and limited experience with VGLB. It was found that procedural and fluoroscopy times improved significantly with more VGLB experience in the VGLB group.

For the safety of the VGLB catheter, 2 important safety issues were observed in the initial experience.[36] The first one was the relatively high rate of cardiac perforation (3%). The inability to use an over-the-wire technique when positioning the VGLB catheter probably accounted for the increased rate of cardiac tamponade. With the development of a softer atraumatic catheter tip, the risk of perforation should be reduced. The second safety event was phrenic nerve palsy. Phrenic nerve injury has been described with other balloon catheters including CB. However, unlike with the CB catheter, the anatomical location of lesion delivery can be tailored according to anatomy with the VGLB catheter. Therefore, delivery of a more antral lesion set around the right-sided PVs in locations that are susceptible to phrenic nerve injury may help decrease this complication.

  Circular Radiofrequency Catheters Top

Circular multielectrode RF catheters were developed to address the technical difficulties of point-to-point PV antral ablation with focal RF catheters. The first developed one is the 10-pole PV ablation catheter (PVAC, Medtronic Ablation Frontiers, Carlsbad, CA, USA). It was designed from a typical circular mapping catheter shape and is capable of delivering duty-cycled unipolar and bipolar RF energy, thereby potentially creating a contiguous circumferential lesion with minimal repositioning requirement [Figure 4]. The initial data appeared promising with regard to shorter procedural times and short-term success rates comparable to those of focal irrigated RF ablation. Bulava randomized 102 patients with paroxysmal AF to PVAC-based or conventional three-dimensional mapping-based focal RF ablation. After a mean follow-up of 200 ± 13 days, 77% in the PVAC group and 71% in the focal RF group were in sinus rhythm and free from symptomatic or documented AF recurrence (P = 0.80).[43] Bittner randomized 80 consecutive patients with AF (55% with paroxysmal AF) to PVAC-based or three-dimensional mapping-based focal RF ablation. After a mean follow-up of 254 ± 99 days, 72% in the PVAC group and 68% in the focal RF group were free from AF (P = 0.48).[44] The procedural and fluoroscopy times were lower in the PVAC group (171 ± 40 min vs. 224 ± 27 min, P < 0.01; 26 ± 8 min vs. 35 ± 9 min, P < 0.001, respectively).[44] There was one randomized study comparing PVAC and CB. This randomized study, the AF-COR study, randomized 110 patients with AF (69% with paroxysmal AF) to PVAC or CB. After the index ablation procedure, complete freedom from AF, without antiarrhythmic drugs, was seen in 46% in the CB group and 34% in the PVAC group after 12 months (P = 0.2).[45] The author attributed the low treatment efficacy in this study to the presence of persistent AF and relatively long duration of AF (mean 8 years) in the study population.
Figure 4: LAO view with the pulmonary vein ablation catheter in the antral region of each pulmonary vein: right superior pulmonary vein RSPV (a), left superior pulmonary vein (b), right inferior pulmonary vein (c), and left inferior pulmonary vein (d). Multipolar catheters in coronary sinus, left atrial appendage, and high right atrium for differential pacing. Reproduced from Wieczorek M, Hoeltgen R, Brueck M, et al. Pulmonary vein isolation by duty-cycled bipolar and unipolar antrum ablation using a novel multielectrode ablation catheter system: first clinical results. J Interv Card Electrophysiol 2010;27:23.31, with permission from Springer. Copyright © 2009, Springer.

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However, increased vigilance for asymptomatic cerebral emboli (ACE) showed an alarming high incidence of these lesions after PVAC ablation (37.5–38.9%), and the rate was significantly higher than with CB (4.3–5.6%) or irrigated-tip RF (7.4–8.3%).[46],[47] In addition, multiple and larger ACE was noted after PVAC ablation. While the clinical importance of ACE after interventional cardiac procedures remains to be demonstrated, an association with neuropsychological decline has been described.[48] Higher chance of heat-related generation of coagulum and char in a system without external irrigation could be one of the reasons for ACE formation. Investigations into other possible mechanisms showed PVAC ablation with the distal and proximal electrodes in close proximity caused high current densities and increased the risk of ACE.[49]

Another circular RF catheter which is equipped with external irrigation was then developed with a hope to keep the simplicity and elegance of the design but minimize the complications. The advantages of this catheter, nMARQ irrigated circular decapolar mapping and ablation catheter (Biosense Webster Inc., Diamond Bar, CA, USA), over PVAC are the presence of irrigation, which lowers the electrode temperature to reduce charring, and the compatibility with the CARTO 3 system (Biosense Webster Inc., Diamond Bar, CA, USA), which allows more precise antral ablation with three-dimensional electroanatomical mapping [Figure 5]. The data on feasibility of nMARQ were promising. Among the published studies so far, the overall acute PVI rate was around 99%.[50],[51],[52] Touch-up ablation with focal catheter was rarely needed (0–2.2%) to complete PVI.[52],[53] Procedural and fluoroscopy times were short with a rapid learning curve.[52],[53] With regard to safety, one series reported a similarly high incidence of ACE up to 33% when compared to previous reports of the PVAC.[50] In one study, charring was noted in patients using bipolar energy delivery or with overlapping of the proximal and distal electrodes during energy application.[52] Therefore, another study carried out special precautions such as using unipolar energy delivery only and avoiding overlapping the proximal and distal electrodes to minimize ACE, and it showed that incidence of ACE could be reduced to zero with these special precautions.[51] High incidence of thermal esophageal lesions (33%) and a dreadful case of an esophago-pericardial fistula was also reported.[50],[54] Since the report of esophago-pericardial fistula, modified energy settings with reduced power and duration, especially for posterior walls were adopted in most centers. One series showed thermal esophageal injury could be significantly reduced with limited power and RF application time at the posterior wall.[55] A causal connection between multielectrode ablation and observed esophageal lesions by passive heating of an intraluminal temperature probe was suggested previously.[56] One study performed a nonrandomized comparison between using and not using a thermal esophageal probe in nMARQ ablation and demonstrated a significant reduction in thermal esophageal lesions when not using a thermal esophageal probe (0% vs. 28%, P < 0.0001).[57] Unlike other single-shot ablation tools, phrenic nerve palsy seldom occurred with nMARQ catheter.[52],[53]
Figure 5: (a) nMARQ™ ablation catheter. (b) nMARQ™ Multi-Channel Ablation System indicating energy (w), electrode temperature (t), and local impedance for each electrode. (c and d) Fluoroscopic image of the nMARQ™ in the right superior pulmonary vein (c) and the left inferior pulmonary vein (d). (e and f) Carto3 images of the nMARQ™ in the antrum of the right inferior pulmonary vein (e) and the left superior pulmonary vein (f ). Reproduced from, with permission from John Wiley and Sons. Copyright © 2013, John Wiley and Sons.[51]

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Follow-up data are only available in a few publications. In the Scaglione series, 17 of 25 patients (68%) with paroxysmal AF were free from AF without antiarrhythmic drugs at a 6-month follow-up.[51] In the Stabile series, 102 of 140 patients with paroxysmal AF (73%) and 28 of 40 patients with persistent AF (70%) were free from atrial arrhythmias after a mean follow-up of 13.9 months.[53] In the Deneke series, 43 of 65 patients (66%) were free from AF after a 12-month follow-up.[57] Data on comparison of nMARQ catheter with other ablation tools are currently lacking.

  Latest Techniques to Improve Durability of Pulmonary Vein Isolation Top

Adenosine triphosphate injection

Dormant PV conduction induced by ATP injection after initially successful PVI was first reported by Arentz et al.[58] Experiment in canine models showed that PVs with dormant conduction showed less RF-induced depolarization than nondormant PVs, allowing ATP-induced hyperpolarization to restore excitability and then conduction in dormant PVs.[59] ATP-guided additional ablation until disappearance of dormant conduction has been proposed as an adjunctive approach to establish durable PVI and thus reduce the recurrence of AF. Three observational studies showed promising results by ATP-guided PVI with a significant reduction in the incidence of AF recurrence when compared with historical control.[60],[61],[62] The relative risk reduction ranged from 32.5% to 50%. Moreover, two recent large-scale multicenter randomized trials, ADVICE and UNDER-ATP, have provided conflicting results on the benefit of ATP-guided PVI.[63],[64] In ADVICE study, among 534 patients with paroxysmal AF, 284 (53%) had dormant conduction revealed by adenosine and were randomized to additional adenosine-guided ablation or no further ablation. The event-free rate from recurrent atrial arrhythmias at 1 year after ablation with the 3-month blanking period was 69.4% and 42.3%, respectively, with relative risk reduction of 56% (P< 0.001).[63] In contrast, the result of UNDER-ATP study did not support ATP-guided ablation. The UNDER-ATP study randomly assigned 2113 patients with paroxysmal, persistent, or long-standing AF to either ATP-guided PVI or conventional PVI. Among patients assigned to ATP-guided PVI, dormant conduction was provoked by ATP in 27.6% of patients and additional RF energy was applied to eliminate dormant conduction in these patients. At 1 year, 68.7% of patients in the ATP-guided PVI group and 67.1% of patients in the conventional PVI group were free from atrial arrhythmias after the 3-month blanking period, with no significant difference between groups (P = 0.25).[64] The author in UNDER-ATP study attributed the negative results in this study to the lower rate of dormant conduction (27.6%) when compared to other studies (41–56%).[60],[61],[62],[63],[64] In the UNDER-ATP study, multiple measures including irrigation catheters, advanced three-dimensional mapping systems, deflectable sheaths, and waiting time for more than 30 min to detect spontaneous PV reconnection were used to ensure durable PVI, possibly resulting in lower rate of dormant conduction when compared to other studies. The clinical impact of the ATP-guided ablation might become much smaller when rate of dormant conduction is low under the current advanced ablation technologies and strategies.

Pace-capture-guided ablation

Additional ablation over sites with pace capture along the circumferential antral ablation line has been proposed to reduce reconnection rate of PVs. In the Steven series, operators were blinded to PV electrograms when they were performing PVI by achieving loss of pace capture at 10 mA/2 ms along the circumferential antral ablation line.[65] Analysis of the blinded PV electrograms revealed that even after PVI was achieved, additional sites of pace capture were present in the ablation line in 30 of 60 (50%) PV pairs. After completion of loss of pace capture along the line, PVI was present in 57 of 60 (95%) vein pairs. Thus, pace capture along the line has the potential to identify conduction gaps. In another study using the pace-capture-guided ablation approach, the follow-up data showed a high clinical success rate among patients with paroxysmal AF with <20% of those had recurrence of atrial arrhythmias over a mean follow-up of 1.5 years.[66] A 2-center randomized study included 102 patients with symptomatic paroxysmal AF comparing bidirectional block across the PV ablation line as procedural endpoint (Group 1) versus additional unexcitability to bipolar pacing at 10 mA/2 ms as procedural endpoint (Group 2).[67] After a follow-up of 12 months, 26 of 50 patients (52%) in Group 1 versus 43 of 52 patients (82.7%) in Group 2 were free from atrial arrhythmias (P = 0.001), strongly in favor of pace-capture-guided ablation. There was one nonrandomized study comparing the adenosine-guided ablation versus pace-capture-guided ablation.[68] In this study, 50% of patients in the pace-capture group demonstrated high-output pace capture after PVI, whereas 53% of patients in the adenosine group revealed dormant conduction by adenosine injection. Further ablation was performed to render the ablation line unexcitable in the pace-capture group and eliminate dormant conduction in the adenosine group. Both groups showed similar efficacy with 67.5% in the adenosine group and 65.0% in the pace-capture group being free from AF at a mean follow-up of 329 days (P = 0.814). Further studies are needed to find out the best strategies to ensure durable PVI.

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  References Top

Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-66.  Back to cited text no. 1
Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: A randomized controlled trial. JAMA 2010;303:333-40.  Back to cited text no. 2
Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812-22.  Back to cited text no. 3
Kuck KH, Reddy VY, Schmidt B, Natale A, Neuzil P, Saoudi N, et al. Anovel radiofrequency ablation catheter using contact force sensing: Toccata study. Heart Rhythm 2012;9:18-23.  Back to cited text no. 4
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012;14:528-606.  Back to cited text no. 5
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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