CLINICAL RESEARCH
Europace (2015) 17, 725–731 doi:10.1093/europace/euu331
Ablation for atrial fibrillation
High rate of durable pulmonary vein isolation after second-generation cryoballoon ablation: analysis of repeat procedures Stefano Bordignon, Alexander Fu¨rnkranz, Laura Perrotta, Daniela Dugo, Athanasios Konstantinou, Bernd Nowak, Britta Schulte-Hahn, Boris Schmidt, and Kyoung Ryul Julian Chun* CCB—Cardioangiologisches Centrum Bethanien, Markuskrankenhaus, Wilhelm-Epstein Strasse 4, 60431 Frankfurt Am Main, Germany Received 10 September 2014; accepted after revision 28 October 2014; online publish-ahead-of-print 24 January 2015
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Cryoablation † PV reconduction
Introduction Pulmonary vein isolation (PVI) represents the cornerstone in paroxysmal atrial fibrillation (AF) ablation.1 Traditionally, radiofrequency current (RFC) energy ablation encircling point by point the ipsilateral pulmonary veins (PVs) has been proposed as the standard ablation strategy. However, this approach is limited by a long individual learning curve and high technical complexity. The cryoballoon (CB) system has been introduced to facilitate in obtaining the procedural endpoint of PVI. Importantly, all currently utilized ablation energy sources and ablation strategies are characterized by high rates of
recovered PV conduction along ablation lesions.2 – 4 Therefore, multiple ablation procedures may be often required to obtain chronic PVI.5 The first-generation CB (CB1) was characterized by a nonhomogeneous cooling along the equator region. Therefore, despite feasibility of acute PVI, CB1 ablation was characterized by a high rate of AF recurrence along with resumed PV conduction during follow-up. Interestingly, a typical reconduction gap pattern predominantly along inferior PVs has been described.2 In contrast, the second-generation CB (CB2) enables homogeneous cooling of the distal portion of the balloon (‘north pole’) resulting in improved
* Corresponding author. Tel: +49 69 945028110; fax: +49 69 945028119, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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Pulmonary vein isolation (PVI) using the first-generation cryoballoon (CB1) was characterized by a high rate of recovered pulmonary vein (PV) conduction along with a typical conduction gap pattern in patients with recurrent atrial tachyarrhythmia (ATa). Second generation (CB2) enables more uniform freezing. However, the rate of chronic PVI and PV conduction gap pattern is unknown. ..................................................................................................................................................................................... Methods All patients with ATa recurrence undergoing a second procedure after CB2 or (historical) CB1 PVI (28 mm) were enand results rolled. In all patients, a left atrial three-dimensional electronatomic reconstruction was performed. The rates of chronic PVI and localization of PV conduction gaps were determined and compared between CB1 and CB2. Antral PV re-isolation was performed using irrigated-tip radiofrequency current energy ablation. Of 206 patients (CB2), 18 patients underwent the repeat procedure after 192 (75:245) days. In 6 of 18 (33%) patients, all PVs were electrically isolated whereas in the remaining 12 patients (66%) at least one PV demonstrated PV reconduction. Of 71 PVs [1 left common PV (LCPV)], 55 PVs (77%) were chronically isolated. The right superior PV (RSPV) was characterized by the lowest rate of chronic PVI (RSPV: 56%, LSPV: 76%, RIPV: 83%, LIPV: 94%, LCPV: 100%). Compared with CB1, CB2 ablation resulted in a significantly higher rate of chronic PVI (CB2: 77% vs. CB1: 32%; P , 0.0001) with the greatest improvement along both inferior PVs. ..................................................................................................................................................................................... Conclusion Second-generation cryoballoon atrial fibrillation ablation is associated with a high rate of durable PVI in patients with ATa recurrence. The RSPV represents the PV with the greatest risk for left atrium–pulmonary vein reconnection.
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What’s New? † The new generation cryoballoon (CB2) is associated with a better mid- and long-term follow-up compared with the firstgeneration cryoballoon (CB1). † We first compared CB1 vs. CB2 in terms of durable pulmonary vein isolation (PVI) in symptomatic patients undergoing a second ablation procedure. † CB2 was associated with a 77% rate of durable PVI. † The significant improvement compared with CB1 was related to a better durable isolation of inferior PVs. † The right superior PV is the vein with the highest rate of PV reconnection using CB2.
procedural parameters and resulting in ca. 80% SR after 12 months clinical follow-up.6 – 10 CB2 is also associated with a low acute reconnection rate after adenosine challenge.11 However, the rate of chronic PVI and the conduction gap pattern remains undetermined.
Methods
Index second-generation cryoballoon ablation The simplified single big cryoballoon technique has been described elsewhere.3 In brief, after a single transseptal puncture using the modified Brockenbrough technique (BRK-1 needle, 8.5F SL1 transseptal sheath, St Jude Medical), PV angiographies were performed. The CB delivery sheath (12F, Flex Cath Advance, Medtronic) was advanced into the left atrium (LA). The second generation 28 mm CB was used in conjunction with a multipolar spiral catheter (SC —Achieve, Medtronic) (Arctic Front Advance—CB2, Medtronic) allowing registration of PV conduction and determination of the moment of PVI. Pulmonary vein occlusion was assessed by contrast medium injection through the distal CB lumen. Cryoballoon freeze duration was set to 240 s. The delivery of a bonus application after acute PVI was optional. During ablation of both septal PVs, an octapolar diagnostic catheter (7F ParaHis —Biosense Webster) stimulated the phrenic nerve (PN) from the superior vena cava (12V, 2.9 ms, 1000 ms) to early identify PN dysfunction. A temperature probe (SensiTherm, St Jude Medical) was inserted into the oesophagus to monitor the luminal oesophageal temperature (LET). All relevant procedural data such as minimal CB temperature and LET have been systematically collected.
Repeat ablation procedure after second-generation cryoballoon ablation All patients with documented recurrence of atrial tachyarrhythmias (ATa) lasting .30 s were offered a repeat AF ablation procedure. All repeat procedures were performed under conscious sedation (midazolam, propofol, and fentayl boluses followed by a propofol infusion). After double transseptal puncture, a three-dimensional (3D) electroanatomical (EA) LA map (Carto 3, Biosense Webster) was performed
using a 3.5 mm irrigated-tip radiofrequency (RF) catheter (ThermoCool NaviStar, Biosense Webster). Selective PV angiograms were performed and both ipsilateral PV ostia were tagged in the LA CARTO map as previously described.12 A decapolar spiral catheter (Lasso 15/20 mm, Biosense Webster) was positioned within the proximal PV ostium to assess potential LA– PV reconduction. If LA – PV reconduction was present, the PV spike sequence was analysed to identify the earliest PV activation site. Radiofrequency ablation was guided by PV activation sequence and local map potential along the tagged PV ostium level (Figure 1). Gap location was defined as the site of successful re-isolation of the PV or the site of clear change in the PV electric activation pattern, as previously published.2 All PVs were divided into four quadrants [antero-superior (AS); antero-inferior (AI); postero-inferior (PI); postero-superior (PS)] to categorize the gap location. In patients presenting with AF as the type of ATa recurrence, only re-PVI was performed. In patients presenting with atrial tachycardia (AT), the underlying tachycardia mechanism was elucidated combining 3D EA-mapping with conventional electrophysiological (EP) information such as entrainment manoeuvres. After AT termination, re-PVI was performed in SR.
Comparison: first-generation cryoballoon vs. second-generation cryoballoon Pulmonary vein reconduction data after CB1 procedure were obtained from our centres CB cohort of the recently published ‘Laser vs. CryoStudy’.3 This historical CB1 group served as the comparator.
Follow-up After the ablation procedure, all patients were seen in our outpatient clinic at 3, 6, 9, and 12 months and in 6 months intervals thereafter and obtained a 72 h Holter-ECG. In case of symptoms suggestive of an ATa recurrence, patients received an external event monitor. Atrial tachyarrhythmia recurrence has been defined as documented episodes lasting .30 s.
Objectives and endpoints Primary endpoint To characterize LA– PV reconduction rates and localization of PV conduction gaps after CB2 PV isolation.
Secondary endpoints To compare LA – PV reconduction after CB1 and CB2 PVI ablation. To identify procedural parameters predicting LA – PV reconduction after CB2 ablation. To analyse repeat procedural parameters, complications, and patient outcome.
Statistical analysis All quantitative variables with a normal distribution were reported as mean + standard deviation, and compared using the Student’s t-test. For the descriptive variables comparison, the Pearson’s x2test or the Fisher’s exact test wherever appropriate was used. An odds ratio with 95% confidence interval (CI) was computed to compare PV isolation rates after PVI using the CB1 and CB2.
Results Patients and procedure A repeat AF ablation procedure was performed in 18 of 206 patients (9%) after 192 (75–245) days post-index CB2. The historical CB1 control group consisted of 22 of 70 patients in which the repeat
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All AF ablation procedural data have been collected in the CCB database since May 2010. All CB2 PVI patients undergoing a repeat procedure have been identified. Procedural data from the repeat procedures after CB2 ablation have been analysed. A historical cohort of CB1 ablation repeat procedures from the same institution served as a control group. All the patients gave written consent, and the study was approved by the Institutional Review Board.
S. Bordignon et al.
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Durable PVI after second-generation cryoballoon ablation
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PA LAO RAO LL RL INF SUP
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! V1 20 mm/mV PV 1–2 50 mm/mV PV 2–3 50 mm/mV PV 3–4 50 mm/mV PV 4–5 50 mm/mV PV 5–6 50 mm/mV 62 ms
164 ms
236 ms
Isolation
PV 6–7 50 mm/mV PV 7–8 50 mm/mV PV 8–9 50 mm/mV PV 9–10 50 mm/mV MAP 1–2 50 mm/mV MAP 3–4 50 mm/mV CS 1–2 50 mm/mV Kan1 CS 3–4 20 mm/mV
50 mm/s
Figure 1 Right superior pulmonary vein gap ablation during a repeat RFC procedure after CB2. In the 3D map, the yellow dot represents the site of PV re-isolation and the red dots represent RFC ablation sites. The intracardiac tracings show the progressive delay and entry block developed during spot ablation.
procedure was performed after 139 (89–327) days post-index CB1 (Figure 2). Patients demographic and baseline characteristics have been summarized in Table 1.
Primary endpoint Pulmonary vein reconduction pattern and gap localization after second-generation cryoballoon ablation A total of 71 PVs have been identified including one left common PV (LCPV). Overall, durable electrical PVI was documented in 55 of
71 (77%) PVs. Recovered PV conduction was present in 16 of 71 PVs (23%). Different rates of chronic PVI based on PV location have been observed: LCPV: 100%; LIPV: 94%; LSPV: 77%; RIPV: 83.3%; RSPV: 55.5% (Figure 3). In all reconnected PVs, PV conduction gaps were confined to one sector; the spatial distribution pattern of PV conduction gaps after CB2 ablation is given in Figure 4. Eight out of 16 PV (50%) conduction gaps were localized at the RSPV, thus representing the PV with the highest risk for LA – PV reconduction.
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Secondary endpoints Pulmonary vein reconduction: second-generation vs. first-generation cryoballoon ablation The rate of chronic PVI was significantly increased while comparing CB2 vs. CB1 ablation: (55 of 71, 77% PVs vs. 27 of 85, 32% PVs; P , 0.0001). This significant improvement in lesion durability after CB2 compared with CB1 was strongly dependent on an increased rate of permanent isolation of both inferior PVs (Figure 3). Of note, after CB1 ablation not a single patient (0 of 22 patients, 0%) came
Table 1 Baseline characteristics CB1
CB2
P-value
................................................................................ Baseline characteristics 22
18
Paroxysmal AF Male (%)
22 (100%) 14 (63%)
14 (78%) 9 (50%)
0.46 0.522
Age
62 + 13
69 + 11
0.068
Years of AF LA diameter (mm)
3.0 + 2.0 41 + 4
4.0 + 4.0 41 + 4
0.351 0.917
LV EF (%)
63 + 5
61 + 6
0.296
Time to repeat procedure (days)
139 (89– 327)
192 (75– 245)
0.009
17/22 (77%) 5/22 (23%)
12/18 (67%) 6/18 (33%)
0.497 0.497
Type of recurrence AF AT
17/22 AF
Predictors of pulmonary vein reconduction after second-generation cryoballoon ablation A detailed analysis comparing index and repeat procedural data revealed that reconnected PVs were in trend associated with warmer CB2 temperatures compared with chronically isolated PVs (247.2 + 1.1 vs. 250.1 + 0.78C, P ¼ 0.05). There was a higher rate of bonus freeze in PVs with reconnection (P ¼ 0.046). The other procedural aspects such as total number of CB freezes, single shot isolation, real-time PV recording visualization, and time to isolation were not statistically significantly different (Table 3). Atrial tachyarrhythmia recurrence and ablation The type of clinical ATa recurrence was grouped into AF or AT (Figure 2). Atrial fibrillation was present after CB1 and CB2 in 17 of 22 patients (77%, CB1) vs. 12 of 18 patients (67%, CB2). Atrial tachycardia was present in 5 of 22 patients (23%, CB1) vs. 6 of 18 patients (33%, CB2), respectively (Table 1). All AT recurrences in CB1 were associated with PV reconnection. In CB2, four out of six patients with AT recurrence had all PV persistently isolated. In all patients with PV reconnection re-PVI was performed: CB1—22 of 22 patients (100%) vs. CB2—12 of 18 patients (66%). Additional ablation beyond re-PVI was performed in CB1: anterior line —5 of 22 patients (23%), right atrial cavo-tricuspid line —6 of 22 patients
70 CB1
206 CB2
22 ReDos
18 ReDos
5/22 AT
22/22 pts with PV reconnection
12/18 AF
6/18 AT
12/18 pts with PV reconnection
17/17 Re-PVI
5/5 Re-PVI
10/12 Re-PVI
2/6 Re-PVI
6/17 Addictional ablations
5/5 Addictional ablations
3/12 Addictional ablations
5/6 Addictional ablations
Figure 2 Flowchart displaying arrhythmia recurrence type and ablations performed in the second procedure.
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Number of patients
back with all PVs isolated whereas after CB2 ablation 6 of 18 patients (33%) demonstrated chronic isolation of all PVs (P ¼ 0.048). Therefore, the use of the CB2 vs. CB1 was associated with a significantly higher probability for patients to receive durable PVI for all veins. Further details are given in Table 2.
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Rate of durable PV isolation P = 0.1771
P < 0.0001
P = 0.2500
P = 0.5254
P < 0.0001
P < 0.0001
1/1 100
16/17
90
15/18 55/71
13/17
80
Percentage
70 60
10/18
10/19
50 9/22 40
27/85
30
4/19 4/22
20 10 0/3 0
LSPV
LIPV
LCPV
RSPV
RIPV
Overall
CB1
53
21
0
41
18
32
CB2
76
94
100
56
83
77
Figure 3 Comparison of durable PVI after CB1 (Turquoise) and CB2 (White) procedures. There was an overall significant improvement in the rate
Table 2 Number of PVs reconnected per patient CB1 (n 5 22)
CB2 (n 5 18)
P-value
0 1
0/22 4/22
6/18 9/18
0.048 0.046
2
6/22
2/18
0.257
3 4
6/22 6/22
1/18 0/18
0.104 0.02
At least one PV reconduction
22/22
12/18
0.048
Table 3 CB2 index procedure data and PV reconduction PV isolated
PV reconnected
P-value
................................................................................
................................................................................
PVs reconnected per patient
CB2 ablation: index procedural data
(27%); compared with CB2: anterior line —8 of 18 patients (44%), right atrial cavo-tricuspid line —2 of 18 patients (11%), and roof line —5 of 18 patients (28%). One patient in the CB2 group presented with a trigger from the left atrial appendage (LAA) and therefore received three linear lesions (anterior, roof, and mitral isthmus), resulting in electrical isolation of the LAA.
Number of PVs Total application per vein Bonus freeze
55 2.1 + 0.8
16 1.8 + 0.7
45/55 (82%)
14/16 (88%)
0.046
Mean minimal temperature 8C
250.14 + 0.7
247.18 + 1.1
0.052
Mean occlusion grade
3.5 + 0.5
3.6 + 0.5
0.880
0.125
Real-time PVI
39/55 (71%)
8/16 (50%)
0.141
Time to PVI Single-shot isolation
57.8 + 5.7 44/55 (80%)
72.3 + 17.0 15/16 (94%)
0.337 0.274
Early freeze termination (transient PN weakening)
2 RIPVs/55 (4%)
0/16 (0%)
1.000
Procedural parameters and complications Procedural time and fluoroscopy time of the repeat procedures were similar in CB1 and CB2 groups: 103 + 27 vs. 103 + 55 (P ¼ 0.98) and 13 + 4 vs. 12 + 5 (P ¼ 0.35), respectively. The repeat procedure was complicated by one transient ischaemic attack and one false aneurysm in the CB2 group, and no complications occurred in CB1 repeat procedures. Pulmonary vein stenosis was ruled out in all patients after the index CB PVI by angiograms.
Follow-up The median follow-up after the RFC re-ablation was 190 days (Q1– Q3: 106–450 days) for CB1 and 182 days (Q1–Q3: 105–261 days) for CB2: 3 of 22 patients in CB1 and 2 of 18 patients in CB2 experienced documented ATa recurrences after the repeat procedure (P ¼ 1.00).
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of durable PVI specifically attributed to inferior PVs.
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LPV
Anterior
Anterior
RPV
Figure 4 Spatial distribution of PV reconduction gaps in group CB2.
Discussion
Durability of pulmonary vein isolation Acute PVI has been defined as the cornerstone of AF ablation. However, all currently utilized energy sources and ablation strategies share the limitation of high rates of recovered LA–PV conduction as the major finding in repeat procedures. Since, PV–LA reconnections represent the major determinant of clinical AF recurrences, chronic PVI remains the goal in PAF ablation. Improving PV ablation lesions has been recently attempted by various strategies.4,13,14 The 28 mm CB deploys a circumferential lesion and carries the potential of a ‘singleshot’ PVI device. However, with the CB1 repetitive applications were often required. This limitation has been attributed to the non-uniform CB1 cooling profile. Data regarding permanency of CB1 lesions are scarce and inconsistent. Recently, Ahmed et al. 15 reported a high rate of chronic CB1 PVI (88%), which however is not in line with other studies.2,3,16 Notably, besides using both available balloon sizes (23 and 28 mm), also asymptomatic patients have been investigated. In contrast, in our current study only patients with a clinical ATa recurrence have been investigated. In these selected patients, the use of CB2 compared with CB1 was associated with a significantly higher rate of chronic PVI (77 vs. 33%). The rate of chronic PVI in patients without ATa recurrence, however, remains undetermined. These novel findings fit well into the big picture of previously reported: (i) improved CB2 procedural efficacy17,18 and (ii) high (.80%) 1-year single procedure success rates.6 – 8 Interestingly, CB2 single procedure success rates are in line with different ‘high-dose’ ablation protocols using either RFC or laser energy.19,20 Therefore, it may be speculated whether increased durability of PVI after CB2 ablation explains improved clinical outcome.
Pulmonary vein conduction gap pattern In this study, a significantly higher rate of chronic PVI was observed comparing CB2 and CB1. This improvement was mainly determined
Predictors of pulmonary vein reconduction Analysing index procedural data, no factor predicting recovered PV reconduction could be identified (Table 3). There was just a trend (P ¼ 0.052) towards lower CB temperatures in chronically isolated PVs. Electrophysiological parameters such as ‘real-time PVI’ and ‘time to PVI’ were also statistically not different. In the present data, PVI durability was not related to the application of a bonus freeze. Reconnected PVs had a non-significant longer time to PVI, eventually leading the operator to add a bonus application. Whether a larger
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This study reports for the first time the EP findings in patients with ATa recurrence following 28 mm CB2 PVI ablation. The major findings comprise: (i) a high rate of durable PVI after CB2, (ii) a specific PV reconduction pattern after CB2, and (iii) a significantly higher rate of durable PVI (CB2 vs. CB1).
by higher chronic isolation rates of inferior PVs. Previously, it has been established that CB1 PVI is associated with a typical PV reconduction gap pattern along inferior PVs: specifically, inferior PV sectors have been in contact with the ‘warmer’ surface of the CB1 resulting in typical sites of PV conduction recovery.2 In contrast, the CB2 permits freezing of the entire PV antrum with increased energy, resulting in a faster cryo-lesion formation21 and in an enhanced rate of ‘single-shot’ acute PV isolation.17 The inferior sectors of the PV antrum are also in contact with the coolest CB2 surface, explaining the high rate of permanent PVI recorded in the repeat procedures. Interestingly, improved CB2 cardiac lesion quality has been recently suggested by animal data as well as human biomarker findings.21,22 In addition, according to our data only discrete PV conduction gaps re-appeared after CB2 PVI, which could be successfully closed by focal RFC ablation. Moreover, RFC-induced re-PVI was obtained along the level of PV ostia tagged for antral wide area circumferential RFC ablation, indicating a comparable anatomic level of ablation lesions. This observation needs to be confirmed in a prospective study. In the CB1 group, no patient (0%) demonstrated chronic PVI of all PVs and merely a low rate of chronic PVI (32% PVs) has been observed. In contrast, after CB2, a significantly higher rate of durable PVI has been found (CB2: 77% vs. CB1: 32%, P , 0.0001). The risk of PV reconnection (‘per PV’ and ‘per patient’) was significantly lower in CB2 vs. CB1 (odds ratio: 0.042; CI: 0.002–0.824). These new observations may represent the EP basis explaining improved clinical outcome after CB2 AF ablation.6 – 8 The interesting question whether these findings may also help to define the role of chronic PVI in persistent AF remains to be determined in future studies. A detailed analysis of our data shows that superior PVs do merely show a non-significant improvement of chronic PVI after CB2. First of all, both superior PVs already did show relatively high chronic isolation rates after CB1. Therefore, an absolute but non-significant increase of chronic PVI could be observed after CB2. The majority of recovered PV conduction gaps have been located along the anterior RSPV (50% of all reconnected PVs). This may be explained by different mechanisms: (i) continuous PN stimulation during the initial phase of RSPV ablation may counteract adequate balloon– tissue contact and lead to a non-transmural freeze; (ii) early freeze termination to preserve PN function may also result in increased risks of non-transmural cryo-lesions and increased risk of PV reconduction; (iii) non-alignment of sheath and CB after transseptal LA access, resulting in a lower contact force along the anterior sector of the RSPV. However, in the present series, we observed no PN weakening during RSPV ablation so the correlation between PNP and RSPV conduction recovery could not be studied.
Durable PVI after second-generation cryoballoon ablation
number of recovered PVs may have resulted in statistically significant differences remains open. The clinical importance of an empirical bonus freeze even on PVI durability is still open and is currently under investigation in the prospective, randomized ICE-T Trial (DRKS 00004937).
Atrial tachycardia after second-generation cryoballoon The considerable rate of chronic PVI after CB2 ablation may explain why a relatively high rate of AT instead of AF has been observed as the second clinical arrhythmia. Typically, AF recurrence is linked to recovered PV conduction. Therefore, high rates of chronic PVI may separate PVI responders from PVI non-responders.
Complications Increasing cryoablation power may result in unwanted collateral damage. Importantly, the CB2 has been linked to oesophageal lesions if no temperature limit has been set.23 The optimal dosing strategy of CB2 ablation remains unclear and is currently under evaluation.
Limitations
Conclusions Second-generation cryoballoon AF ablation is associated with a high rate of durable PVI in patients with ATa recurrence. The RSPV represents the PV with the greatest risk for LA –PV reconnection. Conflict of interest: K.R.J.C., A.F., S.B., and B.S. received speaking honoraria from Medtronic. S.B. and L.P. were supported by an educational grant of the European Heart Rhythm Association. All other authors received none.
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J Cardiovasc Electrophysiol 2013;24: 492 –7. 18. Straube F, Dorwarth U, Schmidt M, Wankerl M, Ebersberger U, Hoffmann E. Comparison of the first and second cryoballoon: high-volume single-center safety and efficacy analysis. Circ Arrhythm Electrophysiol 2014;7:293 –9. 19. Bordignon S, Chun K-RJ, Gunawardene M, Urban V, Kulikoglu M, Miehm K et al. Energy titration strategies with the endoscopic ablation system: lessons from the high-dose vs. low-dose laser ablation study. Europace 2012;15:685 –9. 20. Steven D, Sultan A, Reddy V, Lueker J, Altenburg M, Hoffmann B et al. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective two-center randomized trial. J Am Coll Cardiol 2013;62:44–50. 21. Bordignon S, Fu¨rnkranz A, Dugo D, Perrotta L, Gunawardene M, Bode F et al. Improved lesion formation using the novel 28 mm cryoballoon in atrial fibrillation ablation: analysis of biomarker release. Europace 2014;16:987 –93. 22. Andrade JG, Dubuc M, Guerra PG, Landry E, Coulombe N, Leduc H et al. Pulmonary vein isolation using a second generation cryoballoon catheter: a randomized comparison of ablation duration and method of deflation. J Cardiovasc Electrophysiol 2013;24:692–8. 23. Fu¨rnkranz A, Bordignon S, Schmidt B, Bo¨hmig M, Bo¨hmer M-C, Bode F et al. Luminal esophageal temperature predicts esophageal lesions after second-generation cryoballoon pulmonary vein isolation. Heart Rhythm 2013;10:789 –93. 24. Ghosh J, Sepahpour A, Chan KH, Singarayar S, McGuire MA. Immediate balloon deflation for prevention of persistent phrenic nerve palsy during pulmonary vein isolation by balloon cryoablation. Heart Rhythm 2013;10:646 –52.
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The major limitation of this study refers to the fact that only selected patients with symptomatic ATa recurrence after CB PVI have been investigated. Therefore, the rate of recovered PV conduction in the overall patient population remains unknown. Patients were not randomized, hence we report a sequence of patients treated either with CB1 or CB2. A potential impact of a learning curve for the CB2 is unlikely but cannot be excluded. In general, single-centre studies do not reflect real-world settings. However, if two devices are compared in an identical setting, this could be regarded as a strength rather than limitation of a study. Patient selection could also play a role in the presented findings. Since the introduction of CB2, even short-persistent AF patients enrolled for CB ablation may be impacting the rate of non-PV responder in our population. Adenosin testing was not performed after isolation in the index procedures; whether this test as recently described11 could have predicted chronic reconnection in our series remains unknown. No data about rewarming time as previously described24 were collected; whether these data could correlate with PV reconnection rate in our series remains unknown.
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Europace (2015) 17, 725–731 doi:10.1093/europace/euu331
Ablation for atrial fibrillation
High rate of durable pulmonary vein isolation after second-generation cryoballoon ablation: analysis of repeat procedures Stefano Bordignon, Alexander Fu¨rnkranz, Laura Perrotta, Daniela Dugo, Athanasios Konstantinou, Bernd Nowak, Britta Schulte-Hahn, Boris Schmidt, and Kyoung Ryul Julian Chun* CCB—Cardioangiologisches Centrum Bethanien, Markuskrankenhaus, Wilhelm-Epstein Strasse 4, 60431 Frankfurt Am Main, Germany Received 10 September 2014; accepted after revision 28 October 2014; online publish-ahead-of-print 24 January 2015
Aims
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Cryoablation † PV reconduction
Introduction Pulmonary vein isolation (PVI) represents the cornerstone in paroxysmal atrial fibrillation (AF) ablation.1 Traditionally, radiofrequency current (RFC) energy ablation encircling point by point the ipsilateral pulmonary veins (PVs) has been proposed as the standard ablation strategy. However, this approach is limited by a long individual learning curve and high technical complexity. The cryoballoon (CB) system has been introduced to facilitate in obtaining the procedural endpoint of PVI. Importantly, all currently utilized ablation energy sources and ablation strategies are characterized by high rates of
recovered PV conduction along ablation lesions.2 – 4 Therefore, multiple ablation procedures may be often required to obtain chronic PVI.5 The first-generation CB (CB1) was characterized by a nonhomogeneous cooling along the equator region. Therefore, despite feasibility of acute PVI, CB1 ablation was characterized by a high rate of AF recurrence along with resumed PV conduction during follow-up. Interestingly, a typical reconduction gap pattern predominantly along inferior PVs has been described.2 In contrast, the second-generation CB (CB2) enables homogeneous cooling of the distal portion of the balloon (‘north pole’) resulting in improved
* Corresponding author. Tel: +49 69 945028110; fax: +49 69 945028119, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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Pulmonary vein isolation (PVI) using the first-generation cryoballoon (CB1) was characterized by a high rate of recovered pulmonary vein (PV) conduction along with a typical conduction gap pattern in patients with recurrent atrial tachyarrhythmia (ATa). Second generation (CB2) enables more uniform freezing. However, the rate of chronic PVI and PV conduction gap pattern is unknown. ..................................................................................................................................................................................... Methods All patients with ATa recurrence undergoing a second procedure after CB2 or (historical) CB1 PVI (28 mm) were enand results rolled. In all patients, a left atrial three-dimensional electronatomic reconstruction was performed. The rates of chronic PVI and localization of PV conduction gaps were determined and compared between CB1 and CB2. Antral PV re-isolation was performed using irrigated-tip radiofrequency current energy ablation. Of 206 patients (CB2), 18 patients underwent the repeat procedure after 192 (75:245) days. In 6 of 18 (33%) patients, all PVs were electrically isolated whereas in the remaining 12 patients (66%) at least one PV demonstrated PV reconduction. Of 71 PVs [1 left common PV (LCPV)], 55 PVs (77%) were chronically isolated. The right superior PV (RSPV) was characterized by the lowest rate of chronic PVI (RSPV: 56%, LSPV: 76%, RIPV: 83%, LIPV: 94%, LCPV: 100%). Compared with CB1, CB2 ablation resulted in a significantly higher rate of chronic PVI (CB2: 77% vs. CB1: 32%; P , 0.0001) with the greatest improvement along both inferior PVs. ..................................................................................................................................................................................... Conclusion Second-generation cryoballoon atrial fibrillation ablation is associated with a high rate of durable PVI in patients with ATa recurrence. The RSPV represents the PV with the greatest risk for left atrium–pulmonary vein reconnection.
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What’s New? † The new generation cryoballoon (CB2) is associated with a better mid- and long-term follow-up compared with the firstgeneration cryoballoon (CB1). † We first compared CB1 vs. CB2 in terms of durable pulmonary vein isolation (PVI) in symptomatic patients undergoing a second ablation procedure. † CB2 was associated with a 77% rate of durable PVI. † The significant improvement compared with CB1 was related to a better durable isolation of inferior PVs. † The right superior PV is the vein with the highest rate of PV reconnection using CB2.
procedural parameters and resulting in ca. 80% SR after 12 months clinical follow-up.6 – 10 CB2 is also associated with a low acute reconnection rate after adenosine challenge.11 However, the rate of chronic PVI and the conduction gap pattern remains undetermined.
Methods
Index second-generation cryoballoon ablation The simplified single big cryoballoon technique has been described elsewhere.3 In brief, after a single transseptal puncture using the modified Brockenbrough technique (BRK-1 needle, 8.5F SL1 transseptal sheath, St Jude Medical), PV angiographies were performed. The CB delivery sheath (12F, Flex Cath Advance, Medtronic) was advanced into the left atrium (LA). The second generation 28 mm CB was used in conjunction with a multipolar spiral catheter (SC —Achieve, Medtronic) (Arctic Front Advance—CB2, Medtronic) allowing registration of PV conduction and determination of the moment of PVI. Pulmonary vein occlusion was assessed by contrast medium injection through the distal CB lumen. Cryoballoon freeze duration was set to 240 s. The delivery of a bonus application after acute PVI was optional. During ablation of both septal PVs, an octapolar diagnostic catheter (7F ParaHis —Biosense Webster) stimulated the phrenic nerve (PN) from the superior vena cava (12V, 2.9 ms, 1000 ms) to early identify PN dysfunction. A temperature probe (SensiTherm, St Jude Medical) was inserted into the oesophagus to monitor the luminal oesophageal temperature (LET). All relevant procedural data such as minimal CB temperature and LET have been systematically collected.
Repeat ablation procedure after second-generation cryoballoon ablation All patients with documented recurrence of atrial tachyarrhythmias (ATa) lasting .30 s were offered a repeat AF ablation procedure. All repeat procedures were performed under conscious sedation (midazolam, propofol, and fentayl boluses followed by a propofol infusion). After double transseptal puncture, a three-dimensional (3D) electroanatomical (EA) LA map (Carto 3, Biosense Webster) was performed
using a 3.5 mm irrigated-tip radiofrequency (RF) catheter (ThermoCool NaviStar, Biosense Webster). Selective PV angiograms were performed and both ipsilateral PV ostia were tagged in the LA CARTO map as previously described.12 A decapolar spiral catheter (Lasso 15/20 mm, Biosense Webster) was positioned within the proximal PV ostium to assess potential LA– PV reconduction. If LA – PV reconduction was present, the PV spike sequence was analysed to identify the earliest PV activation site. Radiofrequency ablation was guided by PV activation sequence and local map potential along the tagged PV ostium level (Figure 1). Gap location was defined as the site of successful re-isolation of the PV or the site of clear change in the PV electric activation pattern, as previously published.2 All PVs were divided into four quadrants [antero-superior (AS); antero-inferior (AI); postero-inferior (PI); postero-superior (PS)] to categorize the gap location. In patients presenting with AF as the type of ATa recurrence, only re-PVI was performed. In patients presenting with atrial tachycardia (AT), the underlying tachycardia mechanism was elucidated combining 3D EA-mapping with conventional electrophysiological (EP) information such as entrainment manoeuvres. After AT termination, re-PVI was performed in SR.
Comparison: first-generation cryoballoon vs. second-generation cryoballoon Pulmonary vein reconduction data after CB1 procedure were obtained from our centres CB cohort of the recently published ‘Laser vs. CryoStudy’.3 This historical CB1 group served as the comparator.
Follow-up After the ablation procedure, all patients were seen in our outpatient clinic at 3, 6, 9, and 12 months and in 6 months intervals thereafter and obtained a 72 h Holter-ECG. In case of symptoms suggestive of an ATa recurrence, patients received an external event monitor. Atrial tachyarrhythmia recurrence has been defined as documented episodes lasting .30 s.
Objectives and endpoints Primary endpoint To characterize LA– PV reconduction rates and localization of PV conduction gaps after CB2 PV isolation.
Secondary endpoints To compare LA – PV reconduction after CB1 and CB2 PVI ablation. To identify procedural parameters predicting LA – PV reconduction after CB2 ablation. To analyse repeat procedural parameters, complications, and patient outcome.
Statistical analysis All quantitative variables with a normal distribution were reported as mean + standard deviation, and compared using the Student’s t-test. For the descriptive variables comparison, the Pearson’s x2test or the Fisher’s exact test wherever appropriate was used. An odds ratio with 95% confidence interval (CI) was computed to compare PV isolation rates after PVI using the CB1 and CB2.
Results Patients and procedure A repeat AF ablation procedure was performed in 18 of 206 patients (9%) after 192 (75–245) days post-index CB2. The historical CB1 control group consisted of 22 of 70 patients in which the repeat
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All AF ablation procedural data have been collected in the CCB database since May 2010. All CB2 PVI patients undergoing a repeat procedure have been identified. Procedural data from the repeat procedures after CB2 ablation have been analysed. A historical cohort of CB1 ablation repeat procedures from the same institution served as a control group. All the patients gave written consent, and the study was approved by the Institutional Review Board.
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PA LAO RAO LL RL INF SUP
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! V1 20 mm/mV PV 1–2 50 mm/mV PV 2–3 50 mm/mV PV 3–4 50 mm/mV PV 4–5 50 mm/mV PV 5–6 50 mm/mV 62 ms
164 ms
236 ms
Isolation
PV 6–7 50 mm/mV PV 7–8 50 mm/mV PV 8–9 50 mm/mV PV 9–10 50 mm/mV MAP 1–2 50 mm/mV MAP 3–4 50 mm/mV CS 1–2 50 mm/mV Kan1 CS 3–4 20 mm/mV
50 mm/s
Figure 1 Right superior pulmonary vein gap ablation during a repeat RFC procedure after CB2. In the 3D map, the yellow dot represents the site of PV re-isolation and the red dots represent RFC ablation sites. The intracardiac tracings show the progressive delay and entry block developed during spot ablation.
procedure was performed after 139 (89–327) days post-index CB1 (Figure 2). Patients demographic and baseline characteristics have been summarized in Table 1.
Primary endpoint Pulmonary vein reconduction pattern and gap localization after second-generation cryoballoon ablation A total of 71 PVs have been identified including one left common PV (LCPV). Overall, durable electrical PVI was documented in 55 of
71 (77%) PVs. Recovered PV conduction was present in 16 of 71 PVs (23%). Different rates of chronic PVI based on PV location have been observed: LCPV: 100%; LIPV: 94%; LSPV: 77%; RIPV: 83.3%; RSPV: 55.5% (Figure 3). In all reconnected PVs, PV conduction gaps were confined to one sector; the spatial distribution pattern of PV conduction gaps after CB2 ablation is given in Figure 4. Eight out of 16 PV (50%) conduction gaps were localized at the RSPV, thus representing the PV with the highest risk for LA – PV reconduction.
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Secondary endpoints Pulmonary vein reconduction: second-generation vs. first-generation cryoballoon ablation The rate of chronic PVI was significantly increased while comparing CB2 vs. CB1 ablation: (55 of 71, 77% PVs vs. 27 of 85, 32% PVs; P , 0.0001). This significant improvement in lesion durability after CB2 compared with CB1 was strongly dependent on an increased rate of permanent isolation of both inferior PVs (Figure 3). Of note, after CB1 ablation not a single patient (0 of 22 patients, 0%) came
Table 1 Baseline characteristics CB1
CB2
P-value
................................................................................ Baseline characteristics 22
18
Paroxysmal AF Male (%)
22 (100%) 14 (63%)
14 (78%) 9 (50%)
0.46 0.522
Age
62 + 13
69 + 11
0.068
Years of AF LA diameter (mm)
3.0 + 2.0 41 + 4
4.0 + 4.0 41 + 4
0.351 0.917
LV EF (%)
63 + 5
61 + 6
0.296
Time to repeat procedure (days)
139 (89– 327)
192 (75– 245)
0.009
17/22 (77%) 5/22 (23%)
12/18 (67%) 6/18 (33%)
0.497 0.497
Type of recurrence AF AT
17/22 AF
Predictors of pulmonary vein reconduction after second-generation cryoballoon ablation A detailed analysis comparing index and repeat procedural data revealed that reconnected PVs were in trend associated with warmer CB2 temperatures compared with chronically isolated PVs (247.2 + 1.1 vs. 250.1 + 0.78C, P ¼ 0.05). There was a higher rate of bonus freeze in PVs with reconnection (P ¼ 0.046). The other procedural aspects such as total number of CB freezes, single shot isolation, real-time PV recording visualization, and time to isolation were not statistically significantly different (Table 3). Atrial tachyarrhythmia recurrence and ablation The type of clinical ATa recurrence was grouped into AF or AT (Figure 2). Atrial fibrillation was present after CB1 and CB2 in 17 of 22 patients (77%, CB1) vs. 12 of 18 patients (67%, CB2). Atrial tachycardia was present in 5 of 22 patients (23%, CB1) vs. 6 of 18 patients (33%, CB2), respectively (Table 1). All AT recurrences in CB1 were associated with PV reconnection. In CB2, four out of six patients with AT recurrence had all PV persistently isolated. In all patients with PV reconnection re-PVI was performed: CB1—22 of 22 patients (100%) vs. CB2—12 of 18 patients (66%). Additional ablation beyond re-PVI was performed in CB1: anterior line —5 of 22 patients (23%), right atrial cavo-tricuspid line —6 of 22 patients
70 CB1
206 CB2
22 ReDos
18 ReDos
5/22 AT
22/22 pts with PV reconnection
12/18 AF
6/18 AT
12/18 pts with PV reconnection
17/17 Re-PVI
5/5 Re-PVI
10/12 Re-PVI
2/6 Re-PVI
6/17 Addictional ablations
5/5 Addictional ablations
3/12 Addictional ablations
5/6 Addictional ablations
Figure 2 Flowchart displaying arrhythmia recurrence type and ablations performed in the second procedure.
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Number of patients
back with all PVs isolated whereas after CB2 ablation 6 of 18 patients (33%) demonstrated chronic isolation of all PVs (P ¼ 0.048). Therefore, the use of the CB2 vs. CB1 was associated with a significantly higher probability for patients to receive durable PVI for all veins. Further details are given in Table 2.
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Rate of durable PV isolation P = 0.1771
P < 0.0001
P = 0.2500
P = 0.5254
P < 0.0001
P < 0.0001
1/1 100
16/17
90
15/18 55/71
13/17
80
Percentage
70 60
10/18
10/19
50 9/22 40
27/85
30
4/19 4/22
20 10 0/3 0
LSPV
LIPV
LCPV
RSPV
RIPV
Overall
CB1
53
21
0
41
18
32
CB2
76
94
100
56
83
77
Figure 3 Comparison of durable PVI after CB1 (Turquoise) and CB2 (White) procedures. There was an overall significant improvement in the rate
Table 2 Number of PVs reconnected per patient CB1 (n 5 22)
CB2 (n 5 18)
P-value
0 1
0/22 4/22
6/18 9/18
0.048 0.046
2
6/22
2/18
0.257
3 4
6/22 6/22
1/18 0/18
0.104 0.02
At least one PV reconduction
22/22
12/18
0.048
Table 3 CB2 index procedure data and PV reconduction PV isolated
PV reconnected
P-value
................................................................................
................................................................................
PVs reconnected per patient
CB2 ablation: index procedural data
(27%); compared with CB2: anterior line —8 of 18 patients (44%), right atrial cavo-tricuspid line —2 of 18 patients (11%), and roof line —5 of 18 patients (28%). One patient in the CB2 group presented with a trigger from the left atrial appendage (LAA) and therefore received three linear lesions (anterior, roof, and mitral isthmus), resulting in electrical isolation of the LAA.
Number of PVs Total application per vein Bonus freeze
55 2.1 + 0.8
16 1.8 + 0.7
45/55 (82%)
14/16 (88%)
0.046
Mean minimal temperature 8C
250.14 + 0.7
247.18 + 1.1
0.052
Mean occlusion grade
3.5 + 0.5
3.6 + 0.5
0.880
0.125
Real-time PVI
39/55 (71%)
8/16 (50%)
0.141
Time to PVI Single-shot isolation
57.8 + 5.7 44/55 (80%)
72.3 + 17.0 15/16 (94%)
0.337 0.274
Early freeze termination (transient PN weakening)
2 RIPVs/55 (4%)
0/16 (0%)
1.000
Procedural parameters and complications Procedural time and fluoroscopy time of the repeat procedures were similar in CB1 and CB2 groups: 103 + 27 vs. 103 + 55 (P ¼ 0.98) and 13 + 4 vs. 12 + 5 (P ¼ 0.35), respectively. The repeat procedure was complicated by one transient ischaemic attack and one false aneurysm in the CB2 group, and no complications occurred in CB1 repeat procedures. Pulmonary vein stenosis was ruled out in all patients after the index CB PVI by angiograms.
Follow-up The median follow-up after the RFC re-ablation was 190 days (Q1– Q3: 106–450 days) for CB1 and 182 days (Q1–Q3: 105–261 days) for CB2: 3 of 22 patients in CB1 and 2 of 18 patients in CB2 experienced documented ATa recurrences after the repeat procedure (P ¼ 1.00).
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of durable PVI specifically attributed to inferior PVs.
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LPV
Anterior
Anterior
RPV
Figure 4 Spatial distribution of PV reconduction gaps in group CB2.
Discussion
Durability of pulmonary vein isolation Acute PVI has been defined as the cornerstone of AF ablation. However, all currently utilized energy sources and ablation strategies share the limitation of high rates of recovered LA–PV conduction as the major finding in repeat procedures. Since, PV–LA reconnections represent the major determinant of clinical AF recurrences, chronic PVI remains the goal in PAF ablation. Improving PV ablation lesions has been recently attempted by various strategies.4,13,14 The 28 mm CB deploys a circumferential lesion and carries the potential of a ‘singleshot’ PVI device. However, with the CB1 repetitive applications were often required. This limitation has been attributed to the non-uniform CB1 cooling profile. Data regarding permanency of CB1 lesions are scarce and inconsistent. Recently, Ahmed et al. 15 reported a high rate of chronic CB1 PVI (88%), which however is not in line with other studies.2,3,16 Notably, besides using both available balloon sizes (23 and 28 mm), also asymptomatic patients have been investigated. In contrast, in our current study only patients with a clinical ATa recurrence have been investigated. In these selected patients, the use of CB2 compared with CB1 was associated with a significantly higher rate of chronic PVI (77 vs. 33%). The rate of chronic PVI in patients without ATa recurrence, however, remains undetermined. These novel findings fit well into the big picture of previously reported: (i) improved CB2 procedural efficacy17,18 and (ii) high (.80%) 1-year single procedure success rates.6 – 8 Interestingly, CB2 single procedure success rates are in line with different ‘high-dose’ ablation protocols using either RFC or laser energy.19,20 Therefore, it may be speculated whether increased durability of PVI after CB2 ablation explains improved clinical outcome.
Pulmonary vein conduction gap pattern In this study, a significantly higher rate of chronic PVI was observed comparing CB2 and CB1. This improvement was mainly determined
Predictors of pulmonary vein reconduction Analysing index procedural data, no factor predicting recovered PV reconduction could be identified (Table 3). There was just a trend (P ¼ 0.052) towards lower CB temperatures in chronically isolated PVs. Electrophysiological parameters such as ‘real-time PVI’ and ‘time to PVI’ were also statistically not different. In the present data, PVI durability was not related to the application of a bonus freeze. Reconnected PVs had a non-significant longer time to PVI, eventually leading the operator to add a bonus application. Whether a larger
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This study reports for the first time the EP findings in patients with ATa recurrence following 28 mm CB2 PVI ablation. The major findings comprise: (i) a high rate of durable PVI after CB2, (ii) a specific PV reconduction pattern after CB2, and (iii) a significantly higher rate of durable PVI (CB2 vs. CB1).
by higher chronic isolation rates of inferior PVs. Previously, it has been established that CB1 PVI is associated with a typical PV reconduction gap pattern along inferior PVs: specifically, inferior PV sectors have been in contact with the ‘warmer’ surface of the CB1 resulting in typical sites of PV conduction recovery.2 In contrast, the CB2 permits freezing of the entire PV antrum with increased energy, resulting in a faster cryo-lesion formation21 and in an enhanced rate of ‘single-shot’ acute PV isolation.17 The inferior sectors of the PV antrum are also in contact with the coolest CB2 surface, explaining the high rate of permanent PVI recorded in the repeat procedures. Interestingly, improved CB2 cardiac lesion quality has been recently suggested by animal data as well as human biomarker findings.21,22 In addition, according to our data only discrete PV conduction gaps re-appeared after CB2 PVI, which could be successfully closed by focal RFC ablation. Moreover, RFC-induced re-PVI was obtained along the level of PV ostia tagged for antral wide area circumferential RFC ablation, indicating a comparable anatomic level of ablation lesions. This observation needs to be confirmed in a prospective study. In the CB1 group, no patient (0%) demonstrated chronic PVI of all PVs and merely a low rate of chronic PVI (32% PVs) has been observed. In contrast, after CB2, a significantly higher rate of durable PVI has been found (CB2: 77% vs. CB1: 32%, P , 0.0001). The risk of PV reconnection (‘per PV’ and ‘per patient’) was significantly lower in CB2 vs. CB1 (odds ratio: 0.042; CI: 0.002–0.824). These new observations may represent the EP basis explaining improved clinical outcome after CB2 AF ablation.6 – 8 The interesting question whether these findings may also help to define the role of chronic PVI in persistent AF remains to be determined in future studies. A detailed analysis of our data shows that superior PVs do merely show a non-significant improvement of chronic PVI after CB2. First of all, both superior PVs already did show relatively high chronic isolation rates after CB1. Therefore, an absolute but non-significant increase of chronic PVI could be observed after CB2. The majority of recovered PV conduction gaps have been located along the anterior RSPV (50% of all reconnected PVs). This may be explained by different mechanisms: (i) continuous PN stimulation during the initial phase of RSPV ablation may counteract adequate balloon– tissue contact and lead to a non-transmural freeze; (ii) early freeze termination to preserve PN function may also result in increased risks of non-transmural cryo-lesions and increased risk of PV reconduction; (iii) non-alignment of sheath and CB after transseptal LA access, resulting in a lower contact force along the anterior sector of the RSPV. However, in the present series, we observed no PN weakening during RSPV ablation so the correlation between PNP and RSPV conduction recovery could not be studied.
Durable PVI after second-generation cryoballoon ablation
number of recovered PVs may have resulted in statistically significant differences remains open. The clinical importance of an empirical bonus freeze even on PVI durability is still open and is currently under investigation in the prospective, randomized ICE-T Trial (DRKS 00004937).
Atrial tachycardia after second-generation cryoballoon The considerable rate of chronic PVI after CB2 ablation may explain why a relatively high rate of AT instead of AF has been observed as the second clinical arrhythmia. Typically, AF recurrence is linked to recovered PV conduction. Therefore, high rates of chronic PVI may separate PVI responders from PVI non-responders.
Complications Increasing cryoablation power may result in unwanted collateral damage. Importantly, the CB2 has been linked to oesophageal lesions if no temperature limit has been set.23 The optimal dosing strategy of CB2 ablation remains unclear and is currently under evaluation.
Limitations
Conclusions Second-generation cryoballoon AF ablation is associated with a high rate of durable PVI in patients with ATa recurrence. The RSPV represents the PV with the greatest risk for LA –PV reconnection. Conflict of interest: K.R.J.C., A.F., S.B., and B.S. received speaking honoraria from Medtronic. S.B. and L.P. were supported by an educational grant of the European Heart Rhythm Association. All other authors received none.
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The major limitation of this study refers to the fact that only selected patients with symptomatic ATa recurrence after CB PVI have been investigated. Therefore, the rate of recovered PV conduction in the overall patient population remains unknown. Patients were not randomized, hence we report a sequence of patients treated either with CB1 or CB2. A potential impact of a learning curve for the CB2 is unlikely but cannot be excluded. In general, single-centre studies do not reflect real-world settings. However, if two devices are compared in an identical setting, this could be regarded as a strength rather than limitation of a study. Patient selection could also play a role in the presented findings. Since the introduction of CB2, even short-persistent AF patients enrolled for CB ablation may be impacting the rate of non-PV responder in our population. Adenosin testing was not performed after isolation in the index procedures; whether this test as recently described11 could have predicted chronic reconnection in our series remains unknown. No data about rewarming time as previously described24 were collected; whether these data could correlate with PV reconnection rate in our series remains unknown.
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