Active or passive pulmonary vein in atrial fibrillation: Is pulmonary vein isolation always essential? Julien Seitz, MD,* Jérôme Horvilleur, MD,† Laurence Curel, MSc,* Jérôme Lacotte, MD,† Alexandre Maluski, MD,* Ange Ferracci, MD,* Michel Bremondy, MD,* Arnaud Rosier, MD,† Mehran Monchi, MD,† Guillaume Penaranda, MSc,* Jacques Faure, MD,* Sylvain Beurtheret, MD,* André Pisapia, MD, FHRS* From the *Hôpital Saint Joseph, Marseille, France, and †Institut Cardiovasculaire Paris Sud, Hôpital Privé Jacques Cartier, Massy, France. BACKGROUND The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based substrate ablation is not widely performed as a stand-alone strategy. OBJECTIVE To evaluate PV activity in AF perpetuation and efficacy of our patient-tailored ablation strategy (electrogrambased substrate ablation with or without pulmonary vein isolation [PVI]). METHODS One hundred twenty-one patients with paroxysmal (n ¼ 19; 15.7%), persistent (n ¼ 77; 63.6%), or long-standing persistent (n ¼ 25; 20.7%) AF underwent electrogram-based substrate ablation with AF termination end point: sinus rhythm or atrial tachycardia conversion. Before ablation, we classified PVs as “passive” if silent PV or if PV cycle length is greater than left atrial appendage cycle length. No PVI was performed in such cases. RESULTS Passive PVs were observed in 52 of 121 patients (paroxysmal AF ¼ 0%, persistent AF ¼ 40%, and long-standing persistent AF ¼ 76%; P o .0001]). Substrate ablation terminated AF in 95.6% (sinus rhythm conversion in 80.2%). Compared with patients with active PVs, patients with passive PVs had longer AF sustained duration (19.1 ⫾ 29.7 months vs 4.9 ⫾ 11.1 months; P o .0001), larger left atrial diameter (46.9 ⫾ 7.3 mm vs 41.9 ⫾ 6.0

Introduction Triggering or maintaining foci (intermittent bursts) for paroxysmal atrial fibrillation (PAF) have mainly been Dr Pisapia has received speaker fees and honoraria as a consultant from Biosense Webster, St Jude Medical, Sorin group, Medtronic, and Boerhinger Ingelheim. Dr Seitz has received speaker fees and honoraria as a consultant from Biosense Webster, St Jude Medical, Medtronic, and Boerhinger Ingelheim. Dr Ferracci, Dr Faure, and Dr Bremondy have received honoraria from Medtronic, Sorin Group, and St Jude Medical. Dr Horvilleur has received honoraria from St Jude Medical and Medtronic. Dr Lacotte has received honoraria from Biosense Webster, Medtronic, Sorin Group, Meda, and Boston Scientific. Address reprint requests and correspondence: Dr Julien Seitz, Hôpital Saint Joseph, Service de Cardiologie, 26 Bd de Louvain, 13008 Marseille, France. E-mail address: [email protected].

1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.

mm; P ¼ .0014), lower left ventricular ejection fraction (45.4% ⫾ 13.5% vs 55.1% ⫾ 9.4%; P o .0001), and more often structural heart disease (57% vs 33%; P ¼ .02). After a follow-up of 20.39 ⫾ 11.23 months (1.6 procedures per patient), 82% were arrhythmia free with this strategy. CONCLUSIONS PV activity during AF decreases with AF chronicity, left atrial dilatation, and left ventricular ejection fraction. Our patient-tailored ablation strategy without systematic PVI provides good results. KEYWORDS Arrhythmia; Electrophysiology; Catheter ablation; Atrial fibrillation; Substrate; Electrogram; Complex fractionated atrial electrogram ABBREVIATIONS AF ¼ atrial fibrillation; AT ¼ atrial tachycardia; CFAE ¼ complex fractionated atrial electrogram; CL ¼ cycle length; CS ¼ coronary sinus; EGM ¼ electrogram; EP ¼ electrophysiological; FU ¼ follow-up; LA ¼ left atrial/atrium; LAA ¼ left atrial appendage; PAF ¼ paroxysmal atrial fibrillation; PV ¼ pulmonary vein; PVI ¼ pulmonary vein isolation; RA ¼ right atrial/ atrium; RF ¼ radiofrequency (Heart Rhythm 2014;11:579–586) I 2014 Heart Rhythm Society. All rights reserved.

located within the pulmonary veins (PVs).1–3 Pulmonary vein isolation (PVI) has become standard practice in PAF ablation.4,5 Nevertheless, PVI alone is not effective in many cases especially for non-PAF.6 In such cases, atrial substrate ablation is necessary.6–9 Nademanee et al7 first reported an approach for atrial fibrillation (AF) substrate ablation by mapping and ablating complex fractionated atrial electrogram (CFAE) areas as a standalone strategy. This technique associated with PVI and linear ablation has become increasingly popular for persistent AF.6,8,9 To our knowledge, no scientific data are available about the role of PVs in AF perpetuation between the different AF types. Furthermore, data confirming efficacy and reproducibility of defragmentation still remains necessary.10 Finally, http://dx.doi.org/10.1016/j.hrthm.2014.01.009

580 data explaining why such a strategy without PVI could be efficient are also missing. In this observational prospective study, we sought to

 evaluate and compare the proportion of patients with  

active or passive PVs in patients with PAF, persistent AF, and long-standing persistent AF; assess the acute efficacy of electrogram (EGM)-based substrate ablation on AF termination without PVI; and evaluate the long-term outcome of our original hybrid strategy: EGM-based substrate followed by optional PVI (no PVI in the case of PV passivity).

Methods Study population All consecutive patients referred to our centers for symptomatic refractory AF in which substrate ablation was necessary were included (between January 2009 and February 2011 in Hôpital Privé Jacques Cartier and between September 2011 and November 2012 in Hôpital St Joseph). Exclusion criteria were redo ablations (to avoid bias owing to prior ablations, which could affect AF substrate and PV activity) and lone “focal” AF (PAF with a short episode duration of r24 hours without structural heart disease or hypertension, predicting a limited quantity of substrate) in whom we do not perform EGM-based substrate ablation in first intention (PVI only). All the patients gave written informed consent before ablation.

Procedure preparation All antiarrhythmic agents, except β-blockers and amiodarone, in patients with persistent AF and long-standing persistent AF were discontinued at least 5 half-lives before ablation. Amiodarone was intentionally not discontinued in patients with non-PAF in order to increase AF CLs and to facilitate AF termination as in other centers.6,9 Anticoagulation was maintained with low-molecular-weight heparin after the discontinuation of warfarin 3 days before the intervention. All procedures were performed under general anesthesia. Left atrial appendage (LAA) thrombus was ruled out by transesophageal echocardiogram before transseptal puncture. Surface electrocardiogram and bipolar endocardial EGMs (filtered from 30 to 500 Hz) were continuously monitored and stored on a computer-based digital amplifier/recorder system (GE Healthcare, CardioLab, Milwaukee, WI). The following catheters were introduced through the right femoral vein: a deflectable decapolar catheter (2–5–2 mm electrode spacing, Xtrem, ELA Medical, Le-Plessis-Robinson, France) positioned within the coronary sinus (CS), a 3.5-mm irrigated-tip quadripolar ablation catheter (2–5–2 mm interelectrode spacing, ThermoCool or ThermoCool SF, Biosense Webster, Diamond Bar, CA, F or J curve) introduced through a long sheath (Preface multipurpose, Biosense Webster) perfused with heparinized saline, and a deflectable decapolar catheter with a distal ring configuration (lasso catheter, Biosense Webster) introduced through a long sheath in the case of PVI. Heparin was administered intravenously to maintain an

Heart Rhythm, Vol 11, No 4, April 2014 activated clotting time of 300–350 seconds and monitored with activated clotting time measurements every 30 minutes.

AF mapping The procedure workflow is schematized in Figure 1. Mapping was performed while the patient was in AF in order to detect targeted EGMs (Figure 2). For patients who were in sinus rhythm (SR) at the beginning of the procedure, AF was induced by rapid atrial pacing. The AF cycle length (CL) was measured in the LAA because its EGM organization allowed us to record AF CL (Figures 3 and 4). PV mapping was then performed (either with the lasso or the ablation catheter): the catheter was positioned sequentially in the 4 PVs close to the ostium (between 0.5 and 1 cm from the ostium inside the vein) for at least 1 minute of recording within the PV (PV tachycardias occur 3.9 ⫾ 4.2 times/min11). In the case of “silent PV” diagnosis, special attention was paid to check the catheter contact (especially in large veins) in various sites to inspect the entire circumference of the veins. Because of AF irregularity, in order to characterize the CL in each area (LAA and 4 PVs) we decided to average 20 CLs (10 CLs manually measured and averaged twice during the mapping). A rigorous characterization of the excitation frequency during AF is achieved by spectral analysis of the bipolar signal.12 This manual CL measurement method was validated as follows: automatic frequency measurements and conversion into CL were performed in 100 CARTO points (10 different patients); no statistical difference in CL measurements was observed between these 2 methods. A PV was qualified as “Passive” when the CL recorded inside the vein was greater than the CL measured in the LAA, or in case of electrical signal absence (silent PV) (Figure 3).

Figure 1 Ablation procedure workflow and immediate results. AF ¼ atrial fibrillation; EGM ¼ electrogram; PV ¼ pulmonary vein.

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Figure 2 Examples of targeted EGMs targeted by ablation during EGM-based substrate ablation. A and B: Examples of complex fractionated atrial electrograms targeted by ablation. All these EGMs are low-voltage potentials (o0.1 mV). C: “Rapid fire” corresponding to a discrete nonfractionated rapid potential. D: Temporal gradient of activation on the ablation catheter (despite a transient pseudo-organized surface electrocardiogram at this moment, the intracardiac EGMs confirmed AF). ABL ¼ ablation; CS ¼ coronary sinus; EGM ¼ electrogram.

A PV was qualified as “active” when the CL recorded inside the vein was less than or equal to the CL measured in the LAA. According to previous studies, PV CL during “PV tachycardias” represented 60% and 82% of the LAA CL.3,9 Therefore, in patients with PV activity, “rapid firing PV” was defined as discrete EGMs of rapid CL recorded inside the vein with less than 80% of AF CL measured in the LAA (Figures 2 and 4). Finally, electroanatomic left atrial (LA) substrate mapping was performed with a CARTO navigation and mapping system (Biosense Webster, Diamond Bar, CA).

Ablation protocol EGM-based substrate ablation Radiofrequency (RF) applications could be performed anywhere in both atria, including the PV antrum (excluding applications inside the PVs) and in the CS (Figure 1).

Three different types of EGMs considered to be involved in the electrophysiological (EP) processes of AF perpetuation were targeted by ablation: 1. CFAE: Visual choice of ablated fractionated EGMs was made according to the following CFAE definition: multicomponent atrial EGMs, including (1) atrial EGMs with 2 or more deflections and/or perturbation of the baseline and/or continuous electrical activity over a 10-second period or (2) atrial EGMs with a very short CL of r120 ms over a 10-second period.7 The primary targets of ablation were continuous and low-voltage potentials (o0.1 mV) (Figures 2A and 2B). 2. Rapid fires: Discrete EGMs of rapid CL shorter than 80% of the mean AF CL measured in the LAA (Figure 2C). 3. Temporal gradient of activation: Gradient between the EGMs recorded by the distal bipole in relation to the

Figure 3 Patient with passive PVs treated by substrate ablation alone. Examples of intracardiac electrograms recorded in a patient with long-standing persistent atrial fibrillation (2 years) showing a passivity of the 4 PVs. The CARTO picture shows the right atrium, the coronary sinus, and the left atrium in the anterior-posterior view. AF ¼ atrial fibrillation; CFAE ¼ complex fractionated atrial electrogram; CL ¼ cycle length; LAA ¼ left atrial appendage; LIPV ¼ left inferior pulmonary vein; LSPV ¼ left superior pulmonary vein; PV ¼ pulmonary vein; RIPV ¼ right inferior pulmonary vein; RSPV ¼ right superior pulmonary vein.

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Figure 4 Patient with “rapid firing” PVs treated by substrate ablation followed by PVI after sinus rhythm conversion. Electrograms are recorded at different sites in the right and left atria. The CARTO picture shows the right atrium, the coronary sinus, and the left atrium in the left anterior oblique view. CFAE ¼ complex fractionated atrial electrogram; CL ¼ cycle length; LAA ¼ left atrial appendage; LPV ¼ left pulmonary vein; PV ¼ pulmonary vein; PVI ¼ pulmonary veins isolation; RAA ¼ right atrium appendage; RSPV ¼ right superior pulmonary vein; SR ¼ sinus rhythm.

proximal bipole of the ablation catheter (Figure 2D), as described by the Bordeaux group.13 Ablation was performed with “point-by-point” applications (60 seconds or more: as long as there was EGM persistence) guided by the operator’s visual analysis. In the case of ablation on a “critical” area with sudden CL increase or AF termination, a longer RF application was performed (2 minutes minimum with maximal power delivery, depending on the catheter location). The ablation power control settings used were dynamically adapted for each anatomical structure: 35–45 W for the septum; 15–25 W for PV ostia, posterior wall of the LA, and the CS; and 30–40 W for the other segments of the LA and the right atrium (RA). CFAE ablation end point was AF termination, defined as follows: conversion into SR or regularization into stable atrial tachycardia (AT). In such cases, AT was mapped and ablated until SR restoration. The AF “noninducibility” was then tested (rapid atrial pacing from 400 to 100 ms) in all PAF and in non-PAF if AF termination occurred within the second hour of the ablation procedure. No inducibility testing in other cases was performed to avoid excessive procedure time prolongation. In the case of AF termination failure, the substrate ablation end point was the complete elimination of CFAEs. Optional secondary PVI After SR conversion, lasso-guided segmental PVI of all 4 PVs4 was performed as a final ablation step, only in patients with at least 1 active PV not being inactivated by substrate ablation (Figures 1 and 4). As the evaluation of acute efficacy of EGM-based substrate ablation on AF termination was one

of our end points, PVI was not performed before SR restoration even in patients with active PVs.

Follow-up Follow-up (FU) with symptoms and recurrences evaluation were based on clinical examination, 24-hour Holter monitoring, 12-lead electrocardiographic data in outpatient clinic (3, 6, 9, 12, 24, 36, 48, and 60 months maximum), and telephone interviews. Antiarrhythmic medications were discontinued, whenever possible, after a 3-month postablation “blanking period.” Redo procedures were planned in the case of arrhythmia recurrences after this blanking period. The redo ablation strategy was the same as the index strategy.

Statistical analysis Categorical variables are expressed as count and percentages and numerical variables as mean ⫾ SD. Time data are expressed as median (quartile 1–quartile 3). Statistical analysis was performed by using the χ2 test for categorical variables and Wilcoxon test for numerical variables. A P value of o.05 was used to indicate statistical significance. All statistical analyses were performed by using SAS 9.2 software (SAS Institute Inc, Cary, NC).

Results Patient characteristics Between January 2009 and November 2012, 121 patients (mean age 59.69 ⫾ 11.25 years; 72% men) were prospectively enrolled and underwent RF catheter ablation for symptomatic refractory PAF (n = 19; sustained AF episodes

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Table 1 Baseline patient characteristics Age (y) Sex: male AF type Paroxysmal AF Persistent AF Long-standing persistent AF Duration of AF (mo) Duration of maximum sustained AF (mo) Structural heart disease Coronary artery disease Tachycardiomyopathy Mitral valvulopathy Hypertrophic cardiomyopathy Idiopathic cardiomyopathy Hypertension Diabetes LA diameter (mm) LVEF (%)

60.7 ⫾ 10.3 87 (71.9) 19 (15.7) 77 (63.6) 25 (20.7) 48 (36–102) 4 (0.23–9) 34 (27.86) 17 (13.93) 27 (22.13) 10 (8.2) 4 (3.27) 1 (1.3) 67 (54.9) 10 (8.2) 44.5 ⫾ 32.4 51.6 ⫾ 12.1

Values are expressed as mean ⫾ SD or as n (%) Durations are expressed as median (quartile 1–quartile 3). AF ¼ atrial fibrillation; LA ¼ left atrial; LVEF ¼ left ventricular ejection fraction.

o7 days) , persistent AF (n = 77), or long-standing persistent AF (n = 25; sustained AF episodes 41 year). A majority of patients with non-PAF (102 of 121 [84.3%]) were still under antiarrhythmic medications (97 of 121 [80.2%] receiving amiodarone) at the time of ablation. Most patients had a long history of AF (68.56 ⫾ 54.47 months), with a maximum sustained duration of 13.63 ⫾ 32.38 months. Patient characteristics are summarized in Table 1.

EP data Sixty-nine (57%) patients had spontaneous AF at the beginning of the procedure. Sustained AF was induced easily through rapid atrial pacing in the remaining 52 patients in SR. The mean AF CL (measured in the LAA) was 189.54 ⫾ 30 ms.

Active/passive PVs Fifty-two patients (43%) had 4 passive PVs during mapping. According to AF type, the proportion of patients with 4 passive PVs was 0%, 40%, and 76%, respectively, for PAF, persistent AF, and long-standing persistent AF (P ¼ .0001). In non-PAF population, 51% had 4 passive PVs (Figure 5). In the passive PV population, 52% of the PVs were totally silent vs 48% with a PV CL greater than an LAA CL. In univariate analysis, patients with passive PVs compared with patients with active PVs had (Table 2):

    

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20 of 77 (26%) patients with persistent AF, and 3 of 25 (12%) patients with long-standing persistent AF (P ¼ .01).

Ablation results The majority of RF applications were performed in the LA. Additional ablation in the CS and in the RA was performed, respectively, in 102 patients (84.3%) and in 71 patients (58.7%) (Figure 1). During the EGM-based substrate ablation, AF was terminated in 116 (95.9%) patients: 29 converted directly to SR and 87 regularized to AT. Sixty-eight of these 87 ATs were successfully treated by focal ablation and/or lines: 38 macroreentrant circuits (15 peritricuspid, 12 perimitral, and 11 roofs) and 30 foci or microreentries (9 CS ostium area, 6 LAA ridge, and 8 interatrial septum area and 4 elsewhere in the LA). Thus, SR was restored by EGM-based substrate ablation in 97 (80.2%) patients. The major critical areas for termination were as follows: CS ostium area, interatrial septum area, LAA ridge, and anterior LAA base (29%, 9%, 10%, and 15%, respectively). Cardioversion was required for the 24 remaining patients (5 patients still in AF and 19 regularized into AT). In these 116 patients, AF was terminated without PVI even in patients with rapid firing PV. AF was reinduced after SR conversion in 66 patients (14 patients with PAF) and SR was restored again in all of them (mean 3.3 times; range 1–10). In 17 patients, active PVs had been unintentionally isolated or became totally passive after substrate ablation. Segmental PVI was finally performed after SR conversion in 52 patients. Mean procedure and fluoroscopy duration times were 210 ⫾ 60 min (range 90–420 minutes) and 21.3 ⫾ 14.1 minutes (range 4–77 minutes), respectively. Mean RF time was 77.7 ⫾ 29.8 minutes (range 17.3–164.1 minutes).

Outcomes Complications In 185 ablation procedures (including redo procedures), the following complications occurred: 2 periprocedural pericardial effusions, 1 transient ischemic stroke, 1 reversible right

a significantly longer sustained AF duration (P ¼ .0001); a larger LA diameter (P ¼ .0007); a lower LVEF (P ¼ .0002); more structural heart disease (P ¼ .006); and a higher rate of preablation amiodarone therapy (P ¼ .003).

According to AF type, the proportion of patients with at least 1 rapid firing PV was 12 of 19 (63%) patients with PAF,

Figure 5 Proportion of patients with active and passive PVs with regard to AF type. Passive PV is defined as a silent PV or PV CL 4 LAA CL; active PV is defined as PV CL less than or greater than LAA CL. *P ¼ .0001; ** P ¼ .01. AF ¼ atrial fibrillation; CL ¼ cycle length; LAA ¼ left atrial appendage; PV ¼ pulmonary vein.

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Heart Rhythm, Vol 11, No 4, April 2014 Comparison of baseline characteristics in patients with “active” and “passive” PVs

Characteristic

Active PVs (n ¼ 69)

Passive PVs (n ¼ 52)

P

Age (y) Sex: male Sustained AF duration (mo) History of AF (mo) Hypertension Diabetes LA size (mm) LVEF (%) Structural heart disease Preablation amiodarone therapy

59.4 ⫾ 10.3 51 (74) 1.0 [0.13–4.5] 48.0 [34.5–90] 41 (59) 4 (6) 42.4 ⫾ 6.5 55.1 ⫾ 9.9 12 (17.4) 48 (69.5)

60.1 ⫾ 12.5 36 (69) 8.0 [5–20] 60.0 [36–114] 26 (50) 6 (11.5) 47.6 ⫾ 7.3 46.8 ⫾ 13.3 22 (42.3) 49 (94.2)

.61 .98 o.0001* .88 .53 .29 .0007* o.0001* .001* .003*

Values are expressed as mean ⫾ SD or as n (%). Durations are expressed as median (quartile 1–quartile 3). AF ¼ atrial fibrillation; LA ¼ left atrial; LVEF ¼ left ventricular ejection fraction; PV ¼ pulmonary vein. * P o .05.

phrenic nerve injury, 3 groin complications, and 2 transient atrioventricular block not requiring pacemaker implantation. FU After a median FU of 21 [7–28] months (after the first procedure), 57 of 119 (48%) patients were arrhythmia free after 1 procedure and 98 of 119 (82.3%) patients were free from any arrhythmia (AF or AT) after 1.5 ⫾ 0.7 ablations. Fifty patients in SR were still taking antiarrhythmic medications (11 of 24 patients without preablation amiodarone had clinical success at FU with adjuvant antiarrhythmic medications). The 21 remaining patients experienced recurrent arrhythmia (AT or AF), with redo procedures planned but not yet performed. In the case of redo procedures (41 patients), the same ablation protocol was performed. No patients treated by substrate ablation alone during the index procedure underwent PVI during redo procedures (PVs remained passive). SR conversion by ablation during the first procedure was a good predictor of long-term success (82.7% vs 66.6%; P ¼ .048; Figure 6). At the end of FU, of the 69 patients in whom EGM-based substrate ablation was performed as a stand-alone strategy (no PVI), 58 (85.3%) were free from any arrhythmia (32 of 58 patients still on antiarrhythmic medications and 1 patient lost to FU). Of 51 patients with additional PVI, 40 (78.4%) were free from any arrhythmia (19 patients on antiarrhythmic medications).

with good long-term results (82.1% arrhythmia free at the end of FU). In the population with passive PVs (n ¼ 69) treated by EGM-based stand-alone strategy, we confirm its long-term efficacy (84.8% free from any arrhythmia).

“Driving” PVs in PAF perpetuation Very short CLs could have been recorded during AF inside the PVs (mean CL 109.4 ⫾ 26.7 ms). Our results are consistent with previous studies3,12,14 showing that 100% of PV CL is less than or equal to LAA CL and, significantly, most “very short” CLs (rapid fires) in PAF compared with those in non-PAF (Figure 4). The role of “rapid firing PV” in AF starting or maintenance has been well studied and justifies the consensual ablation strategy performing PVI for PAF. Nevertheless, even in patients with rapid firing PVs, AF was terminated without PVI.

Passive PVs and atrial drivers in non-PAF We demonstrated that all 4 PVs were passive in a majority of patient with non-PAF. Our results showed a progressively

Discussion Main findings The present study suggests that the PVs can be passive in AF maintenance (especially in persistent or long-standing persistent AF with structural heart disease, dilated LA, and low LVEF). We confirm the acute efficacy of EGM-based substrate ablation in 121 patients with SR conversion rate of 80.2% (without PVI). In all cases, we performed a “patient-tailored” ablation strategy targeting atrial substrate without systematic PVI,

Figure 6 SR restoration by ablation during first procedure is a significant predictor of long-term success (n ¼ 119). Median follow-up showed up 2 groups: long-term success group and long-term failure group. The SR restoration rate during the first procedure was compared within the 2 groups, with a significant difference. SR ¼ sinus rhythm.

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decreasing role of PVs in AF maintenance with the lengthening of noninterrupted AF duration and myocardial abnormalities (structural heart disease, dilated LA, and impaired LVEF). Rostock et al9 used a stepwise ablation approach in nonPAF and showed that AF termination occurred during PVI in 9% of the procedures. Their good AF termination rates (77%) were achieved through ablation in the LA, CS, and RA in the majority of the patients. This result is consistent with Atienza et al,12 who demonstrated, after mapping with online spectral analysis, a difference in the distribution of maximal dominant frequency sites in patients with PAF (83% in the PV region) vs persistent AF (majority in non-PV locations). Ablation of extra PV maximal dominant frequency sites in persistent AF was associated with a higher long-term ablation success. This decreasing role of PVs in non-PAF may be explained by EP remodeling and scarring of both atria in non-PAF. Verma et al15 demonstrated that non-PAF, lower LVEF, and larger LA size were all related to LA scarring, as detected by contact voltage mapping, which was associated with increased AF recurrences after antral PVI. Recent human studies have directly demonstrated for the first time that a majority of patients with AF exhibit rotors and focal sources in both atria playing an important role in AF perpetuation.16 They also showed that atrial substrate ablation targeting these focal source sites slowed or terminated AF in 53% without PVI and improved outcome of “conventional” ablations.

Efficacy of EGM-based substrate ablation Since the first publication,7 efficacy of CFAE ablation is still debated.10 However, our results are consistent with the work of Nademanee et al,7 showing acute and long-term efficacy of CFAE ablation. Our ablation protocol was performed in complete accordance with the technique first described but included supplementary targeted EGMs: temporal gradient of activation13 and rapid fires. The following differences from previous articles could explain differences in acute and long-term results: voltage of targeted potentials (often o0.1 mV in our protocol), point-by-point applications (60 seconds) without “dragging” (to confirm EGM elimination after RF applications), ablation in the CS and the RA, and dynamic power settings (15–45 W). This technique is reproducible and can easily be taught and learned with a short learning curve (around 10 cases for experienced electrophysiologist). Stabile et al,17 performing antral PVI, showed that electrical isolation of PVs was not decisive for curing AF. Furthermore, Narayan et al16 showed that they could terminate AF by ablating atrial sources without PVI. In our study, even in patients with rapid firing PVs, AF has been terminated without PVI necessity. Some authors suggested that there might be a dynamic interplay between the LA and PVs during AF, with PV tachycardia depending on input from the atrium.3 Performing ablation under amiodarone therapy6,9 (25% and 40%, respectively, in these studies) probably facilitates

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AF termination as the use by some authors of ibutilide during ablation.7 This approach is useful for difficult cases to target active CFAEs and to avoid unnecessary RF applications by slowing AF.

A patient-tailored ablation protocol adapted on PV activity and atrial substrate quantity This ablation protocol focuses on AF substrate areas not only located in the PV regions. Many think that PVI is the cornerstone of AF ablation. We showed that “first step” or additional PVI can be time-consuming and unhelpful in treating some cases of persistent AF with passive PVs. Our technique is similar to the modified stepwise ablation approach,6,9 in which the greatest part of the procedure corresponds to EGM-based substrate ablation (performed after systematic PVI). Atrial core substrate quantity leading to long paroxysmal crises or persistent AF is different in every patient. Our ablation technique is based on an AF termination end point leading to an adaption of RF total duration (range 17.3–164.1 minutes) and of procedure time (range 90–360 minutes) to each patient EP substrate.

Safety data The complication rate reported with this technique was low. The absence of systematic PVI may reduce the risk of PV stenosis and the absence of systematic LA posterior lines (only EGM-based RF applications) may also reduce the esophageal fistula risk.

Study limitations The major limitation of this preliminary study lies in its nonrandomized design. The 4 PVs were systematically isolated for PVI. It would be interesting to perform isolation only for “active” veins to confirm that passive PVs have no role in affecting substrate. Far-field signals from the LAA can be recorded inside the left superior pulmonary vein, which might have led to an overestimation of active PV number (when PV CL is equal to LAA CL). This technique is based on the visual operator validation of targeted EGMs. Nevertheless, this visual analysis can be learned. Short AF CL could lead to artificially fractionated areas, and “bystander” CFAE may have been ablated in our study. A better selection of targeted EGM is an important challenge in the field of AF ablation for the coming years. To obtain an accurate evaluation of AF drivers, a highdensity simultaneous mapping of both atria and CS would be required.16 Monitoring for AF after ablation depended on symptoms and on 24-hour Holter monitoring every 3 months as well as patient reports. Asymptomatic AF could have been missed during FU. The high rate of preablation amiodarone use (80.2%) could have affected PV activity and possibly contributed to

586 the silent PV rate. PV mapping with the ablation catheter may have also overestimated the silent PV rate. Adjuvant postablation antiarrhythmic therapy allowed in our protocol may limit the evaluation of the technique without drugs.

Conclusions The role of PVs in AF maintenance appears to be more important in PAF than in non-PAF (51% of passive PVs in non-PAF). We corroborate the acute efficacy of EGM-based substrate ablation alone, with 80.2% of SR conversion by ablation without PVI. Our “patient-tailored” strategy (EGM-based substrate ablation with or without PVI) provides a good long-term outcome and suggests that PVI is not always necessary in addition to substrate ablation for the treatment of non-PAF.

Acknowledgments We thank the nurses, the technical staff, and the patients.

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Active or passive pulmonary vein in atrial fibrillation: is pulmonary vein isolation always essential?

The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based ...
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