Outcomes After Atrial Fibrillation Ablation in Patients With Premature Atrial Contractions Originating From Non-Pulmonary Veins

JACC: CLINICAL ELECTROPHYSIOLOGY

VOL.

-, NO. -, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

Outcomes After Atrial Fibrillation Ablation in Patients With Premature Atrial Contractions Originating From Non-Pulmonary Veins Ryo Nakamaru, MD,a,b Masato Okada, MD,a Nobuaki Tanaka, MD,a Koji Tanaka, MD,a Yuichi Ninomiya, MD, PHD,a Yuko Hirao, MD,a Takafumi Oka, MD, PHD,a Hiroyuki Inoue, MD,a Kohtaro Takayasu, MD,a Yasushi Koyama, MD, PHD,a Atsunori Okamura, MD, PHD,a Katsuomi Iwakura, MD, PHD,a Hiromi Rakugi, MD, PHD,b Yasushi Sakata, MD, PHD,c Kenshi Fujii, MD, PHD,a Koichi Inoue, MD, PHDa

ABSTRACT OBJECTIVES The aim of this study was to examine the relationship between residual premature atrial contractions (PACs) originating from non-pulmonary veins (non-PV PACs), which do not initiate atrial fibrillation (AF), and AF recurrence after ablation. BACKGROUND Residual atrial ectopic beats that trigger AF from non-PVs (non-PV AF triggers) after catheter ablation are among the major causes of AF recurrence. However, little is known about the impact of non-PV PACs on AF recurrence. METHODS This retrospective study included 565 consecutive patients who underwent first-time AF ablation at our institution. After PV isolation, we infused isoproterenol to provoke non-PV AF triggers and/or non-PV PACs. We excluded 26 patients with non-PV AF triggers and 3 patients who underwent ablation of non-PV PACs, and finally analyzed 536 patients. Non-PV PACs were defined as ectopic beats that were constantly observed with the same intra-atrial activation patterns from non-PVs. RESULTS Residual non-PV PACs during the procedure were observed in 112 patients (21%). There was no significant difference in the AF recurrence rate between patients with non-PV PACs (35 of 112, 31%) and those without (145 of 424, 34%; log-rank p ¼ 0.69), during a median follow-up of 670 days. Age- and sex-adjusted hazards for AF recurrence were also similar between the 2 groups. CONCLUSION The similar AF recurrence rate in patients with and without non-PV PACs suggests that the additional ablation of non-PV PACs has limited effect on AF recurrence. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

From the aDepartment of Cardiology, Sakurabashi Watanabe Hospital, Osaka, Japan; bDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan; and the cDepartment of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan. This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Inoue has received honoraria from Johnson and Johnson KK, Medtronic Japan, Bayer Yakuhin, Nihon Boehringer Ingelheim, Bristol Myers Squibb, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received February 11, 2019; revised manuscript received July 29, 2019, accepted August 6, 2019.

ISSN 2405-500X/$36.00

https://doi.org/10.1016/j.jacep.2019.08.002

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Clinical Significance of Residual Non-PV PACs

ABBREVIATIONS AND ACRONYMS AAD = antiarrhythmic drug AF = atrial fibrillation

T

he pulmonary veins (PVs) are the

the ablation procedure and the retrospective use of

most important source of ectopic

their clinical data for the purposes of this study.

beats

initiating

atrial

fibrillation

(AF) (1). Consequently, electrical disconnection of the left atrial musculature from these

LA = left atrium

arrhythmogenic PVs, called PV isolation

LAA = left atrial appendage

(PVI), is an effective treatment of patients

PAC = premature atrial

with AF. However, 10% to 20% of patients

contraction

have ectopic beats initiating AF from non-

PAF = paroxysmal AF

pulmonary veins (non-PV AF trigger) (2–5),

PV = pulmonary vein

which is 1 of the important causes of AF

PVI = pulmonary vein isolation

recurrence after PVI (6–9). The current expert

SVC = superior vena cava

consensus statement (10) recommends ablation of non-PV AF triggers following PVI because this may reduce AF recurrence (11–16). In contrast, little is known about the relationship between residual premature

atrial contractions (PACs) originating

from non-PVs (non-PV PACs) that do not initiate AF and AF recurrence. Therefore, the ablation strategy for non-PV PACs is currently unclear. The aim of this study was to investigate the impact of residual non-PV PACs following PVI on the AF recurrence after ablation.

DESIGN

PROTOCOL. Details

of

the

electrophysiological

studies and the ablation protocol were described previously (17). Antiarrhythmic drugs (AADs) were discontinued more than 3 half-lives before the procedure. Extensive encircling PVI was performed using an open-irrigated ablation catheter (NaviStar Thermocool, Biosense Webster Inc., Diamond Bar, California).

Successful

PVI

was

defined

as

the

achievement of a bidirectional conduction block between the left atrium (LA) and the PVs. After the completion of PVI, we infused isoproterenol (4–20 m g/min) to provoke non-PV AF triggers and/or non-PV PACs (10). We continued the administration of isoproterenol until AF was induced or the heart rate increased to >130 beats/min. In case systolic blood pressure decreased to <60 mm Hg, we administered

etilefrine

until

it

increased

again

to

>100 mm Hg. Once we observed reproducible non-PV PACs or non-PV AF triggers, we tried to detect the origin by positioning the mapping catheter in the SVC, the right atrium free wall, the coronary sinus

METHODS STUDY

ELECTROPHYSIOLOGICAL STUDIES AND ABLATION

ostium, the interatrial septum, the LA posterior wall, AND

PATIENTS. A

total of 565

consecutive patients with either paroxysmal atrial fibrillation (PAF) (n ¼ 372) or non-PAF (n ¼ 193) underwent first-time radiofrequency catheter ablation for AF at our institution between January 2013 and September 2014. After excluding 26 patients who had non-PV AF triggers and 3 patients who had undergone ablation of non-PV PACs from the superior vena cava (SVC), the remaining 536 patients were included in this retrospective analysis. We divided them into the following 2 groups: patients who had residual non-PV PACs during the procedure were assigned to the nonPV PAC group, and patients without those formed the control group (Figure 1). Non-PV PACs were defined as ectopic beats that were constantly observed with the same intra-atrial activation patterns from non-PVs using multipolar catheters, but that did not initiate any atrial arrhythmia lasting $10s. Furthermore, we defined frequent and rare non-PV PACs as $10 and <10/min during the procedure, respectively. Non-PV AF triggers were defined as ectopic beats

and the LA anterior wall in the vicinity of the left atrial appendage (LAA) (Figure 2). The catheter was manipulated with great care to not mechanically induce beats. When the beats diminished after repositioning of the catheter, they were considered as induced by a mechanical stimulus of the catheter. We performed ablation of non-PV AF triggers whenever possible. In contrast, ablation of non-PV PACs is not generally performed at our institution. The highest frequency of the reproducible non-PV PACs during the procedure was recorded. As mentioned above, patients who received ablation of non-PV PACs from the SVC were excluded from this analysis (n ¼ 3). A cavotricuspid isthmus block was created if common atrial flutter was detected before or during the procedure. The performance of other additional ablations such as linear ablation or complex fractionated atrial electrogram ablation depended on the operator’s judgment. All procedures were performed under conscious sedation with pentazocine, thiamylal sodium, and dexmedetomidine hydroxyzine.

initiating AF lasting $10s and originating from non-

PATIENT FOLLOW-UP. All patients were hospitalized

PVs. The endpoint of this study was AF recurrence,

with continuous rhythm monitoring for 3 days after

which was defined as recurrent atrial tachyar-

the procedure and were scheduled for visits to the

rhythmia lasting for >30s more than 90 days after

outpatient clinic every 1 to 2 months. From 2 years

ablation (10). This study was approved by the ethics

after the procedure, patients were followed up every

committee of Sakurabashi Watanabe Hospital. All

6 months. AADs were discontinued 3 months after the

patients provided written informed consent for both

procedure except for patients with AF recurrence. An

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F I G U R E 1 Study Flowchart

AF ¼ atrial fibrillation; BP ¼ blood pressure; HR ¼ heart rate; ISP ¼ isoproterenol; PAC ¼ premature atrial contraction; PV ¼ pulmonary vein; PVI ¼ pulmonary vein isolation; RFCA ¼ radiofrequency catheter ablation.

electrocardiogram was performed at every visit. A 24-

Continuous variables were analyzed using the Stu-

h Holter recording was recorded 6 months after the

dent’s t-test or Mann-Whitney U test when comparing

procedure. The Holter recording was performed and

2 groups, and the one-way analysis of Kruskal-Wallis

analyzed using the RAC-3203 and DSC-5500 (Nihon

test when comparing among the control, rare non-PV

Kohden, Tokyo, Japan). Analyses were reviewed by the responsible investigating cardiologist. PACs were defined as supraventricular complexes occurring

F I G U R E 2 Catheter Setting for Mapping of Non-PV AF

Triggers or PACs

>30% earlier than expected compared with the previous interval between 2 adjacent R waves in the Holter recording. Additional monitoring was performed depending on the patients’ symptoms. Patients were encouraged to check their pulse rate and rhythm 3 times a day and visit our hospital if they experienced an irregular pulse. In such cases, 24-h Holter

recording

and/or

2-week

cardiac

event

recording was performed to identify AF recurrence. In patients with AF recurrence who underwent a second procedure, the ablation protocol was the same as that in the first one. We searched for the reconnection of PV potentials, identified AF triggers, and attempted to ablate them. STATISTICAL ANALYSIS. Descriptive statistics are

reported as mean  SD or as the median (interquartile

CS ¼ coronary sinus; IAS ¼ interatrial septum; LAA ¼ left atrial

range) for continuous variables, and as absolute fre-

appendage; RA ¼ right atrium; SVC ¼ superior vena cava.

quencies and proportions for categorical variables.

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Clinical Significance of Residual Non-PV PACs

value of <0.05 was considered significant. All statis-

T A B L E 1 Patients Characteristics

tical analyses were performed using JMP 12.2.0 softControl Group (N ¼ 424)

Non-PV PAC Group (N ¼ 112)

p Value

61.7  0.5

64.7  0.9

<0.01

332 (78)

73 (65)

<0.01

BMI, kg/m2

24.4  0.2

23.7  0.3

0.23

LV ejection fraction, %

64.8  0.5

64.3  0.9

0.62

PREVALENCE OF NON-PV PACs. A total of 112 (21%)

LA diameter, mm

38.4  0.3

37.6  0.5

0.24

of 536 patients had residual non-PV PACs during the

Creatinine, mg/dl

0.88  0.02

0.85  0.05

0.58

first procedure. Among them, frequent non-PV PACs

BNP, pg/ml

119.7  12.1

129.9  24.0

0.70

were observed in 65 patients (58%). Among the 353

Paroxysmal

277 (65)

76 (68)

0.86

Persistent

89 (21)

21 (19)

Long-standing persistent

58 (14)

15 (13)

Congestive heart failure

54 (13)

18 (16)

0.35

Hypertension

218 (51)

64 (57)

0.29

Diabetes mellitus

59 (14)

19 (17)

0.45

Previous stroke

33 (7.8)

4 (3.6)

0.14

Coronary artery disease

50 (12)

12 (11)

0.87

the control group. There were no statistically signifi-

Hemodialysis

3 (0.7)

0

1.00

cant differences in the other baseline characteristics

Valvular heart disease

15 (3.5)

8 (7.1)

0.11

between the 2 groups. PVI was successfully per-

Sleep apnea

34 (8.0)

12 (11)

0.35

formed in all patients. The prevalence and distribu-

0, 1

315 (74)

78 (70)

0.34

$2

109 (26)

34 (30)

424 (100)

112 (100)

1.00

complications that required intervention during the

CTI block line

127 (31)

25 (22)

0.10

procedure.

Box isolation of LA

6 (1.4)

3 (2.7)

0.37

Mitral valve isthmus line

5 (1.2)

2 (1.8)

0.68

0

0

-

57.2  1.1

60.2.0  2.1

0.21

-

65 (58)

-

Age (yrs) Male

Type of AF

CHADS2 score

Total dose of ISO, mg Frequent non-PV PACs

patients with PAF, 76 (27%) exhibited non-PV PACs and 36 (13%) of the 183 patients with non-PAF did

BASELINE

CHARACTERISTICS

AND

ABLATION

PROCEDURES. The baseline characteristics of pa-

tients in the 3 groups are summarized in Table 1. The patients were younger and more frequently male in

tion of non-PV PACs are shown in Figure 3. The most frequent origin of non-PV PACs was the right atrium free wall (47%). No patients experienced severe

Findings from the fist procedure

CFAE ablation

RESULTS

(p ¼ 0.64).

Comorbidity

PVI

ware (SAS Institute, Cary, North Carolina).

Antiarrhythmic drug during the 3 months post the first procedure

NUMBER OF PACs IDENTIFIED USING HOLTER RECORDING 6

MONTHS AFTER THE FIRST PROCEDURE. We per-

formed

24-h

Holter

recording

in

499

patients

6 months after ablation except for 37 patients who had a persistent form of AF recurrence at that time.

Class I

118 (28)

36 (21)

0.41

The median number of PACs identified by the Holter

Class II

57 (13)

23 (21)

0.07

recording in the non-PV PAC and control group was

Class III

6 (1.4)

4 (3.5)

0.23

39 (interquartile range: 13 to 381) and 83 (interquartile

Class Ⅳ

83 (20)

21 (19)

0.89

Antiarrhythmic during the Holter ECG recording at 6 months

range: 25 to 558), respectively (Figure 4). Although we did not observe any significant differences in the frequency of AAD intake 6 months after ablation be-

Class I

45 (11)

8 (7.5)

0.37

Class II

25 (6.2)

10 (9.4)

0.28

tween the groups (Table 1), the number of PACs was

Class III

1 (0.3)

1 (0.9)

0.38

significantly larger in the non-PV PAC group than that

Class Ⅳ

33 (8.2)

9 (8.4)

1.00

in the control group (p < 0.01).

Values are mean  SD or n (%). AF ¼ atrial fibrillation; BMI ¼ body mass index; BNP ¼ brain natriuretic peptide; CFAE ¼ complex fractionated atrial electrogram; CHADS2 ¼ congestive heart failure, hypertension, age, diabetes, prior stroke; CTI ¼ cavotricuspid isthmus; ECG ¼ electrocardiogram; ISO ¼ isoproterenol; LA ¼ left atrium; LV ¼ left ventricular; PVI ¼ pulmonary vein isolation.

In addition, the median number of PACs in patients with frequent non-PV PACs (136, interquartile range: 34 to 389) was significantly larger than in those with rare non-PV PACs (52, interquartile range: 19 to 371; p < 0.01) (Online Figure 1).

PAC, and frequent non-PV PAC groups. Categorical

AF

variables were compared using the chi-squared or

recurrence-free survival after the 3-month blanking

RECURRENCE. The

Fisher exact test. Event-free survival was reported as

period is shown in Central Illustration A. During a

the crude event rate and estimated using the Kaplan-

median follow-up of 670 days after ablation, AF

Meier survival function. Pairwise comparisons of

recurred in 180 patients (34%). The AF recurrence

survival rates were made using the log-rank test. Cox

rate was almost equivalent between the non-PV PAC

proportional hazard analyses were performed. A p

(31%, 35 of 112) and the control group (34%, 145 of

Kaplan-Meier

curve

for

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F I G U R E 3 Comparison of Risk for AF Recurrence Based on the Origin of Non-PV PACs

LAPW ¼ left atrium posterior wall; NA ¼ not applicable; other abbreviations as in Figures 1 and 2.

424; log-rank p ¼ 0.69). Similar results were obtained

procedure was significantly higher in the non-PV PAC

when comparing the recurrence rate in the subgroups

group (p ¼ 0.03), approximately half of these patients

of patients with PAF (27% and 30%, respectively; log-

with non-PV PACs during the first procedure did not

rank p ¼ 0.98) and non-PAF (31% and 33%, respec-

have them during the second procedure. Two

tively;

log-rank

p

¼

0.54).

Furthermore,

the

recurrence rate in the patients with frequent and rare non-PV PACs was also similar (35%, 23 of 65 and 26%,

F I G U R E 4 Box-and-Whisker Diagram for Numbers of PACs

Identified Using Holter Recording 6 Months After Ablation

12 of 47) (Online Figure 2). In comparison with the control group, the age- and sex-adjusted hazard for AF recurrence was statistically similar in the patients with non-PV PAC (hazard ratio: 0.83; 95% confidence interval: 0.64 to 1.07; p ¼ 0.14). There was no significant association between the origin of non-PV PACs and the risk of AF recurrence (Figure 3). FINDINGS IN PATIENTS WITH AF RECURRENCE UNDERGOING A SECOND PROCEDURE. Of the 180 pa-

tients with AF recurrence, 134 (74%) underwent a second procedure 315 days (median) after the first procedure. In the non-PV PAC and the control group, 21% (24 of 112) and 26% (110 of 424), respectively, underwent a second procedure. There was no significant difference in the frequency of PV reconnections (p ¼ 1.00), AF triggers from PV (p ¼ 0.70), those from non-PV (p ¼ 0.67), or reconnection of linear ablation (p ¼ 1.00) between the 2 groups (Table 2). Although the prevalence of non-PV PACs during the second

In each box plot, the line in the box indicates the median, the lower and upper boundaries of the boxes indicate the interquartile range, and the whiskers indicate the minimum and maximum values within 1.5 times of the interquartile range. Abbreviation as in Figure 1.

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C E N T R A L IL L U ST R A T I O N Freedom From AF Recurrence After Ablation

A AF-Free Survival Rate, %

100 80 60 40 20 Log rank p = 0.69 0 0

200 400 600 Follow-Up Duration (Days)

800

Number at risk Control

424

336

236

172

18

Non-PV PAC

112

96

74

53

9

B 100 AF-Free Survival Rate, %

6

80 60 40 20 Log rank p = 0.50 0 0

200 400 600 Follow-Up Duration (Days)

800

Number at risk Control

424

381

289

212

44

Non-PV PAC

112

101

82

58

15

Nakamaru, R. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. (A) Freedom from AF recurrence after the first procedure in the non-PV PAC and control groups. (B) Freedom from AF recurrence after the second procedure in the non-PV PAC and control groups. AF ¼ atrial fibrillation; PAC ¼ premature atrial contraction.

patients received additional ablation of frequent and

procedure, the prevalence of non-PV AF triggers

symptomatic non-PV PACs during the second pro-

during the second procedure was 8% (n ¼ 2)

cedure (the SVC and the LA posterior wall). Among

compared with 9% (n ¼ 10) in the 110 patients with

the 24 patients with non-PV PACs during the first

non-PV PACs in the control group. The origin of the

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non-PV AF triggers (the interatrial septum) diagnosed during the second procedure were discordant with

Clinical Significance of Residual Non-PV PACs

T A B L E 2 Comparison of Findings From the Second Procedures

Control Group (n ¼ 110)

Non-PV PAC Group (n ¼ 24)

PV reconnection

105 (96)

23 (96)

1.00

AF triggers from PV

26 (24)

5 (21)

0.70

the AF recurrence rate after the second procedure

AF triggers from non-PV

10 (9.1)

2 (8.3)

0.67

among the groups based on the first procedure (log-

Non-PV PACs

22 (20)

11 (46)

0.02

that of non-PV PACs (the LA posterior wall and the coronary sinus ostium) during the initial procedure. Furthermore, there was no significant difference in

rank p ¼ 0.50) (Central Illustration, Part B). The

Frequent non-PV PACs

p Value

6 (5.5)

5 (21)

0.03

18 (16)

4 (17)

1.00

57.0  2.3

62.1  3.3

0.21

SVC

2 (1.8)

0

0.68

RA free wall

4 (3.6)

0

0.45

0

0

-

LAPW

1 (0.9)

0

0.82

MAIN FINDINGS. The results of the present study

IAS

4 (3.6)

2 (8.3)

0.29

show that: 1) about 20% of all patients who had

LAA

0

0

-

recurrence rate in the patients with frequent and rare

Reconnection of linear ablation

non-PV PACs was 13% (6 of 47) and 22% (14 of 65),

Total dose of ISO, mcg

respectively (Online Figure 3).

Origin of AF triggers from non-PV

DISCUSSION

undergone AF ablation had non-PV PACs; 2) patients with non-PV PACs during the procedure had a larger number of PACs by Holter recording 6 months after ablation; and 3) the presence of non-PV PACs during

CS ostium

Values are n (%) or mean  SD. CS ¼ coronary sinus; IAS ¼ interatrial septum; LAA ¼ left atrium appendage; LAPW ¼ left atrium posterior wall; PAC ¼ premature atrial contraction; PV ¼ pulmonary vein; RA ¼ right atrium; SVC ¼ superior vena cava; other abbreviations as in Table 1.

the procedure was not associated with increased AF recurrence after ablation, even after stratification by their origin. Non-PV PACs did not have a large

COMPARISON WITH PRIOR STUDIES. Several studies

impact on AF recurrence, suggesting that additional

have described that a “non-PV trigger” represents a

ablation of non-PV PACs following PVI would

risk of AF recurrence after PVI and that its ablation

not influence improvement of AF recurrence after

reduces the AF recurrence rate (8–16). However, in

ablation.

these studies, “non-PV trigger” was defined as PACs

LIMITED IMPACT OF NON-PV PACs ON AF RECURRENCE.

The majority of AFs are triggered by PACs originating from PVs and maintained by AF substrates in the PV and PV-LA junction (18). Several studies have indicated variations in the effective refractory period, decremental conduction properties, and multiple conduction pathways in the PVs and PV-LA junction (19,20). These characteristics may be associated with substrate to initiate and maintain AF. In this study, there was no significant difference in the AF recurrence rate between patients with and without non-PV PACs that do not initiate AF. The proportion of patients with AF recurrence who had non-PV AF triggers during the second procedure was also similar between the non-PV PAC and the control group. Non-PV PACs might be lacking the substrate to initiate and maintain AF around them because they would become non-PV AF triggers when they had sufficient AF substrate. Moreover, among the patients with AF recurrence who underwent a second procedure, the sites of non-PV PACs during the first procedure were different from those of the non-PV AF triggers during the second procedure. These data indicate that the progression of the AF substrate did not occur frequently.

that initiated AF. “Non-PV PAC” in this study referred to PACs that did not initiate AF. As mentioned above, it is possible that non-PV AF triggers have sufficient AF substrate around their origin to sustain them, whereas non-PV PACs do not. This difference in the definition

may

explain

the

conflicting

results.

Furthermore, Di Biase et al. (13) reported that empirical LAA isolation improved ablation outcomes in patients with long-standing persistent AF. The LAA has a role not only as a trigger but also as a substrate of AF. Other studies indicated that the presence of frequent non-PV PACs following PVI was associated with AF recurrence after ablation (21,22). Elayi et al. (21)

reported

that

patients

with

non-PV

PACs

(>10/min) had a higher recurrence rate than those without non-PV PACs after AF ablation. The majority of their study population consisted of nonPAF patients (85%), which represents a larger proportion than in our study, where non-PAF patients accounted for about a third (32%) of all patients. This might explain the discrepancy between the prevalence of non-PV PACs in their (44%) and our study (21%) and the different impact on ablation outcomes. Velagic et al. (22) also examined patients

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with PAF (n ¼ 70) who underwent cryoballoon

following successful PVI is not necessarily required to

ablation, and reported that the occurrence of non-

reduce AF recurrence. However, further prospective

PV PACs (>1/10 cycles or >6/min) in response to

randomized studies should be conducted to sub-

isoproterenol was associated with AF recurrence. It

stantiate these findings.

has been reported that the PVI areas identified using cryoballoon ablation are significantly smaller than those established by radiofrequency catheter ablation (23). Because the PV ostia are a frequent site of AF triggers, it can be assumed that PACs that do not initiate AF from this area could more easily progress to AF triggers during the post-procedural follow-up period than PACs from other parts of the atria. In our study, all procedures were performed using radiofrequency catheter ablation, and the difference in ablation methods might have influenced the result.

STUDY LIMITATIONS. There are several limitations to

the present study. First, this is a single-center retrospective study. Second, we may have underestimated AF recurrence because of undetected asymptomatic AF episodes. Third, although the heart rate reached the target heart rate in almost all cases, it is possible that the dose of isoproterenol administered was not sufficient to provoke non-PV AF triggers or PACs in all patients. Fourth, a previous study suggested that severe LA scarring was associated with AF recurrence in patients with PAF (15). Although it is possible that the LA substrate at baseline correlates with the frequency

HOLTER RECORDING 6 MONTHS AFTER ABLATION.

of non-PV PACs, we did not routinely investigate LA

Several studies have examined the association be-

voltage during the procedure. Finally, we defined

tween

recurrence

the frequent non-PV PACs as $10/min. However,

(24,25). The number of PACs recorded by Holter

there is no uniform definition of non-PV PAC to date.

PACs

after

ablation

and

AF

recording reflects the sum of PACs from PVs resulting from the electrical reconnection of isolated

CONCLUSIONS

PVs and those from non-PVs. An increase in PACs from reconnected PVs is the proposed mechanism

In this study, non-PV PACs after PVI were not asso-

underlying the significant association between the

ciated with AF recurrence. Therefore, non-PV PACs

number of PACs and AF recurrence. In the present

may not necessarily be targeted for ablation in addi-

study, the number of PACs from reconnected PVs is

tion to PVI.

assumed to be equivalent between patients with

ACKNOWLEDGMENTS The authors are grateful to the

and without non-PV PACs because the patients’

nursing staff, clinical engineers, and office adminis-

baseline characteristics and ablation strategies were

trators of Sakurabashi-Watanabe Hospital for their

similar. Therefore, the difference in the overall

kind support during this study.

number of PACs shown in Figure 4 was likely due to the non-PV origin of a certain proportion of these

ADDRESS FOR CORRESPONDENCE: Dr. Koichi Inoue,

PACs.

Department of Cardiology, Sakurabashi Watanabe

CLINICAL

IMPLICATIONS. Non-PV

PACs

are

frequently observed after PVI in AF ablation. In this study, non-PV PACs, according to our definition, were observed in as much as 20% of our population, which was a considerably larger proportion than the 5% of patients with non-PV AF triggers. Therefore, defining a strategy for ablation targeting non-PV PACs is an important issue. However, there are no recommendations on this critical issue in the current expert consensus (10). In this study, there was no significant difference in AF recurrence between patients with and without non-PV PACs. Moreover, approximately half of the patients with non-PV PACs during the first procedure did not have them during the second procedure. Although improvement of electrical remodeling might lead to the elimination of non-PV PACs, it is also possible that the induction of non-PV PACs during the procedure is not reproducible. Our results indicate that additional ablation of non-PV PACs

Hospital, 2-4-32, Umeda, Kita-ku, Osaka 5300001, Japan. E-mail: [email protected]. PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: The presence of non-PV PACs was not associated with increased AF recurrence after ablation. Furthermore, the origins of the non-PV AF triggers diagnosed during the second procedure were discordant with those of non-PV PACs during the initial procedure. These results suggest that non-PV PACs may not necessarily be targeted for ablation following PVI. TRANSLATIONAL OUTLOOK: Further prospective randomized studies are needed to elucidate the relationship between residual non-PV PACs and AF recurrence following PVI.

JACC: CLINICAL ELECTROPHYSIOLOGY VOL.

-, NO. -, 2019

Nakamaru et al.

- 2019:-–-

Clinical Significance of Residual Non-PV PACs

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KEY WORDS atrial fibrillation, catheter ablation, non-pulmonary vein, premature atrial contractions

A PP END IX For supplemental figures, please see the online version of this article.

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