The techniques for catheter abla

tion of paroxysmal and

persistent atrial fibrillation: a systematic reviewAtul Verma

Southlake Heart Rhythm Program, Division ofCardiology, Southlake Regional Health Centre,Newmarket, Ontario, Canada

Correspondence to Atul Verma, MD, FRCPC, 105-712Davis Drive, Newmarket, Ontario, Canada L3Y 8C3Tel: +1 905 953 7917; fax: +1 905 953 0046;e-mail: atul.verma@utoronto.ca

Current Opinion in Cardiology 2011,26:17–24

Purpose of review

Ablation for atrial fibrillation has become a widely accepted and practiced treatment for

this arrhythmia. However, the technique for ablation has evolved over time, particularly

for the two distinct groups of paroxysmal and persistent atrial fibrillation. This review

outlines the optimal techniques for ablation of these different subgroups of atrial

fibrillation.

Recent findings

The most commonly applied techniques for atrial fibrillation ablation include isolation of

the pulmonary venous antra, left-atrial linear ablation, and ablation of complex

fractionated electrograms (CFEs) during atrial fibrillation. For patients with paroxysmal

atrial fibrillation, isolation of the pulmonary venous antra appears to be sufficient, with

effective and reproducible outcomes being reported across many centers. For

persistent atrial fibrillation, the outcome of catheter ablation is less efficacious. It is

widely believed that additional ablation targeting the substrate of atrial fibrillation

maintenance is required beyond pulmonary venous isolation. Linear and CFE ablation

have been the most commonly employed adjuvant strategies employed, but neither has

been adequately compared with the other to make definitive recommendations.

Summary

Pulmonary venous antral isolation is the cornerstone of ablation of both paroxysmal and

persistent atrial fibrillation. However, to obtain better outcomes in persistent atrial

fibrillation, further adjuvant ablation, in the form of either linear or CFE ablation, will likely

have to be performed to achieve comparable success rates.

Keywords

atrial fibrillation, catheter ablation, paroxysmal, persistent, review, technique

Curr Opin Cardiol 26:17–24� 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins0268-4705

Introduction

Atrial fibrillation is an increasingly common disease,

which affects patient morbidity and mortality. Atrial

fibrillation ablation has emerged as a promising new

treatment strategy, which offers the possibility of a

durable treatment. However, the technique of atrial

fibrillation ablation is still evolving. While targeting the

triggers of atrial fibrillation may be sufficient for paro-

xysmal atrial fibrillation patients, additional ablation tar-

geting the substrate of atrial fibrillation maintenance may

be required for patients with persistent atrial fibrillation

[1�]. The most commonly employed strategy for trigger-

targeted ablation is isolation of the pulmonary venous

antra from the rest of the left atrium (LA). Indeed, this

has become the cornerstone of all atrial fibrillation abla-

tion [2]. The optimal technique for substrate-based abla-

tion is more elusive, with both linear ablation and target-

ing of complex fractionated electrograms (CFEs) being

the most common [3]. Which of these adjuvant strategies

0268-4705 � 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

should be used, or whether they should be combined,

remains an open question and is the subject of ongoing

clinical investigation.

Differences between paroxysmal andpersistent atrial fibrillationInitial theories suggested that atrial fibrillation was a self-

sustaining arrhythmia perpetuated by multiple wavelets

of re-entry. This multiple wavelet hypothesis suggested

that, as long as the atrium had sufficient area with

adequately short refractory periods, atrial fibrillation

could be initiated and then indefinitely perpetuated

[4]. Much focus was placed on the perpetuation side of

this theory, with early attempts at interventional atrial

fibrillation treatment (i.e. the Maze procedure) attempt-

ing to compartmentalize the atrium into smaller regions

incapable of sustaining multiple wavelets. In recent

years, however, more attention has been devoted to

the initiation of atrial fibrillation. The theory that atrial

DOI:10.1097/HCO.0b013e3283413925

18 Arrhythmias

Key points

� Cornerstone for atrial fibrillation ablation is wide,

antral isolation of the pulmonary veins.

� In paroxysmal atrial fibrillation, wide antral isolation

is likely adequate for good procedural outcome.

� In persistent atrial fibrillation, pulmonary venous

isolation likely must be combined with other sub-

strate-guided ablation to improve procedural out-

come.

� The most commonly used substrate-based targets

for atrial fibrillation ablation are linear ablation and

ablation of complex fractionated electrograms.

fibrillation, in particular paroxysmal atrial fibrillation, was

a triggered arrhythmia was really brought to the forefront

by the observations of Haissaguerre et al. [5]. In their

seminal report, they showed that paroxysmal atrial fibril-

lation was initiated by rapidly firing, repetitive discharges

originating predominantly in the pulmonary venous

antra. The pulmonary venous antra have unique electro-

physiologic properties compared with the rest of the LA,

making the pulmonary venous–LA junction a vulnerable

region for triggered activity and microre-entry. While

non-pulmonary venous triggers have also been described,

they account for no more than 6–10% of atrial fibrillation

triggers [6]. As such, catheter ablation strategies for

paroxysmal atrial fibrillation have focused on isolating

the pulmonary venous antra from the rest of the LA.

In contrast, persistent atrial fibrillation seems to be less

dependent on the pulmonary venous antra for both

initiation and perpetuation [4]. Non-pulmonary venous

triggers occur more commonly in persistent atrial fibrilla-

tion than they do in paroxysmal atrial fibrillation [7].

Furthermore, more of the re-entry sites required for atrial

fibrillation perpetuation are more commonly found out-

side the pulmonary venous–LA junction in persistent

atrial fibrillation [8]. This is likely a result of both the

electrical and structural remodeling that occurs with

chronic atrial fibrillation. Whereas the pulmonary

venous–LA junction provides an electrophysiologically

active region for patients with a normal atrial function,

chronic atrial fibrillation creates diffuse changes in refrac-

tory periods and fibrosis that can promote triggered

activity or re-entry in many different parts of the LA

[9]. Animal models, for example, have demonstrated

microscopic fibrotic changes in the LA which result in

persisting vulnerability to atrial fibrillation despite long

periods of sinus rhythm [10]. Furthermore, human map-

ping studies have shown that LA scarring is more

common in patients with persistent atrial fibrillation,

with or without structural heart disease [11]. It should

not be surprising, then, that ablation strategies focused

exclusively on the pulmonary venous antra will not

achieve as great success in persistent atrial fibrillation.

Techniques of atrial fibrillation ablationThe following sections outline the most commonly

employed techniques for atrial fibrillation ablation used

today.

Pulmonary vein isolation

Ever since the important observations of Haissaguerre

et al. [5], isolation of the pulmonary venous antra has

become the ‘cornerstone’ of all atrial fibrillation ablation

procedures [2]. The technique of pulmonary venous

isolation has evolved over the years. Initially, the pro-

cedure involved a ‘segmental, ostial’ approach in which

the earliest pulmonary venous potentials were targeted at

the tubular ostium of each vein, thereby achieving elec-

trical isolation as guided by a multipolar, circular catheter.

However, this approach was limited by modest efficacy,

frequent pulmonary venous reconnection, and a higher

risk for pulmonary venous stenosis. The technique later

evolved to circumferential pulmonary venous ablation

(CPVA), in which encircling lines of ablation were per-

formed outside and around the pulmonary venous antra

within the LA, without necessarily documenting electri-

cal isolation of the pulmonary venous antra [12]. Although

this technique seemed to have a better outcome than

segmental, ostial ablation, while minimizing the risk of

pulmonary venous stenosis, the technique still had a high

rate of macrore-entrant arrhythmia recurrences because

of residual pulmonary venous connection. Today, most

centers employ an ‘antral’ isolation approach in which

ablative lesions are placed outside the tubular veins in a

circumferential pattern, but with documentation of elec-

trical isolation of the pulmonary venous antra with a

circular mapping catheter [13]. Outcome seems directly

related to resumption of conduction between the pul-

monary venous antra and the LA [14]. Typically,

entrance block into the pulmonary venous antra is the

minimum requirement, with many advocating demon-

stration of both entrance and exit block for best outcome

[15]. Using this approach, many centers are reporting

60–80% success rates in patients with lone, paroxysmal

atrial fibrillation off antiarrhythmic drugs after one

procedure.

Linear ablation

From the early experiences with the Maze surgical pro-

cedure, there has been much interest in creation of linear

lesions, predominantly in the LA, using percutaneous,

catheter-based techniques. Whereas linear ablation may

work by compartmentalizing the LA into smaller regions

incapable of sustaining microre-entry, most of the effect

of linear ablation may be in prevention of macrore-

entrant tachycardias or flutters that can occur post-atrial

fibrillation ablation. Linear ablation may also transect

structures that harbor key ‘rotor’ sites for atrial fibrillation

Techniques for catheter ablation of atrial fibrillation Verma 19

Table 1 Odds ratios and 95% confidence intervals of meta-

analyses of success of catheter ablation of atrial fibrillation

versus antiarrhythmic drug therapy

Study Odds ratio 95% confidence interval

Noheria et al. [28] 3.73 2.47–5.63Nair et al. [27�] 2.86 1.75–4.76Piccini et al. [29] 15.78 10.07–24.73Terasawa et al. [30��] 3.46 1.97–6.09

maintenance, such as the LA posterior wall, roof, mitral

annulus, and septum. Given that the two most common

sites of postablation macrore-entry are the roof and mitral

annulus, these are the sites of the most commonly

employed linear lesions. The roof line is performed by

joining the right and left superior pulmonary venous antra

across the roof, whereas the mitral line can be performed

posteriorly from the left inferior pulmonary venous to the

annulus, or anteriorly from the annulus to the left superior

pulmonary venous. Early experiences using linear abla-

tion alone, attempting to replicate the surgical Maze,

were technically difficult and not successful and were

thus abandoned over time [16]. However, linear ablation

remains an important adjuvant ablation strategy, often in

combination with pulmonary venous isolation. Unfortu-

nately, achievement of complete conduction block across

lines can be very difficult to achieve since lesions must be

both contiguous and transmural [17]. Thus, whereas lines

may prevent recurrent arrhythmias, they may be pro-

arrhythmic if incomplete. Addition of a floor line is less

commonly employed, effectively creating a ‘box iso-

lation’ of the posterior LA wall when combined with

pulmonary venous isolation and the roof line [18], but

data are conflicting as to the utility of such a line. Septal

lines from the mitral annulus to the right superior pul-

monary venous have also been reported, but are techni-

cally very challenging to achieve [19].

Complex fractionated electrograms

Complex fractionated electrograms are electrograms

during atrial fibrillation which either have very short

cycle lengths (<120 ms) compared with other electro-

grams in the LA or are fractionated with two or more

components and a continuous perturbation of the base-

line [20]. These sites may represent critical ‘rotor’ or

‘pivot’ points in which wavelets can turn around and

create opportunities for re-entry that maintains atrial

fibrillation [21]. However, fractionation has also been

shown to occur at sites of passive wavelet collision, which

may not actively participate in the atrial fibrillation pro-

cess [21]. CFE ablation was first proposed as a lone

strategy with reasonable single and double procedural

success rates in both paroxysmal and persistent atrial

fibrillation patients [20]. However, this early, single-

operator experience has not been replicated by other

operators. Part of the limitation is the subjectivity in

the interpretation of CFE. While there is a standardized

definition of CFE, their identification by visual inspec-

tion alone can be very challenging. Furthermore,

although CFE sites have been shown to be both spatially

and temporally stable, beat-to-beat changes may occur,

while averaging the signal over 2–8 s shows little vari-

ation [22]. Thus, automated mapping algorithms have

been developed to improve objectivity in CFE identifi-

cation. Yet, even with the use of such algorithms, CFE as

a lone strategy has not been demonstrated to have

reliable outcomes. Thus, CFE is most commonly used

as an adjuvant strategy in combination with pulmonary

venous isolation and/or linear ablation. The endpoint

should be electrogram elimination with resulting pro-

longation in atrial fibrillation cycle length and possibly

atrial fibrillation regularization/termination.

Other targets

Less commonly employed targets include ablation

of autonomic ganglionated plexi, as identified by high-

frequency stimulation [23], and ablation of sites of high

dominant frequency as identified by Fast Fourier Trans-

form (spectral) analysis of atrial fibrillation electrograms

[24�]. While both approaches may offer additional success

on top of pulmonary venous isolation, data are too limited

at this stage to make any definitive conclusions.

Review of outcomes for paroxysmal atrialfibrillationA number of systemic reviews have been performed

to date comparing the efficacy of catheter ablation of

atrial fibrillation compared with antiarrhythmic drug

therapy [25�,26,27�,28,29,30��]. In all of these reviews,

the patient populations were predominantly paroxysmal

(over 75%). Furthermore, the technique used in these

studies was a pulmonary venous isolation technique

with little to no adjuvant ablation performed. The

results of all of these reviews showed superiority of

radiofrequency ablation over antiarrhythmic drug therapy

with a success rate of 75.7–77% over 12 months when only

randomized trials were included [28,29] and 71% when

randomized trials were combined with prospective cohort

studies [25�] (Table 1). In many of these studies, a single

repeat ablation procedure was required in 10–25% of

patients.

There are relatively fewer data available comparing var-

ious techniques of ablation in patients with paroxysmal

atrial fibrillation. One published systemic review specifi-

cally examined the comparison of various techniques for

paroxysmal atrial fibrillation [30��]. They found five

randomized, controlled trials comparing ostial pulmonary

venous isolation with wide-antral circumferential pul-

monary venous isolation and found a higher success rate

associated with the latter approach. In only the paro-

xysmal patients, three of the trials showed statistically

20 Arrhythmias

Figure 1 Raw pooled success rates (expressed in %) from randomized clinical trial data for various approaches of catheter ablation

for paroxysmal atrial fibrillation

64

71

77

83

20

0

10

20

30

40

50

60

70

80

90

100

Ostial PVI Antral PVI PVI+Lines PVI+CFE CFE only

Pooledsuccessrate (%)

CFE, complex fractionated electrograms; Lines, linear ablation; PVI, pulmonary vein isolation.

significant benefits of wide-antral versus ostial ablation

[31–33], whereas one demonstrated a trend towards

benefit [34]. One showed a benefit of ostial ablation

[35]. Overall, pooled analysis of the 408 paroxysmal

patients shows a success rate of 71% in the wide-antral

group and 64% in the ostial group (Fig. 1). The review

concluded that there existed a moderate level of

evidence showing that wide-antral ablation was better

than segmental ostial ablation for paroxysmal atrial fibrilla-

tion.

There are five trials comparing pulmonary venous iso-

lation with pulmonary venous isolation with linear abla-

tion for paroxysmal patients. Four of the five trials

demonstrated a benefit of linear ablation [36–39],

whereas one did not [40]. In total, a pooled analysis of

795 patients shows a success rate of 77% in the pulmonary

vein isolation (PVI) þ lines group and 74% in the PVI-

alone group. A more recently published study, however,

demonstrated no difference between PVI and PVI with

linear ablation, showing identical success rates (85%)

after one or more procedures at 12 months [41�]. In fact,

this study showed a lower rate of success with lines after

one procedure (51 versus 58%) due to an increased risk

of flutter with lines. When this study is included, the

advantage for lines compared with no lines narrows to

77 versus 73% (Fig. 1). The same meta-analysis men-

tioned earlier [30��] concluded that there was ‘insuffi-

cient’ evidence to make conclusions about the effect of

linear ablation given the substantial heterogeneity of the

lines used and the variance in study sizes.

Finally, three randomized studies examined the role of

adjuvant CFE ablation on top of PVI versus PVI alone in

paroxysmal atrial fibrillation. Two of the studies demon-

strated a nonsignificant trend towards benefit [42�,43],

whereas the third study showed no benefit at all from

additional CFE ablation [44�]. When the data from the

three studies are pooled (total 210 patients), the success

rate of PVI with CFE ablation is 83 versus 72% for PVI

alone. Two of these randomized studies also looked at the

efficacy of CFE ablation alone [42�,44�], and the pooled

success rate was only 20% in a total of 55 patients (Fig. 1).

In summary, wide-antral pulmonary venous isolation has

a better outcome compared with segmental ostial pul-

monary venous isolation. Additional linear ablation does

not seem to add much efficacy in paroxysmal atrial

fibrillation, with the evidence being inconclusive. The

outcome may be very dependent on how well bidirec-

tional block can be achieved across the lines. If linear

block is not achieved, the risk of atrial flutter may be

increased [41�]. Finally, CFE ablation without pulmon-

ary venous isolation does not appear to be an effective

strategy for paroxysmal atrial fibrillation. There appears

to be a trend towards benefit of adding CFE ablation to

PVI in paroxysmal atrial fibrillation, but the evidence is

not conclusive and the total number of patients is small.

The role of adjuvant CFE ablation in paroxysmal atrial

fibrillation likely requires further investigation using

more objective definitions of CFE (e.g. automated algor-

ithms) and consistent ablative endpoints (e.g. total elec-

trogram elimination, noninducibility of atrial fibrillation).

Techniques for catheter ablation of atrial fibrillation Verma 21

Review of outcomes for persistent atrialfibrillationAn excellent systematic review of ablation techniques for

long-standing persistent atrial fibrillation was recently

published [45��]. Overall, the review found much more

variation in the success rates for atrial fibrillation ablation

in persistent atrial fibrillation as opposed to prior reviews

in paroxysmal atrial fibrillation. Thus, the review fell

short of suggesting an optimal technique for ablation

in this population and suggested that further, randomized

study is required. However, it does appear that persistent

atrial fibrillation can be treated by catheter ablation and

that some conclusions can be drawn as to what the

optimal technique may entail.

Whileostialpulmonaryvenousisolationhasmodestsuccess

in paroxysmal atrial fibrillation, the data suggest that this

strategy is inadequate for ablation of persistent atrial fibril-

lation. The review by Brooks et al. identified four studies

examining ostial ablation inpersistentatrialfibrillation,and

the single-procedure, drug-free success rate ranged from

21 to 22% (Fig. 2). Even with multiple procedures and

concomitant antiarrhythmic therapy, the success rate

remained no higher than 54%. When wide-antral pulmon-

ary venous isolation is used, the success rates are better

comparedwithostialPVI,butstillmodest[46–48,49�].The

pooled, single-procedure, drug-free success rate is 44% in

211 patients who underwent wide-antral PVI (Fig. 2). With

repeat procedures and concomitant drug therapy, the suc-

cess rates increase to 59 and 77%, respectively.

Figure 2 Raw pooled success rates (expressed in %) from randomiz

for persistent atrial fibrillation

22

44

0

10

20

30

40

50

60

70

80

90

100

Ostial PVI Antral PVI

Pooledsuccessrate (%)

CFE, complex fractionated electrograms; Lines, linear ablation; PVI, pulmon

There are only two randomized trials examining the use

of linear ablation as an adjunct to pulmonary venous

isolation for persistent atrial fibrillation. One trial

randomized 62 patients to receive either PVI or PVI

and a mitral and roof line in a 1 : 1 fashion [17], whereas

the other randomized 79 patients in a 1 : 2 fashion [39].

Both trials demonstrated a significant advantage of add-

ing linear ablation to PVI. Using 12–18-month follow-up,

the pooled data in 141 patients show a success rate of 54%

with PVI þ linear ablation versus only 23% with PVI

alone (Fig. 2). Interestingly, complete linear block could

be demonstrated for only 72% of mitral lines and 44% of

roof lines in one study [17]. In the other study, mitral and

roof line block was achieved in 31 and 92%, respectively

[39]. Thus, while the trials clearly demonstrate the super-

iority of adjuvant linear ablation, they also show the

difficulty in obtaining complete linear block. From

a review of nonrandomized data, the drug-free, one-

procedure success rate of PVI þ linear ablation ranges

from 48 to 57% [45��], which is better than the outcome

data for PVI alone in persistent atrial fibrillation.

Addition of an inferior LA line connecting the two

inferior pulmonary venous antra, or a ‘floor line’, to

achieve complete isolation of the posterior wall has been

proposed as a modification of the linear ablation method.

Since many atrial fibrillation triggers and maintenance

sites may be located in the posterior LA wall, isolation of

this structure may provide added efficacy. This may be

offset, however, by the potentially proarrhythmic effect

ed clinical trial data for various approaches of catheter ablation

54 56

26

PVI+Lines PVI+CFE CFE only

ary vein isolation.

22 Arrhythmias

of the floor line. According to the review by Brooks et al.[45��], there have been three studies assessing the impact

of posterior wall isolation in combination with PVI in

persistent atrial fibrillation [18,50,51]. However, the suc-

cess rate after one procedure was 42–50%, increasing to

60–63% after multiple procedures. There has been one

randomized trial comparing PVI with PVI and posterior

wall isolation, and it did not show any difference between

the two strategies in 120 patients, with a single-procedure

success rate of 47 and 45%, respectively [52]. Although

this was in a combined population of paroxysmal and

persistent atrial fibrillation, no difference was seen in

either of the subgroups. After two procedures, the success

rate increased to 68% with some patients on drugs. Thus,

the data are not convincing regarding the additive benefit

of posterior wall isolation.

There have been three randomized trials comparing antral

PVI with PVI and CFE ablation in persistent atrial fibrilla-

tion. Two of the studies demonstrated a benefit from

adjuvant CFE ablation [42�,48], whereas one did not

[49�]. When the results of the three studies are pooled (total

220 patients), the one-procedure success rate for PVI was

38 versus 51% for PVIþCFE ablation and the two-pro-

cedure success rate was 72 and 77%, respectively (Fig. 2).

Thus, there appears to be a benefit from additional CFE

ablation,but thetotalnumbersareverysmall.Asummaryof

six studies including nonrandomized data and the three

trials above showed an overall success rate of 54% in 281

patientsafter oneprocedure [53–55]. This is comparable to

the success rates reported for PVI þ linear ablation and

better than that of PVI alone. However, when the role of

CFE ablation without pulmonary venous isolation was

studied in three randomized comparisons [42�,56,57], the

pooled success rate was only 26% (n¼ 76) compared with

a 56% success rate of a comparative strategy involving

pulmonary venous isolation (n¼ 106) (Fig. 2).

Finally, the Bordeaux group has proposed a stepwise

ablation strategy in which pulmonary venous isolation is

followed by CFE ablation and linear ablation until atrial

fibrillation termination [58]. These procedures are quite

long and involve a high level of operator expertise. Yet,

in spite of combining all three techniques, the single-

procedure success rate varies from 48–62% [45��]. More

than half of all patients undergo at least one repeat ablation

procedure, and when all are complete the success rate

ranges from 70 to 88% [45��]. In one trial done outside

Bordeaux, the success rate of one stepwise ablation was

38%, increasing to 81% with two or more procedures [59].

Given the limited amount of data on this strategy coming

largely from one center, it is hard to assess whether

combining all three techniques offers substantial advan-

tage. The single-procedure success rates seem consistent

with pulmonary venous isolation with one of linear ablation

or CFE.

In summary, ostial pulmonary venous isolation is not

an adequate strategy for persistent atrial fibrillation.

Wide-antral pulmonary venous isolation is more effica-

cious than the ostial approach, but still does not seem

as effective as strategies that combine pulmonary

venous isolation with further substrate modification.

Both linear and CFE ablation seem to be effective

strategies when added to pulmonary venous isolation,

but comparative data between the two are absent.

Modification of linear ablation to isolate the entire

posterior LA wall does not seem to add much, and

CFE ablation without pulmonary venous isolation is not

effective. Overall, there are fewer clinical trial data in

the persistent atrial fibrillation subset compared with

the paroxysmals, and prospective, randomized trials

comparing ablative strategies in persistent atrial fibril-

lation are much needed. Hopefully, many of the out-

standing questions regarding the most effective strategy

in persistent atrial fibrillation will be answered by the

upcoming STAR atrial fibrillation 2 trial comparing

pulmonary venous isolation with pulmonary venous

isolation þ lines and pulmonary venous isolationþCFE

ablation (Verma, personal communication).

ConclusionTo date, there are limited clinical data available compar-

ing different techniques of ablation for paroxysmal and

persistent atrial fibrillation. All of the data combined

demonstrate that pulmonary venous antral isolation

should be the cornerstone of ablation of both paroxysmal

and persistent atrial fibrillation. This strategy may be

sufficient for ablation of paroxysmal atrial fibrillation, and

the benefit of routine addition of linear and/or CFE

ablation has not been definitively proven. To obtain

better outcomes in persistent atrial fibrillation, however,

further adjuvant ablation, in the form of either linear or

CFE ablation, will likely have to be performed to achieve

desired outcomes. Overall, this area is rich for further

randomized trial comparison.

AcknowledgementsThere are no direct conflicts of interest or funding supports to disclosefor this publication. Dr Verma has had modest support for speakingengagements pertaining to cardiac electrophysiology and/or ablationand clinical trial financial support from Biosense Webster Inc, St JudeMedical Inc, Medtronic Inc, and Biotronik Inc.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as:� of special interest�� of outstanding interest

Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (pp. 72–74).

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21 Konings KT, Smeets JL, Penn OC, et al. Configuration of unipolar atrialelectrograms during electrically induced atrial fibrillation in humans. Circula-tion 1997; 95:1231–1241.

22 Verma A, Wulffhart Z, Beardsall M, et al. Spatial and temporal stability ofcomplex fractionated electrograms in patients with persistent atrial fibrillationover longer time periods: relationship to local electrogram cycle length. HeartRhythm 2008; 5:1127–1133.

23 Po SS, Nakagawa H, Jackman WM. Localization of left atrial ganglionatedplexi in patients with atrial fibrillation. J Cardiovasc Electrophysiol 2009;20:1186–1189.

24

�Atienza F, Almendral J, Jalife J, et al. Real-time dominant frequency mappingand ablation of dominant frequency sites in atrial fibrillation with left-to-rightfrequency gradients predicts long-term maintenance of sinus rhythm. HeartRhythm 2009; 6:33–40.

This is the only study published thus far prospectively examining the role ofdominant frequency site ablation on the outcome of atrial fibrillation ablation.

25

�Calkins H, Reynolds MR, Spector P, et al. Treatment of atrial fibrillation withantiarrhythmic drugs or radiofrequency ablation: two systematic literaturereviews and meta-analyses. Circ Arrhythm Electrophysiol 2009; 2:349–361.

This is a well performed meta-analysis showing the superiority of ablation com-pared with antiarrhythmic drugs in treating atrial fibrillation.

26 Gjesdal K, Vist GE, Bugge E, et al. Curative ablation for atrial fibrillation: asystematic review. Scand Cardiovasc J 2008; 42:3–8.

27

�Nair GM, Nery PB, Diwakaramenon S, et al. A systematic review of randomizedtrials comparing radiofrequency ablation with antiarrhythmic medications inpatients with atrial fibrillation. J Cardiovasc Electrophysiol 2009; 20:138–144.

This is a well performed meta-analysis showing the superiority of ablation com-pared with antiarrhythmic drugs in treating atrial fibrillation.

28 Noheria A, Kumar A, Wylie JV Jr, Josephson ME. Catheter ablation vs.antiarrhythmic drug therapy for atrial fibrillation: a systematic review. ArchIntern Med 2008; 168:581–586.

29 Piccini JP, Lopes RD, Kong MH, et al. Pulmonary vein isolation for the main-tenance of sinus rhythm in patients with atrial fibrillation: a meta-analysis ofrandomized, controlled trials. Circ Arrhythm Electrophysiol 2009; 2:626–633.

30

��Terasawa T, Balk EM, Chung M, et al. Systematic review: comparativeeffectiveness of radiofrequency catheter ablation for atrial fibrillation. AnnIntern Med 2009; 151:191–202.

This is an excellent meta-analysis of atrial fibrillation ablation that not only shows thesuperiority of ablation over drug therapy, but also attempts to sub-analyze variousapproaches to atrial fibrillation ablation and their comparative efficacies.

31 Arentz T, Weber R, Burkle G, et al. Small or large isolation areas around thepulmonary veins for the treatment of atrial fibrillation? Results from a pro-spective randomized study. Circulation 2007; 115:3057–3063.

32 Nilsson B, Chen X, Pehrson S, et al. Recurrence of pulmonary vein conductionand atrial fibrillation after pulmonary vein isolation for atrial fibrillation: arandomized trial of the ostial versus the extraostial ablation strategy. AmHeart J 2006; 152:537 e1–537 e8.

33 Oral H, Scharf C, Chugh A, et al. Catheter ablation for paroxysmal atrialfibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation.Circulation 2003; 108:2355–2360.

34 Liu X, Long D, Dong J, et al. Is circumferential pulmonary vein isolationpreferable to stepwise segmental pulmonary vein isolation for patients withparoxysmal atrial fibrillation? Circ J 2006; 70:1392–1397.

35 Karch MR, Zrenner B, Deisenhofer I, et al. Freedom from atrial tachyarrhyth-mias after catheter ablation of atrial fibrillation: a randomized comparisonbetween 2 current ablation strategies. Circulation 2005; 111:2875–2880.

36 Pappone C, Manguso F, Vicedomini G, et al. Prevention of iatrogenic atrialtachycardia after ablation of atrial fibrillation: a prospective randomized studycomparing circumferential pulmonary vein ablation with a modified approach.Circulation 2004; 110:3036–3042.

37 Hocini M, Jais P, Sanders P, et al. Techniques, evaluation, and consequencesof linear block at the left atrial roof in paroxysmal atrial fibrillation: a prospectiverandomized study. Circulation 2005; 112:3688–3696.

38 Fassini G, Riva S, Chiodelli R, et al. Left mitral isthmus ablation associatedwith PV Isolation: long-term results of a prospective randomized study.J Cardiovasc Electrophysiol 2005; 16:1150–1156.

39 Gaita F, Caponi D, Scaglione M, et al. Long-term clinical results of 2 differentablation strategies in patients with paroxysmal and persistent atrial fibrillation.Circ Arrhythm Electrophysiol 2008; 1:269–275.

40 Sheikh I, Krum D, Cooley R, et al. Pulmonary vein isolation and linear lesions inatrial fibrillation ablation. J Interv Card Electrophysiol 2006; 17:103–109.

41

�Sawhney N, Anousheh R, Chen W, Feld GK. Circumferential pulmonary veinablation with additional linear ablation results in an increased incidence of leftatrial flutter compared with segmental pulmonary vein isolation as an initialapproach to ablation of paroxysmal atrial fibrillation. Circ Arrhythm Electro-physiol 2010; 3:243–248.

Nice study showing the potential proarrhythmic effects of linear ablation, which,until now, has been considered a mainstay of atrial fibrillation ablation, particularlyfor persistent atrial fibrillation.

42

�Verma A, Mantovan R, Macle L, et al. Substrate and Trigger Ablation forReduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, inter-national trial. Eur Heart J 2010; 31:1344–1356.

One of only a small number of multicenter, randomized trials comparing differentapproaches of atrial fibrillation ablation. This study showed that a combinedapproach of PVI þ CFE ablation was superior to either approach alone in ahigh-burden paroxysmal/persistent atrial fibrillation population. CFE were as-sessed using an automated, computer algorithm.

43 Deisenhofer I, Estner H, Reents T, et al. Does electrogram guided substrateablation add to the success of pulmonary vein isolation in patients withparoxysmal atrial fibrillation? A prospective, randomized study. J CardiovascElectrophysiol 2009; 20:514–521.

24 Arrhythmias

44

�Di Biase L, Elayi CS, Fahmy TS, et al. Atrial fibrillation ablation strategies forparoxysmal patients: randomized comparison between different techniques.Circ Arrhythm Electrophysiol 2009; 2:113–119.

Nice trial comparing different approaches of atrial fibrillation ablation in a strictlyparoxysmal atrial fibrillation population. Here, there was no advantage of CFE þPVI ablation over PVI alone.

45

��Brooks AG, Stiles MK, Laborderie J, et al. Outcomes of long-standingpersistent atrial fibrillation ablation: a systematic review. Heart Rhythm2010; 7:835–846.

Excellent meta-analysis comparing various techniques of ablation for persistentatrial fibrillation. Nice summary of all available study data.

46 Pappone C, Oreto G, Rosanio S, et al. Atrial electroanatomic remodeling aftercircumferential radiofrequency pulmonary vein ablation: efficacy of an ana-tomic approach in a large cohort of patients with atrial fibrillation. Circulation2001; 104:2539–2544.

47 Cheema A, Dong J, Dalal D, et al. Circumferential ablation with pulmonaryvein isolation in permanent atrial fibrillation. Am J Cardiol 2007; 99:1425–1428.

48 Elayi CS, Verma A, Di Biase L, et al. Ablation for longstanding permanent atrialfibrillation: results from a randomized study comparing three different strate-gies. Heart Rhythm 2008; 5:1658–1664.

49

�Oral H, Chugh A, Yoshida K, et al. A randomized assessment of the incre-mental role of ablation of complex fractionated atrial electrograms after antralpulmonary vein isolation for long-lasting persistent atrial fibrillation. J Am CollCardiol 2009; 53:782–789.

Nice article showing that additional CFE ablation did not add efficacy comparedwith PVI alone. However, CFE were assessed by visual analysis alone and not withthe use of a computerized algorithm.

50 Kumagai K, Nakashima H. Noncontact mapping-guided catheter ablation ofatrial fibrillation. Circ J 2009; 73:233–241.

51 Chen J, Off MK, Solheim E, et al. Treatment of atrial fibrillation by silencingelectrical activity in the posterior inter-pulmonary-vein atrium. Europace 2008;10:265–272.

52 Tamborero D, Mont L, Berruezo A, et al. Left atrial posterior wall isolation doesnot improve the outcome of circumferential pulmonary vein ablation for atrialfibrillation: a prospective randomized study. Circ Arrhythm Electrophysiol 2009;2:35–40.

53 Porter M, Spear W, Akar JG, et al. Prospective study of atrial fibrillationtermination during ablation guided by automated detection of fractionatedelectrograms. J Cardiovasc Electrophysiol 2008; 19:613–620.

54 Li XP, Dong JZ, Liu XP, et al. Predictive value of early recurrence and delayedcure after catheter ablation for patients with chronic atrial fibrillation. Circ J2008; 72:1125–1129.

55 Schmitt C, Estner H, Hecher B, et al. Radiofrequency ablation of complexfractionated atrial electrograms (CFAE): preferential sites of acute terminationand regularization in paroxysmal and persistent atrial fibrillation. J CardiovascElectrophysiol 2007; 18:1039–1046.

56 Estner HL, Hessling G, Ndrepepa G, et al. Electrogram-guided substrateablation with or without pulmonary vein isolation in patients with persistentatrial fibrillation. Europace 2008; 10:1281–1287.

57 Oral H, Chugh A, Good E, et al. Randomized comparison of encircling andnonencircling left atrial ablation for chronic atrial fibrillation. Heart Rhythm2005; 2:1165–1172.

58 Haissaguerre M, Hocini M, Sanders P, et al. Catheter ablation of long-lastingpersistent atrial fibrillation: clinical outcome and mechanisms of subsequentarrhythmias. J Cardiovasc Electrophysiol 2005; 16:1138–1147.

59 Rostock T, Steven D, Hoffmann B, et al. Chronic atrial fibrillation is a biatrialarrhythmia: data from catheter ablation of chronic atrial fibrillation aimingarrhythmia termination using a sequential ablation approach. Circ ArrhythmElectrophysiol 2008; 1:344–353.