Thomas Deneke1, 2, Anja Schade1, Joachim Krug1, Karsten Stahl1, Geza-Atilla Szollosi1, Dong-In Shin1, Clemens
Nino Schukro1, Mohamed El Tarahony1, Enrique Murillo1, Semko Aram1, Gabriele Robhirt1, Thomas
Lawo2, Andreas Mugge2, Peter H. Grewe2, Sebastian Kerber1.
1Heart Center Bad Neustadt, Clinic for interventional Electrophysiology, Bad Neustadt/Saale, GER
2Ruhr-University Bochum, Bochum, GER
Corresponding Author: Thomas Deneke, MD, Director Clinic for Invasive Electrophysiology,Heart Center Bad Neustadt,
Salzburger Leite 1, GER-97616 Bad Neustadt a. d. Saale.
Catheter ablation of atrial fibrillation (AF) has
emerged as an effective tool to treat symptomatic
patients with drug-refractory AF. Success is usually
measured as stability of sinus rhythm (SR)
in multiple holter-ECGs after an initial blanking
period of up to 6 months. Success rates in
patients with paroxysmal AF of up to 89% have
been reported. In contrast, AF ablation in persistent
AF has a sufficiently lower success rate after
a single procedure and more procedures/patient
are needed to achieve adequate rhythm control.1,2
In specialized centres the percentage of patients
with persistent AF undergoing ablation procedures
may be in the range of 30%. For these patients, ablation
concepts may implement ablations additional
to effective pulmonary vein isolation (PVI). Ablation
of left atrial regions identified by the existence
of complex fractionated electrograms (CFAE) may
improve outcome in some patients, whereas in addition
linear ablation (LIN) to compartmentalize the
left atrium has been proposed in different studies.
Success rates differ widely depending on patient
selection, experience of the operators and followup.
Also, persistent AF is poorly defined by 1. either
AF lasting longer than 7 days or 2. AF undergoing
conversion by either drugs or electrical cardioversion.
This definition may include a wide variety
of patients with different stages of AF disease
and therefore, success rates may vary widely.1-14
Recurrences after ablation of persistent AF may
include recurrent AF or atrial tachycardia either
due to inconsistent left atrial lesions, reconnected
pulmonary veins (PVs) or as tachycardia originating
from previously not ablated areas of the right
and left atrium.
So far, only a limited number of studies have
looked into predictors of AF recurrence after ablation
of persistent AF. It can be speculated that
1. pre-procedural markers indicating ablation
failure may exist, 2. intra-procedural determinants
of failure and 3. post-procedural predictors
of poorer outcome may be identified. It is
most likely, that there is not a single predictor
but a combination of different factors influencing
outcome in this inhomogeneous patient
group. As always with multivariate prediction
analysis the number of determinants included
in such a model will have effects on outcome of
these statistical methods. In addition, many factors are correlated with each other in a rather complex
way and may therefore not be appropriately
analyzed using simple statistical methodology.
In different studies, persistent AF has been identified
as a significant confounder for a 50 to 55% higher
risk for recurrence mostly in univariate analysis.
This can be explained by the assumption, that a persistent
type of AF includes many confounding variables
that may lead to different results in multivariate
analyses. Again, different stages of atrial disease
may affect success rates of ablation procedures.15-21
Many variables that may affect outcome of ablation
procedures for AF have been evaluated mostly in
either paroxysmal AF patients or in a mixed population.
Only a limited number of studies evaluated
the effect of pre-procedural variables in a
predefined subgroup including only patients with
Left atrial dilation is often associated with AF and vice-versa. Patients with large left atrial dimensions
may have substantial left atrial myopathy
serving as a basis for the perpetuation of AF. Left
atrial dilation results in anisotropic conduction
and regional differences in refractory periods. The
combination of electrical and substrate remodelling
facilitates the onset and perpetuation of AF.
Left atrial dimensions are usually evaluated using
pre-procedural transthoracic echocardiography
and measurements may differ widely intraindividually
and in between observers. Left atrial
volume as a more concise parameter has so far not
been consistently evaluated in ablation studies.
Left atrial size was found to be a major determinant
for recurrence of ablation for persistent AF
in 2 studies. Freedom from AF decreases with increasing
left atrial size up to 46mm but no change
is identified in patients > 46mm left atrial dimensions
7. In a second study by Lo et al.37 left atrial size
was greater in patients with failure of persistent
AF ablation. As a cut-off value left atrial diameter
> 43mm significantly influences 1- and 2-year AF
free survival rates (54% at 1 year, 51% at 2 years
compared to 91% for 1 and 2 year AF free survival
in patients with left atrial diameters < 43mm).7, 37
In contrast, a large cohort analysis by Bhargava et
al.19 and a second study by Wokhlu et al. did not
find left atrial size to be predictive of single procedure
AF ablation success in persistent AF. These
studies appeared to include mostly patients with
shorter duration persistent AF which may explain
some of the discrepancies.
Overall data is controversial and this may in some
part be due to the insufficiency of echocardiographic
measurement of correct left atrial dimensions in
addition to differences in ablation strategies in different
study groups. It can be concluded though,
that increasing left atrial size may negatively affect
rhythm success after ablation of persistent AF but
no clear 2-dimensional cut-off value exists that may
definitely predict failure of the ablation procedure.
Data on duration of persistent AF prior to ablation
is inconclusive. Bhargava et al.19 identified a longer
duration of persistent AF as predictor of failure
after a single ablation procedure (hazard ratio
1.74; p=0.003). A recent study by Rostock et al.7
documented duration of persistent AF longer than
6 months to be an independent predictor for AF
recurrence in persistent AF ablation. McCready
et al.18 did not identify AF duration as predictive
for recurrence of AF (hazard ratio 1.07; p=0.11) in
the overall group of persistent AF. In the group of
patients with a left atrial diameter above 43mm,
duration of AF appeared as an independent predictor
of AF recurrence. Specifically, patients with
long-lasting persistent AF have poorer outcome
after ablation emphasizing the importance of
duration of AF prior to ablation. There does not
appear to be a clear cut-off value for continuous
AF duration indicating a relevant drop-down in
efficacy (apart from 1 year consistent AF as indicated
in the definition of long-lasting persistent
AF). It needs to be stressed that pre-ablation AF
duration in persistent AF cases should include
only the time consistently in AF. In many centres,
extent of ablation strategy is mainly based on duration
of persistent AF prior to the ablation making
multivariate analysis statistically challenging.
It can be concluded though, that long persistence
of AF (> 6 months prior to ablation) negatively
influences recurrence of AF after ablation. Again
no clear cut-off value exists and ablation may be extended to additional areas in these patients.
Hypertensive heart disease is a major risk factor
for the incidence of AF. In mixed populations with
different types of AF hypertension appears to be a
significant predictor of AF recurrence after ablation.
3 studies have evaluated hypertension as a
strator of ablation outcome in persistent AF ablation
in a multivariate model. Whereas hypertension
was a predictor of ablation failure in patients
with persistent AF in the study by Bhargava et al.19
and for very late recurrence in the study by Wilber
et al. (personal communication at Boston AF symposium
2011), it was not a relevant factor in the
study by McCready et al.18
Data remains inconclusive on the predictive role of
hypertension on persistent AF ablation outcome.
The presence of structural heart disease (mostly
coronary artery disease) may affect AF ablation
outcome. In addition, recent publications have
highlighted the role of AF ablation in patients with
left ventricular dysfunction or congestive heart
failure. The prognostic relevance of underlying
ventricular abnormalities on outcome of ablation
strategies has not been clearly elucidated. One
can speculate though, that severely impaired left
ventricular function may lead to more aggressive
ablation strategies to terminate AF. Most studies
evaluating structural or valvular heart disease as
a predictor did not identify a relevant relation to
ablation outcome but 2 studies indicated a significant
association in a mixed AF population. In
a homogenous group of persistent AF, 2 studies
documented contrary findings in relation to AF recurrence
and structural heart disease/cardiomyopathy,
Whereas McCready et al.18 did not find any
relation in 191 patients. Rostock et al.17 identified a
prognostic relevance of congestive heart failure in
a multivariate regression analysis in 395 patients.
Congestive heart failure involved a 10-fold risk for
AF recurrence after the index procedure and after
the final procedure. The existence of coronary
artery disease also predicted a negative outcome
after the final procedure in this study.
Congestive heart failure appears to be an independent
predictor of AF recurrence in patients with
persistent AF as indicated in a single study on
nearly 400 patients undergoing ablation in a center
with high expertise.
A recently published study by Rostock et al.17 indicates
a higher recurrence rate in female patients
after ablation of persistent AF. A second study by
Wilber et al. (personal communication at Boston
AF symposium 2011) on 1404 patients with persistent
or long-standing persistent AF also documented
female gender to be a predictor of very
late recurrence. Other studies have not identified
a gender-specific success rate. In conclusion, there
appears to be an effect of female gender on persistent
AF ablation success specifically during late
follow-up. The gender-specific mechanisms remain
unknown and need to be further evaluated.
There does not appear to be a relevant influence of
age on recurrences of atrial tachycardias after persistent
AF ablation as indicated in different studies.17 -19
The extent of structural remodelling and brain natriuretic
peptide (BNP) levels may be related and
therefore higher pre-procedural BNP levels may
indicate more extensive structural abnormalities.
Baseline BNP levels appear to be higher in
patients with persistent types versus paroxysmal
AF types. Whereas baseline BNP levels are predictive
of ablation outcome in patients with paroxysmal
AF this has not been documented for patients
with persistent and long-standing persistent AF.23
Higher baseline BNP levels do not appear to be a
predictor of AF recurrence in patients with persistent
form of AF but normalization after ablation
Atrial structural remodelling leads to substrate
formation for perpetuation of atrial fibrillation.
Atrial myopathy in these cases includes different
degrees of fibrotic replacement which appears
to be related to the duration of ongoing AF. The
amount of atrial fibrosis can be documented in delayed
enhancement magnetic resonance imaging
(DE-MRI). The percentage of fibrosis is related to
the occurrence of embolic complications during AF and has been identified to be a predictor for
failure of AF ablation in paroxysmal AF patients.24
Staging atrial fibrosis into four categories has identified
a higher proportion of patients with persistent
AF to fall into the stages with more than 20%
fibrosis. Higher stages of atrial fibrosis were related
to higher recurrence rate independent to AF type.
Identifying the degree of atrial fibrosis may help
to select the appropriate ablation strategy and potentially
predict AF recurrence in patients with extensive
(or moderate) atrial fibrosis. Further studies
need to evaluate the potential for pre-ablation
DE-MRI to predict AF recurrence in a homogenous
group of persistent or long-standing persistent AF.
Whether areas of atrial fibrosis can be identified using
intraprocedural bipolar voltage mapping needs
further evaluation but may be a potential intraprocedurally
evaluated factor to predict outcome if
large areas of low voltage areas are documented.
Different procedural characteristics have been evaluated
in their potential to affect outcome in ablation
procedures for persistent AF. While, especially extent
and type of left atrial ablation have been tested,
also termination of AF during the ablation procedure
may be a relevant marker.
There is evidence from 4 randomized trials3, 4, 5, 25 and
2 meta-analyses16, 26 on the effect of different ablation
strategies on outcome in persistent AF. Many studies
have documented the necessity of PVI as a cornerstone
of ablation procedures to treat AF. In addition,
ablation of specific sites identified by unique
appearance of local electrograms (complex fractionated
atrial electrograms, CFAE) has been tested as
a solitary approach or as an add-on to PVI. Other
studies evaluated the usefulness of adding linear
ablations (LIN) (mostly roof-line in between PVI
boxes and left atrial isthmus line in between usually
the left inferior PV and mitral annulus) to PVI.
Triggered by the experience from the Bordeaux
group, an extensive stepwise ablation approach
including PVI, CFAE and linear ablation has been
evaluated in 4 non-randomized trials.13, 14, 27, 28
From the 4 randomized trials it can be concluded,
that PVI is an essential component of
ablation for persistent AF and that proven PVI
(documenting entrance and (? exit block) is superior
to PV-ablation without checking for efficacy.
3, 4, 5, 25 CFAE ablation alone is inferior to PVI
plus LIN and adding right atrial CFAE ablation
to left atrial CFAE ablation does not provide additional
benefit. One study25 documented incremental
benefit from adding CFAE ablation to
PVI whereas a second3 did not. A meta-analysis
of these two trials revealed no evident treatment
effect of adjunctive CFAE ablation.26
Single procedure success rates in patients with
long-standing persistent AF of 37 to 40% for effective
(proven) PVI, of 38 to 57% for PVI plus
LIN, of 24 to 63% for CFAE ablation alone, of 36
to 61% for effective PVI plus CFAE and of 38 to
62% for a stepwise ablation technique have been
published (see figure 1).3 – 14, 16, 25, 26, 27, 28 It appears
though, that results are comparable in between
groups and that adding additional ablation strategies
to PVI produces widely varying results.
These differences may be due to experience of
the operator and the not-clearly defined endpoint
of CFAE or LIN ablation. Additional CFAE ablation
may provide better results (as indicated in one randomized study) but only left atrial CFAE
ablation seems mandatory. Again, the number of
areas that need to be ablated in order to achieve
superior results is not defined. From the presented
studies it appears clear, that all patients ablated of
persistent AF should undergo effective PVI.15, 16, 26
Figure 1: Single procedure rhythm success rates 6 to 12 months after different ablation strategies
for persistent AF presented in different trials (PVI + LIN: N = 417, PVI + CFAE: N= 256,
PVI + LIN + CFAE: N = 341) (from 2, 3, 4, 15, 16, 17, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, 36).
Some centres perform ablation in persistent AF using
termination by ablation as the endpoint of the procedure.
This endpoint may include conversion of AF
to a regularized atrial tachycardia (AT) and effective
ablation of these ATs. Termination of AF during ablation
usually requires a stepwise ablation approach
including PVI plus additional ablations (CFAE ablation,
left and potentially right atrial lines) and may
be achieved in up to 85% of patients with long-lasting
persistent AF.27 A recent analysis of sites of AF
termination identified left atrial CFAE ablation as
the part of the ablation procedure most commonly
associated with AF termination (around 65%).27 Especially
ablation of CFAE sites within the coronary
sinus and at the left atrial appendage were anatomical
regions where ablation led to termination of AF.
Rostock et al.28 document a biatrial component of
persistent AF and the need for right atrial ablation
to terminate AF in approximately ¼ of patients. In a
study on patients undergoing concomitant surgical
AF ablation Deneke et al.29 have identified no beneficial
effect of right atrial ablation on rhythm success.28,
29 There still remains controversy on extending ablation
to the right atrium, which may be needed for
AF termination but may not affect rhythm outcome.
In two studies AF recurrence was significantly
more often in patients without termination during
the ablation procedure but atrial tachycardias
were more common. In the studies by O´Neill
et al.27 and Rostock et al.28 AF termination during
ablation was a prognostic important factor,
whereas a third study by Elayi et al.25 did not
find differences in regard to SR maintenance.
Interestingly, ablation termination of AF can be predicted
by pre-interventional measures like AF cycle
length, which can also be determined on surface ECG.30
Overall, the role of AF termination during ablation
procedures of persistent AF remains unclear but may
be a good endpoint specifically for patients with duration
of continuous AF shorter than 21 months and
AF cycle length longer than 142ms.30 AF cycle length
may be an indicator for a more severely damaged
left atrium. On the other hand, 40% of patients
with long-lasting episodes of AF may remain in
stable SR after multiple AF procedures targeting
only PV isolation.31 Drewitz et al.32 present in
their recent publication that AF cycle length was
the only independent predictor of AF termination
directly into SR whereas a shorter AF cycle
length was indicative of converting AF into regularized
atrial tachycardias before terminating.
Data is conflicting but termination of AF if achieved
in a reasonable time of ablation may be a good
indicator for SR persistence during follow-up.
No studies comparing the effect of different
management strategies during follow-up of patients
after ablation of persistent AF exist. Early
recurrence of AF during the initial phase of
follow-up, antiarrhythmic medication and cardioversion
in cases of persistent AF recurrence
may have effects on long-term rhythm outcome.
Early recurrence of atrial arrhythmia (ERAF) after
ablation of AF may occur in 35% to 46% of
patients and may be due to the transient unstable
atrial remodelling processes after left atrial
ablation including inflammatory response.33, 34,
35 Although ERAF is a common finding, around
50% of these patients do not have AF recurrences
during longer follow-up. Therefore, most centres
have established a " blanking period" after ablation
acknowledging the transient pro-arrhythmogenic
phenomena in the early phase after ablation
(up to 3 months). On the other hand, early
recurrence may be due to recovery of conduction
over left atrial ablation sites and therefore may
be an indicator for later ablation failure. Different
studies identified ERAF as a highly significant
predictor of later recurrence of AF and ablation
failure in mixed paroxysmal and persistent
AF patient groups. In a study by Themistoclakis
et al.33 recurrences within the first 2 months appeared
to implement transient left atrial instability
and were not related to later recurrence,
whereas recurrences of atrial tachycardias after
2 months were associated with AF recurrences
after the blanking period. In the STAR-AF trial36
ERAF also was significantly predicting failure of
ablation, although no decisive data on the subgroup
of patients with persistent AF was made.
Arrhythmia recurring after persistent AF ablation
may either be AF or regular macro-, micro-reentry
of focal atrial tachycardia. These regular atrial
tachycardias may account for 20 to up to 50% of
recurrent arrhythmia6, 17, 25, 37 and is more common
with more extensive ablation approaches.26 Recently,
some studies identified, that the recurrence
of AF is of different impact to the overall outcome
compared to recurrent regular atrial tachycardia
.17, 25, 37, 38 Ablation of subsequent atrial tachycardia
occurring late after persistent AF ablation can
be effectively treated in redo-procedures and the
outcome is superior to ablation of recurrent persistent
AF.39 In a recent study by Ammar et al.38,
regularized atrial tachycardia can be ablated with
high efficacy and outcome is superior compared
to repeat ablation procedures for recurrent persistent
AF after an initial persistent AF ablation procedure.
Recurrence of regular atrial tachycardia
may be assumed to be one step towards effective
rhythm control. It is interesting to note that regular
atrial tachycardias are the dominant recurring
arrhythmia in patients converting to regularized
atrial tachycardia during persistent AF ablation.25
Antiarrhythmic drug medication may affect outcome
after AF ablation procedures. So far, no
studies dedicated to this issue are available with
concisive results. An analysis of patients after intraoperative
concomitant AF ablation for long-standing
persistent AF indicated no additive effects of
sotalol compared to regular ß-blocker medication
.40 Many other studies propose the use of antiarrhythmic
drugs and indicate a higher rhythm success
under antiarrhythmics compared to no use of
rhythm effective drugs. In the recently published
data from the 5A-Study41 antiarrhythmic medication
in the early phase after ablation may stabilize
atrial rhythm in the early post-interventional phase
but the long-term beneficial effect remains unclear.
In patients with recurrent AF early cardioversion to
restore SR may be advocated. Although no comparative
studies are available time in SR may incur on
left atrial re-remodelling and therefore rhythm stability
over follow-up. One study indicates that cardioversion
should be performed within 30 days after
recurrence of AF after ablation. Of interest, in this
study 1/3 of patients with cardioversion for recurrence
of AF maintained SR during follow-up compared
to only 15% of patients with cardioversion
for regular atrial tachycardias. The study presents
similar rates for maintaining SR if cardioversion
was performed within 1 week or within the first
month after onset of AF recurrence. Still, it remains
unclear if earlier cardioversion may further affect
outcome (low patient numbers in subgroups).42, 43
In addition, a second study evaluated the number
of cardioversions needed indicating failure of an
ablation procedure for persistent AF. More than 3
cardioversions within the initial 3 months were associated
with low final success. Or in other words,
recurrence of persistent atrial tachycardias more
than 3 times within the first 3 months after ablation
is highly associated with ablation failure.42, 43
As a conclusion, cardioversion may be used in
the initial phase after ablation of persistent AF to
restore SR. Cardioversion should be performed
early after recurrence (at our institution usually
within 3 days) and may still lead to rhythm success
if performed up to 3 times within the first
3 months after ablation. Cardioversion may be
more effective in patients with recurrence of AF
compared to recurrent regular atrial tachycardia.
Ablation of persistent AF is associated with a
wide variety of success rates mostly due to the
incongruent definition of persistent AF. Patientspecific
pre-procedural factors, operator specific
procedural factors and "institution"-specific factors
during post-interventional follow-up may
affect success or failure of persistent AF ablation.
So far, the complex relation of many of the tested
strators prevents decisive analysis of the statistical
relation to outcome after AF ablation. Also, due
to the inhomogeneous patient groups included
in many studies, the used statistical methodology
may not adequately address the complexity of
the problem. Identifying specific pre-procedural
markers for higher recurrence rate after ablation
procedures in patients with persistent AF would
be most helpful to identify good candidates for
ablation and may help to adapt the ablation strategy.
Further studies on more homogenous patient subgroups and ablation strategies are needed
for a definite individual risk of recurrence analysis.
Table 1: Pre-procedural factors indicated as having predictive value and number of
reference indicating significant relation to recurrence of AF after persistent AF ablation
1.Camm AJ, Kirchhof P, Lip GYH, Schotten U, Savelieva I, Ernst S, van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, de Caterina R, de Sutter J, Goette A, Gorenek B, Heldal M, Hohnloser SH, Kohl P, le Heuzey J-Y, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation. Eur H J 2010; 31: 2369-2429.
2. Natale A, Raviele A, Arentz T, Calkins H, Chen S-A, Haissaguerre M, Hindricks G, Ho Y, Kuck K-H, Marchlinski FE, Napolitano C, Packer D, Pappone C, Prystowski EN, Schilling R, Shah D, Themistoclakis S, Verma A. Venice Chart International Consensus Document on Atrial Fibrillation Ablation. J Cardiovasc Electrophysiol 2007; 18: 560-580.
3. Oral H, Chugh A, Yoshida K, Sarrazin JF, Kuhne M, Crawford , Chalfoun N, Wells D, Boonyapisit W, Veerareddy S, Billakanty S, Wong WS, Good E, Jongnarangsin K, Pelosi F, Bogun F, Morady F. A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation. J Am Coll Cardiol 2009; 53: 782-789.
4. Oral H, Chug A, Good E, Crawford T, Sarrazin JF, Kuhne M, Chalfoun N, Wells D, Boonyapisit W, Gadeela N, Sankaran S, Kfahagi A, Jongnarangsin K, Pelosi F, Bogun F, Morady F. Randomized evaluation of right atrial ablation after left atrial ablation of complex fractionated atrial electrograms for long-lasting persistent atrial fibrillation. Circ Arrhythm Electrophysiol 2008; 1: 6–13.
5. Oral H, Chugh A, Good E, Igic P, Elmouchi D, Tschopp DR, Reich SS, Bogun F, Pelosi F, Morady F. Randomized comparison of encircling and nonencircling left atrial ablation for chronic atrial fibrillation. Heart Rhythm 2005; 2: 1165-1172.
6. Elayi CS, Verma A, Di Biase L, Ching CK, Patel D, Barrett C Martin D, rong B, Fahmy TS, Khaykin Y, Hongo R, Hao S, Pelargonio G, Dello Russo A, Casella M, Santareli P, Potenza D, Fanelli R, Massaro R, Arruda M, Schweikert RA, Natale A. Ablation for longstanding permanent atrial fibrillation: results from a randomized study comparing three different strategies. Heart Rhythm 2008; 5: 1658-1664.
7.Cheema A, Dong J, Dalal D, Marine JE, Henrikson CA, Spragg D, Cheng A, Nazarian S, Bilchick KC, Almasry I, Sinha S, Scherr D, Halperin H, Berger R, Calkins H. Circumferrential ablation with pulmonary vein isolation in permanent atrial fibrillation. Am J Cardiol 2007; 99: 1425-1428.
8.Early MJ, Abrams DJ, Staniforth AD, Sporton SC, Schilling RJ. Catheter ablation of permanent atrial fibrillation. Heart 2006; 92: 233-238.
9. Seow SC, Lim TW, Koay CH, Ross DL, Thomas SP. Efficacy and late recurrences with wide electrical pulmonary vein isolation for persistent and permanent atrial fibrillation. Europace 2007; 1129-1133.
10. Miyazaki S, Kuwahara T, Takahashi A, Kobori A, Takahashi Y, Nozato T, Hikita H, Sato A, Aonuma H, Hirao K, Isobe M. Effect of left atrial ablation on quality of life in patients with atrial fibrillation. Circ J 2008; 72: 582-587.
11. Fiala M, Chovancik J, Nevralova R, Neuwirth R, Jiravsky O, Januska J, Branny M. Termination of long-lasting persistent versus short-lasting persistent and paroxysmal atrial fibrillation by ablation. Pacin Clin Electrophysiol 2008; 31: 985-997.
12. Li XP, Dong JZ, Liu XP, Long de Y, Yu RH, Tian Y, Tang RB, Zheng B, Hu FL, Shi LS, He H, Ma CS. Predictive value of early recurrence and delayed cure after catheter ablation for patient with chronic atrial fibrTakahashi Y, O´Neill MD, Hocini M, Dubois R, Matsuo S, Knecht S, Mahapatra S, Lim KT, Jais P, Jonsson A, Sacher F, Sanders P, Rostock T, Bordachar P, Clémenty J, Klein GJ, Haissaguerre M. Characterization of electrograms associated with termination of chronic atrial fibrillation by catheter ablation. J Am Coll Cardiol 2008; 51: 1003-1010.
14. Haissaguerre M, Hocini M, Sanders P, Sacher F, Rotter M, Takahashi Y, Rostock T, Hsu LF, Bordachar P, Reuter S, Roudaut R, Clémenty J, Jais P. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol 2005; 16: 1138-1147.
15. Balk, EM, Garlitski AC, AlSheik-Ali AA, Terasawa T, Chung M, Ip S. Predictors of Atrial Fibrillationn Recurrence After Radiofrequency Catheter Ablation: A Systematic Review. J Cardiovasc Electrophysiol 2010; 21: 1208-1216.
16.Brooks AG, Stiles MK, Laborderie J, Lau DH, Kuklik P, Shipp NJ, Hsu L-F, Sanders P. Outcomes of long-standing persistent atrial fibrillation ablation: A systematic review. Heart Rhythm 2010; 7: 835-846.
17. Oral, H., Knight, B. P., Tada, H., Ozaydin, M., Chugh, A.,
Hassan, S., et al. (2002). Pulmonary vein isolation for paroxysmal
and persistent atrial fibrillation. Circulation, 105(9), 1077-
17. Rostock T, Salukhe TV, Steven D, Drewitz I, Hoffman BA, Bock K, Servatius H, Müllerleile K, Sultan A, Gosau N, Meinertz T, Wegscheider K, Willems S. Long-term single- and multiple-procedure outcome and predictors of success after catheter ablation for persistent atrial fibrillation. Heart Rhythm 2011; 8: 1391-1397.
18. McCready JW, Smedley T, Lambiase PD, Ahsan SY, Segal OR, Rowland E, Lowe MD, Chow AW. Predictors of recurrence following radiofrequency ablation for persistent atrial fibrillation. Europace 2011; 13: 355-361.
19.Bhargava M, Di Biase L, Mohanty P, Prasad S, Martin DO, Williams-Andrews M, Wazni OM, Burkhardt JD, Cummings JE, Khaykin Y, Verma A, Hao S, Beheiry S, Hongo R, Rossillo A, Raviele A, Bonso A, Themistoclakis S, Stewart K, Saliba WI, Schweikert RA, Natale A. Impac of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: Results from a multicenter study. Heart Rhythm 2009; 6: 1403-1412.
20. Wokhlu A, Hodge DO, Monahan KH, Asivatham SJ, Friedman PA, Hunger TM, Cha Y-M, Shen W-K, Brady PA, Bluhm CM, Haroldson JM, Hammill SC, Packer DL. Long-Term Outcome of Atrial Fibrillation Ablation: Impact and Predictors of Very Late Recurrences. J Cardiovasc Electrophysiol 2010; 21; 1071-1078.
21.Berruezo A, Tamborero D, Mont L, Benito B, Tolosana JM, Sitges M, Vidal B, Arriagada G, Méndez F, Matiello M, Molina I, Brugada J. Pre-procedural predictors of atrial fibrillation recurrence after circumferential pulmonary vein ablation. Eur H J 2007; 28: 836-841
22. Lo L-W, Lin Y-J, Tsao H-M, Chang S_L, Udyavar AR, Hu Y-F, Ueng K-C, Tsai W-C, Tuan T-C, Chang C-J, Tang –H, Higa S, Tai –T, Chen S-A. The Impact of Left Atrial Size on Long-Term Outcome of Catheter Ablation of Chronic Atrial Fibrillation. J Cardiovasc Electrophysiol 2009; 20: 1211-1216.
23.Yamada T, Murakami Y, Okada T, Yoshida N, Toyama J, Yoshida Y, Tsuboi N, Inden Y, Hirai M, Murohara T. Plasma brain natriuretic peptide level after radiofrequency catheter ablation of paroxysmal, persistent, and permanent atrial fibrillation. Europace 2007; 9: 770-774.
24. Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, Badger T, burgon N Haslam T, Kholmovski E, MacLeod R, Marrouche N. Atrial Fibrosis Helps Select the Appropriate Patient and Strategy in Catheter Ablation of Atrial Fibrillation: A DE-MRI Guided Approach. J Cardiovasc Electrophysiol 2011; 22: 16-22.
25.Elayi CS, Di Biase L, Barrett C, Ching CK, al Aly M, Lucciola M, Bai R, Horton R, Fahmy TS, Verma A, Khaykin Y, Shah J, Morales G, Hongo R, Hao S, Beheiry S, Arruda M, Schweikert RA, Cummings J, Burkhardt JD, Wand P, A-Ahmad A, Cauchemez B, Gaita F, Natale A. Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation. Heart Rhythm 2010; 7: 1216-1223.
26. Kong MH, Piccini JP, Bahnson TD. Efficacy of adjunctive ablation of complex fractionated atrial electrograms and pulmonary vein isolation fort he treatment of atrial fibrillation a meta-analysis of randomized controlled trials. Europace 2011; 13: 192-204.
27. O`Neill MD, Wrigh M, Knecht S, Jaïs P, Hocini M, Takahashi Y, Jönsson A, Sacher F, Matsuo S, Lim KT, Arantes L, Derval N, Lellouche N, Nault I, Bordachar P, Clémenty J, Haïssaguerre M. Long-term follow-up of persistent atrial fibrillation ablation using termination as a procedural endpoint. Eur Heart J 2009; 30: 1105-1112.
28.Rostock, T, Steven D, Hoffmann B, Servatius H, Drewitz I, Sydow K, Müllerleile K, Ventura R, Wegscheider K, Meinertz T, Willems S. Chronic Atrial Fibrillation Is a Biatrial Arrhythmia. Data from Catheter Ablation of Chronic Atrial Fibrillation Aiming Arrhythmia Termination Using a Sequential Ablation Approach. Circ Arrhythmia Electrophysiol 2008; 1: 344-353.
29.Deneke T, Khargi K, Grewe PH, von Dryander S, Kuschkowitz F, Lawo T, Müller K-M, Laczkovics A, Lemke B. Left atrial versus bi-atrial Maze operation using intraoperative cooled-tip radiofrequency ablation in patients undergoing open heart surgery: safety and efficacy. J Am Coll Cardiol 2002; 39: 1644-1650.
30. Matsuo S, Lellouche N, Wright M, Bevilacqua M, Knecht S, Nault I, Lim K-T, Arantes L, O`Neill MD, Platonov PG, Carlson J, Sacher F, Hocini M, Jaïs P, Haïssaguerre M. Clinical Predictors of Termination and Clinical Outcome of Catheter Ablation of Persistent Atrial Fibrillation. J Am Coll Cardiol 2009; 54: 788-795.
31. Tilz RR, Chun J, Schmidt B, Fuernkranz A, Wissner E, Koester I, Baensch D, Boczor S, Koektuerk B, Metzner A, Zerm T, Ernst S, Antz M, Kuck K-H, Ouyang F. Catheter Ablation of Long-Standing Persistent Atrial Fibrillation: A Lesson from Circumferential Pulmonary Vein Isolation. J Cardiovasc Electrophysiol 2010; 21: 1085-1093.
32. Drewitz I, Willems S, Salukhe TV, Steven D, Hoffmann BA, Servatius H, Bock K, Aydin MA, Wegscheider K, Meinertz T, Rostock T. Atrial Fibrillation Cycle Length Is a Sole Independent Predictor of a Substrate for Consecutive Arrhythmias in Patients With Persistent Atrial Fibrillation. Circ Arrhythm Electrophysiol 2010; 3: 351-360.
33. Themistoclakis S, Schweikert RA, Saliba WI, Bonso A, Rossillo A, Bader G, Wazni O, Burkhardt DJ, Raviele A, Natale A. Clinical predictors and relationship between early and late atrial tachyarrhythmias after pulmonary vein antrum isolation. Heart Rhythm 2008; 5: 679-685.
34. Choi J-I, Pak H-N, Park JS, Kwak JJ, Nagamoto Y, Lim HE, Park SW, Hwang C, Kim Y-H. Clinical Significance of Early Recurrences of Atrial Tachycardia After Atrial Fibrillation Ablation. J Cardiovasc Electrohysiol 2010; 21: 1331-1337.
35. Bertaglia E, Stabile G, Senatore G, Zoppo F, Turgo P, Amellone C, de Simone A, Fazzari M, Pascotto P. Predictive Value of Early Atrial Tachyarrhythmias Recurrence After Circumferential Anatomical Pulmonary Vein Ablation. Pacin Clin Electrophysiol 2005; 28: 366-371.
36. Verma A, Mantovan R, Macle L, De Martino G, Chen J, Morillo CA, Novak P, Clazolari V, Guerra PG, Nair G, Torrecilla EG, Khaykin Y. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial. Eur H J 2010; 31:134-1356.
37. Shah AJ, Jadidi A, Liu X, Miyazaki S, Forclaz A, Nault I, Rivard L, Linton N, Xhaet O, Derval N, Sacher F, Bordachar P, Ritter P, Hocini M, Jais P, Haissaguerre M. Atrial Tachycardias Arising from Ablation of Atrial Fibrillation: A Proarrhythmic Bump or an Antiarrhythmic Turn? Cardiol Res Pract 2010; 2010: 950763; doi: 10.4061/2010/950763
38. Ammar S, Hessling G, Reents T, Fichtner S, Wu J, Zhu P, Kathan S, Estner HL, Jilek C, Kolb C, Haller B, Deisenhofer I. Arrhythmia Type After Persistent Atrial Fibrillation Ablation Predicts Success of the Repeat Procedure. Circ Arrhythm Electrophysiol 2011; 4: 609-614.
39. Rostock T, Drewitz I, Steven D, Hoffmann BA, Salukhe TV, Bock K, Servatius H, Aydin MA, Meinertz T, Willems S. Characterization, mapping and catheter ablation of recurrent atrial tachycardias after stepwise ablation of long-lasting persistent atrial fibrillation. Circ Arrhythm Electrophysiol 2010; 3: 160-169.
40. Deneke T, Khargi K, Grewe PH, Kuschkowitz F, Laczkovics A, Lemke B. Antiarrhythmic surgery to cure AF – Subgroups and post-operative management. Cardiac Electrophysiol Rev 2003; 7: 259-263.
41. Leong-Sit P, Roux J-F, Zado E, Callans DJ, Garcia F, Lin D, Marchlinski FE, Bala R, Dixit S, Riley M, Hutchinson MD, Cooper J, Russo AM, Verdino R, Gerstenfeld EP. Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study). Six-Month Follow-Up Study. Circ Arrhythm Electrophysiol 2011, 4: 11-14.
42. Baman TS, Gupta SK, Billakanty SR, Ilg KJ, Good E, Crawford T, Ongnarangsin K, Ebinger M, Pelosi Jr F, Bogun F, Chugh A, Morady F, Oral H. Time to Cardioversion of Recurrent Atrial Arrhythmias After Catheter Ablation of Atrial Fibrillation and Long-Term Clinical Outcome. J Cardiovasc Electrophysiol 2009; 20: 1321-1325.
43. Sairaku A, Nakano Y, Oda N, Makita Y, Kajihara K, Tokuyama T, Motoda C, Fujiwara M, Kihara Y.