1. health and fitness
2. therapy

REVIEW
European Heart Journal (2010) 31, 1046–1054
doi:10.1093/eurheartj/ehq079
Controversies in cardiovascular medicine
Drugs vs. ablation for the treatment of atrial
fibrillation: the evidence supporting catheter
ablation
Hoˆpital Cardiologique Haut-Le´veˆque, Avenue de Magellan, 33 604, Bordeaux-Pessac cedex, Universite´ Victor Segalen, France
Received 20 July 2009; revised 26 January 2010; accepted 25 February 2010; online publish-ahead-of-print 23 March 2010
Treatment strategy for atrial fibrillation (AF) is a controversial matter. Catheter ablation is increasingly being used to treat patients with AF,
and recent studies have reported success rates .80% for paroxysmal AF and .70% for persistent AF. The purpose of this work is to review
the evidence supporting catheter ablation and compare it with pharmacological treatment in the management of AF.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Catheter ablation † Rhythm control † Persistent atrial fibrillation † Paroxysmal atrial
fibrillation † Anti-arrhythmic drugs
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia yet
the ideal treatment strategy is hotly debated. Large randomized
trials have failed to demonstrate a mortality benefit of a pharmacologically based rhythm control strategy compared with a ratecontrolled strategy, even in patients with left ventricular
dysfunction.1 – 4 This has led to a widespread belief that restoration
of sinus rhythm by any means is unnecessary, despite the known
increase in morbidity and age-matched mortality risk.5 However,
we believe that restoration of sinus rhythm is a desirable aim.
In an era where AF ablation is becoming standard practice
in centres across the world, it is justified to revisit the evidence
for its application and the role pharmacological treatment of AF
still holds.
Comparing ablation and
anti-arrhythmic drug
Several difficulties arise when trying to compare drugs and ablation
trials, as major differences in design and endpoint definition exist.
Success can, therefore, be defined by the absence of arrhythmia
recurrence during follow-up, or reduction in arrhythmia burden,
or sinus rhythm at last follow-up, or the endpoint can be the
time to first arrhythmia recurrence. These disparities challenge
the possibility to compare the efficiency of each intervention,
and few studies have made direct comparisons between antiarrhythmic drug (AAD) and ablative treatment for AF.
It is also a difficult task to compare ablation trials among themselves, as there is no standard approach for AF ablation and different centres use different strategies and techniques. Moreover,
there is not yet a standardized way to report outcome. The use
of AAD is also variable from study to study. These pitfalls should
be kept in mind while reviewing the data presented.
Sinus rhythm: a worthy quest?
Atrial fibrillation is associated with an excess in mortality and
higher morbidity, with, among other factors, up to five-fold
increased risk of stroke compared with an age-matched AF-free
population when co-morbidities have been adjusted for.6 – 10
However, when large randomized controlled trials tried to demonstrate a benefit of sinus rhythm by pharmacological means, the
results were perhaps surprising. The PIAF study was the first to
suggest that a pharmacological rate control strategy was
* Corresponding author. Tel: +33 5 57 65 64 71, Fax: +33 5 57 65 65 09, Email: isabellenault@gmail.com
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: journals.permissions@oxfordjournals.org.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
Isabelle Nault *, Shinsuke Miyazaki, Andrei Forclaz, Matthew Wright, Amir Jadidi,
Pierre Jaı¨s, Me´le`ze Hocini, and Michel Haı¨ssaguerre
1047
Drugs vs. ablation for the treatment of AF
Methods
A systematic review of the literature using the Pubmed database was
conducted using the terms AAD, AF, surgery, catheter ablation, and
atrial arrhythmia. Eight studies and two review articles were found
comparing AAD and catheter ablation for AF. Randomized controlled
studies on AAD, catheter ablation, and surgical trials for AF were also
reviewed.
Rhythm control
Anti-arrhythmic drugs
AADs have scored rather poorly in maintaining sinus rhythm over
time. In comparative studies, amiodarone consistently stands out as
the most efficient drug to prevent atrial arrhythmia recurrences.
However, even in trials where amiodarone achieved the highest
rate of SR, recurrences occurred in 35%.12 Class 1C AADs were
shown to suppress AF recurrences in 30 to 63% in patients with
repetitive episodes of AF, whereas sotalol efficiently maintained
SR in 32–73%.13 – 16 Newer drugs such as dofetilide successfully
maintained SR at 1 year in 79% of patients with AF and concomitant heart failure, compared with 42% in the placebo group.11
Recently, dronedarone was shown to delay the time to the first
AF recurrence from 53 days in the placebo group to 116 days in
the treatment group. At 1 year, AF had recurred in 64.1% of
patients taking dronedarone compared with 72.5% taking
placebo.17
In trials comparing rate vs. rhythm control strategies using multiple AADs, the rate of sinus rhythm maintenance in the rhythm
control groups ranged from 39% after a mean of 2.3 years in
RACE,3 56% at 1 year,4 to up to 82.4% at 1 year, and 62.6% at
5 years in AFFIRM, considering 34.6% in the rate control group
were also in sinus rhythm at 5 years.1 In the AF-CHF study, 73%
of patients assigned to rhythm control were in sinus rhythm
after a mean follow-up of 3 years compared with ,30% in the
rate control group. However, 58% in rhythm control had experienced at least one recurrence of AF during the follow-up
period2 (Table 1). These results must be interpreted taking into
consideration that in this latter trial, a significant proportion of
patients had paroxysmal AF (33%). In the other trials, a significant
number of patients had persistent AF, and inclusion in the study
often occurred after cardioversion to SR.
Drugs, therefore, have been shown to have limited efficacy in
controlling rhythm. Moreover, the outcome (the rate of patients
in sinus rhythm at last follow-up) was not a true reflection of
rhythm control, nor of AF burden, because episodes of AF occurring between visits were not considered, and efficacy is, therefore,
overestimated.
Atrial fibrillation ablation: rationale
Ablation strategies have evolved rapidly over the past years. Initial
surgical techniques aiming at treating AF were based on the
hypothesis that the fibrillatory process was generated by multiple
wavelets propagating through the atria,18,19 and that compartmentalization of the atria would interrupt re-entry circuits maintaining
the fibrillation and, therefore, render the heart incapable of sustaining AF.20,21 The finding that AF was triggered in most patients
by ectopic activity arising from the pulmonary veins (PVs) then
shifted interest towards abolishing these triggers22 (Figure 1). In
persistent AF however, AF is not dependent solely on PV triggers
and becomes self-sustained by sources and re-entry zones located
outside the veins, as atrial remodelling is promoted by the continuing arrhythmia and leads to the atrium’s ability to sustain further
fibrillation, giving rise to the concept that ‘AF begets AF’.23
Surgical approach to atrial fibrillation
The maze procedure modified to become the Cox maze III procedure consist in creating a series of incisions in both atria to
prevent the formation of macro-re-entrant circuits implicated in
the maintenance of AF.24 These lesions sets have proved to successfully eliminate AF in up to 97% of patients, among whom
76% did not need AADs at 5 years of follow-up (Figure 2).25
However, the need for an open-heart surgery along with inherent
risks and subsequent convalescence restricted the use of this technique mainly to patients undergoing concomitant heart surgery for
other purposes or to patients with contraindications to other
treatments for AF. The development of minimally invasive techniques (MISAA, minimally invasive surgical AF ablation) through
minithoracotomy where ganglionic plexi, PV antrum, and Marshall
vein are ablated and LAA is excised has widened the indication for
surgical management of AF. The complication rate of MISAA is
reported around 8%, whereas it reaches 19% for the Cox maze
III, and the success rates at 1 year from 65 to 91% without
AADs.26 – 28 Patients who may benefit from MISAA include patients
with failure to catheter ablation and patients at high risk of stroke
and contraindication to anticoagulation in whom the excision of
the LAA decreases thrombo-embolic risk. Moreover, the success
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comparable with a rhythm control strategy achieved by drugs and/
or DC cardioversion.4 The RACE and AFFIRM studies further supported these findings by suggesting that both strategies were
equivalent in terms of mortality and adverse event rates including
strokes, and recently, this statement could be extended to patients
with heart failure following the publication of the AF CHF trial.1 – 3
This led to a widespread belief that rhythm control was the strategy of choice for patients with AF. However, what these studies
did not take into account was the effect of the AADs themselves.
When the AFFIRM trial data were re-analysed using an
on-treatment analysis method, it was found that sinus rhythm
was associated with a 47% increase in survival compared with
AF (HR 0.53) and that the use of AADs increased mortality by
49% (HR 1.49).5 Similarly, sinus rhythm conferred a better prognosis both for patients treated with dofetilide and patients taking
placebo, with a 56% reduction in mortality compared with patients
in AF (HR 0.43and 0.38, respectively).11 Therefore, although evidence suggested an advantage of sinus rhythm over AF, this beneficial effect seemed to be mitigated by the adverse effects of
the drugs used to achieve and maintain it. Catheter ablation can
now restore sinus rhythm and obviate the need for long-term
AAD therapy in the majority of patients. Whether a survival advantage can be achieved by restoring sinus rhythm with ablation is an
attractive possibility that is still unanswered.
1048
AFFIRM5
AAD, anti-arrhythmic drug; PAF, paroxysmal AF; PsAF, persistent AF; SR, sinus rhythm.
36% no AF recurrence vs. 25% taking placebo
1 year
No data
266
RACE3
Dronedarone
828
Singh et al.17
73% SR at last follow-up compared with ,30% in the rate control group; 58% in the rhythm control
group had at least one AF recurrence during the study period
3 years
67%/33%
Amiodarone/sotalol/dofetilide
682
AF-CHF2
79% SR vs. 42% in placebo
1 year
No data
Dofetilide
249
DIAMOND
sub-study11
82.4% SR at 1-year follow-up
73.3% SR at 3-year follow-up
62.6% SR vs. 34.6% in the rate control group at 5-year follow-up
1 year
3 years
5 years
No data, .1/3 first
episode
Physician’s choice
2033
39% in SR at the end of the study compared with 10% in the rate control group
2.3 years
100% PsAF
Sotalol/flecanide/
propafenone/amiodarone
127
PIAF4
1 year
100% PsAF
Amiodarone or physician’s
choice
56% in SR at the end of the study compared with 10% in the rate control group
65%; no AF recurrence
36%; no AF recurrence
49%/51%
43%/57%
1.3 years
Strategies for atrial fibrillation catheter
ablation
Amiodarone
Sotalol or propafenone
201
202
CTAF12
.............................................................................................................................................................................................................................................
Follow-up
duration
PAF/PSAF
AAD
n (rhythm
control)
Trial
Table 1 Anti-arrhythmic drugs and maintenance of sinus rhythm
rate after a single procedure in patients with persistent AF seems
higher with MISAA compared with catheter ablation.
Initial attempts at AF catheter ablation consisted of ablating triggers
inside the PV22,29,30; however, it was soon observed that RF injury
inside the veins carried the risk of causing PV stenosis.31,32 The
ablation strategy, therefore, changed to a more proximal and
large encircling of the PV at the antrum, to achieve electrical disconnection of all four PVs with less risk of PV stenosis and a
better long-term outcome.33
Further, substrate modification may be needed in some cases,
especially in persistent AF, to restore and maintain sinus rhythm.
Ablation of complex and fractionated electrograms, although controversial, is reported in most series to be beneficial in organizing
the fibrillating process and in yielding better long-term outcome
when compared with PVI alone.34 – 37 Left atrial linear lesions
between the two upper PVs and between the left lower PV and
the mitral annulus when added to PV isolation also improved procedural and long-term outcome.38,39 The added value of one or
more of these steps in paroxysmal AF ablation is debated, as the
increment in acute success was seen to be at the price of an
increase in subsequent left atrial tachycardia and the need for
additional ablation procedures.40,41 However, in persistent AF,
the combination of two or more of these strategies enhanced efficacy and was associated with a better long-term outcome
(Figure 2).34,42 – 47 Other techniques advocated ablation of ganglionic plexi, as autonomous nervous system activity has been
shown to be closely related to AF in some cases.48
Current guidelines recommend that all patients undergoing catheter ablation for AF have at least electrical isolation of all four
PVs.49 This is usually sufficient to restore durable sinus rhythm in
patients with paroxysmal AF and short arrhythmia episodes,
whereas patients with longstanding persistent AF or with permanent AF often need extensive ablation, including complete lines,
to achieve a satisfactory outcome. Others should have an intermediate approach to target AF substrate in trying and avoiding
excessive ablation potentially leading to left atrial flutters or
complications.
Ablation for paroxysmal atrial fibrillation
Catheter ablation successfully treats paroxysmal AF in 41–94% of
patients, with most recent studies reporting success rates of .80%
(Table 2).33,37,38,40,44,47,50 – 63 PV isolation alone in paroxysmal AF is
reported to achieve durable sinus rhythm without the need for
AADs in 59– 93% of patients,38,51,53,57,58,60,64,65 and the addition
of linear lesions (roof or mitral lines) for patients with ongoing
or inducible AF after PVI achieved long-term success in
82 –91%.38 – 40,47,52,54,59,60 Other studies have used hybrid techniques involving PV isolation and substrate modification with or
without lines (Table 2). When AF inducibility testing is performed
and ablation is continued until AF can no longer be sustained,
success rate can be increased to 91% to the cost of increased
atrial lesions and increased number of procedures.40 In a study
exploring practices and results of catheter ablation for AF in
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Outcome
I. Nault et al.
1049
Drugs vs. ablation for the treatment of AF
restored by isolation of the right superior pulmonary vein, and fibrillation was still seen inside the vein after isolation. This demonstrates
the arrhythmogenicity of the pulmonary veins and suggests that the right superior pulmonary vein was a significant atrial fibrillation trigger
for this specific patient. (A) Isolation of the right superior pulmonary vein restores sinus rhythm. (B) Ongoing atrial fibrillation inside the isolated
right upper pulmonary vein despite atrial sinus rhythm. (C) Position of the circular mapping catheter inside the right superior pulmonary vein,
quadripolar inside the coronary sinus, and RF catheter at the lower part of the ostium of the right superior pulmonary vein, where isolation was
obtained.
centres worldwide between 1995 and 2002, the overall success
rate of ablation for paroxysmal and persistent AF was 52%
without the concomitant use of AADs and an additional 24%
were controlled with a previously ineffective drug.66 However
since then, strategies have evolved and success rates in recently
published studies have been higher.
ablation, and linear ablation achieved higher success rates of 42–
95% without AADs, with most centres reporting success in
.70%.34,42,44 – 47,50,54,73 – 78 Importantly, two or more procedures
were often necessary in order to control persistent AF, and
patients considering ablative treatment should be aware that
approximately half require more than one session.
Ablation for persistent atrial fibrillation
Ablation vs. drugs studies
Pulmonary vein isolation alone to treat persistent AF was reported
to achieve freedom from AF in 20 –61% of cases, although some
reported success rates of up to 95%,67,68 and complex fractionated
atrial electrogram ablation alone was reported to be successful in
9–85% (Table 3).33,35 – 37,43,45,47,55,64,69 – 71 For the majority with
persistent AF however, ablation of PV targets seemed
insufficient.72 Strategies using a combination of approaches such
as PV isolation, complex and fractionated atrial electrogram
Seven studies directly comparing catheter ablation and drugs have
confirmed the fact that sinus rhythm is better maintained following
catheter ablation (Table 4). A total of 763 patients were enrolled in
these studies, 380 in the catheter ablation group and 383 in the
AAD group. In an intention to treat analysis, catheter ablation
resulted in atrial arrhythmia freedom in 79% compared with only
32% in the AAD group (P , 0.001).52,79 – 84 Four studies enrolled
only patients with paroxysmal AF, and catheter ablation achieved
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Figure 1 Example of a case: 65-year-old male with paroxysmal atrial fibrillation. The patient arrived in atrial fibrillation, sinus rhythm was
1050
I. Nault et al.
monitoring and/or daily transtelephonic rhythm stripes were
recorded randomly or as mandated by symptoms.
Atrial fibrillation ablation in
patients with heart failure
Adverse events
52,79 – 80
success in 81% without concomitant AAD therapy.
In comparison, AADs maintained sinus rhythm in only 29% (P , 0.001 vs.
ablation in all four studies). Two other studies included paroxysmal
and persistent AF, and success rate of ablation was 64% compared
with 20% for AADs.81,82 In patients with persistent AF only, AF
freedom was achieved in 75% at 1 year in the ablation group,
with 27% needing more than one procedure. In comparison,
55% in the AAD group had a favourable outcome. However,
these results have to be interpreted taking into account the high
cross-over rate in one of the studies,83,84 and the small number
of patients in the other.84 However, given the important reduction
in absolute and relative risk with ablation in all these studies, if
one would wish to test the hypothesis in another study, only
15 patients per group would be needed to achieve 80% power
with P , 0.05.
In addition to being superior to AADs in maintaining sinus
rhythm, catheter ablation resulted in better symptomatic relief
and better exercise tolerance compared with drug treatment.81
Improvement in quality of life scores occurred in both groups,
but to a greater extent in the ablation group.79,81 Atrial fibrillation
burden was also decreased to a greater extent in patients treated
by ablation, and improvement in exercise tolerance was greater
following ablation compared with AAD therapy.52 All these
results, however, have to be interpreted with caution as the endpoint of AF freedom was imperfectly assessed in all of the studies
since no continuous rhythm monitoring was used; rather, Holter
It is difficult to determine the exact incidence of fatal or lifethreatening arrhythmic events directly attributable to AADs in
trials, since these events are rare, can occur any time over the
course of therapy, and can also be caused by other factors. Nevertheless, in RACE, four patients in the rhythm control group died
suddenly and three had life-threatening ventricular arrhythmia
compared with none in the rate control group and in AFFIRM;
although no significant difference in mortality was evidenced
between the rate and rhythm control group, a sub-analysis
revealed that AAD treatment was associated with a 49% increase
in mortality.1,3,5 The incidence of significant bradyarrhythmia
during AAD treatment varied from 3 to 9% in different
trials.1,2,17,79 The 1-year incidence of adverse events attributable
to amiodarone was, in one study, 0.6% for hepatic toxicity, 0.3%
for peripheral neuropathy, 0.9% for hyperthyroidism, 1% for pulmonary toxicity, and 6% for hypothyroidsm.94
Complications of catheter ablation procedures, on the contrary,
are often more flamboyant and can be directly linked to the intervention. Mortality following catheter ablation of AF is one per
thousand procedures according to a recently published international survey analysing cases from 162 centres worldwide over
more than 10 years, from 1995 to 2006.95 A similar survey
reported in 2005 an overall complication rate of 6% for AF ablation
procedures, including a 1:2000 risk of procedural death, 1.2% risk
of tamponade, 1% risk of stroke or transient ischaemic attack, and
,2% PV stenosis, with 0.6% developing symptoms.66 Others
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Figure 2 Left atrial cutplane (left atrial angiography overlay on
fluoroscopic image, anteroposterior projection). The diagram
shows the typical lesion sets around the pulmonary veins,
drawn proximally to include the antral portion of all PVs. A line
at the roof of the left atrium joins the two upper pulmonary
veins. A line interrupting the left mitral isthmus joins the left
inferior pulmonary vein and the lateral mitral annulus. Linear
lesions are often required in persistent atrial fibrillation
in order to organize atrial fibrillation or to interrupt macro-reentrant atrial tachycardia.
The prevalence of AF in patients with heart failure is estimated to
be between 10 and 50% and is associated with a 1.5 to 3-fold
increase in mortality.85,86 Atrial fibrillation contributes to the
alteration in ventricular function by increasing heart rate, creating
atrioventricular dyssynchrony, and impairing left atrial transport
function, and by the irregularity of the heart rate.87 – 90 Treatment
of AF by catheter ablation has proved to be particularly beneficial
in this population by increasing left ventricular function along with
restoring sinus rhythm and alleviating heart failure symptoms. Ejection fraction was improved after ablation in a population with congestive heart failure and AF.91 Importantly, the benefit was
observed whether or not patients had concurrent structural
heart disease and whether or not heart rate was adequately controlled prior to ablation, extending the advantages of sinus rhythm
beyond the reduction in heart rate.92 In PABA-CHF, 76% of
patients with heart failure and AF undergoing AF ablation improved
their ejection fraction compared with only 25% with atrioventricular junction ablation and biventricular pacing.93 There is, therefore,
evidence that sinus rhythm is desirable in patients with heart failure
and that catheter ablation is effective in achieving it and improving
the patient’s overall condition.
Study
n
Strategy
Follow-up (months)
Procedures (n)
AAD
AF freedom
.............................................................................................................................................................................................................................................
Della Bella50
207
Conventional ablation vs. image integration
(carto merge)
14 + 12
1.3a
0.58
0.88
Van Belle et al.51
Jaı¨s P et al.52
141
53
PVI cryoablation
PVI + lines + defragmentation
15 + 8
12
1.2
1.8
No
No
0.59
0.89
Nademanee et al.37
254
CFAE
27.6
1.7a
13%a
0.89
Wang et al.
Fiala et al.57
106
110
CPVI vs. CPVI + SVC isolation
PVI vs. CPVA
12
48 + 8
1.2
1.3
0.05
No
93 vs. 94%
0.8
Dixit et al.58
77 PAF
4 PVI/arrhythmogenic PVI only
12
1
No
0.65
Arentz et al.33
Chang et al.59
67
88
PVI vs. large PVI
PVI + lines/inducibility testing
15 + 4
12 + 6
1.2a
1
No
Yes
54 vs. 72%
45 vs. 82% (non-inducible)
Verma et al.44
120
PVI + anterior line
12
1
No
85 vs. 87%
Sheikh et al.60
Jaı¨s et al.40
100
74
PVI vs. PVI + lines
PVI + lines/inducibility testing
9
18 + 4
1.3
Yes
No
82 vs. 90%
0.91
Hocini et al.38
90
PVI vs. PVI + roof line
15 + 4
No
69 vs. 87%
Fassini et al.47
Oral et al.61
126
100
PVI vs. PVI + mitral line
CPVA, inducibility testing after ablation
12
6
1
1
50%
No
Oral et al.65
80
Segmental PVI vs. CPVA
6
18% redo PVI group
No
62 vs. 76%
Inducible: 67%; inducible but further ablation: 86%;
not inducible: 85%
67 vs. 88%
56
Drugs vs. ablation for the treatment of AF
Table 2 Catheter ablation for paroxysmal atrial fibrillation
Literature review, paroxysmal AF ablation. Randomized or non-randomized prospective studies including 50 or more patients per group and reporting results for paroxysmal and persistent AF separately. AAD, anti-arrhythmic drug; PAF,
paroxysmal AF; PsAF, persistent AF; SR, sinus rhythm; PVI, pulmonary veins isolation; CPVA, circumferential pulmonary veins ablation; CFAE, complex and fractionated atrial electrograms.
a
Including patients with persistent AF.
1051
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1052
Table 3 Catheter ablation for persistent/chronic atrial fibrillation
Study
n
Strategy
Follow-up (months)
Procedures (n)
AAD
AF freedom
.............................................................................................................................................................................................................................................
O’Neill et al.73
153
PVI + CFAE + lines + RA ablation
34
52% redo
13%
89%
Della Bella et al.50
83
Conventional ablation vs. image intergration (carto merge)
14 + 12
1.3a
61%
69%
Nademanee et al.37
Neumann et al.69
381
53
CFAE
PVI with cryoablation
28 + 20
12
1.68a
1
71%
No
85%
42%
Elayi et al.43
CPVA
PVAI
PVAI + CFAE
PVI vs. large PVI
16/14
Arentz et al.33
47
48
49
43
1
1.3
1.3
1.2a
No
Yes
No
11%/17%/28% (CPVA/PVAI/PVAI+CFAE)
40%/56%/83% (CPVA/PVAI/PVAI+CFAE)
61%/80%/94% (CPVA/PVAI/PVAI+CFAE)
40 vs. 61%
Verma et al.44
80
PVAI + anterior line
12
1
No
78 vs. 82%
Seow et al.78
Oral et al.71
53
100
PVI + line (roof, MI)
CFAE
21.6 + 8.8
13 + 7
1.5
1.48
No
No
62.50%
57
Willems et al.45
62
PVI/PVI + roof + MI
16
1
No
20%/69%
Oral et al.83
Lim et al.70
77
51
CPVA
PVI
12
17+9
1.26
No
17%
74%
45%
Calo et al.46
80
CPVI + mitral and CTI lines + RA ablation
14 + 5
1
50%
61% L ablation vs. 85% L + R ablation
Oral et al.77
Haı¨ssaguerre et al.34
80
60
LACA vs. LA lines
PVI + CFAE + lines
9+4
11 + 6
1.4
1.45
No
12%
72 vs. 75%
95%
Fassini et al.47
61
PVI vs. PVI + mitral line
12
1
50%
36 vs. 74%
Cappato et al.66 (a)
1619
Multiple
12
24
—
No/Yes
66%/90%
43%/70%
15 + 4
Literature review, persistent AF ablation. Randomized or non-randomized prospective studies including 50 or more patients per group and reporting results for paroxysmal and persistent AF separately. AAD, anti-arrhythmic drug; PAF,
paroxysmal AF; PsAF, persistent AF; SR, sinus rhythm; PVI, pulmonary veins isolation; CPVA, circumferential pulmonary veins ablation; CFAE, complex and fractionated atrial electrograms; L, left; R, right.
a
Including patients with paroxysmal AF.
I. Nault et al.
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Drugs vs. ablation for the treatment of AF
Table 4 Randomized trial ablation vs. anti-arrhythmic drug
Study
PAF/PsAF
Ablation strategy (n)
Procedures
(n)
AF freedom
ablation
AAD
(n)
AF freedom
AAD
Complications
.............................................................................................................................................................................................................................................
Krittayaphong
et al.84
100% PsAF
PVI + linear ablation RA (15)
Wazni et al.79
96% PAF/4%
PsAF
PVI (33)
Pappone et al.80
100% PAF
Oral et al.83
78.65
15
40%
Abl: one stroke
1
85%
37
21%
Abl: 3% moderate PV stenosis
AAD: 8.6% bradycardia
CPVA + CTI + mitral line (99)
1
85% without
AAD
99
35%, single drug or
combination
Abl: one TIA, one effusion
AAD: adverse events 16%, pro-arrhythmia 3%
100% PsAF
CPVA + roof and mitral lines
(77)
32% redo rate
74% without
AAD
69
58% (77% cross-over
to ablation)
PM: one each group SSS
Abl: one ANV ablation + PM
Stabile et al.82
67% PAF/33%
PsAF
CPVA + mitral line + CTI (68)
1
65.90%
69
8.70%
Abl: 4.4% (one stroke, one transient phrenic palsy, one
effusion)
Jaı¨s et al.52
100% PAF
PVI + extra PV ablation (53)
1.8
89% without
AAD
59
23%
Abl: two tamponades, two haematomas, one PV stenosis;
AAD: one hyperthyroid, two unrelated death
Forleo et al.81
41% PAF/
59%PsAF
PVI + CTI + roof and mitral
lines (35)
1
80% without
AAD
35
42.90%
Abl: one haematoma; hospitalization: 9% abl. vs. 34% AAD;
adverse events: 3% abl vs. 17% AAD
Literature review on drugs vs. ablation for AF treatment. Results after 1-year follow-up. AAD, anti-arrhythmic drug; PAF, paroxysmal AF; PsAF, persistent AF; PVI, pulmonary veins isolation; CPVA, circumferential pulmonary veins ablation; PM,
pacemaker; SSS, sick sinus syndrome; AVN, atrioventricular node; Abl, ablation group.
1053
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1054
Health economy
Cost-effectiveness of catheter ablation for AF is difficult to determine and to generalize since differences in centres’ experience, use
of technologies, and rates of reimbursement are important factors
in the calculation of costs and vary from centre to centre and from
country to country; therefore, a unique model cannot account for
all situations.103 In France, studies suggested the cost of catheter
ablation for symptomatic drug refractory paroxysmal AF to be
lower than for medical therapy after 5 years,104 whereas in
Canada, catheter ablation for AF was deemed cost neutral compared with medical therapy within 2– 4 years of the procedure
for patients with symptomatic paroxysmal AF.105,106 In the UK,
catheter ablation for symptomatic paroxysmal AF was found
potentially cost-effective on condition that the benefits in terms
of quality of life improvement were maintained at 5 years,107 and
a recent review assessing cost-effectiveness found catheter ablation more effective, however more costly when compared with
rate control treatment.108 In the USA, cost-effectiveness was
dependent on the underlying risk of stroke, the criteria being
met in patients with a moderate risk but not in those at low
risk.109 Whether catheter ablation is cost-effective for patients in
persistent AF will be answered by the Catheter Ablation for the
Cure of AF-2 study, ongoing in 14 European centres.110
Limitations
From these data, catheter ablation seems to be superior to AADs
in restoring and maintaining sinus rhythm over the long term in
patients with both paroxysmal and persistent AF. However,
these conclusions have to be tampered by the following limitations:
endpoints differed between ablation and AAD studies and among
ablation studies themselves; most of patients in ablation studies
were attempting second-line therapy as opposed to AAD trials:
this could partly explain why the success rate of AADs in these
latter trials was much lower than in comparative AAD trials,
where a significant proportion was enrolled after a first episode.
An important proportion of the studies on catheter ablation is
non-randomized or single-centred.108 Several techniques are advocated by different groups worldwide with variable success rates.
The lack of uniformity in ablation techniques, in follow-up intensity,
and in the way to report long-term outcome is a challenge when
trying to interpret and compare results from different groups.
Most data on catheter ablation of AF in the literature stem from
a few high-volume centres which are overrepresented and
may not reflect results obtained in other smaller centres. This
statement also applies to the literature about AF ablation in
patients with heart failure. Most studies report 1-year follow-up
after ablation, which is rather short considering the nature of the
disease in AF.
Conclusion
The available evidence supports the superiority of catheter ablation over medical therapy in the treatment of AF in terms of efficacy in maintaining sinus rhythm. Catheter ablation of AF should,
however, be considered as a closed heart surgical procedure
with all inherent potential of rare but debilitating complications.
It should, therefore, be emphasized that there is consensus in
the current practice guidelines to consider catheter ablation as a
second line treatment for AF, after failure of medical therapy,
and to reserve it for patients who are symptomatic. The future
may hold a greater role for ablation, as we achieve better understanding of AF physiopathology, improve tools allowing faster,
more efficient, and safer procedures, and as ongoing studies are
conducted to assess whether there is a survival advantage with
the ablative treatment of AF.
Funding
I.N. acknowledges financial support from St Jude Medical as a fellowship grant. M.W. acknowledges the financial support from the Department of Health via the National Institute for Health Research (NIHR)
Comprehensive Biomedical Research Centre award to Guy’s & St
Thomas’ NHS Foundation Trust in partnership with King’s College
London and King’s College Hospital NHS Foundation Trust. I.N.
received fellowship support from St Jude Medical.
Conflict of interest: none declared.
References
1. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB,
Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD. A comparison of
rate control and rhythm control in patients with atrial fibrillation. N Engl J
Med 2002;347:1825 – 1833.
2. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG,
Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A,
Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O’Hara G,
Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG,
Thibault B, Waldo AL. Rhythm control versus rate control for atrial fibrillation
and heart failure. N Engl J Med 2008;358:2667 –2677.
3. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA,
Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ. A comparison of rate
control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834 –1840.
4. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial
fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet 2000;356:1789 –1794.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
reported higher rates of PV stenosis, up to 28%; however, severe
reduction in lumen of .70% occurred in only 1–3% of
patients.96 – 99 In the presence of severe symptomatic PV stenosis,
PV stenting was attempted with an acute angiographic success rate
of 95%, and long-term patency of the PV was associated with the
resolution of symptoms.97,100 The most feared complication of
catheter ablation, atrio-oesophageal fistula often leading to fulminant sepsis and death, is very rare. Its true incidence is difficult
to establish with certainty, but was estimated to in 0.01%.101
Different strategies are advocated to try and prevent this fatal
complication, but their efficacy is difficult to evaluate because of
the small number of events. Oesophageal temperature monitoring
and opacification of the oesophagus with barium paste prior to the
procedure have been used as a means of avoiding injury, and a
recent publication reported that the use of conscious sedation
was associated with significantly less endoscopic oesophageal
lesions compared with the use of general anaesthesia.102
Complications of each strategy, therefore, seem to occur at a
similar rate; however, adverse events secondary to catheter ablation are more readily identified compared with those related to
AADs, which are more insidious.
I. Nault et al.
1054a
Drugs vs. ablation for the treatment of AF
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
vein isolation and ganglionic plexi ablation for atrial fibrillation: single-center
experience with 12-month follow-up. Circ Arrhythm Electrophysiol 2009;2:
370 –377.
Edgerton JR, Edgerton ZJ, Weaver T, Reed K, Prince S, Herbert MA, Mack MJ.
Minimally invasive pulmonary vein isolation and partial autonomic denervation
for surgical treatment of atrial fibrillation. Ann Thorac Surg 2008;86:35–38.
Discussion 39.
Funatsu T, Kobayashi J, Nakajima H, Iba Y, Shimahara Y, Yagihara T. Long-term
results and reliability of cryothermic ablation based maze procedure for atrial
fibrillation concomitant with mitral valve surgery. Eur J Cardiothorac Surg 2009;
36:267 –271. Discussion 271.
Chen SA, Hsieh MH, Tai CT, Tsai CF, Prakash VS, Yu WC, Hsu TL, Ding YA,
Chang MS. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses,
and effects of radiofrequency ablation. Circulation 1999;100:1879 – 1886.
Haı¨ssaguerre M, Shah DC, Jaı¨s P, Hocini M, Yamane T, Deisenhofer I, Chauvin M,
Garrigue S, Clementy J. Electrophysiological breakthroughs from the left atrium
to the pulmonary veins. Circulation 2000;102:2463 –2465.
Robbins IM, Colvin EV, Doyle TP, Kemp WE, Loyd JE, McMahon WS, Kay GN.
Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation
1998;98:1769 –1775.
Yu WC, Hsu TL, Tai CT, Tsai CF, Hsieh MH, Lin WS, Lin YK, Tsao HM, Ding YA,
Chang MS, Chen SA. Acquired pulmonary vein stenosis after radiofrequency
catheter ablation of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol
2001;12:887 – 892.
Arentz T, Weber R, Burkle G, Herrera C, Blum T, Stockinger J, Minners J,
Neumann FJ, Kalusche D. Small or large isolation areas around the pulmonary
veins for the treatment of atrial fibrillation? Results from a prospective randomized study. Circulation 2007;115:3057 –3063.
Haı¨ssaguerre M, Sanders P, Hocini M, Takahashi Y, Rotter M, Sacher F,
Rostock T, Hsu LF, Bordachar P, Reuter S, Roudaut R, Clementy J, Jaı¨s P. Catheter ablation of long-lasting persistent atrial fibrillation: critical structures for termination. J Cardiovasc Electrophysiol 2005;16:1125 –1137.
Estner HL, Hessling G, Ndrepepa G, Wu J, Reents T, Fichtner S, Schmitt C,
Bary CV, Kolb C, Karch M, Zrenner B, Deisenhofer I. Electrogram-guided substrate ablation with or without pulmonary vein isolation in patients with persistent atrial fibrillation. Europace 2008;10:1281 –1287.
Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B,
Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation
of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol
2004;43:2044 –2053.
Nademanee K, Schwab MC, Kosar EM, Karwecki M, Moran MD, Visessook N,
Michael AD, Ngarmukos T. Clinical outcomes of catheter substrate ablation
for high-risk patients with atrial fibrillation. J Am Coll Cardiol 2008;51:843 –849.
Hocini M, Jaı¨s P, Sanders P, Takahashi Y, Rotter M, Rostock T, Hsu LF, Sacher F,
Reuter S, Clementy J, Haı¨ssaguerre M. Techniques, evaluation, and consequences of linear block at the left atrial roof in paroxysmal atrial fibrillation: a
prospective randomized study. Circulation 2005;112:3688 –3696.
Jaı¨s P, Hsu LF, Rotter M, Sanders P, Takahashi Y, Rostock T, Sacher F, Hocini M,
Clementy J, Haı¨ssaguerre M. Mitral isthmus ablation for atrial fibrillation.
J Cardiovasc Electrophysiol 2005;16:1157 –1159.
Jaı¨s P, Hocini M, Sanders P, Hsu LF, Takahashi Y, Rotter M, Rostock T, Sacher F,
Clementy J, Haı¨ssaguerre M. Long-term evaluation of atrial fibrillation ablation
guided by noninducibility. Heart Rhythm 2006;3:140–145.
Deisenhofer I, Estner H, Reents T, Fichtner S, Bauer A, Wu J, Kolb C, Zrenner B,
Schmitt C, Hessling G. Does electrogram guided substrate ablation add to the
success of pulmonary vein isolation in patients with paroxysmal atrial fibrillation?
A prospective, randomized study. J Cardiovasc Electrophysiol 2009;20:514 –521.
Haı¨ssaguerre M, Hocini M, Sanders P, Sacher F, Rotter M, Takahashi Y,
Rostock T, Hsu LF, Bordachar P, Reuter S, Roudaut R, Clementy J, Jaı¨s P. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and
mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol 2005;16:
1138 –1147.
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,
Santarelli 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.
Verma A, Patel D, Famy T, Martin DO, Burkhardt JD, Elayi SC, Lakkireddy D,
Wazni O, Cummings J, Schweikert RA, Saliba W, Tchou PJ, Natale A. Efficacy
of adjuvant anterior left atrial ablation during intracardiac echocardiographyguided pulmonary vein antrum isolation for atrial fibrillation. J Cardiovasc Electrophysiol 2007;18:151 – 156.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
5. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL,
Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB,
Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation
Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation
2004;109:1509 –1513.
6. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of
chronic atrial fibrillation: the Framingham study. N Engl J Med 1982;306:
1018–1022.
7. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D’Agostino RB. Impact of atrial
fibrillation on mortality, stroke, and medical costs. Arch Intern Med 1998;158:
229– 234.
8. Atrial Fibrillation Investigators: Atrial Fibrillation, Aspirin, Anticoagulation
Study; Boston Area Anticoagulation Trial for Atrial Fibrillation Study; Canadian
Atrial Fibrillation Anticoagulation Study; Stroke Prevention in Atrial Fibrillation
Study; Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation
Study. Risk factors for stroke and efficacy of antithrombotic therapy in atrial
fibrillation. Analysis of pooled data from five randomized controlled trials.
Arch Intern Med 1994;154:1449 –1457.
9. Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992;326:
1264–1271.
10. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor
for stroke: the Framingham Study. Stroke 1991;22:983–988.
11. Pedersen OD, Bagger H, Keller N, Marchant B, Kober L, Torp-Pedersen C. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with
reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (DIAMOND) substudy. Circulation 2001;104:292 – 296.
12. Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J,
Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of
atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med
2000;342:913–920.
13. Antman EM, Beamer AD, Cantillon C, McGowan N, Goldman L, Friedman PL.
Long-term oral propafenone therapy for suppression of refractory symptomatic
atrial fibrillation and atrial flutter. J Am Coll Cardiol 1988;12:1005 – 1011.
14. Reimold SC, Maisel WH, Antman EM. Propafenone for the treatment of supraventricular tachycardia and atrial fibrillation: a meta-analysis. Am J Cardiol 1998;
82:66N –71N.
15. Bellandi F, Simonetti I, Leoncini M, Frascarelli F, Giovannini T, Maioli M,
Dabizzi RP. Long-term efficacy and safety of propafenone and sotalol for the
maintenance of sinus rhythm after conversion of recurrent symptomatic atrial
fibrillation. Am J Cardiol 2001;88:640 –645.
16. Kochiadakis GE, Marketou ME, Igoumenidis NE, Chrysostomakis SI,
Mavrakis HE, Kaleboubas MD, Vardas PE. Amiodarone, sotalol, or propafenone
in atrial fibrillation: which is preferred to maintain normal sinus rhythm? Pacing
Clin Electrophysiol 2000;23:1883 –1887.
17. Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D,
Aliot EM, Hohnloser SH. Dronedarone for maintenance of sinus rhythm in
atrial fibrillation or flutter. N Engl J Med 2007;357:987 –999.
18. Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation.
Am Heart J 1964;67:200 –220.
19. Allessie MA, Boyden PA, Camm AJ, Kleber AG, Lab MJ, Legato MJ, Rosen MR,
Schwartz PJ, Spooner PM, Van Wagoner DR, Waldo AL. Pathophysiology and
prevention of atrial fibrillation. Circulation 2001;103:769–777.
20. Cox JL, Boineau JP, Schuessler RB, Jaquiss RD, Lappas DG. Modification of the
maze procedure for atrial flutter and atrial fibrillation. I. Rationale and surgical
results. J Thorac Cardiovasc Surg 1995;110:473 – 484.
21. Cox JL, Jaquiss RD, Schuessler RB, Boineau JP. Modification of the maze procedure for atrial flutter and atrial fibrillation. II. Surgical technique of the maze
III procedure. J Thorac Cardiovasc Surg 1995;110:485 –495.
22. Haı¨ssaguerre M, Jaı¨s P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S,
Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:
659– 666.
23. Allessie MA. Atrial fibrillation-induced electrical remodeling in humans: what is
the next step? Cardiovasc Res 1999;44:10– 12.
24. Cox JL, Boineau JP, Schuessler RB, Kater KM, Ferguson TB Jr, Cain ME,
Lindsay BD, Smith JM, Corr PB, Hogue CB et al. Electrophysiologic basis, surgical
development, and clinical results of the maze procedure for atrial flutter and
atrial fibrillation. Adv Card Surg 1995;6:1–67.
25. Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP, Sundt TM III,
Cox JL, Damiano RJ Jr. The Cox maze III procedure for atrial fibrillation: longterm efficacy in patients undergoing lone versus concomitant procedures.
J Thorac Cardiovasc Surg 2003;126:1822 –1828.
26. Han FT, Kasirajan V, Kowalski M, Kiser R, Wolfe L, Kalahasty G, Shepard RK,
Wood MA, Ellenbogen KA. Results of a minimally invasive surgical pulmonary
1054b
60. Sheikh I, Krum D, Cooley R, Dhala A, Blanck Z, Bhatia A, Nangia V, Akhtar M,
Sra J. Pulmonary vein isolation and linear lesions in atrial fibrillation ablation.
J Interv Card Electrophysiol 2006;17:103 –109.
61. Oral H, Chugh A, Lemola K, Cheung P, Hall B, Good E, Han J, Tamirisa K,
Bogun F, Pelosi F Jr, Morady F. Noninducibility of atrial fibrillation as an end
point of left atrial circumferential ablation for paroxysmal atrial fibrillation: a randomized study. Circulation 2004;110:2797 – 2801.
62. Tse HF, Reek S, Timmermans C, Lee KL, Geller JC, Rodriguez LM, Ghaye B,
Ayers GM, Crijns HJ, Klein HU, Lau CP. Pulmonary vein isolation using transvenous catheter cryoablation for treatment of atrial fibrillation without risk of pulmonary vein stenosis. J Am Coll Cardiol 2003;42:752 – 758.
63. Lin WS, Tai CT, Hsieh MH, Tsai CF, Lin YK, Tsao HM, Huang JL, Yu WC,
Yang SP, Ding YA, Chang MS, Chen SA. Catheter ablation of paroxysmal atrial
fibrillation initiated by non-pulmonary vein ectopy. Circulation 2003;107:
3176 –3183.
64. Arentz T, von Rosenthal J, Blum T, Stockinger J, Burkle G, Weber R, Jander N,
Neumann FJ, Kalusche D. Feasibility and safety of pulmonary vein isolation using
a new mapping and navigation system in patients with refractory atrial fibrillation.
Circulation 2003;108:2484 – 2490.
65. Oral H, Scharf C, Chugh A, Hall B, Cheung P, Good E, Veerareddy S, Pelosi F Jr,
Morady F. Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 2003;108:
2355 –2360.
66. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G,
Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of
catheter ablation for human atrial fibrillation. Circulation 2005;111:1100 –1105.
67. Chen MS, Marrouche NF, Khaykin Y, Gillinov AM, Wazni O, Martin DO,
Rossillo A, Verma A, Cummings J, Erciyes D, Saad E, Bhargava M, Bash D,
Schweikert R, Burkhardt D, Williams-Andrews M, Perez-Lugones A,
Abdul-Karim A, Saliba W, Natale A. Pulmonary vein isolation for the treatment
of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol
2004;43:1004 –1009.
68. Ouyang F, Ernst S, Chun J, Bansch D, Li Y, Schaumann A, Mavrakis H, Liu X,
Deger FT, Schmidt B, Xue Y, Cao J, Hennig D, Huang H, Kuck KH, Antz M. Electrophysiological findings during ablation of persistent atrial fibrillation with electroanatomic mapping and double lasso catheter technique. Circulation 2005;112:
3038 –3048.
69. Neumann T, Vogt J, Schumacher B, Dorszewski A, Kuniss M, Neuser H,
Kurzidim K, Berkowitsch A, Koller M, Heintze J, Scholz U, Wetzel U,
Schneider MA, Horstkotte D, Hamm CW, Pitschner HF. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective
3-center study. J Am Coll Cardiol 2008;52:273 –278.
70. Lim TW, Jassal IS, Ross DL, Thomas SP. Medium-term efficacy of segmental
ostial pulmonary vein isolation for the treatment of permanent and persistent
atrial fibrillation. Pacing Clin Electrophysiol 2006;29:374 – 379.
71. Oral H, Chugh A, Good E, Wimmer A, Dey S, Gadeela N, Sankaran S,
Crawford T, Sarrazin JF, Kuhne M, Chalfoun N, Wells D, Frederick M,
Fortino J, Benloucif-Moore S, Jongnarangsin K, Pelosi F Jr, Bogun F, Morady F.
Radiofrequency catheter ablation of chronic atrial fibrillation guided by
complex electrograms. Circulation 2007;115:2606 – 2612.
72. Oral H, Knight BP, Tada H, Ozaydin M, Chugh A, Hassan S, Scharf C, Lai SW,
Greenstein R, Pelosi F Jr, Strickberger SA, Morady F. Pulmonary vein isolation
for paroxysmal and persistent atrial fibrillation. Circulation 2002;105:1077 – 1081.
73. O’Neill MD, Wright M, Knecht S, Jaı¨s P, Hocini M, Takahashi Y, Jonsson A,
Sacher F, Matsuo S, Lim KT, Arantes L, Derval N, Lellouche N, Nault I,
Bordachar P, Clementy J, Haı¨ssaguerre M. Long-term follow-up of persistent
atrial fibrillation ablation using termination as a procedural endpoint. Eur Heart
J 2009;30:1105 –1112.
74. Chen J, Off MK, Solheim E, Schuster P, Hoff PI, Ohm OJ. Treatment of atrial
fibrillation by silencing electrical activity in the posterior inter-pulmonary-vein
atrium. Europace 2008;10:265 –272.
75. Estner HL, Hessling G, Ndrepepa G, Luik A, Schmitt C, Konietzko A, Ucer E,
Wu J, Kolb C, Pflaumer A, Zrenner B, Deisenhofer I. Acute effects and longterm outcome of pulmonary vein isolation in combination with electrogramguided substrate ablation for persistent atrial fibrillation. Am J Cardiol 2008;
101:332 –337.
76. Sanders P, Hocini M, Jaı¨s P, Sacher F, Hsu LF, Takahashi Y, Rotter M, Rostock T,
Nalliah CJ, Clementy J, Haı¨ssaguerre M. Complete isolation of the pulmonary
veins and posterior left atrium in chronic atrial fibrillation. Long-term clinical
outcome. Eur Heart J 2007;28:1862 –1871.
77. Oral H, Chugh A, Good E, Igic P, Elmouchi D, Tschopp DR, Reich SS, Bogun F,
Pelosi F Jr, Morady F. Randomized comparison of encircling and nonencircling
left atrial ablation for chronic atrial fibrillation. Heart Rhythm 2005;2:1165 – 1172.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
45. Willems S, Klemm H, Rostock T, Brandstrup B, Ventura R, Steven D, Risius T,
Lutomsky B, Meinertz T. Substrate modification combined with pulmonary
vein isolation improves outcome of catheter ablation in patients with persistent
atrial fibrillation: a prospective randomized comparison. Eur Heart J 2006;27:
2871 –2878.
46. Calo L, Lamberti F, Loricchio ML, De Ruvo E, Colivicchi F, Bianconi L, Pandozi C,
Santini M. Left atrial ablation versus biatrial ablation for persistent and permanent atrial fibrillation: a prospective and randomized study. J Am Coll Cardiol
2006;47:2504 – 2512.
47. Fassini G, Riva S, Chiodelli R, Trevisi N, Berti M, Carbucicchio C, Maccabelli G,
Giraldi F, Bella PD. Left mitral isthmus ablation associated with PV Isolation:
long-term results of a prospective randomized study. J Cardiovasc Electrophysiol
2005;16:1150 – 1156.
48. Schauerte P, Scherlag BJ, Pitha J, Scherlag MA, Reynolds D, Lazzara R,
Jackman WM. Catheter ablation of cardiac autonomic nerves for prevention
of vagal atrial fibrillation. Circulation 2000;102:2774 –2780.
49. Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ Jr,
Davies DW, Haines DE, Haı¨ssaguerre M, Iesaka Y, Jackman W, Jaı¨s P,
Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL,
Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A,
Ruskin JN, Shemin RJ, HRS/EHRA/ECAS expert consensus statement on catheter, surgical ablation of atrial fibrillation: recommendations for personnel,
policy, procedures and follow-up. A report of the Heart Rhythm Society
(HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and
the European Cardiac Arrhythmia Society (ECAS); in collaboration with the
American College of Cardiology (ACC), American Heart Association (AHA),
and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart
Association, the European Cardiac Arrhythmia Society, the European Heart
Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm
Society. Europace 2007;9:335–379.
50. Della Bella P, Fassini G, Cireddu M, Riva S, Carbucicchio C, Giraldi F,
Maccabelli G, Trevisi N, Moltrasio M, Pepi M, Galli CA, Andreini D,
Ballerini G, Pontone G. Image integration-guided catheter ablation of atrial fibrillation: a prospective randomized study. J Cardiovasc Electrophysiol 2009;20:
258 –265.
51. Van Belle Y, Janse P, Theuns D, Szili-Torok T, Jordaens L. One year follow-up
after cryoballoon isolation of the pulmonary veins in patients with paroxysmal
atrial fibrillation. Europace 2008;10:1271 –1276.
52. Jaı¨s P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M,
Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clementy J,
Haı¨ssaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation 2008;118:2498 – 2505.
53. Kettering K, Weig HJ, Busch M, Laszlo R, Schreieck J. Segmental pulmonary vein
ablation: success rates with and without exclusion of areas adjacent to the esophagus. Pacing Clin Electrophysiol 2008;31:652 –659.
54. 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. Pacing Clin Electrophysiol 2008;31:985–997.
55. Yoshida K, Ulfarsson M, Tada H, Chugh A, Good E, Kuhne M, Crawford T,
Sarrazin JF, Chalfoun N, Wells D, Jongnarangsin K, Pelosi F Jr, Bogun F,
Morady F, Oral H. Complex electrograms within the coronary sinus: timeand frequency-domain characteristics, effects of antral pulmonary vein isolation,
and relationship to clinical outcome in patients with paroxysmal and persistent
atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:1017 –1023.
56. Wang XH, Liu X, Sun YM, Shi HF, Zhou L, Gu JN. Pulmonary vein isolation combined with superior vena cava isolation for atrial fibrillation ablation: a prospective randomized study. Europace 2008;10:600–605.
57. Fiala M, Chovancik J, Nevralova R, Neuwirth R, Jiravsky O, Nykl I, Sknouril L,
Dorda M, Januska J, Branny M. Pulmonary vein isolation using segmental
versus electroanatomical circumferential ablation for paroxysmal atrial fibrillation: over 3-year results of a prospective randomized study. J Interv Card Electrophysiol 2008;22:13 –21.
58. Dixit S, Gerstenfeld EP, Ratcliffe SJ, Cooper JM, Russo AM, Kimmel SE,
Callans DJ, Lin D, Verdino RJ, Patel VV, Zado E, Marchlinski FE. Single procedure
efficacy of isolating all versus arrhythmogenic pulmonary veins on long-term
control of atrial fibrillation: a prospective randomized study. Heart Rhythm
2008;5:174 – 181.
59. Chang SL, Tai CT, Lin YJ, Wongcharoen W, Lo LW, Tuan TC, Udyavar AR,
Chang SH, Tsao HM, Hsieh MH, Hu YF, Chen YJ, Chen SA. The efficacy of inducibility and circumferential ablation with pulmonary vein isolation in patients
with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2007;18:607 – 611.
I. Nault et al.
1054c
Drugs vs. ablation for the treatment of AF
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
106.
107.
108.
109.
110.
atrial fibrillation in patients with heart failure. N Engl J Med 2008;359:
1778 –1785.
Connolly SJ. Evidence-based analysis of amiodarone efficacy and safety. Circulation 1999;100:2025 –2034.
Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G,
Natale A, Packer D, Skanes A. Prevalence and causes of fatal outcome in catheter ablation of atrial fibrillation. J Am Coll Cardiol 2009;53:1798 –1803.
Dixit S, Marchlinski FE. How to recognize, manage, and prevent complications
during atrial fibrillation ablation. Heart Rhythm 2007;4:108 –115.
Prieto LR, Schoenhagen P, Arruda MJ, Natale A, Worley SE. Comparison of
stent versus balloon angioplasty for pulmonary vein stenosis complicating pulmonary vein isolation. J Cardiovasc Electrophysiol 2008;19:673 – 678.
Arentz T, Jander N, von Rosenthal J, Blum T, Furmaier R, Gornandt L, Josef
Neumann F, Kalusche D. Incidence of pulmonary vein stenosis 2 years after
radiofrequency catheter ablation of refractory atrial fibrillation. Eur Heart J
2003;24:963 – 969.
Dill T, Neumann T, Ekinci O, Breidenbach C, John A, Erdogan A, Bachmann G,
Hamm CW, Pitschner HF. Pulmonary vein diameter reduction after radiofrequency catheter ablation for paroxysmal atrial fibrillation evaluated by
contrast-enhanced three-dimensional magnetic resonance imaging. Circulation
2003;107:845 – 850.
Qureshi AM, Prieto LR, Latson LA, Lane GK, Mesia CI, Radvansky P, White RD,
Marrouche NF, Saad EB, Bash DL, Natale A, Rhodes JF. Transcatheter angioplasty for acquired pulmonary vein stenosis after radiofrequency ablation. Circulation 2003;108:1336 –1342.
Doll N, Borger MA, Fabricius A, Stephan S, Gummert J, Mohr FW, Hauss J,
Kottkamp H, Hindricks G. Esophageal perforation during left atrial radiofrequency ablation: is the risk too high? J Thorac Cardiovasc Surg 2003;125:836 – 842.
Di Biase L, Saenz LC, Burkhardt DJ, Vacca M, Elayi CS, Barrett CD, Horton R,
Bai R, Siu A, Fahmy TS, Patel D, Armaganijan L, Tung Wu C, Kai S, Keong
Ching C, Phillips K, Schweikert RA, Cummings JE, Arruda M, Saliba WI,
Dodig M, Natale A. Esophageal capsule endoscopy after radiofrequency catheter
ablation for atrial fibrillation: documented higher risk of luminal esophageal
damage with general anesthesia as compared with conscious sedation. Circ
Arrhythm Electrophysiol 2009;2:108 –112.
Andrikopoulos G, Tzeis S, Maniadakis N, Mavrakis HE, Vardas PE. Costeffectiveness of atrial fibrillation catheter ablation. Europace 2009;11:147 –151.
Weerasooriya R, Jaı¨s P, Le Heuzey JY, Scavee C, Choi KJ, Macle L, Raybaud F,
Hocini M, Shah DC, Lavergne T, Clementy J, Haı¨ssaguerre M. Cost analysis of
catheter ablation for paroxysmal atrial fibrillation. Pacing Clin Electrophysiol
2003;26:292 – 294.
Khaykin Y, Wang X, Natale A, Wazni OM, Skanes AC, Humphries KH, Kerr CR,
Verma A, Morillo CA. Cost comparison of ablation versus antiarrhythmic drugs
as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT
pilot study. J Cardiovasc Electrophysiol 2009;20:7 –12.
Khaykin Y, Morillo CA, Skanes AC, McCracken A, Humphries K, Kerr CR. Cost
comparison of catheter ablation and medical therapy in atrial fibrillation.
J Cardiovasc Electrophysiol 2007;18:907 –913.
McKenna C, Palmer S, Rodgers M, Chambers D, Hawkins N, Golder S, Van
Hout S, Pepper C, Todd D, Woolacott N. Cost-effectiveness of radiofrequency
catheter ablation for the treatment of atrial fibrillation in the United Kingdom.
Heart 2009;95:542 –549.
Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S,
Pepper C, Todd D, Woolacott N. Curative catheter ablation in atrial fibrillation
and typical atrial flutter: systematic review and economic evaluation. Health
Technol Assess 2008;12:1 –198. iii –iv, xi –xiii.
Chan PS, Vijan S, Morady F, Oral H. Cost-effectiveness of radiofrequency catheter ablation for atrial fibrillation. J Am Coll Cardiol 2006;47:2513 –2520.
Bertaglia E, Stabile G, Senatore G, Colella A, Del Greco M, Goessinger H,
Lamberti F, Lowe M, Mantovan R, Peters N, Pratola C, Raatikainen P, Turco P,
Verlato R. A clinical and health-economic evaluation of pulmonary vein encircling ablation compared with antiarrhythmic drug treatment in patients with persistent atrial fibrillation (Catheter Ablation for the Cure of Atrial Fibrillation-2
study). Europace 2007;9:182–185.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on September 9, 2014
78. 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;9:1129 –1133.
79. Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D,
Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D,
Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic
atrial fibrillation: a randomized trial. JAMA 2005;293:2634 –2640.
80. Pappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S, Paglino G,
Mazzone P, Sora N, Greiss I, Santagostino A, LiVolsi L, Pappone N, Radinovic A,
Manguso F, Santinelli V. A randomized trial of circumferential pulmonary vein
ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation:
the APAF Study. J Am Coll Cardiol 2006;48:2340 –2347.
81. Forleo GB, Mantica M, De Luca L, Leo R, Santini L, Panigada S, De Sanctis V,
Pappalardo A, Laurenzi F, Avella A, Casella M, Dello Russo A, Romeo F,
Pelargonio G, Tondo C. Catheter ablation of atrial fibrillation in patients with
diabetes mellitus type 2: results from a randomized study comparing pulmonary
vein isolation versus antiarrhythmic drug therapy. J Cardiovasc Electrophysiol 2009;
20:22–28.
82. Stabile G, Bertaglia E, Senatore G, De Simone A, Zoppo F, Donnici G, Turco P,
Pascotto P, Fazzari M, Vitale DF. Catheter ablation treatment in patients with
drug-refractory atrial fibrillation: a prospective, multi-centre, randomized, controlled study (Catheter Ablation for the Cure of Atrial Fibrillation Study). Eur
Heart J 2006;27:216 –221.
83. Oral H, Pappone C, Chugh A, Good E, Bogun F, Pelosi F Jr, Bates ER,
Lehmann MH, Vicedomini G, Augello G, Agricola E, Sala S, Santinelli V,
Morady F. Circumferential pulmonary-vein ablation for chronic atrial fibrillation.
N Engl J Med 2006;354:934 –941.
84. Krittayaphong R, Raungrattanaamporn O, Bhuripanyo K, Sriratanasathavorn C,
Pooranawattanakul S, Punlee K, Kangkagate C. A randomized clinical trial of
the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation. J Med Assoc Thai 2003;86(Suppl. 1):
S8 –S16.
85. Krahn AD, Manfreda J, Tate RB, Mathewson FA, Cuddy TE. The natural history
of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba
Follow-Up Study. Am J Med 1995;98:476 –484.
86. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact
of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation
1998;98:946–952.
87. Daoud EG, Weiss R, Bahu M, Knight BP, Bogun F, Goyal R, Harvey M,
Strickberger SA, Man KC, Morady F. Effect of an irregular ventricular rhythm
on cardiac output. Am J Cardiol 1996;78:1433 –1436.
88. Linderer T, Chatterjee K, Parmley WW, Sievers RE, Glantz SA, Tyberg JV. Influence of atrial systole on the Frank–Starling relation and the end-diastolic
pressure-diameter relation of the left ventricle. Circulation 1983;67:1045 – 1053.
89. Shapiro W, Klein G. Alterations in cardiac function immediately following electrical conversion of atrial fibrillation to normal sinus rhythm. Circulation 1968;38:
1074–1084.
90. Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to
atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992;69:1570 –1573.
91. Gentlesk PJ, Sauer WH, Gerstenfeld EP, Lin D, Dixit S, Zado E, Callans D,
Marchlinski FE. Reversal of left ventricular dysfunction following ablation of
atrial fibrillation. J Cardiovasc Electrophysiol 2007;18:9 –14.
92. Hsu LF, Jaı¨s P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M,
Pasquie JL, Scavee C, Bordachar P, Clementy J, Haı¨ssaguerre M. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:
2373–2383.
93. Khan MN, Jaı¨s P, Cummings J, Di Biase L, Sanders P, Martin DO, Kautzner J,
Hao S, Themistoclakis S, Fanelli R, Potenza D, Massaro R, Wazni O,
Schweikert R, Saliba W, Wang P, Al-Ahmad A, Beheiry S, Santarelli P,
Starling RC, Dello Russo A, Pelargonio G, Brachmann J, Schibgilla V, Bonso A,
Casella M, Raviele A, Haı¨ssaguerre M, Natale A. Pulmonary-vein isolation for