Download Chronic Atrial Fibrillation Is a Biatrial Arrhythmia

Chronic Atrial Fibrillation Is a Biatrial Arrhythmia
Data from Catheter Ablation of Chronic Atrial Fibrillation Aiming
Arrhythmia Termination Using a Sequential Ablation Approach
Thomas Rostock, MD; Daniel Steven, MD; Boris Hoffmann, MD; Helge Servatius, MD;
Imke Drewitz, MD; Karsten Sydow, MD; Kai Müllerleile, MD; Rodolfo Ventura, MD;
Karl Wegscheider, PhD; Thomas Meinertz, MD; Stephan Willems, MD
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Background—Termination of chronic atrial fibrillation (CAF) can be achieved by catheter ablation using a stepwise
approach. However, there are limited data on the contribution of the right atrium to the CAF process. Furthermore, the
prognostic value of CAF termination remains unclear.
Methods and Results—Eighty-eight patients (61⫾10 years of age) underwent de novo ablation of CAF in 2006 at our
institution. The ablation procedure was performed sequentially in the following order: pulmonary vein isolation,
defragmentation of the left atrium, coronary sinus, and right atrium. Attempted procedural end point was termination
of CAF. Consecutive arrhythmias occurring after AF termination were mapped, and ablation was attempted. AF
termination was achieved in 68 (77%) patients: in 37 (55%) patients it occurred in the left atrium, in 18 (26%) patients
in the right atrium, and in 13 (19%) patients in the coronary sinus. In 54 patients, at least one redo was performed (total
number of procedures: 154). After the first redo, another 30 patients were in sinus rhythm (total 63), 8 patients were in
atrial tachycardia (AT), and 17 patients were in AF. Another 11 patients underwent a second redo. After a mean
follow-up of 20⫾4 months, 71 (81%) patients were in sinus rhythm, 1 (1%) patient was in AT, and 16 (18%) patients
were in AF. Patients with CAF termination had predominantly ATs as recurrent arrhythmias (83%), whereas those
without mainly presented with recurrent CAF (85%). The overall success rate in patients with CAF termination was 95%
compared with 5% of patients without CAF termination in 2 procedures (n⫽12). In almost all redo procedures
attributable to AT, at least 1 AT during redo was documented previously.
Conclusions—AF termination is a prognostic important end point of catheter ablation for CAF. Termination of AF was
achieved in both atria and the coronary sinus, suggesting a biatrial substrate of CAF. Subsequent arrhythmias often recur
during follow-up and, therefore, should be targeted for ablation. (Circ Arrhythmia Electrophysiol. 2008;1:344-353.)
Key Words: ablation 䡲 catheter ablation 䡲 atrial fibrillation 䡲 atrial tachycardia 䡲 mechanisms
P
aroxysmal atrial fibrillation (AF) is predominantly
caused by electric discharges arising from the pulmonary veins (PVs).1 It is therefore the current consensus that
catheter ablation procedures for paroxysmal AF targeting
the PVs should aim for complete electric isolation,2 which
is associated with success rates of about 80%.3 In contrast,
the mechanisms of chronic AF (CAF) are less comprehensively elaborated. Even though the PVs remain a central
target of the majority of catheter ablation approaches for
CAF,4 –7 PV isolation alone may not be sufficient for a
favorable outcome.8 Thus, a variety of lesion sets have
been evaluated to enhance the clinical success rates of
catheter ablation procedures for CAF.6,8 –12 However, the
procedural end points did not predict the clinical outcome,
and the majority of patients had to be cardioverted at the
end of the procedure. The first study reporting on a
predictive procedural end point was described by Haissaguerre et al.4,5 The aim of this stepwise ablation approach was to terminate chronic AF by ablation to either
sinus rhythm (SR) or atrial tachycardia (AT), which was
Editorial see p 324
Clinical Perspective see p 353
associated with a so-far unreported high success rate of 95%
of patients being in SR after 1 year. Nevertheless, there are
only limited data on clinical and electrophysiological
follow-up of ⬎1 year. Thus, the aim of the present study was
to evaluate acute success rates of termination of CAF using a
sequential ablation approach, with special regard to the
distribution of critical structures for termination in both the
Received February 11, 2008; accepted September 15, 2008.
From the Departments of Cardiology (T.R., D.S., B.H., H.S., I.D., K.S., K.M., R.V., T.M., S.W.), and Medical Biometry and Epidemiology (K.W.),
University Hospital Eppendorf, Hamburg, Germany.
Correspondence to Thomas Rostock, MD, Department of Cardiology, University Hospital Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
E-mail [email protected]
© 2008 American Heart Association, Inc.
Circ Arrhythmia Electrophysiol is available at http://circep.ahajournals.org
344
DOI: 10.1161/CIRCEP.108.772392
Rostock et al
Biatrial Substrate of CAF
345
left and right atrium (RA) and to assess the prognostic value
of CAF termination for the long-term follow-up.
Methods
Study Population
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This study comprised 88 consecutive patients (mean age, 61⫾10
years; 11 women) with CAF who underwent an index procedure
between January and December 2006. All patients were in AF for at
least 3 months before the index procedure and presented with an AF
cycle length (AFCL) ⱕ155 ms. The median duration of chronic AF
before the procedure was 12 months (range, 3 to 264 months).
Twenty-four (27%) patients had a history of at least 1 unsuccessful
attempt at electric cardioversion. The mean left atrial (LA) diameter
was 50⫾7 mm, and the mean left ventricular ejection fraction was
57⫾13%. Structural heart disease was present in almost two thirds
(n⫽56; 64%) of the patients, consisting of hypertensive heart disease
in 37 (42%) patients, which was associated with a coronary artery
disease in 18 (20%) patients, valvular heart disease in 8 (9%)
patients, of whom 4 patients had previously undergone surgical valve
replacement (1 aortic valve, 3 mitral valve) without intraoperative
ablation, and 11 (13%) patients with impaired left ventricular
function (dilative cardiomyopathy in 6) and a left ventricular ejection
fraction ⱕ50%.
A total of 36 (41%) patients were on amiodarone. Twenty-one
(24%) patients were treated with ␤-blocker, and no patient was on
any class-I-antiarrhythmic drug or on sotalol. All patients gave
written informed consent. Antiarrhythmic drugs, with the exception
of amiodarone, were ceased at least 5 half-lives before the procedure.
PV isolation was the first step in all procedures and was performed
as described previously.8 In brief, the posterior wall of the ipsilateral
veins was initially targeted and an ablation line was deployed in a
distance of 1 to 1.5 cm proximal from the PV ostium, which has been
labeled by the Lasso catheter. Ablation started at the superior aspect
of the LA posterior wall, and the line was continued around the entire
vein including the anterior aspect as required to achieve complete
electric disconnection. The PVs were isolated individually or as
ipsilateral pairs. PV isolation was defined by elimination or dissociation of all PV potentials recorded by the Lasso catheter.
Electrophysiological Study
LA Defragmentation
All patients underwent transesophageal echocardiography within 48
hours before the procedure to exclude atrial thrombi. The procedure
was performed under sedation with propofol and under continuous
monitoring of blood pressure and saturation.
Surface electrocardiograms and bipolar endocardial electrograms
were continuously monitored and stored on a computer-based digital
amplifier/recorder system (Bard Electrophysiology).
The following catheters were introduced via a femoral vein access:
(1) a steerable decapolar catheter (Inquiry, IBI, Irvine Biomedical
Inc) was positioned within the coronary sinus (CS); (2) a decapolar
diagnostic catheter for circumferential mapping of the PVs (Lasso,
Biosense-Webster); (3) a nonsteerable quadripolar diagnostic catheter (Inquiry, IBI, Irvine Biomedical Inc) was placed in the right atrial
appendage; and (4) a 3.5-mm externally irrigated-tip ablation catheter (Biosense-Webster) was used for mapping and ablation. The
Lasso and ablation catheter were stabilized with long sheaths (SL0,
Daig, Inc, St. Jude Medical) continuously flushed with heparinized
saline solution. Access to LA was achieved by a single transseptal
puncture with the 2 catheters placed into the left atrium via the same
puncture. A single bolus of 50 IU/kg body weight heparin was
administered after transseptal puncture.
As the second step, characteristic electrograms and electrogram
behaviors considered to be involved in the electrophysiological
processes of chronic AF were targeted in the LA. These targets were
characterized as follows4,12:
Radiofrequency Ablation
The ablation procedure was performed using a sequential ablation
approach by means of a modified stepwise ablation as described by
Haissaguerre et al.4,5,12 The following steps were carried out in a
fixed order unless the patient converted from AF to either SR or AT
before finalizing all ablation steps (Figure 1). RF current was applied
with a maximum power output of 30 W using an irrigation rate of 10
to 30 mL/min (0.9% saline infused with the Cool Flow Pump,
Biosense Webster) for the PVs, 35 W and an irrigation rate between
30 and 60 mL/min in the LA, and up to 30 W in the RA. Ablation
within the CS was performed with a maximum of 25 W, and the
irrigation rate was manually adjusted to keep the tip-temperature
below 42°C. In case of high impedances, the power setting was
reduced to 20 W.
Figure 1. Study protocol and subsequent ablation steps.
PV Isolation
●
●
●
●
●
Continuous electric activity without an interspersing isoelectric
line
High-frequency complex fractionated activity (multiple, highfrequency deflections of a single electrogram)
Locally short AFCL or intermittent local burst activity
Activation gradient between the electrogram recorded by the distal
bipole in relation to the proximal bipole of the ablation catheter
Local spreading of centrifugal activation
Before ablation for LA defragmentation, the individual AF behavior
in terms of AFCL and fractionation had been roughly evaluated at
the LA appendage (LAA), the LA posterior wall, the lateral LA, and
the LA septum to get an expeditious overview of the patient’s
specific AF process. Defragmentation was defined as the conversion
of complex, fractionated, or continuous electrograms into more
discrete, regular, and synchronous activation.4,12 All regions of the
LA were considered to harbor potential substrates critical for AF
perpetuation. Because the AFCL after PV isolation often remains
short,12 mapping of specific targets as described above is rather
challenging because of contingently occurring passively activated
fractionation potentially caused by a short local AFCL.13 Hence, the
first step of LA defragmentation was uniquely performed by completely looping the ablation catheter within the LA such that the
distal tip was placed at the LA roof by the site of the superior aspect
of the previously applied RF lesions for left PV disconnection. Then,
the catheter was dragged back toward the right superior PV while the
local roof electrograms were mapped and ablated accordingly.
Mapping and ablation was then continued at the LA septum by
continuously dragging back the catheter. After elimination of fractionation or slowing of local AFCL at the LA septum, the endocardial aspect of the CS at the inferior LA was mapped. Ablation of the
inferior LA was started medially at the septum with the ablation
catheter facing the CS ostium endocardially and continued toward
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December 2008
the lateral endocardial aspect vis-à-vis the distal CS. Using this
single maneuver, a relatively large area potentially involved in the
individual chronic AF processes (roof, LA septum, inferior, and
lateral LA, respectively) can be mapped and ablated. When the
AFCL was prolonged, sites with specific electrogram characteristics,
as described earlier, were targeted in virtually all areas of the LA.
Defragmentation of the LA was finished when the described electrogram characteristics were no longer found at any LA site or when
the AFCL in the LA was longer than the one in the CS or the RA.
Table.
Procedure-Related Data
Index
Procedure
No.
Redo
Procedure
P
88
66
293 (120–440)
210 (60–360)
⬍0.001
Fluoroscopy time, min
75 (22–138)
47 (7–95)
⬍0.001
No. of RF applications
62 (22–122)
29 (4–78)
⬍0.001
Procedure duration, min
Defragmentation/Electric Isolation of the CS
When AF did not terminate during LA ablation, defragmentation was
performed within the CS. The ablation was started in the distal CS
and the ablation catheter was continuously withdrawn toward the CS
ostium. End points of CS ablation were elimination of complex
fractionation, slowing of the local AFCL, or electric isolation.
Electric isolation was defined as either complete disappearance of all
atrial signals in the CS or occurrence of a dissociated activity. When
the AF activity in the CS itself was converted into discrete synchronous electrograms with a significant prolongation of the AFCL, no
further attempt was made to isolate the CS completely.
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Right Atrial Defragmentation
Right atrial ablation was performed as the final step in all patients
without prior AF termination during LA or CS ablation. Targets and
end points of RA ablation were similar to those described for
defragmentation of the LA. The superior vena cava (SVC) was
mapped in all cases. A SVC driver was defined as a specific
sequence with the earliest activation within the SVC (activation of
the RA from the SVC) or as the presence of a shorter AFCL in the
SVC when compared with the RA.
Procedural End Points
The attempted procedural end point was termination of AF and,
whenever possible, termination of subsequent ATs with the achievement of SR by ablation only. When AF termination had not been
achieved, the procedure was stopped after a maximum of 6 hours or
if a maximum of 5 L of fluid had been administered to the patient via
the catheter irrigation. The patient was then externally cardioverted.
If AF was terminated by ablation and converted to AT, conventional techniques were used to identify the underlying mechanism
and subsequent ablation was commenced. Conversion from AF to
AT was defined as the occurrence of an organized atrial rhythm with
a consistent atrial activation sequence (assessed by the CS, HRA, and
mapping catheter) and by a monomorphic P-wave morphology.
Follow-Up
All patients were regularly seen every 3 months in our outpatient
clinic. Before these visits, the patients received at least 2 Holter
ECGs. Furthermore, detailed evaluation of the patients’ symptoms
suggestive for potential AF recurrences was performed. In case of
arrhythmia recurrences within the initial 3 months after the index
procedure, irrespective of the arrhythmia mechanism (AF or AT), the
patients were cardioverted. All recurrent arrhythmias occurring
during the follow-up were documented by a 12-lead ECG and
compared with the arrhythmias mapped and ablated during the
procedures. An interval of at least 3 months was required between
2 procedures.
Antiarrhythmic drug treatment, including amiodarone, was discontinued after the index procedure in all patients. Patients with
recurrence of CAF within the initial 3 months after the index
procedure were cardioverted and treated with amiodarone. These
patients were scheduled for a redo procedure 3 months after the
index procedure and amiodarone was discontinued afterward. Patients with recurrences after the initial 3 months underwent primary
reablation.
Statistical Analysis
Continuous data are given as median and range or mean⫾SD.
Comparison between groups (ie, AF termination versus no AF
termination, index versus redo procedure) was carried out using
either the Student t test or the Wilcoxon rank-sum test when
appropriate. A 2-tailed probability value of ⬍0.05 was considered to
be statistically significant. The 95% confidence intervals are given
for the success rates after each procedure and for the total result.
The authors had full access to and take full responsibility for the
integrity of the data. All authors have read and agree to the
manuscript as written.
Results
Procedural Data
A total of 154 ablation procedures were performed in the 88
study patients. Of these, 33 patients underwent a single
ablation procedure, whereas 54 patients had at least one redo
procedure (median number of procedures per patient with at
least one redo 2 [range, 2 to 4]). The procedure-related data
of index and redo procedures are shown in the Table. Thus,
the mean procedure duration and fluoroscopy time were
significantly shorter and less RF applications were necessary
for the redo compared with the index procedures.
Termination of AF during Ablation
During the index procedure, termination of AF was achieved
in 68 (77%) patients (Figure 2). Of these, termination
occurred in 37 (54%) patients in the LA (Figure 3, top), in the
CS in 13 (20%) patients (Figure 3, bottom), and in the RA in
18 (26%) patients. The baseline AFCL of the LAA and RAA
did not differ significantly between patients with AF termination in the LA and RA. However, in patients with AF
termination in the RA after PV isolation, the AFCL of the
RAA was significantly shorter than the one in the LAA (148
ms [143 to 158 ms] versus 162 ms [153 to 164 ms]; P⫽0.01).
No significant AFCL gradient between LAA and RAA was
observed after PV isolation in patients with AF termination in
the LA or CS (159 ms [152 to 166 ms] versus 156 ms [148 to
162 ms]; P⫽0.20).
Direct conversion to SR was observed in 8 patients (5
during PV isolation, 1 RA septum, 1 RA lateral, and 1 LA
lateral), whereas in 60 patients, AF was converted to AT.
During the index procedure, AF was not terminated in 20
(23%) patients. Of these, the procedure was stopped prematurely in 13 patients because of a fluid administration ⱖ5 L
via the externally irrigated tip ablation catheter (after a mean
procedure duration of 298⫾29 minutes), and in 7 patients
after reaching a procedure duration of ⱖ6 hours. These end
points exclusively occurred during the final step of RA
ablation.
Patients with a CAF duration ⬍6 months had significantly
shorter procedure durations (248 minutes [120 to 420 minutes] versus 338 minutes [190 to 440 minutes]; P⬍0.001),
and required a lower number of RF applications (52 [22 to
Rostock et al
Biatrial Substrate of CAF
347
Figure 2. Distribution of termination sites of
chronic AF. An outer ring labels sites of termination at the posterior LA. (LA: LAA⫽10, PVs⫽8, inferior⫽6, septum⫽5, roof⫽3, lateral⫽2, posterior⫽2, anterior⫽1; CS: ostium⫽6, proximal⫽5,
distal⫽2; RA: anterior⫽10, septum⫽6, lateral⫽2).
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111] versus 69 [36 to 122]; P⫽0.001) when compared with
patients with CAF lasting ⬎6 months before the procedure.
Twenty-three of 54 patients presented with recurrence of
CAF after the first procedure (1 patient refused redo). Of
these 22 patients, AF was terminated in 7 (32%) patients. AF
termination occurred in 4 patients in the LA, in 1 patient in
the CS, and 2 patients in the RA. In 12 (55%) patients, no AF
termination was achieved in 2 ablation procedures. Further-
Figure 3. Top, Termination of AF
directly to SR. The ablation catheter is
positioned at the LA roof, which displays a rapid and high-fractionated
electric activity (A). RF delivery at that
site initially organized fractionation to
discrete potentials (B) and finally terminated AF to SR (C). Of note, complete roof-line block occurred during
ablation indicated by the occurrence
of clearly separated double potentials
during SR (arrows), suggesting a close
relation of the interatrial connection
(Bachmann’s bundle) to the roof-line.
Bottom, Focal AF within the proximal
CS (Map), which was conducted to
the atria in a relative regular fashion
mimicking atrial tachycardia (HRA),
whereas the distal CS was isolated
indicated by a dissociated rhythm (CS
3/4). Ablation at that site resulted in
AF termination and conversion to
atrial tachycardia.
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December 2008
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Figure 4. A, Flowchart of the patient flow
with regard to arrhythmia termination during each procedure and outcome in terms
of an arrhythmia-free follow-up (SR) or
arrhythmia recurrences (No SR). The
arrows indicate how many patients are in
SR after each procedure (left panel), how
many patients have undergone a redo
procedure, and how many patients finished the study without the achievement
of SR. B, The histogram demonstrates the
arrhythmia outcomes after each procedure with regard to SR, AF, and AT,
respectively, and with 95% confidence
intervals shown in brackets.
more, in 3 patients with AF termination during the index
procedure and AF recurrences, AF was not terminated during
the redo procedure (Figure 4).
Characterization of Subsequent Arrhythmias
During the index procedure, subsequent ATs occurred after
AF termination in 60 patients (Figure 5). A total number of 98
different ATs were found in those 60 patients, with a median
number of 1 [1 to 4] AT per patient. These ATs were
characterized as focal in 31 and reentry in 67 cases. Focal
ATs were observed at the LA septum (n⫽9), LA anterior wall
(n⫽4), RA anterior wall (n⫽4), proximal CS (n⫽4), RA
lateral wall (n⫽3), LA inferior (n⫽3), RA septum (n⫽2), and
LAA (n⫽2). Macroreentrant ATs consisted of perimitral
flutter (n⫽24), LA roof-dependent flutter (n⫽17), cavotricuspid isthmus flutter (n⫽12), and CS ostium reentry (n⫽10). Of
note, microreentrant circuits were demonstrated at the LAA
ridge in 3 patients and at the LA septum in 1 patient. These
microreentrant ATs were characterized by consistent entrainment with the shortest postpacing interval (ⱕ⫹20 ms of AT
cycle length) at the site where ⱖ80% of the AT cycle length
was displayed by the 2 bipoles of the ablation catheter (Figure
6). These ATs were eliminated by focal ablation in all cases.
A total of 28 (32%) patients required linear ablation (mitral
isthmus: n⫽10, roof line: n⫽9, both lines: n⫽17) either for
AF termination or ablation of subsequent macroreentrant
tachycardias during the index procedure. Mitral isthmus
block was achieved in 21 patients (78%) and roof line block
in 23 patients (88%). Only 4 of 18 patients (22%) with AF
termination required linear ablation. Termination of AT with
conversion to SR was not achieved in 22 patients because of
exceeding procedure durations of 6 hours (n⫽13), fluid
administration of ⱖ5 L (n⫽8), and occurrence of tamponade
(n⫽1). In 5 of these patients, AT was terminated to SR by
overdrive pacing, whereas the remaining patients required
external cardioversion.
Rostock et al
Biatrial Substrate of CAF
349
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Figure 5. Termination of AF and consecutive arrhythmias that occurred before obtaining SR. CTI – Flutter⫽common type atrial flutter.
Follow-Up and Recurrent Arrhythmias
The mean follow-up was 20⫾4 months. Among the 88 study
patients, 33 (38%) patients were free of any recurrent arrhythmia after a single procedure, including 1 patient without AF
termination during ablation. At least one redo procedure was
performed in 54 patients at a mean of 8⫾4 months. The most
favorable outcome was observed in patients with AF termination during the index procedure. Approximately one half of
these had arrhythmia recurrences. However, only 6 patients
presented with AF, whereas the majority (n⫽30) had ATs and
no further episodes of AF. On the other hand, in 12 patients
without AF termination during either index or redo procedure, AF recurred and persisted. These patients were not
scheduled for a second redo procedure. After the first redo
procedure, a total of 63 (72%) patients were arrhythmia-free
during follow-up. Another 11 patients required a second redo
procedure of whom 1 patient underwent a third redo procedure. Finally, a total of 71 (81%) patients were free of any
recurrent arrhythmias, whereas 16 patients had recurrence of
AF (2 with paroxysmal AF) and 1 patient had AT (Figure 4).
Four patients with recurrences (2 AT, 2 PAF) were taking
amiodarone during follow-up.
All but 5 patients demonstrated electric reconduction of at
least 1 PV (1.5⫾0.9 PVs per patient). During redo procedures, patients with AT presented with a mean of 1.9⫾0.9
tachycardias (75 reentry, 18 focal), consisting of perimitral
flutter (n⫽27), LA roof-dependent flutter (n⫽19), cavotricuspid isthmus flutter (n⫽16), and CS ostium reentry (n⫽7).
Microreentrant circuits were found at the LAA ridge in 3
patients and at the anterior wall in another 3 patients (Figure
5). Focal ATs were observed in the proximal CS (n⫽4), at the
LA roof (n⫽4), at the LAA (n⫽3), RA septum (n⫽3), PV
ostium (n⫽2), RA posterior (n⫽1), and LA inferior (n⫽1).
Interestingly, in 30 patients, at least 1 AT observed during the
redo procedure had been documented previously either during an earlier ablation procedure or during the initial 3
months of follow-up.
Characteristics of Patients not Benefiting
From Ablation
A strong procedural predictor for recurrence of chronic AF
was the failure to terminate AF by ablation during the 2
procedures. All 12 patients in whom AF was not terminated
during the index and redo procedure demonstrated recurrence
of CAF. Epidemiologically, these patients were characterized
by larger LA diameter (54⫾5 mm versus 48⫾7 mm;
P⫽0.005), an impaired left ventricular function (50⫾14%
versus 58⫾12%; P⫽0.048), and a longer duration of CAF
(44⫾49 months versus 17⫾21 months; P⫽0.001). Of note,
patients without AF termination in 2 ablation procedures and
with CAF recurrence had significantly shorter baseline AFCL
than patients with AF termination (124⫾4 ms versus 146⫾4
ms; P⫽0.001; Figure 7). Furthermore, all but one of these
patients had a structural heart disease (dilative cardiomyopathy in 4 patients, congestive heart failure in 2 patients,
coronary artery disease in 3 patients, and hypertensive heart
disease in 2 patients).
Adverse Events
During a total of 154 procedures, 2 patients developed
pericardial tamponade (1 during left lateral defragmentation
and 1 during ablation at the RA anterior wall), which were
successfully managed by pericardiocentesis. In another patient, a transient ischemic attack occurred 1 day after the
procedure that completely recovered. A transient dissociation
between the RA and LA was observed in 1 patient (without
any electric activity in the RA and an AT in the LA), which
recovered within 1 hour after its occurrence. An electric
isolation of the LAA with slow dissociated activity was
observed in 1 patient. Because ablation was immediately
interrupted, the LAA conduction recovered within 15 minutes. There were no phrenic nerve injuries.
Discussion
This study demonstrates that termination of CAF by ablation
can be achieved in a substantial number of patients using a
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December 2008
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Figure 6. AT with a cycle length of 230 ms, which occurred after termination of AF during the index procedure. The ablation catheter is
positioned at the anterior ridge of the LAA. Of note, the distal and proximal bipole of the ablation catheter (Map) cover almost the entire
tachycardia cycle length. This tachycardia was characterized by consistent concealed entrainment with a postpacing interval of ⫹10
ms, indicating a microreentry at the anterior LAA ridge. Focal ablation with a single RF application at that spot led to AT termination
and conversion to a different AT.
sequential ablation approach. Our study provides evidence
that AF termination is associated with a high-success rate
during the long-term follow-up, revealing termination of AF
as an important procedural end point. However, a considerable number of patients required ablation in the RA and the
CS to achieve AF termination, indicating a biatrial substrate
of CAF. Of note, CAF typically converts to clinically relevant
ATs demonstrated by its reoccurrence during follow-up. This
is particularly the case after unsuccessful ablation or when
electric recovery of the critical substrate occurs. Finally, this
study identified patient characteristics associated with low
procedural and clinical success rates of ablation, ie, longstanding CAF, short AFCL, and structural heart diseases with
concomitantly impaired cardiac function.
Mechanistic Insights From Ablation (Termination)
of Chronic AF
Different approaches for catheter ablation of AF have been
described mainly focusing on electrophysiological end points
of the arrhythmia substrate (eg, PV isolation, voltage reduction) rather than on the arrhythmia itself. Only 2 studies used
AF termination by ablation as the procedural end point.4,5,11
Haissaguerre et al4,5 were the first to describe an approach
with ablation of the AF substrate validated by electrophysi-
ological criteria, thereby progressively increasing the AFCL
and finally aiming to terminate the arrhythmia. Although
other studies, which had not sought to influence or terminate
the arrhythmia by ablation, reported an incidental termination
rate of ⬍30% by LA ablation,6,10,14,15 termination of CAF was
achieved in 87% of patients using the stepwise ablation
approach.4,5
Unlike in patients with paroxysmal AF, where the arrhythmia processes are predominantly confined to the PVs and its
junction to the LA, the multiple mechanisms of CAF require
an individually tailored approach.16 Nademanee et al11 first
described the ablation of complex fractionated atrial electrograms (CFAE) with promising results in terms of AF termination and long-term outcome. However, this procedure
merely targeted CFAE defined as fractionated electrograms
composed of 2 or more deflections or continuous deflections
of a prolonged activation complex with a cycle length ⱕ120
ms. In the study by Haissaguerre et al,4,5 4 different targets for
AF substrate ablation were distinguished: (1) areas of continuous electric activity (closest to the definition of CFAE),
(2) temporal activation gradient between proximal and distal
ablation bipoles, (3) spatial centrifugal activation, and (4)
areas of short cycle length activity. The suspected mechanisms behind these electrogram characteristics consist of
Rostock et al
Biatrial Substrate of CAF
351
Figure 7. Progression of the mean AFCL during
ablation in comparison of patients with CAF termination in LA, CS, RA, and those without termination. The mean baseline AFCL was significantly
shorter in patients without termination when compared with patients with AF termination. DC indicates external cardioversion.
Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017
slow conduction, eg, when a wavelet traverses through a
critical isthmus (1), microreentrant sources (rotors) or sites of
“pivot-pointing” around a cornerstone of a functional line of
block (2), and focal electric activity (3 and 4). When
starting a CAF ablation procedure, the initial AFCL used
to be short, indicating a complex interaction of multiple
and simultaneously operating AF processes. Thus, accurate
identification of areas that contribute actively to CAF often
remains challenging, particularly considering the cycle
length dependency of CFAE.13 Therefore, it is a reasonable
approach to start the procedure by targeting the sites with
the greatest impact on AFCL prolongation, ie, the PVs,
LAA, and inferior LA, and thereby facilitating a conceivable mapping of CAF.4,17
Swartz et al18 were the first to report on CAF termination
by ablation. In their series, biatrial linear lesions were created
in an attempt to replicate the Maze procedure, which resulted
in a remarkable success rate of up to 90%. In the study by
Nademanee et al,11 although achievement of AF termination
occurred in a relatively high number of patients, no data were
provided on the association between AF termination and
clinical outcome. Thus, it has remained unclear whether there
is a direct prognostic relation between AF termination by
ablation or, in other words, whether failure to terminate CAF
is associated with a worse long-term outcome. In their
subsequent series of patients treated for CAF using the
stepwise ablation approach, Haissaguerre and colleagues19
reported that patients with CAF termination rarely presented
with AF recurrences during the follow-up, whereas the
predominant recurrent arrhythmia in those patients was AT.
In addition to these findings, our study demonstrates a direct
relationship between failure to terminate CAF (in 2 procedures) and an unfavorable clinical outcome. Thus, the concept of AF termination by ablation emerges as a reasonable
procedural end point with a high prognostic value for the
clinical outcome.
Biatrial Substrate of Chronic AF
Historically, initial attempts of ablation procedures to treat
AF have been performed in the RA. Nevertheless, right atrial
linear ablation merely resulted in a modest reduction of AF
recurrences.20,21 Because the PVs were recognized as a
crucial substrate harboring AF sources,1 ablation procedures
with the intention to cure AF predominantly concentrated on
the LA and its adjacent great thoracic veins. This concept was
further corroborated by the observation of an activation
gradient from the left atrium to the RA,22 which is characteristically observed in patients with paroxysmal AF.23,24 However, this activation gradient was not demonstrated in patients
with long-standing AF,19 indicating the involvement of both
atria in the CAF process. Furthermore, data from biatrial
multielectrode mapping derived from electrophysiological
investigations and epicardial mapping performed at the time
of cardiac surgery suggested the presence of AF sources in
both atria.25,26 Although these data indicate a contribution of
the RA to the CAF process, only a limited number of studies
have investigated the impact of right atrial ablation on either
the long-term outcome or termination rate of CAF. Nademanee16
reported in their subsequent series of patients treated by
electrogram-guided ablation that 15% of the patients did require
ablation in the RA. Similarly, the stepwise ablation approach
necessitated RA ablation in 20% of patients to terminate CAF.21
Thus, previous data from observational studies underline
the contribution of RA substrates in the pathophysiology of
CAF. Furthermore, the demonstration of AF termination by
catheter ablation clearly indicates the presence of localized
right atrial arrhythmogenic sources driving AF. Those data
are therefore strikingly in line with the results of our present
study, revealing that AF termination occurred in one fourth of
patients during ablation in the RA, and thus providing an
accumulating body of evidence for the concept of “chronic
AF is a biatrial arrhythmia.”
Mechanisms and Clinical Relevance of
Subsequent ATs
Mechanisms of recurrent arrhythmias after PV isolation (both AF
and AT) have been described to be predominantly related to the
PVs themselves, comprising gap-related PV tachycardias and
macroreentry around ipsilateral PVs.27–29 However, the clinical
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December 2008
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significance of subsequent arrhythmias documented after termination of AF at the index procedure or during follow-up has
remained unclear.
The occurrence of ATs after extensive AF ablation has
generally been recognized as a procedure-related proarrhythmogenic side effect. Those ATs can be localized at virtually
all sites of the atria and their adjacent thoracic veins and
consist of macroreentry, microreentry, and focal tachycardia,
whereas the discrimination of the latter 2 is often challenging.30 Jais et al31 described ATs with a small circuit localized
to the anterior LA in patients who had undergone previous
AF ablation but without prior ablation at the anterior LA.
Thus, a potential mechanism of these ATs— other than being
proarrhythmic because of RF-induced slow conduction or
incomplete/recovered lesions—might be an “organization” of
the arrhythmia from AF to AT by diminishing the capability
to fibrillatory conduction of the substrate and thereby facilitating AF driving circuits to become apparent.
Using the stepwise ablation approach, it has been described
that patients with AF termination and conversion to AT
commonly present with ATs as recurrent arrhythmias, which
demonstrated a similar distribution to those contributing
initially to the maintenance of AF.5 This finding is supported
by the results of the present study. The majority of ATs
ablated during redo procedures were previously observed
during an earlier procedure, particularly when those ATs
were not targeted for ablation (because of a long-procedure
duration), were unsuccessfully ablated or when recovery of
the critical substrate occurred, indicating their clinical significance and the need of ablation treatment, subsequently.
Study Limitations
In the present study, no quantitative analysis of complex
fractionation has been performed. Thus, no information can
be provided with regard to the impact of each ablation step on
the distribution on electrogram fractionation.
All procedures were performed without using a 3-dimensional
mapping system. Therefore, we did not assess the scar burden
during redo procedures. However, considering a similar ablation
approach used in the present study compared with that described
by Haissaguerre et al,4,5 a comparable scar burden as described
by Takahashi et al32 can be assumed.
In 13 patients, the procedure was stopped prematurely because of
an extensive fluid administration. The use of a 3-dimensional
mapping system in conjunction with an (nonirrigated) 8-mm catheter tip might have prevented reaching this end point.
Because the baseline AFCL was ⱕ155 ms in all patients, a
relatively large portion of the LA displayed CFAE. Therefore, it
cannot be excluded that areas with CFAE caused by a short
AFCL (and thereby, passively activated and not actively involved in the AF process13) have been ablated. Pretreatment with
amiodarone before ablation may prolong the baseline AFCL and
consequently reduce the amount of passive fractionation.
An extensive ablation procedure as described in this study may
have the potential to create conditions critical for the development
of (new) ATs, particularly macroreentrant and microreentrant
tachycardias and, thereby, might be in part proarrhythmogenic.
The follow-up consisted of symptom-based and conventional
24-hour or 48-hour Holter monitoring for the assessment of AF
recurrences. Although the majority of patients were in persistent AF
when presenting with AF as their recurrent arrhythmia, asymptomatic recurrences might be missed during follow-up.
Conclusions
Termination of AF by ablation is an important prognostic end
point of catheter ablation for CAF. AF termination can be
achieved using a sequential ablation approach in both atria
and the CS, indicating a biatrial substrate of CAF. Subsequent
arrhythmias do often occur and successive ablation of those
arrhythmias is mandatory to achieve an arrhythmia-free
follow-up. Epidemiological and electrophysiological parameters, ie, exceedingly long-standing chronic AF, short AFCL,
and concomitant structural heart diseases with impaired
cardiac function, may help to identify patients with a potentially unfavorable outcome of CAF ablation.
Disclosures
None.
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CLINICAL PERSPECTIVE
Chronic atrial fibrillation (CAF) is a complex arrhythmia with the involvement of multiple atrial substrates, including the
great thoracic veins. The contribution of the right atrium to the CAF process has remained unclear, thus far. Considering
that termination of CAF by ablation is a result of the elimination of all arrhythmogenic substrates critical for arrhythmia
perpetuation, atrial fibrillation (AF) termination occurring in the right atrium may be an indicator for participation of the
right atrium in the fibrillatory process. In the present study, we performed a modified sequential ablation approach
consisting of pulmonary vein isolation and defragmentation of the left atrium, coronary sinus, and the right atrium in a
predefined order. CAF termination was achieved in 77% of patients. Interestingly, AF terminated in almost one half of the
patients during ablation outside the left atrium (26% in the right atrium and 19% in the coronary sinus). Patients with AF
termination predominantly presented with atrial tachycardia as the recurrent arrhythmia. After a follow-up of 20⫾4
months, 95% of patients with CAF termination were in sinus rhythm. However, almost all patients without CAF
termination in two procedures had AF recurrence and remained in CAF. These data indicate that “CAF is a biatrial
arrhythmia.” Furthermore, AF termination has emerged as an important prognostic end point of catheter ablation for CAF.
Chronic Atrial Fibrillation Is a Biatrial Arrhythmia: Data from Catheter Ablation of
Chronic Atrial Fibrillation Aiming Arrhythmia Termination Using a Sequential Ablation
Approach
Thomas Rostock, Daniel Steven, Boris Hoffmann, Helge Servatius, Imke Drewitz, Karsten
Sydow, Kai Müllerleile, Rodolfo Ventura, Karl Wegscheider, Thomas Meinertz and Stephan
Willems
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Circ Arrhythm Electrophysiol. 2008;1:344-353; originally published online December 2, 2008;
doi: 10.1161/CIRCEP.108.772392
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