Controversies in
Arrhythmia and
Electrophysiology
Is Ablation to Termination the Best Strategy
for Ablation of Persistent Atrial Fibrillation?
Ablation to Termination Is Not the Best Strategy
During Ablation
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Rakesh Latchamsetty, MD; Hakan Oral, MD
Mechanistic Considerations
“I’ll follow him around the Horn, and around the
Norway maelstrom, and around perdition’s flames before I give him up.”
-Captain Ahab, Moby Dick
“The mysterious thing you look for your whole life
will eventually eat you alive.”
-Laurie Anderson on Moby Dick
Rapid and repetitive depolarizations originating within or at
the antra of the pulmonary veins (PVs) and the other thoracic
veins are the predominant mechanism in the initiation and
perpetuation of paroxysmal atrial fibrillation (PAF).1–3 Antral
isolation of PVs and elimination of focal triggers and drivers
from other thoracic veins often result in termination and noninducibility of PAF in response to various pharmacological
and pacing protocols. Patients with PAF whose AF terminated
during ablation and were rendered noninducible, also were
more likely to remain in sinus rhythm during long-term clinical follow-up.4,5 In essence, termination and noninducibility in
these patients suggested successful elimination of the primary
mechanism of AF and absence of additional mechanisms and
may have simply facilitated selection of patients whose AF
was thoracic vein dependent. The subset of patients with PAF
who remain in AF after PVI may have residual mechanisms,
which may be fewer, more likely to be focal triggers and
more readily amenable to mapping and additional ablation in
patients with paroxysmal than persistent AF.
Based on these observations in PAF and limited efficacy of PVI in patients with persistent AF, termination to
sinus rhythm was also pursued as a procedural end point in
patients with persistent AF using a variety of ablation strategies. The key for evaluating the validity and efficacy of each
of these approaches is a sound understanding of the prevailing mechanism(s) of human AF (Figure).6–10 However, to date,
O
ptimal strategy and end points for ablation of persistent
atrial fibrillation (AF) have not been well established.
Although antral pulmonary vein isolation (PVI) is often effective for ablation of paroxysmal AF, it is an insufficient standalone strategy for many patients with persistent AF. Selection
of adjunctive targets and determination of procedural end
points are variable and at the discretion of the operator. Several
studies suggested that termination of AF should be the procedural end point during ablation in patients with persistent AF,
as a higher probability of maintaining sinus rhythm after the
ablation was reported, despite a long procedure duration and a
high rate of repeat ablation procedures. However, these studies were not consistently reproducible, and conversion usually occurred to an atrial tachycardia rather than sinus rhythm
after extensive ablation. In patients with persistent AF, there
is insufficient experimental, mechanistic, or clinical evidence
to support termination of AF during ablation as a procedural
end point.
Response by Lim et al on p 980
Received March 18, 2015; accepted July 6, 2015.
From the Department of Internal Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor.
Correspondence to Hakan Oral, MD, University of Michigan Health System, CVC, SPC 5853, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5853.
E-mail [email protected]
(Circ Arrhythm Electrophysiol. 2015;8:972-980. DOI: 10.1161/CIRCEP.115.001722.)
© 2015 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org
972
DOI: 10.1161/CIRCEP.115.001722
Latchamsetty and Oral Ablation of Persistent Atrial Fibrillation 973
these mechanisms have been primarily based on extrapolation
of observations from experimental models.
In persistent AF, a multicomponent system is likely to be
critical with a continual interplay between a trigger/initiator/driver and a perpetuator(s). Termination of AF has been
thought to indicate effective elimination of these components
of AF and therefore should subsequently translate into an
improvement in clinical outcomes. However, several assumptions are made to reach this conclusion:
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1.Although spatiotemporal stability of high-frequency rotors of AF has been demonstrated in experimental models that used optical mapping techniques, it is also recognized that these drivers are stable for only a few hundred
milliseconds to a few seconds and meander for several
centimeters. It has been suggested that these rotors may
have anchor points at usually targeted sites during catheter ablation, such as the antrum of the PVs and fixed
anatomical landmarks. It is not clear whether the rotors
use the same path or anchor at similar sites during consecutive episodes of AF. Even if rotors could be accurately identified and mapped in real-time, termination of
AF during ablation at that time point would only indicate
that rotors sustaining AF at that instant were eliminated
and no other mechanisms were simultaneously operative. This does not necessarily indicate that the targeted
site is no longer able to sustain any future potential rotors nor does it preclude the existence of other potential
sites to harbor future rotors.
2.It has long been recognized that pathogenesis of AF is
often progressive.11–13 Therefore, effective elimination of
prevailing mechanisms of AF during ablation may not
prevent development of new mechanisms with subsequent clinical recurrences.
3.Even if all mechanisms of AF are successfully ablated,
recovery of conduction is a frequent limitation of current
ablation technology. Recurrences may not necessarily
indicate incomplete ablation.
4.It is important to recognize the nuance between termination and noninducibility of AF. In patients with paroxysmal AF, both termination and noninducibility have been
sought as procedural end points and predict a higher
probability of maintaining sinus rhythm after ablation.
However, in patients with persistent AF, reinduction after termination of AF is often not attempted, as it is likely
to reinduce AF.14 Although termination may indicate effective suppression or elimination of mechanisms of AF
operative at a certain point in time, it does not rule out
Figure. A schematic illustration of pathogenesis of atrial fibrillation. Reprinted from Nishida et al10 with permission of the publisher. Copyright
©2014, Wolters Kluwer Health. AF indicates atrial fibrillation; AP, action potential; and PV, pulmonary vein.
974 Circ Arrhythm Electrophysiol August 2015
the presence of residual drivers/perpetuators, which may
be elicited with attempts at reinduction or potentially be
dormant at the time of the procedure. For example, in a
recent study, a dominant driver could not be identified
for ≈40% of the duration of AF.15
5.Persistent AF encompasses a broad spectrum of patients
with mild to severe electroanatomical remodeling. It is
well recognized that duration of AF and left atrial size
play an important role in response to therapy. A recent
study also suggested that the longer the duration of AF,
the greater the number of rotors present.15 Therefore,
comparative analysis of outcomes can be challenging in
patients with persistent or long-standing persistent AF.
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Experimental and Clinical Evidence
Surgical Experience
Initial attempts at nonpharmacologic long-term rhythm control for AF consisted of the surgical cut-and-sew maze technique.16 The original version of this technique was ultimately
abandoned because of its technical complexity, development
of sinus node dysfunction, and left atrial dysfunction.17 Modifications led to the Cox maze III procedure, which mitigated
these issues and was technically less demanding.18 Subsequent
revisions of the maze technique involved alternative energy
sources and less invasive approaches, however, at the cost of a
decrease in procedural efficacy.19
Although stand-alone surgical maze procedures have largely
been supplanted by less invasive catheter ablation procedures,
the original cut-and-sew technique did produce favorable longterm outcomes and at least conceptually provide a paradigm for
attainable long-term results through atrial substrate modification. A single-center study of 112 patients who underwent the
Cox maze III procedure for lone atrial fibrillation had an 83%
freedom from AF off antiarrhythmic medications (no difference
between the paroxysmal and persistent groups) at a median
follow-up of 5.9 years.20 It is important to note that these results
were produced by a purely anatomic strategy designed to compartmentalize the atria and limit adequate substrate to initiate
and maintain AF and did not use any real-time mapping strategy
to identify drivers or perpetuators of AF. Many of these patients
eventually required cardioversion after the procedure or before
discharge but still maintained sinus rhythm in the long-term,
highlighting the fact that acute conversion to sinus rhythm is
not essential for long-term success.
Catheter Ablation
No single strategy has been clearly demonstrated to offer superior outcomes in patients with AF compared with antral PVI.
Several studies, however, attempted to determine the role of
additional ablation after PVI in patients with persistent AF.
These approaches included ablation of complex-fractionated
atrial electrograms (CFAE), targeting local cycle length (frequency) gradients, linear ablation between fixed anatomical
structures, isolation of the superior vena cava, ablation of the
coronary sinus or ligament of Marshall, electrical isolation
of the left atrial appendage, targeting ganglionated plexi, or a
combination of these approaches as in the step-wise ablation
approach.21–28 End points of these ablation strategies can be
variable. When an anatomic ablation strategy such as linear
ablation and isolation of other thoracic veins is pursued, termination often is not sought after as a procedural end point. However, when electrogram-guided or hybrid approaches (such as in
stepwise ablation) are used, either conversion to sinus rhythm
or atrial tachycardia or a reduction in AF activation rate is frequently the intended end point of ablation, yet it may not always
be achievable. To date, whether termination of AF during ablation indeed improves clinical outcomes remains unclear.
CFAE Ablation
Ablation of CFAEs was originally proposed as a method to
eliminate triggers and drivers of AF,26 with termination of
AF during ablation in 91% of patients and freedom from
AF in 91% of patients at 1-year follow-up (inclusive of 47%
patients with paroxysmal AF). However, in subsequent studies, both the termination and clinical efficacy rates have been
lower at 33% to 50%.29,30 CFAEs have been defined as atrial
electrograms with a short cycle length (<120 ms), fractionation, or continuous electric activity and can be identified
either manually or with automated algorithms. CFAEs have
been proposed to indicate sites of slow conduction, wavefront
collision, pivot points for high-frequency sources, reentrant
circuits, ganglionated plexi, or fibrillatory conduction whose
benefit as a target can range from specific rotor elimination
or containment, to modification of autonomic input, to simple debulking of the atria because of extensive ablation.31–34
CFAEs lack specificity as targets and may prompt extensive
unnecessary ablation with the risk of an increase in complications, including atrial contractile dysfunction, proarrhythmia
in the form of atrial flutter or tachycardia, inadvertent isolation of the left atrial appendage, and thromboembolic events.
Although few earlier studies suggested incremental benefit of
CFAE ablation in addition to PVI in patients with persistent
AF,35 a recent trial that randomized 589 patients undergoing
ablation of persistent AF to PVI alone versus PVI and CFAE
ablation versus PVI and linear ablation showed no difference
among the groups in terms of freedom from AF at 18 months
after ablation (59% versus 49% versus 46%; P=0.15).36
Linear Ablation
Linear ablation can be performed to interrupt existing or
potential macroreentrant atrial circuits and can also serve to
debulk/compartmentalize the atrial substrate. The most commonly applied linear lesion sets are the left atrial roof and
mitral isthmus lines. In patients with persistent AF, linear
ablation likely provides additional benefit to PVI in overall
sinus rhythm maintenance,37 however, may increase the risk of
recurrent macroreentrant atrial tachycardias.38 Although linear
ablation alone has previously been shown to convert some
patients in AF directly to sinus rhythm,39 it is primarily used to
Latchamsetty and Oral Ablation of Persistent Atrial Fibrillation 975
address macroreentrant tachycardias that AF can organize into
(or at times may coexist during AF40) and to further debulk
atrial substrate. Although linear ablation alone rarely terminates AF, in a stepwise ablation strategy, linear ablation was
required in ≤80% of patients with persistent AF after isolation
of the PVs and ablation of complex electrograms to terminate
AF. The 2 possible explanations of this observation are
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1.Sites where linear ablation is typically performed usually harbor residual drivers of AF, which become manifest and perpetuate AF after elimination of other drivers
elsewhere in the atria.
2.Linear ablation simply results in debulking and compartmentalization of the atria similar to the classic maze procedure and eliminates fibrillatory conduction without targeting specific drivers of AF. In fact, redo procedures are
frequently performed after stepwise ablation, and the predominant recurrent arrhythmia is an atrial flutter or tachycardia, which may have been initiated by the same trigger
or driver that would have initiated AF if it were not for
elimination of fibrillatory conduction by linear ablation.
Real-Time Mapping of Focal
Sources and Rotors
Spectral Mapping of Sites With a High DF
Real-time mapping in an attempt to identify ablation targets
through spectral analysis has been proposed following the
observation that sites where AF termination occurred during
ablation often had higher DF.41 Decreases in DF as measured in
the coronary sinus and elimination of intra-atrial or interatrial
DF gradients have been predictive of long-term success and
maintenance of sinus rhythm in some studies.27,42,43 However,
prospective attempts targeting high DF sites have not consistently produced improved long-tem efficacy. The limitations of
spectral mapping to identify sites with the highest DF include:
1. Spatiotemporal instability of the high-frequency sources:
rotors have been recognized to meander in experimental
models and may not last for more than a few hundred
milliseconds.44
2.Most current mapping strategies are limited to the endocardium, whereas studies have shown reentrant circuits also using epicardial and intramural substrates.45
Although endocardial ablation can achieve transmural
lesions, strictly endocardial mapping to reliably identify
high-frequency sources may be inadequate.
3.Spectral mapping is sensitive to far-field contamination
particularly from the left atrial appendage and the ventricle. Accurate spectral mapping requires high-density
mapping, preferably optical mapping, which is not feasible in the clinical setting.
4.A trigger or driver may engage and initiate a perpetuator or rotor, which may have a higher DF than the trigger itself. Ablation of the higher frequency perpetuator
may not necessarily result in elimination of the primary driver(s) of AF. In a prior study, rotors were most
prevalent around the antrum of the PVs where primary
triggers of AF in the form of PV tachycardias have been
long recognized to exist.15
In a recent study, 117 patients with persistent AF were randomized to PVI alone versus PVI and targeting of areas with
high-frequency atrial electrograms. Clinical outcomes were
similar at 6 and 12 months. Only 12% of patients converted
to sinus rhythm during targeting of high-frequency atrial
electrograms.46
Mapping of Focal Sources and Rotors
Subsequent to the demonstration of rotors as a mechanism
critical to perpetuation of AF in experimental models that used
optical phase maps with voltage-sensitive dyes, panoramic
electrogram mapping of the atria using multipolar basket
catheters with off-line phase analysis using Hilbert transformation has been reported to demonstrate rotors in early clinical studies (focal impulse and rotor modulation [FIRM]).47,48
These sites were targeted by focal ablation in conjunction with
PVI. In the pivotal Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation
(CONFIRM) study, an improvement in 1- to 3- year outcomes
when compared with a control group of patients who underwent antral PVI was reported.47,49 The FIRM-blinded success
rates in these studies, however, were considerably lower than
in most other studies and reported at 38%, during nearly 3
years of follow-up.47 Although termination to sinus rhythm
was achieved with low duration of energy application, overall
conversion to sinus rhythm during ablation was still only near
50% in both persistent and paroxysmal patients.28 Limitations
of the FIRM approach may include:
1.Reproducibility of the results of the original study.
2.Electrograms with sufficient quality for any meaningful analysis can often not be recorded in >50% of the
electrograms of a basket catheter and interpolation of the
missing data is a crucial component of the FIRM analysis. However, interpolation depends on many assumptions, which may not be valid. Moreover, interpolation
of data based on reverse solution of a Hilbert transform
can be inherently problematic. In a recent study, off-line
analysis of data from patients undergoing FIRM-guided
ablation demonstrated that there was no difference between rotor and distant sites in DF or Shannon entropy,
and there was no rotational activation at FIRM-identified
rotor sites in the vast majority of the patients.50
3.Phase maps generated by FIRM analysis demonstrate sustained, stable rotors for minutes if not longer.
However, both experimental models and analysis of
body surface maps suggest that rotors often are not stable for extended periods of time.
Body Surface Mapping
In a recent study, ablation was guided by mapping of driver
domains using noninvasive body surface mapping in patients
with persistent AF.15 The median number of driver domains
976 Circ Arrhythm Electrophysiol August 2015
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targeted increased from 2 to 6 as the duration of AF became
longer. Unlike in FIRM-guided ablation, drivers were often
unstable, lasting for a mean of ≈400 ms. There was no driver
activity recorded in ≈40% of the duration of AF. It was estimated that 80% of the drivers were reentrant and 20% were
focal, and 30% resided in the right atrium. Because the drivers
were unstable, the investigators used a density/cluster map of
putative target sites in the descending priority of prevalence.
AF terminated to sinus rhythm in 30% and to an atrial tachycardia in 55%. There was an inverse relationship between
AF termination rate and the duration of AF. Despite additional linear ablation in some patients, AF termination rate
was 15% in patients with long-standing persistent AF. Driver
regions tended to cluster around the antrum of the PVs and
the appendages. Reentrant drivers were also identified close
to focal drivers. Compared with patients who had typical
stepwise ablation (without body surface mapping), a similar
proportion of patients were in sinus rhythm at 12 months of
follow-up, however, the duration of ablation was significantly
shorter in the driver-mapping group. Although the authors
report that patients who had termination of AF were more
likely to remain in sinus rhythm than those without termination (85% versus 63%, P=0.045), patients who had longstanding persistent AF were less likely to terminate.
Therefore, it is possible that termination of AF simply
identifies patients who have lesser electroanatomical remodeling and more likely to remain in sinus rhythm regardless of
the ablation strategy. Furthermore, termination to sinus rhythm
occurred in only 30% and the majority of patients converted
to an atrial tachycardia, which may simply be because of
elimination of fibrillatory conduction rather than the ablation
of specific drivers. These patients may be more susceptible
to recurrences either through residual drivers or because of
incomplete linear ablation. Limited spatiotemporal resolution,
short sampling duration (5 s), the need to sample electrograms
only between QRS complexes, extensive signal processing,
Table. need for interpolation with assumptions on phase mapping,
and inherent inability of the algorithms to detect macroreentrant circuits should be taken into consideration when interpreting the results of this early study. In 85% of the patients
with long-standing persistent AF, in whom extensive electroanatomical remodeling is expected, drivers could not be identified and AF could not be terminated. The instability of the
drivers and extensive meandering reported can be explained by
the limited resolution of the mapping system and three-dimensional nature of the rotors more as filaments as reported in
experimental models.51 Endocardial–epicardial dissociation of
reentrant breakthroughs has been demonstrated in experimental models.52 Furthermore, scroll waves have been modeled to
follow the path of least resistance, often parallel to the myocardial fibers which usually run parallel to the atrial endocardium.
Therefore, endocardial breakthroughs may not be readily identified.53 It is also possible that rotors may represent bystander
activation in response to adjacent primary focal discharges.
A helpful approach would have been to compare the driver
maps before and after ablation in patients who did and did
not have termination of AF using both FIRM and body surface mapping approaches. At present, there is limited evidence
that rotors play a causal role in perpetuation of human AF and
whether what is ablated is a true rotor.
There are no established guidelines dictating procedural
end points during ablation of persistent AF. A review of recent
studies in the past 5 years, in which ablation was performed
with a goal of conversion to sinus rhythm in patients with persistent AF shows a large disparity in overall successful conversion to sinus rhythm rate with a range of 14% to 68% (Table).
Long-term success rates ranged from 40% to 75% with the
majority of follow-up cited at about 2 years, similar to the
results of most published studies evaluating outcomes for
ablation of persistent AF. Furthermore, these studies were not
randomized controlled trials.
Clinical Studies and Termination of AF During Ablation
Study
No. of Patients, AF Type
Percent Conversion to SR
During Ablation
Mean Procedure Time
62.5% (29% directly to
sinus, 33% via AT)
Miyazaki et al57 135, persistent AF
(76 long-standing)
PVI, LA/RA substrate
modification
51% (16% directly to
sinus, 36% to AT)
Zhou et al58
PVI, roof line, CFAE ablation
47% (16% directly to
sinus, 31% via AT)
300 min (termination)
vs 330 min (CV)
Komatsu et al59 132, persistent AF
PVI, CFAE ablation
39% (13% directly to sinus)
184 min
Wang et al60
293, persistent AF
Stepwise ablation
45% (11% directly to sinus)
Park et al61
140, long-standing
persistent AF
PVI, left and right CFAE
ablation
68% (24% directly to sinus)
328 min (termination)
vs 376 min (CV)
43% SR without AAD at 19
mo after 1 procedure
Elayi et al54
306, long-standing
persistent AF
PVI, CFAE ablation
14% (2% directly to sinus)
249 min
69% SR without AAD at
25 mo
200, persistent AF
145 min
Outcomes
Pure linear ablation with
bidirectional block
Wu et al
39
120, persistent AF
Primary Ablation Strategy
40% at 5.1 y after single
procedure
74% free from AF at 15 mo
61.5% free from AF at
46.4 mo
68% free from AF at 20 mo
60% to 67% SR
maintenance at 23 mo
AAD indicates antiarrhythmic drugs; AF, atrial fibrillation AT, atrial tachycardia; CFAE, complex-fractionated atrial electrograms; CV, cardioversion; LA, left atrium; PVI,
pulmonary vein isolation; RA, right atrium; and SR, sinus rhythm.
Latchamsetty and Oral Ablation of Persistent Atrial Fibrillation 977
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In the largest of these studies by Elayi et al,54 ablation was
performed in 306 patients with persistent AF. With extensive
ablation (mean procedure time, 249±93 minutes), including antral PV and posterior left atrial isolation, elimination of
CFAEs, and targeting of all atrial tachycardias including linear
ablation, only 14% of the patients ultimately converted to sinus
rhythm. Despite this, 69% of patients maintained sinus rhythm
at 2 years without antiarrhythmic drugs. In this study, conversion to sinus rhythm actually did not predict long-term sinus
rhythm maintenance but rather just the mode of atrial arrhythmia recurrence. In the next largest study by Wang et al, 293
patients underwent stepwise ablation for persistent AF during
which 45% of patients eventually were ablated to sinus rhythm.
Sinus rhythm maintenance at nearly 2 years was similar between
patients ultimately ablated to sinus rhythm versus patients who
underwent cardioversion (67.2% versus 59.8%, P=0.198). Only
few patients (11.3%) who converted directly to sinus rhythm
were found to have improved long-term outcomes.
A recently published study reported the long-term outcomes of a strategy of ablation of persistent AF with a stepwise
approach using PVI, linear ablation, and electrogram-guided
ablation with a procedural end point of AF termination.55 This
study did report a high rate of conversion during ablation to
sinus rhythm at 80% with a mean procedure time of 264 minutes. However, single procedure success rate at 70 months was
only 15%. After a mean of 2.1 procedures per patient, successful maintenance of sinus rhythm was achieved in 65% of the
patients without antiarrhythmic drugs after a median follow-up
of 58 months, although long-term monitoring in these patients
was limited. Despite the high conversion rate during ablation,
these outcomes again are not remarkably higher than in other
studies with much lower rates of conversion to sinus rhythm,
suggesting the benefit during the stepwise approach lies not
primarily with acute AF termination but rather the broader electroanatomic changes to the atrial substrate. This is supported by
the findings in another recent prospective study that randomized
patients undergoing ablation of persistent AF to the stepwise
ablative approach versus a fixed anatomic approach consisting of PVI, mitral isthmus and roof lines, and a cavo-tricuspid
isthmus line. This study showed no significant difference in
freedom from atrial arrhythmias at one year after the ablation
despite shorter procedural and radiofrequency time with the
fixed anatomic approach.56
With the current technology and available outcomes data,
there is lack of sufficient experimental and clinical evidence
to support termination as the procedural end point during
ablation in patients with persistent AF. Extensive ablation
in pursuit of the often elusive goal of AF termination may
lead to unnecessarily lengthy procedures with the risk of an
increase in complications without an improvement in longterm outcomes.
Conclusions
Three fundamental questions remain unanswered: (1) What
are the specific mechanisms of human atrial fibrillation? (2)
Can these mechanisms be accurately identified and targeted?
and (3) Do targeted ablation strategies improve patient outcomes? Until these important questions are answered, there
is little or no justification for pursuing termination of AF as a
procedural end point during catheter ablation of persistent AF.
At an age when we can land a spaceship on a comet; when
we can receive and process signals from outer space, millions of light-years away; and when we can identify the Higgs
boson, can we really not map and understand the mechanisms
of human AF?
We should be able to. However, this will require a broad
scale, open-source, and open-minded collaboration among
physicists, engineers, scientists, and clinicians across the
world with a focus on observing and understanding the nature
first rather than trying to prove a hypothesis. After all, as
Thomas Huxley once said “It is about what is right, not who is
right (or more contemporarily, not whose hypothesis or technology will prevail).”
It is time…
Disclosures
Dr Oral is a founder and equity holder of Rhythm Solutions. Dr
Latchamsetty reports no conflicts.
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Key Words: atrial fibrillation ◼ arrhythmias, cardiac ◼ catheter ablation
◼ pulmonary veins ◼ therapeutics
980 Circ Arrhythm Electrophysiol August 2015
Response to Rakesh Latchamsetty, MD, and Hakan Oral, MD
Han S. Lim, MBBS, PhD; Nicolas Derval, MD; Yuki Komatsu, MD; Stephan Zellerhoff; Arnaud Denis, MD;
Ashok J. Shah, MD; Frédéric Sacher, MD; Mélèze Hocini, MD; Pierre Jaïs, MD; and Michel Haïssaguerre, MD
Downloaded from http://circep.ahajournals.org/ by guest on July 28, 2017
Latchamsetty and Oral acknowledge that current ablation strategies are not well established, and that pulmonary vein isolation is an insufficient stand-alone strategy for many patients with persistent atrial fibrillation (PsAF). The authors correctly
identify some of the challenges facing PsAF ablation, such as the lack of a distinct procedural endpoint, inconsistent findings
between different studies, current technological limitations, and the broad spectrum of patients with PsAF. However, it is
precisely in addressing these issues that AF termination plays a key role. Numerous animal, pharmacological, cardioversion,
and ablation studies have demonstrated that successful termination of the arrhythmia by the various means is associated with
improved outcomes.
Termination of AF indicates successful elimination of the drivers or perpetuators in a particular patient such that AF can no
longer be sustained. The authors discussed several mechanistic considerations for AF termination including the notion that
pathogenesis of AF is often progressive. This is most likely because of the underlying risk factors for AF causing progressive
substrate changes, as shown in recent studies. Therefore, AF ablation should be complemented with strict management of
underlying cardiovascular risk factors and efforts to minimize the extent of atrial remodeling and duration of PsAF before
ablation. From the ablation perspective, termination of AF offers the greatest possibility that AF drivers at the time of the procedure are eliminated. It is true that PsAF encompasses a broad spectrum of patients with mild-to-severe atrial remodeling.
A strategy aiming for AF termination would stratify these patients to mild forms of PsAF where less ablation is required, to
more severe forms of PsAF necessitating further substrate ablation. As mentioned by the authors, catheter ablation endpoints
can be variable—AF termination provides a nonambiguous endpoint that can be measured across different studies. Indeed,
complex-fractionated atrial electrograms lack specificity. Newer mapping techniques, such as panoramic noninvasive and
invasive mapping, provide increased specificity in identifying AF drivers and an unprecedented view of the global AF
process. However, these studies also revealed the dissemination of arrhythmogenic substrate within a 6 to 12-month time
frame, confirming experimental studies, and the involvement of widespread biatrial regions in long-standing PsAF. In the
latter cases, the incidence of AF termination is much lower and difficult to achieve, and it would be important to evaluate if
certain driver regions may diminish during reverse remodeling and thus be spared from extensive ablation to the point of AF
termination. Although current means for achieving AF termination are constrained by technological limitations, they do not
signify that the ends of achieving AF termination are unfitting.
In addressing the current challenges facing PsAF ablation, AF termination provides (1) a distinct procedural endpoint, (2)
an objective measure that can be compared across studies, (3) improved long-term clinical outcomes, (4) a patient-tailored
approach such that patient-specific drivers are targeted, and (5) stratification of the extent of ablation to determine which
patients may require further ablation beyond pulmonary vein isolation, and which patients in whom extensive ablation may
be avoided across the broad spectrum of patients with PsAF.
Is Ablation to Termination the Best Strategy for Ablation of Persistent Atrial
Fibrillation?: Ablation to Termination Is Not the Best Strategy During Ablation
Rakesh Latchamsetty and Hakan Oral
Downloaded from http://circep.ahajournals.org/ by guest on July 28, 2017
Circ Arrhythm Electrophysiol. 2015;8:972-980
doi: 10.1161/CIRCEP.115.001722
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