Who Needs Catheter Ablation And Which Approach?
Duygu Kocyigit MD, Ugur Canpolat MD,Assistant Professor, Kudret Aytemir MD, Professor
Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Catheter ablation therapy for atrial fibrillation (AF) has gained a significant role during maintenance of sinus rhythm compared to anti-arrhythmic medication. Catheter ablation techniques are also improved and progressed over years in parallel to better understanding of disease mechanisms and technological advancements. However, due to invasive nature of the therapy with its pertinent procedural risks, both appropriate patient selection and use of relevant approach should be considered by all electrophysiologists before decide to perform catheter ablation.
Key Words : Catheter Ablation, Atrial Fibrillation.
Correspondence to: Dr. Uğur Canpolat, MD. Hacettepe University Faculty of Medicine, Department of Cardiology, Ankara, Turkey.
Atrial fibrillation (AF) affects approximately 30 million individuals worldwide and is known as a major cause of stroke, heart failure, hospitalizations and death.1 The recognition for the first time that, in a subset of patients, AF was triggered by a rapidly firing focus and could be “cured” with a localized ablation procedure eventually led to the progressive innovations in catheter ablation technologies.2 Percutaneous catheter ablation is now an evidenced and established therapeutic option for rhythm control in selected AF patients with reasonable safety and efficacy.3 However, success rates for persistent AF ablation still remain far lower than paroxysmal AF, despite a large spectrum of ablation strategies.3 Therefore, appropriate AF patient selection with relevant catheter ablation technique should be considered by all electrophysiologists during treatment of AF via rhythm control strategy.
This review addresses current approaches in the field of catheter ablation for AF.
A number of systematic reviews have been performed to evaluate the efficacy of catheter ablation versus antiarrhythmic drug therapy for AF.4-6 The efficacy of radiofrequency catheter ablation for maintaining sinus rhythm (SR) has been found to be superior to current antiarrhythmic drug therapy for providing freedom from symptomatic AF and improving quality of life in selected patient populations.7-9 Studies have also demonstrated a reduction of AF-related symptoms.10 However, evidence is insufficient to determine whether catheter ablation reduces all-cause mortality, stroke, or heart failure (HF).
Evidence supporting the efficacy of catheter ablation is strongest for paroxysmal AF in younger patients with little or no structural heart disease.11
First, reversible causes of AF should be investigated thoroughly prior to giving consideration to catheter ablation. These include evaluation for hyperthyroidism, pulmonary embolism, myocardial ischemia/infarction, heavy alcohol consumption, recent cardiac surgery and other acute inflammatory/infectious processes. Supraventricular arrhythmias, such as atrioventricular (AV) nodal reentry, AV reentry tachycardia, or atrial tachycardia may also serve as triggers for AF, therefore eliminating those supraventricular tachycardia episodes may help limit or eliminate episodes of AF.
Beyond these, determining whether a patient is an appropriate candidate for catheter ablation depends on various factors, including the type of AF (paroxysmal, persistent, or long-standing persistent), severity of symptoms, presence of structural heart disease, candidacy for alternative options such as rate control or antiarrhythmic drug therapy, likelihood of complications, and patient preference.3 When patient preference is excluded, the primary selection criterion for catheter ablation should be the presence of symptomatic AF.3
ACC/AHA guidelines11 have stated that AF catheter ablation:
a) is useful for symptomatic paroxysmal AF [Class I, level of evidence (LOE): A];
b) is reasonable for selected patients with symptomatic persistent AF (Class IIa, LOE: A);
c) may be considered for symptomatic long-standing (>12 months) persistent AF (Class IIb, LOE: B) refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm control strategy is desired.
The difference in recommendations of HRS/EHRA/ECAS guidelines3 from ACC/AHA guidelines is that AF catheter ablation
is reasonable for selected patients with symptomatic persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication
with Class IIa, LOE: B indication.
ESC guidelines12 have recommended catheter ablation of symptomatic
paroxysmal AF in patients who have symptomatic recurrences
of AF on antiarrhythmic drug therapy and who prefer further
rhythm control therapy (Class I, LOE: A). They have also stated that
catheter ablation of AF should be considered as first-line therapy in
selected patients with symptomatic paroxysmal AF as an alternative
to antiarrhythmic drug therapy, considering patient choice, benefit,
and risk (Class IIa, LOE: B).12 HRS/EHRA/ECAS guideline3 have
additionally mentioned that catheter ablation as first-line therapy
could be considered in persistent AF (Class IIb, LOE: C) and might
be considered in long-standing persistent AF patients (Class IIb,
LOE: C).
It is not recommended to perform catheter ablation for AF in patients
who cannot receive anticoagulant therapy during and following
the procedure (Class III, LOE: C).11
At last but not least, when catheter ablation is found appropriate
for a patient, some patient characteristics that are known to increase
the incidence and burden of AF should be corrected prior to catheter
ablation to improve procedural outcomes. For instance, recent studies
have demonstrated the importance of weight loss and sleep apnea
treatment prior to ablation.13
Catheter Ablation In Special Patient Populations
The safety and efficacy of catheter ablation are less well established
for some populations of patients, especially very elderly patients, and
patients with significant HF.3
Restoring sinus rhythm has a positive impact on heart failure as
atrial contraction and AV synchrony are important contributors to
total cardiac output. In patients who suffer from symptomatic AF
recurrences on amiodarone therapy, catheter ablation remains as the
sole choice for escalated rhythm control therapy. It is indicated to
improve AF-related symptoms (EHRA score II–IV).12
Studies evaluating the role of catheter ablation for AF in HF
patients have demonstrated an acceptable rate of successful sinus
rhythm maintenance with improvements in left ventricular ejection
fraction (LVEF) and symptoms.14-16 Therefore, most clinicians reserve
AV node ablation/biventricular pacing for elderly patients, patients
with significant comorbidities who would not tolerate catheter
ablation for AF, or patients with preexisting biventricular implantable
cardioverter defibrillators and AF with ventricular response rates
rapid enough to limit the amount of biventricular pacing.
The degree of LVEF improvement varies according to patient
characteristics.17 For instance, where the LV dysfunction is thought
to be due to AF itself, AF catheter ablation and maintenance of sinus
rhythm may result in a marked improvement. Improved rate control
or cardioversion with antiarrhythmic drug therapy may help predict
the outcomes of catheter ablation in such cases. On the other hand,
in patients with HF who develop AF, a rhythm-control strategy is
not superior to a rate-control strategy.18
Due to the extent of remodeling and underlying heart disease, recurrence19
and complication rates are higher in this population. A
meta-analysis had reported that the single-procedure efficacy of AF catheter ablation was lower in patients with systolic dysfunction, but
a similar success rate could be achieved among patients with and
without systolic dysfunction with repeat procedures.20 Recently, in a
study including 81 patients with LVEF≤45%, Rillig et al.21 showed
that single-procedure success rates after PVI during 6 years of follow-
up were low (35.1%). In patients with single- or multiple-procedure
ablation success, a higher improvement of LVEF was observed.
Another long-term follow-up study has shown that at 5 years, 60.7%
of patients with systolic heart failure had clinical recurrence of AF.22
In a systematic review23 including 26 randomized controlled trials,
clinical trials, and observational studies of patients with left ventricular
systolic dysfunction undergoing catheter ablation for AF, efficacy
in maintaining sinus rhythm at a mean follow-up of 23 months
was found to be 60%. Left ventricular ejection fraction significantly
improved during follow-up by 13%. A recent meta-analysis of 4
trials (n=224) which randomized HF patients (LVEF<50%) with
persistent AF to a rate control or AF catheter ablation strategy, AF
catheter ablation has been reported to be superior to rate control in
improving LVEF, quality of life and functional capacity.24
Other than systolic heart failure, severe diastolic left ventricular
dysfunction has also been shown to result in a higher risk of AF
recurrence after catheter ablation.25
Age was shown to be an independent predictor of AF recurrence
following catheter ablation for AF.26 Hsieh et al.27 compared outcomes
after catheter ablation for AF and AV node ablation in 71
patients >65 years at a mean follow-up of 52 months. Patients who
had ablation of AF were more likely to have symptomatic AF, less
persistent AF, better New York Heart Association functional class
and less heart failure than the patients who underwent AV node ablation.
However, the prevalence of stroke, mortality and other complications
were similar between the AF ablation and AV node ablation
groups. Corrado et al.28 showed that catheter ablation for AF in
174 patients older than 75 years resulted in a clinical efficacy of 73
and 80% after single and repeat ablation procedures, respectively at a
mean follow-up of 22 months. Zado et al.29 also compared the safety
and efficacy of catheter ablation in three groups of patients: <65, 65-
74, and ≥75 years over a 27 month follow-up period. Patients over
the age of 75 were more likely to demonstrate a partial response to
ablation and require antiarrhythmic drug therapy. Another study had
stratified 1548 patients who underwent AF ablation according to age
<45, 45–54, 55–64 and ≥65 years. Outcomes, defined as rare or no
AF with or without antiarrhythmic drugs, were similar in all groups
with an 82–88% success rate.30 In another study, 35 octogenarians
undergoing AF ablation were compared to 717 younger patients also
undergoing RF ablation. They found similar success rates of 78 and
75%, respectively.31 Another study looked prospectively at 103 octogenarians
compared with 2651 younger patients, and found 69% of
octogenarians were free of AF compared with 71% of their younger
peers.32 However, both Spragg et al.33 and Shah et al.34 reported that
older age has been significantly associated with a higher risk of complications,
suggesting careful assessment of the risk/benefit profile in
these patients before catheter ablation for AF.
Patients With Hypertrophic Cardiomyopathy (HCM)
ACC/ AHA guidelines11 have stated that AF catheter ablation
can be beneficial in patients with HCM in whom a rhythm-control strategy is desired when antiarrhythmic drugs fail or are not tolerated
(class IIa, LOE: B). Contreras-Valdes et al.35 have compared
long-term arrhythmia control among patients with HCM and a
non-affected cohort and found that the efficacy of AF ablation is significantly
lower compared with non-affected patients, irrespective of
the number of procedures or use of antiarrhythmic drugs and when
present, left ventricular outflow obstruction could be a strong predictor
of recurrence. Gaita et al.36 have demonstrated that 64% of 24
AF patients with HCM had AF-free survival at a mean follow-up
of 19 months following catheter ablation. Similarly, Bunch et al.37
have shown that 1 year AF-free survival was 62% in 33 patients with
HCM. Okamatsu et al.38 have reported that during a mean follow-up
of 21 months, sinus rhythm was maintained in 59% of HCM patients
who underwent catheter ablation for AF. On the other hand,
Bassiouny et al.39 have reported that only 29% of HCM patients who
underwent catheter ablation had no documented recurrent atrial arrhythmia
after a single procedure after a follow-up of 35 months.
Patients With Mechanical Mitral Valve (MMV)
Previous studies have demonstrated that catheter ablation of AF in
patients with MMV is feasible and safe but is associated with higher
recurrence than in patients with native valve.40-43 Lakkireddy et
al.42 have shown that at 12 months, 80% of patients in the mitral or
aortic prosthetic valve group were in sinus rhythm after an average
of 1.3 procedures. Hussein et al.43 have reported that of 81 patients
with MVR, 56 (69.1%) were arrhythmia free while not taking antiarrhythmic
drugs, 11 (13.6%) had their arrhythmia controlled with
antiarrhythmic drugs that had previously failed, and 14 (17.3%) had
drug-resistant AF and were managed with rate control. In this study,
all MMV patients underwent ablation under therapeutic international
normalized ratio. No entrapment of catheters or stroke had
occurred and there were no differences in terms of procedure-related
complications between the groups.
A recent study has compared the efficacy and long-term outcome
of pulmonary vein (PV) antrum isolation (PVAI) alone versus extended
PVAI plus non-PV trigger elimination for the treatment of
AF in patients with MMV.44 It was found that compared with the
standard PVAI alone, a strategy including extended PVAI and non-
PV trigger elimination was associated with a higher 12-month and
long-term arrhythmia-free survival in patients with MMV undergoing
AF ablation. Very late recurrence occurred in up to 18.8% of
patients undergoing extensive ablation, with focal AT being the most
common type of recurrent arrhythmia.
ACC/AHA guidelines11 state that radiofrequency (RF) catheter
ablation (RFCA) can be considered in athletes with AF episodes.45
Recovery of PV conduction may necessitate re-ablation in certain
patients.46 Patients with persistent AF are more likely to need a repeat
ablation than those with paroxysmal AF.47 Current guidelines
do not specify when re-ablation should be performed; however, it is
generally recommended to withhold repeat procedures for a 3-month
period after the first procedure as residual areas of conduction in the
PVs may take time to become clinically apparent.3
Recent studies have demonstrated that severity of atrial fibrosis
was associated with decreased response to catheter ablation.48-51 The tissue characterization of the LA wall regarding atrial fibrosis on
DE-MRI was found to be correlated with electroanatomic voltage
mapping (EAVM).49 Relying on this, identification and acute targeting
of gaps in atrial ablation lesions sets have been investigated using
a real-time MRI system.52,53 Major limitation is that this modality
requires extensive MRI experience, and its reproducibility is still under
investigation.
Approaches In AF Ablation
The early percutaneous catheter ablation procedures were designed
to mimic a surgical Cox maze procedure, which was based on the
‘multiple wavelet hypothesis’ for AF. This hypothesis suggested that,
as long as the atrium had a sufficient area with adequately short refractory
periods, AF could be initiated and then indefinitely perpetuated.
Therefore, the early attempts at interventional AF treatment
aimed to decrease arrhythmia perpetuation by compartmentalizing
the atrium into smaller regions incapable of sustaining the critical
number of circulating wavelets.
Today, the most common goal, particularly for ablation of paroxysmal
AF in younger patients whose atria have undergone little or
no atrial remodelling, is complete PV isolation (PVI) with unidirectional
or bidirectional conduction block. PVI alone is much less
successful for AF control dominated by “substrate” (persistent and
long-standing persistent AF) when there has been extensive and
irreversible atrial remodelling. In such cases, some other strategies
including successful isolation of sites of non-PV triggers; elimination
of sites harboring complex fractionated atrial electrograms (CFAE);
linear ablation with bidirectional block; ablation of sites harboring
ganglionated plexi (GP); ablation utilizing electrogram analysis to
eliminate sites of AF rotors or other drivers; ablation with a goal
of conversion to SR during ablation; or ablation until the absence
of any atrial arrhythmias during attempts at re-induction must be
considered.
Following PVI, data supporting the use of any particular strategy
over another for improved long-term clinical outcomes is inconsistent
and adjunctive strategies to PVI are often selected based on operator
experience and preference.54-57 Heterogeneity between patient
populations may be explanatory to explain the variation in the results
of outcome studies. Besides, the different end-points, follow-up periods
and protocols often limit comparisons of studies (Also see “Success
rates of AF ablation”).
Ablation Approaches Targeting PVs
Rapidly firing foci initiating paroxysmal AF arise most commonly
from LA myocardial sleeves that extend into the PVs.2 These observations
led to the development of segmental PVI as the cornerstone
for ablation strategies.58 An ablation strategy of encircling the PVs
with RF lesions guided by 3D electroanatomical mapping was subsequently
developed by Pappone et al.59 Strategies then shifted to
target the atrial tissue located in the antrum rather than the PV itself
(“segmental PV ablation” or “wide area circumferential ablation”) following
the recognition of both PV stenosis as a complication of RF
delivery within a PV, or the PV antrum. And today, circumferential
isolation of PVs has become the standard therapy for paroxysmal AF.
Most clinicians have identified their primary endpoint for PV ablation
as the elimination (or dissociation) of the PV potentials recorded
from a circular multipolar electrode catheter. 10% rely on exit
block as an endpoint for the ablation procedure.3
Ablation Approaches Not Targeting PVs
Additive strategies to PVI have been sought, particularly in persistent
and long- standing persistent AF patients, to improve outcomes
of catheter ablation.
The rationale underlying creating linear LA lesions60 originates
from the surgical Cox maze procedure, and follows the ‘multiple
wavelet hypothesis’ that postulates that compartmentalizing the LA
into smaller regions incapable of sustaining micro re-entry will improve
outcomes. Added benefits include the potential effect on the
macro re-entrant tachycardias that can occur post-AF ablation.
Unfortunately, achievement of complete conduction block across
linear lesions can be very difficult to achieve since the lesions have
to be both contiguous and transmural. Thus, whereas complete lines
may prevent recurrent arrhythmias, if incomplete they may be proarrhythmic
and result in higher prevalence of LA flutter.61 Therefore,
the addition of linear lesions confers no benefit when compared to
PVI alone in paroxysmal AF patients.56,62 A slight advantage has been
suggested in persistent AF patients where two small, randomized trials
have demonstrated a significant benefit.62,63 However, the recent
Substrate and Trigger Ablation for Reduction of Atrial Fibrillation
Trial Part II trial (STAR- AF II) has failed to show any beneficial effect
of linear ablation in addition to PVI in persistent AF patients.57
The sites of origin for non-PV atrial triggers include the posterior
wall of the LA, the superior vena cava, the inferior vena cava, the
crista terminalis, the fossa ovalis, the coronary sinus, behind the Eustachian
ridge, along the ligament of Marshall, and adjacent to the
AV valve annuli.64 Furthermore, re-entrant circuits maintaining AF
may be located within the right and left atria. In selected patients,
elimination of only the non-PV triggers has resulted in elimination
of AF.65,66
Complex fractionated atrial electrograms are regarded to represent
areas of slow conduction, conduction block, or ‘pivot’ points for a
local AF perpetuating re-entry. The primary endpoints during RF
ablation of AF using this approach are either complete elimination
of the areas with CFAEs, conversion of AF to sinus rhythm, and/or
non- inducibility of AF. For patients with paroxysmal AF, the endpoint
of the ablation procedure using this approach is non- inducibility
of AF. For patients with persistent AF, the endpoint of ablation
with this approach is AF termination. Similar to linear lesion, studies
have demonstrated that CFAE ablation as a lone ablation strategy
is inadequate for both paroxysmal and persistent AF.67,68 Likewise,
in the paroxysmal AF population there appears to be limited benefit
for adjunctive CFAE ablation.62,67,69,70 In those with persistent AF,
observational and randomized studies have demonstrated that ablation
of CFAE areas, in addition to PVI, improves the procedural
outcome.62,67,71,71 Recent STAR- AF II trial, on the other hand, has
failed to demonstrate any beneficial effect of CFAE ablation in addition
to PVI in persistent AF patients.57 One of the limitations of
targeting CFAEs with ablation has been the extensive amount of
ablation needed. Half of the clinicians have stated that they routinely
employed CFAE-based ablation as part of an initial ablation procedure
in patients with long-standing persistent AF.3
Adding GPs to other ablation targets has been shown to improve
ablation success.73,74
Other Unestablished Ablation Strategies
A) Voltage Map-Guided Substrate Modification: Box Isolation Of
Fibrotic Areas (BIFA)
The regional localization and the extent of the fibrotic LA substrate
can be visualized during the intervention in sinus rhythm applying
EAVM; this allows the use of a new patient-tailored ablation
strategy, BIFA, for the circumferential isolation of the significantly
affected fibrotic areas (e.g., <0.5 mV). An individualized substrate
modification using BIFAs may be added to circumferential PVI in
patients with paroxysmal AF, or who have very substantial regional
LA fibrosis detected in the first ablation session. However, in patients
with massive fibrosis, failure of the initial ablation is likely regardless
of the applied ablation concept, and further ablation procedures
should be discouraged and avoided.
There are several limitations of methods for identifying substrates.
Voltage maps using point-by-point mapping not only take time, but
the measured voltage also depends on the rhythm (sinus, atrial fibrillation,
atrial extrasystole), the electrode contact with tissue, and the
atrial myocardium thickness. Therefore, clear limits or definitions for
a normal voltage (e.g., >1.5mV, >2.0mV) and a highly abnormal voltage
(e.g., <0.5 mV) do not exist.
B) Focal Impulse And Rotor Modulation (FIRM)
The follow-up results of FIRM strategy, in which a 64-pole basket
catheter is advanced into the left and right atria to demonstrate
focal impulse and rotors, have revealed that patients who underwent
FIRM-guided ablation maintained higher freedom from AF versus
those who underwent conventional ablation.75 AF sources were analyzed
to be co- incidentally ablated in 45% of conventional cases.76
These results were also confirmed in a multicenter study.43
Ensuring Durable Isolation
Various techniques have been proposed to identify regions of incomplete
ablation and/or residual gaps within the index ablation
line. One technique is the use of intravenous adenosine to differentiate
permanent PV-atrial block from dormant conduction. Not
all studies have been in agreement concerning adenosine application.
77-81 Results of Adenosine Following Pulmonary Vein Isolation
to Target Dormant Conduction Elimination [ADVICE] trial has
recently been published,82 supporting that adenosine administration
should be considered for incorporation into routine clinical practice.
An alternative strategy is the ‘pace-capture guided’ approach, where,
after completion of PVI, the antral ablation line encircling the ipsilateral
PVs is mapped while pacing from the ablation catheters distal
electrode pair.83,84 Where local LA capture is identified, additional
ablation can be performed with the goal of closure of the residual
gaps. And also, to attain durable PVI, waiting time after PVI is also
important. In a study, Yamane et al.85 demonstrated that provocation
and elimination of time- and ATP-induced early PV re-connection
is recommended not only at 30 minutes but also at 60 minutes after
PVI to improve its efficacy.
Radiofrequency energy is by far the dominant energy source that
has been used for catheter ablation of AF. RF energy achieves myocardial
ablation by the conduction of alternating electrical current through myocardial tissue. The tissue resistivity results in distribution
of RF energy as heat, and the heat then conducts passively to deeper
tissue layers. Most tissues exposed to temperatures of 50°C or higher
for more than several seconds will show irreversible coagulation necrosis,
and evolve into non-conducting myocardial scar. High power
delivery and good electrode–tissue contact promote the formation of
larger lesions and improve procedure efficacy. Most clinicians employ
irrigated tip catheters for delivering RF energy.3 Comparative trials
of irrigated tip and large tip RF technologies versus conventional
RF electrodes have demonstrated increased efficacy and decreased
procedure duration in the ablation of AFlu,86,87 but only limited trials
of large tip and open irrigation catheters have been performed in
patients undergoing AF ablation.
Cryoablation has more recently been developed as a tool for AF
ablation procedures. Cryoablation systems work by delivering liquid
nitrous oxide under pressure through the catheter to its tip or
within the balloon, where it changes to gas, resulting in cooling of
surrounding tissue. This gas is then carried back through the reciprocating
vacuum lumen. The mechanism of tissue injury results from
tissue freezing with a creation of ice crystals within the cell that disrupts
cell membranes and interrupts both cellular metabolism and
any electrical activity in that cell. In addition, interruption of microvascular
perfusion may interrupt blood flow, similarly producing
cell death. Complete vein occlusion is required for the creation of
circumferential PV lesions and electrical PVI using the cryoballoon
ablation catheter.88
The reported complications related to catheter ablation of AF may
include vascular access complications such as hematoma, retroperitoneal
bleeding, pseudoaneurysm, arteriovenous fistula; myocardial
perforation and pericardial tamponade; pulmonary vein stenosis;
phrenic nerve palsy; thromboembolic events including transient
ischemic attacks and stroke; atrioesophageal fistula; and death.
Cryoablation is known to cause less patient discomfort and require
lower doses of conscious sedation when compared with RFCA.
It also carries a low risk of thrombus formation89 and therefore, a
decreased risk of embolization and stroke. Cryoenergy leaves the
connective tissue matrix intact and theoretically, is less likely to lead
to myocardial perforation and tamponade compared with RFCA.
However, a recent study of 133 consecutive patients undergoing AF
ablation has found a similar incidence of pericardial effusions between
those treated with cryoballoon ablation and radiofrequency
ablation.90 Otherwise, both procedures have similar risks of injury
of adjacent structures (esophagus, phrenic nerves, vagus nerves, lung
parenchyma). Although ostial cryoablation reduced the incidence of
PV stenosis significantly, the risk still has not been eliminated. Despite
animal models showing greater risk of PV stenosis with RFCA91
and lack of evidence of collagen deposition or PV stenosis 3 months
post-cryoablation,92 PV stenosis may also complicate cryoablation.
Clinical data from a small series have shown esophageal ulcerations
with cryoablation, but no progression to fistula.93
Although point-by-point RF energy and cryoballoon ablation are
the two standard ablation systems used for catheter ablation of AF
today, balloon-based ultrasound ablation,94 and laser based ablation
systems95 also have been developed for AF ablation.
Multielectrode Circumferential Ablation Catheters
The principal purpose of the multielectrode circular ablation cath eter systems is to provide ablation and mapping on a single platform.
96,97 The PV ablation catheter (PVAC, Medtronic Ablation
Frontiers, Carlsbad, CA) is a 9F deflectable circular multi-electrode
catheter that enables mapping and circumferential PV ablation.
The latter is the irrigated multi-electrode nMARQ ablation system
(Biosense Webster, Inc., Diamond Bar, CA, USA), which allows
multi-electrode ablation. The key difference in the nMARQ system
is its integration into the CARTO3 platform (Biosense Webster,
Inc., Diamond Bar, CA, USA) allowing full visualization of the
catheter loop and electrodes, as well as the fact that the catheter is
irrigated with 10 irrigation holes per electrode (completely surrounding
the electrodes). Recently, multicenter registries including patients
referred for paroxysmal or persistent AF underwent PVI by the
nMARQ ablation system have shown high acute success rates and
shorter procedural times.98,99 However, several recent studies have reported
a higher incidence of silent microemboli following ablation
with a multielectrode ablation catheter.100-101
Electroanatomic Mapping Systems
Electroanatomic mapping systems combine anatomic and electrical
information by a catheter point-by-point mapping, allowing an
accurate 3D anatomic reconstruction of the targeted cardiac chamber.
There are two different electroanatomic mapping systems that
are widely used in clinical practice. The current generation of the
CARTO mapping system (CARTO-3, Biosense Webster, Diamond
Bar, CA, USA) relies on both a magnet-based localization for visualization
of the ablation catheter and an impedance-based system that
allows for both tip and catheter curve visualization as well as simultaneous
visualization of multiple electrodes.102 The second electroanatomic
mapping system is an electrical impedance mapping system
(NavX, St. Jude Medical Inc., Minneapolis, MN, USA) using voltage
and impedance for localization.103 The use of these 3D mapping systems
has been demonstrated to reduce fluoroscopy duration.102,103 To
further improve anatomic accuracy of the maps, the 3D images may
be integrated with computed tomography (CT) or magnetic resonance
imaging (MRI).104 However, it should not be forgotten that
CT or MRI images are not real-time images, and that the accuracy
of image integration is dependent on the accuracy of the image fusion.
Furthermore, another potential limitation of electroanatomic
mapping is the relatively static nature of the geometry, which may
need to be updated during the procedure because of changes in anatomy
(volume status and tissue edema) or if the location reference has
moved. The development of 3D intracardiac echo (ICE) probes may
overcome the limitations in geometry creation as one could navigate
the real-time 3D image. It has been demonstrated that RFCA of
paroxysmal AF using the CARTO 3 system and ICE could be performed
safely without fluoroscopy.105
Overall, studies on the use of mapping systems on safety and efficacy
of AF ablation have revealed contradictory results.106-108 Most
clinicians prefer using these systems when performing AF ablation
excluding cases where a balloon-based ablation system is used.3
Special Issues In Catheter Ablation
It has been shown that RFCA of AF performed under therapeutic
international normalized ratio (INR) does not increase bleeding
risk and reduces the risk of emboli.109-110 Although in guidelines, it
is recommended to use novel oral anticoagulant agents with caution
for patients undergoing catheter ablation because of the lack
of approved antidotes in the event of cardiac tamponade,11 recently in Active-controlled multi-center study with blind-adjudication designed
to evaluate the safety of uninterrupted Rivaroxaban and uninterrupted
vitamin K antagonists in subjects undergoing cathEter
ablation for non-valvular Atrial Fibrillation (VENTURE- AF) trial,
it has been shown that the use of uninterrupted oral rivaroxaban was
feasible and event rates were similar to those for uninterrupted VKA
therapy.111
Periprocedural protamine administration following catheter ablation
to reverse heparin- mediated effects have been shown to allow
quicker sheath removal and minimize the risk of potential vascular
complications without causing an increase in thrombotic events.112-114
Success Rates Of AF Abalation
A meta-analysis of 4 prospective, randomized clinical trials reported
that 76% of patients treated with catheter ablation were free of
AF compared with 19% of patients randomized to antiarrhythmic
drugs.115 Another meta-analysis involving 63 AF ablation studies
reported that the single-procedure success of ablation with no antiarrhythmic
drug therapy was 57%, the multiple-procedure success
rate with no antiarrhythmic drug therapy was 71%, and the multiple
procedure success rate with antiarrhythmic drugs was 77%. In comparison,
the success rate for antiarrhythmic drug therapy was 52%.6
Medical Antiarrhythmic Treatment or Radiofrequency Ablation
in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial116 compared
first-line catheter ablation of AF to antiarrhythmic drugs in
294 patients. At 2 years, significantly more patients in the ablation
group were free from any AF and symptomatic AF. Quality of life
was significantly better in the catheter ablation arm. In Radiofrequency
Ablation vs. Antiarrhythmic Drugs as First-Line Treatment
of Paroxysmal Atrial Fibrillation (RAAFT-2) trial,9 the recurrence
rate of AF was significant lower after ablation compared with antiarrhythmic
drugs after 2 years among 127 patients with paroxysmal
AF without previous antiarrhythmic drug treatment. Quality of life
improved in both treatment groups. Takigawa et al.117 have reported
long-term follow-up results of catheter ablation of paroxysmal
AF in 1220 patients. AF recurrence–free survival probabilities at 5
years were 59.4% after the initial catheter ablation and 81.1% after
the final catheter ablation (average, 1.3 procedures). Similar results
were found when cryoenergy was used for ablation of AF for treatment-
naive patients in Sustained Treatment of Paroxysmal Atrial
Fibrillation (STOP- AF) trial.118 There is only little evidence from
prospective, randomized, multicenter clinical trials in patients with
chronic AF. However, the recently published prospective randomized
Tailored Treatment of Persistent Atrial Fibrillation (TTOPAF)
trial in patients with persistent and long-standing persistent AF
demonstrated a significant greater reduction of AF at 6 months after
ablation compared with medical treatment.119 Despite an identical
outer shape with the first-generation (Arctic Front; Medtronic Inc,
Minneapolis, MN) (Arc- CB), modifications to the refrigerant injection
system has allowed improved cooling of the distal balloon
hemisphere in the second-generation cryoballoon (Arctic Front Advance;
Medtronic Inc, Minneapolis, MN) (Arc- Adv- CB). Several
studies have compared the safety and efficacy of cryoablation in
patients who underwent ablation with either first or second-generation
cryoballoon120-123 and have shown that Arc-Adv-CB attained
high rates of acute PV isolation within a significantly faster and less
complex procedure. Recently, Metzner et al.124 have reported that the
use of second-generation 28-mm cryoballoon for PVI resulted in 1-year success rates of 81% for PAF, 77% for short-term persistent
AF. Mugnai et al.125 have reported that at a mean follow-up of 23
months, the success rate was similar for both RFCA and cryoablation
groups. Procedural times were significantly shorter in the cryoablation
group. Complication rates were similar in both groups except
for phrenic nerve palsy that was uniquely observed in the CB group.
Wasserlauf et al.126 have compared 1 year outcomes of cryoballoon
and RFCA and shown that cryoballoon ablation was associated with
equivalent 1-year freedom from AF rate as RFCA for paroxysmal
AF. Procedure and fluoroscopy times were shorter for cryoballoon
ablation. Aryana et al.127 have recently shown that freedom from AF/
atrial flutter/tachycardia at 12 months following a single procedure
without antiarrhythmic therapy was statistically significantly greater
with CB-2 (76.6%) versus RF (60.4%). This difference was evident
in patients with paroxysmal AF, it did not reach significance in those
with persistent AF.
Currently, there is a lack of evidence and a large debate about the
optimal ablation strategy in patients with non-paroxysmal AF. A
previous meta-analysis of studies reporting the results of catheter ablation
of persistent and long-standing persistent had concluded that
the success rate of different strategies is similar, provided that pulmonary
vein isolation was performed.128 A recent systematic review and
meta- analysis of randomized and non- randomized controlled trials
reporting clinical outcomes after catheter ablation for persistent atrial
fibrillation, which included 46 studies containing 3819 patients,
has concluded that catheter ablation results in a significantly greater
freedom from recurrent AF compared with medical therapy. The
most efficacious strategy was reported to be the combination of isolation
of the PVs with limited linear ablation within the LA.129
It should not be forgotten that although most trials evaluate success
of ablation in terms of long-term maintenance of SR, clinical
improvement following ablation is often under-evaluated in studies.
This clinical improvement may be attributed to a decreased AF burden,
alteration in the severity of AF, or changes in overall cardiac
function, both in patients with paroxysmal130,131 or persistent AF.132 A
study has shown that catheter ablation significantly improved quality
of life for patients with persistent AF whereas medical therapy
had no appreciable effect.133 There is currently no data on the impact
of catheter ablation on mortality. Its impact on mortality (and other
secondary outcomes) is being explored in the ongoing Catheter
Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation
(CABANA) trial.
Rhythm control strategy using an invasive catheter ablation therapy
is both effective and safe, however, selection of both appropriate
patients and ablation technique should be personalized considering
various factors like availability of the devices, operators’ experience,
patient co-morbidities, presence of structural heart disease and patient
consent. Thus, we can propose that one strategy does not fit to
all AF patients when catheter ablation was chosen as an therapeutic
option.