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Cardiac Arrhythmia 2
Catheter ablation of atrial arrhythmias: state of the art
Geoffrey Lee, Prashanthan Sanders, Jonathan M Kalman

Catheter ablation is at the forefront of the management of a range of atrial arrhythmias. In this Series paper, we discuss Lancet 2012; 380: 1509–19
the underlying mechanisms and the current role of catheter ablation for the three most common atrial arrhythmias See Editorial page 1446
encountered in clinical practice: focal atrial tachycardia, atrial flutter, and atrial fibrillation. The mechanisms of focal See Comment page 1448
atrial tachycardia and atrial flutter are well understood, and these arrhythmias are amenable to curative catheter ablation This is the second in a Series of
with high success rates. In most cases, paroxysmal atrial fibrillation is initiated by triggers located within pulmonary vein three papers about cardiac
musculature. Circumferential ablation to isolate this musculature is associated with high success rates for elimination of arrhythmia

paroxysmal atrial fibrillation in selected populations. Because of the problem of recurrent pulmonary vein connection, Department of Cardiology,
Royal Melbourne Hospital,
more than one procedure will be needed in about 30% of patients, and new technologies are being developed to reduce Melbourne, VIC, Australia
this occurrence. The mechanisms that sustain persistent atrial fibrillation are not well understood and are the subject of (G Lee MBChB,
continuing investigation. As such, ablation approaches and technologies for this arrhythmia are still evolving. Prof J M Kalman PhD);
Department of Medicine,
University of Melbourne,
Introduction be either an anatomic structure such as a pulmonary vein Melbourne, VIC, Australia
Atrial arrhythmias include a range of different rhythm or valve annulus or a functional obstacle caused by (G Lee, J M Kalman); Centre for
disturbances that encompass almost the full range of heterogeneities in tissue electrical properties. The classic Heart Rhythm Disorders, Royal
arrhythmia mechanisms. The three most frequently example of macro-re-entry is typical atrial flutter, but Adelaide Hospital, Adelaide,
SA, Australia
encountered arrhythmias, which are the focus of this included within this category are various forms of atypical (Prof P Sanders PhD); and
review, are focal atrial tachycardia, atrial flutter, and flutter. On ECG, atrial flutter is classically described as University of Adelaide,
atrial fibrillation. Generally, these arrhythmias respond having a so-called saw-tooth appearance, attributable to the Adelaide, SA, Australia
poorly to antiarrhythmic drugs, and patients frequently presence of continuous electrical activity. (P Sanders)

have recurring and at times debilitating symptoms. Atrial fibrillation is defined by the presence of atrial Correspondence to:
Prof Jonathan M Kalman,
Throughout the past decade, major technological advances fibrillatory waves that show variation in rate (interval) and Department of Cardiology, Royal
in cardiac electrophysiology have brought catheter ablation morphology. The dominant classification of atrial fibrill- Melbourne Hospital, Melbourne,
to the forefront of treatment algorithms for these ation is according to arrhythmia duration and termination.3 VIC 3050, Australia
arrhythmias. In this Series paper, we provide an overview jon.kalman@mh.org.au

of the underlying mechanisms, relevant anatomy, and ECG considerations

catheter-based treatment of these arrhythmias. ECG cannot reliably distinguish tachycardia mechanism.
No effective rate cutoff exists to differentiate focal atrial
Classification of atrial arrhythmias tachycardia from atrial flutter, and when viewing a 12-lead
The nomenclature surrounding the classification of atrial ECG snapshot, it can be difficult to distinguish between
arrhythmias continues to be unclear. Broadly, organised atrial fibrillation with coarse fibrillatory waves and atrial
atrial tachycardias can be classified into two categories flutter. The distinction can be made with a careful analysis
according to the arrhythmia mechanism: focal or macro- of P wave morphology and rate, which should be constant
re-entry. Atrial fibrillation is a disorganised rhythm and in atrial flutter and variable in atrial fibrillation.
its classification according to underlying mechanism is
still evolving. Focal atrial tachycardia
Focal atrial tachycardias are defined by early atrial General considerations
activation from a discrete site with radial spread to the Focal atrial tachycardia is classified as a type of supra-
periphery.1 They can be paroxysmal or incessant and at ventricular tachycardia. It is the least common form of
times present as repetitive short bursts of tachycardia with
one or more intervening sinus beats (figure 1). Such
repetitive bursts can resemble short paroxysms of atrial Search strategy and selection criteria
fibrillation. On electrocardiogram (ECG), P waves might We searched PubMed for reports published between
be discernible before each QRS complex. However, at 1980, and 2012, with the search terms “atrial fibrillation”,
rapid rates during sustained tachycardia, P waves can be “atrial flutter”, and “atrial tachycardia” in combination with
difficult to distinguish because of superimposition on the the term “ablation”. We mainly selected publications from the
preceding QRS or T wave. In this case, the arrhythmia past 5 years, but did not exclude frequently referenced and
appears as a regular supraventricular tachycardia. highly regarded older publications. We also pursued articles
Atrial flutter is due to a large re-entrant circuit (the referenced in primary sources and their relevant citations and
macro-re-entry circuit; typically >2 cm in diameter)2 selected those we judged relevant.
occurring around a central obstacle. This obstacle might

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this arrhythmia (after atrioventricular node re-entry and low side-effect profiles.7 In refractory cases, class Ic
atrioventricular re-entry tachycardia) and accounts for (flecainide and propafenone) or class III (sotalol and
just 10–15% of patients referred for catheter ablation of amiodarone) antiarrhythmics can be considered. The
supraventricular tachycardia.4 Although generally benign, routine use of these drugs should be balanced against
up to 25% of patients will present with frequent their uncertain and relatively poor efficacy and risk of
paroxysms or incessant activity, with a third of these significant side-effects including ventricular pro-
patients eventually developing a tachycardia-mediated arrhythmia.7 In view of the poor efficacy of drugs alone,
cardiomyopathy.5 The underlying mechanism(s) of focal catheter ablation of atrial tachycardia is considered a first-
atrial tachycardia might include abnormal automaticity, line7 therapy in patients with recurrent symptoms or those
triggered activity, or re-entry.6 However, it is frequently with incessant focal atrial tachycardias or a tachycardia-
not possible to precisely establish which of these mediated cardiomyopathy.
mechanisms is responsible, and the distinction is of Most focal atrial tachycardias occur in the absence of
minor relevance to patients undergoing ablation. structural heart disease, although localised abnormalities
Definitive data showing the superiority of one anti- at the tachycardia origin, including fibrosis, might be
arrhythmic drug over another in the treatment of present.8 Tachycardia foci are not randomly distributed
focal atrial tachycardia are not available, and most infor- throughout the atria, but are localised to characteristic
mation comes from small and mainly observational anatomical sites8,9 (figure 2). Roughly 75% occur in the
studies. Calcium-channel blockers and β blockers are right atrium, with the most common site of origin being
often recommended as first-line agents because of their the superior and middle parts of the crista terminalis.

Figure 1: Burst of atrial tachycardia

The rhythm strip shows fast repetitive bursts of a focal non-sustained atrial tachycardia mimicking atrial fibrillation. At the electrophysiological study, the focus was
mapped to the right superior pulmonary vein and ablated.

A Anatomic distribution of focal atrial tachycardias B Anatomic distribution of mitral and tricuspid annular atrial tachycardias

RAA (0·6%)
Superior Left fibrous
trigone
LAA (0·6%)
Right fibrous AV
CT (31%)
trigone
Anterior

(19%)
LPV
RPV

HB MV

TV
CS
Posterior
Atrial Inferior
TA (22%) Perinodal (11%) tachycardia
CS os (8%) foci
Tricuspid annulus (22%) Mitral annulus (4%)

L or R septal (4%)

Figure 2: Anatomic distribution of atrial tachycardias

(A) Common anatomic distribution of focal atrial tachycardias showing rough percentage distribution recorded in our laboratory; the atrioventricular annuli have
been removed. (B) Common anatomic distribution of mitral and tricuspid annular atrial tachycardias. AV=aortic valve. CS (os)=coronary sinus (ostium). CT=crista
terminalis. HB=His bundle. LAA=left atrial appendage. LPV=left pulmonary veins. MV=mitral valve. RAA=right atrial appendage. RPV=right pulmonary veins.
TA=tricuspid annulus. TV=tricuspid valve.

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Arrhythmias from this anatomic site have also been A LA electroanatomical map: external view (posterior LA) Internal view
referred to as sinus node re-entry. In the left atrium, foci LSPV Earliest site RSPV 30 ms
are most often noted at the ostium of the pulmonary veins. of activation LSPV
Because of the characteristic anatomic clustering of in LSPV
LAA
atrial foci within the atria, the P-wave morphology on the
surface ECG might provide important clues to the site of
origin of the atrial tachycardia before catheter ablation.9
Kistler and colleagues9 developed an algorithm that LIPV
prospectively localised the atrial site of origin in 93% of LIPV LA ridge
cases. Lead V1 was most useful in differentiating between
left (positive P wave) and right (negative P wave) atrial RIPV
focal sites.
–40 ms
Mapping and ablation of focal atrial tachycardia
B LA electroanatomical map: external view (LAO) TEE (three chamber view)
Anatomic localisation of the atrial focus is undertaken
RSPV Earliest site 20 ms
during sustained tachycardia or in the presence of of activation
Ablation
LSPV catheter
frequent atrial ectopy, which are necessary prerequisites at AMC
LAA MV leaflets at AMC
for mapping. In some cases, the focus is quiescent and LA
cannot be induced, precluding mapping. In the area of LMCA
interest, precise mapping is done with a steerable AoV
ablation catheter to locate the earliest site of activation.
The use of three-dimensional (3D) computerised map-
ping systems allows superimposition of colour-coded LV
activation times on the atrial anatomy.10 This approach
identifies a central region of earliest activity with radial Aortic root
–75 ms
propagation (figure 3). Radiofrequency energy is then
Figure 3: Three-dimensional electroanatomical mapping of focal atrial tachycardias
delivered to this focus. Focal site of early activation (red) is shown, with radial propagation away from that central site. The activation
Catheter ablation of atrial tachycardia is a highly map was superimposed onto the patient’s cardiac CT scan, taken the day before the procedure and imported into
effective treatment with most studies reporting acute the mapping system. (A) Earliest site of activation, mapped to the posterior aspect of the LSPV ostium. Posterior
success rates in excess of 85–90%. Major complications external view (A, left side) and endoluminal or internal view looking from within the left atrium into the mouth of
the LSPV (A, right side) are shown. (B) Earliest site mapped to the aortomitral continuity. The anatomic relation
are rare.8 The outcomes of patients presenting with between the mitral annulus and the aortic root can be clearly appreciated (B, left side). The location of the ablation
cardiomyopathy secondary to incessant atrial tachycardia catheter at the site of earliest atrial activation during atrial tachycardia is shown on the TEE image (B, right side).
are excellent, with most patients recovering left ventricle AMC=aortomitral continuity. AoV=aortic valve. LA=left atrium. LAA=left atrial appendage. LAO=left anterior
function within months.5 oblique. LIPV=left inferior pulmonary veins. LMCA=left main coronary artery. LSPV=left superior pulmonary vein.
LV=left ventricle. MV=mitral valve. RIPV=right inferior pulmonary veins. RSPV=right superior pulmonary vein.
TEE=transoesophageal echocardiogram.
Atrial flutter
General considerations
Atrial flutter represents a heterogeneous group of arrhyth- terminalis (which extends from the superior vena cava to
mias defined mechanistically by the presence of a large the inferior vena cava on the posterior aspect of the
circuit around a central obstacle, which can be a fixed atrium) acts as a conduction barrier that facilitates re-
anatomical structure or a functional electrophysiological entry by preventing a short-circuiting of the annulus.15 At
line of block. Generally, the unique anatomy of the atrium the crista terminalis, cell-to-cell coupling is relatively
is an important determinant of the location of a flutter poor in the transverse direction and therefore transverse
circuit. The most common form is best known as typical conduction might be slow or blocked at this structure.
atrial flutter and is characterised by the presence of classic The critical isthmus of the flutter circuit is in the floor of
saw-tooth flutter waves in the inferior leads of the ECG. the right atrium between the inferior tricuspid annulus
The presence of atrial flutter usually suggests an and the inferior vena cava—the cavotricuspid isthmus.16
underlying predisposition to atrial fibrillation, which Figure 4A shows the essential elements of typical atrial
will eventually be identified in most of these patients.11 flutter. In about 15% of circuits, the wavefront rotates in
Indeed, atrial flutter is generally initiated through a a clockwise direction.
transitional phase of atrial fibrillation.12 The circuits involved in atypical flutter are highly
The circuit for typical atrial flutter is located in the variable and involve a range of anatomical boundaries
right atrium and is defined by well described anatomical (figures 4, 5). Atypical flutters can be classified broadly
barriers.13,14 In simple terms, the circuit can be viewed into three categories: no previous atrial surgery;
as a broad activation wavefront that rotates around previous corrective atrial surgery (congenital and
the anteriorly located tricuspid annulus in the valvular heart disease); and previous atrial fibrillation
counterclockwise direction. Posteriorly, the crista ablation. Despite the range of different disorders and

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A Typical right atrial flutter B Lower loop re-entry

SVC

PV

CT
FO

CS

ER

The IVC forms the

IVC central area of block
Cavotricuspid isthmus

Figure 4: Right atrial flutter circuits

Anatomical circuits of typical atrial flutter (A) and lower loop re-entry (B). The atrioventricular annuli that sit anteriorly (in front) have been removed for clarity. Red
arrows represent the activation path for each putative circuit. Blue arrows represent the cavotricuspid isthmus, which forms the narrowest part in each of the flutter
circuits shown. Linear ablation through this crucial isthmus prevents both atrial flutter circuits. Yellow arrows represent passive activation of atrial tissue that is not
part of the active circuit. Typical flutter involves a circuit around the tricuspid annulus (A). Note that the crista terminalis (CT) forms a complete line of conduction
block (yellow double lines), forcing the re-entrant circuit to go superiorly around the tricuspid annulus. Lower loop re-entry involves a smaller circuit around the
IVC (B). The grey arrow represents a small gap in transverse conduction at the low crista terminalis, which facilitates this circuit. CS=coronary sinus. CT=crista
terminalis. ER=Eustachian ridge. FO=fossa ovalis. IVC=inferior vena cava. PV=pulmonary vein. SVC=superior vena cava.

A Perimitral flutter B Left atrial flutter circuits C After previous atrial surgery
Around mitral annulus Around scar and
Spontaneous pulmonary veins
posterior left
atrial scar

Circuits formed
Around ipsilateral around suture Flutter circuit around
pulmonary veins lines and scar a pericardial ASD patch
tissue

Figure 5: Atypical flutter circuits

Red arrows represent the activation path for each circuit. Yellow arrows represent passive activation wavefronts. Grey areas represent areas of spontaneous electrical scar on the posterior left atrial wall.
Perimitral flutter (A) involves a circuit that rotates around the mitral annulus, with the right atrium activated passively. Posterior atrial scarring (grey areas) in the context of atrial disease results in regions
of slow conduction, which allow development of this arrhythmia. Left atrial flutter (B) can also involve circuits around the pulmonary veins or circuits around pulmonary veins and areas of posterior left
atrial scar, with the right atrium activated passively. Atypical flutter circuits can also form around suture lines and scar tissue from previous atrial surgery (C) or around prosthetic material such as an ASD
patch (C) or an atrial conduit. An area of slowed conduction due to previous surgical incisions and chronic atrial dilatation is usually present, and this assists re-entry. ASD=atrial septal defect.

operations, stereotypical anatomic locations have been terminalis; figure 4B).21 Left atrial atypical flutter usually
described in each of these different settings. occurs in the presence of significant structural heart
In patients without previous atrial surgery, various disease, such as heart failure or mitral regurgitation, which
circuits have been described.17,18 In the right atrium, these result in atrial enlargement.22 In these chronically dilated
include circuits in the lateral wall of the atrium (free wall atria, regions of fibrosis develop that serve as obstacles to
flutter),19,20 or around the inferior vena cava (lower loop re- normal conduction and stabilise re-entrant circuits. These
entry with slow transverse conduction across the crista circuits can be single or multiple (dual loop re-entry) and

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frequently occur around the mitral annulus or pulmonary

veins22 (figure 5). A Dual-loop left atrial flutter B Right atrial flutter after ASD repair
(anteroposterior view) (right lateral view)
In patients with previous atrial surgery, suture lines, 60 ms 99 ms
scar, or prosthetic material can form the critical central SVC
Common channel for LSPV Critical isthmus in a Scar
barrier around which re-entry occurs, which has dual-loop circuits channel surrounded
variously been referred to as incisional or scar-mediated RSPV
by islands of scar
re-entrant tachycardia. This disorder usually occurs in
Posterior
the context of surgical correction of congenital or LAA
RA
valvular heart disease.23,24
Although the ECG pattern of typical flutter is Scar
LIPV
characteristic, the flutter wave morphology of atypical
flutters is highly variable and rarely gives a clue to precise
RIPV Scar
anatomic location. Antiarrhythmic drugs are frequently TA
ineffective and more than 50% of patients will eventually Mitral
annulus
cross to a rate-control strategy because of an inability to IVC
maintain sinus rhythm.25 Catheter ablation is regarded as a –150 ms 213 ms
first-line therapeutic option for patients with a first episode Figure 6: Three-dimensional (3D) mapping and ablation of atypical flutter circuits
of typical atrial flutter26 and for flutter appearing after 3D electroanatomical map of an atypical flutter circuit, termed dual-loop left atrial flutter (A), and an atypical
antiarrhythmic treatment of atrial fibrillation.27 Indications flutter in a patient who has had previous surgical repair of an atrial septal defect (B). (A) The activation map is
for ablation of atypical flutter include recurrent or poorly superimposed on the patient’s imported atrial CT scan. Two flutter circuits are occurring simultaneously within the
left atrium; one rotates counterclockwise around the mitral valve annulus, whereas the other rotates clockwise
tolerated episodes and failed antiarrhythmic drug therapy. around the right-sided pulmonary veins. The two circuits share a common isthmus (*). Ablation through this
common isthmus eliminated both circuits. (B) Atrial geometry is created by the computerised 3D mapping system
Mapping and ablation of atrial flutter as the ablation catheter is moved around the chamber; a CT scan was not done. Islands of electrical scar (grey)
Catheter mapping of atrial flutter involves activation, within the right atrium are due to surgical incisions and chronic atrial stretch (dilation). The critical isthmus (*) of
the flutter circuit is a channel of viable tissue bordered by two areas of scar. Ablation at this isthmus terminated the
entrainment, and 3D computerised mapping. Activation atrial flutter. Both examples (A and B) show continuous atrial loops, which are the hallmarks of macro-re-entry.
mapping consists of catheters with several electrodes that The mapping system displays the full colour range of activation times (early activation is red and late activation is
can identify the direction of wavefront propagation. During blue/purple). Where early and late activation meet is the so-called head meets tail of a re-entrant circuit. ASD=atrial
septal defect. IVC=inferior vena cava. LAA=left atrial appendage. LIPV=left inferior pulmonary veins. LSPV=left
entrainment mapping, pacing during tachycardia from
superior pulmonary vein. MA=mitral annulus. RA=right atrium. RIPV=right inferior pulmonary veins. RSPV=right
different anatomic sites in the atrium identifies which superior pulmonary vein. SVC=superior vena cava. TA=tricuspid annulus.
sites are within the re-entrant circuit and which are
activated passively.28 3D computerised mapping is used to
reconstruct the 3D anatomy (with or without the use of an are then used to confirm that the ablation line is
imported CT scan detailing atrial anatomy) with super- complete (figure 7).30
imposition of colour-coded activation times to accurately The acute procedural success rate is now in excess of
show the location of even very complex circuits.10 Macro- 95%, with a 5–10% incidence of flutter recurrence in
re-entrant circuits will show as continuous loops, with 1–2 years of follow-up.31,32 Major complications are rare.31 A
activation timing spanning the cycle length and a region randomised study of ablation versus antiarrhythmic drugs
where early activation meets late activation (the so-called as first-line treatment of typical flutter reported sinus
head meets tail of a re-entrant loop; figure 6). rhythm in 80% and 36% of patients, respectively, at
Computerised mapping systems are generally not 21 month follow-up.25 The incidence of atrial fibrillation
needed for ablation of simple circuits of known anatomic after ablation of atrial flutter is time-dependent, and with
location, such as typical flutter. However, 3D mapping is of long-term follow-up it can occur in up to 80%.32 These data
crucial importance for delineating the more complex reinforce the need to consider continuing anticoagulation
circuits of atypical flutter, particularly in the context of in patients who have a CHADS2 score of greater than 1
abnormal atrial anatomy, multiple circuits, and regions of (one point assigned for congestive heart failure [C],
scar (figure 6). Successful ablation is dependent on hypertension [H], age 75 years or older [A], or diabetes [D],
identification of a narrow critical isthmus (figure 6) in the and two for previous stroke or transient ischaemic attack
re-entrant circuit, which can be interrupted either with a [S2]), despite undergoing successful flutter ablation, or to
line or focal point of ablation. follow-up closely for development of atrial fibrillation.
During ablation of typical atrial flutter, sequential or Outcomes for ablation of atypical flutters are more
continuous radiofrequency lesions are given to form a variable and depend on the type of heart disease and extent
contiguous linear lesion extending from the tricuspid of atrial pathology. Generally, patients who have had
annulus to the inferior vena cava, transecting the simpler surgical procedures (eg, atrial septal defect [ASD]
cavotricuspid isthmus (mean distance 2–3 cm).29 This repair, mitral valve repair) will have better outcomes than
ablation line prevents conduction at the narrowest patients who have had several operations for complex
point of the circuit and atrial flutter usually terminates congenital heart disease (eg, Mustard repair, Fontan
just as the line is being completed. Mapping techniques repair). In these populations, ablation is generally used as

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part of a general strategy that might also include open atrial fibrillation. This section will focus on the underlying
surgical approaches. Nevertheless, ablation strategies can mechanisms of atrial fibrillation in the context of catheter
yield highly effective palliation. ablation, the common techniques, and the outcomes of
these techniques.
Atrial fibrillation Guidelines from the American College of Cardiology,
General considerations American Heart Association, and European Society of
Over the past decade, catheter ablation has evolved to Cardiology recommend catheter ablation for patients with
become a routine procedure for selected patients with atrial fibrillation who remain symptomatic despite
optimum medical therapy (table).3 However, the
2012 expert consensus statement from the Heart Rhythm
A Pacing lateral to ablation line B Society, European Heart Rhythm Association, and
I
II European Cardiac Arrhythmia Society on catheter and
HIS 1, 2 VI 600 surgical ablation of atrial fibrillation includes ablation as a
CS 1, 2 V6
Halo reasonable first-line option for selected patients with
HIS
19, 20 paroxysmal atrial fibrillation.3 These recommendations
CS 1, 2 represent expert consensus and are not always supported
by data from comparative trials. Additionally, the statement
specifies that these complex and technically demanding
CS 9, 10 P procedures be done by operators with appropriate training
Halo 1, 2
in experienced centres.
In highly symptomatic patients with atrial fibrillation,
catheter ablation has resulted in substantial improvement
in quality of life.33 At present, no large prospective
CS 9, 10
randomised studies have been undertaken that show an
P outcome benefit from atrial fibrillation ablation, either in
Linear ablation line
Halo 19, 20 terms of stroke reduction or mortality benefit, and
600
information in this regard is largely restricted to single-
Halo 1, 2 185 ms centre retrospective series. As such, for asymptomatic
patients or those who are minimally symptomatic, rate
C Pacing septal to ablation line D I control is an acceptable alternative to rhythm control.34 The
II
VI
Catheter Ablation versus Antiarrhythmic Drug Therapy for
HIS 1, 2 300 310 Atrial Fibrillation trial (CABANA; NCT00911508) is a
CS 1, 2 V6
Halo HIS prospective multicentre randomised study (in progress) of
19, 20
CS 1, 2
ablation versus medical therapy in patients with atrial
fibrillation and one or more risk factors for stroke. The
primary endpoint is mortality and secondary endpoints
CS 9, 10 include cardiovascular mortality and disabling stroke.
Halo 1, 2
Mechanisms: focal drivers, rotors, and multiple
wavefronts
P In the past decade, understanding of the cellular and
CS 9, 10
molecular mechanisms underlying atrial fibrillation
195 ms has advanced significantly. Studies have emphasised
the importance of ion channel remodelling, changes in
Halo 19, 20
600 P
signalling pathways, oxidative stress, altered calcium
handling, changes in atrial architecture, and altered
Halo 1, 2 195 ms connexin expression in the pathogenesis of atrial
Figure 7: Testing for complete conduction block in the cavotricuspid isthmus after typical atrial flutter ablation fibrillation.35
The schematics (A and C) show blue and white representations of the electrode catheters positioned within the heart. Until relatively recently, the multiple wavelet hypothesis
Blue represents the catheter shaft and white the recording electrodes, with each pair representing one recording was the dominant conceptual model of atrial fibrillation.
bipole. The positions of the circular mapping catheter around the tricuspid annulus (Halo), His bundle (HIS), and
The hypothesis is based on a computer model developed
coronary sinus (CS) catheters are shown. Red dots represent ablation points, which create a line of conduction block
through the cavotricuspid isthmus. (A and B) Pacing (P) is undertaken lateral to the ablation line; because a block has by Moe and colleagues36 and is supported by mapping data
formed across the ablation line, the activation wavefront (green arrow) is forced to travel clockwise around the from animals and human beings.37,38 Atrial fibrillation was
tricuspid annulus. Intracardiac electrograms (B) confirm sequential clockwise activation around the tricuspid annulus thought to be characterised by several randomly wan-
(Halo bipole 1, 2 → Halo bipole 19, 20, with CS bipole 9, 10 activated last). This activation takes 185 ms to complete.
dering wavefronts that vary in position, number, and size.36
(C and D) Pacing (P) is then done septal to the ablation line; again, because of conduction block across the ablation
line, activation (green arrow) now occurs sequentially in a counterclockwise direction around the tricuspid annulus In recent years, increasing evidence suggests that focal
(CS bipole 9, 10 → Halo bipole 19, 20 → Halo bipole 1, 2). This activation takes 195 ms to complete. drivers and rotors (one or more atrial re-entrant circuits)

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have an important role in the underlying mechanism of

Indication class*
atrial fibrillation.
The mechanisms underlying paroxysmal atrial fibril- Symptomatic atrial fibrillation refractory or intolerant to at least one class 1 or 3 antiarrhythmic drug

lation (defined by the presence of episodes that terminate Paroxysmal: catheter ablation is recommended I
spontaneously within 7 days) and persistent atrial Persistent: catheter ablation is reasonable IIa
fibrillation (episodes lasting longer than 7 days and not Longstanding persistent: catheter ablation could be considered IIb
self-terminating) are considerably different. Symptomatic atrial fibrillation before initiation of class 1 or 3 antiarrhythmic drug
In 1998, Haissaguerre and colleagues39 described the Paroxysmal: catheter ablation is reasonable IIa
presence of focal drivers originating from within atrial Persistent: catheter ablation could be considered IIb
muscular extensions into the pulmonary veins. Very Longstanding persistent: catheter ablation could be considered IIb
high frequency electrical activity (>300–400 bpm) from a *Class indicates level of evidence. Reproduced and modified from the 2012 Heart Rhythm Society, European Heart
focal source caused non-uniform conduction to the Rhythm Association, and European Cardiac Arrhythmia Society expert consensus statement on catheter and surgical
atrium, resulting in atrial fibrillation. Since that seminal ablation of atrial fibrillation,3 by permission of Springer.
finding, others have also shown that pulmonary vein foci Table: Class of consensus indications for catheter ablation of atrial fibrillation
represent the crucial initiating trigger to paroxysmal
atrial fibrillation in 85–95% of patients. In the remainder
of patients, foci outside the pulmonary veins seem to be Other mapping data from patients with persistent
responsible. The pathophysiological processes leading to atrial fibrillation suggest that dissociation between
development of these focal triggers are not known. the epicardial and endocardial atrial layers results in
Furthermore, whether the underlying mechanism of breakthrough wavefronts that continually renew and
this focal activity is due to enhanced automaticity,40 drive the atrial fibrillation process—a mechanism akin
triggered activity,41,42 or localised pulmonary vein re-entry to multiple wavelet re-entry. These two mechanisms are
is unclear.43 Nevertheless, an appreciation of the im- not mutually exclusive. Importantly, in patients with
portance of pulmonary vein musculature in initiation of different forms of structural heart disease, the under-
paroxysmal atrial fibrillation has led to development of lying mechanism of atrial fibrillation is most probably
highly effective ablation strategies to electrically isolate quite heterogeneous.
these veins.44,45 The uncertainty surrounding the mechanism of per-
In patients with persistent atrial fibrillation, the sistent atrial fibrillation and our inability to establish
mechanisms are less clear. Pulmonary vein foci might precise mechanisms in individual patients is shown in the
be important for arrhythmia initiation in a subset of myriad of different ablative approaches to this arrhythmia
patients. However, in those with more persistent atrial and the disappointing success rates.52
fibrillation and those with structural heart disease,
mechanisms that maintain rather than initiate the Ablation of paroxysmal atrial fibrillation
arrhythmia play the dominant part. These mechanisms Pulmonary vein isolation is the cornerstone of catheter
are located within atrial myocardium, and the develop- ablation for patients with paroxysmal atrial fibrillation.53
ment of atrial remodelling is of crucial importance to This method is an empirical approach based on the
the persistence of atrial fibrillation.46 Atrial remodelling knowledge that most focal triggers occur within pul-
refers to the electrical and structural changes that develop monary vein muscular sleeves. Detailed assessment of
in the atrium as a result of atrial fibrillation itself and the the anatomic location of several triggers is not feasible.
presence of a range of coexisting disorders. Heart failure, The current approach to isolation targets the proximal
hypertension, valvular heart disease, and obstructive pulmonary vein antrum, thereby minimising the risk of
sleep apnoea lead to atrial structural changes or re- stenosis (figure 8). The most widely used and assessed
modelling, including atrial enlargement and regional technique is that of point-by-point irrigated radio-
fibrosis, forming the prerequisite substrate for persistent frequency ablation. 3D mapping is routinely used to
atrial fibrillation.46 accurately delineate anatomy with or without the use of
The exact mechanism responsible for the maintenance an imported CT scan (figure 8). More recently, in an
of persistent atrial fibrillation is not known. Recently, attempt to simplify the procedure, various one-shot
accumulating evidence from animal studies has shown technologies for circumferential isolation of the pul-
the important role of atrial rotors in driving persistent monary veins have been developed.54–56 The cryoballoon
atrial fibrillation.47,48 Mapping studies of human beings and a circumferential radiofrequency ablation catheter
have shown the presence of atrial rotors in patients with are the most advanced of these technologies. However,
persistent atrial fibrillation.49,50 A recent study has shown neither the promise of shorter procedure and fluoroscopy
that catheter ablation of these rotors might lead to times nor the goal of improved efficacy and safety have
termination of persistent atrial fibrillation.51 The efficacy of been definitively realised.54,57 Irrespective of technology
this potentially exciting new approach to the ablation of used, the endpoint for antral pulmonary vein ablation is
persistent atrial fibrillation will need to be verified by large demonstration of complete conduction block into and
multicentre studies. out of the pulmonary vein.

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A 3D electroanatomical mapping B Acute PV isolation terminates atrial fibrillation

Posterior RIPV and LA in Acute
LSPV RSPV LA and RA revert back to sinus rhythm but
view atrial fibrillation RIPV
Pulmonary vein RIPV still in atrial fibrillation
during ablation isolation
antrum
LAA

ISOLATION

ECG 80 850 590 520 1270 1400 1380

ABL

HIS

RIPV CSd
LIPV
CS

LSPV RSPV
Right lateral
view
CSp
PV 1, 2

LIPV PV 9, 10

RIPV

CS

Figure 8: Ablation of paroxysmal atrial fibrillation

(A) Three-dimensional (3D) mapping system images from a paroxysmal atrial fibrillation ablation procedure. A cardiac CT scan is done before the procedure and the 3D left atrial image is imported into
the mapping system. In this case, the mapping system shows a common left pulmonary vein ostium and proximal branching of right-sided pulmonary veins. Detailed knowledge of these anatomic
variants helps with the mapping and ablation procedure. Small blue dots identify the anatomic course of the oesophagus posterior to the left atrium. Ablation lesions are denoted by red dots. On the
left is one proximal ring around the left common pulmonary vein and on the right the RSPV and RIPV are isolated individually. (B) Intracardiac electrograms from this atrial fibrillation ablation show
that RIPV isolation terminated atrial fibrillation. The surface electrocardiogram (ECG) leads and intracardiac signals from the ablation catheter (ABL), His bundle (HIS), coronary sinus distal (CSd),
coronary sinus proximal (CSp), and circular pulmonary vein (PV) mapping catheter positioned within the right inferior pulmonary vein are displayed from top to bottom. Note the extremely rapid
chaotic atrial activity within the PV. At the start of ablation, the patient has atrial fibrillation, shown by the irregular ECG and the presence of fast irregular electrical activity in all recording sites. When
the RIPV becomes acutely isolated (red arrow), atrial fibrillation terminates into sinus rhythm. Regular surface P waves can now be seen with regular electrical activity on the HIS and CS catheters.
However, the now electrically isolated RIPV continues to fibrillate (high-frequency disorganised activity). Because of electrical isolation, this activity can no longer drive the rest of the atrium into atrial
fibrillation. The left common pulmonary vein and RSPV had already been isolated before RIPV isolation. LA=left atrium. LAA=left atrial appendage. LIPV=left inferior pulmonary vein. LSPV=left
superior pulmonary vein. RA=right atrium. RIPV=right inferior pulmonary vein. RSPV=right superior pulmonary vein.

Several randomised clinical trials have compared and the multiple procedure success rate of antiarrhythmic
the outcomes of atrial fibrillation ablation with anti- drugs was 77%.61 More recently, studies have reported
arrhythmic drug therapy or with rate-control drugs alone.33 long-term 5 year follow-up data;62–64 in patients with
A meta-analysis of these trials described an overall success paroxysmal atrial fibrillation, sinus rhythm was achieved
rate of catheter ablation of 77·8% compared with 23·3% in about 80–92% of patients after repeat procedures.62–64
for drug therapy.58 Several other meta-analyses of random-
ised clinical trials reported similar results.59 Ablation of persistent atrial fibrillation
The most common reason for recurrence of paroxysmal In paroxysmal atrial fibrillation, the ablation strategy
atrial fibrillation after a pulmonary vein isolation procedure is based on an understanding of the anatomic region
is pulmonary vein reconnection, which has been reported crucial to arrhythmia mechanism (pulmonary vein muscle
in 85–100% of patients undergoing a second procedure for sleeves). In patients with persistent atrial fibrillation,
symptomatic recurrence.60 Repeat procedures are needed especially those with longlasting (ie, >12 months) atrial
in 20–30% of patients undergoing ablation of paroxysmal fibrillation, the picture is much less clear. A wide range of
atrial fibrillation. approaches have been published targeting very varied
One meta-analysis specifically assessed success rates putative arrhythmia mechanisms. Beyond circumferential
after single and repeat ablation procedures and took into pulmonary vein isolation, approaches to ablation of
account continuing need for antiarrhythmic treatment.61 persistent atrial fibrillation continue to include linear
The single and multiple procedure success rates of ablation, ablation of complex fractionated atrial electro-
antiarrhythmic therapy were 57% and 71%, respectively, grams (CFAEs), ablation of autonomic ganglia, and

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isolation of other venous structures including the coronary range from 3·9–4·5%.69,70 Recognised major complications
sinus and superior vena cava. Additionally, hybrid or include death (in 1 of 1000 patients), stroke, cardiac
stepwise approaches that include two or more of these tamponade, atrio-oesophageal fistula, or clinically sig-
procedures have been described. Each of these approaches nificant pulmonary vein stenosis. These studies69,70
is empirical: the mechanisms have not been shown in incorporate results from a heterogeneous population
patients specifically and they are predicated on unproven undergoing a variety of ablation procedures between
assumptions about arrhythmia mechanism. This con- 1999 and 2007. With increasing experience, a high-volume
trasts with ablation of atrial tachycardia and atrial flutter centre reported that complication rates decreased from
for which the individual patient-specific mechanism is 11·1% in 2002, to 1·6% in 2010 (p<0·05), with no
clearly defined at the time of the procedure. complications associated with permanent sequelae since
Disappointingly, the single procedure success rates have 2005.71 In patients younger than 70 years with pre-
largely been under 50% and in some instances as low as dominantly paroxysmal atrial fibrillation without signifi-
20–30%. A recent systematic review of outcomes of cant structural heart disease, pulmonary vein antral
persistent atrial fibrillation ablation concluded that the isolation is safe and associated with a very low risk of
varying ablation techniques (including pulmonary vein major complications (<1%).72 Factors that have been
isolation alone, pulmonary vein isolation with linear associated with higher complication rates include older
ablation, pulmonary vein isolation with CFAE ablation, age, previous stroke, and advanced structural heart disease,
and the stepwise procedure) resulted in similar results but data are inconsistent.
(mean single procedure success rate of 47%).52 Clinical
outcomes were improved with repeat procedures with Future challenges
success rates approaching 65%. For paroxysmal atrial fibrillation the major challenge is the
Studies with longer-term follow-up (2–5 years) have creation of enduring pulmonary vein isolation, because
reported multiple procedure success rates ranging pulmonary vein reconnection is the overwhelming reason
between 57% and 63%, and in many series persistent for recurrence. Early data suggest that catheters that
atrial fibrillation is an independent predictor of late recur- register tissue contact force and thereby improve lesion
rence.65,66 Other factors that have been associated with efficacy might result in lower rates of pulmonary vein
lower long-term success rates have included older age, reconnection.73,74 In patients with persistent atrial fibrill-
increased left atrial size, obesity, sleep apnoea, and ation, a better understanding of (probably heterogeneous)
structural heart disease.65,67 However, findings have not arrhythmia mechanisms is needed so that ablation
been consistent and most trials have enrolled a relatively approaches can be targeted to a clearly shown mechanism.
small number of patients with advanced age, marked left Advances in technology have played a major part in our
atrial enlargement, or advanced structural heart disease ability to ablate these arrhythmias; further improvements
(including significant left ventricular dysfunction). in catheter design and mapping capabilities will no doubt
Efficacy of catheter ablation in these subgroups needs lead to better understanding and outcomes. By acting on
further assessment. the evolving substrate for atrial fibrillation, treatment of
coexisting disorders might improve ablation outcomes or
Proarrhythmia: development of atrial tachycardia after even slow clinical progression of atrial fibrillation so that
atrial fibrillation ablation ablation may be deferred. Studies are in progress.
New atrial tachycardias can appear for the first time after
atrial fibrillation ablation. After simple pulmonary vein Conclusion
isolation, such arrhythmias are seen infrequently. How- Catheter ablation is now at the forefront of the treatment
ever, with more extensive atrial ablation, especially that algorithm for a broad range of atrial arrhythmias. In
including linear ablation or widespread ablation of patients with focal atrial tachycardia and typical atrial
fractionated electrograms, recurrent atrial tachycardia can flutter, it is a first line therapy with efficacy in excess of
occur in 30–50% of patients. The most frequently reported 90%. For patients with a range of complex atypical
mechanisms include atrial macro-re-entry (large circuits) flutters, it is a highly effective approach in those not
or small re-entrant circuits (1–2 cm), both occurring readily controlled with antiarrhythmic drugs. For patients
around regions of previous ablation. These stable circuits, with previous atrial surgery or more complex congenital
compared with atrial fibrillation, result in more rapid heart disease, late flutter recurrence or atrial fibrillation
ventricular response rates, more frequently need development is common, but ablation nevertheless
cardioversion, and might actually be associated with an might offer a highly effective palliation.
increase in symptoms.68 For these reasons, many labora- In symptomatic patients with atrial fibrillation, catheter
tories now limit the amount of extensive ablation done. ablation has resulted in substantial improvements in
quality of life. Success rates in selected paroxysmal atrial
Complications fibrillation patients might be in excess of 80%, although
The risk of major complications of radiofrequency catheter several procedures are frequently needed, and complication
ablation of atrial fibrillation was previously reported to rates have fallen to around 1% in low-risk populations.

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More data are needed to understand the role and outcomes 10 Natale A, Breeding L, Tomassoni G, et al. Ablation of right and left
of ablation in broader subgroups, including elderly people ectopic atrial tachycardias using a three-dimensional
nonfluoroscopic mapping system. Am J Cardiol 1998; 82: 989–92.
and those with significant structural heart disease 11 Moubarak G, Pavin D, Laviolle B, et al. Incidence of atrial fibrillation
(including left ventricular dysfunction and atrial enlarge- during very long-term follow-up after radiofrequency ablation of
ment). For patients with persistent atrial fibrillation, the typical atrial flutter. Arch Cardiovasc Dis 2009; 102: 525–32.
12 Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and
role of catheter ablation continues to evolve, as does our atrial flutter mechanisms and clinical implications.
understanding of the crucial underlying mechanisms. J Am Coll Cardiol 2008; 51: 779–86.
Contributors 13 Cosio FG, Arribas F, Barbero JM, Kallmeyer C, Goicolea A.
Validation of double-spike electrograms as markers of conduction
GL did the detailed scientific literature search, drafted and revised the
delay or block in atrial flutter. Am J Cardiol 1988; 61: 775–80.
manuscript, and created the original figures. PS contributed to scientific
14 Kalman JM, Olgin JE, Saxon LA, Fisher WG, Lee RJ, Lesh MD.
literature inclusions; revised the manuscript, figures, and bibliography;
Activation and entrainment mapping defines the tricuspid annulus
and responded to the reviewers. JMK did the detailed literature search; as the anterior barrier in typical atrial flutter. Circulation 1996;
revised the manuscript, figures, and bibliography; responded to the 94: 398–406.
reviewers; and approved the final report. 15 Olgin JE, Kalman JM, Fitzpatrick AP, Lesh MD. Role of right atrial
Conflicts of interest endocardial structures as barriers to conduction during human type
PS has served on the advisory board of Bard Electrophysiology, I atrial flutter: activation and entrainment mapping guided by
Biosense-Webster, Medtronic, St Jude Medical, Merck, and Sanofi-Aventis, intracardiac echocardiography. Circulation 1995; 92: 1839–48.
and has received lecture fees or research funding from Bard 16 Olshansky B, Okumura K, Hess PG, Waldo AL. Demonstration of
Electrophysiology, Biosense-Webster, Medtronic, and St Jude Medical. an area of slow conduction in human atrial flutter. J Am Coll Cardiol
1990; 16: 1639–48.
JMK is the recipient of research funding and fellowship support from
Medtronic, St Jude Medical, and Johnson & Johnson Medical. GL declares 17 Kalman JM, Olgin JE, Saxon LA, Lee RJ, Scheinman MM, Lesh MD.
Electrocardiographic and electrophysiologic characterization of
that he has no conflicts of interest.
atypical atrial flutter in man: use of activation and entrainment
Acknowledgments mapping and implications for catheter ablation.
GL is the recipient of a research scholarship from the National Health and J Cardiovasc Electrophysiol 1997; 8: 121–44.
Medical Research Council of Australia (NHMRC). JMK is the recipient of a 18 Yang Y, Cheng J, Bochoeyer A, et al. Atypical right atrial flutter
grant from NHMRC (604908). patterns. Circulation 2001; 103: 3092–98.
19 Kall JG, Rubenstein DS, Kopp DE, et al. Atypical atrial flutter
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