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REVIEW
Cavotricuspid isthmus-dependent atrial flutter:
clinical perspectives
This article was published in the following Dove Press journal:
Research Reports in Clinical Cardiology
Sok-Sithikun Bun
Decebal Gabriel Lațcu
Ahmed Mostfa Wedn
Karim Hasni
Nadir Saoudi
Department of Cardiology, Princess
Grace Hospital, Monaco (Principality),
Monaco, Monaco
Abstract: The precise circuit of cavotricuspid isthmus (CTI)-dependent atrial flutters
(AFLs) has been well characterized, but the recent arrival of ultrahigh-resolution mapping
systems has further improved our understanding of this “old”arrhythmia. CTI-dependent
AFL may be the arrhythmia for which the electrocardiograph (ECG) correlation with the
mechanism may be the highest. Once the diagnosis is made (predominantly based upon the
surface ECG), the therapeutic options are precisely defined, with radiofrequency catheter
ablation representing an efficient strategy with a high success rate and few complications.
This article will focus on the clinical perspectives for CTI-dependent AFL.
Keywords: typical atrial flutter, cavotricuspid isthmus-dependent, catheter ablation
Introduction
Since its first description more than a century ago, our understanding of cavotricuspid
isthmus (CTI)-dependent atrial flutter (AFL) has significantly improved, using recent
advanced ultrahigh-resolution (UHR) mapping systems. Our knowledge of CTI-depen-
dent AFL has evolved from a relatively simple and unique electrocardiograph (ECG)
pattern corresponding to a right atrial (RA) macroreentry to different forms of atrial
tachycardias (ATs) propagating through the CTI (or even short-circuiting with epicardial
connections).
1
Once the diagnosis of CTI-dependent AFL is made (mainly based upon the
surface ECG), the therapeutic strategy is well standardized, and radiofrequency (RF)
catheter ablation (or with cryotherapy) may be performed with high success rate and low
complications and recurrence rate. A close follow-up of the patient will be suggested to
detect the occurrence of atrial fibrillation (AF).
Definition and classification of CTI-dependent
flutters
The term flutter was first used in 1887 by Mac William who described the visual
phenomena resulting from “faradic stimulation of the auricles which sets them into
a rapid flutter”.
2
The first ECG recording of AFL (with characteristic sawtooth
waves in the inferior leads) appeared 23 years later with Jolly and Ritchie, using the
Cambridge model of Einthoven’s string galvanometer.
3
Lewis was the first to explain the mechanism of this arrhythmia by a single-wave
circus movement.
4
The macroreentrant mechanism was later proven by detailed
mapping in the operating room, the use of steerable multipolar catheters, transient
tachycardia entrainment and systems that allowed sequential or simultaneous record-
ing of a large number of endocardial points acquired during the arrhythmia.
Correspondence: Sok-Sithikun Bun
Department of Cardiology, Princess
Grace Hospital, Monaco (Principality),
Pasteur Avenue, Monaco, Monaco
Tel +3 779 798 9771
Fax +3 779 798 9732
Email sithi.bun@gmail.com
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AFL classically refers to the ECG pattern of an undu-
lating wave with no electrical silence in at least one lead of
the surface ECG. In 1970, a classification of AFL was
proposed by Puech and Grolleau based upon the ECG
morphology.
5
The most type of AFL was called “com-
mon”if negative biphasic flutter waves with a sawtooth
pattern were present in the inferior ECG leads, and pre-
ceding the positivity in V1; AFL was named “atypical”or
“rare”if a sawtooth pattern was observed in the frontal
plane but now best seen in lead I.
In 2001, an international group of experts proposed the
definition of AFLs as follows: AFL refers to the ECG aspect
of a regular AT with a rate ≥240 beats/min lacking an iso-
electric baseline between deflections.
6
Of note, all experts
agreed to the fact that neither rate nor lack of isoelectric
baseline was specific for the tachycardia mechanism. AFL
is named typical if the inferior pivot point is the CTI, i.e. the
area bounded anteriorly by the inferior part of the tricuspid
valve and posteriorly by the inferior vena cava (IVC) orifice.
This article will focus on the clinical features of CTI-
dependent AFL. Non-CTI-dependent AFL will be
excluded from this review.
Typical AFLs
Counterclockwise (CCW) typical flutter
This is the most frequent form of AFL. The mechanism is
a macroreentrant circuit confined within the RA, with
a descending wavefront in the lateral wall and an ascend-
ing wavefront on the septum with passive activation of the
left atrium (LA). The tricuspid valve represents the ante-
rior bound of the circuit, whereas the posterior one is
a combination of anatomic obstacles (orifices of superior
vena cava superiorly, IVC inferiorly, and Eustachian ridge
posteriorly) and anatomo-functional barriers (region of the
crista terminalis, see below).
7–9
The characteristic “saw-
tooth”pattern is usually present in the inferior ECG leads.
In lead V1, the flutter wave shows an initial isoelectric line
followed by a positive component which typically falls
later than the negative component of the inferior leads
(Figure 1). This gives an “overall impression of an upright
flutter wave in V1 which becomes inverted by V6”.
10
This classical presentation may manifest some morpho-
logical variations, giving rise to a classification into 3
types of ECG patterns for CCW CTI-dependent flutters,
based on the presence and type of the initial positive
I
II
III
VR
VL
VF
V1
V2
V3
V4
V5
V6
Figure 1 Typical counterclockwise atrial flutter with variable atrioventricular transmission and alternating right and left bundle branch block.
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deflection.
11
It was reported that the presence of a terminal
positive component of the F-wave in CCW CTI-dependent
AFL may identify patients with a high likelihood of heart
disease and a higher incidence of AF and LA enlargement.
CCW lower loop reentry
In 1999, Cheng et al described the circuit of lower loop
reentry as a variant of typical flutter.
12
The circuit is located
in the lower RA, but is also CTI dependent. It is character-
ized by: 1) an early breakthrough in the lower RA, 2)
a wavefront collision in the high lateral RA or septum,
and 3) a conduction through the CTI. The LA and the
septum are activated in a similar sequence to CCW typical
AFL, giving negative F waves in the inferior ECG leads.
In one study including 12 patients with positive flutter
wave in the inferior ECG leads, it was found that the CTI–
dependent AFL involved a reentrant circuit around the IVC,
but now with a CW rotation (CW lower loop reentry). In all
but 1 patient, entrainment pacing confirmed that the whole
reentrant circuit was totally located in the lower RA.
13
Dual-loop reentry during typical flutter
The circuit is composed by a CCW loop around the tricuspid
valve, but sharing a common anterior channel with a CW loop
around a lateral atriotomy scar. This may occur after postatrial
septal defect surgical closure.
14
RF delivery within the CTI
transforms the tachycardia without any pause to a second
tachycardia with different axis and morphology, but nearly
the same cycle length owing to rotation around the periatriot-
omy loop alone. This second tachycardia requires ablation of
a second isthmus: between a natural obstacle and one end of
the atriotomy. This tachycardia may also be observed without
any atriotomy incision, but in the presence of an unexpected
scar located on the lateral wall.
15
Clockwise typical flutter
In approximatively 10–30% of typical AFLs, the reentrant
circuit and the anatomical/functional barriers are identical
within the RA, but propagates in a CW direction around
the tricuspid valve in a left anterior oblique perspective.
16
In the initial series, the classic “sawtooth”pattern was
observed in 14 of 18 out of CW AFL. They are frequently
associated with a “positive flutter wave in the inferior
leads“, but the early description also reported a shorter
plateau phase, a widening of the negative component of
the F-wave, and a negative and frequently bifid F-wave in
V
1.
A positive F-wave in V6 follows after the negative one
in V1 (Figure 2).
Intraisthmus reentry
This form of CTI-dependent AFL has been recently
described.
17
Surface ECGs show typical CCW pattern in
the majority of the patients. Fractionated potentials covering
about 34–71% of the tachycardia cycle length are always
recorded within the CTI. The ablation may be successfully
performed in the area with maximal fractionated potentials
duration. Although still debated, the circuit is confined within
the CTI itself and bounded by the medial part of the CTI and
the CS ostium on the septal side. Interestingly, in the initial
description, some parts of the circuits considered could be
located outside the CTI region and could occur in the pre-
sence of a proven complete bidirectional CTI block.
18
ECG modifications of typical AFLs
In the era of AF ablation, significant modification of inter-
and intra-atrial propagation after circumferential pulmon-
ary vein isolation (and even more after extensive lesions)
is almost always accompanied by a flutter wave distortion
that is also encountered during sinus rhythm.
19
These
previous atrial lesions make very challenging any attempt
of location of the site/chamber of origin based on the
flutter wave morphology (Figure 3).
20
Recently, even bia-
trial circuits have been reported using UHR mapping sys-
tem, and including the CTI as part of this biatrial circuit.
21
CTI as a zone of slow conduction/
role of the crista terminalis/ECG
correlation
Previous studies demonstrated that CTI was a zone of slow
conduction using an electroanatomical noncontact mapping
system.
22
More recently, an UHR mapping system revealed
that approximatively 58% of the patients had a slowing of
the conduction impulse in the CTI.
23
In contrast, another
study showed that the conduction velocity (CV) was not
decreased in the CTI, in comparison with the other RA
structures, using the same technology.
24
In our series of
patients, CTI was constantly a zone of slow conduction in
all patients.
25
32 patients were mapped either during
ongoing CCW (n=25), or CW (n=3) AFL, or during cor-
onary sinus pacing at 400 ms (n=1), 500 ms (n=1), or 600
ms (n=3). CTI CV was significantly lower (0.56±0.18 m/s)
in comparison with the lateral CV (1.31±0.29 m/s;
p<0.0001) and the septal border CV of the CTI (1.29
±0.31 m/s; p< 0.0001). In our population of CTI ablation
using UHR mapping system, only one patient experienced
an AFL recurrence of 32 (3.1%) after a mean follow-up of
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20±13 months. Nine patients of 32 (28%) presented an AF
recurrence during the follow-up.
The transverse conduction block in the crista terminalis
has been reported to be a major determinant in the arrhyth-
mogenesis of CTI-dependent AFL.
26,27
Recent data with
UHR showed that the crista terminalis was inconstantly
observed during AFL, and that a more posterior line of the
block may also be involved in 16 of 22 patients.
Our group published that there was an excellent corre-
lation between the plateau phase on the surface ECG that
can be measured in the inferior ECG leads and the extra
isthmus conduction time either CW or CCW, once the line
of block has been created within the CTI.
28
Nevertheless,
a recent study by Sau et al showed that the CV within the
CTI was not correlated to the sawtooth pattern on the
surface ECG. There is still room for further studies for
ECG analyses in AFL.
Epidemiology/clinical presentation
AFL in not as frequent as AF (less than one-tenth as often
as AF).
29
The MESA database reported an overall inci-
dence of AFL of about 88 for 100,000 person-years with
80,000 new AFL cases in the USA annually.
30
The inci-
dence is approximatively 2.5 times higher in men than in
women, and dramatically increases with age, as compared
to AF (5/100,000 before the age of 50 vs 587/100,000 in
those older than 80 years old).
31
Identified risk factors are chronic pulmonary dis-
ease, heart failure, previous stroke, and myocardial
infarction. The associated conditions are thyrotoxico-
sis, pericardial disease, valvular heart disease, post-
open-heart surgery, and congenital heart disease. AFL
mayoccurinthefollow-upofpatientshavingbeen
repaired for a congenital heart defect (Mustard,
Senning, or Fontan).
I
II
III
VR
VL
V1
V2
V3
V4
V5
V6
VF
II
Figure 2 Clockwise cavotricuspid isthmus-dependent atrial flutter with 4:1 atrioventricular conduction and a complete right bundle branch block. It may be difficult to
characterize the presence of positive flutter waves in the inferior leads, but the plateau phase is obviously shortened. The negativity of the flutter waves is also difficult to
interpret in lead V1.
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Clinical presentation
AFL may usually manifest with paroxysmal palpitations or
short-breathing. Symptoms are more marked when AFL is
paroxysmal, and when the ventricular rate answer is fast.
Rarely, it may be revealed by the presence of
a tachycardia-induced cardiomyopathy, and the ablation
will then allow the left ventricular function to recover
once the sinus rhythm has been restored. The characteris-
tics of these patients have been reported in a French cohort
(103 of 1,269 patients referred for AFL ablation): they
were found to be younger, with a lower prevalence of
ischemic cardiomyopathy, and a lower use of AAD, in
comparison with patients with systolic dysfunction unre-
lated to AFL.
32
The tolerance may be lower in case of 1:1
atrioventricular conduction (8%). Factors favoring the
occurrence of 1:1 conduction are: younger age, history of
AF, absence of structural heart disease, and obviously the
presence of Ic AAD.
33
The key for diagnosis will be the 12-lead ECG. As the
atrioventricular transmission is almost always 2:1, manoeu-
vers to increase the degree of AV block such as carotid
massage may be required. In other cases, the adenosine
injection (Figure 4), by the shortening of the atrial refractory
periods, may also induce AF (Figure 5). Sometimes, the
diagnosis may be established using the pulsed doppler on
the mitral valve (Figure 6). A recurrence of CTI-dependent
AFL may manifest with a prolonged cycle length (related to
the lengthening of the conduction within the CTI), which can
be recorded on the 12-lead ECG.
AFL and AF are often considered as “fellow-travelers”.
In the study published by Peyrol et al, patients presenting
with isolated AFL (n=44) were compared to patients pre-
senting with combined AFL and AF (n=32): they had
more frequently a prior history of cardiac surgery (pre-
sence of an atriotomy) and were less exposed to the use of
AAD in comparison with patients with both AFL and
AF.
34
Interestingly, data from the recent Danish nation-
wide cohort study revealed a higher mortality risk after
CTI ablation compared to patients undergoing an initial
AF ablation. The authors reported a higher rate of heart
failure and renewed (non-AF) arrhythmia management in
AFL.
35
In another national cohort study from Taïwan, the
net clinical outcomes with anticoagulation were observed
in solitary AFL with a CHA
2
DS
2
-VASc score ≥4. Solitary
AFL without anticoagulation had better clinical outcomes
than patients with combined AFL and AF.
36
Therapeutic options
As suggested by the recent international guidelines, med-
ical therapy is limited for CTI AFL, and catheter ablation
is an efficient strategy, which may be proposed as a first-
line therapy if nontolerated.
Figure 3 Example of counterclockwise cavotricuspid isthmus-dependent atrial flutter with 3:1 atrioventricular conduction, and mimicking sinus tachycardia in a 76-year-old
female patient who benefited from a previous procedure of pulmonary vein isolation and left atrial defragmentation.
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For acute therapy, intravenous beta-blockers or calcium
antagonists are recommended for acute control in patients with
AFL who are hemodynamically stable at first intention (syn-
chronized direct current cardioversion if hemodynamically
unstable).
For chronic therapy, CTI ablation is recommended with
a low incidence of complications in patients with recurrent or
poorly tolerated typical AFL (cardioversion with AAD for
patients with infrequent AFL recurrences or refusing
ablation).
37
Not surprisingly, class Ic AAD should not be used in
the absence of atrioventricular blocking agents because of
the risk of slowing atrial rate, leading to 1:1 conduction.
Catheter ablation
The procedure is well standardized, and the endpoints have
been described three decades ago. After the initial attempts at
direct current fulguration,
38
CTI-dependent AFL are easily
amenable to RF catheter ablation with a high success rate,
independent of the direction of the rotation, with the same
endpoints.
39–41
Careful confirmation of CTI dependency of
the circuit is always the first step of the procedure, using
entrainment-guided mapping techniques. Performing
a continuous line of ablation across the CTI has become the
standard therapeutic approach. A complete corridor (line of
double potentials) may be recorded all along the line.
42
The
first endpoint is obviously the arrhythmia interruption, but
should be associated with the presence of a persisting complete
CTI bidirectional conduction block, which should be assessed
by pacing techniques.
43
More recently, some authors have
proposed an ablation technique targeting preferentially high-
voltage electrograms within the CTI, corresponding anatomi-
cally to muscle bundles.
44
This therapeutical approach is now proposed as a first-line
therapy with high success rate,
45
rare complications, and
uncommon late recurrences in experienced hands, even in
elderly patients.
46
In a pooled population of patients experiencing AF and/or
AFL with a prolonged follow-up, it was reported that those
who benefited from a CTI ablation (37% with a history of
AF) had a better survival rate than other patients.
47
From this
study, the authors concluded that among patients with atrial
tachyarrhythmias, those with AFL who undergo CTI ablation
independently have a lower risk of stroke and/or death of any
cause, whether a history of AF is present or not.
For AF ablation procedures, the CTI ablation is recom-
mended only if the patient had a history of CTI-dependent
AFL, or if induced during the procedure.
48
Figure 7 shows an
I
Adenosine 24 mg
II
III
VR
VL
VF
Figure 4 Example of cavotricuspid isthmus-dependent atrial flutter with 1:1 atrioventricular conduction, unmasked by the adenosine injection.
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example of ectopies originating from the right superior pul-
monary vein, and inducing a CTI-dependent CCW AFL. The
CTI line was performed during the same procedure, on top of
the PVI.
Technology used
Different technologies have been used and validated for CTI
ablation. A 8-mm closed-tip catheter, or a 4 mm-catheter, may
be used, either with or without irrigation.
49
Remote magnetic
navigation,
50
a gold-tip catheter,
51
as well as cryotherapy have
also been used to perform the CTI line.
52
More recently,
contact-force guided catheters may also be used for CTI-
dependent AFL with a good efficacy and safety profile.
53,54
Some authors also used mini electrodes at the 8-mm tip of the
ablation catheter for better discrimination of the local electro-
grams within the CTI.
55
Recurrences after CTI ablation
Although rare, the recurrences may be seen, either with a CCW
or CW rotation.
56
The latter patients were younger in our
experience, with a shorter plateau duration on the surface
ECG. The other form of recurrence may be the occurrence of
an intraisthmus reentry. Careful entrainment mapping just out-
side the CS ostium can facilitate the diagnosis of this unusual
variant.
57
Finally, patients may elicit a recurrence in the pre-
sence of an endocardial block. This may be explained by the
possibility to observe an endo-epicardial breakthrough that
may represent a shortcut despite obvious endocardial conduc-
tion block.
58
If confirmed with an UHR mapping system, the
target will then become the endocardial breakthrough of the
circuit (Figure 8).
Thromboembolic therapy management
Lone AFL has a risk of stroke at least as high as lone AF
and carries a higher risk for subsequent development of
AF than in the general population.
59
The international guidelines then recommend that intra-
venous anticoagulation may be considered in case of emer-
gency cardioversion, continued for 4 weeks after sinus
rhythm has been established. Stroke prevention is
Adenosine
6 mg
Atrial fibrillation
Atrial fibrillation
Atrial flutter
I
II
V1
V5
I
II
V1
V5
Figure 5 Example of cavotricuspid isthmus-dependent atrial flutter in a 73-year-old female patient operated with a biological aortic valve prosthesis, with alternate 6:2
Wenckebach atrioventricular conduction. The adenosine injection will induce atrial fibrillation by shortening the atrial refractory periods, but then resolve into the initial
flutter after the washout of the drug, with a now 1:1 atrioventricular conduction (under sotalol).
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recommended with the same indications as in AF among
patients with typical AFL and associated episodes of AF.
Question remains for patients presenting for isolated
AFL documented before the apparition of AF.
60
New AF
occurs in ≥25% after RF ablation of isolated typical AFL
after a mean follow-up of 2.5±1.8 years (in a cohort of 315
patients).
61
Obstructive sleep apnea and LA enlargement
were independently associated with the development of
Figure 6 Recording during echocardiographic examination with the pulsed doppler on the mitral valve, suggesting the presence of an atrial flutter by the absence of
individualized A waves.
I
II
III
VL
VF
V1
V2
V3
CS p
CS d
RSPV
RSPV
1-2
10-11
Figure 7 Right superior pulmonary vein extrasystoles inducing counterclockwise cavotricuspid isthmus-dependent atrial flutter. The patient underwent a combined
procedure of pulmonary vein isolation coupled with a CTI line.
Abbreviations: CS d, distal coronary sinus; CS p, proximal coronary sinus; RSPV, circular mapping catheter inserted in the right superior pulmonary vein.
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new AF. Interestingly, most AF episodes will occur in the
2 years after CTI ablation.
62
A HATCH score >2 may be used to better identify the
patients most likely to develop new AF during the follow-up.
63
A recent nationwide cohort study (219,416 individuals) com-
pared the rate of ischemic strokes, heart failure hospitalization,
and all-cause mortality among AF, AFL, and matched control
cohorts over a decade. AF and AFL cohorts exhibited higher
rates of heart failure hospitalization and all-cause mortality in
comparison to the control cohort. Interestingly, the incidence of
ischemic strokes was only significantlyhigherintheAFL
group at CHA
2
DS
2
-VASc of 5–9 compared with that in the
control group. The authors raise the question of a possible
overtreatment (with anticoagulation) in patients with lone
AFL, if we follow the recommendation of the international
guidelines.
64
Conclusion
CTI-dependent flutter is an “old”arrhythmia and may be
one of the best examples of good ECG correlation with the
endocavitary mechanism of the arrhythmia. The treatment
is well standardized (after confirmation of the isthmus-
dependency of the circuit), i.e. the realization of
a complete CTI line of the block. It is associated with
a high success rate and low complication. Recent advances
in UHR mapping system are still helping us to evolve our
knowledge of this arrhythmia.
Abbreviation list
AAD, antiarrhythmic drug; AF, atrial fibrillation; AFL, atrial
flutter; AT, atrial tachycardia; CCW, counterclockwise; CS,
coronary sinus; CTI, cavotricuspid isthmus; CV, conduction
velocity; CW, clockwise; ECG, electrocardiographic; EP,
electrophysiological; IVC, inferior vena cava; LA, left
atrium; PVI, pulmonary vein isolation; RA, right atrium/
atrial; RF, radiofrequency; UHR, ultrahigh resolution.
Disclosure
Drs Bun and Latcu received some consultant fees from
Boston Scientific. The authors report no other conflicts of
interest in this work.
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SEPT
POST
310 ms
ANT
AB
CD
LAT
CS
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CS
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TV
IVC
TV
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Figure 8 Endoepicardial connection in the presence of an endocardial cavotricuspid isthmus line of block. Electroanatomical activation maps in an inferior projection
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