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Balloon catheter ablation to treat paroxysmal atrial fibrillation:
What is the level of pulmonary venous isolation?
Vivek Y. Reddy, MD,* Petr Neuzil, MD,† Andre d’Avila, MD,* Margaret Laragy, BS,*
Zachary J. Malchano, MS,* Stepan Kralovec,† Steven J. Kim, MS,‡ Jeremy N. Ruskin, MD*
From the *Cardiology Department, Homolka Hospital, Prague, Czech Republic, †Cardiac Arrhythmia Service,
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, and ‡St. Jude Medical, Inc.,
Minnetonka, Minnesota.
BACKGROUND Unlike the initial balloon ablation catheters that
were designed to deliver ablation lesions within the pulmonary
veins (PVs), the current balloon prototypes are fashioned to deliver lesions at the PV ostia.
OBJECTIVE Using electroanatomical mapping, this study evaluates the actual location of ablation lesions generated by cryobased, laser-based, or ultrasound-based balloon catheters.
METHODS In a total of 14 patients with paroxysmal atrial fibrillation, PV isolation was performed using either a cryoballoon
catheter (8 patients), laser catheter (4 patients) or ultrasound
balloon catheter (2 patients). Patients underwent preprocedural
computed tomographic/magnetic resonance imaging. An intracardiac ultrasound catheter was used to aid in positioning the balloon catheter at the PV ostium/antrum. In all patients, sinus
rhythm bipolar voltage amplitude maps (using either CARTO with
computed tomographic/magnetic resonance image integration or
Introduction
Electrical pulmonary venous (PV) disconnection is an effective means to treat patients with paroxysmal atrial fibrillation (AF).1– 8 Because of the technical difficulties associated with point-to-point ablation using a standard spot
ablation catheter with the left atrium (LA), there has been a
significant effort in developing alternative ablation catheter
designs to quickly and easily isolate PVs. The first such
device tested clinically was an ultrasound balloon ablation
catheter that delivered energy in a radial fashion at the level
of the diameter of the balloon, hence necessitating that the
balloon catheter be placed within the PV when delivering
energy.9 This balloon design was suboptimal because the
level of electrical isolation typically excluded the proximal
Supported in part by the Deane Institute for AF and Stroke Research,
and an NIH K23 award (HL68064) to Dr. Reddy. Drs. Reddy and Neuzil
have received research grant support from Cryocath Technologies, Inc,
Cardiofocus, Inc, Biosense-Webster, Inc, and St Jude Medical, Inc. Dr.
Kim is an employee of St Jude Medical, Inc. Address reprint requests
and correspondence: Dr. Vivek Y. Reddy, Cardiac Arrhythmia Service,
Massachusetts General Hospital, 55 Fruit Street, GRB-109, Boston, Massachusetts 02114.E-mail address: [email protected]. (Received May 4,
2007; accepted November 1, 2007.)
NavX mapping) were generated at baseline and after electrical PV
isolation as confirmed by use of a circular mapping catheter.
RESULTS Electrical isolation was achieved in 100% of the PVs.
Electroanatomical mapping revealed that after ablation with any
of the 3 balloon catheters, the extent of isolation included the
tubular portions of each PV to the level of the PV ostia. However,
the PV antral portions were left largely unablated with all 3
balloon technologies.
CONCLUSION Using the current generation of balloon ablation
catheters, electrical isolation occurs at the level of the PV ostia,
but the antral regions are largely unablated.
KEYWORDS Catheter ablation; Balloon catheter; Cryoablation; Laser; Focused ultrasound; Electroanatomical mapping; Atrial fibrillation
(Heart Rhythm 2008;5:353–360) © 2008 Heart Rhythm Society. All
rights reserved.
portions of the vein, so PV triggers of AF located at this
region would not be included in the ablation lesion.10 Also,
from a safety perspective, the intravenous location of the
energy delivery resulted in PV stenosis.
Since this first-generation device, balloon ablation catheters have evolved considerably.11 There are now 3 major
balloon-based ablation devices at various stages of clinical
evaluation: (1) cryoballoon ablation, (2) endoscopic laser
ablation, and (3) high-intensity focused ultrasound (HIFU).
Each of these has been fashioned to be placed at the PV
ostia so as to theoretically isolate the veins outside their
tubular portion. In this study, detailed electroanatomical
mapping (EAM) was performed after balloon ablation using
each of these 3 ablation strategies in patients with paroxysmal AF to assess the true anatomical location of electrical
PV isolation.
Methods
All procedures were performed after written informed consent according to institutional guidelines at the Massachusetts General Hospital and Homolka Hospital. In a total of
50 patients with paroxysmal AF in whom at least 1 membrane-active antiarrhythmic drug had failed, we performed
1547-5271/$ -see front matter © 2008 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2007.11.006
354
Heart Rhythm, Vol 5, No 3, March 2008
Figure 1
Catheter cryoballoon ablation system. A: The balloon ablation catheter is shown inflated after having been advanced through a deflectable sheath
(in black). The balloon catheter has a central lumen through which a guidewire can be advanced (as shown). B: Occlusion of the targeted PV ensures
circumferential balloon–tissue contact, and consequently electrical PV isolation. By injecting contrast through the balloon catheter central lumen, the left
superior PV is highlighted without evidence of periballoon contrast leak. C: In another example, ICE was also helpful to both identify the position of the
balloon catheter as well as to assess for periballoon leak. In this image, the back face of the balloon catheter is seen occluding the left inferior PV—flow
from the left superior PV is seen on color flow Doppler. ICE ⫽ intracardiac echocardiography; PV ⫽ pulmonary vein.
catheter ablation using either a cryoablation, laser, or HIFU
balloon ablation catheter. The cohort of patients discussed
in this report represents the 14 patients within this group
who underwent detailed LA-PV EAM both before and after
ablation.
Ablation procedures
Procedures were performed either with conscious sedation
or under general anesthesia. After standard femoral vascular
access, dual transseptal punctures were performed with fluoroscopic and intracardiac ultrasound (Acunav, SiemensUltrasound, Mountain View, California) guidance. Intravenous heparin was instituted before the transseptal puncture.
EAM of the LA-PVs was performed at baseline using either
a magnetic EAM system (CARTO, Biosense-Webster, Inc,
Diamond Bar, California) or an electrical impedance-based
EAM system (NavX, St Jude Medical, Inc, Minnetonka,
Minnesota). In selected patients, custom software was used
to register and project the electrical information onto a
patient-specific volumetric 3-dimensional image derived
from preacquired computed tomographic (CT) or magnetic
resonance (MR) imaging. Bipolar electrogram voltage amplitude data were displayed.
After baseline mapping, electrical PV isolation of all PVs
was performed using 1 of the 3 balloon ablation technologies as detailed below. Intracardiac echocardiography (ICE)
was used to aid in balloon catheter positioning at the various
PV ostia. Electrical PV isolation was established using a
circular 10-pole or 20-pole multielectrode mapping catheter
(Lasso, Biosense-Webster, Inc) to verify both entrance and
exit conduction block.
Cryoablation
The cryoablation balloon system is a deflectable catheter
with a balloon-within-a-balloon design wherein the cryo
refrigerant (N2O) is delivered within the inner balloon (Figure 1). There is a constant vacuum applied between the
inner and outer balloon to ensure the absence of refrigerant
leakage into the systemic circulation in the event of a breach
in the integrity of the inner balloon. The cryoballoon catheter used was 23 mm in diameter. The deflated balloon
catheter is deployed through a 12F deflectable sheath. Once
within the LA, the inflated balloon is positioned at the PV
ostium (with ICE guidance) to temporarily occlude blood
flow from the targeted PV. Each balloon-based cryoablation
lesion lasts 4 minutes.
Laser ablation
The laser ablation catheter system incorporates an endoscopic visualization capability using a 2F endoscope positioned at a proximal location in the balloon (Figure 2). A
deflectable sheath is also used to deliver this 12F balloon
catheter. Once in the LA, the 20-, 25-, or 30-mm-diameter
balloon is inflated and positioned at the PV ostia under ICE
guidance. The endoscope allows the operator to visualize
the internal face of the balloon and identify areas of balloon–tissue contact (blanched white) versus blood (red). An
optical fiber that projects a 90° to 150° arc is advanced and
rotated to the desired location for energy delivery. Once the
proper location is identified, a diode laser is used to deliver
laser energy at 980 nm (5.5 to 6.5 W/cm for 60 to 120
seconds/lesion).
HIFU ablation
The HIFU catheter is a 14F system that, once inflated,
consists of a fluid-filled balloon in front of a smaller CO2
filled balloon (Figure 3). Energy from a radially directed
ultrasound transducer reflects off this air–fluid interface to
project forward and concentrate energy to deposit just beyond the face of the balloon. Contact with the atrial tissue is
Reddy et al
Balloon Isolation of Pulmonary Veins
355
Figure 2 Endoscopic laser balloon ablation system. A: The balloon ablation catheter is shown inflated after having been advanced through a deflectable
sheath (in blue). An aiming beam is projected from an optical fiber as an arc that can be rotated and advanced/retracted. When the proper location is selected,
the laser energy is transmitted via this same optical fiber. The mini-endoscope is located at the proximal end of the balloon catheter (near the white light)
and is facing forward. B: ICE is helpful to identify the position of the balloon catheter relative to the vein; in this image, the balloon is at the ostium of the
left superior PV, as well as straddling the ostium of the left inferior PV. C, D: Two examples of the images seen through the endoscope. Red represents blood,
and white represents the blanched balloon–tissue contact. The green arc of the aiming beam is manipulated to select the locations to deliver the laser energy.
The endoscopic field of view is partially obstructed (as outlined by the dotted lines) by the central lumen of the balloon catheter. Abbreviations as
in Figure 1.
not necessary for ablation with this catheter. This deflectable catheter is delivered using a nondeflectable 14F sheath.
ICE was used to verify proper positioning of the catheter.
Lesions were delivered using either a 20- or 25-mm-diameter balloon catheter for 40 to 60 seconds per lesion.
Results
Of the 50 patients who underwent balloon catheter ablation, preablation and postablation EAM was performed
on 8, 4, and 2 patients with the cryoablation, laser, and
HIFU balloon catheters, respectively. The average LA size
was 43.6 ⫾ 3.9 mm for the complete patient cohort and
41.5, 46.8, and 45.5 mm for the patients treated with the
cryoballoon, laser balloon, and HIFU balloon catheters,
respectively. The majority of the patient cohort (9 of 14,
64%) had 4 relatively distinct PVs: 4 and 2 patients had
either a discrete left common PV or right middle PVs,
respectively. The individual details for these patients are
shown in Table 1.
Respective examples of use of each of the balloon ablation catheters are shown in Figures 1 to 3. Electrical isolation of the PVs was achieved in 54 of 54 veins, as verified
by using a circular mapping catheter placed just inside (that
is, within the first 2 to 3 mm) of the respective PVs. To
determine the extent of this electrical isolation, electroanatomical bipolar voltage amplitude substrate mapping of the
LA-PVs was performed at baseline and postablation (Figures 4 to 6). Regardless of the balloon ablation energy
source, the extent of isolation included the tubular portions
of each PV. For a quantitative analysis, the bipolar voltage
amplitudes of the electroanatomical points acquired from
each pair of ipsilateral veins was calculated. The preablation
and postablation amplitudes of the left PVs were 0.5 ⫾ 0.8
mV (number of electroanatomical points measured per
patient ⫽ 56 ⫾ 20) and 0.1 ⫾ 0.2 mV (number of points ⫽
61 ⫾ 34), respectively. For the right PVs, the preablation
and postablation amplitudes were 0.8 ⫾ 0.9 mV (number of
356
Heart Rhythm, Vol 5, No 3, March 2008
Figure 3
High-intensity focused ultrasound balloon ablation system. A: Shown in this schematic of the HIFU catheter is the reflective interface created
by the anterior fluid-filled balloon (in blue) and the posterior CO2 gas-filled balloon. The radially directed ultrasound energy is reflected forward to create
a circumferential zone of concentrated ablative energy just beyond the fact of the balloon. B: An ICE catheter is placed within the coronary to visualize the
HIFU catheter positioned at the ostium of the left inferior PV. As shown, the balloon catheter does not need to be in contact with the LA-PV tissue for
effective ablation. HIFU ⫽ high-intensity focused ultrasound; LA ⫽ left atrium; other abbreviations as in Figure 1.
electroanatomical points measured per patient ⫽ 60 ⫾ 40)
and 0.1 ⫾ 0.1 mV (number of points ⫽ 46 ⫾ 20), respectively. But as shown in Figures 4 to 6, the antral portions
of the PVs were not ablated with the balloon ablation
catheters.
There were no complications in the patients studied in
this report. During a mean follow-up of 461 ⫾ 109 days
(range 309 to 609), 4 of 14 patients had clinical recurrences
of atrial fibrillation (Table 2). This included 2 patients who
had undergone cryoballoon ablation and 2 patients who had
undergone laser balloon ablation. Because of the frequency
of clinical symptoms, 2 of these patients (the 2 cryoballoon
ablation patients) underwent repeat catheter ablation. In
both of these patients, the repeat procedure revealed resumption of electrical conduction into the PVs. Focal ablaTable 1
tion using standard radiofrequency ablation isolated the PVs
in both of these patients, and there was no inducible AF with
rapid atrial pacing or during the infusion of Isuprel (up to 20
␮g/min).
Discussion
The key findings of this study are: (1) the 3 balloon ablation
catheter designs are all capable of electrically isolating the
PVs outside the tubular portions of the PVs at the level of
the PV ostia, and (2) the PV antra are left largely unaffected
by this ablation stratagem.
The importance of PV isolation during catheters ablation
of paroxysmal AF has been established as a result of several
key clinical observations.1– 8 First was the initial description
that the PVs harbor foci that initiate AF, and that in indi-
Individual patient information
PV sizes (mm)
Patient no.
Ablation
energy source
Balloon
diameter(s) (mm)
LA size
(mm)
Mapping
system
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Cryo
Cryo
Cryo
Cryo
Cryo
Cryo
HIFU
HIFU
Cryo
Laser
Laser
Cryo
Laser
Laser
23
23
23
23
23
23
20
20,
23
20,
25,
23
25,
20,
41
43
39
48
37
37
43
48
43
46
47
44
47
47
EiEAM
MEAM
MEAM
EiEAM
EiEAM
EiEAM
EiEAM
EiEAM
MEAM
EiEAM
EiEAM
MEAM
EiEAM
EiEAM
25
25
30
30
25
LSPV
LIPV
21
19
LCPV
26
15
21
19
18
20
27
14
18
14
18
15
19
20
17
19
19
17
15
18
14
22
RSPV
RIPV
22
26
16
20
18
13
23
25
16
18
20
21
21
21
15
19
21
23
12
15
17
21
19
18
19
16
20
19
RMPV
6
9
Cryo ⫽ cryoablation; EiEAM ⫽ electrical impedance-based electroanatomical mapping; HIFU ⫽ high-intensity focused ultrasound; LA ⫽ left atrium; LCPV
⫽ left common pulmonary vein; LIPV ⫽ left inferior pulmonary vein; LSPV ⫽ left superior pulmonary vein; MEAM ⫽ magnetic electroanatomical mapping;
PV ⫽ pulmonary vein; RIPV ⫽ right inferior pulmonary vein; RMPV ⫽ right middle pulmonary vein; RSPV ⫽ right superior pulmonary vein.
Reddy et al
Balloon Isolation of Pulmonary Veins
357
Figure 4
Level of electrical isolation using the cryoballoon ablation catheter. Shown are baseline and postablation bipolar voltage amplitude maps of the
LA-PVs. After registering the magnetic electroanatomical mapping data with the patient’s 3-dimensional magnetic resonance image, the voltage amplitude
electrogram information was projected onto the 3-dimensional image. In the color range shown, red represents low amplitude (ⱕ0.1 mV) and purple high
amplitude (ⱖ1 mV). Abbreviations as in Figure 3.
viduals with paroxysmal AF ablation of these foci could
eliminate AF. However, direct targeting of these foci fell out
of favor for 2 reasons: (1) it was difficult and time consuming
to evoke these PV triggers during any given procedure, so it
was common to see clinical recurrences from a different focus
either within the same PV or from another PV, and (2) excessive ablation within the veins caused PV stenosis. This initial
approach was followed by a strategy of routine electrical isolation of all PVs in any given patient. Although initially
performed within the tubular portions of the PVs in a segmental fashion using a circular mapping catheter to guide
the procedure, this was again followed by clinical recurrences from foci just proximal to the ablation line (as well
as PV stenosis). Accordingly, the procedure has now
evolved to an extraostial ablation strategy involving placement of the lesions outside the PVs, a procedure that is
somewhat facilitated by the use of EAM systems.
Although this current approach to ablation of paroxysmal
AF has a good efficacy and acceptable safety profile, it
remains a technically difficult procedure requiring skilled
operators. This has prompted the intense development of
catheter systems to rapidly and safely isolate the PVs. But
this has not proven to be an easily tractable problem, in
large part because of the complexity of the PV anatomy.
The variability in both PV shape and anatomy is well
established.12–14 Instead of round PVs that join the LA
chamber in a perfectly orthogonal manner, the PVs have an
oval configuration, often combine with the ipsilateral vein
before joining the LA proper, and typically have an oblique
angle with which they join the LA. In addition, the junction
of the PVs with the LA is not distinct and often includes an
antrum that may include a large portion of the posterior
LA.14 In fact, some investigators contend that the complete
posterior LA must be ablated or otherwise electrically excluded to achieve the best clinical outcome.15
Three balloon catheter technologies using different ablation energy sources have evolved to negotiate this anatomical complexity. The cryoablation balloon catheter is advanced to each PV ostium, and forward pressure is applied
to completely occlude blood flow. Because the cyrorefrigerant is delivered to the whole face of the balloon, any tissue
in contact with the balloon is ablated. This can be safely
performed because experimental and clinical results have
shown that cryothermal ablation is associated with minimal
risk of PV stenosis.16,17 On the other hand, the diode laser
balloon catheter uses a strategy involving an endoscope to
allow the operator to visualize balloon–tissue contact, and
an adjustable lasing element to tailor the lesion to the
appropriate location.18 By varying the location of this adjustable aiming beam, a series of arcs of laser energy are
applied to the tissue at only the desired locations. This
provides a greater flexibility to both the location of the
358
Heart Rhythm, Vol 5, No 3, March 2008
Figure 5
Level of electrical isolation using the laser and HIFU balloon ablation catheters. A: Using the electrical impedance-based electroanatomical
mapping system, the LA-PV anatomy was constructed and the projected bipolar voltage amplitude maps are shown after ablation using the laser balloon
catheter (left, anterior view; right, posterior view). B: Similarly, after ablation using the HIFU catheter, posterior views of the baseline and postablation
voltage maps are shown. Abbreviations as in Figure 3.
energy deposition and the total amount of energy applied to
each site; for example, a greater amount/duration of energy
could be applied anteriorly along the ridge between the
left-sided PVs and LA appendage than that applied along
the posterior wall near the course of the esophagus. Alternatively, because the HIFU balloon ablation catheter is
designed to concentrate the energy beyond the face of the
balloon surface, contact with the tissue is not required for
ablation. Ablation with this technology can be performed in
a piecemeal fashion with the HIFU balloon catheter delivering a series of sequential lesions as it is precessed about
the long axis of the PV.19 –21 This is feasible because HIFU
energy is associated with minimal thromboembolic risk
even when sonicating directly into blood.
The results from the present study show the actual location of the ablation lesion set when using these 3 balloon
technologies. As shown, all PVs can be isolated at the level
of the PV ostia and, importantly, outside their tubular portions. However, it must also be noted that in large part, the
PV antra are not ablated. The clinical impact of not addressing this tissue in the lesion set is unknown. Despite the lack
of effect on the antra, the preliminary clinical experience
with these balloon ablation catheters in patients with paroxysmal AF has revealed an approximately 70% arrhythmia-free success rate at 1 year, a result similar to that seen
with radiofrequency ablation.17,18,21 Despite the relatively
small number of patients in this series, it is interesting to
note the results of the patients re-studied for clinical recur-
rences. The cause of the recurrences was not PV antral or
other extrapulmonary triggers, but rather a resumption of
electrical continuity with the PVs. This again speaks to the
importance of the adequacy of the level of PV isolation.22
Indeed, as shown in Figure 7, the level of isolation seen
during point-to-point radiofrequency ablation is similar
to that seen with the balloon ablation catheters. Thus, for
patients with paroxysmal AF, it remains an open question
whether ablation beyond the level of the PV ostium is
really necessary.
It should be noted that for each of these balloon systems,
there is the potential for modifying these devices to allow
for a more extensive LA ablation zone. The most intuitive
initial step is to simply increase the diameter of the ablative
balloon element. However, the preliminary clinical experience with this approach has been disappointing in large part
because the atrial tissue is less distensible than initially
expected. When larger cryoballoons or laser balloons were
used, circumferential contact with the tissue, a known requirement for efficacy with these balloon systems, could not
be achieved. Because of the poor compliance of the atrial
chamber, it seems that a better alternative will be to make
the balloons more compliant to the tissue, a concept currently being explored in second-generation systems. The
HIFU system, on the other hand, does not need tissue
contact to be effective. But to easily use this technology to
ablate the PV antra, it will be necessary to improve the
navigability of this catheter. For example, by incorporating
Reddy et al
Balloon Isolation of Pulmonary Veins
359
Figure 6 Level of electrical isolation after standard radiofrequency catheter ablation. In a patient with paroxysmal AF, electrical PV isolation was
performed using a 3.5-mm irrigated-tip radiofrequency ablation catheter under electrical impedance-based electroanatomical mapping guidance to place an
extraostial ablation lesion set. Shown are the baseline (A) and postablation (B) voltage amplitude maps of the LA-PVs. Abbreviations as in Figure 3.
an EAM capability (whether magnetic-based or electrical
impedance-based) into the catheter, it may be possible to
stitch together a series of ablation lesions incorporating the
PV antra as the balloon is widely precessed about the orifice
of each vein.
Unlike patients with paroxysmal AF, there is considerable evidence that catheter ablation of persistent/permanent AF may require ablation beyond electrical isolation of the PVs. Particularly for those patients with
permanent AF, it seems necessary to perform a staged
ablation strategy involving linear ablation, ablation of
sites of complex fractionated electrograms, and ablation
within the coronary sinus and right atrium.23 It is less
likely that the balloon ablation paradigm of electrical PV
isolation alone would be adequate for these patients.
Further clinical work is necessary to investigate these
hypotheses.
Limitations
Because of the complexity of the LA-PV anatomy, it is
difficult to quantify the level of PV isolation beyond that
described in this report. However, this does not detract from
the main conclusion of this investigation, namely that balloon ablation incorporates electrical isolation of the PV
ostia but not antra.
Table 2
Patient follow-up
Patient Duration of
AADs
Clinical
Repeat
no.
follow-up (days) discontinued? recurrence? procedure?
1
2
3
4
5
6
7
8
9
10
11
12
13
14
609
595
593
574
552
529
408
390
394
394
396
395
310
309
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes
No
Yes
No
Yes
No
AADs ⫽ antiarrhythmic drugs.
No
Yes
No
No
No
Yes
No
No
No
No
No
Yes
No
Yes
Yes
Yes
No
No
360
Implicit in this study is the assumption that catheter
ablation using these balloon catheters is technically easier to
perform than point-to-point using a standard spot ablation
catheter. However, this assertion must be proven in a comparative study.
This report does not address the ability to make permanent isolating lesion sets. It has been shown that in paroxysmal AF patients with post–radiofrequency ablation clinical recurrences, PV reconnection is a critical factor. As
shown by the patients with clinical recurrences, the predictors of achieving permanent PV isolating lesions with the
balloon-based ablation catheters remain to be identified in
future evaluations.
Conclusion
When treating patients with paroxysmal atrial fibrillation,
balloon ablation catheters are able to isolate the PVs outside
the level of the tubular vein. However, the current generation of balloon ablation catheters leaves the veins’ proximal
antral regions unablated.
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