Pulmonary Vein Stenosis after Catheter Ablation

DOI: 10.1161/CIRCEP.113.001111
Pulmonary Vein Stenosis after Catheter Ablation:
Electroporation versus Radiofrequency
Running title: van Driel et al.; PV Stenosis after Ablation: Electroporation vs RF
Vincent J.H.M. van Driel, MD1*; Kars G.E.J. Neven, MD1,2*; Harry van Wessel, BSc1;
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
Bastiaan C. du Pré, MD1; Aryan Vink, MD, PhD3; Pieter A.F.M. Doevendans,, MD,, PhD1;
Fred H.M. Wittkampf, PhD1
Department
ent ooff Card
ent
Cardiology,
dio
i logy, University Medical Center,
Cen
nte
ter, Utrecht, The
T e Netherlands;
Th
N therlands; 2Departm
Ne
Department
m of
3
ologgy, Alfriedd Krupp
ol
K up
Kr
pp Hospital,
Hosp
Ho
s it
sp
ital
a , Essen,
al
Esssen, Germany;
Germ
many;
y De
y;
Department
Depa
arttmeent off Pa
Path
Pathology,
th
hol
olog
ogy,
og
y U
University
n ve
ni
v
Rhythmology,
Medical
Medica
Me
call Center,
Centerr, Utrecht,
Utrreccht,, The
Thee Netherlands.
Net
ethherllan
nds..
* contributed
cont
n ri
nt
ribu
bute
bu
t d eq
te
equally
qua
uallly
1
Correspondence:
V.J.H.M. van Driel, MD
University Medical Center
Division of Heart and Lungs
Department of Cardiology
PO Box 85500
3508 GA Utrecht
The Netherlands
Tel: +31-88-7557269
Fax: +31-88-7555472
E-mail: [email protected]
Journal Subject Codes: [22] Ablation/ICD/surgery
1
DOI: 10.1161/CIRCEP.113.001111
Abstract:
Background - Radiofrequency (RF) ablation inside pulmonary vein (PV) ostia can cause PV
stenosis. A novel alternative method of ablation is irreversible electroporation, but the long-term
response of PVs to electroporation ablation is unknown.
Methods and Results - In 10 six-month old pigs (60-75 kg), the response of PVs to circular
electroporation and RF ablation was compared. Ten consecutive non-arcing, 200 joules (J)
electroporation applications were delivered 5 to 10 mm inside one of the two main PVs, using a
custom deflectable 18 mm circular decapolar catheter. Inside the other PV, circular RF ablation
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
was performed using 30 watts RF applications via an irrigated 4 mm ablation catheter. PV
angiograms were made before ablation, immediately after ablation and
months
d aafter
fter
ft
er 3 mo
mont
nths
nt
hs ssurvival.
u vii
ur
PV diameters and heart size were measured. With electroporation ablation,
ation, PV ostial
osttia
iall diameter
diam
di
a e
am
decreased 11±1
11±10%
±10%
±1
0 directly
0%
dir
irecctlly after ablation, but had increased
incrreased 19±11% aafter
in
f er 3 months. With RF
ft
ablation, PV
remained
V ostial
ostial diameter
diam
meterr decreased
dec
ecre
reas
re
ased
as
ed
d 223±15%
3±15%
3±
% ddirectly
irect
ctly aafter
fterr abl
ft
ablation
bllat
atio
ionn aand
io
ndd re
rema
main
ma
ined
e 77±17%
±17
±1
±17%
smaller after
21±7%
increase
during
err 3 months
m nths
mo
h than
hs
tha
han pre-ablation
pree-ablation
e-ab
bla
lati
t onn diameter
diaameter despite
deesppit
ite
te a 221
1±7
7% incr
creaase in he
hheart
arrt sizee ddu
u
aging from
months.
m 6 too 9 mont
n hs.
nt
Conclusions
200
applications
n - In this
ns
thi
his porcine
hi
porc
po
r in
i e model,
mode
d l, multiple
mullti
tipl
ipl
ple circumferential
circumf
i
ferentia
i l 20
00 J electroporation
ellecctr
t opporationn ap
appl
p icaa
pl
inside the PV
P ostia
ost
stia
ia do
do not
not affect
afffe
f ct
c PV
PV diameter
d amet
di
am
meter
ter aatt 33-month
-month
-m
mon
onth
th
h follow-up.
fol
ollo
loww up
up.. RF aablation
blat
bl
atio
tio
i n in
iinside
side
si
de P
PV
V ostia
causes considerable PV stenosis directly after ablation, which persists after 3 months.
Key words: catheter ablation, pulmonary vein, pulmonary vein stenosis, radiofrequency,
electroporation ablation, radiofrequency ablation
2
DOI: 10.1161/CIRCEP.113.001111
Introduction
Circular electroporation ablation is a novel technique for pulmonary vein (PV) isolation. In a
previous animal study, feasibility and safety of circular electroporation for the creation of PV
lesions were investigated after a 3-week survival period. One to 4 sequential, non-arcing
electroporation applications of 200 joules (J) eliminated PV electrograms in most ostia.1
However, the long-term risk of PV stenosis after electroporation ablation still is unknown.
The present animal study was performed to investigate the response of the PV to an
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
excessive number of circular electroporation applications compared too circular RF ablat
ablation
attio
ionn after
a 3-month survival period.
Methods
All 10 porcine
were
performed
after
Animal
Experimentation
cinee experiments
exp
xper
erim
er
im
imen
men
e tss w
erre pe
erf
r or
orme
m d af
afte
teer prior
prio
pr
ior approval
io
appr
ap
prov
pr
oval
ov
all ffrom
r m th
ro
thee An
A
imal
im
al E
Experiment
x er
xp
erim
im
men
e t
Committee of the
University
Guide
Care
and
the
h Utrecht
Utr
trec
echt
ec
htt U
n ve
ni
vers
rsit
rs
ityy and
it
an in
an
i ccompliance
om
mpliaanc
ncee wi
with
t tthe
th
he G
u de ffor
ui
or C
arre an
nd Us
Usee of
Laboratory
y Animals
Anima
Animals.
alss.2 E
Each
Ea
ach
h aanimal
niima
mall (6
((60-75
(60
0-75
75 kkg)
g)) wa
w
was
ass in
iintubated
ntu
t ba
batteed an
aand
d an
aanesthetized
esth
es
thet
th
ettiz
i ed
d aaccording
ccor
cc
o di
d ngg tto
o
standard procedures.1
The porcine left atrium (LA) has 2 PVs suitable for circular catheter ablation: one right or
septal PV (RPV) and one inferior PV (IPV) (Figure 1). The RPV enters the LA in close
proximity to the atrial septum and fossa ovalis. Before their entrance into the LA, multiple
branches merge into a common RPV tubular segment of approximately 10-15 mm in length. The
IPV has an approx. 12 mm long tubular segment, and the RPV has an approx. 15 mm long
tubular segment after the confluence of a septal and a lateral branch (Figure 1).
First, a coronary sinus catheter was inserted via the right jugular vein as fluoroscopic
reference for transseptal access. A quadripolar catheter was inserted via the right jugular vein
into the right ventricular apex for back-up pacing. Transseptal puncture was performed through
3
DOI: 10.1161/CIRCEP.113.001111
the right femoral vein. A deflectable 8 French (F) sheath (Agilis™, St. Jude Medical,
Minnetonka, MN) facilitated LA catheterization. A temporary screw-in pacing wire (6416,
Medtronic Inc., Minneapolis, MN) was inserted via the right femoral vein and fixated in the
atrial septum to serve as positional reference for the NavX™ 3D Navigation system (St. Jude
Medical, Minnetonka, MN).
The LA geometry (including part of the PVs) was reconstructed using the NavX™
system and a standard deflectable quadripolar irrigated ablation catheter with a 4 mm distal
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
electrode (Thermocool™, Biosense Webster Inc., Diamond Bar, CA). Thereafter, angiography
of
anggio
ogr
graa
both PVs was performed using the antero-posterior (AP), 30 degrees (o) righ
right
ghht an
ght
ant
anterior
teriior ooblique
te
bliiq
bl
iq
d 300o le
left
ft aanterior
n errio
nt
ior oblique (LAO) projecti
projections
tion
ti
o s for the IPV;
on
V aand
nd AP, 30o cranial andd 30o
(RAO) and
caudal projections
ject
je
ctions
tions for thee RPV.
RPV
PV
V. After
Affter
te PV angiography,
angiograp
angio
ogrraphy
hy,, bo
bboth
th
h PVs
PVss were
weree alternately
altterrnateely ab
ablate
ablated
ed uusing
t ora
tropo
rati
tioon or RF
ti
F energy.
y
either electroporation
Electroporation
r i n ab
ratio
ablation
blati
tion
ion
A custom deflectable,
ddeflectable
efl
flecttabl
ble 7F
7F, 18 mm circ
circular,
cii llar decapolar
de
la el
electroporation
l tr
ati
tio catheter
thett containing
taiiniin 2 mm
m
ring electrodes separated by 4 mm spacing was introduced through the deflectable sheath in the
right femoral vein (Figure 2). This catheter was deployed in the common tubular segment of one
of the 2 PVs. Inside the PV, ten cathodal 200 J shocks were delivered between all electrodes of
the electroporation catheter and a large indifferent skin electrode (7506, Valley Lab Inc.,
Boulder, CO) on the shaven lower back. An external, monophasic defibrillator (Lifepak™ 9,
Physio-Control Inc., Redmond, WA) was used for energy delivery.1, 3, 4 During each application,
current and voltage waveforms were recorded on a dual channel oscilloscope (Tektronix™ TDS
2002B, Beaverton, OR). For each ablation, a different position of the electroporation catheter
was chosen to cover the complete tubular segment. Ten applications of 200 J were always
4
DOI: 10.1161/CIRCEP.113.001111
delivered even when all PV electrograms had already been eliminated. All electroporation
catheter positions were stored with the NavX™ system. After each application, the circular
electroporation catheter was reconnected to the NavX™ and electrophysiological recording
system (Cardiolab™, General Electric Healthcare, Waukesha, WI) to check electrode integrity
and to visualize the electrode positions on the NavX™ system.
RF ablation
The other PV was circumferentially ablated approximately in the middle of the common tubular
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
segment using sequential 30-watt RF applications delivered via the 4 mm irriga
irrigated
g ted ablation
ablaati
tion
o
on
catheter and a saline flow rate of 17 ml/min. Maximal electrode temperature
eratur
uree was
was se
sett at 442
2oC
C.
ly,, m
maximal
a im
ax
mal
a RF
RF duration per vein was set
seet at
at 15 minutes.
s PV
V isolation was not the
Intentionally,
objective or
or endpoint
enndpoint forr electroporation
elecctrropor
oraationn orr R
or
RF
F ab
ablation.
blattioon.
angi
giiog
ogra
raph
ra
aphy was pe
performe
m d direct
me
ctly
ct
ly aft
ly
ftter ablating
abl
blat
bl
atiing both
at
both
hP
V usi
Vs
ing tthe
he same
PV angiography
performed
directly
after
PVs
using
fluoroscopic
i setti
ic
settings
inggs as tthe
he ppre-ablation
re-ab
bla
l tiion P
PV
V angi
angiograms.
gioggrams.
gi
Follow-up
All catheters were removed and the animals were allowed to recover and kept under daily
surveillance. After a 3-month survival period, PV angiography was repeated in all animals using
the same techniques as described above. Thereafter, the animals were euthanized by
exsanguination.
Histological investigation
After fixation, the common tubular segment of the both PVs, from antrum to approximately the
level of branching, was sliced in 3 circular 4-mm long segments and embedded in paraffin.
Elastic van Gieson stained sections of the pulmonary side of each of those segments were
scanned. Of each section, the percentage of the perimeter showing a myocardial sleeve was
5
DOI: 10.1161/CIRCEP.113.001111
measured using ImageJ (National Institutes of Health). The ablated PVs were compared to
control PVs from untreated animals.
Angiographic analysis
Three investigators, blinded for the type of therapy, analyzed all PV angiograms. PV diameters
were measured from the PV angiograms taken before ablation, directly after ablation and at 3
months and in all 3 projections. When PV narrowing was obvious at 3 months, PV diameters
were always measured at that location. When no narrowing was visible, all measurements were
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taken in the middle of the common tubular segment. All measurementss were taken at th
the
he en
eendsystolic phase (maximal PV filling and diameter). Diameters measuredd in the
the 3 projections
projjec
ecttio
ionns
ns were
averaged to
obtain
The
o ob
obta
tain
ta
in
n 1 value
value
ue for the PV diameter. Th
he ppercent
ercent change
g inn PV
P diameter was
calculated rel
rrelative
e ative to the ppre-ablation
re-ab
blatiion ddiameter.
i metter.
ia
As a measure
transversal
diameter
measured
mea
easu
ea
sur
ure off he
hheart
artt size,
i the
the llargest
arges
esst tr
tra
ansversall he
hheart
artt di
ar
iameter
t wass m
easuredd ffrom
rom the
pre-ablation
angiograms
n andd 33-month
-mont
nthh angi
nt
gioggrams taken
gi
tak
ken iinn the
th
he AP projection.
proje
j cti
je
tion.
Statistical analysis
l i
Data are expressed in mean ± standard deviation (SD) or as mean (95% confidence interval). A
P-value of 0.05 was used as the level of statistical significance. Special software (SPSS Statistics
20, IBM Inc., Armonk, NY) was used for statistical analysis. A repeated measures analysis-ofvariance (ANOVA) of percentage change in diameter was performed to compare the RF and
electroporation ablation measurements between the 3 independent and blinded investigators. The
effect of ablation technology on the presence of a (part of the) myocardial sleeve in histological
sections, corrected for depth of those sections, was investigated in a binary logistic mixed model.
The growth in heart size between the acute and the 3- month procedure was investigated with a
paired t-test.
6
DOI: 10.1161/CIRCEP.113.001111
Results
None of the electroporation applications resulted in catheter or electrode failure. All shocks
resulted in smooth voltage and current waveforms, demonstrating the absence of arcing and
barotrauma. The 3-month survival period was uneventful in all animals. Because of technical
difficulties, IPV angiography directly post-ablation was not performed in 2 animals.
Average RF application time was 12.3 ± 5.9 minutes. In 2 IPVs (animal #2 and #4) more
than 15 minutes of RF was necessary to complete the “circle” due to frequent catheter
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dislodgement.
Angiographic analysis
Repeated mea
measures
ANOVA
significant
between
m
asuures
rees AN
A
OVA showed no significan
OV
nt in
iinteraction
teraction be
etwee
eeen investigators and
methods (p=0.35).
directly
ablation,
p=0.3
p=0
=0.35).. With R
=0
RF
F ablation,
abllation
ab
on, PV
on
V diameters
diaameeteers decreased
decreeasseedd 233 ± 15
15%
5% ddirect
irectly
ly
y af
after
fteer abl
ablat
blat
bl
and remained
diameters.
ned 7 ± 17%
17%
7 small
smaller
l er after 3 m
ll
months,
onth
thss, when
th
when comp
compared
mpared
mp
ed w
with
itth pr
ith
pre-ab
pre-ablation
bla
lati
tion ddiameters
ti
iametters An
example off RPV
after
RF
ablation
shown
Figure
Directly
after
P ddiameter
PV
iamete
teer change
h g af
ft R
fter
F ab
bla
l tion iiss sh
hown in
in F
ig
guree 3.
3 D
irectlly af
afte
terr
te
electroporation
ablation,
10%,
after
ation
ati
tio abl
ablation
blati
ti
PV ddiameters
ia te ddecreased
ed
d 111
1 ± 10
10%
% bbutt had
had
d increased
i
ed
d 119
9 ± 11
11%
% af
f 3
months, when compared to pre-ablation diameters (Figure 4). Repeated measures ANOVA
demonstrated a highly significant difference in long-term (3 months) response between RF and
electroporation ablation (26%), p=0.006, 95% CI (9.54;42.01) (Table). The acute change in PV
diameter was not statistically analyzed.
During aging of the animals from 6 to 9 months, the heart diameter, measured in the
anterior-posterior projection, increased 21 ± 7%. (p<0.001) (Figure 4).
Histological analysis
Due to various reasons, unrelated to the degree of PV stenosis, 3 hearts were not available for
histological analysis of PV sleeves. Of the remaining hearts, 1 inferior PV had accidently been
7
DOI: 10.1161/CIRCEP.113.001111
cut off during heart explantation. Consequently, only 7 RPVs and 6 IPVs could histologically be
analyzed for the presence of a myocardial sleeve 3 months after ablation. In total 37/39
histological sections made from these 13 PVs were eligible for analysis. Of these 13 PVs, 7 had
been treated with RF and 6 with electroporation.
The 3 control PVs from 2 untreated pigs revealed complete sleeve coverage and normal
vessel wall of the vein (figures 5a and 5b). In the histological sections of the PVs treated with
RF, scar tissue surrounded the PV (figure 5c). In addition, intimal proliferation, necrotic
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
myocardium, and proliferation of the elastic lamina were found (figuree 5d)
5d),
comparable
), comp
parablee tto
o
previous findings of Taylor et al.5 Three months after ablation, the median
diann sleeve
sllee
eeve
ve ccoverage
overrag
ov
agee was
nd 00%
% at
a 4m
m, 8 mm, and 12 mm dista
tannce from the P
ta
V an
aantrum,
trum, respectively.
40%, 13% and
mm,
distance
PV
Conversely,
nversely,
n
versely, the PVs
ve
PVs treated
treeated
ed
d with
witth IRE
IR
RE ablation
ab
blation
on are
re surrounded
surroun
unded by
un
by healt
healthy
healthy
hy connective
connectiv
con
onnect
cttiv
art from
f om
fr
om the
the ablated
abl
b ated
bl
t d myocardial
myocaard
rdiial sl
sleeve,
lee
eeve
vee, onl
only
ly min
ly
minor
inor
in
or iintimal
ntim
imall hyperplasia
hyperpl
plas
pl
asiia was prese
as
tissue. Apart
present,
comparablee to our fi
find
findings
din
ings
g wi
gs
with
ithh coronary
y arteri
arteries
ies iinside
nside
id el
electroporation
lectropo
t po
pora
r tiionn llesions.
esiions.4 Me
Median
Medi
d an sleeve
di
s
coverage in
n th
these PV
PVs was
as 0% att all
ll three
th ddepths.
depths
epth
ths With
With RF,
RF the
th myocardial
m ocardial
diall sleeve
slee
le e was
as ttotal
totally
ottall
absent in 9 of 20 sections; while with electroporation the myocardial sleeve was absent in 14 of
17 sections (p=0.01; OR 16.96; 95% confidence interval 2.0-142.7).
Discussion
In this porcine animal model, electroporation and RF ablation were purposely delivered inside
the PVs to provoke stenosis. In the absence of previous porcine studies about PV stenosis or
narrowing in response to RF ablation, we alternated circular RF and electroporation ablation
between the 2 suitable PVs, thereby using the animals as their own control. Despite a significant
growth of the animals and heart size (21 ± 7%) during aging from 6 to 9 months, PVs that had
been ablated with RF reduced in diameter whereas those ablated with electroporation grew in
8
DOI: 10.1161/CIRCEP.113.001111
size: -7 ± 17% versus +19 ± 11%, (p=0.006).
Given the large myocardial lesions obtained with circular 200 J electroporation ablation
in previous studies, histological analysis of the PVs was not part of the original study protocol.1, 3
This analysis was later added to the protocol to be absolutely sure about the effectiveness of
electroporation ablation. However, 3 hearts were no longer available. Data of the histological
sections of 13 PVs from the remaining 7 hearts suggest that the absence of PV stenosis with
electroporation ablation is not due to ineffective applications.
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With focal trigger ablation and ostial PV isolation using RF energy
rg
gy in humans as ooriginally
rigg
ri
described by Haïssaguerre et al, PV stenosis did occur in a relatively large
rge nnumber
umbe
um
berr off ppatients,
attie
ienn up
With
ith
h segmental
seg
egme
m nttall PV isolation, PV stenos
me
stenosis
sis still
still did occur
u inn approximately
approximately 2% of
to 27%.6-9 Wi
patients.10 Wi
Wide area circumferential
circcumfferrenttiaal ablation
ab
bla
l tiion of the
the PV
PV antrum
ant
ntrrum has
ha si
significantly
ign
niffic
icantlly reduced
reedu
duceed this
th
1
b sti
till
ti
ll is
ll
is associated
associiatted
d withh a 0.4%
0.4%
% risk
riskk off PV
PV narrowing.
narrrow
na
owiingg.11
ow
incidence, but
still
Results
sults off the
h present
preesentt study
dy sug
suggest
gge
g st th
that
hat PV
V stenosis
stenosis
i mayy not
not bee an issue
issue with
with circular
circu
circu
electroporation
ation
ati
tio ablation
abl
blati
ti att th
the settings
ttiin used
tt
sed
d iinn tthe
he present
ntt st
study,
t d eeven
en when
hen
he it is
i (accidentally)
(accidental
(a id tall
performed inside PVs.
Electrical PV isolation was not the end point of our RF and electroporation applications.
The shift from ostial to antral RF ablation has reduced the incidence of PV stenosis after PV
isolation with RF energy.12 This suggests that not PV isolation, but the depth of the applications
inside the PV relates to the risk of PV stenosis.
PV stenosis is a well-known complication for thermal ablation.5-12 With 10 circular 200 J
applications inside the PVs we tried hard to provoke such a response. Although difficult to
compare, total energy delivered with electroporation was 2.000 J while 10 minutes of RF at 30
watts results in a total energy delivery of 18.000 J. With this in mind, our histological data
9
DOI: 10.1161/CIRCEP.113.001111
suggest that electroporation is far more effective in ablating the myocardial sleeve.
The histological analysis of PVs treated with RF vs. electroporation showed that RFtreated PV sections had more unaffected myocardial sleeve as compared to electroporationablated PV sections. This suggests that at least not more myocardial sleeve was ablated with RF
than with electroporation. Next, similar to the article of Taylor et al.,5 we analyzed the presence
of pathological changes associated with PV stenosis. We found that PVs treated with RF had
intimal proliferation, necrotic myocardium, proliferation of the elastic lamina, and large amounts
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of scar tissue surrounding the myocardial sleeve, whereas electroporation-ablated
ion-ablated PVs oonly
nlyy
nl
showed minor intimal proliferation, comparable to our previous report.
t.4
Despite
s it
spit
itee th
thee hi
higher
high
g er amount of successfully ab
abla
ablated
l ted myocar
la
myocardial
rdi
d all ssleeve,
l eve, histological
le
changes associated
socciated with PV
V sstenosis
teenosi
siis seem
em too bee lless
esss ppresent
ressen
nt in
n the
he ele
electroporation-ablated
ecttrooporatiionn-ab
blatted P
PVs.
These findings
i
ings
aalso
lsoo correspo
ls
correspond
pondd withh our
ou previous
prev
ev
vio
ious
u res
results,
ullts,4 whi
which
hich
h sshowed
howed
ho
d tha
that
hatt m
ha
myocardial
yocardi
diiall ttissue
i
is more prone
one to electroporation
ellectropo
poration
po
i damage
damag
ge as compa
compared
p redd to
t other
oth
her structures,
sttruc
u turees, suchh as con
connective
connectiv
onne
on
nectiv
ne
tissue. Thiss demonstrates
tissue
d
stt te that
thatt scarring
in off connective
connecti
cti
ti e ti
tiss e surrounding
s rro nding
di the
the PV
PV is
is the
the explanation
e pla
la
for PV stenosis after RF ablation.
Acute narrowing after RF application may relate to heat.13 Clinically, RF ablations will
never or only rarely be performed inside the common tubular segment of PVs and therefore acute
PV stenosis in humans may have only infrequently been reported.14, 15 With electroporation
ablation, holes in the cell membrane may cause acute depolarization and contraction as suggested
by coronary spasm that we observed directly after epicardial applications on these arteries in
other still unpublished studies. However, this resolved spontaneously within 30 minutes.
Limitations
Differences in anatomy and architecture between human and porcine LA and PVs are a serious
10
DOI: 10.1161/CIRCEP.113.001111
limitation for this study. To the best of our knowledge a porcine model has never been used to
study the effects of ablation on PV diameter. Therefore, the animals were used as their own
control by alternating electroporation and RF energy between the 2 PVs.
The fundamental cause of PV narrowing still is unknown and therefore one cannot be
sure that a porcine model using young animals is valid for the elderly human population.
In this study, we used quantitative PV angiography to assess the degree of PV stenosis.
Although quantitative PV angiography is a widespread and commonly used method to assess the
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
degree of luminal stenosis, PV angiography using computed tomography
more
p y mayy have been
ph
beeen m
accurate but this technology was not available in our animal facility.
Conclusions
ns
In this porcine
cine
cin
ne model,
mode
mo
del,
de
l multiple
l,
mul
ulti
tipl
ti
p e circular
pl
c rccul
ci
u arr 200
2000 J electroporation
eleect
c ro
r pooraati
tion
on aablations
blat
bl
attio
ionns iinside
n id
ns
de PV
PVss did
did not
not affect
no
a
PV diameter
Conversely,
considerable
e at
er
a 33-month
-mon
-m
onth
on
th ffollow-up.
ollo
ol
l wlo
w-up
up.. Co
up
C
nvver
erse
sely
se
ly
y, RF
F ablation
abl
blat
attio
on inside
insi
in
siidee PVs
PVss caused
cause
auseed co
au
ons
nsid
ider
id
erabll PV
er
stenosis, due
uee to scarring
u
sca
carrrin
i g off connective
con
o nect
ctiv
tivee ti
ttissue
ssue
ss
ue ssurrounding
uurrro
oun
u di
dingg the
the PV.
PV
V..
Acknowledgments: The authors wish to thank the staff of the Department of Experimental
Cardiology of the University Medical Center Utrecht for technical assistance during the
experiments and the Department of Biostatistics, Utrecht University for statistical analyses.
Conflict of Interest Disclosures: Fred Wittkampf is a consultant for St. Jude Medical, Atrial
Fibrillation division. Both Fred Wittkampf and Harry van Wessel are co-inventors of circular
electroporation. The other authors have no conflicts of interest to disclose.
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11
DOI: 10.1161/CIRCEP.113.001111
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Doevendans PA. Myocardial lesion depth with circular electroporation ablation. Circ Arrhythm
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T, H
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Table 1: Data of the 10 Animals.
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
Animal
PV
Ablation
method
#1
RPV
#2
#3
#4
#5
#6
#7
#8
#9
#10
PV diameter
before
(mm)
3 months
(mm)
(m
m)
change
c
ch
(
(%)
RF
13.8
11
11.7
.7
7
-15
IPV
V
CE
C
24.9
.9
33.0
333 0
+32
RPV
CE
12.7
12.8
0
IPV
IP
PV
RF
R
223.0
3.00
25.3
2 .3
25
+10
RPV
R V
RP
RF
RF
116
16.3
6.33
11
11.9
1.9
-27
IPV
IP
V
CE
22.1
22.1
25.1
255 1
+13
RPV
RP
PV
C
CE
113.3
13
.33
16.0
16
0
+20
IPV
IP
V
RF
23.44
23
21.8
21
8
-7
RPV
RF
16.4
10.7
-35
IPV
CE
21.6
24.3
+13
RPV
CE
15.8
20.6
+30
IPV
RF
19.6
20.1
+3
RPV
RF
16.8
17.9
+6
IPV
CE
19.0
25.8
+36
RPV
CE
16.7
18.2
+9
IPV
RF
21.1
25.0
+19
RPV
RF
17.5
13.2
-25
IPV
CE
20.8
26.1
+26
RPV
CE
13.8
14.5
+6
IPV
RF
21.0
20.4
-3
Pulmonary vein (PV) diameters before ablation and after 3 months survival were measured by angiography. The
percentage change in diameter is listed in column 6. At 3 months, the average change in PV diameter was -7 ± 17%
with radiofrequency (RF) ablation and + 19 ± 11% with circular electroporation (CE) ablation. RPV: right PV, IPV:
inferior PV.
13
DOI: 10.1161/CIRCEP.113.001111
Figure Legends:
Figure 1: Simplified outline of the porcine left atrial (LA) anatomy (antero-posterior view).
Because of their size only the right PV (RPV) and inferior PV (IPV) are eligible for catheter
ablation, and have been sketched. The PV tubular segments are marked in gray.
Figure 2: The custom deflectable, 7F, 18 mm circular, decapolar electroporation ablation
Downloaded from http://circep.ahajournals.org/ by guest on November 19, 2016
catheter containing 2 mm ring electrodes separated by 4 mm spacing used in this study.
y.
Figure 3: An
example
An ex
xam
ampl
plee of aangiograms
pl
ngiograms of the right ppulmonary
ullmonary veinn (RPV)
(RPV
PV) before (series 1) aand
PV
after radiofrequency
(RF)
ablation
was
frequency (RF
fr
F) abla
lattionn ((series
la
seriies
e 2 and
andd 33).
). Angiography
Angio
i gr
io
grap
aphyy w
as pperformed
errfo
f rmed
ed
d uusing
sinng tthe
he
antero-posterior
projections.
teriorr (AP),
(AP
AP),
), 30
30 degrees
degr
grees caud
caudal
udal (Ca
ud
(Cau
Cauu 30)
Ca
300) andd 300 ddegrees
eg
greess cranial
cranial
i (Cr
C 330)
Cr
0) proje
projection
j cti
tion
Directly after
RF
ablation,
RPV
showed
ostial
ft R
fter
F ab
blatiionn, RP
R
V angiograms
angi
giiogr
g ams sh
howed
d considerable
consiiderab
bllee ddecrease
ecre
reease off osti
ial di
ddiameter
a ett in
am
all 3 projections
follow-up
angiography
ctions
ti
(series
(s ie 2).
2) After
Aftte 3 months
Af
nth
ths follo
foll
llo
p RPV
RPV angiograph
io
h was
as repeated
tedd andd still
s
showed significant decrease of the ostial PV diameters (series 3).
Figure 4: Graph showing the relative pulmonary vein (PV) diameter change directly after
electroporation or radiofrequency ablation (post), and after 3 months follow-up (FU). The preablation PV diameter and diameter of the heart served as baseline and were set as 100% (pre).
The black line represents the mean growth in heart diameter for all 10 animals, measured in the
anterior posterior projection before ablation and at 3 months. The vertical lines indicate the
respective standard deviations.
14
DOI: 10.1161/CIRCEP.113.001111
Figure 5: Elastic-Van Gieson stained sections of a control PV (panels A and B), a PV treated
with RF ablation (panels C and D), and a PV treated with 10 circular electroporation applications
(panels E and F). Panels B, D and F are magnifications of panels A, C, and E, respectively. The
control PV shows complete sleeve coverage and normal vessel wall. The PV treated with RF
shows a partially undamaged myocardial sleeve, intimal proliferation, necrotic myocardium, and
proliferation of the elastic lamina. In addition the vein is surrounded by scar tissue. The PV
treated with electroporation shows a completely ablated myocardial sleeve surrounded by
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healthy connective tissue. The differences in luminal area or shape of the ppulmonary
vein
ulmonary
y vei
eiin iin
panel A versus panels C and E is the result from minor differences in fixati
fixation
tiion ttechnique.
echhniq
ec
hniq
iquee.
* Undamaged
connective
gedd myocardial
m occar
my
ardial
all sleeve. ^ Healthy connect
ctiv
ct
i e tissue. ~ Scar
iv
S arr ttissue
Sc
i sue surrounding the PV.
is
% Ablated my
sleeve.
Intimal
Proliferation
elastic
lamina.
myocardial sl
leeevee. § Int
nttimall hhyperplasia.
nti
yperplaasia. # Pr
yp
Prol
olif
ol
ifeerattio
if
on ooff ela
asttic lam
a in
am
na.
PV: pulmonary
naryy vein,
vein
ve
in
n, RF:
RF
F: radiofrequency.
radi
diofrequ
di
f uen
ency.
15
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Pulmonary Vein Stenosis after Catheter Ablation: Electroporation versus Radiofrequency
Vincent J.H.M. van Driel, Kars G.E.J. Neven, Harry van Wessel, Bastiaan C. du Pré, Aryan Vink,
Pieter A.F.M. Doevendans and Fred H.M. Wittkampf
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Circ Arrhythm Electrophysiol. published online June 23, 2014;
Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue,
Dallas, TX 75231
Copyright © 2014 American Heart Association, Inc. All rights reserved.
Print ISSN: 1941-3149. Online ISSN: 1941-3084
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circep.ahajournals.org/content/early/2014/06/17/CIRCEP.113.001111
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