DOI: 10.1161/CIRCULATIONAHA.112.092544
Cerebral Embolization During Transcatheter Aortic Valve Implantation:
A Transcranial Doppler Study
Running title: Kahlert et al.; Cerebral Embolization During TAVI
Philipp Kahlert, MD1; Fadi Al-Rashid, MD1; Philipp Doettger, MS1; Kathrine Mori, MS1;
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Björn Plicht, MD1, Daniel Wendt, MD2; Lars Bergmann, MD, DESA3;
Eva Kottenberg, MD, DESA3; Marc Schlamann, MD4; Petra Mummel, MD5; Dagny Holle, MD5;
Matthias Thielmann, MD, FAHA2; Heinz G. Jakob, MD, FECTS2; Thomas K
Konorza,
onor
on
orza
or
zaa, MD1;
Gerd Heusch, MD, FACC, FAHA, FESC, FRCP6; Raimund Erbel, MD, FESC, F
FACC,
ACC,
AC
C F
C,
FAHA
AHA
AH
A1;
Holger Eggebrecht, MD, FESC, FACC1
1
Dep
Dept
D
ept
pt of Ca
Card
Cardiology;
rdio
rd
olo
logy
g ; 2 De
gy
Dept
p ooff Th
pt
Thor
Thoracic
orac
acicc aand
nd C
Cardiovascular
arddioovasscu
ar
cula
larr Sur
Surgery,
urrge
gery
ry,, We
West-G
West-German
-Ger
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mann He
Hear
Heart
artt Ce
Cent
Center
n er
3
Clinic
Clin
inicc ffor
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or A
Anaesthesiology
naes
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are
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Medicine;
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Inst
nst of
of Diagnostic
Diag
Di
iag
a no
nost
s icc and
st
and
n
Essen; Cl
Int
In
Interventional
te
tervention
onal R
Radiology
adio
olo
ogy and
and Ne
Neur
Neuroradiology;
uror
orradioloogy; 5D
Dept
ept
pt ooff N
Neurology,
euuroology, 6In
Inst
nst ffor
or P
Pathophysiology,
atho
hoph
ho
ph
hyssiolo
ogy,
Essen
Esse
Es
seen Un
University
niv
ver
ersity
ty H
Hospital,
ospi
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pita
pi
tal,
l U
l,
University
nive
ni
veersi
sitty
ty D
Duisburg-Essen,
uisb
sbbur
urgg--Es
E se
s n, E
Essen,
sseen,
en, Ge
Germ
Germany
rman
anyy
an
Address forr Correspondence
Corr
Co
rres
rr
espo
es
pond
po
n en
nd
encce
Philipp Kahlert, MD
Department of Cardiology
West-German Heart Center Essen
University Duisburg-Essen
Hufelandstr. 55
45122 Essen, Germany
Tel: +49-201-723-84805
Fax: +49-201-723-5931
E-mail: [email protected]
Journal Subject Codes: [23] Catheter-based coronary and valvular interventions: other; [53]
Embolic stroke; [59] Doppler ultrasound, Transcranial Doppler etc.
1
DOI: 10.1161/CIRCULATIONAHA.112.092544
Abstract:
Background - Transcatheter aortic valve implantation (TAVI) is associated with a higher risk of
neurological events for both the transfemoral (TF) and the transapical (TA) approach than
surgical valve replacement. Cerebral magnetic resonance imaging revealed even more new,
albeit clinically silent lesions from procedural embolization. Yet, main source and predominant
procedural step of emboli remain unclear.
Methods and Results - Eighty-three patients underwent TF- (Medtronic CoreValve [MCV]:
n=32, Edwards Sapien [ES]: n=26) and TA-TAVI (ES: n=25). Serial transcranial Doppler (TCD)
examinations prior, during and three months after TAVI were used to identify high-intensity
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
transient signals (HITS) as a surrogate for microembolization. Procedural HITS were detected in
y during
g manipulation
p
g
all ppatients,, ppredominantly
of the calcified aortic valve while ppositioning
and implanting the stent-valves. The balloon-expandable ES prosthesis caused si
sign
gnif
gn
i iccan
if
antl
tlyy mo
tl
more
significantly
HITS during positioning (ESTF: 259.9 [184.8-334.9], ESTA: 206.1[162.5-249.7], MCVTF: 78.5
[25.3-131.6],
25.3-131.6]], p<0.001), the self-expandable MCV
MC
CV pr
pprosthesis
osthesis during impl
implantation
p antation (MCVTF: 397.1
[302.1-492.2],
302
02.1
.1--4922.2
.2]], ES
ESTF: 88.2
888.22 [70.2-106.3],
[70
7 .22-1066.3],
] ES
ESTA
110.7
10.77 [82.
[82.0-139.3],
2.00 13
1 9.3]
3]], p<
p<0.
p<0.001).
0.00
001). Ov
Overall, there
the
h re
r were
T : 11
nnoo significant
sig
i nificantt differences
dif
iffe
feereencees
es between
bet
etwe
ween
en
n TFTF- and
and TA-TAVI
TA-TAV
TA
A I and
AV
an
nd between
betw
be
tweeenn th
the
he MCV
MCV an
andd th
the
he ES
E
pr
ros
o th
t es
esis. No H
IT
TS were
were ddetected
etec
ecte
tedd at
a bbaseline
aseliine an
asel
andd at 33-months
-m
monnth
hs ffollow-up.
olllow--up
-up.
p. T
here w
here
as one
one major
majoor
prosthesis.
HITS
There
was
procedural
proc
oced
edural
al sstroke
trok
oke re
resu
resulting
sultin
ng in
n de
deat
death
athh andd one
one minor
mino
nor procedural
prroc
oced
edur
ural
al stroke
stro
roke
ke with
withh full
fu l recovery
rec
e ovver
ery at 33months follo
follow-up
oww up iin
n th
thee MC
MCV
V gr
grou
group.
oup.
ou
p.
Conclusions - Procedural HITS were detected by TCD in all patients. While no difference was
observed between the transfemoral and the transapical approach using the balloon-expandable
ES stent-valve, TF-TAVI with the self-expandable MCV prosthesis resulted in the highest
amount of HITS, predominantly during implantation.
Key words: aortic valve stenosis; cerebral ischemia; transcatheter aortic valve implantation;
valves; transcranial Doppler
2
DOI: 10.1161/CIRCULATIONAHA.112.092544
Introduction
Transcatheter aortic valve implantation (TAVI) has evolved as the new standard-of-care for
inoperable patients with severe, symptomatic aortic valve stenosis1 and to a viable treatment
option for high-risk, yet operable patients2, as recently demonstrated in the Placement of Aortic
Transcatheter Valves (PARTNER) trial. However, the increased risk of stroke associated with
TAVI over that with surgical aortic valve replacement remains a concern3. In contrast to surgical
aortic valve replacement, strokes and transient ischemic attacks were more frequent after TAVI
than after surgical aortic valve replacement with 30-day event rates of 5.5 % vs. 2.4 %,
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
respectively2. Apart from clinically apparent neurological events, TAVI is associated with
frequent new, clinically silent lesions on post-procedural cerebral magnetic reson
resonance
on
nan
nce
imaging
maging4,5,6,7, most likely caused by procedural release of atherosclerotic or calcific debris from
he ao
aort
rtaa or tthe
rt
he ccalcified
alci
al
cified aortic valve3,8. TAVI ent
entails
ntaiils several pro
nt
procedural
oce
c du
uraal st
ssteps
eps which can cause
the
aorta
cerebral
ce
ereebr
b al embolization,
embol
oliz
izattio
iz
on, notably
not
otab
ably
ab
ly wire
wire passage
passsagee of
of thee aortic
aort
rtticc valve,
vaalv
ve, balloon
ballo
alloon
on
n vvalvuloplasty,
alvu
al
vulo
vu
lopl
pllas
a ty
t ,
advancement
ad
dvanc
vanc
ncem
emen
entt of the
en
the semi-rigid,
sem
emii-ri
r giid, large-bore
lar
arge
ge-b
-b
borre device
devi
devi
vice
c through
ce
thhrou
hrouugh the
the aortic
aortiic aarch,
rcch, ppositioning
osit
osit
itio
ionnin
ning
ng ooff th
tthee
metallic stent-valve
stent
nt-v
-v
val
a ve within
wit
i hi
h n the
the annulus
annu
an
nulu
nu
l s and
lu
and crushing
crus
cr
rus
ushi
h ng of
hi
of the
the stenotic
sten
st
enot
en
o icc native
ot
nati
na
tiive leaflets
lea
e fl
flet
etss du
et
duri
during
r ng
implantation. The precise source and procedural step of embolization, however, remain unclear.
The present study reports the results of serial transcranial Doppler (TCD) prior, during
and after transfemoral (TF) or transapical (TA) TAVI using either CE-marked device;
microemboli were quantified during each procedural step.
Patients and Methods
Patient Population
Between August 2009 and May 2011, 204 consecutive high-risk patients with severe
3
DOI: 10.1161/CIRCULATIONAHA.112.092544
symptomatic aortic valve stenosis underwent TAVI using one of the currently CE-approved
bioprostheses (Edwards SAPIENTM / Edwards SAPIENTM XT [ES], Edwards Lifesciences Inc.,
Irvine, CA, USA; n=140 [69%] and Medtronic Corevalve [MCV], Medtronic Inc., Minneapolis,
MN, USA; n=64 [31%]) at our institution. Of these 204 patients, 83 (41%) were ultimately
included in the present study: 32 (39%) underwent TF-TAVI with the self-expandable MCV
prosthesis (group 1), 26 (31%) TF-TAVI (group 2) and 25 (30%) TA-TAVI (group 3) with the
balloon-expandable ES prosthesis. One-hundred twenty-one patients were excluded from the
study: 107 patients had poor acoustic windows and were unsuitable for TCD examination and 14
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
refused to participate.
Patients with symptomatic severe aortic valve stenosis were considered for
for TAVI
TAV
AVII if they
the
heyy
had a logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE) • 20
% or ssurgery
urgeery
urge
r was
ass cconsidered
onsidered at excessive risk du
ue tto
o comorbiditi
ies
e and
ndd oother
ther risk factors not
due
comorbidities
efllected by E
uroS
ur
oSCO
oS
CO
ORE
E ((e.g.
e.g.
e.
g. pporcelain
orrce
cela
laain
n aor
rtaa or pprior
riorr cchest
hesst rradiation).
he
adiiattion
ad
tion).
)
).
reflected
EuroSCORE
aorta
The in
The
indi
diccattion
tion ffor
or T
or
AVII in tthe
AV
he ind
ndiv
nd
ivid
iv
dua
u l pa
atieent
ent was
was di
ddiscussed
scus
usse
us
s d by
se
by cconsensus
onse
on
sens
nsuus ooff
ns
indication
TAVI
individual
patient
cardiologistss (P
(PK,
K, T
K, R
E,, H
E)), ca
ccardiac
rdiaac su
rd
surg
rgeo
rg
eons
eo
ns (D
(DW,
W, M
T, H
J aand
J)
nd ccardiac
ardi
ar
diac
di
a aanaesthetists
ac
naes
na
esth
es
thetists (LB,
th
TK,
RE,
HE),
surgeons
MT,
HJ)
EK) while patient’s preference alone was not considered sufficient. TAVI in these patients was
approved by the local authorities, and patients gave informed consent.
Patients were excluded from TAVI in the presence of any of the following conditions:
bicuspid aortic valve, aortic annulus diameter < 18 or > 27 mm, severe iliofemoral artery disease
(TF only), unprotected left main coronary disease, recent myocardial infarction or
cerebrovascular event, sepsis or active endocarditis, severe aortic atheroma (TF only), left
ventricular (LV) or atrial thrombus, active peptic ulcer, bleeding diathesis or hypersensitivity to
anti-platelet therapy.
4
DOI: 10.1161/CIRCULATIONAHA.112.092544
Transcatheter Aortic Valve Implantation Procedure
TAVI was performed either transfemorally or transapically in a hybrid operating room using
standard techniques9,10. The balloon-expandable, trileaflet bovine ES prosthesis was used for
both TF- and TA-TAVI, whereas the self-expandable, trileaflet porcine MCV stent-valve was
only used for retrograde, transfemoral access.
TF-TAVI was performed preferably under anaesthetist-controlled conscious sedation
with percutaneous right- or left-sided femoral artery access and closure (Perclose ProGlide,
Abbott Vascular Inc., Redwood City, CA, USA). After insertion of the large-bore delivery sheath
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
into the access vessel, the native valve was crossed with a left Amplatz diagnostic 6 French
ridg
ri
dgew
dg
ew
wat
ater
er,, N
er
J
coronary catheter and a straight-tip 0.035” guidewire (both Cordis Corporation, B
Bridgewater,
NJ,
USA). A stiff 0.035” inch guidewire (Amplatz Super Stiff, 260 cm, 3 mm J-tip, Boston Scientific
Corp
Co
rpor
rp
orat
atio
tio
ion,
n N
attic
ick,
k MA, USA) with a manuall
ly be
ent curve at th
he gu
uid
dewire
ew tip was then placed
Corporation,
Natick,
manually
bent
the
guidewire
deep
p into the LV
V apex
apeex over
ovver a standard
sta
tand
ndaard
nd
ard 6 French
Freench pigtail
pigtaill cath
ccatheter.
ath
hetter
er. Ba
Ball
lloo
ooon ao
aor
rtic
rti
ic vvalvuloplasty
alvu
al
vuulo
lopllasty
asty
yw
as
deep
Balloon
aortic
was
subsequently
ubs
bseq
eque
eq
uent
nttly pperformed
errfo
orm
rmed
ed
d uusing
s ng a 220
si
0 or 223
3 mm ba
bballoon
lllooon ca
catheter
ath
theeter
er uunder
nder
nd
er rrapid
apiid
id rright
ight
ig
h vventricular
ht
enttric
en
iccullar
faci
cili
lita
li
tate
ta
tee later
lat
a er passage
pas
assa
sagee of
sa
of the
the stent-valve.
s en
st
entt va
tvalv
lve.
lv
e. F
inal
in
ally
al
ly,, th
ly
thee de
ddelivery
liive
very
ry ssystem
yste
ys
tem
m co
cont
ntai
nt
a ning the
ai
pacing to facilitate
Finally,
containing
manually crimped and loaded prosthesis was introduced into the LV with retrograde passage of
the aortic valve. After positioning using fluoroscopic, angiographic and eventually
echocardiographic guidance, the balloon-expandable stent-valve was rapidly deployed by
balloon inflation under rapid right ventricular pacing at 160-220/min, whereas the selfexpandable prosthesis was deployed stepwise with or without accelerated pacing (100 to
120/min) to prevent dislocation into the ascending aorta during premature ventricular beats.
TA-TAVI was performed under general anaesthesia using a left antero-lateral
minithoracotomy. After placement of purse-string sutures, the LV apex was punctured and a
5
DOI: 10.1161/CIRCULATIONAHA.112.092544
standard 0.035” J-tip guidewire advanced antegradely across the aortic valve and directed
through the aortic arch down to the descending aorta using a right Judkins 6 French diagnostic
coronary catheter. After exchange to a stiff guidewire and exchange to the large-bore delivery
sheath, balloon aortic valvuloplasty was performed. The crimped ES bioprosthesis was then
introduced and positioned within the aortic annulus under fluoroscopic, angiographic and
echocardiographic guidance and, finally, implanted using rapid right ventricular pacing at160220/min.
Before the procedure, all patients received acetylsalicylic acid (100 mg/d), clopidogrel
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
(75 mg/d after a loading-dose of 300 mg/d) and ceftriaxon (2 g) as single-shot antibiotic
prophylaxis. During the procedure, intravenous heparin was administered to achi
hiev
evee an
ev
n aactivated
ctiv
ct
ivat
iv
ated
achieve
clotting time (ACT) above 250 s for the entire procedure; ACT was measured every 30 minutes.
Cath
Ca
thet
th
eteers
et
ers we
w
re ccarefully
areefully flushed with saline to aavoid
ar
v id air embolism,
vo
m and
ndd gguidewires
u dewires were
ui
Catheters
were
horrou
o ghly cleaned
cleean
ned
d before
before
ore ca
cath
thet
th
eter
er iinsertion
nser
ns
errtionn too av
voiid for
fformation
orma
rmatiion off tthrombi
hrom
hr
ombi
om
bi on
on their
thei
th
eir surface.
ei
s rf
su
r ac
ace.
e.
thoroughly
catheter
avoid
He
emo
mody
dyna
dy
naami
micc st
tab
bil
ilit
itty du
duri
ing tthe
he eentire
ntiire
nt
ire pr
proc
o ed
oc
edur
urre wa
as as
ass
sure
redd by th
re
tthee at
tte
tenndin
ndin
ingg ca
car
rdiiac
Hemodynamic
stability
during
procedure
was
assured
attending
cardiac
anaesthetist uusing
s ng a ppulmonary
si
u mo
ul
m na
nary
r aartery
rte
t ry ccatheter
a he
at
hete
t r fo
te
fforr in
inva
v siive hhemodynamic
va
emo
mody
dyyna
nami
micc mo
mi
m
n to
ni
tori
ring
ri
ng. After the
ng
invasive
monitoring.
procedure, acetylsalicylic acid was continued indefinitely while clopidogrel was discontinued
after 6 months. In patients with atrial fibrillation, phenprocoumon and clopidogrel were
administered for 6 months and clopidogrel then exchanged for acetylsalicylic acid.
Assessment of Neurological Status and Cognitive Function
All patients underwent clinical and neurological examination at baseline, after the procedure when anaesthetist-controlled conscious sedation or general anaesthesia was reversed - and at 3
months. Neurological status was assessed using National Institute of Health Stroke Scale
(NIHSS) rating11. The Mini Mental State Examination (MMSE)12 and the Montreal Cognitive
6
DOI: 10.1161/CIRCULATIONAHA.112.092544
Assessment (MoCA) test13 were used to evaluate global cognitive function based on the brief
neuropsychological test protocol proposed by the National Institute of Neurological Disorders
and Stroke and the Canadian Stroke Network14. At 3 months, the modified Rankin Scale (mRS)15
was assessed to characterize the patient´s neurological impairment during daily activities with
reference to pre-TAVI activities by grading no (0), no significant (1), slight (2), moderate (3),
moderately severe (4) and severe (5) disability and death (6). Postprocedural neurological events
were assessed according the standardized endpoint definitions for TAVI trials proposed by the
Valve Academic Research Consortium (VARC)16.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Preoperative Assessment of Potential Sources of Embolism
Prior to the procedure all patients were searched for possible sources of embolis
embolism
sm us
uusing
in
ng
electrocardiography, echocardiography and carotid artery ultrasonography. The history of any
previous
pr
rev
vio
iouus
us eembolism
mbolis
mb
issm w
was
as recorded.
Transoesophageal
Transooes
esop
oppha
haggeal
al eechocardiography
choocar
ch
ocarrdi
diog
ogra
rapphyy was
was mandatory
m nddattor
ma
oryy as
as ppart
arrt off tthe
he ppreinterventional
reiinte
re
interrven
rven
e ti
tion
nal
TAVI
detect
contrast,
thrombi,
TA
AVI eevaluation
valu
va
lu
uat
atio
ionn and
and us
used
ed too de
ete
tect
ct sspontaneous
po
ont
ntan
aneo
an
ous
u eecho
cho co
ont
ntra
rast
st, intr
st
iintra-cardiac
ntr
traa card
adia
iacc th
thro
romb
mbi,, llow
mb
ow
w lleft
eftt
atrial appenda
appendage
daage ((LAA)
LAA)
LA
A) ppeak
eakk ve
ea
velocities
elo
loci
ciiti
t ess ooff <5
<555 cm
cm/s
m/s bby
y pu
puls
pulsed-wave
lsed
ls
ed-w
ed
-w
wav
ve Do
Dopp
Doppler
pple
pp
l r17, pa
le
pate
patent
tent
te
n foramen
ovale (PFO) or other intracardiac shunts as well as aortic atheromata. Presence, thickness and
characteristics of the atheroma (mobile / protruding / sessile) in the ascending aorta, aortic arch,
and descending thoracic aorta were graded as absent, mild (< 4 mm without complex features),
moderate (> 4 mm without complex features) or severe (any size with protruding or mobile
components)18.
Carotid Duplex ultrasound was used to detect plaque burden and carotid stenoses.
Stenoses of common, internal and external carotid arteries were measured as reduced diameter
and graded with consideration of all information from B-mode, pulsed-wave and color flow
7
DOI: 10.1161/CIRCULATIONAHA.112.092544
Doppler19. Carotid stenoses were considered significant if > 70% diameter reduction.
Transcranial Doppler Examination
Simultaneous TCD of both middle cerebral arteries (MCA) was performed in a supine position
from a transtemporal window using a multigate Multi-Dop T Digital system (DWL
Compumedics Germany GmbH, Singen, Germany) with software for automated HITS detection
(QL, version 2.5) and 256-point fast Fourier transformation. Two pulsed-wave 2-MHz Doppler
probes were fixed to the patient head using a size-adjustable head mounting system (Dia Mon,
DWL Compumedics Germany GmbH, Singen, Germany) to prevent movement during recording
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
and used to insonate the MCAs at a depth of 50-56 mm with a sample volume of 9-13 mm. The
pulse repetition frequency was set to 7 kHz and the detection threshold for HITS
S adj
djusste
dj
tedd to 9
adjusted
dB to reduce artefacts20. A fast sweep speed of 4 s display duration was chosen and the Doppler
ve
elo
oci
city
ty range
ran
ange
ge spectrum
spe
pecctrum
pe
ct
maximum velocity.
veloccit
i y. D
op er velocity and powe
oppl
velocity
adjusted to the expectedd maximum
Doppler
power
M-Mode
M
-M
Mode spect
spectrograms
ctro
ro
ogrram
ms we
wer
were
re m
re
monitored
onit
on
itoore
it
ored ssimultaneously
imuulttaneeou
uslyy ((Figure
Figu
Fi
gure
gu
re 11).
).
At bbaseline
asel
as
elin
in
ne an
andd 3 mo
mont
months
n hs ffollow-up,
nt
ollo
ol
loww-up
wup,, TC
up
TCD
Dw
was
ass pe
performed
erf
rfor
orm
med fo
med
forr 330
0m
minutes.
in
nut
utes
e . Du
es
D
During
riing T
TAVI,
AVI,
AV
I,
TCD was pe
performed
erffor
orme
medd fr
me
from
o ffemoral
emor
em
oral
or
a oorr le
al
left-apical
eft
ft-a
-aapi
p ca
call pu
punc
puncture
nctu
nc
ture
re uuntil
ntil
nt
ill vvalve
a ve iimplantation
al
mpla
mp
lant
la
n at
nt
atio
io
on or ccompletion
ompletionn
of eventual postimplantation manoeuvres such as postdilatation and snaring.
HITS detection and artefact rejection were based on automated software analysis in
conjunction with on-line human observation using standard criteria21. Two experienced
observers (PD, KM) recorded all procedural details in order to recognize artificial false-positive
signals and attribute signals to the procedural steps. Time-stamped signal recording on a hard
drive was used for further off-line analysis by the two observers who had to agree that signals
met the identification criteria of HITS and were not artefacts from patient movement, catheter
flushing or contrast injections.
8
DOI: 10.1161/CIRCULATIONAHA.112.092544
HITS during TAVI were separately counted during: (1) antegrade (TA) or retrograde
(TF) wire passage of the aortic valve, (2) introduction and propagation of the stiff guidewire into
the LV apex (TF) or the descending aorta (TA), (3) introduction and placement of the balloon for
preparatory valvuloplasty, (4) balloon valvuloplasty, (5) introduction and propagation of the
loaded delivery device towards the aortic annulus, (6) positioning of the stent-valve, and (7)
valve implantation.
Statistics
Categorical data are presented as frequencies and percentages. Continuous variables are
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
indicated as mean and 95% confidence interval (95% CI) throughout the text; median, lower
Q1) and upper (Q3) quartiles are additionally given in the tables. Categorical da
dat
ta w
ta
erre
(Q1)
data
were
compared between groups using Ȥ2- or Fisher’s exact test; continuous variables were compared
us
sin
ng t-t
tt-test
-test
test ffor
or ddependent
epen
ep
e dent and independent samp
ples
les or Wilcoxonn ssigned-rank
igne
needd-ra
r nk or Mann-Whitneyusing
samples
U test,
teest, respectively.
respecti
tive
veely
y. Th
T
Three-group
reere
e gr
egrooup
oup co
comp
comparison
mpaarisoon wass pperformed
erfforrmeed using
usiing
us
ing 1-way
1-wa
1wayy ANOVA
ANOV
AN
OV
VA or KruskalKrusk
rusk
skaalWallis
Wall
Wa
llis
ll
is test
tes
estt for
for continuous
co
onttin
inuuouus
us variables;
varria
iabl
bles
bl
es;; pairwise
es
paairrwi
wisse comparison
com
ompa
paariisoon with
with
th Bonferroni
Bonnfe
f rrronni correction
corr
co
rrec
rr
ecttio
tion was
was
as
performed for
fo
or variables
v ri
va
riab
able
ab
lees where
whher
eree there
ther
th
e e was
er
waas a significant
sign
si
gnif
gn
ific
if
ican
ic
antt difference
an
diiff
ffer
ereenc
er
ncee between
beetw
twee
eenn groups.
ee
grou
gr
ou
ups
ps.. Three-group
Thre
Th
r e-group
comparisons for binary or continuous variables adjusting for demographic and preprocedural
parameters were calculated using logistic regression or general linear models, the latter preceded
by a logarithmic transformation where indicated. Multivariable regression analysis was
performed to detect variables associated with increased procedural HITS. Eight variables
identified at univariate linear regression analysis with the dependent variable HITS (p<0.20) and
deemed of clinical importance were included into the multivariable model. All p-values are twosided and a p-value <0.05 was considered significant. All analyses were performed using SPSS
(version 19.0, IBM SPSS, Chicago, IL, USA). The authors had full access to the data and take
9
DOI: 10.1161/CIRCULATIONAHA.112.092544
responsibility for their integrity. All authors have read and agree to the manuscript as written.
Results
Patient Characteristics
Patients who were excluded from the study had a slightly higher STS-score than included
patients, were more often female and had more often diabetes mellitus, while a history of
smoking and prior cardiac surgery was less frequent. Despite this potential selection bias, the
present patient cohort nevertheless reflects typical TAVI patients who are elderly, have severe,
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
symptomatic aortic stenosis and are at increased surgical risk due to age and comorbidities. The
characteristics of three patient groups (group 1: TF-TAVI with MCV prosthesis,
prosthesiss, gr
grou
oupp 2: T
ou
F
Fgroup
TFTAVI with ES valve, group 3: TA-TAVI) are summarized in Table 1. Patients undergoing TATA
AVII hhad
ad hhigher
igheer lo
ig
llogistic
gistic EuroSCORE than TF-p
-p
pat
atie
i nts (29.3[23.8-34
4.7
.7]
7] vs. 17.7[13.1-22.4] and
TAVI
TF-patients
(29.3[23.8-34.7]
16
6.11[1
[ 2.6-199.6
.6]] pe
perc
cent,
ent, pp<0.001),
< .0
<0
.001
01),
01
), aand
nd ddiabetes
iaabe
bete
tes mel
m
ellittus w
as m
o e fr
or
ffrequent
eque
eq
uentt iin
n pa
pati
tien
ti
ents
en
ts
16.1[12.6-19.6]
percent,
mellitus
was
more
patients
un
ndeerg
rgoi
o ngg TF-TAVI
TFF TA
TAVI
VI using
ussing
sing the
the ES
ES valve
valv
va
l e (50
lv
(50 vs.
vs 21.9
21.9 and
annd
nd 20
20 percent,
perrcen
pe
rcent,, p=0.028).
p=0.0
=0.0
028
8).
undergoing
Neur
Ne
urol
ur
olog
ol
ogic
og
ical
ic
al S
tatu
ta
tuss an
tu
and
d Cognitive
Cogn
Co
gnit
gn
itiv
it
ivee Function
iv
Func
Fu
ncti
nc
tion
ti
on Prior
Pri
rior
or TAVI
TAV
AVII
Neurological
Status
At baseline, focal neurological deficits were observed in 4 patients. One patient of group 1 was
blind and one had an impaired motor function of the left leg due to multiple sclerosis, accounting
for NIHSS ratings of 3 and 2. One patient of group 2 and one of group 3 had an NHISS rating of
1 due to minor facial palsy from a prior stroke. For the other patients NIHSS rating was 0.
Cognitive function by MMSE and MoCA test at baseline revealed no major impairments with
scores of 27.9 (27.5-28.3) and 23.4 (22.7-24.0), respectively, and no differences between groups
(online data supplement, Table 1).
Preinterventional Screening for Sources of Embolism
Aortic atheromata were present in all TAVI patients (Table 2) and graded as mild in 72 (87%)
10
DOI: 10.1161/CIRCULATIONAHA.112.092544
and moderate in the remaining 11 (13%) patients. Severe atheroma was considered as an
exclusion criterion for TF-TAVI in groups 1 and 2, but also not found in the TA-TAVI group. A
single patient in group 2 had a porcelain aorta. Twenty (24%) patients were in permanent atrial
fibrillation and 61 (73%) patients had reduced left atrial appendage peak velocities which were
found significantly more frequent in TF-TAVI patients treated with the MCV prosthesis than in
the other two patient groups. Spontaneous echo contrast was found in 14 (17%) patients, but no
intracardiac thrombi were seen. A PFO was present in a single patient each of groups 2 and 3,
and 9 (11%) patients had a prior cerebral ischemic event. Carotid artery stenosis with > 70%
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
diameter reduction was seen in 2 (2%) patients, luminal narrowing between 30 and 70% in 27
33%) and below 30% in the remaining 54 (65%) patients. Sixty-three (76%) pat
atie
ient
n s re
nt
rece
ceiv
ce
ived
iv
ed
(33%)
patients
received
tatins. Overall, variables indicating potential sources for embolism were not significantly
statins.
di
ifffer
eren
entt am
en
amo
ongg groups
grou
gr
o ps except for left atrial appendage
appe
pend
pe
nd
dage velocities
s. Off nnote,
ote there were also no
ote,
different
among
velocities.
di fer
diff
e ences in tthese
hesse vvariables
he
aria
iaabl
bles
ess bbetween
etwe
et
ween
we
en ppatients
atien
ntss in-- and
andd excluded
excl
xclud
ded in
in th
thee st
tud
udyy.
differences
study.
Proc
Pr
o ed
oc
edur
ural
ur
al R
essullts
Procedural
Results
TAVI was technically
tec
ecchn
hnic
iccal
ally
ly successful
suc
u ce
cess
s fu
ss
ul in all
alll patients;
pat
atie
ieent
nts;
s m
s;
orta
or
t lit
ta
ityy at 330
it
0 da
ddays
ys aand
nd aatt 3 months
mon
onth
thss was 8.4%
th
mortality
and 12.0%, respectively (Table 3). Implantation of the stent valve prostheses resulted in a
postinterventional mean transaortic gradient of 9.9 (8.8-10.9) mm Hg and an aortic valve area of
1.70 (1.61-1.80) cm2 (p<0.001 vs. baseline). Overall, procedural data were not different among
groups except for prosthesis´ size, procedure time and fluoroscopy time which remained
statistically significant variables after adjustment for age, gender, logistic EuroSCORE and
diabetes mellitus. Procedure time was lowest in patients undergoing TF-TAVI with the MCV
prosthesis and highest in TA-TAVI patients, while fluoroscopy time was lowest in TA-TAVI
patients and highest in TF-TAVI patients with ES implantation.
11
DOI: 10.1161/CIRCULATIONAHA.112.092544
Non-neurological procedural complications related to the vascular access site occurred in
5 TF-TAVI patients (group 1: n=2, group 2: n=3) and required endovascular (group 1: n=2,
group 2: n=2) or surgical repair (group 1: n=1, group 2: n=0). With the MCV prosthesis,
dislocation of the stent-valve was observed in 4 patients during the first implantation attempt,
resulting in subsequent valve retrieval, recrimping and reimplantation. Three patients became
hemodynamically unstable during the implantation, 1 in group 1 due to volume depletion and 2
in group 2 due to new onset tachycardic atrial fibrillation requiring cardioversion and due to lowoutput failure requiring short-term cardiopulmonary resuscitation, catecholaminergic support >
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
0.1 μg / kg / min and switch from anaesthetist-controlled conscious sedation to general
anaesthesia.
Postdeployment valvuloplasty within the same session was performed in 11 (group 1:
n=
=8, group
group
roup 2:
2: n=1,
n=
=1,
1, group
group 3: n=2, p=0.04) and snaring
sna
nariing in 2 patien
na
ntss (gr
grou
oupp 1: n=2, group 2: n=0,
ou
n=8,
patients
(group
ggroup
rou
up 3: n=0, p=
=0..19
95) iin
n or
orde
derr to
de
o dim
ddiminish
iminnishh re
esidua
ual pa
ua
arava
ravaalv
vul
ulaar re
regu
gurg
rgit
itat
attio
ionn fr
rom iincomplete
ncompl
nco
omp ete
p=0.195)
order
residual
paravalvular
regurgitation
from
ten
ntt-fr
fram
fr
amee expa
eexpansion
xpaanssio
ionn oorr ttoo
oo llow
ow
w iinitial
nitia
itiaal im
imp
plan
an
nta
t tioon,
on, re
resp
speecti
sp
tive
ti
v ly
ve
ly..
stent-frame
implantation,
respectively.
Transcranial
all D
oppl
op
pler
pl
e E
er
xami
xa
m na
nati
t on
ti
o
Doppler
Examination
Baseline TCD revealed no HITS in any patient. During TAVI, however, HITS were observed in
every patient of each group. A similar amount of HITS was observed for all three approaches
(Figure 2, Table 4) during antegrade (TA) and retrograde (TF) wire passage of the aortic valve,
introduction and propagation of the stiff guidewire into the LV apex (TF) or the descending aorta
(TA). Introduction and placement of the balloon for preparatory balloon valvuloplasty was
associated with slightly less HITS, especially for the transfemoral approach. During subsequent
balloon valvuloplasty the amount of HITS was again similar to the previous steps and not
different between groups. Introduction and propagation of the loaded delivery devices towards
12
DOI: 10.1161/CIRCULATIONAHA.112.092544
the aortic annulus resulted in a similar HITS frequency as during introduction of the
valvuloplasty balloon. During positioning of the stent-valve within the native aortic annulus, a
considerable increase of HITS was noted in all groups. This increase in HITS was three-times
more pronounced with the transfemoral and transapical ES valve than the MCV prosthesis.
Conversely, significantly more HITS were observed during stepwise implantation of the MCV
prosthesis than during rapid ES valve implantation via the transfemoral or transapical approach.
There was no difference in overall periprocedural HITS between transfemoral and
transapical ES valve implantation and only a trend towards more HITS during transfemoral
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
MCV implantation. There was also no difference between the number of HITS in the right and
eft MCA (group 1: 330.2 [260.4-400.1] vs. 281.5 [227.3-335.6], p=0.109; groupp 2: 243.8
243
43.8
.88
left
197.3-290.1] vs. 238.4 [185.1-291.7], p=0.594; group 3: 217.4 [169.7-265.1] vs. 266.9 [210.6[197.3-290.1]
3223.
3.3]
3],, p=0.108).
3]
p=
=0.
0.1108)
8)).
323.3],
pati
pa
t ents
ts off group
grou
gr
oupp 2 who
ou
who ha
ad th
he MC
CV prosthesis
prrossth
theesis
esis dislocated
dis
islo
loca
catted during
duuriing the
the first
fir
irstt
The 4 patients
had
the
MCV
mpl
plan
anta
an
tati
tion
on aattempt
ttem
tt
empt
em
p hhad
pt
ad
d aan
n ad
addi
diti
di
tion
ti
onal
all 1136.8
36..8
36
.8 ((27.5-304.8)
2 .527
.5-30
-304.8
04.8)
8) HI
HITS
T dduring
TS
urin
ur
ingg init
iinitial
nitia
iall po
ia
pos
sition
sit
ti nin
ng,
g
implantation
additional
positioning,
an
nd the
th
he subsequent
s bs
su
bseq
eque
uent
ue
n retrieval
ret
etri
riev
e al process.
ev
pro
roce
cess
ce
sss. Without
With
Wi
t ouut a counterpart
th
coun
co
untterrpa
un
part
rt in
in both
b th
bo
h ES
ES groups,
grou
gr
o ps, this
dislocation and
additional step was not included in the comparison but adds to the higher HITS rate in the MCV
group.
Postdeployment valvuloplasty resulted in additional 21.6 (16.1-27.1) HITS (group 1: 19.5
[12.5-26.5], group 2: 23, group 3: 27 and 31, p=0.331), which was less than the HITS during
preparatory valvuloplasty prior to valve implantation in these patients (21.6 [16.1-27.1] vs. 58
[23.0-93.0], p=0.049). The 2 patients with snaring of the MCV prosthesis had 9 and 14
additional HITS.
Acute Neurological Outcome
13
DOI: 10.1161/CIRCULATIONAHA.112.092544
We observed 2 procedural strokes, both in group 2. The patient requiring cardiopulmonary
resuscitation and vasoactive support suffered a major stroke and died 3 days later (mRS=6). One
further patient experienced a stroke resulting in right-sided hemiparesis and accounting for an
immediate postinterventional NIHSS rating of 8. Three points were scored for impairment of
motor leg function, two points for impairment of motor arm function, one point for limb ataxia
and two points for severe aphasia. The neurological symptoms continuously regressed, resulting
in NIHSS rating of 3 (2 points for impairment of motor leg function and one point for limb
ataxia) after 4 days and at discharge. Due to full recovery without sequelae at 3-months followDownloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
up (NIHSS rating: 0, mRS: 0), this stroke was graded minor.
ngess in
nN
IHSS
IH
SS
In the other patients, there were no neurological complications with chan
changes
NIHSS
coring, and a postprocedural MMSE score of 27.7 (27.3-28.2) indicated no decline in cognitive
scoring,
fu
unccti
tioon
on compared
com
o pare
reed to
t baseline (p=0.521); a postprocedural
posttpr
p ocedural MoCA
A score
scor
orre of
o 24.0 (23.3-24.6)
function
howed
ow
w even a slight
s ig
sl
ght but
butt significant
signnif
ific
ican
antt incline
an
in
nclline (p=0.001),
(p
p=0.0001),, probably
pro
roba
babl
ba
blyy ddue
ue to
o a llearning
eaarn
nin
ingg ef
effe
f ct ((online
fe
on
nli
l ne
showed
effect
da
ta supplement,
sup
uppl
plem
pl
emen
em
en
nt,, Table
Table 1).
1).
data
Follow-up
During 3-months follow-up, there were no late neurological events, and TCD at 3 months
showed no HITS. Clinical examination showed no sequelae in the patient with the periprocedural
stroke in group 2 accounting for a NIHSS rating of 0 and a mRS of 0. In all three patient groups,
neither a new neurological deficit nor a new disability or any progressive deficit in cognitive
function were observed. Accordingly, the NIHSS rating remained unchanged compared to
baseline, and there was no decline (even a minimal increase) in the MMSE (28.3 [28.0-28.7])
and MoCA (24.3 [23.6-24.9]) scores (p vs. baseline < 0.001) (online data supplement, Table
1).
14
DOI: 10.1161/CIRCULATIONAHA.112.092544
Potential Determinants of procedural HITS
Univariate linear regression analysis identified logistic EuroSCORE, STS-Score, mean
transaortic gradient at baseline, presence of coronary artery disease, obesity, diabetes mellitus,
aortic atheroma thickness, carotid artery plaque burden, LAA velocity, a prior cerebral ischemic
event, amount of administered heparin during the procedure and valve size to be associated with
an increased frequency of HITS during TAVI. Eight of these parameters (logistic EuroSCORE,
mean transaortic gradient at baseline, aortic atheroma thickness, carotid artery plaque burden,
LAA velocity, prior cerebral event, amount of administered heparin and valve size) were entered
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
into the multivariable model, and mean transaortic gradient at baseline was confirmed as an
ndependent predictor for the frequency of HITS, though the relatively small num
mbe ooff pa
mber
pati
tien
ti
e ts
en
independent
number
patients
n our single-center study and the relatively high number of independent variables eligible for the
in
mult
mu
ltiv
lt
ivaaria
iv
aria
iate
te model
moddel might
might have affectedd the precision
preci
ciision of this analy
ysi
s s ((online
onlline data supplement,
on
multivariate
analysis
T
ab
bl 2).
ble
Table
Discussion
The present, prospective study characterizes the origins of periprocedural embolization in 83
patients undergoing transfemoral or transapical TAVI with both the balloon-expandable ES or
the self-expandable MCV prosthesis. TCD of both middle cerebral arteries revealed cerebral
microembolization as reflected by HITS in all patients during TAVI, notably during
manipulation of the calcified aortic valve while positioning and implanting the stent-prostheses,
reminiscent of what is seen during stent implantation in the coronary circulation22. Despite HITS
in all patients, only two neurological events occurred periprocedurally, and neurocognitive
function during the 3-months follow-up was not impaired.
15
DOI: 10.1161/CIRCULATIONAHA.112.092544
Stroke and neurological events are major complications of both, cardiovascular
interventions and surgery. During isolated surgical aortic valve replacement, stroke is rare with
1.5% in normal-risk and up to 4.5% in elderly, high-risk patients23. For TAVI, however, an
increased rate of neurological events has raised safety concerns. In both, the inoperable cohort B
and the operable cohort A of the PARTNER trial, neurological events within the first 30 days
were observed in 6.7% and 5.5%, respectively, and more frequent than in patients treated with
optimal medical therapy (1.7%) or surgical aortic valve replacement (2.4%)1, 2. In the high-risk
patients eligible for either TAVI or surgical aortic valve replacement, the major stroke rate
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
within 30 days was 3.8% and higher than that after surgical aortic valve replacement with 2.1%.
Seven (58%) of the 12 strokes observed within 30 days after TAVI occurred wit
thinn th
he fi
firs
rstt 2
rs
within
the
first
days. The assignment to TAVI vs. surgical aortic valve replacement was identified as an
ndeepe
pend
nden
nd
entt rrisk
en
iskk ffactor
ac for such early strokes23.
actor
independent
Manipu
Manipulation
pula
latiion ooff a calcified,
la
calc
ca
lciifie
lc
ified,
d, st
ste
stenotic
enotic ao
eno
aortic
orticc vvalve
alv
ve du
during
urin
ng ddiagnostic
iaagno
agnost
stic
ic rretrograde
etro
et
rogr
grrad
adee
catheterization
with
ca
ath
thet
eter
et
e iz
er
izat
atio
at
ionn hhas
io
as be
been
en aassociated
ssoc
ocia
oc
iaate
tedd wit
w
ith
th aan
n incr
iincreased
ncr
crea
eaaseed
ed rate
ratte of
of neurological
neu
euro
ro
olo
logi
giica
call events,
ev
ven
nts
ts,, and
an an
an even
eveen
higher rate off ccerebral
e eb
er
ebra
r l em
ra
eembolization
boli
bo
liza
li
zaati
t on w
was
as ddetected
etec
et
ecte
ec
tedd in
te
i 222%
2%
% ooff ca
cases
ase
sess by ccerebral
ereebr
er
bral
al ddiffusion-weighted
iffu
if
fusi
fu
sion
si
o -weightedd
magnetic resonance imaging24. TAVI exerts an even greater trauma on the calcified valve during
preparatory valvuloplasty, valve passage with the semi-rigid, large-bore delivery catheters
containing the crimped stent-valve, valve positioning and crushing of the native leaflets to the
aortic wall during final implantation. New, but clinically silent lesions were found on cerebral
diffusion-weighted magnetic resonance imaging in 68-91% of patients after TAVI 4,5,6,7 and more
frequent than after surgical aortic valve replacement4. Collectively, these findings support the
notion, that the predominant etiology of periprocedural strokes during TAVI is embolic23 and
that emboli consist of debris from the calcified, native aortic valve or from aortic arch
16
DOI: 10.1161/CIRCULATIONAHA.112.092544
atheromata which are common in the elderly patients undergoing TAVI3,8.
Indeed TCD identified cerebral microembolization as a common event in each of the
procedural TAVI steps, both for the balloon-expandable ES and the self-expandable MCV as
well as for the transfemoral and the transapical approach, and the calcified aortic valve as the
main source of emboli: most HITS were recorded during valve manipulation, and mean
transaortic gradient at baseline - reflecting stenosis severity - was the main determinant of HITS
by multivariate analysis. Apparently, the aortic arch plays only a minor role for periprocedural
stroke and the transapical may therefore not be superior to the transfemoral approach.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
The lower amount of HITS during MCV than ES prosthesis positioning was expected,
ince initial positioning of the MCV prosthesis is rather quick and continuous adj
djjusstm
tmen
ents
en
ts are
are
r
since
adjustments
performed subsequently during stepwise release of the self-expandable stent-frame, whereas
prreccis
isee po
osi
siti
tioonin
ti
in
ng pprior
rior to implantation is moree ttime-consuming
ime-consumingg ffor
or ccorrect
orrrect placement of the ES
or
precise
positioning
valv
ve.
e Convers
rsel
ely,, m
el
oree HI
HITS
TS w
eree rrecorded
ecordeed dur
eco
ring the
he rrelatively
elattiv
iveelyy sl
slow
ow
w, stepwise
steepw
st
epwise
wisee rrelease
e eaasee ooff th
el
he
valve.
Conversely,
more
were
during
slow,
the
MC
CV pr
pros
osth
theesis
th
esis than
thhan
han during
duuri
ring
ng rapid,
rap
pid
id,, single-shot
singglee-s
sing
-shhot
hot im
impl
lan
nta
tati
tion
ti
on ooff th
he ES
E vvalve,
alve,, su
alve
upp
ppor
orttinng
or
ng tthe
he iidea
deea
MCV
prosthesis
implantation
the
supporting
hat the metallic
metal
alli
licc stent-frame
li
stten
entt-fr
frram
me acts
a ts in
ac
in a grater-like
grat
gr
ater
at
er-l
er
-lik
ikee fashion
ik
fash
fa
shhio
i n sc
scra
rapi
ra
ping
pi
ng ccalcific
a ci
al
cifi
ficc de
fi
debr
brris ffrom
rom
ro
m the native
that
scraping
debris
valve. The duration of aortic valve manipulation apparently also determines cerebral
embolization. In line with such “time is brain” concept, additional HITS were recorded in the 4
patients with MCV dislocation during the initial implantation attempt, which required additional
time and caused additional stress to the aortic valve. A high number of 7 and 26 new cerebral
lesions on diffusion-weighted magnetic resonance imaging in 2 cases of MCV dislocation has
been reported before25. These caveats must be considered for next-generation TAVI devices that
offer repositionability and retrievability and require more extensive valve manipulation.
Surprisingly, the amount of HITS during preparatory balloon aortic valvuloplasty was
17
DOI: 10.1161/CIRCULATIONAHA.112.092544
relatively low. Possibly, endothelial coverage prevents calcific debris from release and
embolization at this stage of the procedure3. Balloon valvuloplasty may only disrupt the
protective endothelial layer and expose friable debris that is subsequently liberated during valve
positioning and implantation. We can currently only speculate whether or not omission of the
preparatory valvuloplasty reduces the risk of embolic stroke. Grube et al. have recently shown
that TAVI using the MCV prosthesis is safe without balloon pre-dilatation and associated with a
5% risk of stroke26. Though this rate was lower than in their non-randomized, historical control
group (11.9%), it is not lower compared to the stroke rates currently reported for the MCV
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
prosthesis in large, multi-center registries, and postdilatation was necessary in 16.7% of cases.
Of note in this context, postdeployment valvuloplasty results in fewer HITS than
n ppreparatory
r pa
re
para
rato
ato
tory
ry
valvuloplasty.
Alth
Al
thou
th
ouughh ccerebral
erebral microembolization du
er
uri
rinng TAVI occur
rre
r d in
n aall
ll patients, neurological
Although
during
occurred
ev
vents
en
n were ra
are w
itth on
nly
ly oone
ne m
ajoor
aj
or aand
nd on
ne mino
ne
nor st
no
tro
oke
ke, iin
n aagreement
gree
gr
eeme
meent w
ith the
ith
the disparity
d spparrit
di
ityy
events
rare
with
only
major
one
minor
stroke,
with
be
etw
twee
eenn frequent
ee
freq
fr
eque
eq
uennt cerebral
cer
ereebr
ebral
ral lesions
leesi
s onns and
and on
only
ly ffew
ew
w nneurological
eurrolo
eu
l gi
lo
giccal
ca ev
eve
ents iin
ents
n th
he ab
abov
ovve me
ment
ntiionned
ned
between
events
the
above
mentioned
neuroimaging
ng sstudies.
t di
tu
d es
e . Th
T
clin
i ic
ical
a rrelevance
al
e ev
el
evan
ance
an
ce ooff si
ssilent
lent
le
n nneuroimaging
nt
euro
eu
roim
ro
imag
im
agin
ag
ingg le
lesi
sion
si
onss an
on
nd th
thee hi
hhigh
gh numberr
Thee cl
clinical
lesions
and
of periprocedural microemboli still remains unclear, but must be resolved when the indication for
TAVI is broadened to younger, lower-risk patients, since silent emboli have been associated with
declining neurocognitive function and deterioration of dementia27. In the present analysis, we did
not observe changes in neurocognitive function. However, subtle behavioral and cognitive
impairments may not have been detected by the crude MMSE and the MoCA test.
The high frequency of lesions on neuroimaging and HITS in TCD calls for procedural
and technical developments to reduce the risk of periprocedural embolization: less traumatic
devices, avoidance of extensive manipulation of the calcified aortic valve (“time is brain”),
18
DOI: 10.1161/CIRCULATIONAHA.112.092544
carotid artery compression during valve positioning and deployment, omission of preparatory
balloon valvulopasty and protection devices are currently under consideration. So far, omission
of preparatory balloon valvuloplasty did not reduce strokes below currently reported rates in a
pilot study26, and only one small feasibility study suggested placement of an embolic deflector
device over the brachiocephalic trunk and the left carotid artery as a safe and promising approach
for active cerebral protection28.
Study Strengths and Limitations
Serial real-time TCD is a standard surveillance technique during neurological interventions such
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
as carotid endarterectomy21,29, and it identified the source and procedural steps of cerebral
embolization in our patients undergoing TAVI. Our single-center study is descri
descriptive,
iptiv
ptiv
ve,, w
without
itho
it
hout
ho
ut
pre-specified power and sample size and without randomization between balloon- and the selfexpandable
ex
xpa
pand
ndab
able
ble pprotheses
roth
th
hese
eses as well as between transfem
transfemoral
emooral and transa
em
transapical
api
p call ac
acc
access,
cess, but nevertheless
reflects
typical
efllects a typic
cal cohort
coh
ohhort of patients
pati
pa
tien
ti
ents
ts currently
currreently
y undergoing
undeerggoin
ng TAVI.
TAV
AVI.
I Surgical
Surgi
urgiicall aortic
ao
orti
rtic
ic valve
val
a ve
replacement
epl
plac
accem
e en
nt encompasses
enccompas
en
mpasse
sees entirely
en
nti
t reely different
dif
ifffere
fere
rent
nt procedural
pro
roce
ro
ceeduuraal steps
step
st
eps and
ep
and was
was therefore
theref
the
ereffor
o e not
noot used
useed ffor
or
comparison.
Unfortunately, characterization of individual emboli for their size and composition is
currently impossible by TCD. Specifically, solid and gaseous emboli are not distinguished by
conventional systems, and even with more sophisticated equipment using dual-frequency
transducer technology such distinction is not sufficiently accurate, especially during procedures
where both occur29. Due to this methodology-inherent limitation of TCD it remains impossible to
clearly attribute HITS to embolic valve material, trapped air or microbubbles released during
catheter flushing and contrast injections. Obviously, the neurological consequences of a few,
large solid emboli are greater than those from multiple gaseous microbubbles. In the present
19
DOI: 10.1161/CIRCULATIONAHA.112.092544
study, however, most emboli were recorded during phases with a high probability of solid
emboli, namely valve positioning and implantation, and phases of catheter flushing and contrast
injections were excluded from the analysis. Assuming that solid rather than gaseous emboli are
associated with new neuroimaging lesions, correlation of HITS with new lesions on
postinterventional magnetic resonance imaging might have been interesting, but was not feasible
in all patients, and our previous neuroimaging studies had already demonstrated a high rate of
new cerebral lesions after TAVI.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Conclusion
Cerebral microembolization, reflected by HITS on TCD, is inherent to TAVI and
nd
d ooccurs
c ur
cc
urss in eeach
ach
ac
procedural phase, predominantly during positioning and implantation of the stent-prostheses,
endderrin
ingg the
the calcified
caalc
lciifie
ifi d aortic valve the mainn source
souurc
r e of emboli. HIT
IT
TS, hhowever,
owever, were not
ow
rendering
HITS,
asso
oci
c ated wit
th an
an increased
inc
ncre
reas
ased
as
ed rate
rate
ate of nneurological
eurolo
ogi
giccal deficits
defici
de
ciitss oorr acut
aacutely
cutel
elyy im
impa
pairred nneurocognitive
pa
eurroccog
eu
cognit
itiive
it
ive
associated
with
impaired
fu
unc
ncti
tion
ti
o . The
on
The “real”
“reeal”
“r
eal”
l neurological
neu
uro
rolo
ogi
g caal ri
ris
sk ooff th
sk
thee TA
TAV
VI pprocedure
ro
oceedu
dure
ree aand
nd tthe
he ffeasibility,
eaasi
sibi
bili
bi
lity
ty,, sa
ty
saf
fety
ty
y aand
nd
function.
risk
TAVI
safety
efficacy of up
upco
comi
co
ming
mi
ng sstrategies
tratteg
tr
egie
i s to rreduce
ie
e uc
ed
ucee th
thee ri
risk
sk ffor
or cer
ereb
er
ebra
eb
raal em
embo
oli
liza
zati
za
tion
ti
on nneed
eedd fu
ee
furt
rthe
rt
h r study.
upcoming
cerebral
embolization
further
Acknowledgements: We thank Nils Lehmann from the Institute of Medical Informatics,
Biometry and Epidemiology of the University Hospital Essen for his advice.
Conflict of Interest Disclosures: Philipp Kahlert and Matthias Thielmann are clinical proctors
for Edwards Lifesciences Inc. and have received honoraria payments. Holger Eggebrecht is a
clinical proctor for Medtronic Inc. and has received honoraria payment.
20
DOI: 10.1161/CIRCULATIONAHA.112.092544
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23
DOI: 10.1161/CIRCULATIONAHA.112.092544
Table 1. Patient Characteristics.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Overall
TAVI
(n=83)
Group 1
TF-TAVI with MCV
(n=32)
Group 2
TF-TAVI with ES
(n=26)
Group 3
TA-TAVI with ES
(n=25)
p
80.6 (79.3-81.8)
81 (77; 84)
35 (42.2)
79.4 (77.0-81.8)
80 (74; 82.75)
11 (34.4)
82.5 (80.4-84.7)
83 (79.75; 87)
16 (61.5)
80 (78.3-81.7)
80 (77.5; 83)
8 (32)
0.093
20.7 (17.8-23.5)
17.6 (10.8; 29.2)
6.7 (5.7-7.7)
5.0 (3.5; 9.5)
81 (97.6)
17.7 (13.1-22.4)
15.0 (7.5; 23.6)
5.6 (3.9-7.2)
4.1 (2.7; 6.2)
32 (100)
16.1 (12.6-19.6)
13.7 (9.8; 19.8)
7.2 (5.5-8.9)
6.5 (3.8; 10.1)
25 (96.2)
29.3 (23.8-34.7)
(23..88-34
34.7
34
.7))
27.6 (19
(19.6;
34.2)
19
9.6;
6; 34
34.2
.2))
.2
(5.6-9.6)
7.6 (5
(5.6
.6-9
.6
-9.6
6)
5.5 (4.1; 10.2)
24 (96)
<0.001
<0.00 *
<0
Hyperlipidemia,
rlipidemia, n (%))
60 (72.3)
27 (84.4)
20 (76.9)
13 (52)
0.062
0.06
Diabetes
tes
es mellitus,
mel
elli
litu
li
tuss, n (%)
tu
(%)
%
25 (30.1)
7 (21.9)
9)
(50)
13 (50
50))
5 (20)
0.028 †
0.02
Smoking,
in
ing,
ng n (%)
(%)
%
18 (21.7)
(21
21.7
.7))
(18.8)
6 (1
(18.
8.8)
8)
(30.8)
8 (3
(30.
0 8)
8
4 (1
((16)
6)
0.399
0.39
Obesity,
ty, n (%)
(%)
42 ((50.6)
5 .6))
50
13 ((40.6)
1
40.6))
16 ((61.5)
6 .5)
61
13 ((52)
52)
52
2)
0.281
0.28
Coronary
nary
a artery
art
r ery disease,
e n (%)
%
%)
46
46 (55.4)
(55
5 .44)
18
1 (56.3)
(56.3))
14
1 (53.8)
(53
5 .8)
14 (56)
(56
5 )
0.220
0.22
Prior cardiac
card
ca
r iac
rd
ac surgery,
surg
su
r er
ery,
y, n (%)
(%)
199 (22.9)
(22
22.9
2.9
. )
10 ((31.3)
1
31.3
31
.3))
2 (7
(7.7)
7 )
7 (28)
(2
28))
0.081
0.
.08
(49.2-54.1)
51. (49
51.7
49.2
2-5
-54.
54 1)
1
(45.7-54.4)
550.1
0.1
0.
1 (4
(45
5.77-54
54.4)
4)
53.0
53.0
0 (48.5-57.5)
(48.5-5
5-57.
7 5))
52.3
52.
2.3
3 (48.3-56.2)
(48
(4
8.3-56
56.2
.2))
0.572
0.57
0.
5
55 (45;
(45
45; 58
58))
14 ((16.9)
16.99)
59.5)
55 ((40.5;
40.5;
5 59
.5)
5)
5 (1
((15.6)
5.6)
6
55 (50;
58.5)
(50
50; 58
.5)
5)
(11.5)
3 (1
(11.
5))
55 ((43;
43; 59
43
59))
(24)
6 (2
24))
0.463
0.
46
Aortic valve area, cm2
0.68 (0.64-0.72)
0.66 (0.59-0.73)
0.68 (0.61-0.75)
0.71 (0.62-0.80)
0.645
Mean transaortic gradient, mm Hg
0.70 (0.52; 0.80)
50.1 (45.5-54.7)
0.63 (0.50; 0.79)
50.5 (43.4-57.7)
0.70 (0.60; 0.80)
51.0 (45.2-56.8)
0.70 (0.55; 0.89)
48.6 (36.9-60.3)
0.915
49.8 (35.8; 59.2)
52.3 (35.0; 61.8)
49.8 (45.3; 55.3)
47.1 (29.3; 57.3)
Age, years
Female gender, n (%)
Logistic
tic EuroSCORE, %
STS Score, %
Arterial
al hypertension, n (%)
Ejection
on fraction,
fra
ract
ctiion
ion, %
Renal dysfunction, n ((%)
%)
Continuous variables are presented as mean (95% CI) (first row) and median (Q1; Q3) (second row).
Pairwise comparisons with Bonferroni correction were performed for variables where there was a significant difference between groups:
* group 1 vs. group 2: p=1.0
group 1 vs. group 3: p=0.003
group 2 vs. group 3: p<0.001
† group 1 vs. group 2: p=0.075
group 1 vs. group 3: p=1.0
group 2 vs. group 3: p=0.075
24
0.053
00.051
.05
0
0.520
0.52
DOI: 10.1161/CIRCULATIONAHA.112.092544
Table 2. Potential Sources of Embolism.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Aortic atheroma, n (%)
- mild
- moderate
- severe
Aorticc atheroma thickness, mm
Porcellain
llain aorta, n (%)
Atrial fibrillation, n (%)
velo
oci
city
ty
y, cm/s
cm/
LAA velocity,
LA
AA velocity
v locity (<55
ve
(<5
<55
55 cm/s),
cm/s
cm
/ss),
) n (%)
(%)
Low LAA
aneou
o s echo contras
ou
ast,
t, n ((%)
%)
Spontaneous
contrast,
a diac
ar
a thrombi, n (%)
Intracardiac
for
o am
amen
m n ovale,, n (%)
(%)
Patentt foramen
id ar
rte
tery
ry st
tenoosi
teno
sis,
s n ((%)
%)
Carotid
artery
stenosis,
id ar
arte
tery
y pplaques
laqu
q es 30qu
0-70%,
%, n ((%)
%))
Carotid
artery
30-70%,
id artery plaques
es < 30%,
30%
0 , n (%
(%))
Carotid
id artery
arte
ar
tery
ry plaque
pla
laqu
quee burden,
burd
bu
rden
en %
Carotid
Prior cerebral ischemic event, n (%)
Statin therapy n (%)
Overall
TAVI
(n=83)
Group 1
TF-TAVI with MCV
(n=32)
Group 2
TF-TAVI with ES
(n=26)
Group 3
TA-TAVI with ES
(n=25)
p*
72 (87)
11 (13)
0 (0)
26 (81)
6 (19)
0 (0)
23 (88)
3 (12)
0 (0)
23 (92)
2 (8)
0 (0)
(0)
0.520
0.2 (0.2-0.3)
0.2 (0.2; 0.3)
1 (1.2)
20 (24.1)
51.0 (46.4-55.6)
47.5 (37.6; 59.1)
661
1 (7
(73.
3 5)
3.
(73.5)
1 ((16.9)
14
16.
16
6 9))
0 (0
((0))
(2.
2 4))
2 (2.4)
2 (2
.44)
(2.4)
27 ((33)
33))
33
544 ((65)
6 )
65
20
4 ((15.8-24.9)
15 8-24
24 9)
20.4
20 (0; 30)
9 (10.8)
63 (75.9)
0.2 (0.2-0.3)
0.2 (0.2; 0.3)
0 (0)
6 (18.8)
43.9 (39
39.9
.9-4
-47.8)
(39.9-47.8)
43.6 (37.6;
(37.
37.6;
6 551.5)
1.5)
330
0 (93.
93 8)
8
(93.8)
7 ((21.9)
21
1.9)
9)
0 (0)
0
(0)
0
0 (0)
1 (3
.1)
1)
(3.1)
10 ((31)
31))
2 ((66)
21
666)
220.3
0 3 (1
(12
2 0-28
28 6)
(12.0-28.6)
10 (0; 30)
1 (3.1)
22 (68.8)
0.2 (0.2-0.3)
0.2 (0.2; 0.3)
1 (3.8)
9 (34.6)
(43.0-59
9.1
.1))
51.0 (43.0-59.1)
48.7 (35.
5.8;
5.
8 64.
4.0)
0)
(35.8;
64.0)
118
8 (6
(69.
9.2)
2)
(69.2)
4 (1
((15.4)
5 4)
5.
0 (0
((0)
0)
(3.
3.8))
1 (3.8)
1 (3
(3.8
.88)
(3.8)
6 (2
((23)
3))
19 (73
733)
(73)
21
2 ((13.1-29.2)
13 1-29
29 2)
21.2
20 (10; 30)
6 (23.1)
20 (76.9)
(0.2-0.3)
0.2 (0
0.2-0
2-0
0.3))
(0.2;
0.2 (0
.2;
.2
2; 0.3)
0.3)
3
0 (0)
5 (20)
59.3 (48.3-70.1)
55.4 (43.2; 76.3)
113
3 (5
((52)
2)
3 (12)
(12
12)
2)
0 (0
((0)
0)
(4)
1 (4)
0 (0
(0))
111
1 (4
((44)
4))
14 ((56)
56))
56
119.6
9 6 (1
(11
1 7-27
27 5)
(11.7-27.5)
20 (0; 30)
2 (8)
21 (84.0)
0.992
0.
0
99
0.614
0.61
0.31
0.316
0.017
0.017†
00.002
. 02 ‡
.0
0 53
0.
0.533
11.000
1.
00
0.51
0.514
11.000
.00
0
0.2
.27
7
0.275
0.
444
0.440
00.896
89
9
0.054
0.258
Continuous variables are presented as mean (95% CI) (first row) and median (Q1; Q3) (second row).
*: Adjustment for age, gender and the two significantly different variables in baseline patient characteristics (logistic EuroSCORE and diabetes mellitus) did not
change rating of significance.
Pairwise comparisons with Bonferroni correction were performed for variables where there was a significant difference between groups:
† group 1 vs. group 2: p=0.318
group 1 vs. group 3: p=0.030
group 2 vs. group 3: p=0.663
‡ group 1 vs. group 2: p=0.042
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p=0.624
25
DOI: 10.1161/CIRCULATIONAHA.112.092544
Table 3. Procedural Data.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
General anaesthesia (GA), n (%)
Conscious sedation (CS), n (%)
Switch from CS to GA, n (%)
Hemodynamic instability, n (%)
p
, n (%)
( )
Vascular complications,
esis´ size, n (%)
Prosthesis´
- 23 mm
- 26 mm
- 29 mm
dure time, min
Procedure
Fluoroscopy
time,
min
oscop
opyy ti
ime
me,, mi
m
n
Contrast
astt volume,
vol
olum
lume,
e mll
Administered
n ster
ni
e ed heparin, IU
er
U
Aortic vvalve
TAVI,
a ve area post T
al
A I, ccm
AV
m2
Mean trans
transaortic
nsao
aort
rti
tic
ic ggradient
radi
ra
dient po
post
stt
g
TAVI,, mm H
Hg
y-mor
o ta
tality
ty n,, %
30-day-mortality
3-month-mortality n, %
Overall
TAVI
(n=83)
33 (39.8)
50 (60.2)
1 (1.2)
3 (3.6)
( )
5 (6.0)
Group 1
TF-TAVI with MCV
(n=32)
2 (6.2)
30 (93.8)
0 (0)
1 (3.1)
( )
3 (9.4)
Group 2
TF-TAVI with ES
(n=26)
6 (23.1)
20 (76.9)
1 (3.8)
2 (7.7)
( )
2 (7.7)
18 (22)
30 (36)
35 (42)
68.0 (60.0-75.5)
56.0 (45.0; 82.0)
12.0 (10.3-13.3)
10.4 (7.2; 14.7)
169.4
16
69.
9.44 (153.1-185.6)
( 533.1
(1
. -1185.6
. )
1566 (1
15
(120
20;; 20
20
208)
8)
(120;
(6412.7-7515.0)
66963.9
963
96
63.99 (641
(6
6412.
12.77-75
7 15
75
15.0))
8000)
7000
0 (5000;
(5000
00 ; 80
000
00))
1.700 (1.61-1.80)
( .6
(1
.6161 1.800)
11.67
.67 (1
.6
(1.38;
1 8; 22.00)
.000)
0
99.99 (8
9.
(8.8-10.9)
.8
8-1
-10
10.9)
0.9)
8 (25)
24 (75)
48.5 (42.5-54.4)
45.5 (39.0; 50.75)
(10.5-14.3)
12.4 (10.
0.55-14
1 .3)
14
10.6 (9
9.7
.7;
7; 16.1)
6
(9.7;
170.5
17 5 (145.4-195.5)
(145
(1
45.44-195.5)
1
)
1146
46 ((122.5;
122.
12
2 5; 189.5)
189
8 .5))
66828.1
828.1 (6072.1-7584.1)
(6072.1-75
-7 84.1)
4 )
6000
0 ((5000;
5000;
0 88000)
000))
11.68
.688 (1.
(1.57-1.79)
57-1
7 .79)
79)
11.68
. 8 (1
.6
(1.4
.45;
5 11.90)
.90)
.9
0))
(1.45;
99.5
.5
5 ((8.5-10.6)
8.55-10
5-10.6)
6)
14 (54)
12 (46)
0 (0)
59.3 (50.4-68.2)
55.0 (47.25; 67.25)
(13.4-19.2)
16.3 (13.4-1
19.
9.2)
2)
(11
11.4; 20.1)
200.1
.1)
1)
13.9 (11.4;
199.77 (165.1-234.2)
(165
(1
6 .1-2
-234
34.2
.2))
180 (1
(148
4 .75;
.775; 2228.75)
28.7
28
.75)
5
180
(148.75;
6327.0
6 27
63
2 .00 ((5556.4-7097.4)
5556
55 .44-7
-709
0 7.
7 4))
7500)
66000
60
00 (5000;
(5000;
0
75
500)
0)
1.688 (1
(1.46-1.91)
.46-1.91
9 )
11.58
. 8 (1
.5
((1.28;
.28;
28; 11.98)
.9
98))
99.33 (6
9.
(6.6
(6.6-12.0)
6.6
6-1
-122.0)
2.0)
99.4
.4 ((7.0;
7 0; 112.0)
7.
2.0)
2.
0)
7 ((8.4)
8.4)
8.
4)
10 (12.0)
99.4
.4
4 ((7.7;
7 7;; 111.9)
7.
1 9)
1.
3 ((9.4)
9.4)
9.
4)
4 (12.5)
77.9
.9 ((5.5;
5.5;
5; 113.9)
3.9)
3.
9)
2 ((7.7)
7.7)
7.
7)
3 (11.5)
Group 3
TA-TAVI with ES
(n=25)
25 (100)
0 (0)
0 (0)
0 (0)
( )
0 (0)
p*
<0.001 †
<0.001 ‡
0.614
0.498
0.372
< .0 §
<0
<0.001
4 (1
((16)
6)
6)
10 ((40)
40))
40
11 (44)
101.2 (83.2-119.3)
<0.0
<0.001 ||
88.0 (75.0; 122.5)
<0.001 #
6.3 (4.3-8.3)
<0.0
5.5 (4.2; 7.2)
136.6
0.009
136.
13
6.66 (114.0-159.1)
(1144.0-159
(1
59.1)
0 00 **
0.
1120
20 ((95;
95;; 17
95
176)
6)
7800.0
780
800.
0.00 (6424.5-9175.5)
( 42
(6
4 4.
4.55 91
175.55)
00.209
.2
10000)
7500 (5000;
(5000
0 ; 1000
0 0)
11.76
1.
766 (1.
(1.54-1.98)
1.54-1.98)
9
0.7
0.764
11.69
.699 (1
.6
(1.35;; 22.08)
.08)
08)
10.9
10.9 (8.6-13.2)
(8
8.66-13
13.2)
3.2)
0.476
0.4
110.0
0.00 (8
0.
((8.1;
.1;
.1
1 13.5)
2 ((8)
8)
3 (12)
11.000
.0
1.000
Continuous variables are presented as mean (95% CI) (first row) and median (Q1; Q3) (second row).
*: After adjustment for age, gender and the two significantly different variables in baseline patient characteristics (logistic EuroSCORE and diabetes mellitus) differences in the
use of general anaesthesia and conscious sedation as well as in the amount of contrast volume lost significance.
Pairwise comparisons with Bonferroni correction were performed for variables where there was a significant difference between groups:
† group 1 vs. group 2: p=0.192
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p<0.001
‡ group 1 vs. group 2: p=0.369
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p<0.001
§ group 1 vs. group 2: p<0.001
group 1 vs. group 3: p=0.045
group 2 vs. group 3: p<0.001
|| group 1 vs. group 2: p=0.012
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p<0.001
# group 1 vs. group 2: p=0.054
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p<0.001
** group 1 vs. group 2: p=0.474
group 1 vs. group 3: p=0.150
group 2 vs. group 3: p=0.009
26
DOI: 10.1161/CIRCULATIONAHA.112.092544
Table 4. Procedural HITS.
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Overall
TAVI
(n=83)
Group 1
TF-TAVI with MCV
(n=32)
Group 2
TF-TAVI with ES
(n=26)
Group 3
TA-TAVI with ES
(n=25)
p*
31.0 (23.0-38.9)
28.3 (11.6-45.0)
27.5 (16.7-38.4)
37.9 (25.5-50.4)
0.078
17 (7; 47)
12.5 (5; 32)
17 (7.5; 52.75)
36 (12; 60)
35.2 (28.8-41.6)
34.6 (23.3-45.9)
39.7 (29.3-50.0)
31.4 (18.6-44.2)
26 (10; 56)
25.5 (12.25; 49)
32 (21.5; 59.5)
21(7;
21
1(7
(7;; 62
62))
22.9 (18.4-27.4)
20.0 (11.3-28.6)
19.5 (13.4-25.6)
30.1
1 (21.7-38.5)
(21.7-38
3 .5
38
.5))
19 (8; 33)
13.5 (4.5; 23.75)
17 (8.75; 28.25)
30 (18.5; 35)
34.6 (26.9-42.3)
38.0 (24.2-51.7)
26.3 (12.3-40.3))
39.0 (25.8-52.2)
29 (8; 44)
29 (9; 53.25)
53
3.25
2 )
25
14.5 (2.75;
(2.75
7 ; 35)
75
5)
35 (22; 47)
19.2
19.2 (13.9-24.4)
(13
13.99-2
-24.
4.4)
4))
15.3
15.
5.3
3 (7.1-23.4)
(7.1
(7
.1-2
-23.4)
4)
21.0
21.0 (12.4-29.7)
(1
12.
2 44 29
29.7
.7))
22.3
22.3 (10.6-34.0)
(10
10.6
.6-3
-34.
4 0)
11 (3;
(3; 23)
23)
6 (2.25;
(2.
2.25;
5 15.75)
15.775)
(5.75;
114.5
4 5 (5
4.
(5.7
.75;
5; 224.5)
4.5)
5)
9 ((0.5;
0 5;
0.
5 229)
9
9)
Valve Positioning
P si
Po
s ti
t oning
173.7
1 3.
17
3 7 (137.1-210.4)
(1
137
3 .1-210
1 .4))
122
12
22 (38;
38 2269)
6 )
69
78.5
7 .5 (25.3-131.6)
78
(25.3-1
5
31.6)
24 ((8.5;
8 5;
8.
5 87.75)
87.
7 75
7 )
259.9
25
9.9
.9 (184.8-334.9)
(184
8 .8
.8-334.9
.9)
22200 (113.5;
22
(1133.5;
5; 327.5)
3227.
7.5)
5
206.1
(162.5-249.7)
20
2
06.
6.1 (162
6 .5
.5-2
-249
49.7)
298)
2207
07 (119;
(11
1 9;
9 298
9 )
<0.001‡
<0
<
.00
Valve Im
IImplantation
plan
anta
nta
tati
tion
ti
on
214.1
214
21
4.1
1 (1
((165.4-262.7)
65
5.44-2
-262
262
62.7
.7)
397.1
(302.1-492.2)
397
39
7.1 (3
7.1
(302
02.1
02
.1-49
492
49
2.2)
2
2)
888.2
8.2
2 (70.2-106.3)
( 0.2
(7
2-10
2-10
1 6.
6.3)
3)
1110.7
10.77 ((82.0-139.3)
8 .00-139
82
-1
139
39.3
.3)
3)
<0.001§
<0.0
<0
00
122
12
2 (80;
(80
(8
0; 2256)
0;
56))
56
(221.75;
317
31
7 (2
(221
21.75
75;
5; 5506.25)
06.25)
25)
99
99 (56.25;
(56
(5
6.25
25;; 113)
25
113)
994
4 (53;
(53
(5
3; 1173)
3;
73))
73
(473.0-584.4)
5528.7
52
8 7 (4
8.
(473
73.0-584
73
584
4.4)
4)
605.6
6 5.6 (495.3-716.0)
60
(495
(4
9 .3-7
95
3-716
16
6.0)
0)
482.2
482.
48
2 2 (394.8-596.6)
(394
(3
9 .8-5
8-5
596.6)
6)
478.6
478.
47
8 6 (396.1-561.0)
(3
3966.1
1-5
- 61.0)
473 (338; 642)
541.5 (367.5; 778.5)
425.5 (331.75; 590.25)
524 (317; 611)
Aortic Valve Passage
Stiff Guidewire
Propagation
gation and Placement of
the Valvuloplasty
alvuloplasty Balloon
Balloon
Aortic
Valvuloplasty
on Aort
r ic Valvu
ulo
lopl
p assty
Delivery
ery Device
Devic
i e
Sum of all Procedural
Steps
Procedural
al St
Step
epss
ep
0.252
0.010
0.
0.01
01 †
0.068
0.06
0.195
0.19
0.093
0.09
Variables are presented as mean (95% CI) (first row) and median (Q1; Q3) (second row).
*: Adjustment for age, gender and the two significantly different variables in baseline patient characteristics (logistic EuroSCORE and diabetes mellitus) did not
change rating of significance.
Pairwise comparisons with Bonferroni correction were performed for variables where there was a significant difference between groups:
† group 1 vs. group 2: p=1.0
group 1 vs. group 3: p=0.012
group 2 vs. group 3: p=0.066
‡ group 1 vs. group 2: p<0.001
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p=1.0
§ group 1 vs. group 2: p<0.001
group 1 vs. group 3: p<0.001
group 2 vs. group 3: p=1.0
27
DOI: 10.1161/CIRCULATIONAHA.112.092544
Figure Legends:
Figure 1. Transcranial Doppler (TCD) of a patient at rest (A) and during implantation of a MCV
prosthesis (B). No high-intensity transient signals (HITS) are observed at rest, while several
signals are monitored during valve deployment.
Figure 2. Procedural HITS were detected during all steps of the TAVI-procedure. Most HITS,
however, occurred upon manipulation of the calcified aortic valve during positioning and
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
implantation of the stent-valves. While the balloon-expandable ES prosthesis caused
ignificantly more HITS during positioning, the self-expandable MCV prosthesis
is ccaused
ause
au
sedd mo
se
more
re
significantly
HITS during implantation.
28
Velocity
[cm/s]
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Velocity
[cm/s]
1 se
1second
second
TF-TAVI - ES
TA-TAVI - ES
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
TF-TAVI - MCV
Cerebral Embolization During Transcatheter Aortic Valve Implantation: A Transcranial
Doppler Study
Philipp Kahlert, Fadi Al-Rashid, Philipp Doettger, Kathrine Mori, Björn Plicht, Daniel Wendt, Lars
Bergmann, Eva Kottenberg, Marc Schlamann, Petra Mummel, Dagny Holle, Matthias Thielmann,
Heinz G. Jakob, Thomas Konorza, Gerd Heusch, Raimund Erbel and Holger Eggebrecht
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Circulation. published online August 16, 2012;
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circ.ahajournals.org/content/early/2012/08/13/CIRCULATIONAHA.112.092544
Data Supplement (unedited) at:
http://circ.ahajournals.org/content/suppl/2012/08/13/CIRCULATIONAHA.112.092544.DC1
http://circ.ahajournals.org/content/suppl/2013/05/12/CIRCULATIONAHA.112.092544.DC2
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
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SUPPLEMENTAL MATERIAL
SUPPLEMENTAL TABLES
Table 1. Neurocognitive Testing.
MMSE
Overall
Group 1
Group 2
Group 3
TAVI
TF-TAVI with MCV
TF-TAVI with ES
TA-TAVI with ES
(n=83)
(n=32)
(n=26)
(n=25)
p
baseline
27.9 (27.5-28.3)
28 (27; 29)
28.0 (27.5-28.5)
28 (27; 29)
27.3 (26.1-28.6)
28 (27; 29)
28.3 (27.8-28.8)
28 (28; 29)
0.625
post TAVI
27.7 (27.3-28.2)
28 (27; 29)
27.7 (26.9-28.4)
28 (27; 29)
27.6 (26.4-28.7)
28 (27; 29)
28.0 (27.4-28.5)
28 (27; 29)
0.911
3-months follow-up
28.3 (28.0-28.7)
29 (28; 29)
28.4 (27.9-28.9)
28 (28; 29)
28.1 (27.0-29.1)
29 (27; 29)
28.6 (28.1-29.0)
29 (28; 29)
0.840
baseline vs. post TAVI
p=0.521
p=0.488
p=0.400
p=0.256
baseline vs. 3 months
p<0.001
p=0.083
p=0.003
p=0.096
post TAVI vs. 3 months
p=0.001
p=0.048
p=0.079
p=0.023
Pairwise comparison
MoCA
baseline
23.4 (22.7-24.0)
24 (21; 25)
23.9 (22.9-24.9)
24 (22; 26)
23.4 (22.0-24.8)
25 (20; 26)
22.6 (21.4-23.8)
23(21; 24)
0.283
post TAVI
24.0 (23.3-24.6)
25 (22; 26)
24.2 (23.1-25.3)
25 (22; 26)
23.9 (22.4-25.4)
25 (22; 26)
23.7 (22.7-24.7)
24 (21; 25)
0.829
3-months follow-up
24.3 (23.6-24.9)
25 (23; 26)
24.4 (23.3-25.5)
25 (23; 26)
24.2 (22.7-25.7)
25 (22; 26)
24.1 (23.0-25.3)
25 (23; 25)
0.930
baseline vs. post TAVI
p=0.001
p=0.288
p=0.029
p=0.009
baseline vs. 3 months
p<0.001
p=0.192
p=0.001
p<0.001
post TAVI vs. 3 months
p=0.270
p=0.620
p=0.381
p=0.559
Pairwise comparison
Variables are presented as mean (95% CI) (first row) and median (Q1; Q3) (second row).
Table 2. Multivariate Regression Analysis.
estimator b
95 % confidence interval
p
Logistic EuroSCORE, %
-1.106
-6.667 – 4.455
0.692
Mean transaortic gradient at baseline, mm Hg
3.979
0.197 – 7.760
0.040
Aortic atheroma thickness, µm
-0.395
-0.943 – 0.153
0.154
Carotid artery plaque burden, %
-0.887
-4.510 – 2.737
0.626
LAA velocity, cm/s
-1.171
-4.684 – 2.342
0.507
Prior cerebral ischemic event, n
-104.940
-321.794 – 111.915
0.336
Prosthesis´ size, 23 / 26 / 29 mm
18.396
-10.616 – 47.407
0.209
Administered heparin, IU
0.005
-0.023 – 0.034
0.709
Page 220
220
Circulation
Mai 2013
patients porteurs de stimulateurs cardiaques et essai d’abolition de la fibrillation atriale par électrostimulation des oreillettes) a
porté sur 2 580 patients âgés de plus de 65 ans qui étaient porteurs d’un stimulateur cardiaque bicavitaire et atteints d’hypertension artérielle, mais n’avaient aucun antécédent de FA. Des études électrophysiologiques non invasives ont été régulièrement
pratiquées sur une période de deux ans dans un sous-groupe de 485 patients. Il n’a pas été relevé de différences entre les
caractéristiques cliniques des patients chez lesquels des tachyarythmies atriales avaient été décelées par le stimulateur au cours
de la première année et de ceux qui étaient demeurés indemnes de tels troubles. Chez les premiers, il a été noté un allongement
des durées des ondes P déclenchées (153 ± 29 ms versus 145 ± 28 ms ; p = 0,046) et détectées (128 ± 46 ms versus 118 ± 25 ms ;
p = 0,06) et une plus forte propension au développement de FA induites à l’occasion des études électrophysiologiques (23,5 %
versus 13,6 % ; p = 0,03). Aucun différence n’a, en revanche, été objectivée entre les deux groupes de patients en ce qui concerne
leurs temps de récupération sinusale corrigés à 90 battements/min (388 ± 554 ms versus 376 ± 466 ms ; p = 0,86), la durée de leur
période réfractaire atriale efficace à 90 battements/min (250 ± 32 ms versus 248 ± 36 ms ; p = 0,70) et le raccourcissement de cette
dernière en adaptation à la fréquence (14 ± 13 ms versus 12 ± 14 ms ; p = 0,11). Il n’a pas été identifié de différence significative
entre les modifications du substrat électrophysiologique enregistrées au cours des deux ans chez les patients ayant présenté des
tachyarythmies atriales et chez ceux qui en sont demeurés indemnes.
Conclusions—L’allongement de la durée des ondes P favorise le développement de tachyarythmies atriales chez les patients
porteurs d’un stimulateur cardiaque, ce qui n’est pas le cas des modifications de la période réfractaire atriale efficace. (Traduit
de l’anglais : Relevance of Electrical Remodeling inHuman Atrial Fibrillation. Results of the Asymptomatic Atrial Fibrillation
and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial Mechanisms of Atrial
Fibrillation Study. Circ Arrhythm Electrophysiol. 2012;5:626–631.)
Mots clés : fibrillation atriale 䊏 électrophysiologie 䊏 hypertension artérielle 䊏 stimulateurs cardiaques 䊏 remodelage
Les embolies cérébrales lors de remplacements
valvulaires aortiques percutanés
Une étude par Doppler transcrânien
Philipp Kahlert, MD ; Fadi Al-Rashid, MD ; Philipp Döttger, MS ; Kathrine Mori, MS ; Björn Plicht, MD ;
Daniel Wendt, MD ; Lars Bergmann, MD, DESA ; Eva Kottenberg, MD ; Marc Schlamann, MD ;
Petra Mummel, MD ; Dagny Holle, MD ; Matthias Thielmann, MD ; Heinz G. Jakob, MD ;
Thomas Konorza, MD ; Gerd Heusch, MD ; Raimund Erbel, MD ; Holger Eggebrecht, MD
Contexte—Qu’il soit pratiqué par voie transfémorale ou transapicale, le remplacement valvulaire aortique percutané (RVAP)
augmente le risque d’accident neurologique comparativement à l’approche chirurgicale. L’imagerie par résonance magnétique
cérébrale a montré que la fréquence des lésions nouvelles, cliniquement silencieuses, secondaires à la migration de microemboles
est plus élevée lors de l’emploi de cette technique ; pour autant, on ignore quelle est l’origine principale de ces microemboles et à
quel temps de l’intervention ils sont le plus susceptibles d’être libérés.
Méthodes et résultats—Des RVAP ont été réalisées chez 83 patients par abord transfémoral (Medtronic CoreValve [MCVTF], n = 32 ;
Edwards Sapien [ESTF], n = 26) ou par voie transapicale (ESTA , n = 25). Des explorations par écho-Doppler transcrânien ont été
pratiquées avant, pendant et 3 mois après les RVAP en vue de rechercher les éventuels hypersignaux transitoires (HST) tenant
lieu de marqueurs de la présence de microemboles. De tels HST ont été mis en évidence chez tous les patients pendant la période
opératoire, principalement lors de la manipulation de la valve aortique calcifiée alors que le stent-valve était positionné et
implanté. L’emploi de la prothèse ES expansible sur ballonnet a donné lieu à un nombre d’HST (moyenne [IC à 95 %])
significativement supérieur au cours de son placement (ESTF : 259,9 [184,8–334,9] ; ESTA : 206,1 [162,5–249,7] ; MCVTF : 78,5
[25,3–131,6] ; p <0,001) et celui de la prothèse MCV auto-expansible lors de son implantation (MCVTF : 397,1 [302,1–492,2] ;
ESTF : 88,2 [70,2–106,3] ; ESTA : 110,7 [82,0–139,3] ; p <0,001). Globalement, il n’a pas été noté de différence significative entre
les abords transfémoral et transapical ni entre les implants MCV et ES. Aucun HST n’a été décelé à l’entrée dans l’étude
ni au terme de la période de suivi de 3 mois. Dans le groupe traité par prothèses MCV, un accident vasculaire cérébral
peropératoire majeur, ayant entraîné le décès du patient, et un autre de type mineur, qui avait totalement régressé au 3ème mois,
ont été enregistrés.
Conclusions—L’écho-Doppler transcrânien a objectivé des HST peropératoires chez tous les patients. Alors qu’aucune différence
n’a été relevée entre les voies transfémorale et transapicale lors de l’emploi du stent-valve ES expansible sur ballonnet, les
RVAP pratiquées par abord transfémoral en utilisant l’implant MCV auto-expansible ont induit le taux d’HST le plus élevé,
essentiellement lors de l’implantation dudit implant. (Traduit de l’anglais : Cerebral Embolization During Transcatheter Aortic
Valve Implantation. A Transcranial Doppler Study. Circulation. 2012;126:1245–1255.)
Mots clés : rétrécissement valvulaire aortique 䊏 ischémie cérébrale 䊏 remplacement valvulaire aortique percutané 䊏 valves 䊏
écho-Doppler transcrânien
12:48:15:04:13
Page 220