DOI: 10.1161/CIRCULATIONAHA.113.005539
Reverse Remodeling in the Perspective of Decision-Making for
Mitral Valve Repair with the MitraClip
Running title: Rosenhek; Reverse Remodeling after MitraClip Therapy
Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017
Raphael Rosenhek, MD
Dept
p of Cardiology, Medical University
Univ
iveersity
iv
er
of Vienna,, Vi
ienn
enna, Austria
Dept
Vienna,
Add
Ad
dresss for
dres
for Correspondence:
Corres
Corr
espo
pond
nden
dence
ce::
Address
Raphael
h l Rosenhek,
Rosenhhek
k MD
Raphael
Department of Cardiology
Vienna General Hospital, Medical University of Vienna
Waehringer Guertel 18 – 20
1090 Vienna, Austria
Tel: +43 (1) 40400 4614
Fax: +43 (1) 40400 4216
E-mail: [email protected]
Journal Subject Code: Cardiovascular (CV) surgery:[38] CV surgery: valvular disease
Key words: Editorial
1
DOI: 10.1161/CIRCULATIONAHA.113.005539
Degenerative and functional mitral regurgitation (MR) constitute two separate disease entities:
while the pathophysiological problem is directly addressed by a successful intervention on the
valve in the first case, the underlying ventricular disease persists in the latter.
Indications for surgery in mitral regurgitation are well defined for degenerative MR,
where the relief of the valve lesion leads to a relief on the left ventricular volume overload. The
timing of surgery is based on symptoms, left ventricular size and function, atrial fibrillation and
pulmonary hypertension1, 2. When following these criteria, surgery is associated with
symptomatic improvement and also with a survival benefit. Nevertheless, up to 50% of patients,
Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017
in particular when they are elderly or present with comorbidities or reduced ventricular function
are denied surgery despite having a clear indication for intervention3.
Criteria for surgical intervention are less well defined in functional mitral regurgitation,
where
wher
wh
eree the
er
the valve
v lve is structurally
va
str
t ucturally normal and regurgitation
regurg
rgiitaation is causedd by
rg
b an
an imbalance
im
between
closing
cl
lossin
i g and te
tethering
eth
heriing fo
for
forces
rces rrelated
rces
elate
lateed to a vventricular
enttriiculaar
ar pat
pathology
tholo
logy
gy
y4, wh
whic
which
ichh is
i nnot
ott eentirely
ntir
nt
irel
e y corrected
el
co
orrrecte
ecte
tedd by
the
he relief
reli
re
lief
li
ef of
of MR.
MR.. From
MR
From
m the
the surgical
suurgi
urgi
giccal experience
exp
per
erie
ienncee it iiss kn
ie
known
now
wn th
that
at a va
valve
alv
lvee in
intervention
nte
terv
rven
rv
en
nti
tion
on lleads
eaadss tto
o an
n
initial
nitial reduct
reduction
tio
on off M
MR,
R, alt
although
lttho
houg
ug
gh th
the
he re
recurrence
ecu
curr
rren
rr
ence
en
cee rrate
atee is
at
i hhigh
ighh an
ig
and
nd a su
surv
survival
rviv
rv
ival
iv
al bbenefit
en
nef
efit
it hhas
a not been
as
demonstrated so far5. Furthermore the surgical risk is frequently non-negligible and as a result
indications for surgery are not strong unless there is an indication for coronary artery bypass
surgery1, 2. On a general basis, the first approach in these patients is the initiation of a heart
failure therapy including cardiac resynchronization therapy, which has a proven survival benefit.
Nevertheless, a percutaneous approach for the therapy of MR is an attractive concept for
the management of inoperable and selected high-risk patients. The percutaneous MitraClip
system has been adapted from the surgical edge-to-edge technique proposed by Alfieri6. When
introducing a novel technique into clinical practice, several important questions need to be
2
DOI: 10.1161/CIRCULATIONAHA.113.005539
addressed regarding the safety of implantation, the efficacy in reducing MR, the effect on
symptomatic improvement, the effect on left ventricular remodeling and last but not least the
effect on overall survival. Obviously these question need to be answered for degenerative and for
functional MR.
The EVEREST I study was performed to demonstrate the feasibility, safety and efficacy
of the procedure7. In a systematic review it has been shown that the MitraClip can be safely and
effectively implanted in high-risk surgical patients8. While in the EVEREST II trial
(randomizing patients to MitraClip or surgical therapy), the majority of patients had degenerative
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mitral regurgitation, data from postapproval studies such as ACCESS-EU9 trial and the TRAMI
registry
egistry10 indicate that the larger part of patients being treated in clinical practicee ha
have
ave ffunctional
unct
un
ctio
ct
iona
io
n l
MR. These studies have confirmed an efficacious reduction in MR severity and symptomatic
improvement
mpr
prov
ovem
ov
em
men
e t for
fo
or th
thee majority of the patients.
The present
prres
esen
entt paper
en
paapeer by Grayburn
Gra
rayb
ybuurn
yb
urn et
et al.
l.111 hass the
the merits
mer
erit
itts to demonstrate
demon
onsstrrat
atee th
the
he ef
effe
effect
fect
fe
ct ooff the
t he
reduction
edu
duct
ctio
ct
i n of M
io
MR
R oon
n rreverse
eveers
ev
erse lleft
eftt ve
ef
vent
ventricular
n ri
nt
ricu
cula
cu
larr and
la
an
nd left
leeftt atrial
atrriaal remodeling
remo
re
mode
mo
deeliing after
aftter
e M
MitraClip
ittra
r Cli
Clip
ip
implantation
mplantationn iin
n 80
801
01 pa
pati
patients
tiien
ents
ts w
with
itth se
severe
eve
v re M
MR
R de
deri
derived
riive
vedd fr
from
om tthe
he E
EVEREST
VERE
VE
REST
RE
ST III,
I tthe
I,
he E
EVEREST
VEREST II
VE
high risk study and the continued access EVEREST II (REALISM) study, as well as in 80
surgically treated patients. The study has the merits to separately assess the entities of
degenerative and of functional MR.
In patients with degenerative MR a reduction of the left ventricular end-diastolic volume
(LVEDV) from 140±40 to 120±35 ml was observed, while the end-systolic volume (LVESV)
remained rather stable with 53±21 and 50±20 ml at baseline and at 12 months, respectively.
These findings are explained by an effective reduction of volume overload.
In patients with functional MR, a reduction in LVEDV from 166±52 to 151±49 ml and of
3
DOI: 10.1161/CIRCULATIONAHA.113.005539
the LVESV from 96±41 to 87±41 ml was observed. Furthermore, significant residual MR (3-4+)
was associated with significantly less ventricular remodeling both in degenerative and in
functional MR as compared to lesser residual MR. Finally, reverse left atrial remodeling was also
related to the magnitude MR reduction observed with the intervention. Thus, the greater the
reduction of MR, the more reverse remodeling can be expected.
The documented reverse remodeling in this large series is another important piece of
information supporting the concept of percutaneous correction of MR. These data may also be
seen in the context with the findings of the MitraSwiss registry that included 100 patients in
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which the magnitude of residual MR after a MitraClip intervention was predictive of 1-year
survival
urvival12.
It needs to be noted that the inclusion criteria for the EVEREST II trial, required an
ej
ejection
jeccti
tion
on fraction
fra
ract
ctiionn > 25
ct
2 % and a left ventricular end-systolic
end
nd-ssystolic diamet
nd
diameter
etter
e < 555
5 mm for inclusion13 and
in
n the
thhe
he EVEREST
EVERE
EST II
II high-risk
high
hi
gh
h-rris
iskk trial,
trial,
tria
l, patients
pat
atie
iennts with
wi an
an eje
ejection
ecttio
ionn frac
ffraction
racttioon
on < 20
20%
0% orr a lleft
0%
eftt ve
ef
vent
ventricular
tri
ricu
cu
ulaar
end-systolic
mm
en
ndd sy
syst
stol
olic
ic ddiameter
iame
ia
mete
me
terr > 60 m
m14 w
were
ere ex
ere
excluded.
xcl
cluuded
uded
ed.. Ind
IIndeed,
ndeed
ed,, th
ed
thee av
ave
average
erag
erag
agee ej
ejec
ejection
eccti
tion
on fraction
fra
racctio
ctio
ion at bbaseline
assellin
i e
nt analysis
ana
n ly
lysi
s s was
si
w s 44±11%
wa
44±1
44
±1
11% for
forr patients
pat
a ie
ient
n s with
nt
wit
i h functional
fu
unc
ncti
tion
ti
onal
on
al MR
MR and
and 62±8%
62±
2 8% for
for tthose
h se with
ho
inn the present
degenerative MR. The endsystolic diameters at baseline were 46±7 mm and 34±7 mm for
patients with functional and degenerative MR, respectively. It is thus not proven that a similar
extent of reverse remodeling can be expected in patients with very poor ventricular function and
excessive left ventricular dilation. The potential futility of an intervention needs to be considered
in such cases.
From the currently available data, it is justified to consider a MitraClip implantation in
inoperable or high-risk patients with degenerative MR, when their valve anatomy is suitable1. In
secondary MR the MitraClip procedure should be considered in inoperable or high-risk patients
4
DOI: 10.1161/CIRCULATIONAHA.113.005539
after the optimization of medical therapy and having considered cardiac resynchronization
therapy1. While there is increasing evidence, that in functional MR the procedure leads to
reduction of MR, symptomatic improvement and reverse ventricular remodeling, the important
question, regarding a potential survival benefit remains unanswered yet. A sufficiently powered
randomized study comparing the survival of patients with functional MR receiving optimal
medical therapy to those undergoing a MitraClip implantation is eagerly awaited. In the
meantime a careful risk-assessment and individualized decision-making is required15. The impact
on reverse remodeling is one additional element to consider in the decision process.
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ottt an
andd Ed
Edwa
ward
wa
rds
rd
Conflict of Interest Disclosures: Dr. Rosenhek reports lecture fees from Abbot
Abbott
Edwards
Lifesciences
Refe
Re
fere
fe
renc
re
nces
es::
es
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7
Reverse Remodeling in the Perspective of Decision-Making for Mitral Valve Repair with the
MitraClip
Raphael Rosenhek
Circulation. published online September 6, 2013;
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Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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