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Myocardial gene expression of microRNA-133a and myosin heavy and light chains, in conjunction with clinical parameters, predict regression of left ventricular hypertrophy after valve replacement in patients with aortic stenosis.
[wolf-hirschhorn syndrome]
Left
ventricular
(
LV
)
reverse
remodelling
after
valve
replacement
in
aortic
stenosis
(
AS
)
has
been
classically
linked
to
the
hydraulic
performance
of
the
replacement
device
,
but
myocardial
status
at
the
time
of
surgery
has
received
little
attention
.
To
establish
predictors
of
LV
mass
(
LVM
)
regression
1
year
after
valve
replacement
in
a
surgical
cohort
of
patients
with
AS
based
on
preoperative
clinical
and
echocardiographic
parameters
and
the
myocardial
gene
expression
profile
at
surgery
.
Transcript
levels
of
remodelling-related
proteins
and
regulators
were
determined
in
LV
intraoperative
biopsies
from
46
patients
with
AS
by
RT-PCR
.
Using
multiple
linear
regression
analysis
,
an
equation
was
developed
(
adjusted
R
²
=
0
.
73
;
p
<
0
.
0001
)
that
included
positive
[
preoperative
LVM
,
microRNA-
133
a
,
serum
response
factor
(
SRF
,
which
is
known
to
be
a
transactivator
of
miR-
133
)
and
age
]
and
negative
[
body
mass
index
(
BMI
)
,
Wolf-
Hirschhorn
syndrome
candidate
-
2
(
WHSC
2
,
which
is
a
target
for
repression
by
miR-
133
a
)
,
β-myosin
heavy
chain
,
myosin
light
chain-
2
,
diabetes
mellitus
,
and
male
gender
]
independent
predictors
of
LVM
reduction
.
Aortic
valve
area
gain
or
the
reduction
in
transvalvular
gradient
maintained
no
significant
relationships
with
the
dependent
variable
.
Logistic
regression
analysis
identified
microRNA-
133
a
as
a
significant
positive
predictor
of
LVM
normalisation
,
whereas
β-myosin
heavy
chain
and
BMI
constituted
negative
predictors
.
Hypertrophy
regression
1
year
after
pressure
overload
release
is
related
to
the
preoperative
myocardial
expression
of
remodelling-related
genes
,
in
conjunction
with
the
patient
's
clinical
background
.
In
this
scenario
,
miR-
133
emerges
as
a
key
element
of
the
reverse
remodelling
process
.
Postoperative
improvement
of
valve
haemodynamics
does
not
predict
the
degree
of
hypertrophy
regression
or
LVM
normalisation
.
These
results
led
us
to
reconsider
the
current
reverse
remodelling
paradigm
and
(
1
)
to
include
criteria
of
hypertrophy
reversibility
in
the
decision
algorithm
used
to
decide
timing
for
the
operation
;
and
(
2
)
to
modify
other
prevailing
factors
(
overweight
,
diabetes
,
etc
)
known
to
maintain
LV
hypertrophy
.
Diseases
Validation
Diseases presenting
"aortic stenosis"
symptom
22q11.2 deletion syndrome
oligodontia
wolf-hirschhorn syndrome
This symptom has already been validated
