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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
"diabetes mellitus"
symptom
acute rheumatic fever
adrenal incidentaloma
adrenomyeloneuropathy
allergic bronchopulmonary aspergillosis
alpha-thalassemia
child syndrome
cholangiocarcinoma
cohen syndrome
congenital adrenal hyperplasia
congenital toxoplasmosis
cowden syndrome
cushing syndrome
cystinuria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
fabry disease
familial hypocalciuric hypercalcemia
malignant atrophic papulosis
neuralgic amyotrophy
pyomyositis
sneddon syndrome
typhoid
werner syndrome
wolf-hirschhorn syndrome
This symptom has already been validated
