Editorial
Assessment and management of
low-gradient, low ejection
fraction aortic stenosis
Christophe Tribouilloy, Franck Lévy
Low-gradient, low ejection fraction aortic
stenosis (AS) represents about 5–10% of
all cases of severe AS and is the most
challenging subgroup of patients to man-
age.1 2 The term low-gradient, low ejec-
tion fraction AS is usually applied to
patients with a mean gradient ,30 mm
Hg (or 40 mm Hg), an aortic valve area
(AVA) ,1 cm2, and an ejection fraction
(EF) ,35% (or 40%).1–7 Low EF in such
patients may be caused by severe low-
flow AS with inadequate compensatory
left ventricular hypertrophy, called after-
load mismatch, but also by another
myocardial disease (such as extensive
fibrosis, associated cardiomyopathy or
myocardial infarction (MI)),5 in which
case, AS is not the primary problem. The
essential difficulty for clinicians is to
distinguish true severe low-flow AS,
responsible for low EF, from pseudo-
severe AS comprising mild-to-moderate
AS associated with another cause of left
ventricular dysfunction (LVD). A very
low gradient may be seen in true severe
low-flow AS, while the decreased AVA
seen in pseudo-severe AS reflects poor
opening of the aortic valve directly related
to low transvalvular flow. For the clin-
ician, the two main questions in low-
gradient, low ejection fraction AS are:
How severe is the AS? Which patients can
benefit from surgery?
HOW SEVERE IS THE AORTIC STENOSIS?
Determining the true severity of low-
gradient, low ejection fraction AS may be
a challenging problem. Physical examina-
tion is often misleading with a soft
systolic ejection murmur despite severe
AS. Echocardiography is the key examina-
tion for visualising the aortic valve, and
measuring the maximum aortic velocity,
pressure gradient, valve resistance, AVA
and EF. As initially reported by deFilippi
Inserm, ERI 12, Amiens, France and University Hospital
Amiens, France
Correspondence to: Professor C Tribouilloy,
Department of Cardiovascular Disease, Avenue René
Laënnec, 80054, Amiens Cedex 1, France; tribouilloy.
christophe@chu-amiens.fr
1526
et al,6 dobutamine echocardiography is
extremely helpful to potentially distin-
guish severe from non-severe AS.
Dobutamine may increase the stroke
volume (SV) and consequently the aortic
transvalvular flow. Contractile reserve
(CR) during dobutamine echocardiogra-
phy is currently defined by an increase of
SV .20%.2 7 In pseudo-severe AS, an
increase of SV results in an increase of
AVA to reach a non-severe range
(.1.2 cm2), whereas the gradient
(,30 mm Hg) is not significantly altered
owing to the larger AVA.3 The additional
value of a new index derived from
dobutamine echocardiography, the pro-
jected effective AVA at a flow rate of
250 ml/s, has been proposed to distin-
guish patients with true severe low-
gradient, low ejection fraction AS from
patients with pseudo-severe disease.8
In this issue of Heart, Burwash et al,
using dynamic positron emission tomo-
graphy, demonstrate that patients with
true severe low-gradient, low ejection
fraction AS have a marked tendency to
higher resting myocardial blood flow and
more severe impairment of myocardial
flow reserve than patients with pseudo-
severe AS (see page 1627).9 Although
these preliminary data are promising,
larger studies are necessary to confirm
the value of these parameters to distin-
guish these two entities and to determine
their possible role and feasibility in
routine clinical practice. The same group
reported that B-type natriuretic peptide is
significantly lower, but with a consider-
able overlap of values, in pseudo-severe
low-gradient, low ejection fraction AS
than in true severe AS.10
In true severe low-gradient, low ejec-
tion fraction AS, the dobutamine-induced
increase of SV leads to a marked increase
of gradient with only a slight change in
AVA.3 6 7 These patients are considered to
have severe low-gradient, low ejection
fraction AS with CR. In contrast, in some
patients, dobutamine infusion does not
induce any change in SV and conse-
quently no change in gradient or
AVA.3 6 7 These patients are considered
to have low-gradient, low ejection frac-
tion AS without CR, but the severity of
AS remains undetermined. In these
patients, severe aortic valve calcification
on echocardiography, fluoroscopy or CT
is an indicator of considerable AS.
WHICH PATIENTS CAN BENEFIT FROM
SURGERY?
In selected patients with low-gradient,
low ejection fraction AS, aortic valve
replacement (AVR) is associated with a
dramatic improvement of long-term sur-
vival compared with medical manage-
ment.2 7 11 12 Moreover, among patients
who survive AVR, an improvement in
functional status is usually seen and the
EF increases by at least 10% in more than
80% of cases.4 Perioperative mortality in
low-gradient, low ejection fraction AS
ranges from 8 to 21% in recent publica-
tions.1 3 7 11 12
In a multicentre European study, we
reported a significant decrease of opera-
tive mortality, from 20% in the 1990s to
10% over the past 5 years.12 Perioperative
mortality and lower long-term postopera-
tive survival are mainly related to older
age, presence of comorbidities, very low
pressure gradient (,20 mm Hg), severe
associated coronary artery disease or
history of MI, and absence of CR with
dobutamine.1 12 A high operative mortal-
ity of about 30% is reported in patients
with low-gradient AS without CR.2 4 7 12
Conversely, those patients with CR had
an operative mortality of only 5–8%.
Patients with severe AS and CR therefore
have an acceptable operative risk and
AVR may improve long-term survival
and functional status in most cases.2 7
In the recent European guidelines,
surgery is advised in this group of patients
with CR.2 Because of the very high
operative risk in the absence of CR, many
clinicians consider that the absence of CR
constitutes a contraindication to AVR.
However, in these patients, the prognosis
with medical management is extremely
poor and there is a trend, in a small
patients series, towards better survival
after AVR.7 Moreover, in those patients
who survive the perioperative period,
functional status improved in more than
90% of cases and LVEF improved by
.10% in more than 60% of cases.4
Perhaps the main determinant for low
preoperative EF in these patients without
CR is an afterload mismatch that cannot
be corrected by inotropic stimula-
tion (dobutamine). Therefore, the
absence of CR with dobutamine in low-
gradient, low ejection fraction AS does
Heart December 2008 Vol 94 No 12

not systematically indicate irreversible
LVD. According to the European guide-
lines,2 ‘‘surgery can be performed in these
patients but decision-making should take
into account clinical condition, in parti-
cular the presence of comorbidity, degree
of valve calcification, extent of coronary
artery disease and feasibility of revascu-
larisation’’. Thus the decision for AVR
surgery should be made case by case and
the absence of CR should not be con-
sidered to be an absolute contraindication
to AVR. In our opinion, surgery could be
considered in patients with calcified aortic
valve without CR in the absence of
scarring due to extensive MI and excessive
comorbidities, and in the presence of a
basal mean gradient .20 mm Hg. A heart
transplant should also be considered in
eligible patients. As the currently available
data are unable to identify clearly the
subset of patient who will have a better
outcome with surgery, further studies
must be conducted in large series of
patients with low-gradient, low ejection
fraction AS without CR. In the near
future, percutaneous AVR could be a
valuable alternative for surgical high-risk
patients with low-gradient, low ejection
fraction AS.
Patients with pseudo-severe AS should
be carefully followed up to detect any
change in the severity of AS and of LVD.
Medical treatment, which may induce
inverse remodelling, must be systemati-
cally optimised. In patients with increased
QRS duration and ventricular asyn-
chrony, cardiac resynchronisation should
be discussed. AVR is classically not
recommended in reports of pseudo-severe
Heart December 2008 Vol 94 No 12
AS. For example, patients with low-
gradient, low ejection fraction AS with
an AVA on dobutamine echocardiography
clearly greater than 1.3 cm2 and with
another cause of LVD, such as a large scar
of MI, are not suitable for AVR. However,
because the increased afterload due to the
‘‘moderate’’ AS may be not well tolerated
in the presence of a severe associated LVD,
surgery, in our opinion, should be care-
fully discussed in some patients with an
AVA of about 1.2–1.3 cm2 on dobuta-
mine. Unfortunately, the currently avail-
able data on pseudo-severe AS are too
limited to allow any definitive conclu-
sions about the management of these
patients, and further multicentre studies
including larger number of cases are
mandatory in this heterogeneous subset
of patients.
Competing interests: None declared.
Heart 2008;94:1526–1527.
doi:10.1136/hrt.2008.142745
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Editorial
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1527
 Assessment and management of
low-gradient, low ejection fraction aortic
stenosis
Christophe Tribouilloy and Franck Lévy

Heart 2008 94: 1526-1527 originally published online July 31, 2008
doi: 10.1136/hrt.2008.142745

Updated information and services can be found at:

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References This article cites 11 articles, 10 of which can be accessed free at:
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