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Transcript
Low-Gradient Aortic Stenosis
Operative Risk Stratification and Predictors for Long-Term Outcome:
A Multicenter Study Using Dobutamine Stress Hemodynamics
Jean-Luc Monin, MD; Jean-Paul Quéré, MD; Mehran Monchi, MD; Hélène Petit, MD;
Serge Baleynaud, MD; Christophe Chauvel, MD; Camélia Pop, MD; Patrick Ohlmann, MD;
Claude Lelguen, MD; Patrick Dehant, MD; Christophe Tribouilloy, MD, PhD; Pascal Guéret, MD
Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017
Background—The prognostic value of dobutamine stress hemodynamic data in the setting of low-gradient aortic stenosis
has been addressed in small, single-center studies. Larger studies are needed to define the criteria for selecting the
patients who will benefit from valve replacement.
Methods and Results—Six centers prospectively enrolled 136 patients with aortic stenosis (96 men; median age, 72 years
[range, 65 to 77 years]; median aortic valve area, 0.7 cm2 [range, 0.6 to 0.8]; mean transaortic gradient, 29 mm Hg
[range, 23 to 34 mm Hg]; cardiac index, 2.11 L · min⫺1 · m⫺2 [range, 1.75 to 2.55 L · min⫺1 · m⫺2]). Left ventricular
contractile reserve on the dobutamine stress Doppler study was present in 92 patients (group I) and absent in 44 patients
(group II). Operative mortality was 5% (3 of 64 patients) in group I compared with 32% (10 of 31 patients) in group
II (P⫽0.0002). Predictors for operative mortality were the lack of contractile reserve (odds ratio, 10.9; 95% confidence
interval [CI], 2.6 to 43.4; P⫽0.001) and a mean transaortic gradient ⱕ20 mm Hg (odds ratio, 4.7; 95% CI, 1.1 to 21.0;
P⫽0.04). Predictors for long-term survival were valve replacement (hazard ratio, 0.30; 95% CI, 0.17 to 0.53; P⫽0.001)
and left ventricular contractile reserve (hazard ratio, 0.40; 95% CI, 0.23 to 0.69; P⫽0.001).
Conclusions—In the setting of low-gradient aortic stenosis, surgery seems beneficial for most of the patients with left
ventricular contractile reserve. In contrast, the postoperative outcome of patients without reserve is compromised by a
high operative mortality. Thus, dobutamine stress Doppler hemodynamics may be factored into the risk-benefit analysis
for each patient. (Circulation. 2003;108:319-324.)
Key Words: valves 䡲 hemodynamics 䡲 surgery 䡲 cardiomyopathy 䡲 echocardiography
P
atients with severe aortic stenosis (AS), left ventricular
(LV) dysfunction, and low transaortic pressure gradients
(low-gradient AS) represent a common medical challenge
considering their high operative mortality1– 6 and dismal
spontaneous prognosis.3,5 Dobutamine stress hemodynamics
can differentiate between patients with true severe (fixed) AS,
who are likely to benefit from valve replacement, and those
with primary cardiomyopathy and nonsevere (relative) AS,
for whom medical therapy may be indicated.7,8 Previous
studies3,4 have also suggested that dobutamine stress Doppler
data can help stratify operative risk in this setting. Unfortunately, the four latter studies were relatively small, singlecenter studies.3,4,7,8 Therefore, we conducted a multicenter
study including a large cohort of patients with low-gradient
AS to (1) confirm the value of dobutamine stress Doppler
data for operative risk stratification; (2) define better the
prevalence of relative AS; and (3) identify independent
predictors for long-term outcome in these patients.
Methods
Study Population
All consecutive patients with symptomatic, severe AS (valve area
ⱕ1 cm2)9 and a low cardiac index (ⱕ3.0 L · min⫺1 · m⫺2) were
eligible if their mean transaortic pressure gradient (MPG)
wasⱕ40 mm Hg.3 Exclusion criteria were severe comorbidities,
more than mild aortic or mitral regurgitation, and atrial fibrillation.
The study was approved by local review boards, and informed
consent was obtained from the patients before all procedures. From
April 1994 to January 2002, 136 patients were prospectively enrolled
in 6 centers in France. Preliminary data from one center were
published in a previous report3; 43 patients from this series (with
extended follow-up data) were included in the present report.
Dobutamine Stress Hemodynamic Studies
All patients underwent a comprehensive Doppler echocardiographic
study using commercially available ultrasound systems. Details of
the dobutamine stress hemodynamic protocol have been previously
described.3 Briefly, after the baseline measurements, dobutamine
was infused up to a maximal dose of 20 ␮g/kg per minute. LV
Received February 12, 2003; revision received April 29, 2003; accepted May 2, 2003.
From the Departments of Cardiology, Henri Mondor Hospital, Créteil (J.-L.M., P.G.); University Hospital, Amiens (J.-P.Q., C.T.); General Hospital,
Saint-Dizier (C.P.); General Hospital, Lorient (S.B., C.L.); Clinique Saint-Augustin, Bordeaux (C.C., P.D.); Department of Cardiac Surgery, University
Hospital, Strasbourg, France (H.P., P.O.); and the Department of Intensive Care, University Hospital Sart Tilman, Liège, Belgium (M.M).
Correspondence to Dr J.L. Monin, Department of Cardiology, Henri Mondor Hospital, 51 Avenue De Lattre de Tassigny, 94010 Créteil, France. E-mail
[email protected]
© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000079171.43055.46
319
320
Circulation
July 22, 2003
TABLE 1.
Baseline Clinical and Hemodynamic Data
Variable
Group I
(n⫽92)
Group II
(n⫽44)
P
Age, y
72 (66–78)
72 (65–77)
0.92
62 (67)
34 (77)
0.23
11/7/50/10/4/10
11/3/14/4/3/9
0.12
15/53/32
16/53/30
0.97
40
43
0.73
Coronary disease, 0/1/2/3-vessel, %
60/21/4/15
57/9/18/15
0.03
Previous myocardial infarction, n (%)
14 (15)
8 (18)
0.59
Diabetes, n (%)
18 (20)
4 (9)
0.12
Hypertension, n (%)
20 (22)
7 (16)
0.42
116 (100–130)
118 (100–131)
0.78
80 (70–89)
81 (70–90)
0.63
0.15
Male sex, n (%)
Center of origin,
Amiens/Bordeaux/Créteil/
Lorient/Reims/Strasbourg, n
NYHA class, II/III/IV, %
Coronary artery disease, %
Systolic blood pressure, mm Hg
Heart rate, bpm
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End-diastolic LV diameter, mm
LVEF
Stroke volume, mL
Cardiac index, L 䡠 min⫺1 䡠 m⫺2
Aortic valve area, cm
2
MPG, mm Hg
Aortic valve resistance, dyne 䡠 s 䡠 cm⫺5
59 (56–66)
61 (55–65)
0.31 (0.23–0.35)
0.30 (0.27–0.35)
0.92
46 (37–55)
51 (45–57)
0.06
2.0 (1.7–2.5)
2.3 (1.9–2.6)
0.054
0.7 (0.6–0.8)
0.8 (0.7–0.9)
0.045
27 (22–35)
30 (23–34)
0.39
216 (171–278)
208 (196–259)
0.81
Values are median (range), n (%), or as indicated.
outflow tract diameter was assumed to be constant at different flow
states, and the baseline value was used to calculate stroke volume
according to standard formulae.10 Transaortic gradients were calculated using the simplified Bernoulli equation.11 Aortic valve area was
calculated by the continuity equation.12 Aortic valve resistance was
calculated according to the standard formula.13 LV ejection fraction
(EF) was calculated according to the biplane Simpson’s rule14 in 100
patients, visually estimated15 in 19 patients, and not available in 15
patients.
Clinical Decisions and Follow-Up
Therapeutic decisions for each patient were left to the discretion of
the referring physicians who had knowledge of individual dobutamine stress hemodynamic data. Clinical data at follow-up were
obtained in all patients at a median interval of 14 months (range, 7
to 29 months) by direct patient examination or telephone interview.
Evaluated end points at follow-up were survival and New York Heart
Association functional class.
Data Analysis
The dobutamine stress hemodynamic studies were evaluated off-line
in each center by a single experienced echocardiographer who was
blinded to the clinical data. All data from each center were then
centralized in Liège, Belgium, for statistical analysis. LV contractile
reserve during dobutamine infusion was defined by an increase in
stroke volume of ⱖ20% compared with baseline values3; patients
were then divided into 2 groups according to the presence (group I)
or absence (group II) of contractile reserve. Relative AS was defined
by an increase in valve area ⱖ0.3 cm2, with a final valve area ⬎1 cm2
on dobutamine stress hemodynamics.3,7
Statistical Analysis
Continuous data are presented as median values and corresponding
25th and 75th percentiles. Univariate analysis was performed using
nonparametric statistical tests. To identify the cut point in baseline
transaortic MPG that would define the ranges of severity, MPG was
plotted against perioperative mortality (ie, death within 30 days after
valve replacement), and the lowess smoothing function, using locally
weighted least squares, was used.16 Survival curves were established
by the Kaplan-Meier estimation method. Variables that were significantly associated with perioperative mortality by univariate analysis
were entered into a multiple logistic regression model to allow for
the determination of independent parameters. Variables that were
significantly associated with long-term survival were included in a
Cox proportional hazards model to assess their independent association with survival. Two-tailed probability values ⬍0.05 were
considered statistically significant. Analyses were done using
STATA software (version 7.0, Stata Corp).
Results
Clinical Characteristics
The study population included 40 women and 96 men aged a
median of 72 years (range, 65 to 77 years) with a median
aortic valve area of 0.7 cm2 (range, 0.6 to 0.8 cm2), median
MPG of 29 mm Hg (range, 23 to 34 mm Hg), median LVEF
of 0.30 (range, 0.24 to 0.35), median cardiac index of 2.11 L
· min⫺1 · m⫺2 (range, 1.75 to 2.55 L · min⫺1 · m⫺2), and median
aortic valve resistance of 216 dyne · s · cm⫺5 (range, 181 to
283 dyne · s · cm⫺5). Symptoms at first presentation were
congestive heart failure in 133 patients, with associated
angina or syncope in 11 and 2 patients, respectively; isolated
angina or syncope were reported in 1 and 2 patients, respectively. Coronary angiography was performed in 121 patients,
with no significant stenosis in 65 patients (54%); single-,
double- or triple-vessel disease was present in 18, 12, and 21
patients, respectively. Five patients had patent coronary
artery bypass grafts (CABG). According to dobutamine stress
hemodynamics, LV contractile reserve was present in 92
patients (group I, 68%) and absent in 44 patients (group II,
32%). Baseline data by group are presented in Table 1;
Monin et al
Low-Gradient Aortic Stenosis
321
TABLE 2. Results of Univariate Analysis for Potential Predictors of
Perioperative Mortality
Survivors After
Valve Replacement
(n⫽82)
Death Within 30
Days After Valve
Replacement
(n⫽13)
P
15/6/39/5/5/12
4/1/7/0/1/0
0.60
71 (63–75)
72 (70–78)
0.14
55 (67)
11 (84)
0.20
0/14/44/24
0/2/6/5
0.80
13 (16)
4 (31)
0.22
Coronary artery disease, 0/1/2/3-vessel, n
53/15/5/9
5/2/2/4
0.12
Associated coronary bypass surgery, n (%)
20 (24)
7 (54)
0.03
Contractile reserve, n (%)
61 (74)
3 (23)
0.001
MPG ⱕ20 mm Hg, n (%)
3 (4)
4 (31)
0.006
0.32 (0.27–0.36)
0.30 (0.20–0.31)
0.08
58 (55–63)
62 (58–67)
0.09
Diabetes mellitus, n (%)
14 (17)
2 (15)
0.88
Hypertension, n (%)
16 (19)
4 (31)
0.35
Variable
Center of origin,
Amiens/Bordeaux/Créteil/
Lorient/Reims/Strasbourg, n
Age, y
Male sex, n (%)
NYHA class, I/II/III/IV, n
Previous myocardial infarction, n (%)
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LVEF
End-diastolic LV diameter, mm
Values are median (range), n (%), or as indicated.
patients from group II had significantly more extensive
coronary artery disease (P⫽0.03), and the difference in aortic
valve area was of borderline significance (P⫽0.045). Otherwise, there was no significant difference between groups.
Dobutamine Stress Hemodynamic Studies:
Differences Between Groups
Dobutamine stress Doppler data were obtained in all consecutive patients, and stress hemodynamic studies were well
tolerated in all cases (premature ventricular or atrial contractions in 28 patients, no sustained arrhythmia). Dobutamine
peak dose and heart rate acceleration were strictly comparable between the groups. In group I, stroke volume increased
by 33% (range, 26% to 46%), LVEF by 12 ejection fraction
(EF) units (range, 7 to 15 EF units), aortic valve area by 0.1
cm2 (range, 0.1 to 0.2 cm2), and MPG by 47% (range, 33% to
67%). The corresponding increases in group II were as
follows: stroke volume, 10% (range, 2% to 13%); LVEF, 7
EF units (range, 3 to 13 EF units); aortic valve area, 0.0 cm2
(range, 0.0 to 0.1 cm2); and MPG, 32% (range, 21% to 56%;
all P⬍0.006 compared with group I). Valve resistance remained relatively unchanged in both groups (2% versus 12%;
P⫽0.23).
Clinical Outcome: Therapeutic Decisions
In group I, 70% of patients (64 of 92) underwent aortic valve
replacement, with associated CABG in 30% (19 of 64). In
this group, one patient died preoperatively of acute coronary
occlusion during coronary angiography; the 27 remaining
patients were treated medically for the following reasons:
older age or comorbidities (n⫽10), patient refusal for surgery
(n⫽8), and patients thought to have nonsevere AS (n⫽9). In
group II, 70% of patients (31 of 44) underwent valve
replacement, with CABG in 26% (8 of 31). The 13 remaining
patients from group II were treated medically for older age or
comorbidities (n⫽7) or patient refusal for surgery (n⫽6).
Perioperative Mortality
Overall perioperative mortality was 14% (13 of 95 patients);
it was 5% in group I (3 of 64 patients) compared with 32%
(10 of 31 patients) in group II. Relative risk for perioperative
death in group II was 6.88 (95% confidence interval [CI], 2.0
to 23.2; P⫽0.0002). With associated CABG, operative mortality was 11% in group I (2 of 19 patients) compared with
62% in group II (5 of 8 patients; relative risk in group II, 5.9;
95% CI, 1.4 to 24.5; P⫽0.005). Considering baseline MPG,
the cut point for ranges of operative risk was 20 mm Hg; thus,
operative mortality was 10% (9 of 86 patients) in patients
with a MPG ⬎20 mm Hg compared with 44% (4 of 9
patients) in patients with a MPG ⱕ20 mm Hg. In the entire
population, 53 patients had a baseline MPG ⬎30 mm Hg,
64% of these (34 of 53) were in group I and 36% were in
group II (19 of 53). In this latter subgroup, operative
mortality was 11% (5 of 47); it was none (0 of 29) in group
I compared with 28% (5 of 18) in group II. By univariate
analysis (Table 2), LV contractile reserve, MPG
ⱕ20 mm Hg, and associated CABG were related to perioperative mortality. According to multivariate analysis, independent predictors for operative mortality were the lack of
contractile reserve (odds ratio for perioperative death, 10.9;
95% CI, 2.6 to 43.4; P⫽0.001) and a baseline MPG
ⱕ20 mm Hg (odds ratio for perioperative death, 4.7; 95% CI,
1.1 to 21.0; P⫽0.04).
Long-Term Survival
Kaplan-Meier survival estimates by group are shown in the
Figure; estimated 3-years survival after valve replacement
was 79% in group I (95% CI, 62% to 89%), and survival after
322
Circulation
July 22, 2003
underwent valve replacement, revealing a moderately calcified aortic valve.
Discussion
Kaplan-Meier survival estimates by group and treatment.
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surgery was significantly improved compared with medical
treatment (Table 3). In contrast, improvement in long-term
survival after valve replacement was not significant in group
II (P⫽0.07). Survival duration under medical therapy was not
different between the groups. According to Cox proportional
hazard analysis, two parameters were independently associated with long-term survival: aortic valve replacement (hazard ratio, 0.30; 95% CI, 0.17 to 0.53; P⫽0.001) and LV
contractile reserve (hazard ratio, 0.40; 95% CI, 0.23 to 0.69;
P⫽0.001).
Low-gradient AS refers to patients with AS, severe LV
dysfunction, low cardiac output, and low transaortic pressure
gradients.1–5,17 These patients are characterized by high operative risk and a dismal spontaneous prognosis.1–5,17 In this
situation, the cause of LV dysfunction may be true, severe AS
with afterload mismatch18 or primary cardiomyopathy with
nonsevere AS.3,4,7,8 We report the first multicenter study
involving a large cohort of these patients; the main results are
(1) confirmation that operative risk is well stratified by
dobutamine stress hemodynamics; (2) justification for risk
stratification in patients with a baseline MPG between 30 and
40 mm Hg; (3) a cut point for high operative risk in terms of
MPG at 20 mm Hg; and (4) the rare occurrence of relative AS.
Definition of Low-Gradient AS
In group I, postoperative improvement in functional status
occurred in nearly all surviving patients; only 1 patient with
prosthesis-patient mismatch remained in New York Heart
Association class III after valve replacement. Thus, good
functional results after valve replacement occurred in 84% of
patients (54 of 64) in group I compared with 45% of patients
(14 of 31) in group II (P⫽0.002). Functional outcome under
medical therapy was equally poor in both groups; good
functional results occurred in 18% (5 of 28) and 7% (1 of 14)
of patients from groups I and II, respectively (P⫽0.15).
As stated in current practice guidelines, severe AS with
normal cardiac output generally implies a transaortic MPG
ⱖ50 mm Hg.9 Thus, in any given patient, a calculated valve
area ⱕ1 cm2 with a MPG ⱕ40 mm Hg may be related to
reduced stroke volume. In previous studies, low-gradient AS
was defined by a MPG ⱕ30 mm Hg2,7,17,18 or
ⱕ40 mm Hg.1,3,4 In recent studies, operative risk for valve
replacement varied from 8% to 21%2,5 when MPG was
ⱕ30 mm Hg and from 11% to 18% when MPG was
ⱕ40 mm Hg.1,3,4 Thus, it was important to determine the cut
point for ranges of operative risk in terms of MPG; this cut
point was a MPG ⱕ20 mm Hg in the present study. Interestingly, in the 53 patients with a MPG between 30 and
40 mm Hg, the proportion of patients without LV contractile
reserve was the same as in the whole population, and
operative mortality was 28% (5 of 18) in the patients without
reserve compared with zero (0 of 29) in patients with
contractile reserve. Thus, our results, supported by others,1,4
demonstrate that operative risk stratification is justified in
patients with a MPG between 30 and 40 mm Hg.
Patients With Relative AS
Predictors for Operative Mortality
Seven patients met the criteria for relative AS; their main
characteristics and outcomes are outlined in Table 4. Outcomes were favorable without valve replacement in 3 of 6
patients. After 65 months of follow-up, patient 2 finally
underwent aortic valve replacement for progression of AS. In
contrast, 2 patients under medical therapy died from cardiac
causes, and one patient who had undergone isolated CABG
died suddenly 22 months after surgery. Finally, patient 7
In the setting of low-gradient AS, known predictors for
operative mortality were previous myocardial infarction,6
small-sized aortic prosthesis,2 or LV contractile reserve.3,4
We published a previous report on operative risk stratification
by dobutamine stress hemodynamics,3 but the subgroup of
operated patients without contractile reserve in that study was
very small (6 patients), and thus no definitive conclusions
could be drawn. In the present study, 31 patients without
reserve underwent valve replacement, and the high operative
mortality in this subgroup was confirmed with much improved statistical power compared with the earlier report. The
other independent predictor for operative mortality was a
baseline mean transaortic gradient ⱕ20 mm Hg. Neither
previous myocardial infarction nor associated CABG was an
independent predictor for operative mortality in this series.
Functional Outcome
TABLE 3. Cox Proportional Hazard Analysis of the Effect of
Surgical Treatment on Survival Duration in the 2 Groups
Hazard Ratio
for Death
95% Confidence
Interval
P
Group 2, medical
1.0
Group 1, medical
0.61
䡠䡠䡠
0.27–1.35
Reference
Group 2, surgical
0.47
0.31–1.05
0.07
Group 1, surgical
0.12
0.05–0.3
0.001
0.22
Predictors for Long-Term Survival
In case of low-gradient AS, postoperative improvement in LV
function due to the release of afterload mismatch may be
Monin et al
Low-Gradient Aortic Stenosis
323
TABLE 4.
Hemodynamic Parameters and Outcomes in the 7 Male Patients With Relative AS
Patient/
Age, y
MPG, mm Hg,
Baseline/
Dobutamine
Valve Area,
cm , Baseline/
Dobutamine
Coronary
Artery
Disease
Treatment
Outcome,
Follow-Up
Duration
12/25
0.8/1.2
1-vessel
Medical
Stable, NYHA II, 14 months
2/47
9/19
0.9/1.3
No significant stenosis
Medical
NYHA IV to I, 65 months
3/70
13/20
1.0/1.3
1-vessel
PTCA
NYHA III to II, 6 months
4/83
18/24
0.9/1.3
Angiography not performed
Medical
Death (congestive heart failure), 14 months
5/69
27/43
0.6/1.1
1-vessel
Medical
Death (congestive heart failure), 1 month
6/57
12/15
0.8/1.2
3-vessel
Isolated CABG
Sudden death, 22 months
7/68
37/40
1.0/1.4
3-vessel
Valve replacement⫹CABG
NYHA IV to I, 14 months
1/66
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related to LV contractile reserve,2,3 which may be paralleled
with myocardial viability in chronic coronary artery disease.
It is currently admitted that in chronic ischemic cardiomyopathy, long-term survival is improved by myocardial revascularization provided myocardial viability is present.19 Thus, it
is not surprising that independent predictors for long term
survival in the present study were valve replacement and LV
contractile reserve. Conversely, in most of the patients
without contractile reserve, LV function may be irreversibly
damaged due to previous myocardial infarction or extensive
myocardial fibrosis6; therefore, these latter patients are less
likely to benefit from valve replacement.6 Of course, in the
absence of contractile reserve, calculated valve area remains
unreliable, so heterogeneity is possible with regard to AS
severity and response to valve replacement in group II.
Moreover, the predictive value of the lack of contractile
reserve for postoperative changes in LV function is still
unknown. Nevertheless, our results demonstrate that despite a
trend toward better survival after valve replacement, the
outcome of patients without reserve is compromised by high
operative mortality. In contrast to previous reports,1 associated coronary artery disease did not influence long-term
survival in the present study, although operative mortality
was increased in patients with associated CABG.
follow-up. Thus, currently available data on relative AS
remain too scarce to allow any definitive conclusion, and
further studies are mandatory concerning this rare subset of
patients.
Relative AS
This first multicenter study confirms the prognostic value of
dobutamine stress hemodynamics for operative risk stratification and long-term outcome in the setting of low-gradient
AS. Our results confirm that patients with a contractile
reserve have an acceptable operative risk and that valve
replacement may improve long-term survival and functional
status in most cases; thus, surgery may be recommended in
most of these patients. In contrast, despite a trend toward
better survival after valve replacement, the outcome of
patients without reserve is compromised by high operative
mortality, especially in those with a baseline MPG
ⱕ20 mm Hg or associated coronary artery disease. Therefore,
individual patients should not be denied the potential benefits
of valve surgery on the basis of the absence of contractile
reserve alone; however, we suggest that this important
parameter should be considered, in addition to other risk
factors, in the risk-benefit analysis for each patient.
Relative AS refers to primary LV dysfunction with nonsevere
AS.3,4,7,8 In such cases, AS severity may be overestimated due
to the inaccuracy of both Gorlin and continuity equations at
low-flow states20 and/or the inability of the left ventricle to
open a mildly calcified valve fully due to severely decreased
stroke volume.13 Previous studies reported up to one-third of
patients meeting the criteria for relative AS and a fairly good
prognosis under medical therapy at midterm follow-up in
these patients.7,8 In our study, this situation was rarely
encountered because only 7 of 136 patients met the criteria
for relative AS; this number is reduced to 5 patients if
recently revised criteria are applied.4 Six patients in this
subgroup did not undergo valve replacement, and 3 of them
died after a relatively short period of follow-up. This result is
supported by Nishimura et al,4 who reported several deaths
among medically treated patients with relative AS. In contrast, 3 patients in our series did relatively well under medical
therapy, including one patient who finally underwent valve
replacement for progression of AS after 65 months of
Study Limitations
The 100% success rate of Doppler interrogation during
dobutamine infusion in this study may not reflect daily
practice; thus, when Doppler data are not available, a dobutamine hemodynamic study in the catheterization laboratory
is also safe and effective.4 The lack of significant benefit of
valve replacement on long-term survival in group II may be
due to the relatively small number of patients in this group;
therefore, we have insisted on the trend toward a benefit of
valve surgery in this group. A limitation of our study is that
patients were not randomized for treatment and that therapeutic decisions were made by the referring physicians, who
had knowledge of dobutamine stress hemodynamic data. Our
opinion is that randomization of such patients would be
unethical considering their dismal spontaneous prognosis.
Furthermore, in our study, the proportion of operated patients
was comparable in both groups; this confirms that for the
majority of physicians, the prognostic value of dobutamine
stress hemodynamics is not yet fully established.
Conclusions
Acknowledgment
This study was supported in part by a grant from the Fédération
Française de Cardiologie.
324
Circulation
July 22, 2003
References
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1. Blitz LR, Gorman M, Herrmann HC. Results of aortic valve replacement
for aortic stenosis with relatively low transvalvular pressure gradients.
Am J Cardiol. 1998;81:358 –362.
2. Connolly HM, Oh JK, Schaff HV, et al. Severe aortic stenosis with low
transvalvular gradient and severe left ventricular dysfunction: result of
aortic valve replacement in 52 patients. Circulation. 2000;101:
1940 –1946.
3. Monin JL, Monchi M, Gest V, et al. Aortic stenosis with severe left
ventricular dysfunction and low transvalvular pressure gradients: risk
stratification by low-dose dobutamine echocardiography. J Am Coll
Cardiol. 2001;37:2101–2107.
4. Nishimura RA, Grantham JA, Connolly HM, et al. Low-output, lowgradient aortic stenosis in patients with depressed left ventricular systolic
function: the clinical utility of the dobutamine challenge in the catheterization laboratory. Circulation. 2002;106:809 – 813.
5. Pereira JJ, Lauer MS, Bashir M, et al. Survival after aortic valve
replacement for severe aortic stenosis with low transvalvular gradients
and severe left ventricular dysfunction. J Am Coll Cardiol. 2002;39:
1356 –1363.
6. Powell DE, Tunick PA, Rosenzweig BP, et al. Aortic valve replacement
in patients with aortic stenosis and severe left ventricular dysfunction.
Arch Intern Med. 2000;160:1337–1341.
7. deFilippi CR, Willett DL, Brickner ME, et al. Usefulness of dobutamine
echocardiography in distinguishing severe from nonsevere valvular aortic
stenosis in patients with depressed left ventricular function and low
transvalvular gradients. Am J Cardiol. 1995;75:191–194.
8. Schwammenthal E, Vered Z, Moshkowitz Y, et al. Dobutamine echocardiography in patients with aortic stenosis and left ventricular dysfunction:
predicting outcome as a function of management strategy. Chest. 2001;
119:1766 –1777.
9. Task Force on Practice Guidelines (Committee on Management of
Patients with Valvular Heart Disease). ACC/AHA guidelines for the
management of patients with valvular heart disease: a report of the Am
College of Cardiology/Am Heart Association. J Am Coll Cardiol. 1998;
32:1486 –1588.
10. Nishimura RA, Miller FA Jr, Callahan MJ, et al. Doppler echocardiography: theory, instrumentation, technique, and application. Mayo Clin
Proc. 1985;60:321–343.
11. Currie PJ, Seward JB, Reeder GS, et al. Continuous-wave Doppler echocardiographic assessment of severity of calcific aortic stenosis: a simultaneous Doppler-catheter correlative study in 100 adult patients. Circulation. 1985;71:1162–1169.
12. Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive estimation of valve area
in patients with aortic stenosis by Doppler ultrasound and twodimensional echocardiography. Circulation. 1985;72:810 – 818.
13. Cannon JD Jr, Zile MR, Crawford FA, et al. Aortic valve resistance as an
adjunct to the Gorlin formula in assessing the severity of aortic stenosis
in symptomatic patients. J Am Coll Cardiol. 1992;20:1517–1523.
14. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography:
American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am
Soc Echocardiogr. 1989;2:358 –367.
15. Stamm RB, Carabello BA, Mayers DL, et al. Two-dimensional echocardiographic measurement of left ventricular ejection fraction: prospective
analysis of what constitutes an adequate determination. Am Heart J.
1982;104:136 –144.
16. Cleveland WS. Robust locally weighted regression and smoothing scatter
plots. J Am Stat Assoc. 1979;74:829 – 836.
17. Brogan WC, Grayburn PA, Lange RA, et al. Prognosis after valve
replacement in patients with severe aortic stenosis and a low transvalvular
pressure gradient. J Am Coll Cardiol. 1993;21:1657–1660.
18. Carabello BA, Green LH, Grossman W, et al. Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis
and advanced congestive heart failure. Circulation. 1980;62:42– 48.
19. Afridi I, Grayburn PA, Panza JA, et al. Myocardial viability during
dobutamine echocardiography predicts survival in patients with coronary
artery disease and severe left ventricular systolic dysfunction. J Am Coll
Cardiol. 1998;32:921–926.
20. Burwash IG, Thomas DD, Sadahiro M, et al. Dependence of Gorlin
formula and continuity equation valve areas on transvalvular volume flow
rate in valvular aortic stenosis. Circulation. 1994;89:827– 835.
Low-Gradient Aortic Stenosis: Operative Risk Stratification and Predictors for Long-Term
Outcome: A Multicenter Study Using Dobutamine Stress Hemodynamics
Jean-Luc Monin, Jean-Paul Quéré, Mehran Monchi, Hélène Petit, Serge Baleynaud, Christophe
Chauvel, Camélia Pop, Patrick Ohlmann, Claude Lelguen, Patrick Dehant, Christophe Tribouilloy
and Pascal Guéret
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Circulation. 2003;108:319-324; originally published online June 30, 2003;
doi: 10.1161/01.CIR.0000079171.43055.46
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