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Sex Differences in Left Ventricular
Geometry in Aortic Stenosis*
Impact on Outcome
Donna L. Milavetz, MD; Sharonne N. Hayes, MD; Susan A. Weston, MS;
James B. Seward, MD; Charles J. Mullany, MB, MS; and
Véronique L. Roger, MD, MPH
Objective: This study of surgical aortic stenosis characterized sex differences in left ventricular
(LV) geometry and outcome.
Materials and methods: We examined 92 women and 82 men who underwent echocardiography
before valve replacement for aortic stenosis.
Results: Women had a smaller cavity size (LV end-diastolic diameter 48.2 ⴞ 7 mm in women vs
53.6 ⴞ 7.6 mm in men; p ⴝ 0.0001) and higher ejection fraction (59% in women vs 54% in men;
p ⴝ 0.02). LV mass was greater in men than women (300.4 ⴞ 88 g in men vs 250.6 ⴞ 85.8g in
women; p ⴝ 0.0055) but when corrected for body surface area, the difference was not significant.
The prevalence of LV hypertrophy was similar in both sexes (51% in women vs 49% in men;
p ⴝ 0.62). The 5-year survival was 82% in women and 79% in men (p ⴝ 0.9).
Conclusion: Several descriptors of LV geometry differed between men and women. These
differences were largely eliminated after normalizing for body surface area. No differences in
surgical mortality or long-term outcome were noted.
(CHEST 2000; 117:1094 –1099)
Key words: aortic valve disease; outcome left ventricular geometry; sex difference
Abbreviations: AS ⫽ aortic stenosis; BMI ⫽ body mass index; EF ⫽ ejection fraction; LV ⫽ left ventricular;
LVEDD ⫽ LV end-diastolic diameter; LVESD ⫽ LV end-systolic diameter
everal studies have emphasized the existence of
S sex
differences in the left ventricular (LV) adap-
tation to aortic stenosis (AS).1–3 Supernormal LV
function, a smaller LV chamber size, and thicker
walls have been observed more frequently in women
with AS. Sex differences in LV structure and adaptation to exercise paralleling such differences in LV
geometry have also been documented.4,5 Controversy remains, however, on the impact of such sex
differences on outcome. In some series,6 this pattern
of LV geometry has been associated with increased
surgical mortality in women, whereas other series
failed to identify sex as an independent predictor of
adverse outcome after valve replacement.7–9 The
published studies are heterogeneous with regard to
the prevalence of coronary disease and the overall
*From the Division of Cardiovascular Diseases and Internal
Medicine (Drs. Milavetz, Hayes, Seward, and Roger), the Section
of Biostatistics (Ms. Weston), and the Division of Thoracic and
Cardiovascular Surgery (Dr. Mullaney), Mayo Clinic and Mayo
Foundation, Rochester, MN.
Manuscript received April 15, 1999; revision accepted October 5,
1999.
Correspondence to: Veronique L. Roger, MD, MPH, Division of
Cardiovascular Diseases and Internal Medicine, Mayo Clinic
Rochester, 200 First Street SW, Rochester, MN 55905
operative mortality reported. This issue, therefore,
needs to be examined in a larger series of patients
with isolated AS.
The present study was designed to examine clinically used indicators of LV geometry in a large series
of men and women with surgical AS and to test the
hypothesis that there was no sex association in LV
geometry and outcome after valve replacement in AS.
Materials and Methods
All patients undergoing aortic valve replacement for AS between 1990 and 1992 were considered for inclusion in the study.
Patients were included if they met the following criteria: age
⬎ 20 years at aortic valve replacement; absence of coronary
artery disease as determined by preoperative coronary angiography (threshold of 50% for the significance of a stenosis); absence
of concomitant valvular heart disease requiring surgical correction; and no more than mild aortic regurgitation, as determined
by Doppler echocardiography.
The hemodynamic severity of AS and LV function were
assessed by echocardiography with commercially available ultrasound systems. By using the American Society of Echocardiography measurement techniques, short-axis measurements of the
LV end-diastolic (LVEDD) and end-systolic diameter (LVESD)
were obtained, and the ejection fraction (EF) was calculated
using the modified Quinones method whenever possible.10 The
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Clinical Investigations
Table 1—Demographics and Clinical Characteristics at Time of Operation*
Variable
Women
Men
p Value
N
Age, yr†
NYHA III or IV, %
Syncope, %
CHF, %
Angina, %
Hypertension, %
Body surface area, m2†
BMI, kg/m2†
Overweight, %
Charlson index
Sum of diseases
92
71 (64.5, 77.5)
59
16
32
29
65
1.69 (1.55, 1.81)
24.88 (22.14, 28.13)
40
82
68 (58, 76)
51
16
22
43
38
1.99 (1.87, 2.10)
26.50 (24.26, 29.59)
37
—
0.051
0.32
0.94
0.16
0.067
0.001
⬍0.0001
0.017
0.87
1.51 ⫾ 1.31
1.72 ⫾ 1.49
0.43
*CHF ⫽ congestive heart failure; NYHA ⫽ New York Heart Association.
†Presented as medians with IQR of 25th and 75th percentiles.
ⱖ 27.3 kg/m2 in women and ⱖ 27.8 kg/m2 in men.19 The
Charlson index,20,21 a validated summary method of classifying
comorbidity to predict short- and long-term mortality from
medical records, was used to measure the severity of comorbid
illnesses.
Coronary angiography was performed in all patients as part of
the preoperative evaluation.
EF was visually estimated when no M-mode measurement could
be obtained.10,11 Diastolic relative wall thickness was calculated
as the ratio of twice the posterior wall thickness to LVEDD.12,13
On the basis of published data,6 we stratified patients by sex
according to a relative wall thickness ⬎ 0.66 vs ⱕ 0.66 to examine
outcomes. LV mass was calculated from the M-mode measurements by the method of Devereux and Reichek.14 LV hypertrophy was defined using two different thresholds for the LV mass
index: published values from the Mayo Clinic,15 ⬎ 132 g/m2 for
women and ⬎ 144 g/m2 for men, and the criteria of Devereux et
al,16 ⬎ 110 g/m2 for women and ⬎ 134 g/m2 for men.
Aortic valve area and mean gradient were assessed by twodimensional and Doppler echocardiography with established
techniques.17,18 The recording of the optimal transvalvular Doppler signal was ascertained by systematic recordings from all
ultrasound windows. The aortic valve area was calculated using
the continuity equation using the maximal transstenotic velocity
recorded by continuous-wave Doppler; the velocity in the LV
outflow tract recorded by pulsed-wave Doppler; and the LV
outflow tract diameter measured from the parasternal long-axis
view.17,18 Severe AS was defined as an aortic valve area ⬍ 0.7 cm2.
Overweight status was defined as a body mass index (BMI)
Follow-Up
All participants in the study had provided prior approval for use
of their medical records for research protocols. The protocol and
follow-up survey were approved by our Institutional Review
Board.
Postoperative morbidity (defined as sepsis, low cardiac output
state, renal insufficiency requiring dialysis, permanent pacemaker
implantation, inotropic support ⬎ 3 days postoperatively, ventricular arrhythmia requiring therapy, encephalopathy or neurologic
disorder, and bleeding requiring reoperation) and mortality
(within 30 days or same hospital stay) were examined through
detailed review of the medical records. Long-term outcome was
evaluated by a follow-up questionnaire designed by our Survey
Table 2—Doppler Echocardiography Variables at Aortic Valve Replacement*
Variable
Women
n
Men
n
p
Value
AVA, cm2
AVA index, cm2/m2
Mean gradient, mm Hg
LVEDD, mm
LVEDD index, mm/m2
LVESD, mm
LVESD index, mm/m2
EF, %
Septal wall thickness, mm
Posterior wall thickness, mm
Relative wall thickness
LV mass, g
LV mass index, g/m2
LVH, %
Cardiac output, L/min
Cardiac index, L/min/m2
0.63 ⫾ 0.14
0.37 ⫾ 0.08
58.5 ⫾ 21.8
48.2 ⫾ 7
28.6 ⫾ 3.7
30.0 ⫾ 8.8
17.8 ⫾ 4.8
59.2 ⫾ 13.4
13.3 ⫾ 3
12.7 ⫾ 2.5
0.54 ⫾ 0.15
250.6 ⫾ 85.8
148.2 ⫾ 47.5
51
5.5 ⫾ 1.3
3.2 ⫾ 0.79
88
88
91
64
64
62
62
91
52
52
50
50
50
92
65
65
0.69 ⫾ 0.15
0.36 ⫾ 0.09
59.6 ⫾ 14.4
53.6 ⫾ 7.6
27.8 ⫾ 7.7
35.2 ⫾ 10.3
18.5 ⫾ 8.4
53.9 ⫾ 15.8
14.1 ⫾ 2.7
13.2 ⫾ 2.6
0.51 ⫾ 0.14
300.4 ⫾ 88
150.5 ⫾ 37.3
49
5.8 ⫾ 1.8
2.8 ⫾ 0.78
76
76
81
51
51
48
48
82
42
42
40
40
40
82
51
51
0.0026
0.23
0.14
0.0001
0.0103
0.0008
0.93
0.02
0.17
0.29
0.47
0.0055
0.62
0.76
0.30
0.0031
*AVA ⫽ aortic valve area; LVH ⫽ LV hypertrophy.
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Table 3—Perioperative and Late Deaths
According to Sex
Deaths, n (%)
Perioperative
Late
Cardiac
Noncardiac
Women
Men
p Value
4 (4.3)
10 (11)
1 (1.0)
9 (9.8)
3 (3.7)
9 (11)
1 (1.2)
8 (9.8)
0.82
0.98
0.94
0.91
Research Center, focusing on the functional status of the patient.
Nonresponders received a follow-up phone interview. Death
certificates were obtained for all patients who died after hospital
discharge. Late-outcome deaths occurring after hospital discharge were categorized as cardiac if attributable to myocardial
infarction or congestive heart failure or if death occurred suddenly and unexpectedly. All other deaths during the follow-up
period were defined as noncardiac.
Statistical Analysis
The data are presented in the text and tables as mean ⫾ SD for
normally distributed variables or medians and interquartile
ranges in the case of nonnormal distributions (age, body surface
area, and BMI). LV geometry was compared across the sexes
using crude values, indexed values (divided by the body surface
area), and adjusted values using multiple linear regression analysis to adjust for sex and body surface area. Comparisons of the
baseline characteristics between men and women were performed using the two-sample t test or the Wilcoxon rank sum test
for continuous variables and by the ␹2 or Fisher’s Exact Test for
categorical variables.
In comparing the effect of perioperative complications on
perioperative survival, the Pearson ␹2 test was used instead of
survival analysis owing to the small number of deaths and the
short follow-up time.
Kaplan-Meier curves were constructed to estimate survival
after aortic valve replacement. Cox proportional hazards models
were constructed to examine the association between several
preoperative clinical and echocardiographic variables and death.
Significance was judged at the level of p ⫽ 0.05.
Results
tended to be older than men but equally symptomatic. Women were smaller than men in terms of body
surface area. Men had a higher median BMI than
women, but there was no sex difference in the
percent classified as overweight. The Charlson index
was also similar for men and women.
Hemodynamic Severity of AS and LV Systolic
Function
Stenotic Indexes
The aortic valve area was smaller in women, but
when corrected for body surface area, this difference
was not significant. There was no sex difference in
mean gradient.
LV Function and Geometry
There were significant differences in LV function
between men and women despite a similar degree of
AS (Table 2). In particular, EF and cardiac index
were all higher in women.
The LVEDD was larger in men, but after indexing
the direction, the sex difference was reversed and
the index value was larger in women. This was not
observed with the use of regression analysis, where
there was no sex difference in the adjusted LVEDD.
No sex differences were observed in the septal or
posterior wall thickness between the two groups. LV
mass was lower in women, but after indexing, the LV
mass index was similar. Fifty-one percent of the
women and 49% of men (p ⫽ 0.76) had LV hypertrophy using laboratory-based criteria. Using the
criteria of Devereux et al,16 53% of the women and
49% of men had LV hypertrophy (not significant).
Twelve percent of women vs 8.5% of men had a
relative wall thickness ⬎ 0.66 (p ⫽ 0.46).
Five patients had missing LVESD and 59 patients
had missing LVESD and LVEDD. The analyses
were repeated excluding the patients with missing
diameters, and the results were unchanged.
Baseline Characteristics
Outcome
Two hundred thirteen patients underwent valve
replacement during the study period. Thirty-two
patients underwent coronary revascularization plus
aortic valve replacement, and seven patients underwent other valve replacements in addition to the
aortic valve. The remaining 174 patients met all
entry criteria and are the subject of this study.
Ninety-two (53%) were women and 82 were men.
All but one female patient (99%) responded to the
follow-up questionnaire sent in December 1994.
One female patient’s information was missing at the
time of the analysis. Demographic and baseline
Doppler echocardiographic data are presented in
Table 1. At the echocardiographic study, women
Mean follow-up was 1,269 ⫾ 320 days. Seven patients died within 30 days or during the same hospital
stay after aortic valve replacement. There was no sex
difference in perioperative mortality (Table 3). A
total of 19 late deaths were noted: 10 in women and
9 in men (p ⫽ 0.98). The causes of late death are
listed in Table 3.
At last follow-up, 89% of the women and 88% of
the men were in New York Heart Association classes
I and II.
There were no sex differences in Kaplan-Meier
survival curve estimates (p ⫽ 0.9) (Fig 1). The 5-year
Kaplan-Meier survival estimates were 82% for
women and 79% for men.
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Clinical Investigations
function and LV geometry were noted. The EF and
cardiac index were higher in women, but the differences in LV geometry were mainly related to sex
differences in body surface area. Indeed, after adjusting for body surface area, the only sex difference
in LV geometry was a small but statistically significant increase in the LVEDD index in women. The
cardiac index was higher in women, in keeping with
the greater EF and LVEDD index. Operative mortality and long-term outcome after valve replacement
did not differ according to sex.
LV Geometry
Figure 1. Kaplan-Meier survival curve indicates that 79% of
men and 82% of women were alive after valve replacement for
isolated AS. NS ⫽ not significant.
The following variables were included as candidate variables in multivariate models to identify
predictors of survival: age, sex, EF, LV mass and
mass index, and wall thickness-to-radius ratio. Only
increasing age was significantly associated with
poorer survival (p ⬍ 0.0018).
In the subgroup of patients with a relative wall
thickness ⬎ 0.66, there was no sex-related difference
in long-term mortality. Two of 11 women (18%) and
one of seven men (14%) died (p ⫽ 0.8).
Discussion
In the present series of men and women with
isolated severe AS, significant differences in LV
Several studies have indicated that women with
severe AS are more likely than men to respond to the
pressure load with concentric hypertrophy1,2,6,22 and
hyperdynamic (supernormal) LV systolic function.
Table 4 summarizes selected findings of some of
these studies. The series differ in terms of design,
number of patients, and prevalence of coronary
artery disease. Not unexpectedly, they also differ
with regard to the prevalence of sex differences in
LV geometry.
The studies by Carroll et al1 and by Douglas et al22
can be informally compared with the present series,
because patients with coexisting coronary artery
disease were excluded from all three series, which all
pertained to patients with severe AS, with similar
degrees of valvular obstruction, referred to cardiac
catheterization, aortic valve replacement, or valvuloplasty. All three series reported supernormal systolic
performance in women with higher fractional shortening, EF, and cardiac index.
Table 4 —Published Studies and Present Series: Sex Differences in LV Geometry Variables*
Variable
N
CAD prevalence, %
Hypertension prevalence, %
LVEDD, mm
LVEDD index, mm/m2
LVESD, mm
LVESD index, mm/m2
EF or fractional shortening
Septal wall thickness, mm
Posterior wall thickness, mm
Relative wall thickness in
diastole
LV mass, g
LV mass index, g/m2
LVH, %
Cardiac output, L/min
Cardiac index, L/min/m2
Rohde
et al3
Douglas
et al22
Legget
et al5
Aurigemma
et al2
Present
Series
Carroll
et al1
44
45
NA
⫹
NA
⫹
NA
⫹
—
—
NA
232
0
NA
⫹
—
⫹
—
⫹
—
—
⫹
82
NA
44†
⫹
NA
⫹
NA
—
NA
—
—
65
62
NA
⫹
—
⫹
—
⫹
—
—
⫹
174
0
52†
⫹
⫹
⫹
—
⫹
—
—
—
63
0
NA
⫹
—
⫹
⫹
⫹
—
—
—
⫹
⫹
NA
NA
NA
⫹
—
⫹
—
⫹
⫹
⫹
NA
⫹
—
—
—
NA
NA
NA
⫹
—
—
—
⫹
⫹
⫹
NA
NA
⫹
*Denotes a statistically significant sex difference for the variable; — denotes the lack of statistically significant sex difference for the variable.
†The prevalence of hypertension was higher in women than in men (Legget et al,5 prevalence of hypertension was 32% in men and 55% in women,
p⫽0.04; present study data in Table 1) CAD ⫽ coronary artery disease; NA ⫽ not available. See footnote of Table 2 for other abbreviation.
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Systolic and diastolic cavity dimensions were also
uniformly smaller in women. Although there was no sex
difference in wall thickness, LV mass was greater in
men than in women. This is not unexpected because
the calculation for LV mass incorporates the cavity
dimensions, which are higher in men. The studies
differ with regard to the existence of sex differences in
indexed values. This may reflect differences in body
habitus among the three studies. The use of indexed
values to adjust echocardiographic dimensions remains
controversial.23 Although we elected to present index
values in the present study, when linear regression
analysis was used, no sex difference in LVEDD was
found in our series. This further underscores the
limitation of controlling for body size by adjusting for
body surface area.
The prevalence of LV hypertrophy using predefined as well as laboratory-specific criteria did not
differ according to sex in the present study, which is
at odds with the findings reported by Douglas et al.22
In that series, however, the population was older and
had a greater prevalence of heart failure, which is
likely to affect LV geometry and could conceivably
confound some of the sex-specific findings. The lack
of control for hypertension may also compromise the
interpretation of these findings. In an exploratory
analysis of the present series, excluding persons with
a history of hypertension resulted in nonclinically
significant changes of the sex differences in LVEDD,
EF, and cardiac index. With regards to LV mass
index, excluding patients with hypertension indicated a significantly lower LV mass index in women
(130.7 ⫾ 35.6 in women vs 151.7 ⫾ 30.2 g/m2 in
men; p ⫽ 0.043), adding more support toward the
lack of an excessive degree of hypertrophy in women
as compared with men. Although these results have
to be interpreted with caution inasmuch as they were
obtained from secondary analyses, survival analysis
stratified by hypertension status did not unmask any
sex difference in outcome. Thus, although there is
some consistent evidence across published studies
that LV function indexes in severe AS differ according to sex, some uncertainties remain with regard to
sex-specific patterns of LV geometry (mass index,
relative wall thickness, prevalence of LV hypertrophy) associated with severe AS in clinical practice.
Outcome
Regardless of their interpretation, the sex differences discussed above pose an important clinical
question because some series have reported worse
operative mortality for valve replacement in patients
with concentric LV hypertrophy, small cavity size,
and hyperdynamic LV systolic function.2,6 Inasmuch
as these findings are more prevalent in women, they
raise the concern of possible excess operative mortality among women with surgical AS. Yet there is
little data on the outcome associated with the reported sex-differences in LV geometry.2,3,5,22
The outcome of the present population does not
support this concern of an excess operative mortality
among women inasmuch as no sex difference in
postoperative or long-term outcome was noted. In
contrast to other reports,8,9 our study represents a
group of patients with isolated AS. Excluding coexisting coronary artery disease is important to assist in
the interpretation of the outcomes, because its presence may adversely and independently affect outcome.2,6 Indeed, revascularization adds a small increase in the operative risk of aortic valve
replacement, which could conceivably apply more to
women.9 It has been suggested that because women
are older at the time of revascularization, have
smaller target vessels, and have more comorbid
illnesses, this increases mortality rates from revascularization procedures compared with men.24 Finally,
in some of these series, the operative mortality for
valve replacement was 22%,6 which is higher than
the reported average mortality for aortic valve replacement in other studies of 4.2 to 6.6%,9,25–28
raising the concern about selection bias and limited
relevance to the general population.
The present series differs from previous reports in
that it included a large number of consecutive
patients who underwent aortic valve replacement for
AS during the study period without associated coronary disease. The evaluation of patients with AS is
routinely conducted using Doppler echocardiography,29 which protects from the selection biases outlined above and positively impacts the generalizability of our data. The operative mortality in the present
series is similar to previously reported figures.
Limitations
This study was retrospective, and it is conceivable
that some determinants of outcome were not captured at aortic valve replacement. In this surgically
defined population, the decision made by the physician to refer the patient for aortic valve replacement
may have been influenced by factors possibly confounding the association between sex or other variables and outcome.
Some determinants of LV geometry were not captured in our series. In particular, no measure of wall
stress was obtained. However, all clinically used indexes
of LV geometry were included. Although our study
showed that women had a higher EF and a larger
LVEDD index, and that ⬎ 50% of the women had LV
hypertrophy, intracavitary flow acceleration was not
routinely assessed. For consistency, we elected to use
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Clinical Investigations
measurements similar to those used in previous studies;
however, LV volume measurements are important in
the analysis of LV geometry and should be the subject
of future studies. Volumetric measures of the LV would
have been desirable but were not performed routinely
in our practice during the study period.
It has been suggested that a relative wall thickness
ⱖ 0.66 is associated with a trend toward increased
mortality.6 No increased mortality was associated
with a relative wall thickness ⱖ 0.66 in our series, but
the series may lack power for this analysis.
Summary
In this large clinical series of surgical AS, there were
sex differences in LV geometry, but these differences
were largely related to differences in body surface area.
No sex difference in outcome was observed.
ACKNOWLEDGMENT: The authors thank Sara L. Osborn
Butler for help with data collection, Michelle Gayari for assistance with data analysis, and Paulette E. Schurhammer for
excellent secretarial support.
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