JACC Vol. 22, No . 6
November l5, 1993 :367983
1 679
VALVULAR DISEASE
Left Ventricular Hypertr - -_ Ti .Lyand
wic
J
_a,'air y
After Aortic Valve
Replacement for Aortic Stc-. osis
A fligli Risk Subgroup Identified by Preoperative Relative Wall Thickness
DAVID A . ORSINFI .T .1, MD, GERARD P . AURIGEMMA, IUD, FACC, STEPHEN BATTISTA, M
STEVEN KRENDEL, BS, WILLIAM H . GAASCH, MD . FACC
Worcester, Massachusetts
Objectives . We investigated the relation between the extent and
pattern of left ventricular hypertrophy and surgical outcome in 54
patients undergoing aortic valve replacement for severe aortic
sleftos6.
Background. Previous `work from our laboratory has demon .
strated that a subgroup of patients, mostly elderly women with
Doppler evidence of abnormal intracaviiary llow acceleration, had
an unexpectedly high in-hospital mortality rate after aortic valve
replacement for aortic stenosis . We hypothesized that marked
concentric hypertrophy, rather than the Doppler signal itself, was
related to the poor outcome .
Methods. A retrospective analysis of the clinical, hemodynamic
and echocardiographic data in patients who survived aortic valve
replacement versus those who died in the hospital was performed .
Results . There were no differences between the 42 survivors
and 12 nonsurvivors with regard to the clinical or hemodynamic
variables . Of the echocardiographic variables analyzed, diastolic
relative wall thickness was found to be significantly different
between the two groups . Patients who died had significantly
greater relative wall thickness (mean ± SD) than those who
survived (0.72 ± 0.38 vs . 0.56 it 0.15, p = 0.04). Analysis by
gender demonstrated that the relation between ventricular geometry and mortality held true only for women .
Conclusions . We conclude that excessive ventricular hypertrophy, manifested as a markedly increased relative wall thickness, is
associated with a significantly increased risk of postoperative
mortality after aortic valve replace nient for aortic stenosis .
Left ventricular hypertrophy in patients with aortic stenosis
is generally characterized by an increased myocardial mass
and a, hange in ventricular geometry that preserves a normal
relation between systolic wall stress and ejection fraction .
Thus, the development of concentric hypertrophy is generally considered to be an appropriate and beneficial adaptation that compensates for high intracavitary pressure (1,2) .
After valve replacement, left ventricular systolic pressure
falls, a systolic unloading occurs and, at least initially,
ejection fraction increases (3) . In some patients an abnormal
high velocity intrp ,.avitary Doppler flow signal appears (4,5) .
This flow phenomenon appears to represent a postoperative
unloading effect in hypertrophic hearts and does not necessarily signify left ventricular outflow obstruction (6,7) . After
aortic valve replacement, patients with intracavitary flow
acceleration appear to have increased postoperative compli-
cations and an increased early mortality rate (4) . However, it
would seem unlikely that intracavitary flow acceleration
itself might be responsible for these malefic consequences in
the early postoperative period . A more likely muse of
postoperative morbidity is the presence of marked or excessive left ventricular hypertrophy .
We therefore designed the present study to test the hypothesis that the pattern and extent of hypertrophy, as determined
by preoperative echocardiography, was related to the high
postoperative morbidity and mortality rates seen in patients
undergoing aortic valve replacement for aortic stenosis .
From the Noninvasive Laboratory, Division of Cardiology, University of
Massachusetts Medical Center and the Division of Cardiology, Medical
Center of Central Massachusetts, Worcester, Massachusetts . This study was
presented in part at this 4lst Annual Scientific Session of the American College
of Cardiology, Dallas, Texas, April 1992 .
Manuscript received December 17, 1992 ; revised manuscript received
April 28, 1993, accepted June 9, 1993.
Address for comes 2Qndance : Dr. Gerard P. Aurigemma, Division of
Cardiology, University of Massachusetts Medical Center, 55 Lake Avenue
North, Worcester, Massachusetts 01655 .
01993 by the American College of Cardiology
(J Am Coll Cardiol 1993,22 .1679-83)
Methods
Study patients . All patients who underwent aortic valve
replacement for severe aortic stenosis from dune 1987 to
October 1990 were identified . Patients with previous aortic
valve surgery and those undergoing concomitant mitral
valve surgery were excluded . A total of 164 patients were
thus identified . Fifty-four patients had complete preoperative echocardiographic studies and constitute the current
study group . Data from 28 of these patients have been
reported elsewhere (4) . Echocardiographic data were reviewed by an investigator unaware of clinical and catheterization data . Clinical and demographic data were obtained
from a review of the patients' hospital records .
0735-1097193/$6,00
1680
JACC Vol . 22, No . C
November 15, 1993 :1679-83
ORSINELLI ET AL .
LEFT VENTRICULAR HYPERTROPHY AND AORTIC VALVE REPLACEMENT
Table 1 . Clinical/Hemodynamic Data
Age (q)
Gender (% male)
AVA (cm2)
Mean gradient (mm Hg)
CAD (%)
Ejection fraction (%)
LVEDP (mm Hg)
Cardiac index (liters/min per m 2 )
Total
(n = 54)
Survivor
(n = 42)
Nonsurvivor
(n = 12)
p
Value*
71 ± 12
44
0.60 ± 0.23
59 ± 24
46
62 18
18 ±8
2 .3 0.6
70 ± 12
48
0.61 ± 0.24
59 ± 23
48
61 20
1 8
2 .2 0.6
72 ± 11
33
0 .59 ± 0 .16
59 ± 26
42
65 20
IS 5
2.5 0.6
NS
NS
NS
NS
NS
NS
NS
NS
*SurvivoT versus nonsurvivor . Values presented are mean value ± SD or percent . AVA = aortic valve area;
CAD - coronary artery disease ; LVEDP - left ventricular end-diastolic pressure.
Echocardiography . M-mode, two-dimensional and Dopp-
ler echocarfiography were performed using commercially
available equipment (Hewlett-Packard series 77020A, HewlettPackard Medical Products) . Standard apical, parasternal and
subcostal views were obtained . Two-dimensionally guided
M-mode recordings were obtained from the parasternal window, and strip chart recordings were made at a paper speed of
so mm/s .
From the M-mode recordings, the following measurements were made using American Society of Echocardiography standards (8) : interventricular septal thickness, posterior wall thickness, left ventricular end-diastolic dimension
and left ventricular end-systolic dimension . Left ventricular
mass was calculated from the M-mode measurements using
the formula described previously by Troy et al . (9) and
modified by Devereux et al . (IM and was indexed to body
surface area. Diastolic relative wall thickness was calculated
as twice the posterior wall thickness divided by the left
ventricular end-diastolic dimension (i 1) .
Chlbe cacheatake. Left and right heart catleteriza,
tion was performed using fluid-filled catheters, and pressure
measurements were recorded in a standard fashion . Cardiac
output determinations were performed using either the Fick
principle for oxygen or the thermodilution method . The
Gorlin equation was used to calculate the aortic valve area
(12) . Left ventricular ejection fraction was calculated using
the area-length method from the right anterior oblique ventriculogrant (13) . Coronary artery disease was defined as the
presence of a _>50% stenosis involving a major coronary
artery .
StatistieL Continuous variables are express ,.-d as mean
value ± SD . Comparisons between continuous variables
were performed using a two-tailed unpaired Student t test .
DiO'Iotomous variables were compared using contingency
table and chi-square analysis . A p value of < 0.05 was taken
as statistically significant .
Results
St* paftlL There were no significant differences in
age, gender or in-hospital mortality between the 54 study
patients and the remaining 110 patients who underwent
aortic valve replacement during the cAy period and did not
have preoperative echocardiography . Thus, the 54 study
patients are representative of our larger experience with
aortic stenosis and aortic valve replacement .
Hemodynamic data (Table 1) . The patient group had
severe aortic stenosis (mean valve area 0 .60 ± 0 .23 cm2 ,
mean transvalvular gradient 59 ± 24 mm Hg) and preserved
left ventricular systolic function (ejection fraction 62 t
18%) . Among the 54 study patients, 12 patients (22%) died in
the hospital . There were no differences between survivors
and nonsurvivors in terms of age, gender, aortic valve area,
mean transvalvular aortic gradient, presence of coronary
artery disease, left ventricular ejection fraction, left ventricular end-diastolic pressure or cardiac index .
1kbwKardNqpph1bc data (Table 2) . The study population
had increased left ventricular wall thickness with normal left
ventricular chamber dimensions . The mean relative wall
thickness was 0 .60 ± 0 .23 . The mean left ventricular mass
was 282 ± 77 g, and the mass index was 159 ± 43 g/m 2 . Of
the echocardiographic variables evaluated, only the enddiastolic relative wall thickness proved to be significantly
different between survivors and nonsurvivors . Patients who
died in the hospital had a significantly higher relative wall
thickness (0.72 ± 0,38 vs . 0 .56 ± 0.15, p = 0 .04) . When
defining a markedly increased relative wall thickness, a
value of 0.66 was found to be the best partition value for the
overall study group in terms of discriminating between
survivors and nonsurvivors . Using this cut point, relative
wall thickness values of >0 .66 were associated with a trend
toward increased mortality (42% vs . 179o, p = 0 .07)
Gender differences (Table 3). We analyzed our mortality
data by gender in view of recent work demonstrating gender
differences in elderly patients with pressure overload hypertrophy due to aortic stenosis (14-16) . Among the 30 women,
there were no differences between survivors and nonsurvivors with regard to age, any hemodynamic variable or the
presence of coronas ; disease . However, women who died in
the hospital had significantly greater septal thickness, posterior wall thickness and relative wall thickness and smaller
left ventricular systolic and diastolic dimensions (Table 3) .
JACIC V& 22 . No . 6
November 15, 1993 :1679-83
ORSINELLt ET AL .
LEFT VENTRICULAR HYPERTROPHY AND AORTIC VALVE REPLACEMENT
1681
Table 2 . Echocardiographic Data
Total
In = 54)
Survivor
(a = 42)
Nonsurvivor
ST (mm)
PWT (mm)
15 ± I
15±3
16±5
NS
14 ± 3
15 ± 4
LVEDD (mm)
LVESD (mm)
47 ± 8
13 ± 3
48±7
29 ± 10
30±9
46±9
26±14
0.06
NS
LV mass (g)
282 ± 77
277 ± 79
301 ± 70
LV mass index (g/m 2 )
159 ± 43
157 ± 45
0 .56±0 .15
166 ± 34
0.72±0 .38
1 .1 ±0 .2
1 .1 ±0 .2
37 ± 14
47 ± 24
RWT
STIPWT
% Fractional shortening
0.60 ± 0 .23
L! ± 0 .2
39 ± 17
In = 12)
p
Value*
NS
NS
NS
0.04
NS
0.09
*Survivor versus nonsurvivor . Values presented are mean value ± Sly, LV = left ventricular ; LVEDI3 left
ventricular end-diastolic dimension ; LVESD = left ventricular end-systolic dimension, PWT = posterior left
ventricular wall thickness : KWT = relative wall thickness . ST - interventricular septal thickness .
Among women with relative wall thickness values >0 .66,
the mortality rate was 63% 15 of 8) versus 14% (3 of 22) in
women with values <0 .66 (p = 0 .007) .
A similar analysis of the 24 men failed to demonstrate any
significant differences between survivors and nonsurvivors
with regard to age, hernodynamic variables or the presence
of coronary disease . With respect to echocardiographic
variables, with the exception of septal thickness (15 ± 3 imi
in those who lived vs . 12 ± 2 mm in those who died, p <
0 .05), there were no significant differences between the men
who lived and those who died .
Impact of coronary artery disease . We attempted to determine the influence of coronary artery disease on left
ventricular geometry, in view of recent work highlighting the
impact of epicardial coronary disease on left ventricular
structure in aortic stenosis (17) . There were no differences
between the 2' patients with and the 29 without coronary
artery disease, . .j any hemodynamic or echocardiographic
variable examined .
When the subgroup of 25 patients with coronary artery
disease was analyzed, several differences emerged between
the patients who survived and those who died in the hospital .
The patients with coronary artery disease who died had
higher relative wall thickness (0 .88 ± 0 .55 vs . 0 .57 ± 0 .19,
p = 0.04), higher ejection fraction (81 ± 7% vs . 59 ± 16%,
1) = 0 .02) and a higher cardiac index (2 .8 ± 0 .6 liters/m2, p =
0.01) . When the group was classified into patients with and
without markedly increased relative wall thickness (relative
wall thickness >010, patients with a high relative wall
thickness had a fivefold increase in mortality (3 142%] of
7 vs . 2 111%] of 18, p = 0 .07) .
Discussion
Our principal finding is that a pattern of left ventricular
hypertrophy characterized by a marked increase in relative
wall thickness is associated with a poor outcome after aortic
valve replacement in patients with aortic stenosis . The mean
value for relative wall thickness was significantly lower in
survivors than in nonsurvivors . This association was present
in the study group as a whole, in women and in the subgroup
with coronary artery disease .
These findings extend our previous observations (4) and
suggest that the combination of increased relative wall
thickness, high ejection fraction and, in some cases, abnormal intracavitary flow acceleration appears to identify a
group of patients with significant morbidity and mortality
after aortic valve replacement for aortic stenosis . Moreover,
our current findings suggest that there is an important
clinical consequence of the recently described gender differ-
Table 3 . Echocardiographic Data in Women
Survivor
(n = 22)
Nonsurvivor
(n = 30)
ST (mm)
15 ± 4
14 ± 3
PWT (mm)
LVEDD (mm)
12±2
18 ± 4
16±4
0.005
13 ± 3
46 ± 7
28 ± 11
47±6
42±8
NS
31±9
21±12
0.03
0.85 ± 0A 0
315 ± 77
0.002
0.04
174 ± 34
NS
11 .2±0 .3
NS
51 ± 24
0 .05
Total
LVESD (mm)
RWT
0h1
0 .27
LV mass (g)
266
78
0.53 ± 0.13
248 ± 72
LV mass index (glm')
ST/PWT
157
1 .2
46
0.2
150 ± 49
1 .2±0.2
40
20
35 ± 16
% Fractional shortening
(n = 8)
*Survivor versus nonsurvivor . Values presented are mean value ± SD . Abbreviations as in Table 2 .
p
Value*
0.002
1 682
ORSINELLI ET AL
LEFT VENTRICULAR HYPERTROPHY AND AORTIC VALVE REPLACEMENT
ences in left ventricular structure in left ventricular pressure
overload hypertrophy (14-16) .
previous studies. Although several investigators (18-23)
have reported results of aortic valve replacement for aortic
valve disease, no previous study has examined surgical
outcome as a function of ventricular geometry . However, a
number of observations tend support to our observations .
Lytte et al . (18) reported the results of aortic valve replacement in 500 patients . The strongest univariate predictor of
operative mortality was female gender, followed by aortic
regurgitation and age . This finding is particularly striking in
view of the lack of difference in extent of coronary artery
disease or vcrltiicttiair 6ly •. ftrction between women and men .
Preoperative ejection fraction did not appear to influence
in-hospital operative mortality,
men undergoing aortic
tai et al . (20) reported data on
valve replacement, The operative mortality was highest in the
u , i up with "preserved" ejection fraction . They also found
that left ventricular systolic pressure was inversely related to
mortality and speculated that "high left ventricular systolic
pressures may be reflective of systemic arterial hypertension,
or left ventricular hypertrophy or both" (20)
The operative mortality in the present series is higher than
in previous series of patients undergoing aortic valve replacement (18-23) . This finding most likely reflects the older age of
our study patients than that of patients in most series (1821,23) and, perhaps, the higher proportion of women in our
series than in many others (18-23) . We cannot exclude the
possibility that the higher mortality rate in patients with a high
relative wall thickness is related to factors that were not
assessed in our study . Because this is a consecutive series of
patiequs, these factors should be evenly divided among all
patients . Nonetheless, our findings may not be applicable to
centers with a lowe operative mortality rate .
Our data cone=t ; sting the impact of coronary disease differ
from the findings of Vekshtein et al . (17), who showed that
epicardial coronary artery disease was associated with diminished left ventricular systolic function and a lower mass/
volume ratio, We observed no differences in left ventricular
geometry between patients with and without coronary disease. However, Vekshtein et al. (17), classified their patients
into those with angiographically normal coronaries, nonobstructive disease and obstructive disease and compared
patients with any degree of coronary disease to patients
without disease . When they compared their patients with
obstructive coronary disease to those with either normal
coronary arteries or nonobstructive disease, no differences
in left ventricular structure were found (17).
The reason for the poor surgical outcome in
patients with aortic stenosis with a marked increase in
relative wall thickness is not apparent. We previously observed that a subset of these patients developed systemic
by tension and a low cardiac output state in the early
postoperative period despite the presence of a normal left
ventricular ejection fraction (4) . On the basis of our experience, ischemic systolic dysfunction (24) does not appear to
JACC Vol . 22, No . 6
November 15,199,1 :1679-83
account for the poor outcome in view of the preserved
systolic function that we observed (4) .
Although the development of left ventricular hypertrophy
is generally considered to be a beneficial adaptation to high
intracavitary pressures, recent evidence has highlighted the
adverse cardiovascular risk associated with left ventricular
hypertrophy in hypertensive patients (25-29) . Koren et al .
(27) found that a pattern of concentric hypertrophy was
associated with the highest risk of adverse events in hypertensive patients . Patients with concentric remodeling (normal left ventricular mass and increased relative wall thickness) also experienced a higher morbidity . Ohali et al . (29)
found that left ventricular hypertrophy was associated with
increased mortality both in patients with and in patients
without coronary disease .
There are several potential mechanisms whereby excessive left ventricular hypertrophy may confer increased morbidity and more !ity after aortic valve replacement . First,
optimal cardiol , ,;section during ischemic arrest is difficult to
achieve in hypertrophic hearts . Second, abnormalities in
coronary flow reserve (30,31), which may be especially
prominent in hypertrophied hearts, may contribute to ischemia and its consequences . A third potential adverse consequence of left ventricular hypertrophy is an exacerbation of
diastolic dysfunction (24,32,33) . Diastolic dysfunction, especially exacerbated by superimposed ischemia, might lead to
impaired filling despite elevated pulmonary venous pressure .
Impaired diastolic function could explain the hemodynamic
sequelae that we observed . This hypothesis is supported by
the observation that several patients responded to volume
replacement and the addition of calcium channel or betaadrenergic blocking agents, or both (4) .
Limitations of the study . The present study has several
important limitations . First, it is retrospective, and therefore
the clinical data on the patients may be incomplete . Of
importance, we were unable to accurately define a history of
hypertension or the duration of aortic stenosis in the patient
group, both of which could influence the development and
pattern of left ventricular hypertrophy . Patients who had
preoperative echocardiography represent a subgroup of patients undergoing aortic valve replacement at our institution,
and it might be argued that the patients whose condition was
more compromised had undergone echocardiography preoperatively . However, there was no significant mortality difference between those who did or did not undergo preoperative echocardiography .
Conclusions. In patients with aortic stenosis, a pattern of
concentric left ventricular hypertrophy denoted by high
relative wall thickness and, on occasion, an abnormal high
velocity intracavitary Doppler signal (4) identifies a group of
patients with a high risk of postoperative morbidity and
mortality. Preoperative echocardiography may thus play a
significant role in preoperative risk assessment of patients
with aortic stenosis and may also help guide therapeutic
interventions in the postoperative period .
JACC Vol. 22, No . 6
November 15, 1993 :1679-83
ORSINELLI ET ALEFT VENTRICULAR HYPERTROPHY AND AORTIC VALVE REPLACEMENT
We acknowledge the technical assistance of Andrea Sweeney, RDCS.
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