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Subendocardial Blood Flow
Children with Congenital Aortic Stenosis
L. JEROME KROVETZ, M.D., PH.D.,
AND
J. PARKER KURLINSKI, M.D.
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SUMMARY Subendocardial blood flow may be estimated from
the ratio of flow to the subendocardium to myocardla oxygen consumption. The first may be estimated from the diastolic pressure time
index (area between aortic and left ventricular (LV) preure during
diastole) and the latter by the tension time index (integral of LV
pressure during systolic ejection).
Subendocardial flow index (SEFI) averaged 1.27 (0.96-1.78) in 13
children with normal aortic valves. SEFI averaged 0.88 (0.43-1.65) in
asymptomatic children with congenital aortic stenosis and was never
greater than 0.9 in symptomatic children. Aortic valve area and
sYstolic pressure difference did not correlate well with symptoms
SEFI and aortic valve area increased in 26 of 28 patients after surgery. However, 23 of 28 had varying degrees of aortic regurgitatin
following valvotomy. Since calculation of SEFI is not affected by aortic regurgitation, it would appear to be a more useful measure of surgical success than aortic valve area.
POOR CORRELATION between symptoms and pressure
difference across the left ventricular outflow tract obstruction in congenital aortic stenosis has been noted previously.'-' We had a vivid example of this in a six-year-old boy
with congenital aortic stenosis who had episodes of apparent syncopal attacks. At cardiac catheterization, peak systolic pressure difference averaged only 54 mm Hg and the
calculated aortic valve area was 0.8 cm2. Both suggested
only moderate obstruction in a child of his size. Following
another and better documented syncopal episode a few
weeks after the catheterization, valvotomy was carried out
with subsequent relief of symptoms.
The presence of dizziness, syncope, or congestive heart
failure correlates poorly with peak systolic pressure difference.2 In one study of 32 patients with syncope,5 18 had peak
systolic pressure differences greater than 100 mm Hg, but
five had less than 50 mm Hg across the outflow tract. Little
relationship between symptoms and aortic valve area or aortic valve index was noted in another study.' Poor correlation has been noted between presence of symptoms, electrocardiographic and roentgenologic findings and the systolic
pressure difference6 or aortic valve index.1 4 In a study of
supravalvar aortic stenosis in adults,7 angina, the most common symptom, was often disproportionately severe to the
degree of obstruction as measured by the pressure
difference.
Since the subendocardial flow index was shown to have a
good correlation with the severity of obstruction,8' we
decided to compare this index with peak systolic pressure
difference and calculated valve area in children with congenital aortic stenosis.
The clinical histories were examined by each author without
knowledge of catheterization findings or subsequent clinical
course. Patients were considered to be asymptomatic if they
had been free of symptoms for at least one year prior to
catheterization. Patients were classified as mildly symptomatic if they had a history of exercise intolerance, fatigue,
excessive sweating, feeding difficulties, or dizziness without
true syncope. Patients who had syncopal attacks, dyspnea at
rest, angina or congestive heart failure were considered to be
severely symptomatic. No patient in this study had a history
of infective endocarditis or one suggesting coronary artery
disease.
A total of 45 children (36 male, nine female) with adequate clinical, catheterization and angiographic data were
located. The average age at catheterization was 9.5 years,
with a range of one month to 16 years. Thirty-three of these
children had valvar, seven discrete subvalvar, four supravalvar aortic and one combined valvar and subvalvar
stenosis.
Thirty-five patients underwent two or more catheterizations, including 28 who were catheterized before and after
open-heart repair of their lesions. The other seven children
were recatheterized either because of a change in their
clinical status or as part of a study of the natural history of
aortic stenosis. Two patients were catheterized three times
each, twice prior to and once after successful surgical treatment of subvalvar aortic stenosis. All of the patients with
more than one catheterization demonstrated a significant
change in at least one of the indicators of severity considered
in this investigation; hence, for the purpose of this study,
each of the 82 catheterizations was considered as a separate
data point.
In addition, data from three patients apparently recovered
from endocardial fibroelastosis, one patient with a ligated
anomalous left coronary artery, four patients with small
ventricular septal defects (pulmonary-to-systemic flow ratio
of less than 2:1), one patient with mild aortic insufficiency,
and four normal patients were analyzed. These 13 children
are referred to as the control group.
Aortic valve area was calculated from a modified Gorlin
formula'0 as follows:
Materials and Methods
Data were examined for all patients under 16 years of age
with congenital aortic stenosis catheterized at the Johns
Hopkins Hospital between 1963 and 1973. Patients with cardiac lesions other than aortic insufficiency were excluded.
From the Departments of Pediatrics and Biomedical Engineering, The
Johns Hopkins University School of Medicine, The Johns Hopkins Hospital,
Baltimore, Maryland.
Supported in part by research grants from NHLI (HL-14207-03 and HL17996) and the General Clinical Research Centers Program of the Division of
Research Sources (RR-52), NIH.
Address for reprints: L. Jerome Krovetz, M.D., Division of Pediatric Cardiology, Department of Pediatrics, University of Virginia Hospital,
Charlottesville, Virginia 22901.
Received February 12, 1975; revision accepted July 9, 1976.
Valve
area
=
CO X 1000
co_______________
SEP
X HR X 29.5 x v'-
where CO = cardiac output in ml/min, SEP = systolic
ejection period in seconds/beat, HR = heart rate in
961
962
CIRCULATION
beats/min, and AP = the mean pressure difference between
left ventricle and aorta during the systolic ejection period.
Puyau et al.1' demonstrated that the valve area calculated
using 29.5 as the constant in Gorlin's hydrodynamic formula
was closer to the surgically measured orifice in children than
the 44.5 usually used. Cardiac output was calculated by indicator dilution technique in 61 instances, by Fick method in
five, average of Fick and dye in five, and was not available
for 11 patients. Surface area was estimated from the
nomogram of Sendroy and Cecchini'2 and aortic valve index
calculated.
Calculation of the Subendocardial Flow Index
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In 35 catheterizations, pressure recordings of catheter
pull-backs from the left ventricle across the site of the
obstruction to the root of aorta were recorded on analog
magnetic tape. The simultaneously recorded ECG signal
was sent to an R wave detector whose output was connected
to the priority interrupt module of a Varian Model 620/L
minicomputer to separate each pulse beat for subsequent
analysis. Analog-to-digital conversion was performed at a
rate of 200 samples per minute and approximately 15 waves
digitized and recorded on LINC tape. Consecutive left ventricular waveforms were then displayed on a Tektronix 4010
display unit. Pressure waveforms during which PVCs occurred and the next two successive waves were omitted. The
average R to R interval was computed for at least 5 pressure
waveforms, each wave linearly interpolated or extrapolated
to this wave length, and the waveforms averaged. This approach reduces the nonperiodic artifact by the square root of
the number of waves averaged.
The diastolic pressure time index (DPTI) was measured as
the area between aortic pressure and left ventricular pressure
during diastole (fig. 1). Tension time index (TTI) was computed as the integral of the left ventricular pressure during
the systolic ejection period. Subendocardial flow index was
FIGURE 1. Redrawn graphic display used for calculation of the
subendocardialflow index. The tension time index (TTI) is the area
under the left ventricular curve during the time when left ventricular pressure is greater than aortic pressure. Diastolic pressure time
index (DPTI) is the area under the aortic curve during the period
when aortic pressure is greater than left ventricular pressure. The
subendocardialflow index is the ratio of the DPTI (the pressure and
time when subendocardialflow occurs) to TTI which is proportional
to myocardial oxygen consumption.
VOL 54, No 6, DECEMBER 1976
obtained by dividing DPTI by TTI. The averaged waveforms were then displayed on a graphics display terminal
along with the pertinent calculations and printed out on a
Tektronix 4610 hardcopy unit for the permanent record (fig. 1).
The remaining 47 catheterizations were calculated in a
similar manner utilizing the original oscillographic tracings
recorded at 200 mm/sec. Nine simultaneous left ventricular
and root of aorta pressure tracings were available, while 38
catheterizations involved sequential left ventricular and root
of aorta pressure tracings.
For the latter cases, aortic and left ventricular pressure
tracings with identical R to R intervals during the same
stage of respiration were selected. The tracings were superimposed and DPTI and TTI calculated by planimetry of the
areas described above. The values for SEFI were obtained
by dividing DPTI by TTI. In addition, a coronary artery
oxygen supply/demand ratio was calculated for 94 of the 95
catheterizations by multiplying SEFI by the arterial oxygen
content."3
Aortic root angiograms were performed during each
catheterization; 70 of these were available for review to
assess the presence and severity of aortic insufficiency (Al).
Where the cineangiograms were not available, the original
observer's description was relied upon to assess the severity
of AI. Al was graded as 1 + (trivial) if present on only one
cardiac cycle, 2+ (mild) if present on two or more cardiac
cycles, 3+ (moderate) with opacification of entire LV cavity,
and 4+ (4evere) with opacification of entire LV cavity and
elevation of LV end-diastolic pressure. For analyses involving pressure difference, aortic valve area, or aortic valve
index, the five patients with 3+ or 4+ AI were eliminated.
Subendocardial flow was compared for varying degrees of
aortic regurgitation and no significant differences were
found by Student's t-tests. Therefore, subendocardial flow
index values were included in later analyses without respect
to the presence of aortic insufficiency.
No significant difference was found between the mean
aortic valve area and mean aortic valve index, probably due
to the fact that the mean surface area for this group of
patients was close to 1 M2. Correlation coefficients for AP
versus valve area and AP versus aortic valve index were
-.51 and -.54, respectively. Correlation coefficients for
subendocardial flow index versus valve area and versus aortic valve index were 0.70 and 0.65, respectively.
Results
Subendocardial flow index (SEFI) for the 13 patients in
the control group averaged 1.27, with a range of 0.96 to 1.78.
All of the children with congenital aortic stenosis (AS) having either mild or severe symptoms had SEFI below this
range (fig. 2). SEFI was reduced even for asymptomatic AS
patients, averaging 0.88 with a range of 0.43 to 1.65.
Slightly less significant differences between asymptomatic
and symptomatic patient groups were found for aortic valve
area (fig. 3). Eleven of the 29 asymptomatic patients had
valve areas less than 0.75 cm2, a value usually considered to
indicate surgically important narrowing (fig. 3). A similar
lack of differentiation between asymptomatic and symptomatic groups was found for the systolic pressure difference
across the aortic valve (fig. 4). Six of the 29 symptomatic
patients had pressure differences across their valves less than
or equal to 50 mm Hg.
BLOOD FLOW IN AS/Krovetz, Kurlinski
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Subendocardial flow index correlated better with aortic
valve area (r = 0.70) than did the pressure difference across
the left ventricular outflow tract obstruction (r = - 0.51).
The values obtained for SEFI were compared to those
modified by using the arterial oxygen content. The
coefficient correlation was 0.968. In no instance was there a
change in the estimation of the degree of severity when
arterial oxygen content was taken into account. This would
imply that variation of arterial oxygen content was not as
important as the ratio of DPTI/TTI in these children even
though the oxygen content ranged from 12.2 to 21.1 ml/dl.
Table 1 shows that of 24 patients who had either mild or
severe symptoms, seven had only an abnormal SEFI. In six
other patients, both a low SEFI and a small aortic valve area
were found. In 11 symptomatic patients, all the hemodynamic measurements were in agreement in indicating a
high degree of stenosis. In no symptomatic patient was the
pressure difference across the LV outflow tract the only
positive finding. None of the symptomatic patients had
SEFI > .90. However, there were nine asymptomatic
patients who had a low SEFI and aortic valve area as well as
a pressure difference of more than 75 mm Hg, so that the
discrimination was not complete.
Subendocardial flow index and aortic valve area increased
in all except two of the patients following surgical repair (fig.
5). However, over 80% of these children had some degree of
aortic regurgitation following valvotomy. Because estimation of aortic valve area depends upon forward flow through
the valve, AI may invalidate this measurement. Calculation
of SEFI is not affected by aortic regurgitation. Furthermore, because AI decreases DPTI in proportion to the
decrease in diastolic pressure, it would appear to be a more
useful measure of surgical success than aortic valve area.
Left maximum spatial vector (LMSV) was calculated
from the vectorcardiograms in 44 patients. A correlation
963
0
2.5-
S
S
2.0S
IS.D. E
-1.5'
4
0*
4
w
.
-i
MEAN
4c
a
-
> 1.0-
.5.
S
IS.D.
-
0
S.~~~~~
*- P<.OI- oF-PC.50-*
- PC.005-
m
MILD
NONE
SEVERE
FIGURE 3. Aortic valve areas grouped by symptoms for patients
with left ventricular outflow obstruction, excluding those with
moderate or severe A!. Eleven of the 29 symptomatic patients had
aortic valve areas, > .75 cm2 and three were above 1.2 cm2.
coefficient of 0.35 was found between LMSV and systolic
pressure difference across the valve and only 0.10 between
LMSV and SEFI. LMSV averaged 1.88 mv for the asymptomatic patients with aortic stenosis, 1.81 mv for patients
with mild symptoms and 2.6 mv for those with severe symptoms. This latter value was elevated almost entirely by one
200-
1.8I.6-
150-
1.41.2-
IS.D.
E
2
I
1.0.
MEAN
n.
o
4
I-
.8
.6-
I
0
D
IS.0.
0
510
IS.D.
MEAN
I
501
.400
.2-
-PCOO P0
M
PC005
NONE
MILD
IS.D.
-N.S.
I
d
m
SEVERE
FIGURE 2. Subendocardial flow index grouped by symptoms for
patients with left ventricular outflow obstruction. There was no
difference between those with mild or severe symptoms. All of the
symptomatic patients had DPTI/TTI < 0.9.
NONE
-
0
1 - N.S.P
PCw05
I
MILD
34
F
SEVERE
FIGURE 4. Peak systolic left ventricular to root of aorta pressure
differences grouped by symptoms, excluding those with moderate or
severe AL Six of the 29 symptomatic patients had a AP < 50 mm
Hg, while six of the asymptomatic patients had AP > 100 mm Hg.
964
CIRCULATION
VOL 54, No 6, DECEMBER 1976
TABLE 1. Correlation of Symptoms and Preoperative Catheterization Findings
Severe stenosis indicated by:
Low SEFI (<.90)
Low SEFI & low AV area
(<.75sqcm)
Low SEFI & high LV-aortic
pressure (>75 mm Hg)
Low SEFI <.90 + low AV area
+ high LV-Ao pressure
.8-
Asymptomatic
Symptomatic
1.6-
10
7
1.4-
2
6
.2-
1
0
1.0-
,
9
11
a-
a
subject with a LMSV of 4.85 mv; there was no statistically
significant difference among these three groups. There was a
small but statistically insignificant decrease in LMSV in
nine patients following surgery.
.
.6- MEAN
IS. D.
.4-
.2-
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Discussion
Despite the simplicity of its calculation, the area beneath
the LV pressure curve during systole, termed the tension
time index (TTI) by Sarnoff et al.,1 gives a reasonable approximation of myocardial oxygen consumption.
Left ventricular subendocardial muscle (in contrast to
subepicardial muscle) must receive most, if not all, of its
flow during diastole due to the high intramyocardial compressive forces in the subendocardium that reduce systolic
perfusion. Buckberg et al.,8 by constricting the supravalvar
aorta in dogs, demonstrated a lowering of the subendocardial flow index. Homogeneous myocardial flow distribution was maintained over a wide range of subendocardial
flow index values in the dogs, until values of .7 or below were
achieved, and then relative underperfusion of the subendocardium was seen. During control periods, 80% of left coronary artery flow in dogs occurred in diastole and though the
total flow rose as the supravalvar aorta was constricted, the
increase in flow occurred predominantly during systole. The
proportion of flow during diastole fell progressively with increasing aortic constriction and averaged 34% of total flow
with severe constriction and the proportion of total flow perfusing the subendocardial muscle fell significantly.
In their calculations of the subendocardial flow index9 in
18 control patients and in one patient each with valvar aortic
stenosis and supravalvar aortic stenosis, they demonstrated
that the relationship between oxygen needs (TTI) and the
available subendocardial blood supply (DPTI) seem to be
distributed in a similar manner. Both of their patients with
left ventricular outflow tract obstruction had SEFI values
significantly below .7. Increased coronary artery perfusion
pressure may occur in SVAS'8 18 but does not increase subendocardial flow.9
Values for SEFI in our investigation are slightly higher
than those calculated by Vincent et al.9 because our calculation of TTI excludes the periods of isometric ventricular
contraction and relaxation. In our series, all 29 studies in
symptomatic patients had SEFI values below .9 (fig. 2).
Four patients with pressure differences across their valves
greater than 50 mm Hg had SEFI values greater than .9
(.92, .96, .98, 1.06). Also, there were only two patients with
valve areas less than .75 cm2 and subendocardial flow index
values greater than .9 (.96, 1.03). Lewis et al."7 also analyzed
the relationship between the T wave configuration of the
-
P<.001
-
I~~~~~~~~~~~~~~~~~~~~
I
PRE-OP
POST-OP
FIGURE 5. Effect of aortic valvotomy on subendocardial flow indexfor 23 patients with aortic stenosis. SEFI increased in all except
two cases.
electrocardiogram and demonstrated
with supply/demand ratio.
a
strong correlation
A modified index has been proposed which multiplies
DPTI by oxygen content."' Comparison of this modified coronary artery oxygen delivery ratio to SEFI was done for 94
catheterizations in our present study. The correlation coefficient obtained was 0.968, suggesting that arterial oxygen
content was not a major determinant in the degree of variation of myocardial oxygen supply/demand ratios. Data
from two other studies in the literature were also compared
for SEFI alone and SEFI multiplied by arterial oxygen content. For the 80 children of the study by Lewis et al.,'7 the
correlation coefficient was 0.96, and for the 10 neonates described by Lakier et al.'8 it was 0.93.
SEFI showed an excellent correlation with the presence of
symptoms (fig. 2). No patient with either mild or severe
symptoms had an SEFI > 0.90. Of particular interest in this
regard are the findings in six patients who exhibited changes
in symptomatology prior to recatheterization (table 2). In
four instances SEFI worsened with the development of
symptoms and in two instances spontaneous relief of symptoms was accompanied by an increase in SEFI.
An unexpected finding was that mildly symptomatic
patients did not differ significantly from severely symptomatic patients for any of the measures studied. This would
imply that at least in the pediatric age range, our so-called
mild symptoms are as meaningful as severe symptoms in the
assessment of the disease.
Poorer correlation of systolic pressure across the obstruction and symptoms was found in our study (fig. 4). The
presence of severe symptoms showed a statistically significant difference (P < 0.05) while the mildly symptomatic
patients did not differ from the asymptomatic group.
Furthermore, six of the asymptomatic patients had pressure
differences of over 100 mm Hg while six of the symptomatic
patients had pressure differences of less than 50 mm Hg.
In spite of a number of theoretical objections about the
965
BLOOD FLOW IN AS/Krovetz, Kurlinski
TABLE 2. Selected Data of Six Patients with Congenital Aortic Stenosis and a Spontaneous Change in Symptoms
Pt
Age
Sex
Site of
stenosis
JD
5
F
Valvar
M
Valvar
M
Valvar
F
Valvar
M
Valvar
M
Subvalvar
JK
MS
LP
RM
MG
13
6
10
11
14
10
13
7
12
9
DPTI
TTI
NA
-
0.78
70
16
24
-55
57
45
36
65
46
78
0.91
1.74
2.38
1.08
0.97
0.96
1.34
1.22
2.55
0.73
0.66
1.93
2.16
1.03
0.73
0.95
0.96
1.18
1.82
0.73
0.70
0.75
1.65
0.75
0.58
1.07
0.74
0.86
1.54
0.67
192
0.70
0.46
0.45
1+
0
Exer. intol.
26
Angina
1+
0
0
2+
2+
0
0
0
1+
1+
Exer. intol.
0
0
Angina
0
Exer. intol.
Angina
0
0
Exer. intol.
Exces. sweating
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use of aortic valve area, statistically significant differences
were seen between the asymptomatic and both the mildly
and severely symptomatic groups (fig. 3). However, the
presence of aortic regurgitation invalidates this measurement since the forward aortic valve flow is required for its
estimation while the usual dye dilution or Fick method
measures net flow.
Subendocardial blood flow can be estimated easily from
cardiac catheterization data and appears to be a sensitive index of ischemia that should be considered when surgical intervention is being entertained. It should be noted, however,
that we are not certain of the exact numerical value below
which surgical intervention is desirable. Further, DPTI
tends to be decreased with increasing heart rates in the
presence of severe stenosis'7 so that exact numerical values
may be exceedingly hard to evaluate. As patients with AS
age and begin to have associated coronary artery obstruction disease, attempts to estimate the supply/demand ratio
of the LV myocardium may seriously overestimate potential
supply. DPTI is a useful indicator of subendocardial blood
flow only in the presence of maximally dilated and unobstructed coronary arteries.
References
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Cardiol 30: 1, 1972
2. Eddleman EE Jr, Frommeyer WB Jr, Lyle DP, Bancroft WH Jr, Turner
ME Jr: Critical analysis of clinical factors in estimating severity of aortic
valve disease. Am J Cardiol 31: 687, 1973
Ao valve
index
(Cm2/m2)
Symptoms
1+
13
Peak LV to
root of Ao Valve area
(mm Hg)
(cm2)
Ao
insuff
3. El-Said G, Galioto FM Jr, Mullins CE, McNamara DG: Natural hemodynamic history of congenital aortic stenosis in childhood. Am J Cardiol
30: 6, 1972
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67, 1972
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R: Hemodynamic determinants of oxygen consumption of the heart with
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stenosis. Am Heart J 82: 300, 1971
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Evaluation of subendocardial ischemia in valvar aortic stenosis in
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Subendocardial blood flow in children with congenital aortic stenosis.
L J Krovetz and J P Kurlinski
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Circulation. 1976;54:961-965
doi: 10.1161/01.CIR.54.6.961
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1976 American Heart Association, Inc. All rights reserved.
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