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 FREE ACCESS | RESEARCH ARTICLE

Angina Pectoris in Patients With Aortic Stenosis and Normal

Coronary Arteries
Mechanisms and Pathophysiological Concepts
Barbara K. Julius, Martin Spillmann, Giuseppe Vassalli, Bruno Villari, Franz R. Eberli, and Otto M. Hessthe
Division of Cardiology, University Hospital, Zurich, Switzerland.
Originally published 18 Feb 1997 https://doi.org/10.1161/01.CIR.95.4.892 Circulation. 1997;95:892–898

Abstract
Background The incidence of angina pectoris (AP) in patients with severe aortic stenosis (AS) and
normal coronary arteries has been reported to be 30% to 40%. The exact pathophysiological
mechanism, however, is not known. The purpose of this work was to evaluate the various
hemodynamic and angiographic determinants of myocardial perfusion in 61 patients with severe AS.

Methods and Results In a retrospective analysis, 61 patients with severe AS and without significant
coronary artery disease were studied. Thirty-three patients with atypical chest pain and
angiographically normal arteries served as control subjects. Patients were divided into two groups:
32 with AP and 29 without AP. Quantitative coronary angiography was performed in 59 patients and
22 control subjects. Coronary flow reserve was determined in 29 patients and 7 control subjects by
use of coronary sinus thermodilution technique. Patients with AP had a lower left ventricular (LV)
muscle mass, an increased LV peak systolic pressure, and increased wall stress than those without
AP. Vessels of the left coronary artery were smaller and coronary flow reserve was lower in patients
with AP than in those without. Inadequate LV hypertrophy with an increased wall stress was found in
patients with AP but not in patients without AP.

Conclusions Myocardial ischemia in patients with severe AS can occur in the absence of coronary
artery disease and appears to be due to inadequate LV hypertrophy with high systolic and diastolic
Informed consent was obtained from all patients. Premedication consisted of chlordiazepoxide (10
mg PO) 1 hour before the procedure. All vasoactive substances were withheld at least 24 hours
before catheterization. LV pressure was measured transseptally with an 8.5F Brockenbrough
catheter; aortic pressure was measured with a fluid-filled 8F pigtail catheter introduced retrogradely
from the right femoral artery. Pulmonary artery pressure was measured with a conventional 7F
Cournand catheter. Mean coronary perfusion pressure was calculated from mean aortic pressure
minus mean right atrial pressure. Mean systolic pressure gradient and aortic valve area were
calculated according to standard formulas. The degree of aortic regurgitation was assessed by the
angio-Fick technique.

LV angiograms were obtained simultaneously in the right and left anterior oblique projections at a
filming rate of 50 frames per second. LV volumes and ejection fraction were calculated by use of the
area-length method.14 LVMM was determined according to the method of Rackley et al.15
Circumferential stress was calculated from the end-systolic and end-diastolic cine frames by use of
a simplified version of Mirsky's16 thick-wall model: Midwall Stress (Kilodynes/Centimeter Squared)=
(p×b/h)[1−(h/2b)−(b2/2a2)]×1.332, where p is LV pressure (millimeters of mercury), h is LV wall
thickness (centimeters), a is the midwall semimajor axis [(L+h)/2, centimeters], and b is the midwall
semiminor axis [(D+h)/2, centimeters].

Selective left and right coronary angiographies were carried out from the right femoral artery
(Judkins technique, 8F catheters) with multiple views for optimal visualization of the coronary
arteries. Only patients with angiographic evidence of no focal narrowing ≥50% were included in the
present analysis. Coronary artery size was determined by quantitative coronary angiography. A
subgroup of patients (n=29) underwent coronary sinus blood flow measurements for determination
of coronary flow reserve.

Quantitative Coronary Arteriography

Quantitative evaluation of coronary angiograms was performed in 59 of 61 patients and 22 of 33
control subjects with a semiautomatic computer system.171819 The system is based on a 35-mm film
projector (Tagarno 35 CX), a slow-scan CCD camera for image digitalization, and a computer
workstation (Apollo DN 3000) for image storing and processing. Contour detection was carried out
with use of a geometric-densitometric edge-detection algorithm.182021 The method of computerized
analysis of coronary angiograms was described in detail elsewhere.1720212223

The proximal cross-sectional areas of the three major coronary vessels (LAD, LCx, and RCA) were
measured from two or three end-diastolic cine frames. The proximal cross-sectional areas of the
LAD and LCx were defined as the vessel segment immediately beyond the bifurcation of the left
main coronary artery over a length of ≈1 cm. The computer traced this segment automatically and
calculated the mean area over this segment. A circular lumen was assumed because only patients
with coronary arteries showing no angiographic evidence of focal coronary narrowing ≥50% were
included. The proximal cross-sectional area of the RCA was defined as the vessel segment 1 to 2
cm distal to the coronary ostium. A vessel segment over a length of ≈1 cm was analyzed, and the
mean cross-sectional area was calculated in the same way as for the LCA. For each vessel
segment, measurements in different projections were obtained and averaged to correct for biological
variations in coronary artery dimensions.192324 Calibration was performed automatically by use of
the proximal part of the 8F Judkins catheter as a scaling device.1725 As an index of the enlargement
of the coronary arteries with respect to the degree of LV hypertrophy, the cross-sectional area of the
LCA (LAD+LCx) per 100 g of LV angiographic mass was calculated.1726

Coronary Blood Flow Measurements

Measurements of coronary sinus blood flow were performed after diagnostic catheterization in 29 of
the 61 patients and 7 of the 33 control subjects. Coronary blood flow was measured by the coronary
sinus thermodilution technique.27 A 7F thermodilution catheter (CCS-7 U-90 A or B, Webster
Laboratory) was introduced from the right femoral vein into the coronary sinus. Correct positioning
was checked by measurement of oxygen saturation and injection of small amounts of contrast
medium before and after measurements. The signals of the external (mixing temperature of blood
and saline) and internal (temperature of the injected saline) thermistors were recorded on an
Electronics for Medicine VR-12 oscillograph at a paper speed of 5 mm/s. Saline at room
temperature was infused through the thermodilution catheter at a rate of 50 mL/min, and coronary
sinus blood flow (CSBF, mL/min) was calculated according to the formula of Ganz et al.27 Coronary
resistance (CR, mm Hg×min/mL) was calculated according to the following formula: CR=
(MAP−CSP)/CSBF, where MAP is mean aortic pressure and CSP is mean coronary sinus pressure
(both in millimeters of mercury). Normalization per 100 g LVMM was carried out for coronary sinus
blood flow and coronary resistance by use of angiographic mass. Coronary sinus blood flow was
determined at rest and after infusion of 0.5 mg/kg body weight dipyridamole over 15 minutes. This
duration of infusion of dipyridamole was chosen to minimize the systemic effects of dipyridamole on
heart rate and blood pressure.28 In no case were adverse effects of dipyridamole encountered.

Coronary flow reserve was calculated as coronary sinus blood flow after dipyridamole infusion
divided by the sinus blood flow at rest, and coronary resistance ratio was calculated as the
resistance after dipyridamole infusion divided by resistance at baseline. Coronary venous and
arterial oxygen saturation was measured to calculate oxygen content before and after infusion of
dipyridamole. Because the contrast medium (ventriculography, coronary angiography) may alter
coronary dynamics,29 the baseline value of coronary sinus blood flow was recorded at least 20
minutes after any previous contrast material injection. It has to be realized that not total but flow of
the LCA is predominantly measured.

Statistical Analysis
Statistical comparisons of hemodynamic and angiographic data among the patients were carried out
by a one-way ANOVA followed by the Newman-Keuls test. A value of P<.05 was considered
statistically significant. Linear regression analysis was carried out by the least-squares method; in all
figures with linear regressions, the 95% confidence limits are included. Data in all tables and figures
are reported as mean±SD unless otherwise indicated.

Results
Clinical Data
The two groups did not differ with respect to age, body surface area, hemoglobin (14.8±1.4 versus
14.7±1.2 mg%, P=NS), cholesterol level (5.8±1.3 versus 6.6±3.6 mmol/L, P=NS), and history of
hypertension. However, the AP+ group had a higher NYHA class than the AP− patients (2.4±0.6
versus 1.9±0.6, P<.005), whereas AP− patients more often reported episodes of syncope than AP+
patients (37% versus 63%, P<.05). The cardiothoracic ratio was similar in both groups (0.51±0.04
versus 0.51±0.06, P=NS). There was no difference between the two groups with respect to the
Sokolow-Lyon index (3.7±0.9 versus 3.9±1.5 mV, P=NS) or the presence of LV strain in the resting
ECG. Because of changes in the resting ECG, only 26 of 48 exercise ECGs could be reliably
evaluated. However, ST-segment depression was significantly more pronounced in AP+ than in AP−
patients (0.20±0.13 versus 0.10±0.12 mV, P<.05).

Hemodynamic Data
Tables 1 through 3 summarize the hemodynamic and angiographic data. Resting heart rate was
similar in both groups (73±14 versus 72±11 bpm, P=NS). No significant difference was found
between the groups with regard to mean aortic and mean pulmonary artery pressures, LV end-
diastolic pressure, cardiac index, arteriovenous oxygen difference, diastolic aortic pressure, and
rate-pressure product. However, there was a significant elevation of LV peak systolic pressure in
AP+ compared with AP− patients (204±28 versus 187±35 mm Hg, P<.05).

Angiographic Data
LVMM ranged from 83 to 619 g in the two patient groups. AP− patients had a larger muscle mass
index than AP+ patients (Table 2). No differences were detected with respect to LV ejection fraction,
stroke volume index, aortic valve area, or systolic pressure gradient. End-systolic (368±79 versus
325±80 dynes·103/cm2, P<.05), peak systolic (528±90 versus 458±92 dynes·103/cm2, P<.01), and
end-diastolic wall stress (53±24 versus 37±18 dynes·103/cm2, P<.01) were significantly elevated in
AP+ patients.

Quantitative Coronary Angiography

Both proximal LAD and LCx tended to be smaller in AP+ patients (11.0±3.2 versus 12.6±3.5 mm2,
P<.1, and 10.3±2.6 versus 11.9±4.9 mm2, P<.05, respectively) than in AP− patients. There was a
significant difference in total cross-sectional area of the LCA between the two groups (20.7±4.8
versus 24.1±6.9 mm2, P<.05). Although RCA size was similar in AP+ patients and control subjects
(8.9±2.3 versus 9.0±4.7 mm2, P=NS), its size was significantly increased in AP− patients (11.7±4.0
mm2; P<.01 versus AP+). Normalization of coronary artery size per 100 g muscle mass was
associated with a loss of the significant differences between the groups.

Coronary Flow Measurements

The subgroup of patients in which coronary flow measurements were studied did not differ
significantly from the patient population as a whole with regard to the degree of aortic stenosis,
LVMM, or LV wall stress. Of the 29 patients, 27 had no angiographic evidence of atherosclerosis,
and only 2 showed minor irregularities of the arterial wall in the coronary angiogram, 1 with and 1
without anginal symptoms.

Resting coronary sinus blood flow was significantly higher in patients with aortic stenosis than in
control subjects (252±99 versus 170±35 mL/min, P<.05), whereas no difference was observed
between the two subgroups (227±75 versus 260±94 mL/min, P=NS). Maximal blood flow, however,
was significantly reduced in AP+ compared with AP− patients (341±114 versus 481±215 mL/min,
P<.05). There was no significant difference in coronary resistance at rest or after administration of
dipyridamole between the two groups or control subjects. Conversely, coronary flow per 100 g
LVMM was significantly lower in AP+ patients compared with control subjects (Fig 1) and was
significantly lower after infusion of dipyridamole in AP+ patients compared with AP− patients or
control subjects. There was no difference in coronary resistance per 100 g LVMM at rest or after
infusion of dipyridamole between AP+ and AP− patients or control subjects (Fig 1).

Coronary flow reserve was significantly reduced in AP+ compared with AP− patients or control
subjects (Fig 2). Correspondingly, coronary resistance ratio was increased in AP+ compared with
AP- patients or control subjects (Fig 2).

Correlations
There was a significant correlation between LCA and LVMM for all patients (r=.60, P<.0001; Fig 3),
with no difference in slope or intercept between the two groups. Other correlations were found
between coronary resistance ratio and arteriovenous oxygen difference (r=.51, P<.005) or
pulmonary vascular resistance (r=.60, P<.001).

Discussion
The occurrence of AP in patients with severe aortic stenosis is usually associated with an advanced
stage of the disease. Ross and Braunwald11 have shown that survival is severely impaired in the
presence of angina (mean survival, ≈5 years), syncope (survival, ≈3 years), or heart failure (survival,
≈1.5 years). The pathogenesis of AP in the absence of significant coronary artery narrowing,
however, is not yet clear, although it has been assumed that in the presence of severe myocardial
hypertrophy with an increased extravascular resistance, a reduction in subendocardial perfusion
may occur.530 Parallel to subendocardial hypoperfusion, a reduction in coronary flow reserve has
been reported in severe aortic valve disease8103132 that was restored after successful valve
replacement with normalization of LVMM.31 However, not all patients with severe aortic stenosis
develop AP; eg, 51% of our patients with severe operative aortic stenosis had no anginal pain.
Thus, the purpose of the present study was to evaluate the pathophysiological mechanisms involved
in the development of AP.

LV Hypertrophy and Myocardial Perfusion

Most of our patients (78%) had severe LV hypertrophy with a mass >200 g,33 which represents
approximately a doubling of the normal LVMM compared with control subjects. Interestingly, our
AP+ patients had a smaller LVMM than the AP− patients, suggesting that not the total mass but the
appropriateness of LV hypertrophy is essential for the development of anginal symptoms.
Inappropriate myocardial hypertrophy seems to be involved in the pathophysiology of AP because
LVMM was relatively too small for the high wall stress in our study group (Fig 4). However, ejection
fraction is maintained despite an increased wall stress, suggesting an augmentation or at least the
maintenance of myocardial contractility.

The role of ventricular wall stress in the presence of LV hypertrophy has been widely discussed.
Wall stress is an important determinant of myocardial oxygen consumption, myocardial contractile
state, and diastolic function.34 A high wall stress has been associated with a less favorable
prognosis because of electrical instability and myocardial hypoperfusion.34 According to Gaasch,35
the ratio of LV radius to wall thickness has been used to classify the appropriateness of LV
hypertrophy (Fig 4) into inappropriate (low wall stress), appropriate (normal wall stress), or
inadequate (high wall stress). Inadequate hypertrophy in association with abnormal stress-
shortening relations has been associated with changes in myocardial contractility and thus may
predict an impaired postoperative outcome in these patients. Primary and secondary changes in the
neurohumoral, molecular, metabolic, and genetic systems have been discussed and are thought to
influence cardiac hypertrophy in response to chronic pressure overload.3637 In particular, a decrease
in myosin ATPase activity, a transition of myosin heavy chains, and an increase in insulin-like growth
factor-I have been described.38 Moreover, an activation of the sympathetic nervous system and
renin-angiotensin system as well as a primary genetic disposition have been discussed to influence
left ventricular hypertrophy.34

Parallel to the inadequate LV hypertrophy and increased wall stress (Fig 4), smaller coronary
arteries with a reduced coronary flow reserve were observed in the present study, supporting the
concept that the adaptation of the LV and its coronary size are inadequate in respect to actual
loading conditions. This may explain the occurrence of AP.

Other determinants of myocardial oxygen consumption such as heart rate, myocardial contractility,
ejection time, and hemoglobin were comparable in the two groups except for systolic and diastolic
wall stress, as discussed above. Thus, not only is the oxygen supply reduced (decreased coronary
flow reserve), but at the same time oxygen demand is enhanced (increased wall stress). This
mismatch between supply and demand could explain the occurrence of subendocardial ischemia
with AP.

Myocardial Ischemia in Pressure-Overload Hypertrophy

Metabolic studies of patients with aortic stenosis have shown that coronary sinus lactate is normal at
rest. Under conditions of metabolic stress, however, most patients with aortic stenosis and normal
coronary arteries elicit either a decrease in lactate extraction or an increase in lactate production as
an indicator of myocardial ischemia.3940 In patients with high pressure gradients, coronary blood
flow cannot be increased under stress.39 Clinical signs of myocardial ischemia have been gained in
aortic stenosis from exercise thallium-201 tomography with perfusion defects in 43% of all patients
with normal coronary arteries.41 Furthermore, ST-segment analysis of 24-hour Holter monitoring
showed transient myocardial ischemia in patients with hypertensive LV hypertrophy and normal
coronary angiograms.30

Clinical Implications
From a clinical standpoint, inadequate LV hypertrophy with small coronary arteries and reduced
coronary flow reserve can explain the occurrence of subendocardial ischemia during high flow
situations such as exercise (Fig 5). Activation of the sympathetic system with coronary
vasoconstriction and elevation of systolic blood pressure do not seem to be likely because heart rate
was similar in the two groups. Thus, other factors such as a lack of growth stimuli or molecular
changes may be responsible for the inadequate LV hypertrophy with increased wall stress and
reduced coronary flow reserve (Fig 5).
Study Limitations
In a study subgroup, coronary flow and flow reserve were assessed by coronary sinus
thermodilution technique. This method is unable to measure the flow in specific ventricular layers or
regions27 and may be inaccurate after interventions leading to coronary sinus reflux.42 In the
absence of coronary artery disease and no known movement of the catheter, the thermodilution
technique, however, is adequate for measuring relatively slow and large changes of coronary blood
flow such as that observed in our study.

For the measurement of maximal vasodilator capacity, dipyridamole was used.2943 It is recognized
that dipyridamole at the chosen dose (0.5 mg/kg) does not always produce maximal coronary
vasodilation.44 Dipyridamole infusion lasted 15 minutes to minimize systemic effects on heart rate
and blood pressure.2845 A decrease in blood pressure would have been detrimental in patients with
aortic stenosis.

Determination of coronary artery size was performed by quantitative coronary angiography. Other
determinants of coronary artery size such as age, body surface area, physical working capacity,
vessel dominance, and coronary vasomotor tone have been evaluated. First, variable effects of age
on LCA size have been reported.4647 In the present study, there was a positive correlation in control
subjects (r=.62) but no correlation in either patient group. Thus, no clear statement on the effect of
age on coronary artery size can be made from the present data. Second, body size may have a
direct effect on coronary dimensions. However, no correlation was found in control subjects or in the
two patient groups. Because no differences in body surface area between control subjects and
patients with aortic stenosis were found, this factor is unlikely to have influenced the results of our
study. Third, physical working capacity has been reported to directly influence coronary artery
size.17 Although all patients had a significantly lower working capacity than control subjects, their
coronary artery size was significantly larger. Thus, it is unlikely that the enlargement in coronary
artery size was mediated by physical working capacity. However, AP+ patients had a lower working
capacity and smaller coronary arteries than AP− patients, probably because symptom-limited
exercise testing was performed.

It is well known that a close relation exists between myocardial territory size and proximal coronary
diameter.4849 In the present study, however, coronary dominance was the same in control subjects
and patients with aortic stenosis. Moreover, after the patients were grouped according to LCA or
RCA dominance, the same patterns of variation in the LCA and RCA dimensions were observed.

Conclusions
The present study confirms that ≈50% of all patients with severe aortic stenosis have AP, which was
found to be associated with inadequate LV hypertrophy, increased LV peak systolic wall stress, and
small coronary artery dimensions with a reduced coronary flow reserve. This suggests that
myocardial ischemia may be due to hypoperfusion of the myocardium under high-flow and high-
demand situations such as those seen in severe pressure- and volume-overload hypertrophy.

Selected Abbreviations and Acronyms

AP = angina pectoris

AP− = without AP

AP+ = with AP

LAD = left anterior descending coronary artery

LCA = left coronary artery

LCx = left circumflex artery

LV = left ventricle/left ventricular

LVMM = LV muscle mass

NYHA = New York Heart Association

RCA = right coronary artery

Download figure | Download PowerPoint
Figure 1. Coronary sinus blood flow (CSBF; top) and coronary resistance (CR; bottom) before
and after dipyridamole infusion. Resting coronary blood flow per 100 g LVMM is similar in all
three groups, whereas maximal flow is significantly lower in AP+ than in AP− patients or
control subjects. Conversely, there is no difference in resting or minimal coronary resistance
per 100 g LVMM between the three groups.
Download figure | Download PowerPoint
Figure 2. Coronary flow reserve (CFR; top) and coronary resistance ratio (CRR; bottom) in
AP+ patients and control subjects. Coronary flow reserve is significantly reduced in AP+
patients compared with AP− patients or control subjects. Conversely, coronary resistance ratio
is significantly increased in AP+ and AP− patients compared with control subjects.
Download figure | Download PowerPoint
Figure 3. Correlation between LVMM and LCA cross-sectional area (CSA). A linear relation
was observed between these two parameters, indicating adequate vessel growth with regard
to LVMM. C indicates control subjects. Given are the regression line and the 95% confidence
limits.

Download figure | Download PowerPoint

Figure 4. Relationship between LV circumferential peak systolic wall stress (Speak) and LVMM
in AP+ and AP− patients. AP+ patients have an increased wall stress with inadequate
hypertrophy compared with AP− patients. See text for explanations.
 Download figure | Download PowerPoint
Figure 5. Pathophysiology of myocardial ischemia in AP+ patients. LV hypertrophy tends to
normalize LV wall stress, but in the presence of inadequate hypertrophy, wall stress is
elevated. This leads to an increase in myocardial oxygen consumption and augmentation of
extravascular compressive forces. As a result, coronary flow reserve is reduced. Because of
LV hypertrophy, diffusion distance is increased and capillary density is decreased.
Mechanisms in the presence of inadequate hypertrophy are shown by open arrows.

Table 1. Hemodynamic Data

HR, LVEDP, LVSP, mm MAP, mm MPAP, AVDO2, CI,

bpm mm Hg Hg Hg mm Hg % L·min−1·m−2

Control 66±9 10±4 117±21 93±14 18±5 19±4 3.8±0.8

subjects

AP+ 73±14* 20±9† 204±28† 89±16 20±7 22±4* 3.1±0.6†

patients

AP− 72±11‡ 16±5§ 187±35§ǁ 95±13 18±5 23±5‡ 2.9±0.6§

patients

HR indicates heart rate; LVEDP, LV end-diastolic pressure; LVSP, LV peak systolic pressure;
MAP, mean aortic pressure; MPAP, mean pulmonary artery pressure; AVDO2, arteriovenous
oxygen difference; and CI, cardiac index. Data are mean±SD.

*P<.05 AP+ vs C.

†P<.01 AP+ vs C.
‡P<.05 AP− vs C.

§P<.01 AP− vs C.

ǁP<.05 AP+ vs AP−.

Table 2. Angiographic Data

EDVI, mL/m2 SVI, mL/m2 EF, % MNSER, s−1 h, cm LMMI, g/m2

Control subjects 84±19 47±9 67±8 2.1±0.3 0.8±0.2 70±24

AP+ patients 114±26* 63±18* 59±11* 1.8±0.3* 1.2±0.2* 136±43*

AP− patients 119±25† 67±14† 58±12† 1.7±0.4† 1.3±0.2†‡ 168±71†‡

EDVI indicates end-diastolic volume index; SVI, stroke volume index; EF, LV ejection fraction;
MNSER, mean systolic ejection rate; h, left ventricular end-diastolic wall thickness; and LMMI,
LVMM index. Data are mean±SD.

*P<.01 AP+ vs C.

†P<.01 AP− vs C.

‡P<.05 AP+ vs AP−.

Table 3. LV Circumferential Wall Stress

Sed, kdynes/cm2 Ses, kdynes/cm2 Speak, kdynes/cm2

Control subjects 40±25 278±71 442±104

AP+ patients 53±24* 368±79* 528±90†

AP− patients 37±18ǁ 325±80‡§ 458±92ǁ

Sed indicates LV circumferential end-diastolic wall stress; Ses, LV circumferential end-systolic wall
stress; and Speak, LV circumferential peak systolic wall stress.

*P<.06 AP+ vs C.

†P<.01 AP+ vs C.
 ‡P<.05 AP+ vs AP−.

§P<.05 AP+ vs C.

ǁP<.01 AP+ vs AP−.

Footnotes
Correspondence to Otto M. Hess, MD, Cardiology, University Hospital, 3010 Bern, Switzerland.

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wall stresses and a reduced coronary flow reserve. The cause of inadequate LV hypertrophy,
however, remains unclear.

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The incidence of angina pectoris in patients with aortic stenosis has been reported to range between
30% and 40% in the absence of associated coronary artery disease.123456 AP is a typical symptom
in patients with aortic stenosis.1267 The pathophysiological mechanism of angina is not clear but
seems to be due to unbalanced myocardial oxygen supply and demand. This may be explained in
part by a reduction in coronary flow reserve,8910 although no correlation between AP and coronary
flow reserve has been reported. Since patients with AP and severe aortic stenosis have a worse
prognosis than those without symptoms,6111213 hemodynamic factors as well as myocardial
perfusion have been evaluated with regard to the pathogenesis of AP in the absence of coronary
artery disease.

Methods
Study Population
Sixty-one patients (mean age, 59±11 years; range, 35 to 81 years) with severe predominant aortic
stenosis and without significant coronary artery disease who underwent diagnostic catheterization at
our institution between 1977 and 1994 were included in the present analysis. Patients with moderate
or severe mitral valve disease and/or significant coronary artery disease (≥50% stenosis) were
excluded. Of the 61 patients with aortic stenosis, 69% had concomitant aortic regurgitation that was
mild (≤5%) or moderate (≤25%). Mean regurgitant fraction as determined by the angio-Fick method
was 19%. However, patients were selected on the basis of their valve area; ie, only patients with an
aortic valve area ≤1.0 mm2 were considered to have predominant aortic stenosis. The following
clinical symptoms were evaluated: AP, dizziness, syncope, and heart failure. Functional
classification according to the NYHA was assessed in each study subject. Patients were divided into
two groups according to the presence or absence of AP. There were 32 patients (24 men, 8 women;
age, 59±11 years) with a history of typical AP and 29 patients (24 men, 5 women; age, 60±11 years)
without AP. Of the group with AP, 27 patients had no angiographic evidence of coronary
atherosclerosis, 3 had irregularities of the arterial wall, and 2 had nonsignificant coronary artery
stenosis of <50%. In the group without AP symptoms, 22 patients had no angiographic evidence of
atherosclerosis, 5 had irregularities of the arterial wall, and 2 showed nonsignificant coronary artery
stenosis. Thirty-three patients (24 men, 9 women; age, 50±9 years) with normal coronary arteries at
catheterization and atypical chest pain served as control subjects.

Cardiac Catheterization