Review Aortic stenosis, angina pectoris, and coronary artery disease E. William Hancock, M.D. Stanford, Calif.
The presence of coronary artery disease in patients with aortic stenosis was noted in many pathologic studies prior to the advent of cardiac surgery. '.'° Most authors considered the prevalence of coronary disease to be about that which would be expected on the basis of the age and sex of the patients with aortic stenosis. Some felt that there was increased association, 5 however, while others believed that coronary disease was less frequent in patients with aortic stenosis than would be expected. ~' ~' 9 Relatively little attention was given to the problem of associated coronary disease during the period of development of surgical t r e a t m e n t for aortic stenosis in the 1950's and early 1960's. ''-'G Emphasis was placed on the hemodynamic evaluation of the valvular lesion and, while the association of coronary disease in some patients was recognized, it did not appear to be frequent in the patients considered for surgery, who in that era were largely under 60 years of age. In any event it was not amenable to systematic diagnosis or definitive surgical therapy. With the advent in the 1960's of coronary arteriography, and with the increasing application of open-heart surgery to patients in the older age groups, "-~ a renewal of interest in the subject occurred. The report of Linhart and associates, ~:' indicating that significant coronary artery disease was present in 63 per cent of a consecutive series of patients with aortic stenosis, was particularly influential. Other pathologic and arteriographic studies also demonFrom the Division of Cardiology, Stanford University School of Medicine, Stanford, Calif. This work was supported in part by N I H Grants Nos. HL-5866 and Program Project Grant No. I PO1-HL-15833. Received for publication April 24, 1975. Address all correspondence to: E. William Hancock, M.D., Cardiology Division, Stanford University School of Medicine, Stanford, Calif. 94305.
382
strated a frequent association. 24--~:' With the advent of coronary artery bypass surgery and its increasingly frequent use in combination with valve replacement surgery in the 1970's,:'..... the diagnostic aspects of this problem assumed a new importance. The diagnosis of coronary artery disease in patients with aortic stenosis is usually considered to be very difficult, since angina pectoris and electrocardiographic (ECG) changes are produced by either condition. There also remains some uncertainty about the true incidence of coronary artery disease in patients with aortic stenosis, particularly in those with and without angina pectoris and those in various age groups. The present study was undertaken to provide some answers to these questions. Patients studied and methods
This study deals primarily with 173 patients, who represent all of the patients seen at this institution during the years 1970 to 1973, inclusive, who were 40 years of age or older, had hemodynamically significant aortic valvular stenosis as an essentially isolated valvular lesion,, and had a technically satisfactory selective coronary arteriogram as part of their cardiologic evaluation. The group includes 156 who later had surgical treatment for aortic stenosis at this institution, with or without simultaneous coronary bypass surgery. T h e cardiac catheterization and angiographic studies were performed at this institution in 100 of these and elsewhere in 56. Also included are 17 who did not have aortic valvular surgery for various reasons, even though cardiac catheterization did show hemodynamically significant aortic stenosis; all but one of these, a man who died suddenly the day before scheduled surgery, had their angiographic studies
March, 1977, Vol. 93, No. 3, pp. 382-393
Aortic stenosis, angina pectoris, and coronary artery dLsease Table I. T h e n u m b e r of patients with tour grades of coronary artery disease in the coronary
arteriogram, according to age and the presence or absence of angina pectoris Age (yr.) 40-49
50-59
60-69
70-81
Sererity of ('oFon~Fy disease
Angiml
No angina
Angina
0
4
2
14
8
6
8
1
1
+ + +
1 1
1 0
7 3
5 0
10 ll
1 2
3 7
4 0
+ + +
3
0
15
:1
25
6
17
4
d No angina
in this institution. Reference is also made to the 148 patients 40 years of age or older who had surgical t r e a t m e n t of isolated aortic valvular stenosis during 1970 to 1973 without preoperative coronary arteriography. Aortic stenosis was considered h e m o d y n a m i cally significant if the calculated aortic valve area was less than 0.80 cmY per square meter.' .... One patient was included although the aortic valve area was 1.1 cm.=' per square m e t e r because the stenosis was considered significant both clinically and at the time of operation, and aortic valve replacement was carried out. In four patients the cardiac o u t p u t and hence the aortic valve area were not determined, but in each of these the transaortic systolic pressure gradient exceeded 40 mm. Hg and severe stenosis was confirmed at operation. Eleven patients were included although the left ventricular pressure had not been determined; in each of these the aortic stenosis was obviously severe at the time of operation and aortic valve replacement was carried out. A twelfth patient who was included although the gradient and valve area were not determined had mild to m o d e r a t e aortic stenosis at operation and had d e b r i d e m e n t - v a l v o t o m y procedure r a t h e r t h a n aortic valve replacement; coronary arteriogr a p h y was normal in this patient and his symptoms of m o d e r a t e dyspnea and angina on effort were therefore a t t r i b u t e d to m o d e r a t e aortic stenosis. Patients with mixed aortic stenosis and regurgitation were included if the stenosis was considered the p r e d o m i n a n t lesion. This conclusion required a d e m o n s t r a t i o n of a pressure gradient of more t h a n 50 mm. Hg, an arterial pulse of slowrising late-peaked type, and a visual evaluation at the time of operation t h a t the stenosis was marked and was the p r e d o m i n a n t lesion. P a t i e n t s
American Hertrt Journal
Angina
] No angina
A ngin a
No (tnlIDza
with functionally significant mitral valvular disease detected clinically, by cardiac catheterization, or at operation were not included. All of the aortic valves in this series of patients showed calcification, although this was not prerequisite to inclusion. Coronary artery disease was graded absent if the arteries appeared completely normal, and mild if there were areas of irregularity or narrowing of less t h a n 50 per cent of the lumen caliber or if calcification in the vessel wall was seen, without luminal narrowing. It was graded m o d e r a t e if one or more areas of narrowing in the range of 50 to 70 per cent were present, and severe if one or more areas of narrowing greater than 70 per cent were present. Statistical significance was determined by the chi-square method. In much of the analysis the normal and mild cases and the moderate and severe cases are grouped together, giving one group with no significant lesions and a second group with significant occlusive coronary a r t e r y disease. T w o patients were included who had selective study of only one of the two main coronary arteries, showing severe lesions on the side which was visualized. Patients who showed no severe lesions in incomplete studies were not included. Results
T h e n u m b e r of patients with the four grades of coronary a r t e r y disease, according to age and the presence or absence of angina pectoris, is given in Table I. Significant occlusive c o r o n a r y lesions were found in 56 per cent of the total group, including 53 per cent of the 156 surgical patients. This figure may overestimate the true over-all incidence because c o r o n a r y a r t e r i o g r a p h y was performed more f r e q u e n t l y in patients with clinical evidence of c o r o n a r y disease. T h e lower limit
383
Hancock
II. Distribution of significant coronary occ.lusive lesions in 97 patients
Table
70 60--
Single lesions: o
(4 I--
z
LAD~ I,CCA RCA
I
50 -
Ul I-P.
Double lesions:
LMCA--I,AD I,AD-LCCA I,AD-RCA RCA-IA:CA
40 B
6 z
11 3 14
30 -
1 14 1't
6
Triple and quadruple h'sions:
20 10
i
76%
- + ++
LMCA--I,AD-I,CCA LMCA-I.AI)-I{CA LMCA-I,CCA-I{CA I,AD-L('('A-RCA LM(?A-I,AD-LCCA-RCA
1
1 1 26 5
" A b b r e v i a t i o n s : L A I ) = h!ft a n t e r i o r d e s c e n d i n g c o r o n a r y a r t e r y : I,CCA = lelt circumflex c o r o n a r y a r t e r y ; }'~CA = right c o r o n a r y a r t e r y ; L M C A = lett m a i n c o r o n a r y a r t e r y .
AGE
40-49
50-59
60-69
70-83
Fig. 1. The incidence of coronary artery disease in 173 patients with aortic stenosis, according to age. Significant coronary disease ( + + or + + + ) is more frequent in those aged 60 to 69 yeal,'s than tho~ aged 50 to 59 (P = < 0.01). The differences between those aged 40 to 49 and 50 to 59 and between tho~ aged 60 to 69 and 70 to 83 are not statistically significant.
of the true over-all incidence m a y be estimated from the group of 87 surgical patients in 1973, in w h o m coronary a r t e r i o g r a p h y was performed in 59 and significant c o r o n a r y disease was found in 32, or 38 per cent of the total. Thus, the true overall incidence in the surgical patients is p r o b a b l y in the range of 40 to 50 per cent. T h e incidence of significant c o r o n a r y disease increased markedly with age, being 33 per cent in patients aged 40 to 49, 38 per cent in those aged 50 to 59, 64 per cent in those aged 60 to 69, and 76 per cent in those over 70 years of age (Fig. 1). T h e corresponding figures for the 156 surgical patients were 27, 38, 61, and 74 per cent. T h e corresponding figures for the 87 surgical cases in 1973, assuming n o r m a l c o r o n a r y vessels in those n o t studied by c o r o n a r y arteriography, were 0, 12, 55, and 60 per cent. T h u s a n y figure given for the over-all incidence m u s t depend heavily on the age composition of the group in question. There was no over-all difference according to sex, coronary disease occurring in 60 per cent of women and 56 per cent of men. T h e incidence was
384
63 per cent (5 of 8) in w o m e n aged 60 to 69 and 75 per cent (9 of 12) in w o m e n aged 70 and over. Only five w o m e n under age 60 were studied, and only one of these had significant c o r o n a r y disease, a w o m a n aged 42 who had severe type II hypercholesterolemia, multiple previous m y o c a r d i a l infarctions with a ventricular a n e u r y s m , and m o d e r a t e aortic stenosis. T h u s it seems likely t h a t w o m e n under age 60 with aortic stenosis have a lower prevalence of c o r o n a r y disease t h a n do men of the same age, b u t the n u m b e r studied is too small to permit a firm conclusion. T h e distribution of c o r o n a r y occlusive lesions a m o n g the four principal c o r o n a r y arteries is given in Table II. T h e left anterior descending artery was the vessel m o s t frequently involved, and combinations involving two or three m a j o r vessels were more frequent t h a n single-vessel involvement, as is observed in c o r o n a r y artery disease generally. Marked obstruction of the left main c o r o n a r y artery occurred in 10 patients, all of w h o m had multivessel disease. T h e lesions were at the left coronary ostium in three of these patients. Right c o r o n a r y ostial lesions of significant degree were identified in six patients and in two these were the only c o r o n a r y lesions present. Calcification of the left main c o r o n a r y a r t e r y was noted in 27 patients, only two of w h o m showed significant obstruction of t h a t artery, b u t 21 of them had lesions elsewhere in the proximal c o r o n a r y arteries.
Mttrch, 1977, Vol. 9,'3, No. 3
Aortic stenosis, angina pectoris, and coronary artery disease
Table III. T h e n u m b e r of patients with each of four types of chest pain syndromes, according to the severity of occlusive lesions fi)und on coronary arteriography
70
60
Severity of coroll(t~ disease
AS-t)pe ~: a ngin.
i) + + + + ++
17 15 10 16
CA l)-type Nonanginal No pain chest pain angina 8 6 12 44
5 3 1 5
14 8 1 8
"AS-type refers to angina pe¢'toris which occurs only with physical exertion and in as.~ociation with dyspnea on exertion, or ill a fcw instances during paroxysmal t a c h y a r r h y t h m i a s as well. CAl)-type refevs to angina [x,ctoris which occurs on exertion, but without dyspnea on exertion, or which also occurs with emotional st re.~% after lll(~alS, o r at rcst, including n o c t u r n a l angina. Abbreviations are as given in TabIe II.
03 I-Z UJ F-
50
The presence of coronary artery disease in patients with aortic stenosis was noted in many pathologic studies prior to the advent of cardiac surgery. '.'° Most authors considered the prevalence of coronary disease to be about that which would be expected on the basis of the age and sex of the patients with aortic stenosis. Some felt that there was increased association, 5 however, while others believed that coronary disease was less frequent in patients with aortic stenosis than would be expected. ~' ~' 9 Relatively little attention was given to the problem of associated coronary disease during the period of development of surgical t r e a t m e n t for aortic stenosis in the 1950's and early 1960's. ''-'G Emphasis was placed on the hemodynamic evaluation of the valvular lesion and, while the association of coronary disease in some patients was recognized, it did not appear to be frequent in the patients considered for surgery, who in that era were largely under 60 years of age. In any event it was not amenable to systematic diagnosis or definitive surgical therapy. With the advent in the 1960's of coronary arteriography, and with the increasing application of open-heart surgery to patients in the older age groups, "-~ a renewal of interest in the subject occurred. The report of Linhart and associates, ~:' indicating that significant coronary artery disease was present in 63 per cent of a consecutive series of patients with aortic stenosis, was particularly influential. Other pathologic and arteriographic studies also demonFrom the Division of Cardiology, Stanford University School of Medicine, Stanford, Calif. This work was supported in part by N I H Grants Nos. HL-5866 and Program Project Grant No. I PO1-HL-15833. Received for publication April 24, 1975. Address all correspondence to: E. William Hancock, M.D., Cardiology Division, Stanford University School of Medicine, Stanford, Calif. 94305.
382
strated a frequent association. 24--~:' With the advent of coronary artery bypass surgery and its increasingly frequent use in combination with valve replacement surgery in the 1970's,:'..... the diagnostic aspects of this problem assumed a new importance. The diagnosis of coronary artery disease in patients with aortic stenosis is usually considered to be very difficult, since angina pectoris and electrocardiographic (ECG) changes are produced by either condition. There also remains some uncertainty about the true incidence of coronary artery disease in patients with aortic stenosis, particularly in those with and without angina pectoris and those in various age groups. The present study was undertaken to provide some answers to these questions. Patients studied and methods
This study deals primarily with 173 patients, who represent all of the patients seen at this institution during the years 1970 to 1973, inclusive, who were 40 years of age or older, had hemodynamically significant aortic valvular stenosis as an essentially isolated valvular lesion,, and had a technically satisfactory selective coronary arteriogram as part of their cardiologic evaluation. The group includes 156 who later had surgical treatment for aortic stenosis at this institution, with or without simultaneous coronary bypass surgery. T h e cardiac catheterization and angiographic studies were performed at this institution in 100 of these and elsewhere in 56. Also included are 17 who did not have aortic valvular surgery for various reasons, even though cardiac catheterization did show hemodynamically significant aortic stenosis; all but one of these, a man who died suddenly the day before scheduled surgery, had their angiographic studies
March, 1977, Vol. 93, No. 3, pp. 382-393
Aortic stenosis, angina pectoris, and coronary artery dLsease Table I. T h e n u m b e r of patients with tour grades of coronary artery disease in the coronary
arteriogram, according to age and the presence or absence of angina pectoris Age (yr.) 40-49
50-59
60-69
70-81
Sererity of ('oFon~Fy disease
Angiml
No angina
Angina
0
4
2
14
8
6
8
1
1
+ + +
1 1
1 0
7 3
5 0
10 ll
1 2
3 7
4 0
+ + +
3
0
15
:1
25
6
17
4
d No angina
in this institution. Reference is also made to the 148 patients 40 years of age or older who had surgical t r e a t m e n t of isolated aortic valvular stenosis during 1970 to 1973 without preoperative coronary arteriography. Aortic stenosis was considered h e m o d y n a m i cally significant if the calculated aortic valve area was less than 0.80 cmY per square meter.' .... One patient was included although the aortic valve area was 1.1 cm.=' per square m e t e r because the stenosis was considered significant both clinically and at the time of operation, and aortic valve replacement was carried out. In four patients the cardiac o u t p u t and hence the aortic valve area were not determined, but in each of these the transaortic systolic pressure gradient exceeded 40 mm. Hg and severe stenosis was confirmed at operation. Eleven patients were included although the left ventricular pressure had not been determined; in each of these the aortic stenosis was obviously severe at the time of operation and aortic valve replacement was carried out. A twelfth patient who was included although the gradient and valve area were not determined had mild to m o d e r a t e aortic stenosis at operation and had d e b r i d e m e n t - v a l v o t o m y procedure r a t h e r t h a n aortic valve replacement; coronary arteriogr a p h y was normal in this patient and his symptoms of m o d e r a t e dyspnea and angina on effort were therefore a t t r i b u t e d to m o d e r a t e aortic stenosis. Patients with mixed aortic stenosis and regurgitation were included if the stenosis was considered the p r e d o m i n a n t lesion. This conclusion required a d e m o n s t r a t i o n of a pressure gradient of more t h a n 50 mm. Hg, an arterial pulse of slowrising late-peaked type, and a visual evaluation at the time of operation t h a t the stenosis was marked and was the p r e d o m i n a n t lesion. P a t i e n t s
American Hertrt Journal
Angina
] No angina
A ngin a
No (tnlIDza
with functionally significant mitral valvular disease detected clinically, by cardiac catheterization, or at operation were not included. All of the aortic valves in this series of patients showed calcification, although this was not prerequisite to inclusion. Coronary artery disease was graded absent if the arteries appeared completely normal, and mild if there were areas of irregularity or narrowing of less t h a n 50 per cent of the lumen caliber or if calcification in the vessel wall was seen, without luminal narrowing. It was graded m o d e r a t e if one or more areas of narrowing in the range of 50 to 70 per cent were present, and severe if one or more areas of narrowing greater than 70 per cent were present. Statistical significance was determined by the chi-square method. In much of the analysis the normal and mild cases and the moderate and severe cases are grouped together, giving one group with no significant lesions and a second group with significant occlusive coronary a r t e r y disease. T w o patients were included who had selective study of only one of the two main coronary arteries, showing severe lesions on the side which was visualized. Patients who showed no severe lesions in incomplete studies were not included. Results
T h e n u m b e r of patients with the four grades of coronary a r t e r y disease, according to age and the presence or absence of angina pectoris, is given in Table I. Significant occlusive c o r o n a r y lesions were found in 56 per cent of the total group, including 53 per cent of the 156 surgical patients. This figure may overestimate the true over-all incidence because c o r o n a r y a r t e r i o g r a p h y was performed more f r e q u e n t l y in patients with clinical evidence of c o r o n a r y disease. T h e lower limit
383
Hancock
II. Distribution of significant coronary occ.lusive lesions in 97 patients
Table
70 60--
Single lesions: o
(4 I--
z
LAD~ I,CCA RCA
I
50 -
Ul I-P.
Double lesions:
LMCA--I,AD I,AD-LCCA I,AD-RCA RCA-IA:CA
40 B
6 z
11 3 14
30 -
1 14 1't
6
Triple and quadruple h'sions:
20 10
i
76%
- + ++
LMCA--I,AD-I,CCA LMCA-I.AI)-I{CA LMCA-I,CCA-I{CA I,AD-L('('A-RCA LM(?A-I,AD-LCCA-RCA
1
1 1 26 5
" A b b r e v i a t i o n s : L A I ) = h!ft a n t e r i o r d e s c e n d i n g c o r o n a r y a r t e r y : I,CCA = lelt circumflex c o r o n a r y a r t e r y ; }'~CA = right c o r o n a r y a r t e r y ; L M C A = lett m a i n c o r o n a r y a r t e r y .
AGE
40-49
50-59
60-69
70-83
Fig. 1. The incidence of coronary artery disease in 173 patients with aortic stenosis, according to age. Significant coronary disease ( + + or + + + ) is more frequent in those aged 60 to 69 yeal,'s than tho~ aged 50 to 59 (P = < 0.01). The differences between those aged 40 to 49 and 50 to 59 and between tho~ aged 60 to 69 and 70 to 83 are not statistically significant.
of the true over-all incidence m a y be estimated from the group of 87 surgical patients in 1973, in w h o m coronary a r t e r i o g r a p h y was performed in 59 and significant c o r o n a r y disease was found in 32, or 38 per cent of the total. Thus, the true overall incidence in the surgical patients is p r o b a b l y in the range of 40 to 50 per cent. T h e incidence of significant c o r o n a r y disease increased markedly with age, being 33 per cent in patients aged 40 to 49, 38 per cent in those aged 50 to 59, 64 per cent in those aged 60 to 69, and 76 per cent in those over 70 years of age (Fig. 1). T h e corresponding figures for the 156 surgical patients were 27, 38, 61, and 74 per cent. T h e corresponding figures for the 87 surgical cases in 1973, assuming n o r m a l c o r o n a r y vessels in those n o t studied by c o r o n a r y arteriography, were 0, 12, 55, and 60 per cent. T h u s a n y figure given for the over-all incidence m u s t depend heavily on the age composition of the group in question. There was no over-all difference according to sex, coronary disease occurring in 60 per cent of women and 56 per cent of men. T h e incidence was
384
63 per cent (5 of 8) in w o m e n aged 60 to 69 and 75 per cent (9 of 12) in w o m e n aged 70 and over. Only five w o m e n under age 60 were studied, and only one of these had significant c o r o n a r y disease, a w o m a n aged 42 who had severe type II hypercholesterolemia, multiple previous m y o c a r d i a l infarctions with a ventricular a n e u r y s m , and m o d e r a t e aortic stenosis. T h u s it seems likely t h a t w o m e n under age 60 with aortic stenosis have a lower prevalence of c o r o n a r y disease t h a n do men of the same age, b u t the n u m b e r studied is too small to permit a firm conclusion. T h e distribution of c o r o n a r y occlusive lesions a m o n g the four principal c o r o n a r y arteries is given in Table II. T h e left anterior descending artery was the vessel m o s t frequently involved, and combinations involving two or three m a j o r vessels were more frequent t h a n single-vessel involvement, as is observed in c o r o n a r y artery disease generally. Marked obstruction of the left main c o r o n a r y artery occurred in 10 patients, all of w h o m had multivessel disease. T h e lesions were at the left coronary ostium in three of these patients. Right c o r o n a r y ostial lesions of significant degree were identified in six patients and in two these were the only c o r o n a r y lesions present. Calcification of the left main c o r o n a r y a r t e r y was noted in 27 patients, only two of w h o m showed significant obstruction of t h a t artery, b u t 21 of them had lesions elsewhere in the proximal c o r o n a r y arteries.
Mttrch, 1977, Vol. 9,'3, No. 3
Aortic stenosis, angina pectoris, and coronary artery disease
Table III. T h e n u m b e r of patients with each of four types of chest pain syndromes, according to the severity of occlusive lesions fi)und on coronary arteriography
70
60
Severity of coroll(t~ disease
AS-t)pe ~: a ngin.
i) + + + + ++
17 15 10 16
CA l)-type Nonanginal No pain chest pain angina 8 6 12 44
5 3 1 5
14 8 1 8
"AS-type refers to angina pe¢'toris which occurs only with physical exertion and in as.~ociation with dyspnea on exertion, or ill a fcw instances during paroxysmal t a c h y a r r h y t h m i a s as well. CAl)-type refevs to angina [x,ctoris which occurs on exertion, but without dyspnea on exertion, or which also occurs with emotional st re.~% after lll(~alS, o r at rcst, including n o c t u r n a l angina. Abbreviations are as given in TabIe II.
03 I-Z UJ F-
50
