Catheterization and Cardiovascular Diagnosis 2:157-164 (1976)
AORTIC STENOSIS, ANGINA PECTORIS, CORONARY ARTERY DISEASE Roger E. Moraski, M.D., Richard 0. Russell, Jr., M.D., F.A.C.C., John A. Mantle, M.D., and Charles E. Rackley, M.D., F.A.C.C. The data from 88 patients (pts) with aortic stenosis (AS) were reviewed to determine relationships betweenangina pectoris (AP) and coronary artery disease(CAD). Results of surgery performedin 81 of these pts was analyzed. All pts hadcoronary arterlograms, and lesions P 50% were considered significant. Fifty-nine pts had an aortic valve gradient measured at catheterization 2 40 mmHg, and in 29 pts, AS was confirmed at operation. Sixty-elght pts (77%) experienced AP, and 32 had coexisting CAD (47%); 9 of 20 pts without AP had CAD (45%). There were no significant differences Inthe incicknce of AP in pts divided into subgroups by the aortic valve gradknt (40-50, 51-100, 101-200 mmHg) or age (40-59, 6 0 4 1 years). Also, no significant differences were found in the incidenceor extent of CAD between the two age groups; the extent of CAD was similar regardless of the presence or absence of AP. in pts with AP (1) CAD was more likely in pts P 60years of age; (2) CAD was less likely when the aortic valve gradknt was > 100 mmHg, suggesting that AP in these pts was due to hemodynamicallysevem AS. All pts with 3-vessel CAD experienced AP, and the aortic valve gradknt was less in these pts than in those with no CAD or less extensive CAD. in 19 pts with combined AS and CAD who had both the aortic valve replaced and a revascuiarlzatlonoperation only 1of pts died in the hospital, while 3 of 19 pts with combined AS and CAD who had aortk valve replacement alone died. inthis study a signlfkant number of pts with AS experiencedAP, and the presenceor absence of AP did not predict coexisting CAD. Coronary arteriographyis recommended in the evaluation of pts a 40 years of age with AS. The operative mortailty appearsto be decreased in pts with AS and CAD who have combined surgery. Key words: angina pectoris, coronary artery diseaae, aortic valve, calcitic aortic stenosis, valvular heart disease From the University of Alabama Medical Center, Birmingham, Alabama
This research was supported in part by the Myocardial Infarction Research Unit Program, contract no. HL 43-67-1441;the Cardiovascular Research and TrainingCenter, program project grant no. HL 11,3 10 (Division of Heart and Vascular Diseases, National Heart and Lung Institute); and the Clinical Research Unit grant no. MOI-RR00032-13 (General Clinical Research Centers Program, Division of Research Resources), National Institutes of Health. Reprint requests to: C. E. Rackley, M.D., Division of Cardiology, University of Alabama in Birmingham, University Station, Birmingham, Alabama 35294. Received January I , 1975; revision accepted October 2, 1975. 157
0 1 9 7 6 Alan R. Liss, Inc., 150 Fifth Avenue, New York, N.Y. 10011
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INTRODUCTION
The diagnosis of atherosclerotic coronary artery disease in patients with aortic stenosis is difficult since symptoms of myocardial ischemia occur as a manifestation of left ventricular pressure overload (1,2). Surgical correction of aortic stenosis is frequently considered at an age when the incidence of coronary artery disease is significant, and angina pectoris in these patients may be due to coexisting coronary artery disease (3,4). Ischemic heart disease has been implicated as a mechanism for left ventricular dysfunction in certain patients following successful aortic valve surgery (3, and sudden death in the late postoperative period has been associated with severe coronary artery disease (6). Since the combination of saphenous vein bypass grafting with aortic valve surgery has been shown to be feasible (7,8), such revascularization may serve to maintain left ventricular function and reduce morbidity and mortality. The data from 88 patients with aortic stenosis who underwent coronary arteriography over a four-year period were reviewed to determine the incidence of angina pectoris and coronary artery disease. Results of surgical intervention in 8 1 patients was analyzed. METHODS
Sixty-seven men and 21 women with symptoms and physical findings of aortic stenosis comprised the study group. Angina pectoris was defined as substernal or precordial chest discomfort occurring at rest or precipitated by exertion and/or emotional stress, and relieved by rest and/or nitroglycerin. Coronary arteriograms were performed by the Judkins technique (9)in 67patients and by the Sones method (10) in 21 patients; coronary lesions were considered significant if 50% or more of the lumen was stenotic. The left ventricle was catheterized in a retrograde fashion in 57 of the 59 patients whose aortic valve gradient was measured and by the transseptal technique in 2 patients. All patients whose gradient was measured required a peak aortic valve gradient of at least 40 mmHg to be included in the study. In 29 patients the gradient was not measured, but significant aortic valve stenosis was confirmed at surgery. All of these 29 patients had a stenotic aortic valve orifice; 28 patients had heavy calcification of the valve leaflets and ring; 22 patients had severe left ventricular hypertrophy; and 17 patients had bicuspid valve. Poststenotic dilatation of the aorta was observed in 12 patients. The incidence of angina pectoris and coronary artery disease was analyzed for the whole group. Patients were than analyzed by subgroups based on the (1) severity of the aortic valve gradient, (2) age, and (3) extent of coronary artery disease. Eighty-one patients were operated on with the aortic valve being replaced. The operative mortality was analyzed for 3 groups of patients: (1) 43 patients with aortic valve disease alone; (2) 19 patients with aortic stenosis and abnormal coronary arteriograms who underwent aoritc valve replacement alone; and (3) 19 patients with aortic stenosis and coexisting coronary disease who had both aortic valve replacement and saphenous vein bypass surgery. Statistical analysis was done by the standard t test and chi-square methods.
Angina Pectoris in Aortic Stenosis
159
No Angina Pectoris 20 pts.
'AD DtS.
\ I No CAD 36 pts.
32 pts.
\
Angina Pectoris 68 pts.
Fig. 1. Relationship between angina pectoris and coronary artery disease in 88 patients with aortic stenosis. (CAD = coronary artery disease; pts. = patients)
RESULTS
The Group As A Whole The patients ranged in age from 3 1 to 81 years, with a mean age of 59 years. Only 4 patients were less than 40 years of age. Fig. 1 shows the relationship between angina pectoris and coronary artery disease. Sixty-eight of the 88 patients experienced angina pectoris, and 20 patients did not have angina. Thirty-two of the 68 patients with angina pectoris had angiographically demonstrable coronary artery disease; 9 of the 20 patients without angina had coronary artery disease.
Aortic Valve Gradient Fig. 2 demonstrates the incidence of angina pectoris and coronary artery disease in 59 patients divided into 3 groups by the severity of the transaortic valve gradient. In 13 patients with gradients between 40 and 50 mmHg, 8 (62%) had anginapectoris, and 4 of these patients had coronary artery disease. There were 35 p9tients with gradients between 51 and 100 mmHg, and 3 1 or 8% had angina pectoris; 17 of these patients (55%) had coronary artery disease. Eleven patients had measured gradients of more than 100 mmHg: 8 had angina pectoris and only 3 (38%) had associated coronary artery disease (p < 0.05). Fig. 2 also shows the incidence of coronary disease in the 12 patients without angina pectoris. Five patients had gradients between 40-50 mmHg, and 1 patient had coronary artery disease; 2 of 4 patients with gradients between 51 and 100 mmHg, and 2 of 3 patients with gradients greater than 100 mmHg had coronary disease. Analysis By Age
The data were further analyzed by dividing the patients into 3 age groups.
160
Moraski e t a l .
0No Angina
40 -.
35
Angina Pectoris CAD
30
z
25
w e
20
( I
15
U
11
10 5 0
40-50
51-100
101-200
mmHg mmHg mmHg AORTIC VALVE GRADIENT Fig. 2. incidence of angina pectoris and coronary artery disease in 59 patients divided by the severity of the aortic valve gradient.
Patients40 to 59 years of age. There were 39 patients in this age group (Table I). Thirty patients (77%) had angina pectoris, and 16 (41%) had coronary artery disease. Eight patients had one-vessel disease, 6 had two-vessel disease, and 2 patients had three-vessel disease, with a mean of 1.6 vessels diseased per patient. Table I1 shows that 1 1 of the 16 patients with coronary disease had angina pectoris, and 5 patients did not. A mean of 1.7 coronary arteries are diseased per patient in the 11 with angina, and 1.4 vessels per patient are diseased in those patients without angina pectoris. The meangradient in the former group is 77 mmHg (measured in 8 of the 11 patients) and in the latter, 89 mmHg. There is no significant difference between these 2 groups of patients (p > 0.3). Nineteen patients with angina pectoris and 4 patients without angina did not have coronary artery disease. There was no significant difference in the aortic valve gradient in these 2 groups of patients, although only 2 of 4 patients without angina had their aortic valve gradient measured (125 mmHg and 49 mmHg). Patients more than 60 years of age. There were 45 patients in this age group (Table I). Thirty-six (80%) had angina pectoris, and 23 (51%) had coronary artery disease. Eight patients had one-vessel disease, 7 had two-vessel TABLE I .
Incidence of Angina Pectoris and Coronary Artery Disease and Their Relationship to Each Other in Three Age Groups
Age group (years)
No. of patients
Angina pectoris
40-59 60-81 Q value
39 45
30(77%) 36(80%) NS
30-39
4
2(50%)
CAD
16(41"%) 23(5 1 %) NS 2(50%)
No. of vessels per patient 1.6
2 .o NS 1 .o
CAD/ AP
11/30(37%) 20/36(56%) 0.1 1/2
AP = angina pectoris; CAD = coronary artery disease; NS = not significant.
CAD/ noAP
5/9 3/9 NS 1 /2
Angina Pectoris in Aortic Stenosis
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TABLE I I . Extent of Coronary Artery Disease and Severity of Aortic Stenosis in Two Age Groups in the Presence or Absence of Coronary Artery Disease and Angina Pectoris ~~
60-81 years of age
40-59 years of age
CAD
Present
Absent
Angina pectoris
No. of patients
No. of vessels per patient
Present Absent p value
11 5
1.7 I .4 NS
Present Absent p value
19 4
0 0
Gradient mmHg
No. of patients
No. of vessels per patient
Gradient mmHg
77(8 pts) 89 NS
20 3
2.1 1.7 NS
73(16 pts)
9 3 ( 1 3 pts) 125 and 49 NS
16 6
0 0
67(10 pts) 50(4 pts) NS
disease, and 8 patients had three-vessel disease, with a mean of 2.0 vessels diseased per patient. In Table I1 it is seen that 20 of 23 patients with coronary artery disease had angina, and 3 did not. Table I1 also shows that 2.1 vessels per patient are involved in the 20 patients with angina and coexisting coronary artery disease, and 1.7 vessels per patient are diseased in the 3 patients without angina pectons (p = 0.5). The mean gradient measured in 16 of the 20 patients was 73 mmHg and was not measured in the 3 patients without angina. There were no statistically significant differences between the 2 age groups in the incidence of angina pectoris, coronary artery disease, average number of vessels diseased per patient, or incidence of coronary disease in those patients without angina pectoris (p = 0.4). A greater percentage of patients with angina had coronary disease in the older age group (56% vs 37%), but this did not reach significance, p = 0.1 (Table I). Sixteen patients with and 6 patients without angina pectoris did not have coronary artery disease. There was no significant difference in the gradient between these 2 groups of patients (p = 0.2). Patients less than 40 years of age. There were only 4 patients less than 40 years of age. Two had angina pectoris, one with coexisting one-vessel coronary disease, and two did not have angina, but one of these patients also had onevessel coronary disease.
TABLE I l l . Mean Age, Aortic Valve Gradient, and Incidence of Angina Pectoris in Patients With No Coronary Artery Disease, in One-, Two- or Three-Vessel Coronary Artery Disease
No. of vessels diseased
No. of patients
None 1V CAD 2V CAD 3V CAD
47 18 13 10
Age (years) (Mean * SEM)
58 2 58 * 63 * 62 t
77 t 88 * 80 f 53 *
1.5 3.1 2.7 1.8
SEM = standard error of the mean: V
=
Gradient (mmHg) (Mean t SEM)
vessel.
6 (30 pts) 9(13 pts) 9 (9 pts) 4 (7 DtS)
Angina pectoris no. of patients (70) 36(76) 13(72) 9 (69) 1O(100)
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Moraski et at.
Extent Of Coronary Artery Disease
In Table 111 the patients are divided into 4 groups: ( I ) 47 patients with angiographically normal coronary arteries; (2) 18 patients with one-vessel diseasf . (3) 13 patients with two-vessel disease; and (4) 10 patients with three-vessel coronary artery disease. The mean age, mean aortic valve gradient, and incidence of angina pectoris is comparable for the group; the gradient is somewhat lower (53 mmHg) in the patients with three-vessel disease, and 100% of these patients have angina pectoris. Results Of Operation (Table IV)
Forty-three of the 47 patients without angiographically detectable coronary disease underwent aortic valve replacement; 4 patients died postoperatively. Thirty-eight of 41 patients with coronary disease were operated upon. Nineteen patients had aortic valve replacement alone, and 3 of these patients died in the immediate postoperative period. The extent of coronary artery disease occluding at least 50% of the coronary lumen was 1.5 vessels diseased per patient. Nineteen patients had aortic valve replacement combined with saphenous vein bypass surgery; only one patient died. The extent of coronary disease occluding at least 50% of the arterial lumen was 2.1 vessels per patient. These differences are not statistically significant. DISCUSSION
More than 75% of the patients in this series described angina pectoris, and nearly one-half (47%) of these patients were found to have coexisting coronary artery disease (Fig. I). This high incidence of angina pectoris is comparable to that reported by Berndt et a1 (1 1) but is higher than in other studies (1 3).Furthermore, in this group of patients with aortic stenosis the absence of angina pectons did not guarantee that the coronary arteriograms would be normal, as almost one-half of these patients were found to have normal coronary arteriograms. It must be emphasized that angina pectoris was considered present only if patients complained of substernal or precordial chest discomfort which was precipitated by exertion and relieved by rest and/or nitroglycerin. Such pain could also occur at rest and either abate spontaneously or require use of nitroglycerin. Chest pain clearly chest wall in origin or fleeting in nature was not TABLE I V . Comparison of Operative Mortality for Patients With Aortic Stenosis With and Without C A D Undergoing Aortic Valve Replacement Alone or Combined With SVBG in 81 Patients
Isolated aortic stenosis Surgery Patients No. vessels per patient Mortality
Aortic valve 43
0 4(9%)
Aortic stenosis and CAD Aortic valve
Aortic valve and SVRG
19
19
1.5 3(167r)
?.I 1(5';?c)
CAD = coronary artery disease; SVRC = saphenous vein bypass grafting.
Angina Pectoris in Aortic Stenosis
163
considered to be angina pectoris. Therefore, coronary arteriography was found to be essential if coronary artery disease is to be diagnosed in patients with aortic stenosis. In our catheterization laboratory the aortic valve gradient is measured prior to arteriography , as hemodynamic measurements are affected by radiographic contrast agents. The incidence of angina pectoris and coronary disease was thus analyzed to determine whether the transvalvular gradient could predict the presence or absence of coronary artery disease, thus obviating the need for arteriography. The data fail to demonstrate statistical differences in the incidence of angina pectoris or coronary disease in patients with gradients equal to or less than 100 mmHg. However, only 3 (38%) of 8 patients with angina pectoris and gradients over 100 mmHg had coronary artery disease (p < 0.05). This suggests that with severe aortic stenosis, the valvular abnormality plays a greater role in the mechanism of angina pectoris. Conversely, all patients with extensive or three-vessel coronary artery disease have angina pectoris, and the aortic valve gradient is less than in those with either none or less extensive (one- or twovessel) coronary artery disease (Table 111). Left ventricular function in patients with three-vessel disease even without prior myocardial infarction has been described as being depressed (12). Thus, the finding of a lower aortic valve gradient and angina pectoris in all of the patients with three-vessel coronary artery disease suggests that extensive coronary artery disease contributes to impaired myocardial function, which, with pure aortic stenosis, appears late in the course of the disease. It may be that a transaortic valve gradient comparable to that seen in patients with less extensive coronary artery disease cannot be generated. These findings agree with those of Berndt et a1 (1 t). Their patients with aortic stenosis and coexisting coronary artery disease had lower gradients than those without coronary artery disease. Analysis of patients above and below the age of 60 failed to reveal any differences in the incidence of angina pectoris and the presence or extent of coronary artery disease (Table I). Furthermore, the extent of coronary artery disease in patients with and without angina was similar in the two age groups (Table 11). However, a higher percentage of patients in the older age group with angina did have coexisting coronary artery disease (Table I, p = 0.1). If significant narrowing of a coronary artery is taken as 70% or more of the arterial lumen, the incidence of coronary artery disease in patients with angina pectoris becomes significantly higher in the older age group: 17 of 36 (47%) in patients 60 years of age or older vs 7/30 (23%) in patients between 40 and 59 years of age, p = 0.04. In this study, there are only 4 patients less than 40 years of age, since coronary arteriography is usually not performed in patients with aortic stenosis in this age group. It seems, however, that the presence or absence of coronary disease cannot be predicted even in this group: 1 of 2 patients with and without angina had one-vessel coronary artery disease. Although a patient is more likely to have coexisting coronary disease if he is over 60 years of age and is experiencing angina pectoris, the results of this study indicate that it is difficult to predict the presence or absence of angiographically detectable coronary artery disease on the basis of clinical or hernodynamic information. In patients with clinically significant aortic valve stenosis, the definition of the coronary anatomy may prove to be more important than measurement of the aortic
164
Moraski et at.
valve gradient, since myocardial revascularization with the aortocoronary saphenous veingraft can be combined with aortic valve replacement (7,8. 11). The rationale for combining coronary bypass surgery with valve replacement in patients with aortic stenosis and coronary artery disease is to reduce operative mortality, relieve symptoms, and improve long-term survival by preventing subsequent myocardial infarction due to coronary atherosclerosis. Although follow-up studies have shown good relief of symptoms and long-term survival comparable to survival of patients without associated coronary artery disease (8,l l ) , there are no available studies comparing the operative risk of combining aortic valve replacement and myocardial revascularization to aortic valve replacement alone in patients with coronary artery disease. In this study 3 of 19 patients who had only their aortic valve replaced died, while only 1 of 19 patients who underwent the combined operation died; and this latter group of patients had more extensive coronary disease (Table IV). Although the difference in operative mortality does not reach statistical significance in this small group of patients, it is suggested that revascularization does decrease the risk of aortic valve surgery in patients with associated coronary artery disease. ACKNOWLEDGMENTS
We wish to acknowledge the secretarial assistance of Miss Pam Pierce and the technical assistance of Mrs. Charlotte Phillips. REFERENCES I . Bonchek L1, Anderson RP and Rosch J: Should coronary arteriography be performed routinely before valve replacement? Amer J Cardiol 3 1 :462466, 1973. 2 . Fallen EL, Elliott WC and Gorlin R: Mechanisms of angina in aortic stenosis. Circulation 36:48& 488, 1%7. 3 . Coleman EH and Soloff LA: Incidence of significant coronary artery disease in rheumatic valvular heart disease. Amer J Cardiol 25:401404. 1970. 4. Muller C: Aortic stenosis and the so-called rheumatic valvular diseases in a postmortem material. Acta Med Scand 156:4. 1956. 5 . Linhart J W. de la Torre A Ramsey H W and Wheat MW: The significance of coronary artery disease in aortic valve replacement. J . Thor Cardiovasc Surg 55:811-819. 1968. 6 . Roberts WC and Morrow AG: Late postoperative pathological findings after cardiac valve replacement. Circulation (Suppl I ) 35. 36:14842. 1967. 7 . Loop ED, Favaloro RG. Shirey EK. Groves LK and Emer DB: Surgery for combined valvular and coronary heart disease. JAMA 220:372-376, 1972. 8. Berger TJ. Karp RB and Kouchoukos. NT: Valve replacement and myocardial revascularization: results of combined operation in 59 patients. Circulation (Suppl I). 52:126-132. 1975. 9. Judkins MP: Percutaneous transfemoral selective coronary arteriography. Radio1 Clin N Amer V1,3:467-492. 1%8. 10. Sones FM and Shirey EK: Cine coronary arteriography. Mod Conc Cardiovas Dis 3 (7) 1962. I I . Berndt TB, Hancock EW, Shumway N E and Harrison DC: Aortic valve replacement with and without coronary artery bypass surgery. Circulation 50:967-971, 1974. 12. Moraski RE, Russell RO, Jr.. Smith McK and Rackley CE: Left ventricularfunctioninpatients with and without myocardial infarction and either one. two or three vessel coronary artery disease. Amer J Cardiol 35:1-10, 1975.
AORTIC STENOSIS, ANGINA PECTORIS, CORONARY ARTERY DISEASE Roger E. Moraski, M.D., Richard 0. Russell, Jr., M.D., F.A.C.C., John A. Mantle, M.D., and Charles E. Rackley, M.D., F.A.C.C. The data from 88 patients (pts) with aortic stenosis (AS) were reviewed to determine relationships betweenangina pectoris (AP) and coronary artery disease(CAD). Results of surgery performedin 81 of these pts was analyzed. All pts hadcoronary arterlograms, and lesions P 50% were considered significant. Fifty-nine pts had an aortic valve gradient measured at catheterization 2 40 mmHg, and in 29 pts, AS was confirmed at operation. Sixty-elght pts (77%) experienced AP, and 32 had coexisting CAD (47%); 9 of 20 pts without AP had CAD (45%). There were no significant differences Inthe incicknce of AP in pts divided into subgroups by the aortic valve gradknt (40-50, 51-100, 101-200 mmHg) or age (40-59, 6 0 4 1 years). Also, no significant differences were found in the incidenceor extent of CAD between the two age groups; the extent of CAD was similar regardless of the presence or absence of AP. in pts with AP (1) CAD was more likely in pts P 60years of age; (2) CAD was less likely when the aortic valve gradknt was > 100 mmHg, suggesting that AP in these pts was due to hemodynamicallysevem AS. All pts with 3-vessel CAD experienced AP, and the aortic valve gradknt was less in these pts than in those with no CAD or less extensive CAD. in 19 pts with combined AS and CAD who had both the aortic valve replaced and a revascuiarlzatlonoperation only 1of pts died in the hospital, while 3 of 19 pts with combined AS and CAD who had aortk valve replacement alone died. inthis study a signlfkant number of pts with AS experiencedAP, and the presenceor absence of AP did not predict coexisting CAD. Coronary arteriographyis recommended in the evaluation of pts a 40 years of age with AS. The operative mortailty appearsto be decreased in pts with AS and CAD who have combined surgery. Key words: angina pectoris, coronary artery diseaae, aortic valve, calcitic aortic stenosis, valvular heart disease From the University of Alabama Medical Center, Birmingham, Alabama
This research was supported in part by the Myocardial Infarction Research Unit Program, contract no. HL 43-67-1441;the Cardiovascular Research and TrainingCenter, program project grant no. HL 11,3 10 (Division of Heart and Vascular Diseases, National Heart and Lung Institute); and the Clinical Research Unit grant no. MOI-RR00032-13 (General Clinical Research Centers Program, Division of Research Resources), National Institutes of Health. Reprint requests to: C. E. Rackley, M.D., Division of Cardiology, University of Alabama in Birmingham, University Station, Birmingham, Alabama 35294. Received January I , 1975; revision accepted October 2, 1975. 157
0 1 9 7 6 Alan R. Liss, Inc., 150 Fifth Avenue, New York, N.Y. 10011
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Moraski et at.
INTRODUCTION
The diagnosis of atherosclerotic coronary artery disease in patients with aortic stenosis is difficult since symptoms of myocardial ischemia occur as a manifestation of left ventricular pressure overload (1,2). Surgical correction of aortic stenosis is frequently considered at an age when the incidence of coronary artery disease is significant, and angina pectoris in these patients may be due to coexisting coronary artery disease (3,4). Ischemic heart disease has been implicated as a mechanism for left ventricular dysfunction in certain patients following successful aortic valve surgery (3, and sudden death in the late postoperative period has been associated with severe coronary artery disease (6). Since the combination of saphenous vein bypass grafting with aortic valve surgery has been shown to be feasible (7,8), such revascularization may serve to maintain left ventricular function and reduce morbidity and mortality. The data from 88 patients with aortic stenosis who underwent coronary arteriography over a four-year period were reviewed to determine the incidence of angina pectoris and coronary artery disease. Results of surgical intervention in 8 1 patients was analyzed. METHODS
Sixty-seven men and 21 women with symptoms and physical findings of aortic stenosis comprised the study group. Angina pectoris was defined as substernal or precordial chest discomfort occurring at rest or precipitated by exertion and/or emotional stress, and relieved by rest and/or nitroglycerin. Coronary arteriograms were performed by the Judkins technique (9)in 67patients and by the Sones method (10) in 21 patients; coronary lesions were considered significant if 50% or more of the lumen was stenotic. The left ventricle was catheterized in a retrograde fashion in 57 of the 59 patients whose aortic valve gradient was measured and by the transseptal technique in 2 patients. All patients whose gradient was measured required a peak aortic valve gradient of at least 40 mmHg to be included in the study. In 29 patients the gradient was not measured, but significant aortic valve stenosis was confirmed at surgery. All of these 29 patients had a stenotic aortic valve orifice; 28 patients had heavy calcification of the valve leaflets and ring; 22 patients had severe left ventricular hypertrophy; and 17 patients had bicuspid valve. Poststenotic dilatation of the aorta was observed in 12 patients. The incidence of angina pectoris and coronary artery disease was analyzed for the whole group. Patients were than analyzed by subgroups based on the (1) severity of the aortic valve gradient, (2) age, and (3) extent of coronary artery disease. Eighty-one patients were operated on with the aortic valve being replaced. The operative mortality was analyzed for 3 groups of patients: (1) 43 patients with aortic valve disease alone; (2) 19 patients with aortic stenosis and abnormal coronary arteriograms who underwent aoritc valve replacement alone; and (3) 19 patients with aortic stenosis and coexisting coronary disease who had both aortic valve replacement and saphenous vein bypass surgery. Statistical analysis was done by the standard t test and chi-square methods.
Angina Pectoris in Aortic Stenosis
159
No Angina Pectoris 20 pts.
'AD DtS.
\ I No CAD 36 pts.
32 pts.
\
Angina Pectoris 68 pts.
Fig. 1. Relationship between angina pectoris and coronary artery disease in 88 patients with aortic stenosis. (CAD = coronary artery disease; pts. = patients)
RESULTS
The Group As A Whole The patients ranged in age from 3 1 to 81 years, with a mean age of 59 years. Only 4 patients were less than 40 years of age. Fig. 1 shows the relationship between angina pectoris and coronary artery disease. Sixty-eight of the 88 patients experienced angina pectoris, and 20 patients did not have angina. Thirty-two of the 68 patients with angina pectoris had angiographically demonstrable coronary artery disease; 9 of the 20 patients without angina had coronary artery disease.
Aortic Valve Gradient Fig. 2 demonstrates the incidence of angina pectoris and coronary artery disease in 59 patients divided into 3 groups by the severity of the transaortic valve gradient. In 13 patients with gradients between 40 and 50 mmHg, 8 (62%) had anginapectoris, and 4 of these patients had coronary artery disease. There were 35 p9tients with gradients between 51 and 100 mmHg, and 3 1 or 8% had angina pectoris; 17 of these patients (55%) had coronary artery disease. Eleven patients had measured gradients of more than 100 mmHg: 8 had angina pectoris and only 3 (38%) had associated coronary artery disease (p < 0.05). Fig. 2 also shows the incidence of coronary disease in the 12 patients without angina pectoris. Five patients had gradients between 40-50 mmHg, and 1 patient had coronary artery disease; 2 of 4 patients with gradients between 51 and 100 mmHg, and 2 of 3 patients with gradients greater than 100 mmHg had coronary disease. Analysis By Age
The data were further analyzed by dividing the patients into 3 age groups.
160
Moraski e t a l .
0No Angina
40 -.
35
Angina Pectoris CAD
30
z
25
w e
20
( I
15
U
11
10 5 0
40-50
51-100
101-200
mmHg mmHg mmHg AORTIC VALVE GRADIENT Fig. 2. incidence of angina pectoris and coronary artery disease in 59 patients divided by the severity of the aortic valve gradient.
Patients40 to 59 years of age. There were 39 patients in this age group (Table I). Thirty patients (77%) had angina pectoris, and 16 (41%) had coronary artery disease. Eight patients had one-vessel disease, 6 had two-vessel disease, and 2 patients had three-vessel disease, with a mean of 1.6 vessels diseased per patient. Table I1 shows that 1 1 of the 16 patients with coronary disease had angina pectoris, and 5 patients did not. A mean of 1.7 coronary arteries are diseased per patient in the 11 with angina, and 1.4 vessels per patient are diseased in those patients without angina pectoris. The meangradient in the former group is 77 mmHg (measured in 8 of the 11 patients) and in the latter, 89 mmHg. There is no significant difference between these 2 groups of patients (p > 0.3). Nineteen patients with angina pectoris and 4 patients without angina did not have coronary artery disease. There was no significant difference in the aortic valve gradient in these 2 groups of patients, although only 2 of 4 patients without angina had their aortic valve gradient measured (125 mmHg and 49 mmHg). Patients more than 60 years of age. There were 45 patients in this age group (Table I). Thirty-six (80%) had angina pectoris, and 23 (51%) had coronary artery disease. Eight patients had one-vessel disease, 7 had two-vessel TABLE I .
Incidence of Angina Pectoris and Coronary Artery Disease and Their Relationship to Each Other in Three Age Groups
Age group (years)
No. of patients
Angina pectoris
40-59 60-81 Q value
39 45
30(77%) 36(80%) NS
30-39
4
2(50%)
CAD
16(41"%) 23(5 1 %) NS 2(50%)
No. of vessels per patient 1.6
2 .o NS 1 .o
CAD/ AP
11/30(37%) 20/36(56%) 0.1 1/2
AP = angina pectoris; CAD = coronary artery disease; NS = not significant.
CAD/ noAP
5/9 3/9 NS 1 /2
Angina Pectoris in Aortic Stenosis
161
TABLE I I . Extent of Coronary Artery Disease and Severity of Aortic Stenosis in Two Age Groups in the Presence or Absence of Coronary Artery Disease and Angina Pectoris ~~
60-81 years of age
40-59 years of age
CAD
Present
Absent
Angina pectoris
No. of patients
No. of vessels per patient
Present Absent p value
11 5
1.7 I .4 NS
Present Absent p value
19 4
0 0
Gradient mmHg
No. of patients
No. of vessels per patient
Gradient mmHg
77(8 pts) 89 NS
20 3
2.1 1.7 NS
73(16 pts)
9 3 ( 1 3 pts) 125 and 49 NS
16 6
0 0
67(10 pts) 50(4 pts) NS
disease, and 8 patients had three-vessel disease, with a mean of 2.0 vessels diseased per patient. In Table I1 it is seen that 20 of 23 patients with coronary artery disease had angina, and 3 did not. Table I1 also shows that 2.1 vessels per patient are involved in the 20 patients with angina and coexisting coronary artery disease, and 1.7 vessels per patient are diseased in the 3 patients without angina pectons (p = 0.5). The mean gradient measured in 16 of the 20 patients was 73 mmHg and was not measured in the 3 patients without angina. There were no statistically significant differences between the 2 age groups in the incidence of angina pectoris, coronary artery disease, average number of vessels diseased per patient, or incidence of coronary disease in those patients without angina pectoris (p = 0.4). A greater percentage of patients with angina had coronary disease in the older age group (56% vs 37%), but this did not reach significance, p = 0.1 (Table I). Sixteen patients with and 6 patients without angina pectoris did not have coronary artery disease. There was no significant difference in the gradient between these 2 groups of patients (p = 0.2). Patients less than 40 years of age. There were only 4 patients less than 40 years of age. Two had angina pectoris, one with coexisting one-vessel coronary disease, and two did not have angina, but one of these patients also had onevessel coronary disease.
TABLE I l l . Mean Age, Aortic Valve Gradient, and Incidence of Angina Pectoris in Patients With No Coronary Artery Disease, in One-, Two- or Three-Vessel Coronary Artery Disease
No. of vessels diseased
No. of patients
None 1V CAD 2V CAD 3V CAD
47 18 13 10
Age (years) (Mean * SEM)
58 2 58 * 63 * 62 t
77 t 88 * 80 f 53 *
1.5 3.1 2.7 1.8
SEM = standard error of the mean: V
=
Gradient (mmHg) (Mean t SEM)
vessel.
6 (30 pts) 9(13 pts) 9 (9 pts) 4 (7 DtS)
Angina pectoris no. of patients (70) 36(76) 13(72) 9 (69) 1O(100)
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Extent Of Coronary Artery Disease
In Table 111 the patients are divided into 4 groups: ( I ) 47 patients with angiographically normal coronary arteries; (2) 18 patients with one-vessel diseasf . (3) 13 patients with two-vessel disease; and (4) 10 patients with three-vessel coronary artery disease. The mean age, mean aortic valve gradient, and incidence of angina pectoris is comparable for the group; the gradient is somewhat lower (53 mmHg) in the patients with three-vessel disease, and 100% of these patients have angina pectoris. Results Of Operation (Table IV)
Forty-three of the 47 patients without angiographically detectable coronary disease underwent aortic valve replacement; 4 patients died postoperatively. Thirty-eight of 41 patients with coronary disease were operated upon. Nineteen patients had aortic valve replacement alone, and 3 of these patients died in the immediate postoperative period. The extent of coronary artery disease occluding at least 50% of the coronary lumen was 1.5 vessels diseased per patient. Nineteen patients had aortic valve replacement combined with saphenous vein bypass surgery; only one patient died. The extent of coronary disease occluding at least 50% of the arterial lumen was 2.1 vessels per patient. These differences are not statistically significant. DISCUSSION
More than 75% of the patients in this series described angina pectoris, and nearly one-half (47%) of these patients were found to have coexisting coronary artery disease (Fig. I). This high incidence of angina pectoris is comparable to that reported by Berndt et a1 (1 1) but is higher than in other studies (1 3).Furthermore, in this group of patients with aortic stenosis the absence of angina pectons did not guarantee that the coronary arteriograms would be normal, as almost one-half of these patients were found to have normal coronary arteriograms. It must be emphasized that angina pectoris was considered present only if patients complained of substernal or precordial chest discomfort which was precipitated by exertion and relieved by rest and/or nitroglycerin. Such pain could also occur at rest and either abate spontaneously or require use of nitroglycerin. Chest pain clearly chest wall in origin or fleeting in nature was not TABLE I V . Comparison of Operative Mortality for Patients With Aortic Stenosis With and Without C A D Undergoing Aortic Valve Replacement Alone or Combined With SVBG in 81 Patients
Isolated aortic stenosis Surgery Patients No. vessels per patient Mortality
Aortic valve 43
0 4(9%)
Aortic stenosis and CAD Aortic valve
Aortic valve and SVRG
19
19
1.5 3(167r)
?.I 1(5';?c)
CAD = coronary artery disease; SVRC = saphenous vein bypass grafting.
Angina Pectoris in Aortic Stenosis
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considered to be angina pectoris. Therefore, coronary arteriography was found to be essential if coronary artery disease is to be diagnosed in patients with aortic stenosis. In our catheterization laboratory the aortic valve gradient is measured prior to arteriography , as hemodynamic measurements are affected by radiographic contrast agents. The incidence of angina pectoris and coronary disease was thus analyzed to determine whether the transvalvular gradient could predict the presence or absence of coronary artery disease, thus obviating the need for arteriography. The data fail to demonstrate statistical differences in the incidence of angina pectoris or coronary disease in patients with gradients equal to or less than 100 mmHg. However, only 3 (38%) of 8 patients with angina pectoris and gradients over 100 mmHg had coronary artery disease (p < 0.05). This suggests that with severe aortic stenosis, the valvular abnormality plays a greater role in the mechanism of angina pectoris. Conversely, all patients with extensive or three-vessel coronary artery disease have angina pectoris, and the aortic valve gradient is less than in those with either none or less extensive (one- or twovessel) coronary artery disease (Table 111). Left ventricular function in patients with three-vessel disease even without prior myocardial infarction has been described as being depressed (12). Thus, the finding of a lower aortic valve gradient and angina pectoris in all of the patients with three-vessel coronary artery disease suggests that extensive coronary artery disease contributes to impaired myocardial function, which, with pure aortic stenosis, appears late in the course of the disease. It may be that a transaortic valve gradient comparable to that seen in patients with less extensive coronary artery disease cannot be generated. These findings agree with those of Berndt et a1 (1 t). Their patients with aortic stenosis and coexisting coronary artery disease had lower gradients than those without coronary artery disease. Analysis of patients above and below the age of 60 failed to reveal any differences in the incidence of angina pectoris and the presence or extent of coronary artery disease (Table I). Furthermore, the extent of coronary artery disease in patients with and without angina was similar in the two age groups (Table 11). However, a higher percentage of patients in the older age group with angina did have coexisting coronary artery disease (Table I, p = 0.1). If significant narrowing of a coronary artery is taken as 70% or more of the arterial lumen, the incidence of coronary artery disease in patients with angina pectoris becomes significantly higher in the older age group: 17 of 36 (47%) in patients 60 years of age or older vs 7/30 (23%) in patients between 40 and 59 years of age, p = 0.04. In this study, there are only 4 patients less than 40 years of age, since coronary arteriography is usually not performed in patients with aortic stenosis in this age group. It seems, however, that the presence or absence of coronary disease cannot be predicted even in this group: 1 of 2 patients with and without angina had one-vessel coronary artery disease. Although a patient is more likely to have coexisting coronary disease if he is over 60 years of age and is experiencing angina pectoris, the results of this study indicate that it is difficult to predict the presence or absence of angiographically detectable coronary artery disease on the basis of clinical or hernodynamic information. In patients with clinically significant aortic valve stenosis, the definition of the coronary anatomy may prove to be more important than measurement of the aortic
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valve gradient, since myocardial revascularization with the aortocoronary saphenous veingraft can be combined with aortic valve replacement (7,8. 11). The rationale for combining coronary bypass surgery with valve replacement in patients with aortic stenosis and coronary artery disease is to reduce operative mortality, relieve symptoms, and improve long-term survival by preventing subsequent myocardial infarction due to coronary atherosclerosis. Although follow-up studies have shown good relief of symptoms and long-term survival comparable to survival of patients without associated coronary artery disease (8,l l ) , there are no available studies comparing the operative risk of combining aortic valve replacement and myocardial revascularization to aortic valve replacement alone in patients with coronary artery disease. In this study 3 of 19 patients who had only their aortic valve replaced died, while only 1 of 19 patients who underwent the combined operation died; and this latter group of patients had more extensive coronary disease (Table IV). Although the difference in operative mortality does not reach statistical significance in this small group of patients, it is suggested that revascularization does decrease the risk of aortic valve surgery in patients with associated coronary artery disease. ACKNOWLEDGMENTS
We wish to acknowledge the secretarial assistance of Miss Pam Pierce and the technical assistance of Mrs. Charlotte Phillips. REFERENCES I . Bonchek L1, Anderson RP and Rosch J: Should coronary arteriography be performed routinely before valve replacement? Amer J Cardiol 3 1 :462466, 1973. 2 . Fallen EL, Elliott WC and Gorlin R: Mechanisms of angina in aortic stenosis. Circulation 36:48& 488, 1%7. 3 . Coleman EH and Soloff LA: Incidence of significant coronary artery disease in rheumatic valvular heart disease. Amer J Cardiol 25:401404. 1970. 4. Muller C: Aortic stenosis and the so-called rheumatic valvular diseases in a postmortem material. Acta Med Scand 156:4. 1956. 5 . Linhart J W. de la Torre A Ramsey H W and Wheat MW: The significance of coronary artery disease in aortic valve replacement. J . Thor Cardiovasc Surg 55:811-819. 1968. 6 . Roberts WC and Morrow AG: Late postoperative pathological findings after cardiac valve replacement. Circulation (Suppl I ) 35. 36:14842. 1967. 7 . Loop ED, Favaloro RG. Shirey EK. Groves LK and Emer DB: Surgery for combined valvular and coronary heart disease. JAMA 220:372-376, 1972. 8. Berger TJ. Karp RB and Kouchoukos. NT: Valve replacement and myocardial revascularization: results of combined operation in 59 patients. Circulation (Suppl I). 52:126-132. 1975. 9. Judkins MP: Percutaneous transfemoral selective coronary arteriography. Radio1 Clin N Amer V1,3:467-492. 1%8. 10. Sones FM and Shirey EK: Cine coronary arteriography. Mod Conc Cardiovas Dis 3 (7) 1962. I I . Berndt TB, Hancock EW, Shumway N E and Harrison DC: Aortic valve replacement with and without coronary artery bypass surgery. Circulation 50:967-971, 1974. 12. Moraski RE, Russell RO, Jr.. Smith McK and Rackley CE: Left ventricularfunctioninpatients with and without myocardial infarction and either one. two or three vessel coronary artery disease. Amer J Cardiol 35:1-10, 1975.
