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Results of direct coronary artery surgery in women
Results of direct coronary artery surgery in women In the past 4 years, among 260 patients receiving coronary bypass grafts for coronary artery disease and stable angina pectoris, there were 34 women (13 per cent). The operative mortality rate for women was 8 per cent (3 of 34), and one late death due to myocardial infarction occurred in spite of a patent coronary bypass graft. The intraoperative infarction rate was 20 per cent (6 per cent in men). Although preoperative cardiac pump and muscle function parameters were better in women than in men (p < 0.05), postoperatively only 30 per cent of women showed improvement in function as compared with 50 per cent of men. At 6 to 46 months' follow-up, 84 per cent of women were free of angina in contrast with 94 per cent of men. The early (4 month) graft patency rate was 50 per cent (14 of 27 grafts), as opposed to 80 per cent (20 of 25 grafts) in men. These results indicate that, although coronary artery disease shows anatomic similarity in women and men, the result of coronary revascularization in women is inferior to that in the male population.
Hooshang Bolooki, M.D., F.R.C.S.(C),* Abelardo Vargas, M.D., Robert Green, M.D., Gerard A. Kaiser, M.D., and Ali Ghahramani, M.D., Miami, Fla.
Ihe results of saphenous vein grafts in women have usually been reported in combination with those in men and have been considered equally satisfactory.'• - Our experience, however, contrasts with this impression. We have had a larger number of graft closures in women, more technically difficult coronary arteries to work on, and less striking long-term effects on angina pectoris. For those reasons, we made a survey of our results in women who underwent direct myocardial revascularization with a saphenous vein graft. Methods From May, 1969, to October, 1973, 34 women were operated upon. They were From the Divisions of Thoracic and Cardiovascular Surgery and Cardiology. University of Miami School of Medicine, Miami. Fla. 33136. Supported in part by grants from National Heart and Lung Institute, Grant No. HE 13978-03, Heart Association of Greater Miami Inc., and Eli Lilly Research Laboratories, Indianapolis, lnd. Received for publication Aug. 6, 1974. * Research Career Development Awardee, Grant No. HL 70, 670-02.
among 260 patients who underwent myocardial revascularization for stable angina pectoris. Excluded from this study were 4 women seen in the same period who were suffering from so-called preinfarction angina and had emergency myocardial revascularization. All female patients had severe coronary artery disease (18 had multiple vessel involvement) and angina pectoris which was not responsive to conventional medical management including long-acting nitrates (isosorbide dinitrate). One half of them had also received beta blocking agents (propranolol). The age range was 32 to 71 years with an average age of 54 years. Three patients had diabetes mellitus, controlled with drug therapy and diet. Two of these and 2 additional patients had hyperlipidemia (Type IV). Ten women (36 per cent) were overweight. A history of previous myocardial infarction was noted in 4 patients (Table I). All of the women underwent cardiac catheterization studies and hemodynamic evaluation prior to direct myocardial revascu27 1
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Thoracic and Cardiovascular Surgery
Table I. Patient data in women and men after direct myocardial revascularization
Women Men
No.
Average age (yr.)
34 51
54 56
larization. Cardiac catheterization studies were done by Judkin's technique of percutaneous femoral artery approach. The left ventricular angiograms were obtained in the right anterior oblique and left anterior oblique views. Right and left coronary arteriograms were recorded on 35 mm. films with at least two views of each vessel. The cardiac output was calculated by the Fick principle, with blood samples from the pulmonary artery and from the descending aorta being analyzed for oxygen content, and by measurement of oxygen consumption by direct respirometry. Ejection fraction and volumes were calculated from biplane left ventricular angiograms by the methods of Dodge and colleagues" and by assuming the left ventricle to be a thinwall ellipsoid. An index of myocardial contractility was calculated from the left ventricular pressure curves obtained by a transducer catheter prior to left ventricular angiography.' The left ventricular diastolic stiffness (A p/A v) was calculated by the methods of Diamond and Forrester.'1 The surgical procedure was performed by means of cardiopulmonary bypass with normothermia and hemodilution perfusion technique. A reversed segment of the saphenous vein was used for bypass grafting. Sixty-five vein grafts were done in the 34 patients for an average of 1.9 grafts per patient. The anterior descending coronary artery was bypass grafted in every case. Postoperatively, twelve-lead electrocardiograms and serum enzyme studies were obtained in all patients for 3 consecutive days, in order to detect the development of any postoperative myocardial infarction." Postoperative cardiac catheterization studies were conducted in 15 women via methods similar to those described for pre-
Diabetes
Hyperlipidemia
Previous infarction
operative studies. Postoperative follow-up was obtained in all 34 patients. Seventeen patients were seen regularly in an out-patient clinic; others had telephone interviews or were followed by questionnaires. For the purpose of comparison, the clinical courses of 51 consecutive male patients who were operated upon during a sample year (1972) were also analyzed in a similar fashion. Our operative results in this group of patients were similar to those in the entire population of men (226 patients), since operative mortality rate, incidence of perioperative infarction, and graft patency rate have remained unchanged in the past 3 years. The age range for men was 31 to 74 years with an average age of 56 years. The 34 women under study and the 51 men had a comparable extent of coronary artery vessel involvement, previous history of myocardial infarction, and incidence of diabetes and hyperlipidemia (Table I). The preoperative medical management and drug therapy in men was similar to that indicated for women. The results from pre- and postoperative cardiac catheterization studies in 12 of these 51 male patients were available and were used for comparison with those obtained in the female group. Results Clinical course. Three female patients (8 per cent) died in the immediate postoperative period because of myocardial infarction, and 1 died late postoperatively (22 months after surgery). The cause of death in the latter patient was also acute myocardial infarction; she had a patent vein graft to the anterior descending coronary artery. Seven patients (20 per cent) developed infarction in the course of the operation or in the early postoperative
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Table II. Comparison of results of direct myocardial revascularization in women and men Extent of coronary artery disease Women Men
No.
Single
Multiple
34 51
16 23
18 28
Deaths: Operative and late
Perioperative infarct 1 (20%) 3 ( 6%)
3 (8.8%) 1 (2%)
Table III. Comparison of results on follow-up after direct myocardial revascularization in women and men Cardiac
Women Men
Surviving patients
A ngina
31 50
5 (16%) 3 ( 6%)
Late
period (Table II)." The operative and late mortality rate in men was 2 per cent (1 patient), and the perioperative infarction rate was 6 per cent (3 patients). Angiographic data. Fifteen female patients agreed to have postoperative cardiac catheterization studies. Of the 27 coronary bypass grafts studied, only 14 were patent (50 per cent), and the remaining could not be visualized at cardiac catheterization (Table III). In the 12 male patients who had postoperative cardiac catheterization, 20 of the 25 vein grafts were patent (80 per cent). Progression of disease within the grafted and nongrafted native coronary vessels was compared by methods described by Griffith.7 In women, 2 of 15 vessels had developed proximal obstruction of the grafted coronary artery with a patent vein graft. Three other women had progression of coronary artery disease within nongrafted vessels. Thus, regardless of patency of the coronary bypass grafts, most major coronary vessels in female patients remained unchanged postoperatively. In contrast, among 12 men, 6 of the 25 grafted coronary arteries (25 per cent) had developed proximal obstruction with the distal coronary artery and graft patent. In 2 male patients,
infarct No. of
patients 15 12
catlieterization
No. grafts studied
Grafts patent
27 25
14 ( 5 0 % ) 20 ( 8 0 % )
both the vein graft and the grafted coronary artery were occluded. Hemodynamic data. A summary of data in 13 of the 15 women undergoing postoperative cardiac catheterization studies is shown in Table IV and is compared with data in 12 men. Comparison of preoperative values of cardiac index, left ventricular enddiastolic pressure, stiffness, and left ventricular end-diastolic volume in men and women showed a significant difference. Over-all, women had better cardiac function preoperatively than men (p < 0.05); however, after aorto-coronary bypass surgery in most women, there was a depression in each parameter of cardiac function with a significant increase in left ventricular enddiastolic pressure from 8 + 1 (SE) to 14 ± 1 mm. Hg (Fig. 1). Also, left ventricular diastolic stiffness and left ventricular enddiastolic volume were increased postoperatively (p < 0.05). Changes in cardiac index and ejection fraction were not significant (Figs. 2 and 3). Postoperatively in men, there was a statistically significant decrease in left ventricular end-diastolic pressure from 23 + 2 to 13 + 1 mm. Hg (p < 0.001), with a slight improvement in cardiac index and ejection fraction, although these changes were not statistically signif-
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Table IV Cardiac 13 12
Vmax
EDP (mm . Hat
(circ./sec.)
|
1
2
1
2
1
3.1 ± 19* 2.6 ± 0.17
2.7 ± 17 2.7 ± 0.13
2.3 ± 0.2 1.9 ± 0 . 1 8
2.15 ± 19 2.3 ± 0.24
8 ± 1* 23 + 2
No. Women Men
index
2 14 ± It 13 + It
Legend: Cor nparison of preoperative (1) and postopera tive (2) hemodynamic data in men a nd women. Numerical data indicate ventricular stiffness. EDV, End-diastolic volume. Cardiac index is in liters per minute per square meter. *Significant difference (p < 0.05) with the preoperative value of the same parameter in men. tSignificant change (p < 0.05) from the preoperative studies.
60 ;= 3 20
BEFORE Open Grails
AFTER
BEFORE
AFTER Partially Open Grafts
BEFORE Open grafts
AFTER
BEFORE
AFTER Partially open grafts
Fig. 1. Comparison of changes in left ventricular end-diastolic pressure in men and women after aorto-coronary bypass.
Fig. 2. Comparison of changes in ejection fraction in men and women after aorto-coronary bypass.
icant (Figs. 1 to 3 and Table IV). Accumulated data for all men and all women, considering 10 per cent change in cardiac function, showed 50 per cent of the men had an over-all improvement in all parameters as compared with 30 per cent of the women. Follow-up. In the course of 6 months to 3!/2 years of follow-up, 5 of the 31 surviving female patients (16 per cent) have remained symptomatic with severe angina pectoris. All these patients are receiving the same or a larger amount of coronary vasodilator agents than they consumed preoperatively. On late follow-up, 1 woman died of an acute myocardial infarction. This patient had a congenital aneurysm of the left anterior descending coronary artery which was not resected at the time of surgery for coronary bypass graft. However, she developed car-
diac arrest as a result of left ventricular dysrhythmia and myocardial infarction, even though the graft was patent when visualized 1 month previously. Among men, 3 of the 50 surviving patients have angina pectoris, but in only 1 man is its severity comparable to the preoperative level. No late infarction has occurred in male patients. Discussion It was our impression that our female patients were not benefiting from myocardial revascularization by direct coronary surgery to the same extent as our male patients. Along wilh the reports by various investigators indicating development of symptoms of coronary ischemia and myocardial infarction in women without disease of major coronary vessels, 810 this impression encouraged us to look more objectively at our
Volume 69
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275
February, 1975
i f / A
v (mm.
0.20 0.33
EF
Hg/cx.) 1
2
I 0.03* 0.9
0.34 ± 0.04t 0.38 + 0.5
69 62
(%)
EDV 2
1
64 ± 6 65 ± 4
195 ± 30* 285 ± 24
(ml.) 2 219 272
291 36
nean ± SE for each parameter. Only 13 women had complete data. EDP, End-diastolic pressure. EF, Ejection fraction. A p/A v, Left
BEFORE AFTER Open grails
BEFORE
AFTER Partially open grafts
Fig. 3. Comparison of changes in cardiac index in men and women after aorto-coronary bypass.
results in this group of patients. The data presented indicate, over-all, that the effects of myocardial revascularization in women with chronic angina pectoris are inferior to those in men. This finding included a slightly increased operative mortality rate and a threefold increase in the incidence of perioperative myocardial infarction. Also, fewer women had a patent bypass graft, and more women remained symptomatic postoperatively, regardless of patency of coronary bypass grafts. These differences in results were not due to sampling or factors such as technical improvement in coronary surgery, since only a few women (8) were operated upon before 1971, and none of them have had postoperative cardiac catheterization studies. Furthermore, no significant differences in results were seen for men for the sample year (1972) as compared with the entire group of 226 men who were operated upon in the course of the period (1969 to 1973). n
Aorto-coronary bypass grafting can be done with low intraoperative morbidity and mortality rates.'-' " Although effects of this operation on improving the symptoms of angina pectoris have been excellent, its effects on improving cardiac function have been variable.11 In a recent report, we evaluated objectively the effects of this operation on cardiac function. In a group of 21 patients, including 3 women, cardiac function improved in approximately 50 per cent of all who had a successful operation.15 The present studies indicate that less than 30 per cent of women show an improvement in cardiac function after this procedure. In the present series, this finding could be partly related to graft closure, because at least one of the vein grafts was closed in one half of the female patients. One could speculate a number of reasons for closure of the vein grafts: Intraoperative technical difficulties are encountered more frequently with coronary vessels in women than men; the saphenous vein in women is thin walled and, at times, aneurysmal. These problems may be overcome by using an internal mammary graft.I,! The poor results, however, were not solely due to graft closure, since the results were similar in patients with all grafts patent (Figs. 1 to 3). Angina pectoris may develop due to the presence of a number of physiological factors—other than coronary artery occlusion—which enhance oxygen consumption and produce a relative myocardial oxygen deficit. Previous clinical and experimental studies have indicated that factors such as disease within smaller coronary arteries or an increase in myocardial contractility, heart rate, left ventricular diastolic
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2 7 6 Bolooki et al.
volume, and pressure (the left ventricular wall tension) may play an important role in the development of angina. ir ' 1S In the present study, there were no significant changes in heart rate, ventricular systolic pressure, and myocardial contractility in female or male patients after myocardial revascularization.1. However, the preoperative left ventricular end-diastolic volume in women was significantly less than that in men; in contrast to our findings in men, this parameter increased after aorto-coronary bypass in most women. Therefore, it could have played a role in persistence of symptoms of angina pectoris in these patients. In a number of previous reports dealing with patients suffering from clinical symptoms of ischemic heart disease without angiographic evidence of major coronary obstruction, investigators have hypothesized possible involvement of smaller coronary arteries.5"1" On the basis of finding small areas of infarct at autopsy, such a cause could have played a role in 1 of our patients who died 22 months after coronary bypass graft. In other patients, however, we were unable to find any angiographic or necropsy evidence to support this hypothesis. With these findings, we recommend that the preoperative evaluation in women should include an investigation of all factors which enhance oxygen consumption and, theoretically, could produce angina pectoris. Also, factors such as the patient's daily household activity and behavior which were not taken into consideration in this study, and the adequacy of preoperative medical therapy should be considered along with the anatomy of the coronary arteries. While aorto-coronary bypass grafting in women is done with indications similar to those in men, its effect on angina pectoris and cardiac function is not similar. For these reasons, this procedure should be offered to women with a guarded outlook in terms of eventual early and long-term results. REFERENCES 1 Cannon, D. S., Miller, D. C , Shumway, N . E., et al.: The Long-Term Follow-up of Pa-
Thoracic and Cardiovascular Surgery
2
3
4
5
6
tients Undergoing Saphenous Vein Bypass Surgery, Circulation 49: 77, 1974. Collins, J. J., Jr., Conn, L. H., Sonnenblick, E. H., et al.: Determinants of Survival After Coronary-Artery Bypass Surgery, Circulation 48: 132, 1973 (Suppl. III). Dodge, H. T., Sandier, H., Ballew, D. W., and Lord, J. D., Jr.: The Use of Biplane Angiocardiography for the Measurement of Left Ventricular Volume in Man, Am. Heart J. 60: 762, 1960. Sonnenblick, E. H.. Parmley, W. W., Urschel, C. W., et al.: Ventricular Function: Evaluation of Cardiac Contractility in Health and Disease, Progr. Cardiovasc. Dis. 12: 449, 1970. Diamond, G., and Forrester, J. S.: Effect of Coronary-Artery Disease and Acute Myocardial Infarction on Left Ventricular Compliance in Man, Circulation 45: 11, 1972. Bolooki, H., Sommer, L., Faraldo, A., Ghahramani, A., Slavin, D., and Kaiser, G. A.: Significance of Serum Enzyme Studies in Patients Undergoing Direct Coronary Artery
7
8
9
10
11
12
Surgery,
J.
THORAC.
CARDIOVASC.
SURO.
65: 863, 1973. Griffith, L. S., Achuff, S. C , Conti, C. R., et al.: Changes in Intrinsic Coronary Circulation and Segmental Ventricular Motion After Saphenous-Vein Bypass Graft Surgery, N. Engl. J. Med. 288: 589, 1973. Glancy, D. L., Marcus, M. L., and Epstein, S. E.: Myocardial Infarction in Young Women With Normal Coronary Arteriograms, Circulation 44: 495, 1971. Likoff, W.: Myocardial Infarction in Subjects With Normal Coronary Arteriograms, Am. J. Cardiol. 28: 742, 1971. Bemiller, C. R., Pepine, C. J., and Rogers, A. K.: Long-Term Observation in Patients With Angina and Normal Coronary Arteriograms, Circulation 47: 36, 1973. Bolooki, H., Vargas, A., Thurer, R., and Kaiser, G. A.: Objective Assessment of Results of Myocardial Revascularization, Surgery 26: 925, 1974. Favaloro, R. G., Effler, D. B., Groves, L. K., Sheldon, W. C , Shirey. E. K., and Sones, F. M., Jr.: Severe Segmental Obstruction of the Left Main Coronary Artery and Its Divisions: Surgical Treatment by the Saphenous Vein Graft Technique, J. THORAC. CARDIOVASC
SURG.
60:
469,
1970.
13 Reul, G. J., Morris, G. C , Jr., Howell, J. F „ et al.: Current Concepts in Coronary Artery Surgery: Critical Analysis of 1,287 Patients, Ann. Thorac. Surg. 14: 243, 1972. 14 Bourassa, M.G.: Left Ventricular Perform-
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ance Following Direct Myocardial Revascularization, Circulation 48: 915, 1973. 15 Bolooki, H., Mallon, S., Ghahramani, A., Sommer, L., Vargas, A., Slavin, D., and Kaiser, G. A.: Objective Assessment of the Effects of Aorto-coronary Bypass Operation on Cardiac Function, J. THORAC. CARDIOVASC. SURC. 66: 916, 1973.
16 Hutchinson, J. E., Green, G. E., Mekhjian, H. A., and Kemp, H. G.: Coronary Bypass
Grafting in 376 Consecutive Patients, With Three Operative Deaths, J. THORAC. CARDIOVASC. SURG. 67: 7,
1974.
17 Braunwald, E.: The Determinants of Myocardial Oxygen Consumption, Physiologist 12: 65, 1969. 18 Sonnenblick, E. H., Ross, J., Jr., and Braunwald, E.: Oxygen Consumption of the Heart: Newer Concepts of Its Multifactoral Determination, Am. J. Cardiol. 22: 328, 1968.
Hooshang Bolooki, M.D., F.R.C.S.(C),* Abelardo Vargas, M.D., Robert Green, M.D., Gerard A. Kaiser, M.D., and Ali Ghahramani, M.D., Miami, Fla.
Ihe results of saphenous vein grafts in women have usually been reported in combination with those in men and have been considered equally satisfactory.'• - Our experience, however, contrasts with this impression. We have had a larger number of graft closures in women, more technically difficult coronary arteries to work on, and less striking long-term effects on angina pectoris. For those reasons, we made a survey of our results in women who underwent direct myocardial revascularization with a saphenous vein graft. Methods From May, 1969, to October, 1973, 34 women were operated upon. They were From the Divisions of Thoracic and Cardiovascular Surgery and Cardiology. University of Miami School of Medicine, Miami. Fla. 33136. Supported in part by grants from National Heart and Lung Institute, Grant No. HE 13978-03, Heart Association of Greater Miami Inc., and Eli Lilly Research Laboratories, Indianapolis, lnd. Received for publication Aug. 6, 1974. * Research Career Development Awardee, Grant No. HL 70, 670-02.
among 260 patients who underwent myocardial revascularization for stable angina pectoris. Excluded from this study were 4 women seen in the same period who were suffering from so-called preinfarction angina and had emergency myocardial revascularization. All female patients had severe coronary artery disease (18 had multiple vessel involvement) and angina pectoris which was not responsive to conventional medical management including long-acting nitrates (isosorbide dinitrate). One half of them had also received beta blocking agents (propranolol). The age range was 32 to 71 years with an average age of 54 years. Three patients had diabetes mellitus, controlled with drug therapy and diet. Two of these and 2 additional patients had hyperlipidemia (Type IV). Ten women (36 per cent) were overweight. A history of previous myocardial infarction was noted in 4 patients (Table I). All of the women underwent cardiac catheterization studies and hemodynamic evaluation prior to direct myocardial revascu27 1
The Journal of
272
Bolooki et al.
Thoracic and Cardiovascular Surgery
Table I. Patient data in women and men after direct myocardial revascularization
Women Men
No.
Average age (yr.)
34 51
54 56
larization. Cardiac catheterization studies were done by Judkin's technique of percutaneous femoral artery approach. The left ventricular angiograms were obtained in the right anterior oblique and left anterior oblique views. Right and left coronary arteriograms were recorded on 35 mm. films with at least two views of each vessel. The cardiac output was calculated by the Fick principle, with blood samples from the pulmonary artery and from the descending aorta being analyzed for oxygen content, and by measurement of oxygen consumption by direct respirometry. Ejection fraction and volumes were calculated from biplane left ventricular angiograms by the methods of Dodge and colleagues" and by assuming the left ventricle to be a thinwall ellipsoid. An index of myocardial contractility was calculated from the left ventricular pressure curves obtained by a transducer catheter prior to left ventricular angiography.' The left ventricular diastolic stiffness (A p/A v) was calculated by the methods of Diamond and Forrester.'1 The surgical procedure was performed by means of cardiopulmonary bypass with normothermia and hemodilution perfusion technique. A reversed segment of the saphenous vein was used for bypass grafting. Sixty-five vein grafts were done in the 34 patients for an average of 1.9 grafts per patient. The anterior descending coronary artery was bypass grafted in every case. Postoperatively, twelve-lead electrocardiograms and serum enzyme studies were obtained in all patients for 3 consecutive days, in order to detect the development of any postoperative myocardial infarction." Postoperative cardiac catheterization studies were conducted in 15 women via methods similar to those described for pre-
Diabetes
Hyperlipidemia
Previous infarction
operative studies. Postoperative follow-up was obtained in all 34 patients. Seventeen patients were seen regularly in an out-patient clinic; others had telephone interviews or were followed by questionnaires. For the purpose of comparison, the clinical courses of 51 consecutive male patients who were operated upon during a sample year (1972) were also analyzed in a similar fashion. Our operative results in this group of patients were similar to those in the entire population of men (226 patients), since operative mortality rate, incidence of perioperative infarction, and graft patency rate have remained unchanged in the past 3 years. The age range for men was 31 to 74 years with an average age of 56 years. The 34 women under study and the 51 men had a comparable extent of coronary artery vessel involvement, previous history of myocardial infarction, and incidence of diabetes and hyperlipidemia (Table I). The preoperative medical management and drug therapy in men was similar to that indicated for women. The results from pre- and postoperative cardiac catheterization studies in 12 of these 51 male patients were available and were used for comparison with those obtained in the female group. Results Clinical course. Three female patients (8 per cent) died in the immediate postoperative period because of myocardial infarction, and 1 died late postoperatively (22 months after surgery). The cause of death in the latter patient was also acute myocardial infarction; she had a patent vein graft to the anterior descending coronary artery. Seven patients (20 per cent) developed infarction in the course of the operation or in the early postoperative
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February, 1975
Table II. Comparison of results of direct myocardial revascularization in women and men Extent of coronary artery disease Women Men
No.
Single
Multiple
34 51
16 23
18 28
Deaths: Operative and late
Perioperative infarct 1 (20%) 3 ( 6%)
3 (8.8%) 1 (2%)
Table III. Comparison of results on follow-up after direct myocardial revascularization in women and men Cardiac
Women Men
Surviving patients
A ngina
31 50
5 (16%) 3 ( 6%)
Late
period (Table II)." The operative and late mortality rate in men was 2 per cent (1 patient), and the perioperative infarction rate was 6 per cent (3 patients). Angiographic data. Fifteen female patients agreed to have postoperative cardiac catheterization studies. Of the 27 coronary bypass grafts studied, only 14 were patent (50 per cent), and the remaining could not be visualized at cardiac catheterization (Table III). In the 12 male patients who had postoperative cardiac catheterization, 20 of the 25 vein grafts were patent (80 per cent). Progression of disease within the grafted and nongrafted native coronary vessels was compared by methods described by Griffith.7 In women, 2 of 15 vessels had developed proximal obstruction of the grafted coronary artery with a patent vein graft. Three other women had progression of coronary artery disease within nongrafted vessels. Thus, regardless of patency of the coronary bypass grafts, most major coronary vessels in female patients remained unchanged postoperatively. In contrast, among 12 men, 6 of the 25 grafted coronary arteries (25 per cent) had developed proximal obstruction with the distal coronary artery and graft patent. In 2 male patients,
infarct No. of
patients 15 12
catlieterization
No. grafts studied
Grafts patent
27 25
14 ( 5 0 % ) 20 ( 8 0 % )
both the vein graft and the grafted coronary artery were occluded. Hemodynamic data. A summary of data in 13 of the 15 women undergoing postoperative cardiac catheterization studies is shown in Table IV and is compared with data in 12 men. Comparison of preoperative values of cardiac index, left ventricular enddiastolic pressure, stiffness, and left ventricular end-diastolic volume in men and women showed a significant difference. Over-all, women had better cardiac function preoperatively than men (p < 0.05); however, after aorto-coronary bypass surgery in most women, there was a depression in each parameter of cardiac function with a significant increase in left ventricular enddiastolic pressure from 8 + 1 (SE) to 14 ± 1 mm. Hg (Fig. 1). Also, left ventricular diastolic stiffness and left ventricular enddiastolic volume were increased postoperatively (p < 0.05). Changes in cardiac index and ejection fraction were not significant (Figs. 2 and 3). Postoperatively in men, there was a statistically significant decrease in left ventricular end-diastolic pressure from 23 + 2 to 13 + 1 mm. Hg (p < 0.001), with a slight improvement in cardiac index and ejection fraction, although these changes were not statistically signif-
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Table IV Cardiac 13 12
Vmax
EDP (mm . Hat
(circ./sec.)
|
1
2
1
2
1
3.1 ± 19* 2.6 ± 0.17
2.7 ± 17 2.7 ± 0.13
2.3 ± 0.2 1.9 ± 0 . 1 8
2.15 ± 19 2.3 ± 0.24
8 ± 1* 23 + 2
No. Women Men
index
2 14 ± It 13 + It
Legend: Cor nparison of preoperative (1) and postopera tive (2) hemodynamic data in men a nd women. Numerical data indicate ventricular stiffness. EDV, End-diastolic volume. Cardiac index is in liters per minute per square meter. *Significant difference (p < 0.05) with the preoperative value of the same parameter in men. tSignificant change (p < 0.05) from the preoperative studies.
60 ;= 3 20
BEFORE Open Grails
AFTER
BEFORE
AFTER Partially Open Grafts
BEFORE Open grafts
AFTER
BEFORE
AFTER Partially open grafts
Fig. 1. Comparison of changes in left ventricular end-diastolic pressure in men and women after aorto-coronary bypass.
Fig. 2. Comparison of changes in ejection fraction in men and women after aorto-coronary bypass.
icant (Figs. 1 to 3 and Table IV). Accumulated data for all men and all women, considering 10 per cent change in cardiac function, showed 50 per cent of the men had an over-all improvement in all parameters as compared with 30 per cent of the women. Follow-up. In the course of 6 months to 3!/2 years of follow-up, 5 of the 31 surviving female patients (16 per cent) have remained symptomatic with severe angina pectoris. All these patients are receiving the same or a larger amount of coronary vasodilator agents than they consumed preoperatively. On late follow-up, 1 woman died of an acute myocardial infarction. This patient had a congenital aneurysm of the left anterior descending coronary artery which was not resected at the time of surgery for coronary bypass graft. However, she developed car-
diac arrest as a result of left ventricular dysrhythmia and myocardial infarction, even though the graft was patent when visualized 1 month previously. Among men, 3 of the 50 surviving patients have angina pectoris, but in only 1 man is its severity comparable to the preoperative level. No late infarction has occurred in male patients. Discussion It was our impression that our female patients were not benefiting from myocardial revascularization by direct coronary surgery to the same extent as our male patients. Along wilh the reports by various investigators indicating development of symptoms of coronary ischemia and myocardial infarction in women without disease of major coronary vessels, 810 this impression encouraged us to look more objectively at our
Volume 69
Direct coronary artery surgery
Number 2
275
February, 1975
i f / A
v (mm.
0.20 0.33
EF
Hg/cx.) 1
2
I 0.03* 0.9
0.34 ± 0.04t 0.38 + 0.5
69 62
(%)
EDV 2
1
64 ± 6 65 ± 4
195 ± 30* 285 ± 24
(ml.) 2 219 272
291 36
nean ± SE for each parameter. Only 13 women had complete data. EDP, End-diastolic pressure. EF, Ejection fraction. A p/A v, Left
BEFORE AFTER Open grails
BEFORE
AFTER Partially open grafts
Fig. 3. Comparison of changes in cardiac index in men and women after aorto-coronary bypass.
results in this group of patients. The data presented indicate, over-all, that the effects of myocardial revascularization in women with chronic angina pectoris are inferior to those in men. This finding included a slightly increased operative mortality rate and a threefold increase in the incidence of perioperative myocardial infarction. Also, fewer women had a patent bypass graft, and more women remained symptomatic postoperatively, regardless of patency of coronary bypass grafts. These differences in results were not due to sampling or factors such as technical improvement in coronary surgery, since only a few women (8) were operated upon before 1971, and none of them have had postoperative cardiac catheterization studies. Furthermore, no significant differences in results were seen for men for the sample year (1972) as compared with the entire group of 226 men who were operated upon in the course of the period (1969 to 1973). n
Aorto-coronary bypass grafting can be done with low intraoperative morbidity and mortality rates.'-' " Although effects of this operation on improving the symptoms of angina pectoris have been excellent, its effects on improving cardiac function have been variable.11 In a recent report, we evaluated objectively the effects of this operation on cardiac function. In a group of 21 patients, including 3 women, cardiac function improved in approximately 50 per cent of all who had a successful operation.15 The present studies indicate that less than 30 per cent of women show an improvement in cardiac function after this procedure. In the present series, this finding could be partly related to graft closure, because at least one of the vein grafts was closed in one half of the female patients. One could speculate a number of reasons for closure of the vein grafts: Intraoperative technical difficulties are encountered more frequently with coronary vessels in women than men; the saphenous vein in women is thin walled and, at times, aneurysmal. These problems may be overcome by using an internal mammary graft.I,! The poor results, however, were not solely due to graft closure, since the results were similar in patients with all grafts patent (Figs. 1 to 3). Angina pectoris may develop due to the presence of a number of physiological factors—other than coronary artery occlusion—which enhance oxygen consumption and produce a relative myocardial oxygen deficit. Previous clinical and experimental studies have indicated that factors such as disease within smaller coronary arteries or an increase in myocardial contractility, heart rate, left ventricular diastolic
The Journal of
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volume, and pressure (the left ventricular wall tension) may play an important role in the development of angina. ir ' 1S In the present study, there were no significant changes in heart rate, ventricular systolic pressure, and myocardial contractility in female or male patients after myocardial revascularization.1. However, the preoperative left ventricular end-diastolic volume in women was significantly less than that in men; in contrast to our findings in men, this parameter increased after aorto-coronary bypass in most women. Therefore, it could have played a role in persistence of symptoms of angina pectoris in these patients. In a number of previous reports dealing with patients suffering from clinical symptoms of ischemic heart disease without angiographic evidence of major coronary obstruction, investigators have hypothesized possible involvement of smaller coronary arteries.5"1" On the basis of finding small areas of infarct at autopsy, such a cause could have played a role in 1 of our patients who died 22 months after coronary bypass graft. In other patients, however, we were unable to find any angiographic or necropsy evidence to support this hypothesis. With these findings, we recommend that the preoperative evaluation in women should include an investigation of all factors which enhance oxygen consumption and, theoretically, could produce angina pectoris. Also, factors such as the patient's daily household activity and behavior which were not taken into consideration in this study, and the adequacy of preoperative medical therapy should be considered along with the anatomy of the coronary arteries. While aorto-coronary bypass grafting in women is done with indications similar to those in men, its effect on angina pectoris and cardiac function is not similar. For these reasons, this procedure should be offered to women with a guarded outlook in terms of eventual early and long-term results. REFERENCES 1 Cannon, D. S., Miller, D. C , Shumway, N . E., et al.: The Long-Term Follow-up of Pa-
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tients Undergoing Saphenous Vein Bypass Surgery, Circulation 49: 77, 1974. Collins, J. J., Jr., Conn, L. H., Sonnenblick, E. H., et al.: Determinants of Survival After Coronary-Artery Bypass Surgery, Circulation 48: 132, 1973 (Suppl. III). Dodge, H. T., Sandier, H., Ballew, D. W., and Lord, J. D., Jr.: The Use of Biplane Angiocardiography for the Measurement of Left Ventricular Volume in Man, Am. Heart J. 60: 762, 1960. Sonnenblick, E. H.. Parmley, W. W., Urschel, C. W., et al.: Ventricular Function: Evaluation of Cardiac Contractility in Health and Disease, Progr. Cardiovasc. Dis. 12: 449, 1970. Diamond, G., and Forrester, J. S.: Effect of Coronary-Artery Disease and Acute Myocardial Infarction on Left Ventricular Compliance in Man, Circulation 45: 11, 1972. Bolooki, H., Sommer, L., Faraldo, A., Ghahramani, A., Slavin, D., and Kaiser, G. A.: Significance of Serum Enzyme Studies in Patients Undergoing Direct Coronary Artery
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17 Braunwald, E.: The Determinants of Myocardial Oxygen Consumption, Physiologist 12: 65, 1969. 18 Sonnenblick, E. H., Ross, J., Jr., and Braunwald, E.: Oxygen Consumption of the Heart: Newer Concepts of Its Multifactoral Determination, Am. J. Cardiol. 22: 328, 1968.