Does coronary bypass increase longevity?

Does coronary bypass increase longevity? The principal question with coronary bypass is its influence on longevity. To investigate this, we recently studied 1,174 consecutive patients undergoing elective coronary bypass surgery at New York University between 1968 and 1975 (98 percent follow-up). Most patients were operated upon for disabling angina refractory to medical therapy. Patients undergoing concomitant valve replacement, ventricular aneurysmectomy, and emergency bypass surgery were excluded from this analysis. The over-all operative mortality rate was 5.2 percent, decreasing from 28 percent in 1968 to 2 to 3 percent in the last 3 years (1972 to 1975). Multiple grafts (two to six) were used in 88 percent of the group. Angina was cured or greatly improved in 92 percent of surviving patients. The 5 year survival rate (computed by life-table analysis including operative deaths but excluding late, non-cardiae-related deaths) was high, 88 percent. Only 49 deaths from cardiac causes occurred after dismissal from the hospital in the entire group of 1,174 patients. Nonfatal myocardial infarctions were similarly uncommon, 2.6 percent (actuarial analysis). These data show a better survival rate than do previous surgical reports (average late mortality rate of 3 percent per year) and a much greater survival rate than for medically treated patients with double or triple artery disease (5 year mortality rate of 35 and 55 percent, respectively). The significance of these findings are discussed in detail.

O. Wayne Isom, M.D., Frank C. Spencer, M.D., Ephraim Glassman, M.D. (by invitation), Joseph N. Cunningham, M.D. (by invitation), Phyllis Teiko, M.D. (by invitation), George E. Reed, M.D., and Arthur D. Boyd, M.D., New York, N. Y.

Bypass grafting for coronary artery disease has been a major area of clinical investigation at New York University for the past decade. During this time, several reports have described experiences with different aspects of this disease, including the development of the internal mammary artery for bypass grafting, the disappointing results with bypass grafting for congestive heart failure, and the significant improvement following bypass grafting for patients with severe impairment of left ventricular function.v'" Most patients have been operated upon for disabling angina refractory to available medical therapy. This criterion, of course, varied widely with the age of the patient, his temperament, and his occupation. Operation has rarely been done either for mild, stable angina or because of angiographic demonstration of coronary disease with minimal or absent symptoms. Several reports have described an operative mortality rate as low as 1 to 4 percent, usually varying with the From the Departments of Surgery and Medicine, New York University School of Medicine, 560 First Avenue, New York, N. Y. 10016. Read at the Fifty-seventh Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, April 18, 19, and 20, 1977.

28

extent of occlusive disease and the degree of impairment of left ventricular function.' This low operative mortality rate, combined with the dramatic relief of angina in the vast majority of patients, has led to the widespread popularity of coronary bypass, although the procedure continues to be criticized by many as premature and unproved. Separate from the immediate relief of angina are the more long-term considerations of the influence of operation on longevity and protection from future myocardial infarction. Answers to these questions depend upon several factors, including the durability of bypass grafts, the physiological effect of increased flow of blood to the myocardium, and the rate of progression of the underlying atherosclerotic process. In our previous 1974 report of 448 patients, the 5 year survival rate was near 81 percent. To investigate further the crucial question of the influence of coronary bypass on longevity, in the past year we have conducted a detailed analysis of our entire experience with elective coronary bypass, ranging from February, 1968, through December, 1975. This included a total of 1,172 patients. A 97.7 percent follow-up was obtained as patients are followed regularly on an annual basis either by physical examination or telephone inter-

Volume 75

Influence of coronary bypass on longevity

Number 1 January, 1978

29

Table I. Over-all experience Year

Total No. of patients

1968

13

1969

31

1970

74

1971

156

1972

166

1973

213

1974

244

1975

275

Totals

1172

Type of surgery

SCB DCB SCB DCB TCB SCB DCB TCB SCB DCB TCB QCB or more SCB DCB TCB SCB DCB TCB QCB or more SCB DCB TCB QCB or more SCB DCB TCB QCB or more

No. of patients

No. of operative deaths

Operative mortality rate (%)

10 3

3 2

38.5

6 22 3

0

6.5

2 0 0 9 0

12.2

59 4 24 57 67 8

I

6.4

4 5 0

19 56 91

0 3 3

3.6

16 61 123 13

0

4.2

II

3 6 0

31 66 116 31

0

2.7

19 62 108 86

0 3 4 6

4.7

61

5.2

I

3 3

Legend: SCB, Single coronary bypass. DCB, Double coronary bypass. TCB, Triple coronary bypass. QCB, Quadruple coronary bypass.

view. The range of follow-up was between 6 and 91 months, with a mean of 27 months. Methods and patients Eleven hundred and seventy-two patients had elective coronary bypass at New York University between February, 1968, and Jan. I, 1976. There were 967 men, ranging in age from 27 to 79 years, mean age 53 years, and 205 women, age range 26 to 73 years, mean age 57 years. Emergency operations for crescendo angina, those associated with replacement of one or more cardiac valves, and those involving concomitant left ventricular aneurysmectomy were excluded from this study. Patients with ventricular impairment were included in this analysis except when diffuse hypokinesia was present on ventriculography. A previous report from this institution describes our operative experience with patients having diffuse hypokinesia and left ventricular end-diastolic pressures greater than or equal to 20 mm. Hg.3

As mentioned earlier, most patients were operated upon for disabling angina refractory to available medical therapy. Patients with significant obstruction of the left main coronary artery were the only group operated upon for the angiographic demonstration of disease rather than for severity of symptoms. Recently, more liberal indications for operation have been used for patients with occlusive disease of three arteries. Several criteria of inoperability have been evaluated, but the only one found valid was the presence of chronic congestive failure without angina." Inability to visualize vessels beyond the arterial obstruction, age, diabetes, or hypertension, though clearly complicating the operative procedure, were not major contraindications. Hence, at least 95 percent of all patients were "operable. " Cardiopulmonary bypass with a Temptrol bubble oxygenator was used throughout this period of time, though several changes in perfusion technique evolved. In 1971 the pump prime was changed from a blood

The Journal of

30 Isom et al.

Thoracic and Cardiovascular Surgery

Table II. Causes of operative deaths in 1,172 patients undergoing elective coronary bypass grafting Cause of death

No.

Myocardial infarction Low output Arrhythmias Renal failure Sepsis Respiratory Neurologic Hemorrhage from peptic ulcer Complications of reoperation MisceIIaneous*

14 17 8

Total

3 4 5 4 I 2 3 61 (5.2%)

*Graft occlusion, one case; ruptured aorta, one case; thrombosis of superior mesenteric artery, one case.

prime to a nonblood, balanced electrolyte solution containing 25 Gm. of albumin per liter. Initially, flow rates were near 2.5 L. per square meter per minute. After serious complications developed in patients with preexisting hypertension or cerebral atherosclerosis, this policy was changed to one of maintaining perfusion pressure near that existing before bypass. This was accomplished by one of three methods: increasing the flow rate to 3 to 3.5 L. per square meter per minute, increasing the fluid gradient, or using vasopressors. Most operations were performed with a blood temperature of 30° C., although in the past 2 years lower temperatures (25° C.) have been used more frequently. During early years, long periods of ventricular fibrillation were used, 10 to 15 minute periods of aortic cross-clamping being alternated with 3 to 5 minute periods of perfusion. With several findings indicating significant myocardial injury with this technique, in the last 2 to 3 years, the proximal anastomoses have been placed on the aorta initially with the heart beating, either on or off bypass, depending upon the stability of the patient. Subsequently, with a perfusion temperature of 25 to 30° C., the distal anastomoses were performed with the aorta occluded, usually for less than 10 to 15 minutes. The left ventricle was routinely vented, either through the apex or the left atrium, and the left atrial pressure was monitored. Following each anastomosis, air was evacuated from the ventricle and the aorta by means of a small stab wound in the aorta, and the heart was defibrillated and allowed to beat for 5 to 10 minutes, while we observed the electrocardiogram, before the next anastomosis was begun. This technique has resulted in less ventricular injury than have previous methods. The left internal mammary artery was anastomosed to the left anterior descending in approximately 15 per-

cent of the patients. This is considered the graft of choice in younger patients of large stature, and it was used when the mammary artery was as large as the anterior descending. Otherwise, the saphenous vein was used. Anastomoses were performed end to side initially with Tevdek, but interrupted or continuous 6-0 or 7-0 Prolene has been used in recent years. Endarterectomy was carefully avoided in the majority of patients. Postoperatively, blood pressure, electrocardiogram, arterial and mixed venous P0 2 values, central venous pressure, left atrial pressure, and urinary output were monitored continuously. Inadequate cardiac output was managed by increasing blood volume to increase left atrial pressure and by use of inotropic drugs. In this long-term analysis, the causes of both operative and late deaths, status of symptoms in surviving patients, and occurrence of late infarction were all evaluated. All data elements were subjected to computer analysis. Survival and cumulative incidence curves were obtained by the life-table method of Kaplan and Meier. 5 When survival curves were analyzed, operative deaths and late cardiac-related deaths were included, but late, non-cardiae-related deaths were withdrawn "alive" at the time of death.

Results Results are given in Tables I through VII. In Table I are shown the number of patients operated upon annually between 1968 and 1975, the number of bypass grafts performed, and the operative mortality rates. Less than 100 patients were operated annually before 1970, after which the number has gradually increased to between 200 and 300 per year. Because of limited institutional resources and multiple responsibilities for teaching and research in a medical center, the number of bypass operations has been sharply limited to between 200 and 300 per year. This policy has similarly influenced the data, because we have selected patients more seriously disabled for operation. Patients who could not be operated upon within these limitations were referred to other institutions. Illustrated in Table I is the number of bypass grafts performed, with triple bypass grafts increasing in frequency after 1970 and single bypass grafts decreasing. Operative mortality rate was initially high but has ranged between 2 and 4 percent since 1971, with an over-all average for the 8 year period being 5.2 percent. Operative deaths. A total of 61 operative deaths (patients who died within the first 30 days or never left the hospital) occurred among the 1,172 patients (Table II), an over-all mortality rate of 5.2 percent. Thirty-

Volume 75 Number 1 January, 1978

Influence of coronary bypass on longevity

Table III. Causes of late deaths Cause

Sixth

4

Documented myocardial infarction Congesti ve heart failure Sudden and unexplained Sudden (grafts occluded at autopsy) Arrhythmia Reoperation for cardiac disease Pneumonia Pulmonary embolus Hepatitis Renal failure

16 5 II 2 4 5 I

2

I I I I

Totals

48

16

I I

4

3 2

5 2 2

2

2

2

I

3

I

I

1

I

2

nine of these 61 deaths were clearly due to cardiac injury, including 14 cases of myocardial infarctions, 17 of low output syndrome, and eight of arrhythmia. Renal failure, sepsis, respiratory problems, and neurologic injury were rarely a cause of death, a somewhat surprising finding in these patients with diffuse atherosclerosis. Late death. Forty-eight late cardiac-related deaths occurred among the 1,111 patients discharged from the hospital (Table Ill), a surprisingly small number. Thirty-three of the 48 deaths apparently were caused by an acute ischemic episode, with 16 myocardial infarctions, 11 sudden, unexplained deaths, two sudden deaths with the grafts found occluded at autopsy, and four instances of arrhythmia. It seemed significant that only five patients died from congestive heart failure. Five patients died at reoperation because of occlusion of previous grafts. Hepatitis, pulmonary embolism, and renal failure were rarely a cause of death, accounting for one, one, and two deaths, respectively. The frequency distribution of the 48 late deaths is shown in Table Ill. About one third of these occurred in the first year following operation, a fact suggesting either operative injury to the myocardium or inadequate revascularization. The long-term survival, calculated by the actuarial method and including operative deaths, was 88 percent at 5 years and 80 percent at 7 years (Fig. 1). To further emphasize the surprisingly low late mortality rate of each 100 patients operated upon, 95 were discharged from the hospital, and only seven of these 95 died from cardiac causes in the next 5 years. Hence, once a patient was discharged from the hospital, his chances of dying from heart disease in the next 5 years was 7.4 percent or 1.5 percent annually. Late myocardial infarction. Among the 1,111 patients surviving operation, there were 16 fatal myocardial infarctions and 41 nonfatal infarctions in 33 patients. In the group of 41 nonfatal infarctions, 26

7

9

4

5

6

Table IV. Number of late documented myocardial infarctions in 1,111 patients surviving operation Infarction

I

No.

Fatal Nonfatal

16 41

Total

57

Table V. Status of angina in 1, 017 currently surviving patients Patients Status ofangina

No.

%

None or less Equal Worse

935 56 26

91.9 5.5 2.6

Table VI. Activity levels in 1,017 currently surviving patients Patients Activity levels

No.

%

Greater Same Less Less for neurologic causes Less for noncardiac causes

689 162 128 13 25

67.7 15.9 12.6 1.3 2.5

Table VII. Present employment in 1,017 currently surviving patients Patients Employment

No.

%

Full time Part time Retired prior to operation Quit after operation Uncertain

452 58 307 151 49

44.4 5.7 30.2 14.8 4.9

31

The Journal of Thoracic and Cardiovascular Surgery

32 Isom et al.

100

100

90

90

1 ~

J

l

80

~

80

~

70

~

I :!: 1Standard Error

,

,

i

I

2

3

4

5

i

6

70

i

7

patients had one infarct, six had two, and one had three (Table IV). The frequency of infarction in currently surviving patients calculated by the actuarial method is shown in Fig. 2. Ninety-four percent of surviving patients remained free of myocardial infarction for 5 years and 91 percent for 7 years. An even more critical evaluation of the protection from myocardial infarction is depicted in Fig. 3, if one considers that all late cardiac deaths may be due to clinical or subclinical myocardial infarctions. The actuarial curve in Fig. 3 indicates that 87 percent of patients surviving operation remained free of any hazards of myocardial infarction at 5 years and 80 percent at 7 years following operation. The decrease between 5 and 7 years from 87 to 80 percent is probably related both to the greater frequency of operative injury and inadequate revascularization prior to 1971. Graft patency. Only approximately 20 percent ·of patients had a repeat catheterization. In our previous report, the over-all patency of vein grafts between 1 and 2 years following operation was near 70 percent in a group of 201 patients; however, among patients with multiple grafts, more than 92 percent had at least one patent graft. 6 Because symptomatic patients have become increasingly reluctant to undergo repeat catheterization, this has been performed on a minority of patients. Angina. Among 1,017 currently surviving patients, 935 (91.9 percent) are either free of angina or in much improved condition (Table V). Angina remains about the same as that before operation in 56 patients (5.5 percent) and is worse than before in 26 (2.6 percent).

•

i

,

i

2

3

4

5

i

6

I

7

Years Since Operation

Years Since Operation

Fig. 1. Actuarial survival curvefor 1,172patients undergoing elective coronary bypass grafting, 1968 to 1972. All cardiacrelated deaths, both early and late, are included. Noncardiac-related deaths andpatients whowerelostto follow-up were withdrawn alive.

I:!: 1Standard &rar

Fig. 2. Cumulative incidence of myocardial infarction in 1,017 currently surviving patients. Deaths, both early and late, have been excluded. Level of activity. A comparison of the level of physical activity before and after operation is shown in Table VI. About two thirds of the group, 689 patients, have activity levels increased over those before operation, whereas activity levels are similar in 162 patients. Only 128 patients (12.6 percent) had decreased activity because of cardiac symptoms. A somewhat similar evaluation is shown in Table VII, which shows the present employment of the 1,017 patients. Four hundred and fifty-two of the 1,017 current survivors are employed full time (44 percent) and 58 (6 percent) part time. Three hundred and seven (30 percent) had retired before operation and only 151 (15 percent) retired after operation. The work status is uncertain in 5 percent. Hence, the degree of rehabilitation following operation is impressive, especially since many patients were threatened with either retirement or a total change in vocation because of disabling angina before operation. Discussion The influence of bypass grafting on protection from myocardial infarction and longevity. As mentioned in the introduction to this report, the detailed long term evaluation of our total experience, both time consuming and expensive, continues because of the current uncertainty about the effect of bypass grafting described in both scientific and lay publications. Conclusions often have been diametrically opposed, ranging from those which indicate that bypass grafting is of great value to those which indicate that it is overutilized and of dubious benefit. Frequently, strong opinions have been expressed that were based on meager, shortterm data. An additional important consideration in evaluating

Volume 75

Influence of coronary bypass on longevity

Number 1

January, 1978

the long-term effectiveness of bypass grafting is the fact that to date no medical therapy has been shown with long-term randomized studies to benefit coronary disease. The data found in this survey are surprisingly good. The numerical fact, demonstrated in Fig. I, that for each 95 patients leaving the hospital, 88 were alive 5 years later, speaks for itself. This high survival rate is particularly significant with our policy of operating only upon patients disabled by angina refractory to medical therapy. Hence, it is very likely that patients with more extensive disease have been operated upon, which is reflected in the frequency of multiple grafts, with single grafts employed in 11.6 percent and three or more grafts in 55.5 percent (Table I). An additional factor that makes the 88 percent 5 year survival rate surprising is that the data include our total experience and, in retrospect, the techniques employed between 1968 and 1971 were considerably inferior to those used subsequently. More extensive grafting has been done, and far less injury to the myocardium has resulted. These data are partly reflected by the improved results as compared to those in our 1974 report. The 5 year survival rate has risen significantly from 80 to 88 percent, and the frequency of late myocardial infarction has decreased from 7.6 to 4.4 percent. The improved survival rate is reflected in the several other factors described in the different tables, such as frequency of infarction, 4.4 percent of 1,111 patients surviving operation (Table IV); angina eliminated or greatly improved in 92 percent of patients (Table V); physical activity levels greater or the same in 84 percent of patients (Table VI); and employment status of patients either improved or unchanged in 80 percent of patients (Table VII). Considering the diffuse coronary disease often present, congestive heart failure was surprisingly rare as a cause of death, occurring in only five patients. The good results described in this report represent a significant improvement over those in our 1974 report. Somewhat similar data have been reported by others, although the indications and contraindications for operation have varied widely among different groups. 7-9 Stiles and associates? recently reported a 3.4 percent operative mortality rate in 1,532 patients undergoing coronary bypass between 1969 and 1974 at the University of Southern California. The 5 year survival rate including operative mortality was 83.6 percent. Sixtytwo percent of the late deaths were caused by cardiac disease. The experience of Tecklenberg and co1leagues? at Standord University was published recently and revealed a 4.9 percent operative mortality rate in

33

100

III III

90

at

i

~ 80

i ~

70

I! 1 Standard Error

i i '

2 3 4 Years Since Operation

i

5

Fig. 3. Cumulative incidence of either late, cardiac-related death or myocardial infarction in I, III patients surviving operation.

350 patients undergoing bypass surgery between 1968 and 1972. This group included those with stable and unstable angina. The 5 year survival rate in the entire group was slightly higher than 80 percent. The over-all mortality rate in 10,744 patients undergoing bypass surgery between 1967 and 1975 at the Cleveland Clinic reported by Sheldon and Loop" was remarkably low at 2 percent. The 5 year survival rate of 741 consecutive patients undergoing bypass surgery between 1967 and 1970 at the Cleveland Clinic was 83 percent. This improvement is almost surely due to not only more complete revascularization but also to less injury to the myocardium at operation. The magnitude of injury to the myocardium at operation remains the most elusive aspect of coronary bypass and is undoubtedly one of the principal reasons for the conflicting data and conclusions in many reports. Chemical measurements of myocardial injury have shown clearly not only that a patient may survive operation despite extensive myocardial injury, but also that the injury may not even be clinically recognizable. The incidence of operative infarction at this institution has been reported to be less than 10 percent. 10 Although not yet available, it would be ideal to measure quantitatively the grams of myocardium infarcted at operation. Obviously, the relative proportion between the degree of injury and the degree of benefit from revascularization determines the eventual results. The fact that 16 of the 48 late deaths occurred in the first year after operation suggests an operative injury (Table III). If death were due to progression of atherosclerosis, closure of vein grafts, or a detrimental influence of bypass grafts on the development of collat-

34 Isom et al.

eral circulation, a different frequency distribution would be expected, with the majority of deaths appearing 2 or more years following operation. The differences in survival among patients with single, double, and triple vessel disease following bypass grafting are not included in this report, as such data have not been analyzed in detail at this time. Reports from others, however, have shown a surprising similarity of long-term survival in patients with single, double, and triple vessel disease. 11 By contrast, several reports have indicated an almost linear correlation between annual mortality rate and the number of vessels involved, with an annual mortality rate of about 2.5 percent for single vessel disease, almost 7 percent for double vessel disease, and 10 to 11 percent with triple vessel disease.P These striking differences in survival between medical and surgical therapy of patients with single, double, or triple disease suggest a strong beneficial influence from bypass grafting. One separate and most significant question has not yet appeared in surgical reports: How often is a patient dying from coronary disease found at autopsy to have three patent grafts? A theoretical analysis of the question of benefit versus harm from coronary bypass grafting involves at least three major considerations: benefit from bypass grafting; harm from bypass grafting; and the relative balance between the rate of progression of the occlusive atherosclerotic process and the development of collateral circulation. The benefit of bypass grafting depends both upon the amount of increased blood flow to the myocardium, varying with the number of grafts inserted and the extent of occlusive disease, and upon the durability of the grafts. Although significant 5 year data are not yet available, it appears from different reports that 5 year patency for vein grafts will be in the range of 60 to 70 percent. With internal mammary artery grafts, patency at 2 to 3 years is higher than 90 percent, with little change from earlier periods; thus 5 year patency may well exceed 90 percent. Harm from bypass grafting theoretically could develop from at least three mechanisms: operative injury to the myocardium, previously discussed; accelerated closure of stenotic coronary arteries; and inhibition of the development of collateral circulation by the presence of the bypass graft. Several studies have shown that insertion of a bypass graft beyond a proximal stenosis will accelerate progression of the stenotic plaque to complete occlusion." Experiments have demonstrated that because of the changes in resistance to flow of blood, blood perferen-

The Journal of Thoracic and Cardiovascular Surgery

tially flows through the bypass graft. The decrease in flow through the stenotic coronary artery accelerates the stenosing process. Theoretically, the presence of the bypass graft should inhibit the development of collateral circulation, for the strongest natural stimulus to the development of collateral circulation is the pressure gradient between a coronary artery distal to an obstruction and the surrounding vascular bed. Once a bypass graft has been inserted, this pressure gradient, and hence the stimulus for development of collateral circulation, is removed. The 88 percent 5 year survival rate, however, indicates almost certainly that significant harm does not result from bypass grafting. In addition, the frequency distribution of the 48 late deaths in this series, with 16 occurring in the first year, is exactly the opposite of what would be anticipated if the effects of bypass grafts on accelerating closure of stenotic coronary arteries and inhibiting the development of collateral circulation were significant. One would expect to see a higher frequency of deaths 3 to 5 years after operation. Hence, although the theoretical hazards seem plausible, clinically they seem to be of little importance. A third consideration is the basic necessity for bypass grafting. Coronary atherosclerosis is a chronic disease of unknown cause in which the ultimate outcome is basically influenced by the balance between the rate of progression of the atherosclerotic process and the rate of development of collateral circulation. This rate of progression varies widely and, unfortunately, unpredictably among individual patients. To date, no form of medical therapy has demonstrated convincingly either an ability to retard the atherosclerotic process or to enhance the growth of collateral circulation. Cessation of smoking and control of hypertension are the two most significant factors in medical therapy. The value of decreased lipid intake is strongly supported on theoretical grounds but unfortunately has not been proved with long-term data. Excersise programs, weight reduction, and other measures to increase collateral circulation, although theoretically sound, also have not yet demonstrated a major impact on the course of the disease. Fortunately, atherosclerosis developing in the vein grafts, which can be readily demonstrated in the experimental laboratory, has not been a significant factor causing late occlusion of vein grafts. Considerations of techniques of myocardial preservation. As repeatedly emphasized in this report, one of the principal factors influencing results following bypass grafting is the degree of injury to the myocardium at operation. Undoubtedly, in some cases in which a large amount of myocardium is infarcted,

Volume 75 Number 1

January, 1978

not only does the patient survive but also the injury may not even be detected unless selective enzymatic measurements are done or a catheterization is performed some months later. The electrocardiogram probably remains the best tool for detecting gross infarction but clearly does not indicate lesser degrees of injury. The simple fact that wide variations in operative technique exist clearly indicates that no one technique of operation has yet been proved best because of this inability to measure quantitatively the degree of myocardial injury. Current techniques include varying degrees of hypothermia, varying degrees of ischemia, operating with the heart beating or fibrillating, venting or not venting the left ventricle, using potassiuminduced cardioplegia, and other methods. Another reason for the variation in operative technique is that the hazard of myocardial injury varies both with the extent of disease and the degree of myocardial injury that has already occurred from previous infarctions, manifested by decreased contractility of the ventricle. A ventricle with triple vessel disease and an ejection fraction of 0.30 is far more susceptible to injury at operation than is a heart with single vessel disease and a normal ejection fraction. Although different operative techniques are still being evaluated, such as potassium-induced cardioplegia, our strong preference at present is for the technique described in the Methods section." This includes initially attaching grafts to the aorta, with the patient, usually, though not always, on bypass to support the myocardium, and then performing the distal anastomoses during periods of ischemia no longer than 10 to 15 minutes while the myocardium is cooled to at least 25° C. and often lower by the use of topical hypothermia. After each period of ischemia, the "oxygen debt" is corrected by permitting the heart to beat for five to 15 minutes, depending upon the collateral circulation and the electrocardiogram. Periods of prolonged fibrillation are avoided because of numerous data indicating the harmful effects of fibrillation on flow of blood through the collateral circulation.P: 16 The left ventricle almost always is vented and left atrial pressure is monitored. The reason for our strong preference for this operative technique is based on the dramatic results obtained in patients with severe impairment of left ventricular function, published in a previous report from this institution." A particularly significant finding in the past year has been discovery of the fact that myocardial injury often occurs before bypass is started, apparently associated

Influence of coronary bypass on longevity

35

with changes in collateral circulation with induction of anesthesia and performance of the operative incision. 17 This often is not detected by the electrocardiogram but can be detected by serial CPK-MB measurements and also by monitoring left atrial pressure with either a Swan-Ganz catheter inserted before anesthesia is induced to monitor wedge pressure or by promptly opening the thorax and monitoring left atrial pressure. To illustrate, in a few patients who have extensive coronary disease with a normal left atrial pressure, atrial pressures as high as 20 to 30 mm. Hg have been found to develop with induction of anesthesia. These pressures can be corrected promptly within three to five minutes by intravenous infusions of nitroglycerin or nitroprusside. Clearly, this is a field in which further advances in myocardial preservation may be made in the future. In the past, such myocardial injuries were probably erroneously attributed to the operative technique and not recognized as having developed before extracorporeal circulation was started. Indications for operation. As stated several times in this paper, most patients were operated upon for disabling angina refractory to available medical therapy. Patients with mild, stable angina were usually not operated upon. Also patients with few or no symptoms but extensive disease demonstrated on angiography often were not operated upon. Others, of course, sharply disagree with these indications for operation, correctly emphasizing that many patients dying from a massive infarction never have severe angina beforehand. The best method for selecting patients for operation is yet undertain and can be determined best by long-term randomized studies in which patients with comparable disease are randomized for medical and surgical therapy. At New York University, we are currently participating in such a nationwide study, coordinated through the National Institutes of Health. The principal question, of course, in a patient with coronary disease is whether the spontaneous development of collateral circulation will negate the harm from progressive atherosclerotic occlusion. From many clinical experiences, it seems unlikely that many patients with coronary disease will ever require bypass grafting. Perhaps a valid analogy exists for atherosclerotic disease in the lower extremit. Patients who have occlusion of the superficial femoral artery with claudication have an excellent 5 year prognosis with nonoperative therapy, but more severe forms of the disease, producing rest pain or atrophic changes in the foot, have a high risk of amputation within I to 2 years unless operation is done. How to separate the patient who is developing adequate collateral circulation from the one

The Journal of

36 [sam et

at.

who is not is one of the leading present challenges in cardiology. A somewhat somber analysis was published by Kimbiris.t" who restudied 35 patients with angiographic evidence of coronary disease 8 to 50 months after the initial angiograms had been performed (mean 26 months). Sixty-nine percent had an increase in severity of their disease whereas 31 percent showed no significant change. In the fortunate group of 31 percent with no progression of disease, two thirds continued to have significant anginal symptoms whereas one third showed improvement with medical therapy alone. None of the patients with progression of disease had improvement in symptoms. Hence, in this small group, the somber conclusion was that only 10 percent became asymptomatic, probably due to the development of adequate collateral circulation. Randomized studies thus far available have not shown significant differences in survival with medical and surgical therapy, but the great variation in operative techniques used among different groups, with resulting degrees of injury to the myocardium, makes current studies of dubious validity. 19 The long-term data presented in this report, confirmed by similar long-term data from other institutions,"" support the contention that coronary bypass grafting does prolong life.

2

3

4 5 6

7

REFERENCES Spencer FC, Green GE, Tice DA, Glassman EG: Surgical therapy for coronary artery diesase. Curr Probl Surg, 1970 Spencer FC, Green GE, Tice DA, Wallsh E, Mills NL, Glassman EG: Coronary artery bypass grafts for congestive heart failure. J. THORAC CARDIOVASC SURG 63:353, 1971 Isom OW, Spencer FC, Glassman E, Dembrow JM, Pasternack BS: Long-term survival following coronary bypass surgery in patients with significant impairment of left ventricularfunction. Circulation 51,52: Suppll:141, 1975 Mundth ED, Austen WG: Surgical measures for coronary heart disease. N Engl J Med 293:13, 1975 Kaplan EL, Meier P: Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457, 1958 Spencer FC, Isom OW, Glassman E, Boyd AD, Englemann RM, Reed GE, Pasternack BS, Dembrow JM: The long-term influence of coronary bypass grafts on myocardial infarction and survival. Ann Surg 180:439, 1974 Stiles QR, Lindesmith GG, Tucker BL, Hughes RK, Meyer BW: Long-term follow-up of patients with coronary artery bypass grafts. Circulation 54: Suppl 3:32, 1976

Thoracic and Cardiovascular Surgery

8 Sheldon WC, Loop FD: Direct myocardial revascularization-1976. Clevel Clin Q 43:97, 1976 9 Teck1enberg PL, Alderman EL, Miller DC, Shumway NE, Harrison DC: Changes in survival and symptom relief in a longitudinal study of patients after bypass surgery. Circulation 51, 52: Suppl 1: 98, 1975 10 Rose MR, Glassman E, Isom OW, Spencer FC: Electrocardiographic and serum enzyme changes of myocardial infarction after coronary artery bypass surgery. Am J Cardio1 33:215, 1974 11 Presented at Second Henry Ford Hospital International Symposium on Cardiac Surgery, October, 1975 12 Bruschke AVG, Proudfit WL, Sones FM: Progress study for 590 consecutive non-surgical cases of coronary disease followed 5-9 years. I. Arteriographic correlations. Circulation 47: 1147, 1973 13 Glassman E, Spencer FC, Krauss KR, Weisinger B, Isom OW: Changes in the underlying coronary circulation secondary to bypass grafting. Circulation 49, 50: Suppl 2:80, 1973 14 Adams PX, Cunningham IN, Trehan N, Brazier J, Reed GE, Spencer FC: Clinical experience using potassiuminduced cardioplegia with hypothermia in aortic valve replacement. Circulation, submitted for publication, 1978 15 Hottenrott C, Buckberg G: Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial flow. II. Effects of ventricular distention. J. THORAC CARDIOVASC SURG 68:626, 1974 16 Isom OW, Kutin ND, Falk EA, Spencer FC: Patterns of myocardial metabolism during cardiopulmonary bypass and coronary perfusion. J THORAC CARDIOVASC SURG 66:705, 1973 17 Isom OW, Spencer FC, Feigenbaum H, Cunningham J, Roe C: Prebypass myocardial damage in patients undergoing coronary revascularization. An unrecognized vulnerable period (abstract). Circulation 52: Suppl 2:119, 1975 18 Kimbiris D, Lavine P, Van Den Broek H, et al: Revolution-patern of coronary atherosclerosis in patients with angina pectoris. Coronary arteriographic studies. Am J Cardiol 33:7, 1974 19 Mathur VS, Guinn GA, Anastassiades LC, Chahine RA, Korompai FL, Montero AC, Luchi RJ: Surgical treatment for stable angina pectoris-prospective randomized study. N Engl J Med 292:709, 1975

Discussion DR. ARTHUR M. VINEBERG Montreal, Quebec, Canada

Dr. Isom's paper concerns longevity after aorta-coronary artery vein bypass grafts. A follow-up of 2 to 5 years is short, and no mean is given. Neither angina class nor ventricular failure is reported. Results include double and triple coronary obstructions, but the left coronary artery is not mentioned. I have treated 18 patients who underwent right ventricular-mammary artery implants for recurrent pain 1.3

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to 13 years after a left ventricular implant (mean 5.4 years). Our first patient, operated upon 12.5 years after left ventricular implant, died (operative mortality rate 5.5 percent). The left ventricular implant was the only artery open in the heart. Improvement was noted in 88.2 percent, and late deaths had occurred in 22 percent a mean of 6 years after the left ventricular implant operation. Cineangiograms were taken of the left ventricular implant in six cases: All were patent, five showed anastomoses with the left coronary system, and some with the right coronary system. Neither Read's nor Isom's paper mentions locations of significant occlusions or of collaterals arising proximally and filling other coronary arteries retrograde. To compare medical and surgical treatment of coronary artery obstructive disease, we must have this information. For example, one of my patients had 80 percent obstruction of the right and left coronary ostia plus disseminated distal disease without conus branches or collaterals. The condition of this patient improved markedly after a left followed by a right mammary artery implant. Such a case cannot be compared with those patients with triple distal coronary obstructions and proximal collaterals. DR. RICHARD P. ANDERSON Seattle. Wash.

This study represents an enormous amount of work and I congratulate the authors. Several years ago Drs. Rahimtoola, Bonchek, Starr, and I reported on a similar group of 536 patients with chronic angina. The operative mortality rate was 3.4 percent, and the 4 and 5 year actuarial survival estimate was 89 percent.

I would pose a question which our study could not answer: What is the impact of operative mortality on late survival? After a relatively high operative mortality rate in the late 1960's and early 1970's, many have noted a steady reduction in risk. For example, at The Mason Clinic there has been one 30 day death in 275 patients in 2lh years. However, when we look today at survival curves much beyond 4 years, we are looking at patients who survived operation during a time of relatively high risk. Does this mean that potential late deaths were culled out in the operating room, making late survival appear better than it really is? Or does it mean that the presumably greater myocardial damage and undergrafting of early years jeopardized our early patients and made their late survival rates worse than those to be anticipated for patients operated upon more recently? This study might answer these questions by a division into two parts, say around mid-1972, and construction of two survival curves, one for the early and one for the late experience. Thus we may be able to predict a more authentic prognosis for present day patients. Have the data been looked at in this way? DR. IS OM (Closing) I would like to thank Dr. Vineberg for his remarks. With regard to Dr. Anderson's question, we have evaluated that point. The survival curve for the patients operated upon since 1972 is superimposable on the expected survival curve for the age-adjusted population.