Clinical outcome of single versus sequential grafts in coronary bypass operations at ten years’ follow-up

J THORAC CARDIOVASC SURG 1991;101:1076-81

Clinical outcome of single versus sequential grafts in coronary bypass operations at ten years' follow-up To evaluate the long-term outcome of the sequential aorta-coronary bypass grafting technique, we compared the results in 234 patients with single venous grafts (group I) with those of 234 patients with predominantly sequential grafts (group 0). All were symptomatic for angina pectoris before operation and had either three-vessel or left main stem coronary artery disease. Operations were performed from March 1975 to June 1980. The mean foUow-up period was 10.5 years (minimum 8.5; maximum 13.6). The perioperative mortality rate in group I was 3 % and in group II, 1 % (not significant). The survival probability at 5 years after operation for group I was 90 % ± 2 % and for group II, 88 % ± 2 %; at 10 years, 71 % ± 3% and 72% ± 3%, respectively. Multivariate analysis e6cited no risk difference related to graft type: group II versus group I hazard ratio, 0.82; 95% confidence interval 0.58 to 1.16 (not significant~ Regarding depressed left ventricular function versus normal function, an increased risk was observed: 1.9 (95% confidence interval 1.35 to 2.75), as was the case for advanced age: 60 years or more versus less than 60 years, 1.6 (1.1 to 3.5). Thus the sequential venous grafting technique seems to have the same lo-year results as single venous grafts.

Karin Meeter, MD, RolfVeldkamp, MD, Jan G. P. Tijssen, PhD, L. Lex van Herwerden, MD, and Egbert Bos, MD, Rotterdam, The Netherlands

Athough it is generally agreed that the internal mammary artery implant is a better bypass conduit than the saphenous vein.l-? the v.ein is still often used for a variety of reasons.' Therefore a study into the long-term follow-up of patients treated with sequentialversussingle vein grafts is one that is of interest, because the decision on whichtechnique to use is stillfaced daily. The sequential graft was advocated initially because it shortened the operative procedure and made a more complete revascularization possible.f" Later an improvedpatencyrate was reported by Sewell," while Grondin and coworkers'v? pointed out that with the proper technique even anastomosesto very small coronary arteries could be successful. The obvious disadvantage, however, is that the entire revascu1arization depends on the one proximal segment. A closure of this proximal segment would result in a catastrophic decrease in myocardial blood supply. The fear of a closure occurring in the proximal segment has led in From the Department of Cardiology and Thoracic Surgery, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands. Received for publication Oct. 30, 1989. Accepted for publicationAug. 6, 1990. Address for reprints: K. Meeter, MD, Thoraxcentrum, Bd 375, Department of Cardiology, Erasmus University Rotterdam, P.O. Box 1739,3000 DR Rotterdam, The Netherlands.

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many instances to a return to the single-graft technique as advocatedby Kieser,FitzGibbon,and Keon.lO Whether this prudent policy is warranted is, however, not certain. If a proximalstenosisin a sequentialgraft occurs frequently, patients with such grafts would have a poor long-termprognosis. To addressthis possibility, weexamined the operativeresultsof patients whoreceived sequential grafts from 8 to more than 11years ago. Survivaland cause of death of these patients were compared with the findings in patientswhohad received singlegrafts and had undergone operations generally in the same period. Methods The study included consecutive patients with three-vessel or left main-stem coronary artery disease with a first aorta-coronary bypass operation between March 1975 and June 1980. All patients had angina pectoris, stable or unstable, despite the intensive pharmacologic therapy available at that time. No distinction was made between elective or emergency operation. Excluded were those patients with concomitant surgical interventions such as valve replacement and aneurysrnectomy. In May 1977 the surgical team started to use sequential or jump grafts. Gradually the use of single grafts declined, and by 1980 only the sequential technique was applied. The period from which patients were analyzed was chosen to ensure that two groups were created, each consisting of an equal number of patients in which either technique was used. Group I (n = 234) was composed of patients in whom the single-grafting technique had been applied; for the patients in group II (n = 234) the

Volume 101 Number 6 June 1991

technique of sequential grafting was chosen. Some of the operations were concurrent, but in general the single-grafting technique was used before the complete shift to sequential grafts was made. At first the preferred method was a side-to-side anastomosis to the left anterior descending branch and diagonal branch with an end-to-side anastomosis on the circumflex artery. A single graft was placed on the right coronary artery. In ± 50% of the cases this was combined with an intimectomy. After a period of time, this technique evolved into a side-to-side anastomosis on the left anterior descending, diagonal, and circumflex branches, with an end-to-side anastomosis on the descending posterior branch without intirnectomy. The mixed technique was used in 175 patients, whereas 59 patients received only a sequential graft. All were considered to belong to group II. Thus the choice of surgical technique was determined by the period in which the operation was performed, by the technical circumstances, and by the personal choice of the surgeon. As operative procedures had started in 1971, the learning period of the surgical team was avoided by the inclusion of patients operated on from 1975 onward. At catheterization, a vessel was considered diseased when a luminal diameter narrowing of at least 50% was seen in a major coronary artery in more than one projection. This resulted in a classification of one-, two-, or three-vessel or left main-stem disease. At the same catheterization the ejection fraction was calculated, where possible, with the area length method adjusted for single-plane view. The clinical characteristics of the patients are listed in Table I. In all patients the same surgical procedure was followed. After initiation of cardiopulmonary bypass the body temperature was lowered to 28 0 C. The venous material was preferentially obtained from the lower leg. In the case of a sequential graft, the greater saphenous vein was sufficient (± 35 em). For multiple grafts the incision was extended into the thigh, or the small saphenous vein of the calf was used. The vein was harvested under gentle flush with Hanks solution and stored in this medium until use. Single right atrial cannulation was employed. Topical cooling of the heart was performed with saline at 4 0 C; no chemical cardioplegic solution was used. After the start of ventricular fibrillation, with use of intermittent crossclamping, all distal anastomoses were placed. End-to-side and side-to-side anastomoses were made with a 6-0 or 7-0 Prolene continuous suture (Ethicon, Inc., Somerville, N.J.). The end-to-side aorta-venous anastomoses were made with a 5-0 Prolene continuous suture. The intention was to bypass all proximal lesions in the major coronary arteries, making the revascularization as complete as possible. The heart was subdivided into three main areas, supplied by the anterior descending or the circumflex branch of the left coronary artery or by the right coronary artery. Revascularization was considered complete when all three affected areas received at least one bypass graft. When the main stem of the left coronary artery was diseased, revascularization was considered complete only if both branches received a bypass graft. Survival data were collected at the civil registry. Follow-up was complete for 460 of the 468 patients (98%). Missing were three patients from group I and five from group II. The follow-up data were collected on November 28, 1988. Group I had been followed up for a mean of 11.2 years (minimum 8.7; maximum 13.6) and group II for a mean of9.8 years (minimum 8.5; maximum 11.5). When applicable, the cause of death was determined via hospital files or via contact with the general practitioner or the treating specialist. Information on the cause of death was

Single versus sequential CABGs

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Table I. Clinical profile of the patients with single grafts (group I) and a sequential graft (group II) Group I = 234)

Mean age (yr) Male Vascular disease Three-vessel Left main stem Left ventricular function Normal (EF 2:0.55) Impaired (EF <0.55) Unknown

Group II = 234)

p Value

(n

(n

52 ± 7 218 (93%)

55 ± 9 201 (86%)

<0.02

203 (87%) 31 (13%)

191 (82%) 43 (18%)

NS NS

125 (53%) 68 (29%) 41 (18%)

109 (46%) 100 (43%) 25 (11%)

<0.02 <0.02

NS

NS

NS, Not significant; EF, ejection fraction.

obtained for 143 patients of the 149 who had died at the time of follow-up (96% complete). Mortality was divided into perioperative mortality, occurring within 28 days after operation, and late mortality, occurring in the ensuing period. Late mortality was further subdivided into cardiac sudden (death occurring within I hour after onset of complaints), cardiac chronic, cardiac infarction (if registered as such in a hospital), cardiac at reoperation, and noncardiac. The number of patients dying in a certain year expressed as a percentage of the average number at risk in that year was considered the yearly mortality rate. In the first postoperative year the perioperative mortality was not included in the yearly mortality. The probability of survival was estimated by the KaplanMeier method of actuarial survival.'! The curves thus obtained were compared with the log rank test. The Kaplan-Meier method was also used to examine whether the difference in baseline in the two subgroups could influence the probability of survival (univariate analysis). If this test suggested a difference in probability, this variable was used in the Cox proportional hazard model to analyze its predictive value.l? Selected for entry into the multivariate model were the technique applied (i.e., single or sequential grafting), age at operation, and preoperative ejection fraction. The number of distal anastomoses was not considered because this depended on the chosen technique. Dichotomized varia bles were compared in the x2 test or, where appropriate, in Fisher's exact test. In all cases a difference in value or ratio was considered significant only if p was less than 0.05.

Results The data relatingto the operative procedureare shown in Table II. The averagenumberof distal anastomoses in these patients with either three-vessel or left main-stem disease was greater in the patients receiving a sequential graft than in thosewith onlysinglebypass grafts. Consequently the revascularization procedure was more often complete in group II: 90%compared with 70%in group I. The perioperative mortality rate was 1.9% overall (9/ 468)and wasnotsignificantly differentin the twogroups. At follow-up, whichamountedfor the total group to a mean of 10.5 years (minimum 8.5 and maximum 13.6), 149of the 468 studiedpatientshad died.The yearlymor-

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Thoracic and Cardiovascular Surgery

Yearly mortality

%

9

at ri sk

lI68

8

lI39

lI33

lI25

lIlli

lI07

392

375

312

219

7

8

9

10

6

5 II 3 2

o II

5

6

Fig. 1. Yearly mortality expressed as percentage of the average number of patients at risk during the year under consideration.

Table II. Data directly related to the operation for patients receiving single grafts (group I) or a sequential graft (group II) . Group I = 234)

(n

Perioperative mortality Revascularization complete Distal anastomoses

7 (3%) 164 (70%) 3.0 ± 0.8

Group 1/ = 234)

p Value

(n

2 (1%) 211 (90%) 4.0 ± 1.0

NS < 0.0001 P < 0.001

p

NS. Not significant.

tality rate is shown in Fig. 1. In the first six postoperative years, a fluctuation is observed between 2.4% and 1.4% per year (mean, 1.9%). In the seventh postoperative year an increase was found to 3.5%. In the ninth year the percentage rose to 4.8% and subsequently to 7.2%. Of those who died, 86 belonged to group I and 63 to group II. The cause of the deaths is shown in Table III. In group I most patients died either suddenly or of an acute myocardial infarction, together accounting for 57% (48/86), whereas in group II these causes amounted to 42% (27/63). In group II a relatively large number of patients died of chronic cardiac failure-22% (14/63). None of the observed differences were significant. As the observation time differed for the two groups, no conclusions regarding survival could be drawn regarding survival from the absolute numbers of deaths in each group. The actuarial survival curves shown in Fig. 2, however, make a comparison possible. No appreciable difference was found. At 5 years postoperatively 209 patients were at risk in group I; the survival probability was 90% ± 2%. In group II 205 patients were at that time followed up, and

the survival probability was 88% ± 2%. At 10 years . the corresponding figures were for group I 123 (71% ± 3.0%), and for group II 96 (72% ± 3.0%), respectively. The Kaplan-Meier method was used for univariate analysis of factors that might influence survival. No predictive influence was found to be connected to sex, type of vascular disease, that is, left main-stem or th,ree-vessel disease, or completeness of revascularization. Age and preoperative ejection fraction did suggest an influence. Consequently these parameters and the technique of bypass grafting were entered into the multivariate logistic regression analysis. The results of the analysis are expressed as hazard ratios, that is, the death rate (number of events per unit of person-time of follow-up) in a particular category divided by the death rate in a reference category, provided that other characteristics entered into the survival model are equal. The outcome of the analysis is shown in Table IV and confirms the impression from the survival curves in Fig. 2 that the chosen surgical technique does not by itself influence the survival probability. As shown in other studies, older age and depressed left ventricular function do have an adverse influence on longevity. The number of rerevascularizations was recorded as well. In general this was done only when symptoms made it necessary. At 10.5 years after the initial bypass operation (the mean follow-up duration for the entire study group), 88 patients (19%) had undergone at least one rerevascularization. This meant in 76 cases another bypass procedure and in 12 an angioplasty. These cases were distributed virtually equally in the two groups. In

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Single versus sequential CABGs

June 1991

Survival probability (%)

100

80

60

40 183 79+ / - 3 188 82+/-2.5

209 90+/-2 205 88+/-2

234 100 234 100

20

123 Ngroup I 71+/-3 % 96 Ngroup II 72+/-3 %

o-l------.-....:....--.........,.....---r---~--_r_--__r--___, 12

10

14

Survival time (years)

Fig. 2. Actuarial survival curve of patients with single grafts only (group I) and sequential grafts (group II). The

vertical bars indicate the 95% confidence interval.

Table III. Number ofpatients who died during follow-up in group I (single grafts only) and group II (sequential grafts), with. the cause of death as absolute number followed by the percentage Group II

Group I

In = Cause of death Perioperative Late cardiac Sudden Infarction Chronic Reoperation Noncardiac Unknown Total

In =

234)

All

In =

234)

468)

No.

%

No.

7

8

2

3

9

6

32 17 10 4 14

37 20 12 5 16

13 14 14 4 12

21 22 22 6.5 19

45 31 24 8 26

31 21 16 5 17

-..1

--.1

~

-2

--..1

No.

86

%

100

group 137 patients had a second bypass operation (16% of the original number in the group) and seven (3%) underwent angioplasty. Corresponding figures for group II were 39 (17%) and five (2%). Of these patients who were restudied, 21 of the 44 belonging to group II showed a problem in the proximal segment of the sequential graft (closure in 13, stenosis in eight). In nine of the 21, the distal portion was opacified and could have functioned as a collateral vessel. As to symptomatic state at follow-up, no difference could be found between the two groups. Subjective improvement compared with condition before the bypass procedure was reported by 86% of the surviving patients in group I and by 88% in group II. Meaningful data were missing in 17 patients in group 1(11 % of the survivors).

~

63

100

149

%

100

No angina or almost no attacks were experienced by 60% of the patients in group I and 61 % in group II. Discussion The advantages of the sequential grafting technique are evident. The operating time and ischemic arrest time can be shorter. Brower and coworkers' calculated in 1981 that at our institution the implantation of four single grafts would require 23 minutes more of ischemic arrest time than the implantation of a jump graft with four distal anastomoses. Additionally, the revascularization can be more complete because anastomoses can be made on smaller coronary arteries. 8-10 This observation was shared by us. Revascularization was complete in 90% of the patients with a sequential graft and in 70% of those with

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Table IV. Hazard ratio from Cox's regression analysis of survival

Sequential vs, single grafts EF <0.55 vs, EF ~0.55 EF unknown vs, EF ~0.55 Age ~60 yr vs, <60 yr

Hazard ratio

95% CI

P Value

0.82 1.94 1.63 1.63

0.58-1.16 1.35-2.75 1.02-2.60 1.12-2.37

P = 0.26 P <0.001 P <0.05 p<0.012

EF, Ejection fraction; CI, confidence interval.

single grafts. Moreover, it has been reported that the patency of the sequential grafts is relatively favorable compared with that of single grafts. Meurala and associates'! reported a late patency rate of sequential grafts of95% and of 80%for singlegrafts. Althoughothers did not find this difference, the patencyof sequential grafts was not lowerthan the patency of singlegrafts in any study.5, 7, 8 Althoughthe total bloodflow to the myocardium is probably slightly less with the choice of sequential techniquecomparedwith the singlegraft with an equal number of distal anastomoses, the flow velocity in the proximalsegmentof the sequential graft is higher than in each single graft, I4, 15 which might enhance patency. Finally,in the case of a proximal-closure in the graft, we haveobserved an additionaladvantageof the sequential over the single graft. The distal segment of the sequential graft can in that case function as a large collateral vessel, which is impossible for a singleconduit. The obvious disadvantage of the jump graft technique is that a sudden cessation of the additionalbloodflow to the myocardium via the graft would have much more serious consequences when it concerned a sequential rather than a singlegraft. In the caseof a singlegraft only the area supplied by one coronary artery would be affected, whereas with a jump graft this would be the entire left ventricular wall. As the yearly mortality rate increases from ± 2% to ± 4%and more after 5 postoperative years in this study, progression of the atherosclerotic process seems to be a major problem. This same tendency of an increase in mortality was seen in surgically treated patients in the VeteransAdministrationStudy.l" The time at whichthe increasein mortalitywasnoted wassimilarto that which we observed as higher yearlymortality 7 to 8 yearsafter operation. In view of the fact that the increased mortality was seen only in the surgically treated patients,it seems all the more likely that there is a relationship with the surgical procedure. Only loss of patency of the bypass graft(s) could be the cause. As Campeau,'? Loop.l" and their associates have described, after 5 years an accelerated loss of patency of previously functioning grafts

occurs. Therefore the concern about future events in patients with sequential coronary bypass grafts seemed justified. Furthermore, the periodin which the problems could be expected to occur falls within our observation time. Yet the facts do not support the concern. Both the univariate and the multivariate analyses show that patientswitha sequential bypassgraft are not at an additional risk of dying or of having to undergo a second revascularization procedure compared with those patients in whom the singlegraft technique was chosen, at least not withinthe observation time of our study.Furthermore, we have not observed more sudden deaths or deathsresulting froma myocardial infarction inthe group of patients with a sequential graft compared with the group with singlegrafts only. The survival probability of the group of patients included in the study was 89% ± 1.5% at 5 years and 71% ± 2%at 10 years.All patientshad either three-vessel disease or left main-stem coronary artery disease. A third of the patients had depressed left ventricular function. All had anginalsymptoms. These patientscould be regardedas a high-risk group.Long-termsurvival data on . patientswho received sequential grafts havebeenreported only by Bigelow and colleagues.'? They found at 5 yearstheslightlylowersurvivalprobabilityof83% ± 4%. However, their patients were operated on at an earlier period (1970 to 1973). In patients with three-vessel disease and saphenous vein grafts, Loop and coworkers" observed a lo-year survival probability that was exactlythe same'as the one wefound(71%).Thereforethe overall resultsofoperation ofthe patientsincluded inthe studyreportedhereare very similar to those obtained elsewhere. However, there are several areas of criticism. First, the years in which the patientswereoperatedon weredifferent for both groups. The patients who received sequential grafts were generally operated on at a later date than those who received only single grafts. It is conceivable that the anesthetic management and postoperative care had improved through the years, favoring group II patients. However, no significant differences were observed in perioperative mortalityin the twogroups. Moreover, the learningperiod forthe coronaryartery operationin whichsingle grafts alone were used was not included in the studied period, but the learningperiodfor the sequential technique was. If any bias was introduced by the difference in time, it shouldbe against group II patients.Second, this is a retrospective study.The patientswere not randomly allocated to either group. Other factors that are hard to define but that could influence the outcome governed the allocation to either surgicaltechnique. This resulted in a significant difference in clinical characteristics between the two groupsat the time of operation. Patients belong-

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ing to group II were older at operation, more often had an abnormal ejection fraction, and less often had an unknown ejection fraction. All these factors were shown to be risk factors affecting survival. The adverseinfluence of a depressed left ventricular function can be understood, but why failing to measure an ejection fraction should have an adverse influence is unclear unless the majority of these patients had in fact a compromised ventricular function. However, the nature of the multivariate analysis should take care of these inequalities. Only patients with the characteristics to be studied are compared with patients without that characteristic, all other factors being equal. The multivariate analysis showed, with a 95% confidence interval between 0.58 and 1.16, that patients with sequential grafts had the same risk of dying as patients with single grafts. Last, it could be argued that in many patients in group II a true sequential graft was not inserted because they received a single graft on the vessel that sometimes underwent an intimectomy as well. This is a shortcoming of the study that cannot be altered. The technique in which just one sequential graft was inserted was applied at a later date. A study now would not yield an observation time long enough to give meaningful results. Yet the decision of which technique to use is faced daily. Therefore it seemed justified to examine methods that, although they only approximate the techniques applied today, would result in a meaningful study rather than to wait for a later date. By the same token, a longer follow-up time would afford better data. At present relatively few patients out of the group with a sequential graft have been followed up beyond 10 years. Here again it can be reasoned that some data are better than none. In conclusion, we feel confident that the technique of sequential grafting with the reversed saphenous vein is not only easier to employ than the single grafting technique, but that the long-range results are also as good. If no mammary artery implantation is possible or ifan addition to the arterial bypass is necessary, then the sequential venous graft with one anastomosis on the aorta and peripheral anastomoses on all remaining graftable coronary arteries is a good strategy.

REFERENCES I. Cameron A, Kemp HG, Greene GE. Bypass surgery with the internal mammary artery graft: 15 year follow-up. Circulation I986;74(Pt 2):III30-6. 2. Loop FD, Lytle BW, CosgroveDM, et al. Influenceof the internal-mammary-artery graft on 10 year survival and other events. N Engl J Med 1986;314:1-6.

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3. AngeliniGO, Newby AC. The future of saphenous vein as coronary artery bypass conduit. Eur Heart J 1989;10:27380. 4. Bartley TO, Bigelow JC, Page KS. Aortocoronary bypass grafting with multiple sequential anastomoses to a single vein. Arch Surg 1972;105:915-21. 5. Brower RW, van Eijk KF, Spek J, Bos E. Sequential versusconventionalcoronary artery bypasssurgery in matched patient groups. Thorac Cardiovasc Surg 1981;29:158-62. 6. Moreno-Cabral RJ, Mamiya RT, Dang CR. Multiple coronary artery bypass using sequential technique. Am J Surg 1977;134:64-8. 7. Sewell WH, Sewell KV. Technique for the coronary snake graft operation. Ann Thorac Surg 1976;22:58-65. 8. Grondin CM, Limer R. Sequential anastomoses in coronary artery grafting: technicalaspeets and early and late angiographic results. Ann Thorac Surg 1977;23:1-8. 9. Grondin CM, Vouhe P, Bourassa MG, Lesperance J, Bourier M, Campeau M. Optimal patency rates obtained in coronary artery grafting with circular vein grafts. J THORAC CARDIOVASC SURG 1978;75:161-7. 10. Kieser TM, FitzGibbon GM, Keon WJ. Sequential coronary bypass grafts. J THORAC CARDIOVASC SURG 1986; 91:767-72. 11. Kaplan EL, Meier P. Nonparametric estimation from incompleteobservation. J Am Stat Assoc 1958;53:457-81. 12. Cox DR. Regression models and life tables. J R Soc Med (Lond) 1972;34:187-220. 13. Meurala H, Valle M, Hekali P, Somer K, Frick MH, Harjola P-T. Patency of sequential versus single vein grafts in coronary bypass surgery. Thorac Cardiovasc Surg 1982; 30:147-51. 14. Prislean WH, VoegeleLO, Hairston P. Flow in sequential vein grafts with diamond anastomoses. J Cardiovasc Surg 1986;27:477-9. 15. O'Neill MJ, Wolf PO, O'Neill TK, Montesano RM, Waldhausen JA. A rationale for the use of sequential coronary artery bypass grafts. J THORAC CARDIOVASC SURG 1981 ;81 :686-90. 16. The Veterans Administration Coronary Artery Bypass Surgery CooperativeStudy Group. Eleven-yearsurvival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina. N Engl J Med 1984; 311:1333-9. 17. Campeau L, Enjalbert M, Lesperance J, Vaislic C, Grondin CM, Bourassa M. Atherosclerosis and late closure of aortocoronary saphenous vein grafts: sequential angiographic studiesat 2 weeks,I year, 5-7 years and 10-12years after surgery. Circulation 1983;68(Pt 2):II1-7. 18. Loop FO, Sheldon WC, Lytle BW, CosgroveOM, Proudfit WL. The efficacy of coronary artery surgery. Am Heart J 1981;101:86-96. 19. Bigelow JC, Bartley TO, Page S, Krause AH. Long-term follow-up of sequential aortocoronary venous grafts. Ann Thorac Surg 1976;22:507-14.