Vein graft disease: The clinical impact of stenoses in saphenous vein bypass grafts to coronary arteries

Volume 103,

Number 5

May 1992

THORACIC AND CARDIOVASCULAR SURGERY The Journal of

Original Communications

Vein graft disease: The clinical impact of stenoses in saphenous vein bypass grafts to coronary arteries The influence of coronary artery stenoses on patient survival and event-free survival is known, but no studies have reported the long-term outcome of patients with stenoses in saphenous vein bypass grafts. We retrospectively studied 723 patients who underwent a postoperative angiographic study that documented a stenosis of 20 % to 99 % in at least one saphenous vein graft and who did not undergo reoperation or percutaneous transluminal coronary angioplasty within 1 year after that catheterization. The mean foDow-up interval was 83 months (range 1 to 237 months). For comparison, a group of 573 patients who underwent a postoperative catheterization that did not show any vein graft stenosis were also foDowed up. Cox regression analyses were used to identify predictors of late survival, reoperationfree survival, and event-free survival. For the entire group of patients with stenotic vein grafts, moderate or severe impairment of left ventricular function (p < 0.001), interval between operation and catheterization (p < 0.001), older age (p = 0.001), triple-vessel or left main coronary artery disease (p = 0.004~ and stenosis of the vein graft to the left anterior descending coronary artery (p = 0.09) were associated with decreased late survival. Patients with an operation-to-catheterization interval 2':5 years were at particularly high risk, and multivariate analyses of that subgroup confirmed that a stenotic graft to the left anterior descending artery was a strong predictor of decreased survival (p < 0.001), decreased reoperation-free survival (p < 0.001), and decreased event-free survival (p < 0.001). Patients 2':5 years postoperatively with 2':50 % stenosis of vein grafts to the left anterior descending artery had survival of 70 % and 50 % at 2 and 5 years after catheterization, compared with 97 % and 80 % for those with 2':50 % stenosis of the native left anterior descending artery (p = 0.002). Late vein graft stenoses are more dangerous than native coronary stenoses. Late stenoses in saphenous vein grafts to the left anterior descending coronary artery predict a high rate of death and cardiac events and are an indication for reoperation. (J THORAC CARDIOVASC SURG 1992;103:831-40)

Bruce W. Lytle, MD, Floyd D. Loop, MD, Paul C. Taylor, MD (by invitation), Conrad Simpfendorfer, MD (by invitation), John R. Kramer, MD (by invitation), Norman B. Ratliff, MD (by invitation), Marlene Goormastic, MPH (by invitation), and Delos M. Cosgrove, MD, Cleveland, Ohio. With the technical and statistical assistance of Maura J. Schnauffer From the Cleveland Clinic Foundation, Cleveland, Ohio. Read at the Seventy-first Annual Meeting of The American Association for Thoracic Surgery, Washington, D.C., May 6-8, 1991.

Address for reprints: Bruce W. Lytle, MD, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, One Clinic Center, Cleveland, OH 44195.

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Lytle et al.

For hundreds of thousands of patients worldwide, the myocardial blood supply is dependent, at least in part, on saphenous vein grafts. Pathologic changes in saphenous vein grafts can produce stenoses, and the proportion of grafts that become stenotic increases with time.l'" The natural history of patients with native vessel coronary artery disease has been intensively studied. Both randomized and nonrandomized studies of patients with native vessel coronary artery disease have provided guidance as to the indications for surgery.?"! However, the pathology of vein graft stenoses is different from that of native coronary artery stenoses and the clinical implications of vein graft stenoses may be different as well. Few data exist that document the natural history of patients with stenoses in vein bypass grafts to the coronary arteries.F To define the clinical implications of vein graft stenoses, we studied 723 patients who were found at a postoperative angiographic study to have a stenosis in at least one saphenous vein graft. For comparison, we followed up 573 patients who had a postoperative catheterization that did not define stenoses in any vein graft.

Patient population, methods, and definitions With the aid of our computerized cardiovascularinformation registry, we identified 723 patients who fulfilled the following criteria. I. Operation for isolated coronary bypass grafting was performed at The Cleveland Clinic Foundation. (Operations were performed during the years 1970 to 1985.) 2. A postoperativeangiographic study was performedat The Cleveland Clinic Foundation that demonstrated a stenosis of 20% to 99% of the lumen of at least one vein bypass graft to a coronary artery. So long as there was one stenoticveingraft, the patient could, in addition, have other grafts that were totally occluded, stenotic, or that were patent without stenoses. The angiographic study that documented the vein graft stenosis is termed the stenotic cath. 3. No invasive revascularization procedure (bypass grafting or percutaneous transluminal coronary angioplasty [PTCAj) was performed between the operation and the stenotic cath. 4. No cardiac reoperation or PTCA was performed within a year after the stenotic cath. For purposes of comparison, we identified another group of 573 patients (the control group) who underwent bypass grafting and then had a postoperative catheterization that did not demonstrate any stenotic grafts. For this group of patients, all the grafts either were patent without stenoses or were totally occluded.This group also did not undergo PTCA or reoperation within a year of catheterization. Baselinedescriptors of clinical and angiographic variables for both the study group and the control group are listed in Appendix I. All patients were followed up by telephone or letter. The mean follow-up interval after the catheterization that documented the graft stenosis was 83 months (range I to 237 months), and for patients without stenotic vein grafts, 101 months (range 0 to 251 months). Events identified during follow-upwere death, reoperation, PTCA, and myocardial infarc-

tion. Among the 723 patients with stenotic vein grafts, there were 205 deaths, 181 reoperations, 24 PTCAs, and 57 myocardial infarctions during the follow-up period and for those without stenoticveingrafts 200 deaths, 121 reoperations, 22 PTCAs, and 75 myocardial infarctions. Causes of death are listed in Appendix 2. Late survival, reoperation-free survival, and event-free survivalfigures were calculated with the Kaplan-Meier method.!' We wereattempting to definethe impact of the anatomy present at the catheterization on patient outcome. Therefore, if the patient subsequently underwent reoperation or PTCA, we removedthe patient from the sample whena repeat intervention occurred when calculating survival. In calculating reoperationfree survival, we removed patients from the sample if they underwent PTCA and we left them in the sample if they had a myocardial infarction. Multivariate testing was done with the Cox proportional hazard model.!"

Results Univariate testing of the variables listed in Appendix 3 followed by multivariate testing in a Cox proportional hazard model identified the variables listed in Table I as having influence on survival, reoperation-free survival, and event-free survival ofthe entire group of patients with stenotic vein grafts. The interval between operation and the stenotic cath had a very strong impact on late outcome. Therefore, in subsequent testing, we separately analyzed patients on the basis of that interval ( <5 years and 2::5 years). Fig. 1 compares survival for patients with and without stenotic vein grafts separated according to the interval between operation and catheterization. Patients with an operation-to-catheterization interval 2::5 years with (n = 292) and without (n = 212) stenotic vein grafts were included in Cox proportional hazard models (Table 11). A stenosisof20% t099% in a vein graft to the left anterior descending coronary artery (LAD) was associated with decreased survival, reoperation-free survival, and event-free survival. A total occlusion of a vein graft to the LAD decreased survival slightly but was not as strong an indicator of an unfavorable outcome as was a stenotic LAD graft. Stenoses in grafts to the circumflex or right coronary artery did not appear to influence late outcome. In univariate survival comparisons, patients with a stenosis (20% to 99%) in an LAD vein graft had a significantly worse outcome than did patients with a stenosis in grafts to the circumflex or right coronary artery (and no LAD graft stenosis) or no vein graft stenosis (Fig. 2). Results of univariate comparisons done to examine in more detail the outcome of specific subsets of patients with a postoperative catheterization interval of :::::5 years are shown in Table III. Table III focuses on the clinical outcome over the first 2 years after catheterization. For patients with an operation-to-catheterization inter-

Volume 103 Number 5 May 1992

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Fig. 1. Survival of patients with stenotic vein grafts and patients without stenotic vein grafts (control group) according to the interval between operation and catheterization. Both groups of patients with a postoperative interval :::0:5 years had worse survival (p = 0.0001) than both groups with an interval <5 years. However, within each postoperative interval group there was no difference in survival between the control group and the group with vein graft stenoses.

- - No Vein Graft Stenosis - - _. LAD Vein Graft 50-99% .. ---- ... LAD Vein Graft 20-49%

0

n=212

n- 52 n- 30

3

4

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121 25 11

84 18 6

68 8 5

2 YEARS NUMBER AT RISK

148 31 22

Fig. 3. Survival according to the degree of late stenosis in an LAD vein graft. Patients with a moderate (20% to 49%) stenosis in an LAD vein graft had equivalent survival to the control group during the first 2 years after catheterization. However, between 2 and 5 years their survival decreased dramatically, so that over the entire 5 years their survival was significantly worse (p = 0.02) than that of the control group and was not different from that of patients with more severe (50% to 99%) LAD vein graft stenoses (p = 0.90).

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Fig. 2. Patients with postoperative interval to catheterization :::0:5 years. Patients with a circumflex (CX) or right coronary artery (RCA) vein graft stenosis had survival equivalent to that of the control group. Patients with an LAD vein graft stenosis had significantlyworse survival (p = 0.0006) than either of the other two groups. val of 2':5 years, the degree of stenosis in an LAD graft had a slight effect on outcome. Over the first 24 months after catheterization (Table III), patients with a moderate (20% to 49%) stenosis in an LAD vein graft had a survival that was not significantly different from that of patients with no vein graft stenoses. However, the survival of the patients with moderate LAD graft stenoses then worsened, so that over the entire period of follow-up the difference between their survival and that of the control group was significant (p = 0.02) and their survival by 5

20

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Fig. 4. Reoperation-free survival according to the degree of late stenosisin an LAD vein graft. Patients with moderate (20% to 49%) LAD vein graft stenoses had equivalent reoperationfree survival to those with more severe stenoses (p = 0.90), and both groups of patients had worse reoperation-free survival than the control group.

years after catheterization was as bad as that of patients with more severe stenoses (Fig. 3). In addition, the reoperation-free survival of patients with 20% to 49% stenoses was significantly worse than that of the control group (Table III and Fig. 4). Patients with late LAD vein graft stenoses of 50% to 99% had a significantly worse survival than did patients

834

The Journal of Thoracic and Cardiovascular Surgery

Lytle et al.

Table I. Results of Cox proportional hazard models involving all patients with stenotic vein grafts (n = 723): Factors adversely influencing late outcome p Value

Reoperaiion-free

Event-free

Variable

Survival

survival

survival

LVF (MIS) Postop. interval (of cath) * Age (at cath)t 3VD/LMT Stenotic LAD vein graft (20%-99%):1: Functional class at cath No. of stenotic grafts

<0.001 <0.001 0.001 0.004 0.09 NS NS

<0.001 <0.001 NS 0.03 0.008

<0.001 <0.001 NS 0.04 0.007 O.oI 0.001

0.01

0.001

LVF (M/S), Left ventricular function, moderate or severe impairment; Cath, catheterization; 3VD/LMT, native vessel coronary artery disease. stenosis in three vessels or left main coronary artery 2c50%; LAD. left anterior descending coronary artery; NS, not significant. 'Interval <5 years versus 2c5 years. tOlder patients had worse survival. :j:Because patients had either an internal thoracic artery or a saphenous vein graft to the LAD, there was a strong interaction between the variables stenotic LAD vein graft and patent internal thoracic artery graft. In this analysis, patent internal thoracic artery graft was not included.

Table II. Results of Cox proportional hazard models: Variables adversely influencing late results ofpatients with operation-to-postoperative catheterization interval of 2:5 years p Value

Survival LVF (MIS) 3VD/LMT (native vessel) stenoses LAD vein graft stenosis (20%-99%) Age at cath Occluded LAD vein graft No. of stenotic vein grafts Reoperation-free survival LVF (MIS) 3VD/LMT stenosis LAD vein graft stenosis (20%-99%) Patent ITA graft* Indication for cath Age at cath Event-free survival LVF (MIS) 3VD/LMT stenosis LAD vein graft stenosis (20%-99%) Occluded LAD vein graft

<0.001 <0.001 0.001 0.007 0.05 0.05 <0.001 <0.001 <0.001 0.008 0.02 0.03 <0.001 <0.001 <0.001 0.01

ITA, Internal thoracic artery. For other abbreviations see Table I.

'A patent internal thoracic artery graft was associated with increased reoperation-free survival.

with a 50% to 99% stenosis in the native LAD coronary artery (and no graft to the LAD) (Fig. 5). Cox proportional hazard models pertaining to patients who underwent catheterization <5 years after operation are shown in Table IV. These early vein graft stenoses were not identified as factors influencing late outcome. Even stenoses in LAD vein grafts did not appear to decrease survival in univariate (Table V) or multivariate testing. There was a trend toward decreased reoperation-

free survival for patients with LAD vein graft stenoses of 75% to 99% (Fig. 6). Discussion

The purpose of this study was to learn what happened to patients with stenoses in saphenous vein grafts to coronary arteries who did not undergo reoperation. In addition, we wanted to identify variables that were associated with late events to define subsets of patients whose angiographic anatomy predicted such a high-risk late clinical outcome that immediate reoperation should be seriously considered. For comparison, it was necessary to follow up a group of patients who also had undergone bypass grafting but who had no stenotic vein grafts. This enabled us to isolate the influenceof stenotic vein grafts from other factors that might influence the clinical outcome of patients after bypass grafting. This is a nonrandomized, retrospective study. For inclusion in the study, patients had to have a postoperative angiographic study, and since only 24% of patients with stenotic vein grafts had a "routine" postoperative catheterization, it holds that the majority of patients had some postoperative event that led to angiography. In addition, the initial management decision was not to reoperate or to perform PTCA. In general, we have had an aggressive approach to reoperation for patients who have repeat ischemic syndromes after initial bypass grafting. One reason that many of the patients in this study with stenotic vein grafts did not undergo an immediate reoperation is that their symptoms did not seem to indicate reintervention; 84%of patients in the study group had New York Heart Association class I or II symptoms at the time of the catheterization that documented vein graft stenosis. In addition, there were angiographic rea-

Volume 103 Number 5

Vein graft disease

May 1992

Table III. Two-year survival and reoperation-free survival: Operation to catheterization interval

Subgroup I 2 3 4 5 6

8

9 10

II

Graft status

Other criteria

LAD 20%-99% LAD 50%-99% LAD 75%-99% LAD 20%-49% No vein graft stenosis LAD 50%-99% versus No vein graft stenosis LAD 50%-99% versus No vein graft stenosis LAD 50%-99% versus No vein graft stenosis

No.

Survival (%)

82 52

3VD/LMT 3VD/LMT 3VD/LMT LVF(M/S)

18 30 212 42 154 19

76 70 61 86 85 66 0.01 83 46

p

Value

58 14

77 56

No angina]

124

84

p Value

years

Eventfree survival (%)

p Value

0.006*

70 67

0.01* 0.005*

67 61

0.008* 0.001*

0.04* 0.88*

55 76 83 62 0.007 81 42

0.0004* 0.39*

50 76 81 57

0.0002* 0.619*

om *

0.003 78 42

0.004

0.01 3VD/LMT LVF (MIS) No anginat

Reoperationfree survival (%)

~5

835

0.004

77 56 0.008 82

0.009 74 49 0.001 79

'» Value versus subgroup 5. t At catheterization.

sons why we thought these patients were at relatively low risk without reoperation. Moderate or severe impairment of left ventricular function was present in only 24% of patients, and 85% of patients had only one vein graft that was stenotic. For the most part, these patients were treated conservatively not because we thought they would be at high risk during reoperation, but because we thought they would do well without reoperation. Patients with early ( <5-year operation-to-catheterization interval) graft stenoses did do relatively well. The survivalrate was 92% at 5 years and 76% at 10 years after catheterization. Even patients with a relatively tight (75% to 99%) early stenosis of a vein graft to the LAD had a 94% survival at 5 postoperative years. With univariate testing there was a decreased reoperation-free survival for patients with early stenoses in LAD grafts, but when all patients who underwent early recatheterization were tested in multivariate models even stenotic LAD grafts did not have independent influence predicting a decrease in survival, reoperation-free survival, or event-free survival. The observation that most patients with early vein graft stenoses had a good outcome without prompt reoperation must be tempered by the realization that they werea selected subgroup of patients and that reoperation was subsequently used in a considerable number. Patients with late (~5 years) stenoses in vein grafts had a much worse outcome, particularly if they had a stenosis in a vein graft to the LAD coronary artery. Comparison of the overall group of patients with late vein graft stenoses with the control group of patients studied 2:5 years after operation did not show a significant dif-

Table IV. Cox proportional hazard models: Variables influencing the late results ofpatient with operationto-postoperative catheterization interval of <5 years p Value Survival LVF (MIS) Age (at cath) Angina* Reoperation-free survival LVF (MIS) Angina* Patent ITA Age Event-free survival LVF (MIS) Angina * Patent ITA Myocardial infarction*

<0.001 <0.001 0.058 <0.001 <0.001 0.005 0.04 <0.001 0.001 0.005

0.03

For abbreviations see Tables I and II. 'Indication for catheterization.

ference in late outcome (Fig. I). However, the subgroup of patients who had a late stenosis in an LAD vein graft did have decreased survival, reoperation-free survival, and event-free survival when compared with the control group by univariate testing. In addition, when both the group with stenotic vein grafts and the control group with an operation-to-catheterization interval of ~5 years were included in multivariate models, a stenosis in an LAD graft was identified as an incremental risk factor associated with decreased survival, reoperation-free survival, and event-free survival. The observation that a vein graft

8 36

The Journal of Thoracic and Cardiovascular Surgery

Lytle et al.

Table V. Two-year survival and reoperation-free survival: Operation to catheterization interval <5 years

Subgroup 1 2 3

Graft status LAD 50%-99% LAD 75%-99% No vein graft stenosis

No.

Survival (%)

p Value

73 35 361

93 94 98

0.90* 0.25*

Reoperationfree survival (%) 85 86 96

p Value 0.13* 0.02*

*p Value versus subgroup 3.

stenosis had a profound clinical impact when the coronary vessel jeopardized was the LAD is consistent with previous data that have shown the importance of the status of the LAD in determining long-term outcome. Furthermore, a stenotic LAD vein graft predicted a worse outcome than a totally occluded vein graft did. Patients with a patent internal thoracic artery graft (almost always used as a graft to the LAD) had improved late outcome. The indications for prompt reoperation for patients with vein graft stenoses are related to the risk of early death without the operation. The multivariate models tested the influence of the vein graft stenoses over the entire period of follow-up, but we also constructed a series of univariate comparisons to test the impact of a stenotic LAD vein graft over the first 2 years after catheterization. Again, when compared with the control group, patients with an LAD vein graft stenosis 2:50% had a significantly worse outcome. Patients with a lesser degree of stenosis (20% to 49%) in an LAD vein graft had survival equivalent to the control group over the first 2 years, but after that point their outcome became much worse and over the entire follow-up period their survival was the same as that of patients with more severe stenoses. The absence of angina was not helpful in predicting outcome for patients with late stenoses in LAD grafts. Although the subgroup was small (14 patients), survival was only 56% at 2 years for patients with a late LAD vein graft stenosis 2:50% and no angina. As would be expected, left ventricular function and the extent of native vessel coronary artery disease had a significant impact on the outcome of most subgroups of patients, whether they had early or late graft stenoses. The adverse influence of these factors was additive with the effect of a late stenosis in the LAD vein graft. Patients with a late stenosis (2:50%) in an LAD vein graft who also had three-vessel disease or left main stenosis (2: 50%) and moderate or severe impairment of left ventricular function had only a 46% 2-year survival. The incremental risk associated with having a late LAD vein graft stenosis was striking, whereas the risk associated with early vein graft stenoses was slight. The difference probably lies in the different diseases that cause

early and late vein graft stenoses. Early vein graft stenoses are usually caused by intimal fibroplasia. Diffuse, concentric intimal fibroplasia develops in nearly all vein grafts. This fibroplasia is characterized by a proliferative reaction in the intima with spindle cells, presumably smooth muscle cells, imbedded in a matrix of mucopolysaccharides and collagen. Intimal fibroplasia with numerous spindle cells contains relatively little collagen and matures into a less cellular but more fibrotic and often calcified intima. Intimal fibroplasia produces stenoses in some vein grafts, and these stenoses can lead to total occlusion.P Kouz and colleagues'" reported that 27% of vein grafts that were stenotic at I year after operation were occluded at follow-up catheterization at a mean interval of 8 years later. In a previous study involving serial angiograms of vein grafts, we l 2 found that 40% of vein grafts that were stenotic within 5 years after operation had become totally occluded 5 to 12 years after operation. However, the intervals between the identification of early graft stenoses and the follow-up catheterization were relatively long in these studies. It may be that stenoses caused by intimal fibroplasia do predispose to graft occlusion, but that it takes a relatively long time to occur. Intimal fibroplasia may provide the substrate for the development of vein graft atherosclerosis, and some of the graft occlusions that are noted after early stenoses may be delayed until the vein graft atherosclerosis lesion develops. Intimal fibroplasia is not a friable lesion, however, and embolization from grafts with intimal fibroplasia has not been documented. Late vein graft stenoses are usually caused by vein graft atherosclerosis, and the results of this study indicate that it is a much more clinically dangerous lesion than either early vein graft stenoses or native vessel coronary artery disease. The mechanism by which late vein graft stenoses might produce a high rate of clinical events (particularly death) include embolization of atherosclerotic debris and graft occlusion. The vein graft atherosclerosis lesion is distinctly different from native coronary artery atherosclerosis. Native coronary atherosclerosis is usually focal and proximal, with eccentric plaques that have a fibrous cap overlying a pultaceous center of lipid debris. In con-

Volume 103 Number 5

Vein graft disease

May 1992

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Fig. 5. Patients with latestenoses (50% to 99%) in LADvein grafts hadworse survival than eitherpatients with native vessel LAD stenoses (50% to 99%) (p = 0.002) or the control group. Patients with stenotic vein grafts to the LAD had survival of 70% and50% at 2and5postoperative years compared with 97% and 80% for patients with native LAD stenoses. trast, saphenous vein graft atherosclerosis is typically diffuse and concentric. The vein graft atherosclerosis lesions do not have a fibrous cap, and the foam cells and lipid debris are exposed to the bloodstream. In addition, these lesions frequently contain a heavy intimal inflammatory infiltrate that includes numerous multinucleate, lipidcontaining giant cells.!' The lesion is friable and fragile. The extreme fragility is reflected in reports of embolization of atherosclerotic debris from these grafts during both reoperation and PTCA. 17, 18 It is more difficult to prove atherosclerotic embolization in circumstances that donot involve intervention, but it seems logical to speculate that naturally occurring embolization may account for unstable angina or myocardial infarction in patients with atherosclerotic vein grafts.'? In addition, there are data that indicate that atherosclerotic vein graft stenoses are incipient vein graft occlusions. In our previous study ofvein grafts we found that 38% of vein grafts that developed stenoses more than 5 years after operation were occluded at studies that were performed at a mean interval ofonly40 months later.V This is probably a minimum figure for the occurrence of graft occlusion since followup angiographic studies can be performed only for patients who survive. In a study of the pathologic condition of vein grafts removed at reoperation, Solymass and colleagues'? found that vein graft atherosclerosis was a major factor predisposing to thrombosis. Eighty percent of atherosclerotic vein grafts had superimposed thrombosis compared with 40% of grafts with intimal fibroplasia. Studies by other investigators have noted similar findings." 21 Vein graft atherosclerosis and native vessel coronary

- - No VeinGraftStenosis ---- LAD Vein Graft 75-99%

n=361 n= 35

0'---------'---------'-----'----------'-------' 2

NUMBER AT RISK

- - 344 ---- 30

4

321 28

YEARS

6

278 27

8

10

234 20

195 17

Fig. 6. Reoperation-free survival for patients with LAD vein graft stenoses (75% to 99%) compared with the control group with a postoperative interval of <5 years. Patients with a severe (75% to 99%) stenosis in an LAD vein graft had a worse (p = 0.02) reoperation-free survival than patients with no vein graft stenosis.

atherosclerosis are different diseases. The results of this study indicate that natural history data from studies of patients with native vesseldisease cannot be reliably used to predict the outcome of patients with late vein graft stenoses treated without operation. The comparison of patients with the LAD jeopardized by a stenotic vein graft with those who had native LAD lesions highlights the contrast. During the first 2 years after catheterization, 30% of patients with a stenotic LAD vein graft died compared with 3% of those with a native LAD stenosis. This study has important implications for management. We believe that late stenoses in vein grafts to the LAD are an indication for reoperation evenin the absence of severe symptoms. Proof of this hypothesis will require detailed analyses of the results of reoperation for patients with stenotic vein grafts. REFERENCES I. Lytle BW,Loop FD,Cosgrove DM,et al. Long-term (5 to

12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J THORAC CARDIOVASC SURG 1985;89:248. 2. Lawrie GM, LieJT, Morris GC, et al. Vein graft patency and intimal proliferation after aortocoronary bypass: early and long-term angiopathologic correlations. Am J Cardiol 1976;38:856. 3. Bourassa MG, Campeau L, Lesperance J, et al. Changes in graftsand coronary arteries after saphenous vein aortocoronary bypass surgery: results at repeat angiography. Circulation (Suppl II) 1982;65(Pt 2):190. 4. Campeau L,Lesperance J, CorbaraF,et al.Aortocoronary saphenous vein bypass graftchanges 5 to 7 years after surgery. Circulation 1978;58(Pt 2):Il70.

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8 3 8 Lytle et al.

5. Fitzgibbon GM, Leach AJ, Kafka HP, Keon WJ. Coronary bypass graft fate: long-term angiographic study. J Am Coli CardioI1991;17:1075. 6. Neitzel GF, Barborcak JJ, Pintan K, et al. Atherosclerosis in aortocoronary bypass grafts: morphologic study and risk factor analysis 6 to 12 years after surgery. Arteriosclerosis 1986;6:594. 7. Varnauskas E, and the European Coronary Surgery Study Group: Twelve-year follow-up of survival in the randomized European coronary surgery study. N Engl J Med 1988; 319:332. 8. Passamani E, Davis KB, Gillespie MJ, et al. A randomized study of coronary bypass surgery: survival in patients with a low ejection fraction. N Engl J Med 1984;310:750. 9. The Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina. N Engl J Med 1984; 311:1333. 10. Califf RM, Harrell FE Jr, Lee KL, et al. Changing efficacy of coronary revascularization: implications for patient selection. Circulation 1988;78:(Pt 2):1185. II. Proudfit WJ, Bruschke VG, MacMillan JP, Williams GW, Sones FM Jr. Fifteen-year survival study of patients with obstructive coronary artery disease. Circulation 1983; 68:986. 12. Lytle BW, Cosgrove OM, Easley K, RatliffN, Loop FD. Clinical implications of late stenoses in saphenous vein to coronary bypass grafts. J Am Coli Cardiol 1986;7:34A. 13. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;8:699. 14. Cox DR. Regression models and life tables. J R Stat Soc (B) 1972;34:187. 15. Ratliff NB, Myles JL. Rapidly progressive atherosclerosis in aortocoronary saphenous vein grafts. Arch Pathol Lab Med 1989;113:772. 16. Kouz S, Campeau L, Lesperance J, et al. The role of early graft changes attributed to intimal fibrous hyperplasia in late aortocoronary saphenous vein graft closure. J Am Coli Cardiol 1986;7:34A. 17. Douglas J, Robinson K, Schlumpf M. Percutaneous transluminal angioplasty in aortocoronary venous graft stenoses: implications, results and complications [Abstract]. Circulation 1986;74(Pt 2):II363. 18. Keon WJ, Heggtveit HA, Leduc J. Perioperative myocardial infarctions caused by atheroembolization. J THORAC CARDIOVASC SURG 1982;84:849. 19. Grondin CM. The removal of still functioning albeit old grafts: Not in our genes? Ann Thorac Surg 1986;42:122. 20. Solymass DC, Nadeau P, Millette 0, et al. Late thrombo-

sis of saphenous vein coronary bypass grafts related to risk factors. Circulation I988;78(Pt 2):1140. 21. Walts AE, Fishbein MC, Sustaita H, et al. Ruptured atheromatous plaques in saphenous vein coronary artery bypass grafts: a mechanism of acute, thrombotic late graft occlusion. Circulation 1982;65:197.

Discussion Dr. James L. Cox (St. Louis, Mo.). I would like to ask a question of Dr. Lytle in regard to two issues. First, when you speak of the stenoses in the saphenous vein bypass grafts, did you differentiate between a stenosis located at the site of anastomosis and a mid-vein stenosis, and if so, did it make any difference? Dr. Lytle. We excluded patients with stenoses that involved the native artery, Some patients had stenoses in the distal portion of the graft, but they all had something to do with the graft itself. Purely anastomotic stenoses, therefore, were excluded. Dr. Cox. Did you notice any difference in the distribution of the stenoses in the bypass grafts (i.e., the location within the graft) in patients who were catheterized early as opposed to patients who were catheterized late? Dr. Lytle. I cannot answer that. This was a complicated study of a complicated subject, and your question was one of the details that we, so far, have overlooked. What we are talking about here is a different kind of coronary artery disease that involves an incredibly large population of patients-those who have had previous bypass surgery. We do not know much about the natural history of these patients once vein graft disease develops. In clinical practice we are faced with decision-making concerning these patients daily. Weare going to need to study these patients with the same detail that has been used to examine patients with purely native vessel disease. The major thing we learned from this study, and that we have suspected all along, is that patients with vein graft stenoses are different than patients with purely native vessel disease. Dr. Cox. This is a very important paper because all of us do deal with this problem every day. Once you have diagnosed the problem, was the mortality rate different if you simply followed them rather than reoperating on them at that time? Dr. Lytle. The overall mortality rate of reoperation is relatively low. In our experience it has been 3% or 4% pretty consistently. That does not mean that that risk applies to this specific group of patients. In fact, about 600 patients were studied and would have fulfilled the angiographic criteria for inclusion into this study, but who were reoperated on. We have not completed the follow-up of that subgroup of patients from our reaperative series to use for comparison. I think they are the ones that are the most comparable rather than our general series of reoperation patients. I am confident that we are going to be able to do better than a 61% 2-year survival for patients with LAD graft stenoses that do not undergo reaperation.

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Appendix 1. Characteristics at catheterization ofpatients with and without stenotic vein grafts Patients with stenotic vein grafts (N = 723) Variable Men Age (mean) Functional class at cath NYHA I II III IV CHF Indication for cath Angina Myocardial infarction Routine Other LVF Normal-mild Moderate-severe Extent of native vessel disease (2:50% stenosis) LMT IVD 2VD 3VD No. of stenotic vein grafts I 2 3 No. of patent ITA grafts No. of patent vein grafts 0 I 2 2:3

Patients with no stenotic vein grafts (N = 573)

n

%

n

%

p Value

664 57.4 years

91.8

522 57.2 years

91.1

0.64 0.70

310 294 75 49

42.9 40.7 10.4 6.1 6.8

328 186 41 18 17

57.2 32.5 7.2 3.1 3.0

368 67 180 108

50.9 9.3 24.9 14.9

199 69 172 133

34.7 12.0 30.0 23.2

553 170

76.5 23.5

437 136

76.3 23.7

118 49 149 407

16.3 6.7 20.6 56.3

83 75 153 262

14.5 13.1 26.7 45.7

617 98 8 195

85.3 13.6 1.1

None

44

372 269 73 9

<0.001

0.002

<0.001

0.93

<0.001

138 106 288 136 43

NYHA, New York Heart Association; CHF, congestive heart failure; for other abbreviations see Tables I to V.

Appendix continued on page 840.

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Lytle et al.

Appendix 2. Causes of death Patients with stenotic vein grafts Frequency Cardiac deaths Sudden Documented MI Ischemic cardiomyopathy and CHF Arrhythmia Nondocumented, probably cardiac Subtotal Noncardiac deaths Stroke Cerebral hemorrhage Cancer Suicide Trauma Sepsis Respiratory disease Renal failure Liver disease Aortic aneurysm GI bleeding Vascular disease ALS Embolic Bowel obstruction Subtotal Total

58 21

Patients without stenotic vein grafts

Percent

Frequency

28.3 10.2 11.7

61

30.5

17

8.5 7.5

24 7 45

3.4

I

21.9

50

0.5 25.0

155

75.6

144

72.0

7

3.4

I

0.5

6 3

23

11.2

25

3.0 1.5 12.5

I

0.5 1.9 1.5 0.9 1.5 1.5 0.9 0.5

4 3 2 3

3 2

I

15

o 3

I

1.5 0.5

5

2.5

4

2.0 1.5 1.0

3 2

o I I I I

50 205

24.4

MI, Myocardial infarction; CHF. congestive heart failure; GI, gastrointestinal; ALS, amyotrophic lateral sclerosis.

Appendix 3. Variables tested for influence on late survival, reoperation-free survival, and event-free survival Clinical variables Gender Age Symptoms (at cath) (NYHA I, II, III, IV) Indications for cath: Angina Myocardial infarction Routine Other Interval between operation and catheterization: <5 years, ~5 years Angiographic variables Extent of disease (~50%) I VD, 2VD vs. 3VD/LMT Left ventricular function Normal, mild impairment vs. moderate or severe impairment Saphenous vein graft (SVG) stenosis (20-99%): yes/no LAD SVG stenosis Circumflex SVG stenosis Right coronary SVG stenosis Patent internal thoracic artery graft No. of stenotic SVGs LAD SVG: total occlusion SVG, Saphenous vein graft. For other abbreviations see Tables [ to V.

Percent

56 200

0.5 0.5 0.5 0.5 28.0