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The effect of coronary reoperation on the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries
Surgery for Acquired Heart Disease
The effect of coronary reoperation on the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries Does coronary artery reoperation improve the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries? To examine this question, we retrospectively reviewed 1117 patients who had coronary bypass grafting and then underwent a postoperative coronary angiogram that showed a stenosis (2:20 %) of at least one vein graft. Reoperation within 1 month of the postoperative angiogram was performed for 394 patients (REOP group) whereas 723 patients (MED group) received initial medical treatment (no reoperation or percutaneous transluminal coronary angioplasty within 1 year). Compared with the MED group, patients in the REOP group were older, more symptomatic, more likely to have left main stenosis, and had fewer patent bypass grafts (all p < 0.001). In-hospital mortality for the REOP group was 4.3 %. Mean postangiogram follow-up of the entire group was 73 months. On the basis of the interval between the primary operation and the postoperative angiogram, patients were designated as having early « 5 years) or late (2: 5 years) saphenous vein graft stenosis. Univariate and multivariate analyses were used to identify factors influencing the survival of these subgroups. Reoperation was not identified as a variable improving the survival of patients with early vein graft stenoses. For patients with late vein graft stenoses, moderate or severe impairment of left ventricular function (p < 0.0001), advanced age (p < 0.0001), triple-vessel or left main stenosis (p = 0.0011\ and stenosis in a vein graft to the left anterior descending artery (p = 0.0019) decreased survival, whereas reoperation improved survival (p = 0.0007). The improvement in survival with reoperation was particularly strong for patients with a stenotic vein graft to the left anterior descending artery. For that subset, survival was 84% and 74% for the REOP group versus 76% and 53% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.004). For patients with stenotic vein grafts to the right coronary artery or circumflex coronary artery (or both), survival was 92 % and 87 % for the REOP group versus 89 % and 78 % for the MED group at 2 and 4 years after catheterization, respectively (p = 0.13). Even for patients with class I or II symptoms, reoperation prolonged survival (p = 0.002 with multivariate testing). Reoperation improves the survival of patients with late vein graft stenoses, particularly those with stenotic grafts to the left anterior descending coronary artery. (J THoRAc CARDIOVASC SURG 1993;105:605-14)
Bruce W. Lytle, MD, Floyd D. Loop, MD, Paul C. Taylor, MD (by invitation), Marlene Goormastic, MPH (by invitation), Robert W. Stewart, MD (by invitation), Roberto Novoa, MD (by invitation), Patrick McCarthy, MD (by invitation), and Delos M. Cosgrove, MD, Cleveland, Ohio With the technical assistance of Maura J. Schnauffer
From the Cleveland Clinic Foundation, Cleveland, Ohio. Address for reprints: Bruce W. Lytle, MD, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, One Clinic Center, Cleveland, OH 44195.
Read at the Seventy-second Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., April 26-29, 1992. Copyright
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00 +.10
12/6/44186
605
606
Patients with stenoses in saphenous vein (SV) bypass grafts to coronary arteries have a disease that is distinct from native-vessel coronary artery disease. In a recent study of patients with SV graft stenoses, we found that those with late (2':5 years after operation) SV graft stenoses had poor late survival without reoperation, particularly if the left anterior descending coronary artery (LAD) was supplied by a stenotic SV graft. I However, it has not been documented that reoperation improves the survival of patients with stenotic SV grafts. In fact, it has not been shown that coronary reoperation improves the survival of any patient subset. The purpose of this study is to examine the influence of reoperation on the shortand long-term survival of patients with SV graft stenoses. Patient population-methods and definitions This is a nonrandomized retrospective study. With the aid of our computerized Cardiovascular Information Registry, a registry that stores data regarding all patients undergoing coronary angiography or bypass grafting at the Cleveland Clinic Foundation, we identified 723 patients who fulfilled the following criteria: I. Operation for isolated coronary bypass grafting was performed at the Cleveland Clinic Foundation. 2. A postoperative angiographic study was performed that demonstrated a stenosisof 20% to 99% in the lumen of at least one SV graft. 3. No invasiverevascularization procedures (bypass grafting or percutaneous transluminal coronary angioplasty [PTCA]) were performed between the primary operation and the postoperative angiogram. 4. No cardiac reoperation or PTCA was performed within a year after the postoperative angiogram that documented the SV graft stenosis. The initial intention was to treat these 723 patients without reoperation, and they are termed the medical (MED) group. Data concerning this group of patients have been reported previously.'
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We also identified a group of 394 consecutive patients who fulfilled criteria I to 3 in the preceding paragraph, but who underwent isolated coronary reoperation within I month of the angiogram that demonstrated the SV graft stenosis.This group is termed the reoperation (REOP) group. Those reoperations were performed between 1972and 1989.Baselinedescriptors of clinicaland angiographic variables for both the M ED group and the REOP group are listed in Appendix I. The mean follow-up interval after the catheterization that demonstra ted the SV graft stenosiswas 73 months for the entire group, 83 months (range 0 to 237 months) for the MED group, and 55 months (range 0 to 193 months) for the REOP group. Follow-up was conducted by direct examination at the Cleveland Clinic Foundation, telephone, and letter, and the events that were identified were death, reoperation, and PTCA. Routine follow-upis conducted as part of the Cardiovascular Information Registry and specificfollow-up for this study was conducted by dedicated personnel. The numbers of patients experiencing events in the MED group were death, 205, reoperation, 181, and PTCA, 24. Comparable figures for the
April 1993
REOP group were death, 91, rereoperation, 12, and PTCA, 9. Late survival and reoperation-free survival figures were calculated with the Kaplan-Meier method.? When survival was calculated, the patient was censored alive at the time of the occurrence of a repeat intervention (PTCA or reoperation). When reoperation-free survival was calculated, patients were censored alive at the time of a PTCA. Univariate testing of time-related outcome was done by means of Kaplan-Meier curves- and the Cox proportional hazard model! was used for multivariate testing. Results In-hospital mortality. For the patients in the REOP group, in-hospital mortality was 17 of 394 (4.3%). All in-hospital deaths occurred in patients whose primary operation-to-catheterization interval was 5 years or more, which produced an in-hospital mortality of 5.1% (17 of 335) for that subgroup. The variables in Appendix 2 were tested univariately for association with in-hospital mortality: Results for selected variables are shown in Table I. Logistic regression analysis identified only preoperative congestive heart failure (p = 0.0003) and a late stenosis in an SV graft to the LAD (p = 0.002) as factors increasing in-hospital mortality. Overall survival. Data from our previous study, as well as preliminary calculations from this study, indicated that the outcome of patients with stenotic SV grafts who were managed with initial medical treatment varied greatly on the basis of the interval between the operation and the postoperative catheterization that identified the SV graft stenosis. Therefore, in the comparison of the MED and REOP groups in this study, we elected to separate our analyses on the basis of whether the operation-to-catheterization interval was less than 5 years or 5 years or more. In all models testing survival and reoperation-free survival, in-hospital mortality for the REOP group was included in calculations. Patients with early «5 years) stenoses in SV grafts. For the 490 patients with early «5 years) SV graft stenoses, 431 were in the MED group and 59 were in the REOP group. There was a high correlation between treatment group and the patient's symptom status at the time of the angiogram: 42 of 59 (71 %) patients in the REOP group had class III or IV symptoms versus 46 of 431 (11%) in the MED group (p < 0.001). Patients in both the MED and REOP groups were tested in a multivariate model to examine the influence of the variables in Appendix 2 and the treatment group on survival (Table 11). Reoperation did not influence survival significantly. Univariate survival curves for the REOP and MED groups with early SV graft stenoses are shown in Fig. I. When we examined patients who had class III or class IV symptoms at the time that the stenosis-identifying catheterization was performed (46 in the MED group, 42
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Table I. Variables associated (p > 0,10) with reoperation in-hospital mortality: Univariate analyses Patients Primary operation-postop. <5 yr :0:5 yr NYHA functional class
In-hospital Mortality (%) p Value death
angiogram interval 59 0 17 335
0 5.1
0.09
0.07
265 129 IS 68 165
8 9 3 0 14
3.0 7.0 20.0 0 8.5
0.02 0.05 0.002
49
0
0
0.14
17
0
0
1.00
in the REOP group), univariate testing did not show any difference in survival between the MED and REOP groups. However, because 15 (33%) of the MED patients eventually underwent reoperation, reoperation-free survival was better (p = 0.03) for the REOP group so long as the initial reoperation was excluded from consideration. Furthermore, at late follow-up 23 of 31 patients in the REOP group had class I or II symptoms, compared with only II of 31 in the MED group. Late symptom status (New York Heart Association [NYHA] functional class) for the entire group of patients with early SV graft stenoses was as follows: REOP group 1,24, II, 13, III, 5, and IV, 4, versus MED group I, 105, II, 87, III, 78, IV, 30 (p = 0.02). Patients with late (2':5 years) stenoses in SV grafts. Ofthe 627 patients with late (2':5 years) SV graft stenoses, 292 were in the MED group and 335 were in the REOP group. Again, the patients in the REOP group were more symptomatic at the time of their angiogram: 215 of 335 (64%) patients in the REOP group had class III or IV symptoms versus 73 of 292 (25%) in the MED group (p < 0.001). Furthermore, the REOP group contained more patients with left main stenoses and fewer patients with patent SV grafts or patent internal thoracic artery (ITA) grafts (all p < 0.001). The 627 patients with late SV graft stenoses were examined in a multivariate model that tested the variables in Appendix 2 in addition to treatment choice (MED versus REOP). Results of that model are shown in Table III. Moderate or severe impairment of left ventricular function, advanced age, triple-vessel or left main coronary disease, and a stenosis (20% to 99%) in an SV graft to the LAD were all associated with decreased survival. Reoperation increased survival. Survival curves showing
607
Table II. Patients with early «5 years) stenoses in vein grafts: Multivariate model of variables influencing survival (n = 490) Variables Decreasing Survival
p Value
Relative risk
LVF (modjsev) Age (at catheterization) Angina at catheterization Occluded SV graft to LAD 3VDjLMT
0.0001 0.0001 0.0408 0.0286 0.0287
2.55 1.04* 1.54 2.03 1.57
LVF (modlsev}, Left ventricular function, moderate or severe impairment; 3VD/LMT, triple-vessel disease and/or left main stenosis.
'Per year.
Table III. Patients with late (2':5 years) stenoses in vein grafts: multivariate model of variables influencing survival (n = 627) Variables decreasing survival LVF (modjsev) Age (at catheterization) 3VDjLMT LAD vein graft stenosis (20%-99%) Variable increasing survival Reoperation
p Value
Relative risk
0.0001 0.0001 0.0011 0.0019
2.58 1.04* 2.87 1.90
0.0007
0.51
*Per year.
univariate comparisons of the MED and REOP groups for all patients with late stenoses are shown in Fig. 2. Construction of another multivariate model that included only patients with NYHA functional class I or II symptoms at the time of the postoperative angiogram showed that reoperation still was associated with increased survival for that subgroup (Table IV) of patients with late SV graft stenoses. The status of the graft to the LAD was important in predicting the influence of reoperation on late survival. Univariate comparison of survival curves of the MED and REOP groups of patients with late stenoses in SV-LAD grafts (Fig. 3) demonstrates improved survival for the REOP group. When patients with late stenoses in SV-LAD grafts were separated on the basis of the severity of the stenosis, patients with severe (50% to 99%) SV-LAD graft stenoses had better survival statistics throughout the follow-up (Fig. 4, top). For patients with less severe (20% to 49%) SV-LAD graft stenoses (Fig. 4, bottom), survival of the MED and REOP groups was equivalent at 2 years, but the curves diverged between 2 and 4 years after the angiogram such that the improvement in survival for the REOP group approached significance (p = 0.06). Univariate survival curves for patients with totally occluded SV grafts to the LAD are shown in
608
The Journal of Thoracic and Cardiovascular Surgery April 1993
Lytle et al.
100
--
94% F=~;;:~;;~~=--;~-;---l p=0.57
80
...............
~ 0
...J
60
s>a::
40
::J
en
20
•••••• Reoperation group n=59 - - Medical group n=431
00 Number at Risk
2
4
54 402
47 352
YEARS
6
10
35 309
26 237
14 188
Fig. 1. Survival of patients with early «5 postoperative years) stenoses in SV grafts, MED and REOP groups (p = not significant).
100.,---------------------, .,
;? o
80
...J
60
s>a::
40
::J
en
20
Number at Risk
....tT.......~ .r:"_ .""1
.......
. ........
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....
...
"-~t",
"--i. ..,
" - .....,. ....·~:.a6J'....
... ~..~_.
....-.-.-
~ ~
_...
...............
..••.. Reoperation group n=335 - - Medical group n=292 Reoperation group (Reop-free) n=335 Medical group (Reop-free) n=292
2
4
269 211 264 208
157 98 154 97
YEARS
'- . -. - . -.
10
6 74 48 72 47
l
24 25 24 25
7 8 5 6
Fig. 2. Survival and reoperation-free survival of patients with late (2:5 years) stenoses in SV grafts, MED versus REOP. Patients undergoing reoperation had improved survival (p = 0.03). Patients in the MED group had reoperation-free survival of only 48% at 5 years.
Fig. 5 and indicate better survival for the REOP group, although that was not found to be significant in multivariate testing. Patients with patent IT A grafts to the LAD had relatively good survival, even with initial medical treatment, and the outcomes for the REOP and MED groups were comparable (Fig. 6). One hundred twenty-
seven patients with late SV graft stenoses had patent SV-LAD grafts, and there was also no survival difference between the MED and REOP groups for that subset. Because the major purpose of the study was to examine the influence of initial treatment choice (initial medical treatment versus initial reoperation) on the outcome
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609
100,...--------------------, • ••••••
-
~ o
. .J c(
s>IX :::» (/)
80
p=O.004
84%
" •••••• ,.........
74%
' -
-··f
_,.
...... -..................... -.
60 53%
40 20
Number at Risk
•••••• Reoperation group n=165 - - Medical group n=82
2
4
127 53
71 24
YEARS
6
8
10
36
12 4
4 1
8
Fig. 3. Survival of patients with late stenoses in SV grafts to the LAD coronaryartery. Patients undergoing reoperation had improved survival.
of patients with SV graft stenoses and because the circumstances, location, and effectiveness of delayed reoperations for patients with initial medical treatment introduced many potentially confounding variables, we censored the follow-up of patients in the MED group at the time of their delayed reoperation for most analyses. However, for the group shown to benefit the most from immediate reoperation, patients with late SV-LAD graft stenoses, we conducted further analyses in which followup of the MED group was continued beyond delayed reoperation. Of patients with late SV-LAD graft stenoses of 20% to 99%,there were 82 patients in the MED group, of whom 23 underwent delayed (> I year after their angiogram) reoperations, 19 between I and 5 years after the angiogram documenting the SV graft stenosis. Survival at delayed reoperation was good (I death of 23 patients), as was the late survival after delayed reoperation. Therefore the survival figures of the MED group when the followup was continued after delayed reoperation were almost identical to those obtained when the MED group was censored at the time of delayed reoperation. Regardless of the type of statistical method used, survival statistics were better in the REOP group. Two hundred thirty-seven patients with late SV graft stenoseshad neither a stenotic SV -LAD graft nor a patent ITA-LAD graft. One hundred twenty-six patients were treated with initial medical treatment and III with initial reoperation. A multivariate model addressing survival showed that left ventricular function (p = 0.0002) and triple-vessel or left main coronary disease (p = 0.01)
Table IV. Multivariate analysis of variables
influencing the survival ofpatients with late (::0::5 year) stenoses in vein grafts: NYHA functional class I or II symptoms (n = 339) Variables decreasing survival LVF (modjsev) Age (at catheterization) 3VDjLMT LAD vein graft stenosis (20%-99%) Variable increasing survival Reoperation
p Value
Relative risk
0.0001 0.0006 0.0183 0.0188
3.29 1.05 3.14 2.19
0.0020
0.43
decreased survival, whereas reoperation (p = 0.01) was associated with increased survival. Univariate comparison of patients with only late stenoses of SV-right coronary/ or SV-circumflex coronary artery grafts showed a trend (p = 0.13) toward increased survival for the REOP group (REOP group 92% and 87% at 2 and 4 postoperative years, respectively, versus 89% and 78% for the MED group). The high-risk characteristics of a late SV-LAD graft stenosis, triple-vessel or left main stenosis, and moderate or severe impairment of left ventricular function were combined in 74 patients, 47 in the REOP group and 27 in the MED group. Survival at 2 years was 55% for the MED group and 79% for the REOP group (p = 0.0011). Symptoms. For patients with late SV graft stenoses, the symptom status (NYHA functional class) for the late survivors at follow-up was as follows: REOP group I, 189
6 10
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Lytle et al.
100.----------------------, p=0.02 ~
C ':i. > s !5
80
",
73%
..
~ -.".-....... -
I
.
60
_
..
54%
40
l/)
20
•••••. Reoperatioo group 0=141 - - Medical group 0=52
2
4
YEARS
6
100
~
8
10
p=0.06
80
:.l! ~
...J ce 60 > a: 40
s
~
l/)
20
Reoperatioo group - - Medical group
2
4
YEARS
6
8
10
Fig. 4. Survival of patients with stenotic SY-LAD grafts basedon the severity of stenosis. Top, 50% to 99% stenosis; bottom, 20% to 49% stenosis.
(74%), II, 46 (18%), III, 17 (7%), IV,4 (2%); MED group 1,68 (33%), II, 76 (37%), III, 46 (22%), and IV, 16 (8%) (p = 0.0001). Discussion The results of this study indicate that early coronary reoperation improves the survival of patients with late stenoses in SV grafts, with the greatest improvement occurring in those with late stenoses in SV grafts to the LAD. The choice of treatment for the patients in this study was not randomized. Comparison of the clinical and angiographic characteristics of the REOP and MED groups at the time of the postoperative angiogram that identified the SV graft stenoses identifies clear differences between the treatment groups. The patients in the MED group were significantly younger and had less severe symptoms, better left ventricular function, fewer left main lesions, more patent ITA and SV grafts, and were more likely to have early stenoses than were the
REOP group. There obviously was an institutional bias toward reoperation for patients with high-risk characteristics. Our previous study concerning the outcome of patients with SV graft stenoses treated without an initial operation showed that late SV graft stenoses (those demonstrated 5 years or more after operation) predict a much higher rate of death and other cardiac events than do early SV graft stenoses (those demonstrated within 5 years of operation). This clinical difference correlates with a difference in the pathologic features of early versus late SV graft stenoses. Early SV graft stenoses are usually caused by intimal fibroplasia, whereas late SV graft stenoses are more often caused by SV graft atherosclerosis.v? Intimal fibroplasia may cause graft occlusion, and thrombosis superimposed on stenoses caused by intimal fibroplasia has been noted." However, intimal fibroplasia appears to be a relatively stable lesion when compared with fully developed SV graft atherosclerosis.r'' SV graft atherosclerosis is a diffuse, friable, unstable lesion that has caused embolization during manipulation associated with reoperation or PTCA. lo In addition, it may incite thrombosis.!' Because of these different pathologic characteristics and outcomes, we elected to analyze patients with early and late stenoses separately. Patients with early SV graft stenoses were usually (88%) treated without immediate reoperation. Reoperation for patients with early SV graft stenoses was usually used for symptom relief: 71% of patients in the REOP group had class III or IV symptoms. No hospital deaths occurred in the 59 patients who underwent reoperation for early SV graft stenosis. However, reoperation did not appear to improve the overall survival of this subset, mainly because of the relatively good survival of the patients with early SV graft stenoses treated without early surgical intervention. Many of the symptomatic patients in the MED group eventually did undergo reoperation, and the late symptom status of the late REOP group was superior to that for the MED group. However, patients treated without an early operation did not appear to be at a high risk of death, which confirms the relative safety of reserving operation for the presence of severe symptoms. Patients with late SV graft stenoses were in a more dangerous situation regardless of which treatment (MED or REOP) was initially chosen. The in-hospital mortality rate for reoperation was 5.1% for patients with late SV graft stenoses. Furthermore, that mortality rate was particularly high for patients with a stenotic SV graft to the LAD (8.5%), possibly because of the dangerous tendency of SV graft atherosclerosis to produce embolization
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
-
Lytle et al.
100 ., - - - : -97',io ....,---------------------, o':., p=O.0019 .... ". -0
", 81%
....,
80
.~
...........................................
..
~
..J ~
>
sII:
:>
en
6I I
60 40
20
••. . • • Reoperation group - - Medical group
n=39 n=23
4
2
6
8
12 3
2
10
YEARS
36
Number at Risk
15
22 5
Fig. 5. Survival of patients with stenosesin SV grafts, but who also had a totally occluded SV graft to the LAD. Survival was better with reoperation.
-
, ...... -, ,
80
p=O.75
83%
~
~
..J ~
..
"
60
>
s
II:
:>
en
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20
..... , Reoperation group n=59 -
Number at ., •••• Risk
Medical group
47 62
n=83
23
5
28
13
1 7
6
Fig. 6. Survivalof patients with patent ITA grafts to the LAD in addition to at least one stenoticSV graft. Survival was equivalent for the MED and REOP groups.
during reoperation. Patients with patent ITA grafts to the LAD and those with totally occluded SV-LAD grafts (i.e., situations in which the important LAD system is protected from the danger of embolization of atherosclerotic debris from an SV graft) had no in-hospital mortality. These reoperations were performed from 1972 to 1989, and we believe that increased experience and advances in myocardial protection such as retrograde
delivery of cardioplegic solution have decreased the risk of atherosclerotic embolization during reoperation. Despite the in-hospital risk of reoperation, multivariate testing identified reoperation as a factor significantly increasing overall survival of patients with late SV graft stenoses. The improvement in long-term survival achieved by reoperation was related in part to the status of the graft to the LAD. Patients with a late stenosis in an SV-LAD
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The Journal of Thoracic and Cardiovascular Surgery April 1993
Lytle et al.
graft had a much better overall survival with reoperation than with medical treatment, despite the fact that they had an increased in-hospital risk associated with the operation. Patients with a totally obstructed graft to the LAD also had improved survival with early operation. Patients with a patent ITA graft to the LAD were at lower risk without reoperation, and early operation did not appear to improve their overall survival. For patients with neither a stenotic SV-LAD graft (high-risk group) nor a patent ITA-LAD graft (low-risk group), reoperation improved overall survival, but not as dramatically as it did for patients with late SV-LAD graft stenoses. A delayed reoperation (reoperation > 1 year after the angiogram) was done in 23 of the 82 patients with late SV-LAD graft stenoses in the MED group. Those patients who survived with initial medical treatment long enough to undergo a delayed reoperation did well. The large difference in survival between the MED and REOP groups was caused by the high rate of death in the MED group for patients who never underwent a second operation, an observation that argues against the strategy of waiting until symptoms worsen before offering reoperation to patients with late SV-LAD graft stenoses. Whereas it appears that for patients with early SV graft stenoses recommendation for reoperation can be based on the severity of symptoms, that principle does not appear to be the case for patients with late SV graft stenoses. When patients with late SV graft stenoses but only class I or II symptoms were included in a multivariate model, early reoperation improved overall survival, even in the presence of mild symptoms. Many patients in the MED group who did not have an initial repeat operation subsequently did undergo reoperation. In fact, fewer than half of the patients with late SV graft stenoses who were initially in the MED group survived 5 years without reoperation. Furthermore, for patients with either early or lateSV graft stenoses, the late symptom status of the REOP group was superior to that of the MED group. The results of this study indicate that patients with late stenoses in SV grafts to the LAD should undergo reoperation, even if they are not severely symptomatic. The effect of bypass surgery in prolonging life expectancy is clearest for that subset. Patients without SV-LAD graft stenoses but with late stenoses in SV grafts to the circumflex or right coronary system (or both) also appear to have better survival statistics with initial surgical treatment, so long as the LAD is not protected by a patent ITA graft. REFERENCES I. Lytle BW, Loop FD, Taylor PC, et al. Vein graft disease: the clinical impact of stenoses in saphenous vein bypass
grafts to coronary arteries. J THoRAc CARDIOVASC SURG 1992;103:831-40.
2. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;8:699. 3. Cox DR. Regression models and life tables. J R Stat Soc (B) 1972;34:187.
4. Lytle BW, Loop FD, CosgroveDM, RatliffNB, EasleyK, Taylor Pc. Long-term (5 to 10 years) serial studies of internal mammary artery and saphenous vein coronary bypassgrafts. J THORAC CARDIOVASC SURG 1985;89:24858.
5. Ratliff NB, Myles JL. Rapidly progressive atherosclerosis in aortocoronary saphenous vein grafts. Arch Pathol Lab Med 1989;113:772. 6. Bourassa MG, Campeau L, Lesperance J. Changes in grafts and in coronary arteries after coronary bypass surgery. Cardiovasc Clin 1991;21:83. 7. Solymoss BC, Nadeau P, Campeau L. Factors related to atherosclerosisof saphenous vein coronary bypassgrafts. J Am Coil Cardiol 1987;9:85A. 8. Neitzel GF, Barboriat JJ, Pintar R, et al. Atherosclerosis in aortocoronary bypassgrafts: morphologic study and risk factor analysis 6-12 years after surgery. Arteriosclerosis 1986;6:594.
9. Lawrie GM, Lie JT, Morris GC, et al. Vein graft patency and intimal proliferation after aortocoronary bypass: early and long-term angiopathic correlations. Am J Cardiol 1976;38:856.
10. Keon W J, Heggtveit HA, Lecluc J. Perioperativemyocardial infarction caused by atheroembolization. J THORAC CARDIOVASC SURG 1982;84:849-55. 11. 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 occlusions. Circulation 1982;65:197.
Discussion Dr. Jean Paul Cachera (Paris, France). You have given us proof of the superiorityof reoperationsversus medical management in patients with coronary disease, at least in the group of patients with late SV graft stenosis,eventhough your groupsof patients were not selected on a random basis. Our own experience is similar. We have reoperated on 161 patients for recurrent angina pectoris from 1978 to 1991. In 42 patients, 25%, the recurrence of symptoms was correlated with the occlusion or stenosis of one or several SV grafts. In 28 patients, 17%, isolated impairment of the coronary vessels becauseof the progression of artheroscleroticlesions waspresent without significant alterations of the SV grafts. In 96 patients, 58%, simultaneous impairment of native coronary vessels and SV grafts was observed. The mean time elapsed between the primary operation and the reoperation was 93.3 months. The time elapsed betweenthe onset of symptoms and the reoperation was 27.7 months. Twenty-five percent of patients were in functional class II and 75% in class III or IV. The overall hospital mortality was significantly higher than yours (8%, 13/161), and all the deaths
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613
Appendix 1. Characterization at catheterization ofpatients with stenotic vein grafts treated medically (MED) or with reoperation (REOP) MED = 723)
REOP = 394)
(n
(n
N Men 664 Mean age (yr) 57.4 NYHA functional class at cath. I 310 294 II 75 III IV 44 CHF 49 Indications for cath. 368 Angina 67 MI 180 Routine 108 Other LVF Normal-mild 553 Mod-sev 170 Extent of disease 118 LMT IVD 49 2VD 149 3VD 407 No. of stenotic vein grafts 617 I 98 2 8 3 No. with patent 195 ITA grafts No. of patent vein grafts 372 0 I 269 2 73 9 3 Interval after primary operation (yr) 431 <5 :0::5 292
%
N
%
91.8
356 62.0
90.4
42.9 40.7 10.4 6.1 6.8
35 102 128 129 15
8.9 25.9 32.5 32.7 3.8
50.9 9.3 34.9 14.9
290 77 5 22
73.6 19.5 1.3 5.6
76.5 23.5
281 113
71.3 28.7
16.3 6.8 20.6 56.3
118 7 36 233
30.0 1.8 9.1 59.1
85.3 13.6 l.l 27.0
315 72 7 68
79.9 18.3 1.8 17.3
51.5 37.2 10.1 1.2
316 69 8 1
80.2 17.5 2.0 0.3
59.6 40.4
59 335
15.0 85.0
were due to myocardial failure. The mean follow-up in survivors was 40.1 months, and among those survivors there were seven late deaths and four cardiac transplantations. Actuarial survivals were 82.2% at 5 years and 75.6% at 10 years. Fifty-two percent of patients are in functional class I, 38% in class II, and 10% in class III. This study emphasizes the ability of reoperation to provide satisfactory immediate and long-term results. However, since the superiority of the reoperations in late stenosis versus the medical management seems to have been established by your work, could such results have been improved by earlier evaluation of patients as soon as angina recurred? That is my first question. My second question is as follows: In your series of reoperations, did you ever encounter patients who had ITA grafts? If so, which kind of conduit would you recommend at the reoperation? Dr. Jacob Kolff (Johnstown, Pa.). I am a little surprised
p Value
0.40 <0.001
<0.001
0.04
<0.001
0.06
<0.001
0.07 <0.001
P < 0.001
<0.001
about the higher incidence of mortality in the stenotic SV-LAD grafts. What do you do with the stenotic SV-LAD graft? Do you in fact ligate this or do you keep it open? Second when you connect a left ITA to an LAD that has a stenotic SV graft attached to it, are you assured that just the left ITA will always be able to supply the demand needed by that anterior wall? In particular, we had a case in which we ligated the old SV graft to the LAD and could not wean the patient off the pump even with the use of an intraaortic balloon pump. We noticed akinesia of the anterior wall, which all reversed after we reopened the old SV graft. Dr. Lytle. I would like to thank the discussants for their questions. The question about earlier evaluation brings up the issue of prospective reevaluation of patients. Would we have found the same results if we routinely studied patients 10 years after bypass surgery, found some with stenotic SV grafts, and then reoperated on those patients. We cannot answer that ques-
6 14
Lytle et at.
Appendix 2. Variables tested for influence on
in-hospital mortality, late survival, and reoperation-free survival Clinical Gender Age Symptoms (at catheterization) (NYHA I, II, III, IV) Indications for catheterization Angina Myocardial infarction Routine Other Interval betweenoperation and catheterization <5 years, :::: 5 years Angiographic variables Extent of disease(::::50%) IVD, 2VD, versus 3VD/LMT Left ventricular function Normal, mild impairment versus moderate or severe impairment (N/M versus M/S) SV graft stenosis (20%-99%): yes/no SV-LAD graft stenosis SV-circumflex graft stenosis SV-right coronary graft stenosis Patent ITA-LAD graft Total occlusion of LAD graft
tion. Most patients underwent postoperative angiography because of symptoms or some cardiac event, particularly those patients who underwent late postoperative recatheterization. We do from time to time see patients who have undergone routine postoperative studies late after operation and who have significant stenoses in SV-LAD grafts. Most of the time I have recommended reoperation for those patients. In fact, one of the reasons we did this study was that I wanted to make certain that
The Journal of Thoracic and Cardiovascular Surgery April 1993
we were right in recommending a second operation. I think we have been right. The second question concerned conduits at reoperation. If someone has no lower extremity vein and has had both IT As used at the primary operation, a very uncommon situation, then we use whatever we can, inferior epigastric artery and gastroepiploic artery grafts usually. Dr. Kolff's question about how we deal with stenotic LAD grafts is an extremely important question. Our general posture when we reoperate on patients with stenoses in LAD grafts is to replace that SV-LAD graft with another SV-LAD graft. The other alternatives are to leave the old SV graft in place and add an IT A graft to it, or take the old SV graft out and replace it with an ITA graft. That last strategy, to take out a stenotic but not totally occluded vein graft to the LAD and to replace it with an ITA graft is one that can result in anterior wall hypoperfusion. In fact, I would say that is the only situation in which I personally have ever seen the left ITA not provide enough flow to the anterior wall. There are a number of strategies for getting around that problem, the details of which are really beyond the scope of our discussion here. It is an important point, however, and surgeons should be cautious about the maneuver of disconnecting a stenotic (but not totally occluded) vein graft and replacing it with an ITA graft only. If someone does that often enough, sooner or later the same kind of troubles that Dr. Kolff described will result. The issues about the treatment of patients with previous bypass surgery are going to become more important. We certainly do not view this paper as the last word. There is no Coronary Artery Surgery Study or European cooperative study that defines the indications for surgery for persons who have had previous bypass surgery, and reoperative candidates usually have a different disease, vein graft atherosclerosis, than do patients who only have native vessel coronary artery disease. We are going to have to go through the subsets, carefully working out the indications for reoperation. The one thing that we are certain of at this point is that a late stenosis in an SV -LAD graft is an anatomic indication for reoperation.
The effect of coronary reoperation on the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries Does coronary artery reoperation improve the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries? To examine this question, we retrospectively reviewed 1117 patients who had coronary bypass grafting and then underwent a postoperative coronary angiogram that showed a stenosis (2:20 %) of at least one vein graft. Reoperation within 1 month of the postoperative angiogram was performed for 394 patients (REOP group) whereas 723 patients (MED group) received initial medical treatment (no reoperation or percutaneous transluminal coronary angioplasty within 1 year). Compared with the MED group, patients in the REOP group were older, more symptomatic, more likely to have left main stenosis, and had fewer patent bypass grafts (all p < 0.001). In-hospital mortality for the REOP group was 4.3 %. Mean postangiogram follow-up of the entire group was 73 months. On the basis of the interval between the primary operation and the postoperative angiogram, patients were designated as having early « 5 years) or late (2: 5 years) saphenous vein graft stenosis. Univariate and multivariate analyses were used to identify factors influencing the survival of these subgroups. Reoperation was not identified as a variable improving the survival of patients with early vein graft stenoses. For patients with late vein graft stenoses, moderate or severe impairment of left ventricular function (p < 0.0001), advanced age (p < 0.0001), triple-vessel or left main stenosis (p = 0.0011\ and stenosis in a vein graft to the left anterior descending artery (p = 0.0019) decreased survival, whereas reoperation improved survival (p = 0.0007). The improvement in survival with reoperation was particularly strong for patients with a stenotic vein graft to the left anterior descending artery. For that subset, survival was 84% and 74% for the REOP group versus 76% and 53% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.004). For patients with stenotic vein grafts to the right coronary artery or circumflex coronary artery (or both), survival was 92 % and 87 % for the REOP group versus 89 % and 78 % for the MED group at 2 and 4 years after catheterization, respectively (p = 0.13). Even for patients with class I or II symptoms, reoperation prolonged survival (p = 0.002 with multivariate testing). Reoperation improves the survival of patients with late vein graft stenoses, particularly those with stenotic grafts to the left anterior descending coronary artery. (J THoRAc CARDIOVASC SURG 1993;105:605-14)
Bruce W. Lytle, MD, Floyd D. Loop, MD, Paul C. Taylor, MD (by invitation), Marlene Goormastic, MPH (by invitation), Robert W. Stewart, MD (by invitation), Roberto Novoa, MD (by invitation), Patrick McCarthy, MD (by invitation), and Delos M. Cosgrove, MD, Cleveland, Ohio With the technical assistance of Maura J. Schnauffer
From the Cleveland Clinic Foundation, Cleveland, Ohio. Address for reprints: Bruce W. Lytle, MD, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, One Clinic Center, Cleveland, OH 44195.
Read at the Seventy-second Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., April 26-29, 1992. Copyright
1993 by Mosby-Year Book, Inc.
0022-5223/93 $1.00 +.10
12/6/44186
605
606
Patients with stenoses in saphenous vein (SV) bypass grafts to coronary arteries have a disease that is distinct from native-vessel coronary artery disease. In a recent study of patients with SV graft stenoses, we found that those with late (2':5 years after operation) SV graft stenoses had poor late survival without reoperation, particularly if the left anterior descending coronary artery (LAD) was supplied by a stenotic SV graft. I However, it has not been documented that reoperation improves the survival of patients with stenotic SV grafts. In fact, it has not been shown that coronary reoperation improves the survival of any patient subset. The purpose of this study is to examine the influence of reoperation on the shortand long-term survival of patients with SV graft stenoses. Patient population-methods and definitions This is a nonrandomized retrospective study. With the aid of our computerized Cardiovascular Information Registry, a registry that stores data regarding all patients undergoing coronary angiography or bypass grafting at the Cleveland Clinic Foundation, we identified 723 patients who fulfilled the following criteria: I. Operation for isolated coronary bypass grafting was performed at the Cleveland Clinic Foundation. 2. A postoperative angiographic study was performed that demonstrated a stenosisof 20% to 99% in the lumen of at least one SV graft. 3. No invasiverevascularization procedures (bypass grafting or percutaneous transluminal coronary angioplasty [PTCA]) were performed between the primary operation and the postoperative angiogram. 4. No cardiac reoperation or PTCA was performed within a year after the postoperative angiogram that documented the SV graft stenosis. The initial intention was to treat these 723 patients without reoperation, and they are termed the medical (MED) group. Data concerning this group of patients have been reported previously.'
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Lytle et al.
We also identified a group of 394 consecutive patients who fulfilled criteria I to 3 in the preceding paragraph, but who underwent isolated coronary reoperation within I month of the angiogram that demonstrated the SV graft stenosis.This group is termed the reoperation (REOP) group. Those reoperations were performed between 1972and 1989.Baselinedescriptors of clinicaland angiographic variables for both the M ED group and the REOP group are listed in Appendix I. The mean follow-up interval after the catheterization that demonstra ted the SV graft stenosiswas 73 months for the entire group, 83 months (range 0 to 237 months) for the MED group, and 55 months (range 0 to 193 months) for the REOP group. Follow-up was conducted by direct examination at the Cleveland Clinic Foundation, telephone, and letter, and the events that were identified were death, reoperation, and PTCA. Routine follow-upis conducted as part of the Cardiovascular Information Registry and specificfollow-up for this study was conducted by dedicated personnel. The numbers of patients experiencing events in the MED group were death, 205, reoperation, 181, and PTCA, 24. Comparable figures for the
April 1993
REOP group were death, 91, rereoperation, 12, and PTCA, 9. Late survival and reoperation-free survival figures were calculated with the Kaplan-Meier method.? When survival was calculated, the patient was censored alive at the time of the occurrence of a repeat intervention (PTCA or reoperation). When reoperation-free survival was calculated, patients were censored alive at the time of a PTCA. Univariate testing of time-related outcome was done by means of Kaplan-Meier curves- and the Cox proportional hazard model! was used for multivariate testing. Results In-hospital mortality. For the patients in the REOP group, in-hospital mortality was 17 of 394 (4.3%). All in-hospital deaths occurred in patients whose primary operation-to-catheterization interval was 5 years or more, which produced an in-hospital mortality of 5.1% (17 of 335) for that subgroup. The variables in Appendix 2 were tested univariately for association with in-hospital mortality: Results for selected variables are shown in Table I. Logistic regression analysis identified only preoperative congestive heart failure (p = 0.0003) and a late stenosis in an SV graft to the LAD (p = 0.002) as factors increasing in-hospital mortality. Overall survival. Data from our previous study, as well as preliminary calculations from this study, indicated that the outcome of patients with stenotic SV grafts who were managed with initial medical treatment varied greatly on the basis of the interval between the operation and the postoperative catheterization that identified the SV graft stenosis. Therefore, in the comparison of the MED and REOP groups in this study, we elected to separate our analyses on the basis of whether the operation-to-catheterization interval was less than 5 years or 5 years or more. In all models testing survival and reoperation-free survival, in-hospital mortality for the REOP group was included in calculations. Patients with early «5 years) stenoses in SV grafts. For the 490 patients with early «5 years) SV graft stenoses, 431 were in the MED group and 59 were in the REOP group. There was a high correlation between treatment group and the patient's symptom status at the time of the angiogram: 42 of 59 (71 %) patients in the REOP group had class III or IV symptoms versus 46 of 431 (11%) in the MED group (p < 0.001). Patients in both the MED and REOP groups were tested in a multivariate model to examine the influence of the variables in Appendix 2 and the treatment group on survival (Table 11). Reoperation did not influence survival significantly. Univariate survival curves for the REOP and MED groups with early SV graft stenoses are shown in Fig. I. When we examined patients who had class III or class IV symptoms at the time that the stenosis-identifying catheterization was performed (46 in the MED group, 42
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Table I. Variables associated (p > 0,10) with reoperation in-hospital mortality: Univariate analyses Patients Primary operation-postop. <5 yr :0:5 yr NYHA functional class
In-hospital Mortality (%) p Value death
angiogram interval 59 0 17 335
0 5.1
0.09
0.07
265 129 IS 68 165
8 9 3 0 14
3.0 7.0 20.0 0 8.5
0.02 0.05 0.002
49
0
0
0.14
17
0
0
1.00
in the REOP group), univariate testing did not show any difference in survival between the MED and REOP groups. However, because 15 (33%) of the MED patients eventually underwent reoperation, reoperation-free survival was better (p = 0.03) for the REOP group so long as the initial reoperation was excluded from consideration. Furthermore, at late follow-up 23 of 31 patients in the REOP group had class I or II symptoms, compared with only II of 31 in the MED group. Late symptom status (New York Heart Association [NYHA] functional class) for the entire group of patients with early SV graft stenoses was as follows: REOP group 1,24, II, 13, III, 5, and IV, 4, versus MED group I, 105, II, 87, III, 78, IV, 30 (p = 0.02). Patients with late (2':5 years) stenoses in SV grafts. Ofthe 627 patients with late (2':5 years) SV graft stenoses, 292 were in the MED group and 335 were in the REOP group. Again, the patients in the REOP group were more symptomatic at the time of their angiogram: 215 of 335 (64%) patients in the REOP group had class III or IV symptoms versus 73 of 292 (25%) in the MED group (p < 0.001). Furthermore, the REOP group contained more patients with left main stenoses and fewer patients with patent SV grafts or patent internal thoracic artery (ITA) grafts (all p < 0.001). The 627 patients with late SV graft stenoses were examined in a multivariate model that tested the variables in Appendix 2 in addition to treatment choice (MED versus REOP). Results of that model are shown in Table III. Moderate or severe impairment of left ventricular function, advanced age, triple-vessel or left main coronary disease, and a stenosis (20% to 99%) in an SV graft to the LAD were all associated with decreased survival. Reoperation increased survival. Survival curves showing
607
Table II. Patients with early «5 years) stenoses in vein grafts: Multivariate model of variables influencing survival (n = 490) Variables Decreasing Survival
p Value
Relative risk
LVF (modjsev) Age (at catheterization) Angina at catheterization Occluded SV graft to LAD 3VDjLMT
0.0001 0.0001 0.0408 0.0286 0.0287
2.55 1.04* 1.54 2.03 1.57
LVF (modlsev}, Left ventricular function, moderate or severe impairment; 3VD/LMT, triple-vessel disease and/or left main stenosis.
'Per year.
Table III. Patients with late (2':5 years) stenoses in vein grafts: multivariate model of variables influencing survival (n = 627) Variables decreasing survival LVF (modjsev) Age (at catheterization) 3VDjLMT LAD vein graft stenosis (20%-99%) Variable increasing survival Reoperation
p Value
Relative risk
0.0001 0.0001 0.0011 0.0019
2.58 1.04* 2.87 1.90
0.0007
0.51
*Per year.
univariate comparisons of the MED and REOP groups for all patients with late stenoses are shown in Fig. 2. Construction of another multivariate model that included only patients with NYHA functional class I or II symptoms at the time of the postoperative angiogram showed that reoperation still was associated with increased survival for that subgroup (Table IV) of patients with late SV graft stenoses. The status of the graft to the LAD was important in predicting the influence of reoperation on late survival. Univariate comparison of survival curves of the MED and REOP groups of patients with late stenoses in SV-LAD grafts (Fig. 3) demonstrates improved survival for the REOP group. When patients with late stenoses in SV-LAD grafts were separated on the basis of the severity of the stenosis, patients with severe (50% to 99%) SV-LAD graft stenoses had better survival statistics throughout the follow-up (Fig. 4, top). For patients with less severe (20% to 49%) SV-LAD graft stenoses (Fig. 4, bottom), survival of the MED and REOP groups was equivalent at 2 years, but the curves diverged between 2 and 4 years after the angiogram such that the improvement in survival for the REOP group approached significance (p = 0.06). Univariate survival curves for patients with totally occluded SV grafts to the LAD are shown in
608
The Journal of Thoracic and Cardiovascular Surgery April 1993
Lytle et al.
100
--
94% F=~;;:~;;~~=--;~-;---l p=0.57
80
...............
~ 0
...J
60
s>a::
40
::J
en
20
•••••• Reoperation group n=59 - - Medical group n=431
00 Number at Risk
2
4
54 402
47 352
YEARS
6
10
35 309
26 237
14 188
Fig. 1. Survival of patients with early «5 postoperative years) stenoses in SV grafts, MED and REOP groups (p = not significant).
100.,---------------------, .,
;? o
80
...J
60
s>a::
40
::J
en
20
Number at Risk
....tT.......~ .r:"_ .""1
.......
. ........
.... "="ro,.."....
....
...
"-~t",
"--i. ..,
" - .....,. ....·~:.a6J'....
... ~..~_.
....-.-.-
~ ~
_...
...............
..••.. Reoperation group n=335 - - Medical group n=292 Reoperation group (Reop-free) n=335 Medical group (Reop-free) n=292
2
4
269 211 264 208
157 98 154 97
YEARS
'- . -. - . -.
10
6 74 48 72 47
l
24 25 24 25
7 8 5 6
Fig. 2. Survival and reoperation-free survival of patients with late (2:5 years) stenoses in SV grafts, MED versus REOP. Patients undergoing reoperation had improved survival (p = 0.03). Patients in the MED group had reoperation-free survival of only 48% at 5 years.
Fig. 5 and indicate better survival for the REOP group, although that was not found to be significant in multivariate testing. Patients with patent IT A grafts to the LAD had relatively good survival, even with initial medical treatment, and the outcomes for the REOP and MED groups were comparable (Fig. 6). One hundred twenty-
seven patients with late SV graft stenoses had patent SV-LAD grafts, and there was also no survival difference between the MED and REOP groups for that subset. Because the major purpose of the study was to examine the influence of initial treatment choice (initial medical treatment versus initial reoperation) on the outcome
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
Lytle et al.
609
100,...--------------------, • ••••••
-
~ o
. .J c(
s>IX :::» (/)
80
p=O.004
84%
" •••••• ,.........
74%
' -
-··f
_,.
...... -..................... -.
60 53%
40 20
Number at Risk
•••••• Reoperation group n=165 - - Medical group n=82
2
4
127 53
71 24
YEARS
6
8
10
36
12 4
4 1
8
Fig. 3. Survival of patients with late stenoses in SV grafts to the LAD coronaryartery. Patients undergoing reoperation had improved survival.
of patients with SV graft stenoses and because the circumstances, location, and effectiveness of delayed reoperations for patients with initial medical treatment introduced many potentially confounding variables, we censored the follow-up of patients in the MED group at the time of their delayed reoperation for most analyses. However, for the group shown to benefit the most from immediate reoperation, patients with late SV-LAD graft stenoses, we conducted further analyses in which followup of the MED group was continued beyond delayed reoperation. Of patients with late SV-LAD graft stenoses of 20% to 99%,there were 82 patients in the MED group, of whom 23 underwent delayed (> I year after their angiogram) reoperations, 19 between I and 5 years after the angiogram documenting the SV graft stenosis. Survival at delayed reoperation was good (I death of 23 patients), as was the late survival after delayed reoperation. Therefore the survival figures of the MED group when the followup was continued after delayed reoperation were almost identical to those obtained when the MED group was censored at the time of delayed reoperation. Regardless of the type of statistical method used, survival statistics were better in the REOP group. Two hundred thirty-seven patients with late SV graft stenoseshad neither a stenotic SV -LAD graft nor a patent ITA-LAD graft. One hundred twenty-six patients were treated with initial medical treatment and III with initial reoperation. A multivariate model addressing survival showed that left ventricular function (p = 0.0002) and triple-vessel or left main coronary disease (p = 0.01)
Table IV. Multivariate analysis of variables
influencing the survival ofpatients with late (::0::5 year) stenoses in vein grafts: NYHA functional class I or II symptoms (n = 339) Variables decreasing survival LVF (modjsev) Age (at catheterization) 3VDjLMT LAD vein graft stenosis (20%-99%) Variable increasing survival Reoperation
p Value
Relative risk
0.0001 0.0006 0.0183 0.0188
3.29 1.05 3.14 2.19
0.0020
0.43
decreased survival, whereas reoperation (p = 0.01) was associated with increased survival. Univariate comparison of patients with only late stenoses of SV-right coronary/ or SV-circumflex coronary artery grafts showed a trend (p = 0.13) toward increased survival for the REOP group (REOP group 92% and 87% at 2 and 4 postoperative years, respectively, versus 89% and 78% for the MED group). The high-risk characteristics of a late SV-LAD graft stenosis, triple-vessel or left main stenosis, and moderate or severe impairment of left ventricular function were combined in 74 patients, 47 in the REOP group and 27 in the MED group. Survival at 2 years was 55% for the MED group and 79% for the REOP group (p = 0.0011). Symptoms. For patients with late SV graft stenoses, the symptom status (NYHA functional class) for the late survivors at follow-up was as follows: REOP group I, 189
6 10
The Journal of Thoracic arid Cardiovascular Surgery April 1993
Lytle et al.
100.----------------------, p=0.02 ~
C ':i. > s !5
80
",
73%
..
~ -.".-....... -
I
.
60
_
..
54%
40
l/)
20
•••••. Reoperatioo group 0=141 - - Medical group 0=52
2
4
YEARS
6
100
~
8
10
p=0.06
80
:.l! ~
...J ce 60 > a: 40
s
~
l/)
20
Reoperatioo group - - Medical group
2
4
YEARS
6
8
10
Fig. 4. Survival of patients with stenotic SY-LAD grafts basedon the severity of stenosis. Top, 50% to 99% stenosis; bottom, 20% to 49% stenosis.
(74%), II, 46 (18%), III, 17 (7%), IV,4 (2%); MED group 1,68 (33%), II, 76 (37%), III, 46 (22%), and IV, 16 (8%) (p = 0.0001). Discussion The results of this study indicate that early coronary reoperation improves the survival of patients with late stenoses in SV grafts, with the greatest improvement occurring in those with late stenoses in SV grafts to the LAD. The choice of treatment for the patients in this study was not randomized. Comparison of the clinical and angiographic characteristics of the REOP and MED groups at the time of the postoperative angiogram that identified the SV graft stenoses identifies clear differences between the treatment groups. The patients in the MED group were significantly younger and had less severe symptoms, better left ventricular function, fewer left main lesions, more patent ITA and SV grafts, and were more likely to have early stenoses than were the
REOP group. There obviously was an institutional bias toward reoperation for patients with high-risk characteristics. Our previous study concerning the outcome of patients with SV graft stenoses treated without an initial operation showed that late SV graft stenoses (those demonstrated 5 years or more after operation) predict a much higher rate of death and other cardiac events than do early SV graft stenoses (those demonstrated within 5 years of operation). This clinical difference correlates with a difference in the pathologic features of early versus late SV graft stenoses. Early SV graft stenoses are usually caused by intimal fibroplasia, whereas late SV graft stenoses are more often caused by SV graft atherosclerosis.v? Intimal fibroplasia may cause graft occlusion, and thrombosis superimposed on stenoses caused by intimal fibroplasia has been noted." However, intimal fibroplasia appears to be a relatively stable lesion when compared with fully developed SV graft atherosclerosis.r'' SV graft atherosclerosis is a diffuse, friable, unstable lesion that has caused embolization during manipulation associated with reoperation or PTCA. lo In addition, it may incite thrombosis.!' Because of these different pathologic characteristics and outcomes, we elected to analyze patients with early and late stenoses separately. Patients with early SV graft stenoses were usually (88%) treated without immediate reoperation. Reoperation for patients with early SV graft stenoses was usually used for symptom relief: 71% of patients in the REOP group had class III or IV symptoms. No hospital deaths occurred in the 59 patients who underwent reoperation for early SV graft stenosis. However, reoperation did not appear to improve the overall survival of this subset, mainly because of the relatively good survival of the patients with early SV graft stenoses treated without early surgical intervention. Many of the symptomatic patients in the MED group eventually did undergo reoperation, and the late symptom status of the late REOP group was superior to that for the MED group. However, patients treated without an early operation did not appear to be at a high risk of death, which confirms the relative safety of reserving operation for the presence of severe symptoms. Patients with late SV graft stenoses were in a more dangerous situation regardless of which treatment (MED or REOP) was initially chosen. The in-hospital mortality rate for reoperation was 5.1% for patients with late SV graft stenoses. Furthermore, that mortality rate was particularly high for patients with a stenotic SV graft to the LAD (8.5%), possibly because of the dangerous tendency of SV graft atherosclerosis to produce embolization
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 4
-
Lytle et al.
100 ., - - - : -97',io ....,---------------------, o':., p=O.0019 .... ". -0
", 81%
....,
80
.~
...........................................
..
~
..J ~
>
sII:
:>
en
6I I
60 40
20
••. . • • Reoperation group - - Medical group
n=39 n=23
4
2
6
8
12 3
2
10
YEARS
36
Number at Risk
15
22 5
Fig. 5. Survival of patients with stenosesin SV grafts, but who also had a totally occluded SV graft to the LAD. Survival was better with reoperation.
-
, ...... -, ,
80
p=O.75
83%
~
~
..J ~
..
"
60
>
s
II:
:>
en
40
20
..... , Reoperation group n=59 -
Number at ., •••• Risk
Medical group
47 62
n=83
23
5
28
13
1 7
6
Fig. 6. Survivalof patients with patent ITA grafts to the LAD in addition to at least one stenoticSV graft. Survival was equivalent for the MED and REOP groups.
during reoperation. Patients with patent ITA grafts to the LAD and those with totally occluded SV-LAD grafts (i.e., situations in which the important LAD system is protected from the danger of embolization of atherosclerotic debris from an SV graft) had no in-hospital mortality. These reoperations were performed from 1972 to 1989, and we believe that increased experience and advances in myocardial protection such as retrograde
delivery of cardioplegic solution have decreased the risk of atherosclerotic embolization during reoperation. Despite the in-hospital risk of reoperation, multivariate testing identified reoperation as a factor significantly increasing overall survival of patients with late SV graft stenoses. The improvement in long-term survival achieved by reoperation was related in part to the status of the graft to the LAD. Patients with a late stenosis in an SV-LAD
6 12
The Journal of Thoracic and Cardiovascular Surgery April 1993
Lytle et al.
graft had a much better overall survival with reoperation than with medical treatment, despite the fact that they had an increased in-hospital risk associated with the operation. Patients with a totally obstructed graft to the LAD also had improved survival with early operation. Patients with a patent ITA graft to the LAD were at lower risk without reoperation, and early operation did not appear to improve their overall survival. For patients with neither a stenotic SV-LAD graft (high-risk group) nor a patent ITA-LAD graft (low-risk group), reoperation improved overall survival, but not as dramatically as it did for patients with late SV-LAD graft stenoses. A delayed reoperation (reoperation > 1 year after the angiogram) was done in 23 of the 82 patients with late SV-LAD graft stenoses in the MED group. Those patients who survived with initial medical treatment long enough to undergo a delayed reoperation did well. The large difference in survival between the MED and REOP groups was caused by the high rate of death in the MED group for patients who never underwent a second operation, an observation that argues against the strategy of waiting until symptoms worsen before offering reoperation to patients with late SV-LAD graft stenoses. Whereas it appears that for patients with early SV graft stenoses recommendation for reoperation can be based on the severity of symptoms, that principle does not appear to be the case for patients with late SV graft stenoses. When patients with late SV graft stenoses but only class I or II symptoms were included in a multivariate model, early reoperation improved overall survival, even in the presence of mild symptoms. Many patients in the MED group who did not have an initial repeat operation subsequently did undergo reoperation. In fact, fewer than half of the patients with late SV graft stenoses who were initially in the MED group survived 5 years without reoperation. Furthermore, for patients with either early or lateSV graft stenoses, the late symptom status of the REOP group was superior to that of the MED group. The results of this study indicate that patients with late stenoses in SV grafts to the LAD should undergo reoperation, even if they are not severely symptomatic. The effect of bypass surgery in prolonging life expectancy is clearest for that subset. Patients without SV-LAD graft stenoses but with late stenoses in SV grafts to the circumflex or right coronary system (or both) also appear to have better survival statistics with initial surgical treatment, so long as the LAD is not protected by a patent ITA graft. REFERENCES I. Lytle BW, Loop FD, Taylor PC, et al. Vein graft disease: the clinical impact of stenoses in saphenous vein bypass
grafts to coronary arteries. J THoRAc CARDIOVASC SURG 1992;103:831-40.
2. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;8:699. 3. Cox DR. Regression models and life tables. J R Stat Soc (B) 1972;34:187.
4. Lytle BW, Loop FD, CosgroveDM, RatliffNB, EasleyK, Taylor Pc. Long-term (5 to 10 years) serial studies of internal mammary artery and saphenous vein coronary bypassgrafts. J THORAC CARDIOVASC SURG 1985;89:24858.
5. Ratliff NB, Myles JL. Rapidly progressive atherosclerosis in aortocoronary saphenous vein grafts. Arch Pathol Lab Med 1989;113:772. 6. Bourassa MG, Campeau L, Lesperance J. Changes in grafts and in coronary arteries after coronary bypass surgery. Cardiovasc Clin 1991;21:83. 7. Solymoss BC, Nadeau P, Campeau L. Factors related to atherosclerosisof saphenous vein coronary bypassgrafts. J Am Coil Cardiol 1987;9:85A. 8. Neitzel GF, Barboriat JJ, Pintar R, et al. Atherosclerosis in aortocoronary bypassgrafts: morphologic study and risk factor analysis 6-12 years after surgery. Arteriosclerosis 1986;6:594.
9. Lawrie GM, Lie JT, Morris GC, et al. Vein graft patency and intimal proliferation after aortocoronary bypass: early and long-term angiopathic correlations. Am J Cardiol 1976;38:856.
10. Keon W J, Heggtveit HA, Lecluc J. Perioperativemyocardial infarction caused by atheroembolization. J THORAC CARDIOVASC SURG 1982;84:849-55. 11. 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 occlusions. Circulation 1982;65:197.
Discussion Dr. Jean Paul Cachera (Paris, France). You have given us proof of the superiorityof reoperationsversus medical management in patients with coronary disease, at least in the group of patients with late SV graft stenosis,eventhough your groupsof patients were not selected on a random basis. Our own experience is similar. We have reoperated on 161 patients for recurrent angina pectoris from 1978 to 1991. In 42 patients, 25%, the recurrence of symptoms was correlated with the occlusion or stenosis of one or several SV grafts. In 28 patients, 17%, isolated impairment of the coronary vessels becauseof the progression of artheroscleroticlesions waspresent without significant alterations of the SV grafts. In 96 patients, 58%, simultaneous impairment of native coronary vessels and SV grafts was observed. The mean time elapsed between the primary operation and the reoperation was 93.3 months. The time elapsed betweenthe onset of symptoms and the reoperation was 27.7 months. Twenty-five percent of patients were in functional class II and 75% in class III or IV. The overall hospital mortality was significantly higher than yours (8%, 13/161), and all the deaths
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Lytle et al.
613
Appendix 1. Characterization at catheterization ofpatients with stenotic vein grafts treated medically (MED) or with reoperation (REOP) MED = 723)
REOP = 394)
(n
(n
N Men 664 Mean age (yr) 57.4 NYHA functional class at cath. I 310 294 II 75 III IV 44 CHF 49 Indications for cath. 368 Angina 67 MI 180 Routine 108 Other LVF Normal-mild 553 Mod-sev 170 Extent of disease 118 LMT IVD 49 2VD 149 3VD 407 No. of stenotic vein grafts 617 I 98 2 8 3 No. with patent 195 ITA grafts No. of patent vein grafts 372 0 I 269 2 73 9 3 Interval after primary operation (yr) 431 <5 :0::5 292
%
N
%
91.8
356 62.0
90.4
42.9 40.7 10.4 6.1 6.8
35 102 128 129 15
8.9 25.9 32.5 32.7 3.8
50.9 9.3 34.9 14.9
290 77 5 22
73.6 19.5 1.3 5.6
76.5 23.5
281 113
71.3 28.7
16.3 6.8 20.6 56.3
118 7 36 233
30.0 1.8 9.1 59.1
85.3 13.6 l.l 27.0
315 72 7 68
79.9 18.3 1.8 17.3
51.5 37.2 10.1 1.2
316 69 8 1
80.2 17.5 2.0 0.3
59.6 40.4
59 335
15.0 85.0
were due to myocardial failure. The mean follow-up in survivors was 40.1 months, and among those survivors there were seven late deaths and four cardiac transplantations. Actuarial survivals were 82.2% at 5 years and 75.6% at 10 years. Fifty-two percent of patients are in functional class I, 38% in class II, and 10% in class III. This study emphasizes the ability of reoperation to provide satisfactory immediate and long-term results. However, since the superiority of the reoperations in late stenosis versus the medical management seems to have been established by your work, could such results have been improved by earlier evaluation of patients as soon as angina recurred? That is my first question. My second question is as follows: In your series of reoperations, did you ever encounter patients who had ITA grafts? If so, which kind of conduit would you recommend at the reoperation? Dr. Jacob Kolff (Johnstown, Pa.). I am a little surprised
p Value
0.40 <0.001
<0.001
0.04
<0.001
0.06
<0.001
0.07 <0.001
P < 0.001
<0.001
about the higher incidence of mortality in the stenotic SV-LAD grafts. What do you do with the stenotic SV-LAD graft? Do you in fact ligate this or do you keep it open? Second when you connect a left ITA to an LAD that has a stenotic SV graft attached to it, are you assured that just the left ITA will always be able to supply the demand needed by that anterior wall? In particular, we had a case in which we ligated the old SV graft to the LAD and could not wean the patient off the pump even with the use of an intraaortic balloon pump. We noticed akinesia of the anterior wall, which all reversed after we reopened the old SV graft. Dr. Lytle. I would like to thank the discussants for their questions. The question about earlier evaluation brings up the issue of prospective reevaluation of patients. Would we have found the same results if we routinely studied patients 10 years after bypass surgery, found some with stenotic SV grafts, and then reoperated on those patients. We cannot answer that ques-
6 14
Lytle et at.
Appendix 2. Variables tested for influence on
in-hospital mortality, late survival, and reoperation-free survival Clinical Gender Age Symptoms (at catheterization) (NYHA I, II, III, IV) Indications for catheterization Angina Myocardial infarction Routine Other Interval betweenoperation and catheterization <5 years, :::: 5 years Angiographic variables Extent of disease(::::50%) IVD, 2VD, versus 3VD/LMT Left ventricular function Normal, mild impairment versus moderate or severe impairment (N/M versus M/S) SV graft stenosis (20%-99%): yes/no SV-LAD graft stenosis SV-circumflex graft stenosis SV-right coronary graft stenosis Patent ITA-LAD graft Total occlusion of LAD graft
tion. Most patients underwent postoperative angiography because of symptoms or some cardiac event, particularly those patients who underwent late postoperative recatheterization. We do from time to time see patients who have undergone routine postoperative studies late after operation and who have significant stenoses in SV-LAD grafts. Most of the time I have recommended reoperation for those patients. In fact, one of the reasons we did this study was that I wanted to make certain that
The Journal of Thoracic and Cardiovascular Surgery April 1993
we were right in recommending a second operation. I think we have been right. The second question concerned conduits at reoperation. If someone has no lower extremity vein and has had both IT As used at the primary operation, a very uncommon situation, then we use whatever we can, inferior epigastric artery and gastroepiploic artery grafts usually. Dr. Kolff's question about how we deal with stenotic LAD grafts is an extremely important question. Our general posture when we reoperate on patients with stenoses in LAD grafts is to replace that SV-LAD graft with another SV-LAD graft. The other alternatives are to leave the old SV graft in place and add an IT A graft to it, or take the old SV graft out and replace it with an ITA graft. That last strategy, to take out a stenotic but not totally occluded vein graft to the LAD and to replace it with an ITA graft is one that can result in anterior wall hypoperfusion. In fact, I would say that is the only situation in which I personally have ever seen the left ITA not provide enough flow to the anterior wall. There are a number of strategies for getting around that problem, the details of which are really beyond the scope of our discussion here. It is an important point, however, and surgeons should be cautious about the maneuver of disconnecting a stenotic (but not totally occluded) vein graft and replacing it with an ITA graft only. If someone does that often enough, sooner or later the same kind of troubles that Dr. Kolff described will result. The issues about the treatment of patients with previous bypass surgery are going to become more important. We certainly do not view this paper as the last word. There is no Coronary Artery Surgery Study or European cooperative study that defines the indications for surgery for persons who have had previous bypass surgery, and reoperative candidates usually have a different disease, vein graft atherosclerosis, than do patients who only have native vessel coronary artery disease. We are going to have to go through the subsets, carefully working out the indications for reoperation. The one thing that we are certain of at this point is that a late stenosis in an SV -LAD graft is an anatomic indication for reoperation.