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J Thorac Cardiovasc Surg 2000;120:173-184
© 2000 The American Association for Thoracic Surgery
SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE |
From the Department of Thoracic and Cardiovascular Surgerya and the Department of Biostatistics and Epidemiology,b The Cleveland Clinic Foundation, Cleveland, Ohio.
Address for reprints: Eugene H. Blackstone, MD, Department of Thoracic and Cardiovascular Surgery, 9500 Euclid Ave, Desk F25, Cleveland, OH 44195 (E-mail: blackse{at}ccf.org ).
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Abstract |
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 Top Abstract IntroductionPatients and methods Results Discussion Appendix: Discussion References |
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70%) left circumflex (P = .01) and proximal right coronary artery disease (P = .01), as well as any degree of left main trunk stenosis (P < .0001), were associated with reduced long-term survival. Compared with 75% 20-year survival in patients with no non–left anterior descending disease, those with either left circumflex or left main trunk disease experienced a 44% survival, and those with proximal right coronary artery disease, 42%. The most common stated reason for incomplete revascularization was small vessel size. Freedom from reintervention was 89% and 65% at 10 and 20 years, respectively. High-grade left main trunk disease, but, in contrast, mid or distal disease of the right coronary artery, and not left circumflex disease, were risk factors for reintervention. |
Introduction |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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1-7 Realistically, it has been difficult to define complete revascularization and to separate the effect of incomplete revascularization as a surgical strategy from the possibility that incomplete revascularization is a marker for worse coronary artery disease or, perhaps, a more rapid rate of progression of coronary artery disease.
Currently, multiple avenues to achieve some degree of myocardial revascularization are available. In some of the strategies, percutaneous and operative, less complete revascularization is accepted to limit the invasiveness of the procedure. Part of the logic behind these strategies is the thought that the left internal thoracic artery to left anterior descending coronary artery (LITA-LAD) graft is so important that revascularization of other areas is relatively unimportant. Our previous studies of patients receiving LITA-LAD grafts have shown that nonsignificant disease in the territories of the right coronary artery (RCA) and left circumflex coronary artery (LCx) system is a predictor of late events. 8 However, to examine with a larger patient subset the prognostic issues of incomplete revascularization in patients who already have significant stenoses, we studied 2067 patients undergoing operation with an isolated LITA graft solely to the LAD during the years 1971 through 1996, with follow-up extending to 25 years.
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Patients and methods |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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Angiographic data
Stenoses were recorded by CVIR abstractors from the catheterization report for each coronary system as follows. For the LAD system, the maximal stenosis was recorded in the proximal, mid, and distal portions of the LAD, the diagonal branches, a major septal artery, and the ramus intermedius coronary artery if it originated from the LAD. For the LCx system, the maximal stenosis was recorded in the proximal LCx, the lateral branches, posterolateral segments, in the ramus intermedius if it came off the circumflex, and in the posterior descending coronary artery if it originated from the LCx in a left dominant pattern. For the RCA system, the maximal stenosis was recorded in the proximal, mid, and distal RCA, right marginals, and posterior descending coronary artery and posterolateral segments in right dominant patterns.
Incomplete revascularization
We defined incomplete revascularization as the presence of stenosis in the LCx or RCA systems of 50% or greater. This definition assumes that (1) the LITA-LAD graft allows complete perfusion of the LAD system and (2) stenosis of the left main trunk is managed separately in the analyses. In addition to this arbitrary, global dichotomous variable, we investigated the overall maximal LCx and RCA system stenoses, as well as stenosis in each of the segments cited above. For this we used both the "continuous" percent stenosis and variables representing three discrete criteria: (1) stenosis greater than 0 (any stenosis), (2) stenosis of 50% or greater diameter reduction, and (3) stenosis of 70% or greater diameter reduction.
To verify the quality of this information, and to ascertain the recorded reasons non-LAD lesions were not bypassed, we selected a 10% random sample of cases with lesions in the RCA or LCx system greater than or equal to 50% for detailed study. For this, the uniform pseudorandom number generator in the SAS system software (SAS Institute, Inc, Cary, NC) was used. Because of systematic discard of angiograms by the institution and missing records, a total of 268 random records were randomized to obtain the requisite 206 complete records. All coronary angiography reports were reviewed, which in most cases included prints of representative angiographic frames rather than original angiographic films that had been destroyed or returned to the referring institution. For patients catheterized elsewhere, both the outside catheterization report and the report of its review by Cleveland Clinic Foundation cardiologists were examined. Recommendations made by cardiologists preoperatively were recorded. Each operative report was reviewed, along with any other records, such as letters to referring physicians, to record reasons for incomplete revascularization.
Data analysis
The end points for this study were two: (1) all-cause mortality from the time of LITA-LAD grafting and (2) reintervention, either by percutaneous revascularization of any kind (generically designated percutaneous transluminal coronary angioplasty [PTCA]) or reoperation. The primary objective of the data analysis was to determine the association, if any, between unbypassed lesions in the non-LAD coronary systems (left main, LCx, RCA) and these time-related events. Secondary objectives included investigating the pattern of incomplete revascularization across time and identifying the reasons for incomplete revascularization.
Nonparametric estimates of survival and freedom from reintervention were obtained by the method of Kaplan and Meier. 9 A parametric method* was used to resolve the number of phases of instantaneous risk of death (hazard function) and to estimate their shaping parameters. 10
The potential risk factors (variables) obtained from the CVIR database were organized for analysis as in Appendix Table I. Exploratory analyses of these variables included correlation analysis, stratified life table analyses, and decile risk analysis of ordinal and continuous variables to determine possible transformations of scale needed to properly calibrate the variables to outcome.
Multivariable analyses were performed with particular attention to the details of the unbypassed coronary stenoses. Specific so-called interaction analyses were conducted of the coronary lesions identified as risk factors with the pattern of coronary artery dominance, left ventricular function, age, and diabetes. Interaction analysis was also performed of incomplete revascularization (see below). The analyses used a directed technique of entry of variables into the multivariable models. 11 The P value criterion for retention of variables in the final models was .05.
Multivariable logistic regression analysis was used to identify the characteristics of patients with incomplete revascularization. For this, all patient variables were examined, but the only coronary artery variables incorporated into the analysis were those related to the pattern of coronary dominance.
Presentation
Because few patients were followed up longer than 25 years, graphical presentations were truncated at 25 years. Nonparametric Kaplan-Meier time-related estimates are presented as discrete symbols accompanied by asymmetric confidence limits (CL) equivalent to 1 SE. 12 Smooth, solid curves, which are superimposed on the symbols, are completely independent parametric estimates of the distribution of intervals to death or reintervention. These are accompanied by confidence limits equivalent to 1 SE. 10
For informal survival comparison and reference, a predicted US population life table was generated for each patient, specific to his or her sex and age at the time of the operation. These tables were averaged to portray an age-sex–matched population life table. For some comparisons, individual curves were generated for each patient from the multivariable equations and averaged within strata. 13 These were compared with stratified Kaplan-Meier estimates.
For comparisons of survival in patients with disease other than in the LAD system, a cohort of 682 patients was identified with no recognized obstruction of any degree (not just nonsignificant obstruction) in the left main trunk, LCx system, or RCA system. For clarity, only parametric estimates of this cohort are portrayed.
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Results |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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, B ). By way of orientation, this hazard function was similar to that predicted for the age-sex–matched US population after about 8 years. The hazard function consisted of a brief early phase, a small constant hazard phase, and a late rising hazard phase. The early hazard phase accounted for only 9 deaths, the constant hazard phase for 111, and the late hazard phase for 453. Thus, in the nonproportional hazards multivariable models, a risk factor in the late hazard phase of similar magnitude to one in the constant hazard phase will have many times larger impact on survival.
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50%) of the LCx and RCA, with high-grade (70%) stenosis in the LCx system, and with high-grade proximal RCA stenosis.
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). To illustrate the impact of left main trunk disease on survival using raw data, Fig 3 compares patients with left main lesions of any degree (unadjusted for other lesions and patient characteristics) with the subgroup patients having no recognized obstructions other than that in the LAD system. At 20 years, survival was 44% (CL 39%-49%) for patients with any degree of left main disease (Table V) compared with 75% (CL 72%-77%).
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70%) LCx system disease was present preoperatively in 301 patients (Table V). At 20 years, survival among these patients was 44% (CL 41%-47%) (Fig 5). Those with disease in the lateral LCx branches fared somewhat worse (Fig 5, Table V); their increased risk occurred somewhat earlier than it did with other LCx system lesions (constant hazard phase, Table IV).
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). Their survival was worse compared with a group of patients with RCA system disease (50%), including those with proximal RCA disease between 50% and 70%, but without left main or LCx disease of any degree (Fig 6). Survival of both these groups, however, was worse than that for the cohort of patients with no disease appreciated outside the LAD.
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), but were further complicated by the introduction of percutaneous methods in the 1980s (Table VII). Importantly, disease in the mid and distal RCA were risk factors for reintervention, in contrast to the association of proximal RCA disease and death in the dominating late phase of hazard. LCx disease was associated with a reduced rate of reintervention, even though it increased the risk of death. The small number of patients with high-grade (70%) left main trunk disease came rapidly to reintervention, but not those with less severe grades of stenosis.
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Discussion |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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8,14-19 However, in this study the patients with unbypassed lesions in the proximal RCA or in the LCx coronary artery, or any lesion (regardless of severity) in the left main coronary artery, had importantly worse survival than patients without those lesions. The magnitude of the difference between completely and incompletely revascularized patients was substantial and became particularly striking in the second decade after operation. The mechanism for these findings is not clear. Was the increased rate of late death related to the ischemic burden existing at the time of operation, or were these unbypassed lesions markers of a more severe atherogenic diathesis that produced more aggressive progression of native vessel disease during the follow-up period? Our data do not allow us to say. We sought to gain some insight by examining the reasons for incomplete revascularization. Incomplete revascularization was more common in the early years of the coronary bypass era and was usually based on the thought that the unbypassed arteries were not important because of small size or infarction in their distribution. However, they may have been more important than originally recognized.
A second important observation is that left main stenosis of any degree predicted decreased late survival. Again, the question arises whether the negative impact of seemingly "nonsignificant" left main stenoses was related to an underestimation of those stenoses at the time of operation or the rate of subsequent disease progression. Angiographic evaluation of left main coronary lesions can be difficult, and considerable interobserver and intraobserver variability has been noted. 20,21 Intravascular ultrasound has documented the presence of important disease in patients for whom angiograms did not clearly document left main stenosis and may provide a more accurate means for assessing the left main coronary artery in the future. 22
A third lesson from the study is that the likelihood of reintervention may be associated with variables that are not associated with the risk of death, for example, ungrafted distal RCA stenoses. Sergeant, Blackstone, and Meyns 23 have made that observation in the assessment of large numbers of patients with multivessel disease as well.
Importance of incomplete revascularization
The advent of percutaneous and less invasive surgical approaches to myocardial revascularization has raised the issue of the importance of complete revascularization, because those strategies are less consistently able to achieve complete revascularization than standard surgical methods. 24,25 The concept of "functionally adequate revascularization"—restoration of perfusion to vessels judged bypassable that supply normal myocardium—has arisen from the interventional cardiology literature. 26 Some studies of small numbers of patients with multivessel disease undergoing PTCA have not demonstrated a significant difference in 1-year survival when comparing patients receiving "functionally adequate" versus "complete" revascularization. 26 However, those observations are not clearly applicable to the surgical situation. First, patients undergoing multiple PTCAs during the time period when these studies were conducted tended to be patients who were not at a high risk of short-term death regardless of treatment success. 24-26 Second, the follow-up interval of 1 year has little relationship to long-term survival considerations. Third, patients undergoing PTCA are at a relatively high risk of failure of treatment (restenosis) even in those vessels that are treated, making differences between complete and incomplete treatment relatively smaller. Fourth, patients with incomplete revascularization after PTCA are more apt to come to surgical revascularization that may improve their survival. It is of interest that the characteristics of PTCA patients receiving "functionally adequate revascularization" appear to be similar to our patients who received "incomplete revascularization," a group who had inferior long-term outcomes despite LITA-LAD grafting.
Limitations
This study has obvious limitations. It is an observational clinical study. We did not have data regarding myocardial viability or serial angiographic data related to disease progression. The ideal control group, patients with similar multivessel lesions who did not receive bypass grafts, does not exist. Although we infer that complete revascularization might improve outcomes, the evidence for that is indirect and untested.
However, these data do provide some insight into complete revascularization and late outcome. Previous studies of complete versus incomplete revascularization have involved groups of patients with multivessel disease, few of whom received internal thoracic artery grafts. Today, it might be argued that, so long as LAD revascularization is secure with a LITA-LAD graft, revascularization of the other coronary systems does not influence survival and can be either ignored or approached with techniques less likely to lead to long-term patency. The data in this study argue against that concept. Over a 20-year follow-up, the LAD revascularization, while important, is not all-important.
Clinical inferences
As we move into a differently invasive era, techniques of revascularization and combinations of techniques of revascularization will be developed that are appropriate for different situations. Complete revascularization is not the only thing that is important about revascularization strategies, and considerations of periprocedure morbidity always must be strongly considered. However, over the long term, the status of the LAD coronary artery is not the only thing that influences survival.
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Appendix: Discussion |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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Third, any residual lesion of less than 70% on the LCx or RCA territories did not affect survival. These conclusions allow us to draw some considerations.
The concept of complete revascularization has to be revisited in favor of the concept of adequate revascularization. This means that myocardial revascularization has to be guided by the demonstration of ischemia in the target territory when the lesion is not critical. The necessity to graft lesions if less than 70% becomes, after this presentation, less evident.
I have a comment and a few questions for Dr Scott. You demonstrated that the late negative impact of an ungrafted lesion of 70% or greater in the LCx territory or in the proximal RCA is so important that any such lesion is to be grafted during the first operation. I do not think that there is a surgeon in this room who can deny this evident truth. The purpose of minimally invasive coronary surgery is to do the same operation in a different way, not to question whether a severe non-LAD lesion has to be grafted or not.
Furthermore, the natural history of a single-vessel non-LAD disease is favorable. Since medical treatment in the United States had some practical limitation compared with Europe in the past, such as lack of availability of calcium channel blockers, and the modern interventional treatment is relatively recent, do you not think that today the data you showed are, in some way, too old?
Finally, I noticed that, for practical reasons, only 13% of the angiograms were reviewed. Eighteen percent of them showed some mistake, and often a lesion was downgraded to less than 50%. No angiogram with non-LAD coronary arteries normal or with a lesion lower than 50% was examined. Do you not think that the possibility of mistake, 18%, is too high and that all the angiograms need to be carefully checked before giving definite results?
Dr Scott. Thank you, Dr Calafiore, for your remarks. We would certainly agree that most surgeons in this country attempt to bypass coronary arteries with greater than 70% stenoses.
The late postoperative management of patients undergoing coronary bypass surgery has improved over time. Today more patients are treated with platelet inhibitors, and the current availability of multiple medications for altering the patient’s lipid profiles is likely to improve long-term outcomes. We believe these factors are important and can diminish the progression of disease. However, incomplete revascularization is still incomplete revascularization. The main lesson of this study is that over a long period of follow-up the status of the LCx and RCA systems can influence the survival despite effective revascularization of the LAD. The LAD is not the only vessel that influences long-term survival.
In regard to your question about the angiographic accuracy of the information that we presented, we do know that the review of angiograms by multiple readers does show variability, especially in the case of left main disease. Intravascular ultrasound studies of left main disease have shown us that angiographic studies are not perfectly accurate. However, the message of this paper is not going to be changed by some variability in reading angiograms. The important message here is that as surgery evolves and as new techniques and combinations of techniques become possible, we must always remember that optimal complete revascularization is important in achieving long-term survival.
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Acknowledgments |
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Footnotes |
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*Available by anonymous ftp from ftp://uabcvsr.cvsr.uab.edu
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References |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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