Abstract
Objectives. To evaluate 15-year survival after coronary artery bypass grafting (CABG) in relation to grade left main stenosis (LMS) and right coronary artery (RCA) obstruction. Design. Coronary angiographic findings were prospectively collected in 977 patients who had CABG for stable angina during 1994–1995 and were included in the Swedish Coronary Revascularization – Swedish Council of Technology Assessment study. Results. Significant LMS was present in one fifth of the patients and significant RCA obstruction was found in 61% of those with LMS and in 68% of patients without LMS. The patients were categorized as no LMS (Group I), LMS without RCA obstruction (Group II) or significant LMS with significant right coronary artery (RCA) obstruction (Group III). Early mortality did not differ in the three groups and was 1.2, 1.2% and 0.8% in group I, II and III, respectively. Corresponding survival at 15 years was similar 51%, 47% and 47%, respectively. In multivariable analysis older age, smoking, severe angina, positive stress test, hypertension, diabetes mellitus and ejection fraction < 50% were risk factors for death at 15 years. Conclusions. Death 15 years after CABG correlated to clinical variables but was not predicted from presence of LMS with or without significant associated RCA obstruction.
Coronary artery bypass grafting (CABG) has until recently been the standard treatment for patients with unprotected significant left main stenosis (LMS) (Citation1). Percutaneous coronary intervention (PCI) has emerged as an alternative in some patients with unprotected LMS i.e. without patent bypass grafts to the left coronary artery. In propensity score matched series followed up to 10 years mortality have been similar in patients with LMS treated with PCI versus CABG supporting the need for a randomized trial (Citation2–5).
In the randomized SYNTAX (Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) trial survival up to three years was similar after PCI and CABG in patients with isolated LMS but recurrent symptoms were more common after PCI (Citation6). Many patients with LMS have unfavourable anatomy for PCI because in 40% there are distal bifurcation lesion and calcifications (Citation7).
The prospective Swedish coronary revascularization – Swedish Council of Technology Assessment (SECOR/SBU) study had the primary objective to assess the appropriateness of the use of CABG in a population-based cohort of Swedish patients with stable angina pectoris (Citation8). The purpose of the present analysis was to assess survival up to 15 years after CABG in relation to extent of coronary artery disease in these patients. Therefore patients who were operated on during 1994–1995 were classified according to preoperative angiographic findings into three groups as either without LMS, with LMS but no significant RCA obstruction or as with significant LMS and significant right coronary artery (RCA) obstruction.
Material and methods
Patients and operation
Survival results up to six months have been reported previously in the patients who were included in the national SECOR/SBU study (Citation9). From May 1994 through January 1995, 4398 patients were referred for coronary angiography at seven public heart centres in Sweden that performed approximately 92% of all CABG and PCI in Sweden.
Patients were excluded if they declined to participate or deferred intervention (n = 62) had previous CABG (n = 291), had undergone PCI within the previous six months (n = 184), were referred for evaluation of congestive heart failure, arrhythmia, or possible cardiac transplantation (n = 62), had significant valvular heart disease and were considered candidates for valve surgery (n = 528), had emergency coronary angiography (n = 187), were referred for further evaluation (n = 44), were non-Swedish residents (n = 72), had incomplete medical data (n = 113), or were enrolled in other research projects (n = 88). Of the remaining 2767 patients, 687 were referred for PCI and 714 for continued medical treatment. We also excluded those operated on for acute coronary syndrome, those with an acute ST elevation myocardial infarction within 21 days, asymptomatic patients (n = 349) or where date of surgery was missing (n = 40).
Remaining 977 consecutive patients with chronic stable angina underwent CABG between May 9, 1994 and August 28, 1995. Mean age was 64 years (range 33–86), 28% were younger than 60 years, 40% were 60–69 and 32% were 70 years of age or older (). Twenty percent of the patients were females. All patients had been medically treated for more than 3 months with at least one drug from the class of long-acting nitrate, β- blocker or calcium channel blocker. All terms were explicitly defined and have been published previously (Citation8,Citation9).
Table I. Characteristics in 977 patients undergoing coronary artery bypass grafting in relation to grade left main stenosis (LMS) and right coronary artery (RCA) stenosis.
All operations were performed with the aid of cardiopulmonary bypass and the patients received acetylsalicylic acid 160 mg once daily from the first postoperative day. The study complies with the Declaration of Helsinki and was approved by the ethics committee at the Karolinska Institutet.
Data collection
Clinical and laboratory information was prospectively collected using a standardized form. Data collection started when patients were referred for coronary angiography by their cardiologists. The cardiologist entered data about medical history, medication, risk factors, and indication for angiography. The data collection form was then enclosed with the medical record. The cardiologist or radiologist who performed the angiography graded the severity and extent of coronary artery pathology according to a detailed data collection form. These data and the coronary angiogram were then validated at a cardiology conference usually attended by at least one cardiothoracic surgeon, one interventional cardiologist, and the referring cardiologist. Following the review of the medical history and angiographic findings, a recommendation was made for the patient to be referred for CABG, PCI, or continue medical therapy. The patient's physician then discussed the recommendation with the patient. A patient could agree with or decline from the recommendation. Data were reviewed for completeness and accuracy before being entered into the computerized database.
Definitions
Age was categorized into three groups of approximately similar numbers of patients. Smoking included present and previous smokers. Severe angina pectoris was classified as symptoms three or more times a week during the preceding four weeks despite optimal medication. A positive stress test was defined as bicycle exercise stopped at sub maximal workload because of chest pain and/or ST segment depression. Patients were defined as having hypertension if taking anti-hypertensive medication with hyperlipidaemia if taking lipid-lowering agents. Diabetes was identified in those taking insulin or oral hypoglycaemic agents. All coronary angiographies were classified with respect to grade of coronary artery obstruction and segment of the coronary artery having pathology. The most severe lesion in each major coronary artery was classified as either not significant (< 50%), low-grade stenosis (50–69%), high-grade stenosis (70–99%) or complete obstruction (100%). Significant coronary artery disease was defined as ≥ 70% stenosis in one or more major coronary artery branches. Significant LMS was defined as ≥ 50% narrowing of the luminal diameter.
The left ventricular ejection fraction (LVEF) was assessed from preoperative contrast ventriculography or echocardiography and left ventricular function was categorized as normal (≥ 50%), or reduced (< 50%).
Follow-up
Survival status was obtained from the Official Statistics of Sweden Population Register where all the deaths in Sweden are registered with complete coverage. Early mortality was defined as death occurring within 30 days of surgery. All survivors were followed for at least 15 years after the operation.
Statistical analyses
Continuous variables are presented as means with one standard deviation. The patients were categorized according to the angiographic findings as either without LMS (Group I), with significant LMS but no significant RCA obstruction (Group II) or as significant LMS and significant right coronary artery (RCA) obstruction (Group III). Patient characteristics in the three groups with different coronary artery pathology were compared using χ2-tests for categorical variables and analysis of variance for continuous variables. Kaplan –Meier plots of survival up to fifteen years after the operation were calculated. Crude and adjusted hazard ratios (HR) with 95% confidence intervals (CI) of deaths occurring up to 15 years after CABG were calculated using Cox's proportional hazards regression. The largest anatomic group (non-significant left main stenosis) was used as indicator group. The proportional hazards assumption was evaluated graphically and statistically and found to be appropriate. For the patient to general population survival comparison, we computed actual survival for the population alive January 1, 1995 weighted by the patient sample distributions by age (1-year classes) and gender calculated from the Official Statistics of Sweden Population Data Base. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) 12.1 software.
Results
Distribution of coronary artery pathology
LMS of 50% or more was present in 214 (22%) of the 977 patients and 131 (61%) of them also had 70% or more obstruction of the RCA (). Patients in Group III with significant LMS and RCA obstruction were oldest and most frequently had severe angina, a positive stress test, hyperlipidaemia, reduced left ventricular function and received more distal coronary artery anastomoses. History of previous AMI was most common among Group I patients without LMS. Group II with LMS and non-significant RCA lesions had the lowest proportions of patients with previous AMI and reduced LVEF. On average four distal coronary anastomoses were placed and an internal mammary artery graft was used in about 90% of the patients.
Among the 763 patients in Group I without significant LMS, 483 (63%) had triple-vessel disease with significant obstruction of the RCA, 107 (14%) two-vessel disease with proximal stenosis of the left anterior descending coronary artery, 120 (16%) two-vessel disease without proximal stenosis of the left anterior descending coronary artery and the remaining 52 (7%) patients isolated single-vessel disease. Thus 71% of the patients had triple-vessel disease or LMS. High-grade or a complete obstruction of the RCA was present in 516 of the 763 patients (68%) without LMS ().
Table II. Angiographic distribution of grade left main stenosis (LMS) and right coronary artery (RCA) obstructions in 977 patients.
Survival by distribution of stenosis
There were nine deaths within 30 days of the operation (0.9%). Early mortality did not differ in the three groups and was 1.2, 1.2% and 0.8% among patients in Group I, II and III, respectively (p = 0.72).
Crude survival at 5, 10 and 15 years after the operation did not differ significantly in the three groups (, ). During the initial five years survival seemed higher in patients without LMS and at 10 years the prognosis seemed worse in those with isolated LMS. At multivariable adjustment for differences in patient characteristics in the three groups presence of LMS or RCA obstruction did not significantly influence survival at 15 years ().
Figure 1. Survival up to 15 years after coronary artery bypass grafting in relation to severity of left main stenosis (LMS) and right coronary artery (RCA) stenosis.
Table III. Survival after coronary artery bypass grafting in relation to grade left main stenosis (LMS) and right coronary artery (RCA) obstruction.
Table IV. Multivariable analyses of risk factors for death in 977 patients up to 15 years after coronary artery bypass grafting in relation to grade left main stenosis (LMS) and right coronary artery (RCA) obstruction.
Survival among the studied patients was comparable to that of the Swedish population up to 11 years after the operation (). Upper 95% confidence limit and population survival were 72%. After 11 years, survival was superior in the general population.
Figure 2. Survival of all studied patients compared to that in an age, gender and date of surgery adjusted cohort of the Swedish Population. The 95% confidence interval (95% CI) for survival in patients who had coronary artery bypass grafting is shown.
Survival in all patients
In univariate analysis risk factors for death at 15 years in all patients were older age, history of smoking, severe angina, positive stress test, previous acute myocardial infarction, diabetes mellitus, ejection fraction < 50% and five or more distal coronary anastomoses. In multivariable analysis age 60 years or older, smoking, severe angina, positive stress test, hypertension, diabetes mellitus and < 50% left ventricular ejection fraction predicted risk of death at 15 years after CABG ().
Table V. Analysis of risk factors for death in all 977 patients at 15 years after coronary artery bypass grafting.
Discussion
All patients underwent primary isolated CABG during 1994–1995 and were operated on because of chronic stable angina pectoris. Emergency operations, unstable patients and repeat procedures were excluded. About three of four of the patients had extensive coronary artery pathology with triple-vessel disease or LMS and an average of four distal anastomoses per patient indicated complete revascularization. Patients without LMS did not have benign coronary pathology as 63% had triple-vessel disease and history of previous AMI was most common in this group. Despite that patients with isolated LMS to a less extent had reduced LV function and history of previous AMI survival tended to be lowest in this group after ten years. During the decade following the operation PCI was not a treatment offered to patients with LMS. There are therefore no reports of very long-term follow-up after PCI of LMS to be compared to the reported patients. The need for repeat revascularization due to restenosis has been the Achilles heel of PCI (Citation10).
We believe that our classification and grading of coronary artery pathology was valid as the finding at every angiography was prospectively entered into a data form and discussed at a cardiology conference. In medically treated cohorts less degree of LMS has been associated with better survival in contrast to a dismal prognosis in case of high-grade LMS. Conley and co-workers found that three-year survival was 66% if the LMS was 50–70% versus 41% with 70% or greater of LMS (Citation11). If ≥ 70% LMS was associated with concomitant three vessel disease three-year survival was only 37%. Similarly among 105 medically treated patients survival at three years after angiography was 81% if the LMS was 50% compared to 35% in those with 75% or greater LMS (Citation12).
In the present study long-term survival seemed independent of presence of significant LMS at the preoperative angiography. We have previously reported that survival up to five years after CABG does not differ in patients with high-grade versus low-grade LMS (Citation13). Bypass grafts may have better patency if sutured distal to a high-grade coronary obstruction as there is lower graft flow limiting competitive blood flow through the native vessel (Citation14,Citation15). IMA grafts were used in about 90% of the operations and have documented durability with patency rates of about 90% more than ten years after CABG whereas almost half of saphenous vein grafts are occluded or have degenerative changes (Citation16). In some patients an IMA graft sutured to the LAD will not only stay open but also increase in size with time and via coronary collaterals supply blood to a large mass of myocardium (Citation16). The development of coronary collaterals and different progression of native disease were unknown and would have influenced prognosis and made prediction of prognosis difficult from a single preoperative angiography. In fact at re-angiographies done five years after revascularization progression of native coronary artery disease occurred more often than failed revascularization (Citation17). The prognosis among patients after CABG was excellent and similar to that in an adjusted cohort of the Swedish population during ten years. Failure of vein grafts and progression of coronary artery disease may well explain the lower survival after the 11th year.
Already during the 1970s Campeau et al. reported marked better survival after CABG in patients with ≥ 70 LMS and concomitant ≥ 70 RCA obstruction than with medical treatment (Citation18). In a retrospective analysis of 3803 patients with LMS operated on at Cleveland Clinic during 1971–1998 survival at 30 days, 5, 10 and 15 years was 97.6%, 83%, 64% and 44% (Citation19). Worse left ventricular function, diabetes, hypertension, peripheral arterial disease, smoking, and elevated triglycerides decreased long-term survival and use of the internal thoracic artery improved survival (Citation19). The patients were on average two years younger than our patients but about 5% of the operations were emergency operations or performed because of cardiogenic shock. The results compare favourably with the 46% survival at 15 years among our patients with significant LMS. In a previous report from our institution survival at 15 years was 55% in patients without LMS and 42% in those with midshaft or bifurcational LMS (Citation7). Survival at five and ten years was only 74 and 48%, respectively, in patients with insulin-treated type 2 diabetes undergoing CABG at our clinic during 1990–1999 (Citation20). In patients operated on for acute coronary syndrome with an increased risk of early mortality we have previously reported survival at five years of 83% (Citation21).
In contrast Sergeant and co-workers assessed 66% survival at 15 years in a general population of CABG patients and found that use of arterial grafting, extensiveness of sequential grafting, completeness of revascularization and extent of grafting to small coronaries influenced late survival (Citation22). Early mortality after CABG in 1585 patients with LMS correlated to renal failure, higher age and heart failure whereas independent risk factors for three-year mortality are age, renal dysfunction, and chronic pulmonary disease (Citation23).
Limitations of our analyses were relatively few patients in the subgroups but information of angiographies and variables were complete as the patients had been prospectively included in the SECOR/SBU study. Only survival analyses were performed as data from national registers recording information of PCI, redo CABG and hospitalizations due to acute myocardial infarction were incomplete for procedures performed during the 1990s. We also lack follow-up information of changes of medication, symptoms and cardiac events occurring after the operation.
We conclude that among patients with stable angina undergoing CABG one fifth have LMS and more than 60% have associated significant RCA obstruction. Survival 15 years after the operation was not predicted from grade with LMS or associated RCA obstruction but correlated to older age, smoking, severe angina, positive stress test, hypertension, diabetes mellitus and < 50% left ventricular ejection fraction.
Acknowledgements
The authors are grateful to Ann-Sofie Nord who coordinated data collection and to Jan Sélén, Statistics Sweden, for creating the Swedish Population cohort.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
The SECOR/SBU project was supported by grants from the Swedish Medical Research Council and the Swedish Federation of County Councils.
References
- Taggart DP, Kaul S, Boden WE, Ferguson TB Jr.,Guyton RA, Mack MJ. Revascularization for unprotected left main stem coronary artery stenosis stenting or surgery. J Am Coll Cardiol. 2008;51:885–92.
- Brener SJ, Galla JM, Bryant R 3rd,Sabik JF 3rd,Ellis SG. Comparison of percutaneous versus surgical revascularization of severe unprotected left main coronary stenosis in matched patients. Am J Cardiol. 2008;101:169–72.
- Wu X, Chen Y, Liu H, Teirstein PS, Kirtane AJ, Ge C, . Comparison of long-term (4-year) outcomes of patients with unprotected left main coronary artery narrowing treated with drug-eluting stents versus coronary-artery bypass grafting. Am J Cardiol. 2010;105:1728–34.
- Park DW, Seung KB, Kim YH, Lee JY, Kim WJ, Kang SJ, . Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol. 2010;56:117–24.
- Lee SW, Kim SH, Kim SO, Han S, Kim YH, Park DW, . Comparative long-term efficacy and safety of drug-eluting stent versus coronary artery bypass grafting in ostial left main coronary artery disease: Analysis of the MAIN-COMPARE Registry. Catheter Cardiovasc Interv2012.
- Morice MC, Serruys PW, Kappetein AP, Feldman TE, Stahle E, Colombo A, . Outcomes in patients with de novo left main disease treated with either percutaneous coronary intervention using paclitaxel-eluting stents or coronary artery bypass graft treatment in the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial. Circulation. 2010;121:2645–53.
- Jonsson A, Ivert T, Svane B, Liska J, Jakobsson K, Hammar N. Classification of left main coronary obstruction–feasibility of surgical angioplasty and survival after coronary artery bypass surgery. Cardiovasc Surg. 2003;11:497–505.
- Bernstein SJ, Brorsson B, Aberg T, Emanuelsson H, Brook RH, Werko L. Appropriateness of referral of coronary angiography patients in Sweden. SECOR/SBU Project Group. Heart. 1999; 81:470–7.
- Brorsson B, Lindvall B, Bernstein SJ, Aberg T. CABG in chronic stable angina pectoris patients: indications and outcomes (SECOR/SBU). Swedish Societies for Cardiology, Thoracic Radiology and Thoracic surgery/Swedish Council for Technology Assessment in Health Care. Eur J Cardiothorac Surg. 1997;12:746–52.
- Taggart DP. Coronary artery bypass graft vs. percutaneous coronary angioplasty: CABG on the rebound?Curr Opin Cardiol. 2007;22:517–23.
- Conley MJ, Ely RL, Kisslo J, Lee KL, McNeer JF, Rosati RA. The prognostic spectrum of left main stenosis. Circulation. 1978;57:947–52.
- Harris PJ, Behar VS, Conley MJ, Harrell FEJr, Lee KL, Peter RH, . The prognostic significance of 50% coronary stenosis in medically treated patients with coronary artery disease. Circulation. 1980;62:240–8.
- Jonsson A, Ivert T, Nordqvist T, Hammar N. Grade of left main coronary artery stenosis does not influence long-term mortality after coronary artery bypass surgery. Scand Cardiovasc J. 2008;42:323–6.
- Urschel HC, Razzuk MA, Wood RE, Paulson DL. Factors influencing patency of aortocoronary artery saphenous vein grafts. Surgery. 1972;72:1048–63.
- Stinson EB, Olinger GN, Glancy DL. Anatomical and physiological determinants of blood flow through aortocoronary vein bypass grafts. Surgery. 1973;74:390–400.
- Ivert T, Huttunen K, Landou C, Bjork VO. Angiographic studies of internal mammary artery grafts 11 years after coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1988;96:1–12.
- Alderman EL, Kip KE, Whitlow PL, Bashore T, Fortin D, Bourassa MG, . Native coronary disease progression exceeds failed revascularization as cause of angina after five years in the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol. 2004;44:766–74.
- Campeau L, Corbara F, Crochet D, Petitclerc R. Left main coronary artery stenosis: the influence of aortocoronary bypass surgery on survival. Circulation. 1978;57: 1111–5.
- Sabik JF 3rd,Blackstone EH, Firstenberg M, Lytle BW. A benchmark for evaluating innovative treatment of left main coronary disease. Circulation. 2007;116:I232–9.
- Alserius T, Hammar N, Nordqvist T, Ivert T. Risk of death or acute myocardial infarction 10 years after coronary artery bypass surgery in relation to type of diabetes. Am Heart J. 2006;152:599–605.
- Bjessmo S, Ivert T, Flink H, Hammar N. Early and late mortality after surgery for unstable angina in relation to Braunwald class. Am Heart J. 2001;141:9–14.
- Sergeant P, Blackstone E, Meyns B. Validation and interdependence with patient-variables of the influence of procedural variables on early and late survival after CABG. K.U. Leuven Coronary Surgery Program. Eur J Cardiothorac Surg. 1997;12:1–19.
- Ellis SG, Hill CM, Lytle BW. Spectrum of surgical risk for left main coronary stenoses: benchmark for potentially competing percutaneous therapies. Am Heart J. 1998;135: 335–8.