Previous coronary artery bypass grafting as an adverse prognostic factor in unstable angina pectoris

PreviousCoronaryArtery BypassGraftingas an AdversePrognosticFactorin UnstableAnginaPectoris DAVID D. WATERS, MD, ANN WALLING, MD, DENIS ROY, MD, and PIERRE THEROUX, MD

Among 252 patients hospitalized for unstable angina in 1982 and 1983, 54 (21% ) had undergone coronary artery bypass grafting (CABG) a mean of 55 months earlier (range 1 to 168) (CABG patients). This group was compared with a group of 54 randomly selected patients with unstable angina without previous CABG (control patients). The 2 groups did not differ with respect to clinical characteristics at admission or hospital course. Coronary arteriograms, recorded in all but 4 CABG patients, revealed multivessel stenoses of at least 70% luminal diameter in 40 CABG and 32 control patients (p <0.05), but when patent grafts were considered, the groups were comparable. Overall, 48 of 112 grafts were totally occluded and 14 had stenoses at least 70% in diameter. Complete or almost com-

plete revascularization was feasible in 39 of 52 control and only 9 of 42 CABG patients (p
T

he number of coronary artery bypass grafting (CABG) operations performed annually in the United States was estimated to be 70,000 in 1977 and 160,000 in 1981.l As the proportion of patients with coronary artery disease (CAD) who have had CABG increases, the proportion of such patients among those in whom acute coronary events develop is also likely to increase. Between 1982 and 1984 at our institution, patients with previous CABG constituted 16% of patients undergoing CABG, 11% of patients hospitalized with myocardial infarction and 21% of those hospitalized with unstable angina. We previously reported that myocardial infarct size is smaller and infarction is associated with fewer complications in patients with previous CABG compared

with control subjects2 and that occlusion of distal arteries or branches as opposed to proximal main arteries accounts for these differences.3 Because CABG modifies coronary blood supply radically, patients in whom unstable angina develops after CABG may differ from other patients with unstable angina with respect to clinical presentation, response to treatment and course after hospital discharge. This subgroup of patients has not previously been investigated systematically. This study describes clinical and angiographic characteristics and outcome of a large, consecutive series of hospitalized patients with unstable angina who had previous CABG compared with a control group with unstable angina.

From the Department of Medicine, Montreal Heart Institute, and the University of Montreal Medical School, Montreal, Quebec, Canada. Manuscript received February 20, 1986; revised manuscript received April 22,1986, accepted April 23,1986. Address for reprints: David D. Waters, MD, Montreal Heart Institute, 5000 East, Belanger Street, Montreal, Quebec, HlT lC8, Canada.

Patients: Angina was defined as squeezing or burning retrosternal chest discomfort compatible with myocardial ischemia. Unstable angina was classified as (11 new-onset angina (excluding angina before CABG), (2) a worsening pattern of angina, usually including angina at rest or in the absence of a change in activity level or other obvious provoking factors, and (3) myocardial

Methods

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TABLE I

Clinical

ANGINA

AFTER BYPASS

SURGERY

Features of the Two Groups of Patients Controls (n = 54)

p Value

43111 28 19 6 40 45 f 49

56 f 9 39115 23 25 13 40 37 f 50

NS NS NS NS NS NS NS

22 32

21 33

NS NS

12 13 29

11 33

NS

32 30 16 12

31 23 11 16

NS NS NS NS

Post-Bypass (n = 54)

Age (~0 Sex (M/F) Previous MI Previous hypertension Diabetes mellitus Cigarette smoker Duration of angina (months) Previous functional class ccvs 0 to I ccvs II-IV Type of unstable angina New onset Worsening pattern Prolonged rest pain Drugs before admission p blockers Long-acting nitrates Calcium blockers None On admission Heart rate (beatslmin) Systolic BP (mm Hg) Heart failure Ejection fraction

55f a

71 f 14 135 f 20 4 0.59 f 0.12

IO

75 f 16 137 f 20 3 0.54 f 0.17

NS NS NS NS

BP = blood pressure; CCVS = Canadian Cardiovascular Society functional class13; Ml = myocardial infarction; NS = difference not significant.

ischemic pain at rest lasting longer than 15 minutes, usually unrelieved or incompletely relieved by nitroglycerin. Patients with new-onset or worsening angina who also had prolonged myocardial ischemic pain at rest were classified in the third category. Those with elevated cardiac enzyme or isoenzyme levels were excluded. Between March 1982 and October 1983, 252 patients who met this definition were hospitalized in our coronary care unit. Fifty-four (21%) had undergone CABG 1 to 168 months (mean 55) previously. They comprised the study group (CABG patients). For each study patient, the preceding patient admitted to the coronary care unit with unstable angina without previous CABG was selected as a control patient. Patient management: In the coronary care unit all patients underwent the same diagnostic procedures according to a standardized protocol. On admission and on days 1 to 3, a 12-lead electrocardiogram was recorded and serum cardiac enzyme and isoenzyme levels were measured. Patients underwent continuous electrocardiographic monitoring for at least 3 days. We tried to record l&lead electrocardiograms during angina attacks before administering nitroglycerin. However, 20 CABG and 19 control patients had no angina during hospitalization; 28 CABG and 30 control patients already had ST-T abnormalities on their baseline electrocardiograms. Antianginal medication was individualized, but patients who did not become angina free were usually treated with a long-acting nitrate, a calcium antagonist and a ,&adrenergic blocking drug, unless contraindicated, to maximally tolerated doses. In patients refractory to this regimen, intravenous nitroglycerin was

continuously infused. Anticoagulant and antiplatelet drugs were not routinely used to treat patients with unstable angina during this study. All control patients and 50 of the 54 CABG patients underwent coronary arteriography4J during hospitalization. Each angiogram was interpreted by an independent, experienced radiologist. The extent of CAD was graded as l-, 2- or 3-vessel CAD, based on the presence of at least 70% reduction in diameter of the main arteries or branches according to the Coronary Artery Surgery Study criteria.6 In patients who had previously undergone CABG, the same system was used except that a stenosis of at least 70% was required in both the artery and graft, or in the artery distal to the graft anastomosis, for the vessel to be counted. All arteries distal to stenoses at least 50% in diameter were assessedfor operability. Those with a diameter of less than 1.5 mm, those with severe stenoses distal to potential anastomotic sites and those perfusing small amounts of myocardium were not recommended for surgery.7 Complete or almost complete revascularization was considered feasible when all or at least two-thirds of arteries with at least 50% stenoses were acceptable for CABG. Generally accepted angiograghic criteria for percutaneous transluminal coronary angioplasty in patients with unstable angina were followed,8 but these became less restrictive during the study periodVgJO The decision to recommend CABG or coronary angioplasty was based on results of the angiogram and the initial response to medical treatment. Each of the 4 cardiologists who treated the study patients followed generally accepted indications for surgery in unstable angina.11J2In some patients a trial of medical therapy was undertaken after hospital discharge and surgery or angioplasty was performed later if an unacceptable level of angina persisted. Patients were followed regularly for at least 1 year, usually by the cardiologist who treated them in the hospital. None were lost to follow-up. Data analysis: The statistical significance of intergroup differences was assessedwith Student t test or chi-square test. All values are mean f standard deviation.

Results Clinical characteristics: Table I is a list of clinical features of the patients with unstable angina with previous CABG and the control patients. Mean age of the CABG patients was 55 years; most were men and more than half had previously had a myocardial infarction. Duration of angina before hospitalization was similar in the 2 groups. Prolonged pain at rest was the commonest pattern of unstable angina. Most patients were already taking antianginal drugs before admission. No important differences in the clinical features of the CABG and control patients were noted before hospitalization. Status of bypass grafts: The mean number of grafts (distal anastomoses) per patient was 2.31 (range 1 to 41. The 50 patients who underwent arteriography had 112 grafts; 48 were occluded and 64 were patent, of which

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TABLE Ill Outcome for Patients With Unstable Angina With and Without Previous Bypass Surgery

CABG Patients Post-CABG Excluding Grafts Stenoses 270% 0 vessel 1 vessel 2 vessel 3 vessel Left main stenosis Arteriography not Revascularization Complete 1213 <2/3 None

Post-CABG Including Grafts

diameter

CABG = coronary

250% done potential

11 15 13 11 4 4

0 10 17 23 11 4 8 1 22 11

Post-Bypass Patients

Control Patients

1 21 1.5 17 5 0 33 6 12 1

In hospital Death Myocardial infarction Coronary angioplasty

1 4 3

37

12

31

4 5 11 20

1 5 4 IO

50 3

53 8

17 22 16 12 13 28 23 24

38 42 a 3 31 14 4 11


<0.05

46

20 Bypass surgery CCVS class 0 to I II III-IV No cardiac medication p blockers Long-acting nitrates Calcium blockers

p Value

0 5 6 15

Bypass surgery Cumulative to 1 year Death Myocardial infarction Recurrent unstable angina Total patients with adverse events At 1 year Survivors Coronary angioplasty

artery bypass graft.

14 had diameter stenoses of at least 70%. Totally obstructed grafts had been in place for a mean of 60 f 45 months, compared to 45 f 34 months for patent grafts (p >0.05
Control Patients



CCVS = Canadian Cardiovascular Society functional class.r3 For patients with multiple adverse events, only the most severe event was counted.

CABG and 6 control patients underwent coronary angioplasty; 12 CABG and 31 control patients had CABG. Outcome at one year: By 1 year, 20 patients in the CABG group and 10 in the control group had suffered adverse events (p <0.05). Four CABG patients had died, 5 had had myocardial infarction and 11 had been rehospitalized with recurrent unstable angina. By 1 year 1 control patient had died, 5 control patients had suffered myocardial infarction and 4 had been rehospitalized with recurrence of unstable angina. By 1 year, 46 control patients had undergone revascularization (angioplasty in 8, CABG in 381,compared with only 20 CABG patients (angioplasty in 3, CABG in 17, p
Discussion This study describes the clinical and angiographic characteristics of patients with previous CABG in whom unstable angina develops. Such patients are similar to other patients with unstable angina with respect to symptoms and evolution of angina before and during hospitalization. At angiography more than half of their grafts are completely occluded or severely stenotic. When their patent grafts are taken into account, extent and severity of CAD are similar to those of other patients with unstable angina. However, they are much less likely to be good candidates for revascu-

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larization and fewer undergo either coronary angioplasty or repeat CABG during hospitalization or thereafter. During the following year they are more likely to suffer adverse coronary events, primarily recurrent unstable angina. At 1 year they are much less likely to be angina free and much more likely to require antianginal medication. These findings do not imply that a revascularization procedure is optimal therapy for all or most patients with unstable angina. In a randomized trial comparing medical and surgical treatment of unstable angina, severe angina during the first year after hospitalization was more common in medically treated patients irrespective of the number of diseased vessels.l4 Many patients, however, become completely or nearly angina-free with medical therapy and do not require surgery. Because the option for surgery is not available or is relatively contraindicated in many more unstable angina patients with previous CABG compared with other unstable angina patients, it is not surprising that they are more likely to be limited by angina during follow-up. Limitations of the study: Several pathophysiologic mechanisms can probably produce unstable angina; however, the precise mechanism is not usually identified in an individual patient; therefore, the descriptive clinical term unstable angina is routinely used of necessity. The definition of unstable angina in this study is used frequently.15 In some studies the definition of unstable angina requires that reversible ST-T-wave changes indicative of myocardial ischemia be documented during angina at rest. Such a definition excludes many patients; for example, of our 108 study patients, 39 had no angina in hospital and 9 had bundle branch block, a permanent pacemaker or preexcitation syndrome. Many markedly abnormal baseline electrocardiograms do not change during myocardial ischemia; 58 of our patients already had ST-T abnormalities on their baseline tracings and 33 had pathologic Q waves. Although myocardial ischemia was not documented electrocardiographically during angina at rest in many of our patients, all but 4 underwent coronary arteriography. The extent and severity of coronary disease was similar to that generally reported for patients with unstable angina?J7 The in-hospital and l-year mortality and infarction rates in our patients are within the ranges reported,15 suggesting that the patients in our study are not atypical. Graft patency: The proportion of CABG grafts that were completely occluded or severely stenotic, 62 of 112, is higher than that in a consecutive series of postCABG patients who had myocardial infarction, 53 of 121, although the mean interval after surgery was shorter, 55 vs 71 months, in the unstable angina group.3 Both series of patients underwent surgery and were rehospitalized at our institution during the same years. In a series of unselected patients studied 10 to 12 years after surgery, 54 of 147 grafts were occluded, less than in either of these 2 groups. l8 Patients in whom unstable angina or myocardial infarction develops late after CABG may not be typical of all CABG patients; incom-

plete revascularization, lipoprotein abnormalitiedg or other factors may be more common in these patients at the time of surgery. The interval between surgery and unstable angina was not a useful predictor of graft patency. Overall, in about one-third of patients all grafts were patent, in about one-third all grafts were completely occluded or severely stenotic and in one-third there was a combination. Both in this study and in another,16 most patients with unstable angina without previous CABG are good candidates for operation by angiographic criteria. In contrast, using the same angiographic criteria, most CABG patients with unstable angina were not good candidates for reoperation. More frequent reintervention despite angiographic limitations to revascularization might have reduced the incidence of adverse events and improved symptomatic status in the CABG patients. The operative mortality and degree of angina relief after reoperation have improved in recent years20v21 and approach the results with first operations21 Increased use of the internal mammary artery as a bypass conduit, producing better long-term patency rates,22 and substitution of coronary angioplasty for CABG as the initial revascularization procedure may limit the number of patients in whom unstable angina will develop after CABG. Nevertheless, unstable angina in patients with previous CABG is likely to become a more frequently encountered problem. Further studies are needed to determine the optimal management of such patients and to find methods to delay progression of atherosclerosis in bypass grafts and native arteries.

References 1. Braunwald E. Effects of coronary-artery bypass grafting on survival: implications of the randomized coronary artery surgery study. N EngJ J Med 1983;309:1181-1184. 2. Waters DD, Pelletier GB, Hache M, Tberoux P, Campeau L. Myocardial infarction in patients with previous coronary artery bypass surgery. JACC 1984;3:909-915. 3. Crean PA, Waters DD, Bosch X, Pelletier GB, Roy D, Theroux P. Angiographic findings after myocardial infarction in patients with previous bypass surgery: explanations for smaller infarcts in this group compared with control patients. Circulation 1985;71:693-698. 4. Bourassa MG, Lesperance J, Campeau L, Bois M, Saltiel J. Selective coronary arteriography using a percutaneous femoral technique. Can Med Assoc J 1970:102:170-173. 5. Lesperance J, Saltiel J, Petitclerc R, Bourassa MG. Angulated views in the sagittal plane for improved accuracy of cinecoronary angiography. J Roentgenol Rod Ther Nucl Med 1974;121:565-574. 6. Principal Investigators of CASS and Their Associates. National Heart, Lung, and Blood Institute coronary artery surgery study. Circulation 1981; 63:suppl I:I-15. 7. Lesperance J. Bourassa MG, Biron P. Campeau L, Saltiel J. Aorta to coronary artery saphenous vein grafts. Preoperative angiographic criteria for successful surgery. Am J CardioI 1972;30:459-465. 8. Faxon DP, Detre KM, McCabe CM, Fisher L, Holmes DR, Cowley MJ, Bourassa MG, Van Raden M, Ryan TJ. Role of percutaneous transluminal coronary angioplasty in the treatment of unstable angina. Report from the National Heart, Lung, and Blood Institute percutaneous transluminai coronary angioplasty and coronary artery surgery study registries. Am J Cardiof 1983:53:131C-135c. 9. Bentivoglio LG, Van Raden MJ. Kelse SF, Detre KM. Percutaneous transluminal coronarv aneioolastv IPTCAl in oatients with relative contraindications: results of the National Heart, Lung, and Blood Institute PTCA registry. Am J Cardiol 1984;53:82C-88C. 10. Douglas JS Jr, Gruentzig AR, King SB, Hollman J, Ischinger T, Meier B, Craver JM, Jones EL, Waller JL, Bone DK, Guyton R. Percutaneous transluminal coronary angioplasty in patients with prior coronary bypass surgery. ,

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JACC 1983;2:745-754. 11. Special report. National Institutes of Health Concensus - development conference statement, coronary-artery bypass surgery: scientific and clinical aspects. N Engl f Med 1981:304:&W-684. 12. Hecht HS, Rahimtoola SH. Unstable angina. A perspective. Chest 1982;82:466-472. 13. Campeau L. Grading of angina pector/s. Circulation 1976;54:522-523. 14. Unstable angina pectoris: National Cooperative Study Group to compare surgical and medical therapy. II. In-hospital experience and initial follow-up results in patients with one, two and three vessel disease. Am J Cardiol 1978;42:839-848. 15. Julian DG. The natural history of unstable angina. In: Hugenholtz PG. Goldman BS, eds. Unstable Angina. Current Concepts and Management. Stuttgart: Schattauer, 1985:65-70. 16. Alison HW, Russell RO, Mantle JA, Kouchoukos NT, Morashi RE, Rackley CE. Coronary anatomy and arteriography in patients with unstable angina pectoris. Am J Cardiol 1978;41:204-209. 17. Bertrand ME. Diagnostic approach to unstabfe angina with coronary arteriography. In: Ref 15:119-125.

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18. Campeau L, Enjalbert M, LespCance J, Vaislic C, Grondin CM, Bourassa MG. Atherosclerosis and fate closure of aortocoronary saphenous vein grafts: sequential angiographic studies at 2 weeks, I year, 5 to 7 years, and 10 to 12 years after surgery. Circulation 1983;68:suppI11:11-1-H-7. 19. Campeau L, Enjalbert M, Lesp&ance J, Bourassa MG, Kwiterovich P Jr, Wacholder S, Sniderman A. The relationship of risk factors to the development of atherosclerosis in saphenous-vein bypassgrafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery. N Engl f Med 1984;311:1329-1332. 20. Shark WM, Kass RM. Repeat myocardial revascularization in coronary diseases therapy: consideration of primary bypass failures and success of second graft surgery. Am Heart J 1981;102:303-307. 21. Loop FD, Lytle BW. Gill CC, Golding LAR, Cosgrove DM, Taylor PC. Trends in selection and results of coronary artery reoperations. Ann Thorac Surg 1983;36:380-388. 22. Grondin CM, Campeau L, Lesperance J, Ejalbert M. Bourassa MG. Comparison of late changes in internal mammary artery and saphenous vein grafts in two consecutive series of patients 10 years after operation. Circulation 1984;7O:suppl1:1-208-I-212.