European Heart Journal (1992) 13, (Supplement 77), 89-95

Late results following coronary artery bypass grafting H. J. DARGIE

Department of Cardiology, Western Infirmary, Glasgow Gil 6NT, U.K. KEY WORDS: Aircrew licensing, aviation, prognosis, coronary artery surgery.

Introduction Coronary artery bypass surgery, which was introduced by Favorolo in 19681'1, has come of age. The operation is now commonplace, and in experienced centres the mortality is comparable with other types of major surgery. Many improvements in the various aspects of the surgical process have taken place during these years; techniques of anaesthesia, cardiopulmonary bypass, harvesting and handling of vein grafts, and various aspects of perioperative care continue to evolve. But the most important development has been the rather late but subsequent enthusiastic employment of one or both internal mammary arteries as conduits which was pioneered by Green in 1968P1. At the same time, greater confidence in the safety of the operation has encouraged its increased application in higher risk subjects, including those with more than mildly impaired ventricular function and even those with chronic renal failure and other systemic disorders. In assessing the late results of coronary artery bypass grafting (CABG), all these factors have to be considered, though in the specific context of aircrew it is reasonable to assume that, in all respects other than the presence of coronary disease, the subjects will be healthy. That is to say they will be relatively young, free from concomitant disease and, to be considered for further employment, they would need to be free from significant myocardial damage.

Saphenous vein grafts (SVG) In addition to many observational studies, three randomized controlled trials, the European Coronary Surgery Study (ECSS), the Veterans Administration Study (VA) and the Coronary Artery Surgery Study (CASS) have been carried out'3"51. It must be remembered that the results of these trials are strictly applicable only to the specific population concerned and their respective strengths and weaknesses have been extensively reviewed recently. Nevertheless they do provide the best available information concerning the efficacy of coronary surgery in achieving its main goals—the improvement of the quality and the length of life. A brief description of the trials can be found in Table 1. Correspondence: Henry J. Dargie, Department of Cardiology, Western Infirmary, Glasgow Gl 1 6NT. 0195-668X/92/OH0089 + 07 $08.00/0

Early results EFFECT ON SYMPTOMS, EXERCISE CAPACITY AND DRUG TREATMENT

Relief of chest pain was broadly similar in all three trials; after 5 years, about half of the patients treated surgically were free of symptoms, while surgery can be expected to improve symptoms in about three-quarters of the patients. In the CASS study after 5 years, exercise time was greater by about 1 -5 min in the surgical group but the percentage of those with exercise-induced ST segment depression > 1 mm, which was dramatically reduced after one year, was only slightly (though significantly) less than in the medically treated patients. The trend in the European study was similar and the difference in exercise performance between the two groups was not significant after 5 years13"51. In all the trials there' was a striking decrease in both beta-blocker and nitrate therapy in the surgical group; approximately 30% of surgical patients were receiving a beta-blocker after 5 years compared with 70% in the medical group, with a similar trend in nitrate therapy. EFFECT ON SURVIVAL

The survival data at 5 years for comparable patient groups is summarized in Table 2. In the Veterans Administration Study there was a highly significant difference in mortality for patients with left main stem disease. But excluding these patients, there was no significant difference in mortality between the two groups; a trend towards a better surgical mortality disappeared between 7 and 11 years, due, it is widely believed, to progressive occlusion of the vein grafts. In those patients with three vessel disease who had impaired left ventricular (LV) function (LVEF O-35 £50 % stenosis Prior myocardial infarction (%) 61 5-8 Operative mortality (%) Entry date 1972-74

ECSS

CASS

768 780 £65 2:65 M only M&F(10%) 1,2,3 none, 1,2 >0-50 >0-30 £50 £70 46 60 3-3 1-4 1973-76 1975-79

function, the improved survival of surgically treated patients with triple vessel disease and preserved left ventricular function noted in the ECSS was not confirmed by the CASS study. Interestingly, the survival of such surgically treated patients in both studies was identical, while the survival of medically treated patients in the ECSS was poorer. It has been argued that this reflects the greater severity of coronary heart disease in the ECSS patients, since the survival of a much larger group of medically treated patients in the CASS Registry is very similar to the ECSS. Late results

CASS = Coronary Artery Surgery Study; VA = Veterans Administration Study; ECSS = European Coronary Surgery Study; CCS = Canadian Cardiovascular Society.

Table 2 Comparison of survival results among major randomized clinical trials of stable ischaemic coronary disease VA

ECSS

CASS

5

5

Trial years 5

11

12

OVERALL SURVIVAL

In the VA study an initial trend in favour of surgery disappeared after 7 years such that at 11 years survival in the two groups was virtually identical at 58% (Surgery) and 57% (Medical). In the ECSS study at 12 years, survival was slightly but statistically significantly higher in the surgical group at 70-6% compared with 66-7% for those treated medically171. No late difference in survival was found in the CASS study between the surgical and medical groups which was 79% and 82% respectively181.

10 SUB-GROUP ANALYSIS

Two vessel disease Medical Surgical Three vessel disease Medical Surgical

85 79

69 55

88 91

71 67

95 98

83 88

75 81

50 56

82* 94

66* 74

89 92

75 76

CASS = Coronary Artery Surgery Study; VA = Veterans Administration Study; ECSS = European Coronary Surgery Study; * = Significant difference.

medical patients. Surgically treated patients with multivessel disease but without a proximal left anterior descending coronary artery (LAD) stenosis fared no better than medically treated patients, while those with proximal LAD disease did. But even in the presence of a proximal LAD stenosis, if ST segment depression > 1-5 mm on exercise testing was not present, then the prognosis remained equally good in medically and surgically treated patients with respect to both double and triple vessel disease. Another clinical indicator of benefit from surgery was the presence of peripheral vascular disease. In the Coronary Artery Surgery Study there was no difference in survival between medically and surgically treated patients, being 92% and 95% respectively. However, of 160 patients with an ejection fraction between 35 and 50%, 30% of those treated medically were dead at 7 years as compared with 16% of those who had had surgery161. The benefit of surgery was even greater in those who also had triple vessel disease. While the CASS and VA studies are in agreement concerning the survival advantage of surgery in patients with triple vessel disease and impaired left ventricular

The early results from all three trials identified a survival advantage in 'high risk' patients, i.e. those with left main stem disease, triple vessel disease and impaired left ventricular function, proximal disease of the left anterior descending artery in the context of multi-vessel disease and those with evidence of reversible ischaemia on exercise testing. In the European study, the greater surgical benefit in those with a proximal LAD stenosis was confirmed in those with triple vessel disease, of whom 78% had this feature. Similarly the surgical advantage in those with evidence of reversible ischaemia was most evident when the exercise test was strongly positive. The benefit of surgery for those with impaired LV function noted in the early CASS results was confirmed in the 10-year follow-up, survival being 70% and 61% (P < 001) in the surgical and medical groups respectively181. OBSERVATIONAL STUDIES

Even longer follow-up data (10-20 years) are available from large series from various surgical centres^131. For example, in 1698 patients operated on by one surgeon between 1960 and 1975 survival at up to 20 years was 40%, 26% and 20% for single, double and triple vessel disease respectively. At 16-20 years graft patency was 46%. For much of the follow-up period, survival in those with single vessel disease was similar to that expected in an age and sex matched population of normal U.S. men'14'. SYMPTOMS AND QUALITY OF LIFE

While there is continuing debate on the role of surgery in improving survival, its beneficial effect in relieving angina has never been in doubt. Nevertheless, even in the early reports from the randomized trials, there was evidence of attenuation of benefit with time. Data on

Late results following CABG 91

that late angina is due to associated vein graft closure and improved survival to continued perfusion of the LAD. Numerous other single institutional series have been published showing similarresults'26"31'.These studies are, of course, retrospective and no randomized study against vein grafting is likely ever to be performed. Nevertheless, there is a consistency about the patency and survival rates that enhances credibility and encourages clinical confidence in the belief that IMA grafting at least for the LAD is the conduit of choice. The results of bilateral IMA coronary bypass have now been reported in several large series132"34'. In 1087 patients undergoing bilateral IMA and supplemental vein grafts with 3-4 grafts per patient, the 10 and 15 year survival rates were 80 and 60% respectively132'. Patency of either IMA was similar. The patient population had significant coronary heart disease; thus about one-third had unstable VEIN GRAFT ATTRITION The short and long-term fate of reversed saphenous angina, one-third had impaired LV function, one-fifth left vein grafts has been well documented. At 1,5 and 10 years, main stem disease, three-quarters had triple vessel disease rates of occlusion in the best centres are, approximately, and 87-1 % were in NYHA Class III or IV. This patient 10, 20 and 40% respectively116"191. Very early occlusion is group seems very similar to that being referred for CABG largely due to thrombus possibly as a result of technical in a typical European referral centre in 1991. problems especially at the distal anastomosis. SubseWhether bilateral IMA bypasses produce better longquently fibro-intimal hyperplasia may occur, but of term results is as yet the subject of debate. In a small but greatest importance is the apparent acceleration of consecutive series of 100 patients with bilateral IMA occlusion after 5 years which coincides with the attenu- compared with a retrospective series of 100 patients with ation of the early clinical benefit of surgery. Since the single IMA and supplemental vein grafts, patient survival pathology is usually atherosclerosis and, finally, throm- was 74 and 59% respectively (P = 005). Numerous other bosis, conventional but much more strictly applied pre- beneficial effects were reported including freedom from ventive measures should have an important future role. subsequent myocardial infarction, angina and total Anti-platelet therapy with aspirin is now routine and ischaemic events. Operative mortality was 2% vs 9% for further research into vein physiology, especially of the single and bilateral IMA operations respectively133'. In endothelium, may provide further clues as to how to a larger prospective series performed between 1984 and maximise the life of vein grafts. 1986, the results of two surgeons, one of whom practised single IMA and vein grafting and the other full revascularization with bilateral IMAs, were compared. No sigCABG with the internal mammary artery (IMA) nificant differences in any outcome variable could be found1341. It must be emphasized that this first comparison HISTORICAL PERSPECTIVE The internal mammary artery has been used in the is only 4 years after surgery and before acceleration of vein surgical treatment of coronary heart disease for over 40 graft occlusion would be expected to have occurred. years and, following this early work of Vineberg1201, Goetz An important consideration is the peri-operative performed the first IMA bypass to the right coronary complication rate. In the absence of any randomized artery in I9601211. Green put the operation on the surgical study this, together with the long-term results, cannot map in 1968'2' and introduced magnification and micro- be determined with certainty. It is likely that in the best surgical techniques. Bilateral IMA grafts were described centres with experienced surgeons the operative mortality by Bailey in 19691221 and in 1973(23! Edwards used both is likely to be similar and acceptably low. IMAs and the splenic artery to bypass all three major coronary arteries. Summary of study data Despite Green's advocacy and its reputation for patency, few surgeons undertook IMA grafting until 1984 when a Bearing in mind the imperfections of the randomized patency of 95% at 10 years was described as compared studies and the interpretational pitfalls of retrospective with 30% for saphenous vein grafts inserted at the observational studies (however large), a number of clinisame institution124'. The large long term study from the cal conclusions that bear on the management of patients Cleveland Clinic compared 2306 IMA grafts with 3625 with CHD can be drawn. Specific sub-groups can be SVGs to the LAD'231. This non-randomized study con- defined, but, in general, the extent of coronary artery firmed the superior patency but also reported improved disease, the degree of impairment of left ventricular func10-year survival rates of 93-4, 880 and 90% vs 79-5, tion, the severity of symptoms and the ability to provoke 82-6 and 71 % for one, two and three vessel disease respect- reversible ischaemia are the major issues to be considered ively. There was no difference in recurrence rates for in deciding whether to recommend surgery or medical angina, however, which may be consistent with the theory treatment in patients with CHD133-361. the 10 year results has recently been published from the CASS study, a report which also included a censored analysis which took into account the large number (38%) of medical patients who subsequently underwent surgery. At 1 and 5 years after surgery, 66 and 63% in the surgical group and 30 and 38% in the medical group were free of angina. At 10 years, however, the proportion free of angina in the respective groups was closer though still statistically different at 47% and 42% (/>