Coronary Artery Bypass Graft Disease

Coronary artery bypass grafting has come of age. In the last 25 years, intense study identified the patients who benefit from this procedure. However, a parallel effort revealed that although the operation prolongs life in defined subsets of patients [1], its long-term results are not entirely satisfactory [2]. Given time, most vein grafts become occluded. By 10 years after the procedure, 50% of saphenous vein grafts have closed [3]. As grafts fail, symptoms return [4, 5] and the patient is again haunted by the specter of a heart attack, heart failure, rhythm disturbance, and sudden death. Coronary artery disease accounts for many patient visits to internists. Many of these patients now have bypass grafts. After a variable symptom-free period following bypass surgery, often these patients see their physician because of recrudescent angina. Fortunately, as one set of studies identified the developments that cause these symptoms, other studies provided clues about measures that prevent or minimize graft failure and thus increase the benefits of coronary artery bypass grafting. Therefore, to care for these patients effectively, general practitioners, internists, cardiologists, and cardiac surgeons must be knowledgeable about the findings of these studies. This article reviews bypass graft disease and highlights important aspects of its prevention and management. Methods A search of MEDLINE from 1968 to 1994 identified articles on saphenous vein and arterial grafts and on repeat coronary operation. Often particularly informative articles helped to focus the search by referencing relevant articles from which a particular theme could be developed. Some institutions, such as the Cleveland Clinic and the Montreal Heart Institute, did many studies of bypass grafts and disease. The former in particular was disproportionately the source of much useful information. Such articles were also a rich source of relevant referenced material. Saphenous Vein Grafts The saphenous vein graft is used most commonly because it is relatively plentiful, readily accessed, and easily harvested. Although it also provides adequate flow to the recipient artery, its tendency to occlude is an important drawback. Saphenous Vein Graft Attrition Determining an accurate failure rate of saphenous vein grafts was difficult. Among other factors, the observed saphenous vein graft failure rate depends on the reason for restudying the graft. Attrition rates were higher when patients were restudied for symptoms compared with patients restudied solely for a research protocol [5]. In addition, angiography underestimates the severity of lesions in native coronary arteries and especially in vein grafts [6, 7]. Other difficulties I encountered when reviewing the literature included the failure of some investigators to specify whether the occlusion rate was per distal anastomosis, per graft, or per patient [8]. This information is important because saphenous vein grafts may be individual, sequential, or branched Y grafts and are usually placed in multiple arteries in the same patient [8]. Furthermore, in longitudinal studies, not only are consecutive patients not often studied [8], but the same patients are rarely studied successively. Finally, available data on rates of graft occlusion, although not completely irrelevant, may not reflect current experience and the effect of the lessons for prevention revealed by earlier studies. It is difficult to believe, for instance, that within the first month after surgery the graft occlusion rate from thrombosis is still as high as 10% (which was first reported more than a decade ago), despite current knowledge about readily and widely implemented measures that prevent endothelial injury. The reported attrition rate has varied for the reasons previously noted. The attrition rate is highest, 8% to 12%, soon after coronary artery bypass grafting (that is, within the first 4 weeks) [2, 3, 8-10]. By the end of the first year, 12% to 20% of the saphenous vein grafts have closed [2, 3, 8-10]. The occlusion rate subsequently slows to an annual rate of 2% for the next 4 or 5 years [3]. After 5 years, the occlusion rate doubles to 4% per year, so that by 10 years after coronary artery bypass grafting about 50% of the grafts have closed [3]. However, although most grafts are diseased 10 years after bypass grafting, 70% to 80% of grafts that appear normal or minimally diseased at 5 years remain so 10 years after surgery [2, 11]. Mechanisms of Graft Closure and Histopathologic Findings of Graft Lesions Three processes cause saphenous vein graft failure. Although these processes are time-dependent and one or the other predominates at particular points, their occurrences overlap. Thrombosis accounts for graft failure within the first month but continues to occur as long as 1 year after coronary artery bypass grafting. Fibrointimal hyperplasia occurs predominantly after 1 month to 5 years. Vein graft atherosclerosis may begin as early as the first year but is fully developed only after about 5 years [3, 12-14]. Thrombosis Endothelial injury and technical errors predispose veins to thrombosis [3, 12] (Table 1). Certain aspects of saphenous vein harvesting may cause endothelial injury. Apart from the direct physical injury to the vein graft that can occur during harvesting, the pressure used to distend the graft to detect leaks may, if uncontrolled, be as high as 300 mm Hg [12, 13]. Such pressures damage the endothelium. Other important causes of endothelial injury during vein harvesting include ischemia of the vein wall caused by transient loss of luminal blood and vasa vasorum; the nonphysiologic pH of the distending fluid when a fluid other than blood is used to support and dilate the vein before implantation; and exposure to the high and unaccustomed pressures in the arterial circulation [13]. No less important are the effects of various risk factors, including smoking and hypercholesterolemia, that may induce or perpetuate endothelial injury. Table 1. Factors That Promote Early Graft Closure Endothelial injury to vein grafts after harvesting include denudation of the intima that can extend into the media. Damage to the endothelium causes endothelial dysfunction, which decreases production of prostacyclin [15] and nitric oxide [16]. Both of these substances inhibit growth and platelet activation, adhesion, and aggregation. For this reason, these type III injuries, which by definition not only denude the endothelium but also disrupt the internal elastic lamina and the media [17], cause platelet activation, adhesion, and aggregation. Subsequent activation of the clotting cascade eventually causes thrombosis. Technical errors that increase the likelihood of thrombosis include errors in performing the distal anastomosis; excessive or insufficient graft length, which causes kinks and linear tension in the graft; and mismatched sizes of graft and recipient artery, which can compromise flow, promote turbulence, or both. Low graft flow rate is one of the most important factors (Table 1) that increase the likelihood of early graft occlusion [8]. Circumstances that cause a low graft flow rate are small luminal size (< 1.5 mm) of the grafted artery and decreased distal runoff due to severe disease in the recipient artery. The specific artery grafted is also important: The occlusion rate of a saphenous vein graft to the right coronary and circumflex arteries is higher than that for left anterior descending grafts [10]. Other factors that predict early graft failure include endarterectomy of the grafted artery, local atheroma at the arteriotomy site, extension of the arteriotomy into a branch vessel, postoperative smoking, and hyperlipidemia. For sequential grafts, side-to-side anastomoses have higher patency than do end-to-side anastomoses [18], presumably because the former have greater flow. In general, side-to-side and end-to-side anastomoses involving the diagonal and left anterior descending arteries have higher patency rates than do the same types of anastomoses involving other vessels [18]. Nonsequential end-to-side anastomoses to single vessels have higher patency rates than do sequential end-to-side anastomoses to the same position, but rates are similar when the arteries involved in sequential grafts are diagonal and left anterior descending [18]. Fibrointimal Hyperplasia Fibrointimal hyperplasia is also caused by endothelial injury and invariably occurs to some degree [13, 14, 19]. Again, endothelial dysfunction resulting from injury impairs prostacyclin and nitric oxide production [15, 16] and thus decreases the growth and platelet inhibition attributed to these substances. Subsequent platelet activation may release platelet-derived growth factor and basic fibroblast growth factor, which stimulate the smooth-muscle cells of the media to migrate to the intima and to proliferate and synthesize fibrous tissue, including collagen and proteoglycans [20]. The latter process causes the intimal thickening or hyperplasia that generally results in a 25% decrease in the luminal vessel diameter [8]. Evidence shows that basic fibroblast growth factor released from injured endothelial cells [21] is important in fibrointimal hyperplasia. Recent data from a canine model showed that the density of receptors for this growth factor is increased when the vein graft is distended at 200 mm Hg [22]. Vein Graft Atherosclerosis Vein graft atherosclerosis usually occurs with fibrointimal hyperplasia and conforms to the same pathogenetic paradigm as arterial atherosclerosis [23, 24], with some variations. Thus, cellular elements, including platelets, macrophages, and smooth muscle cells, are involved. Growth factors released by these elements govern and modulate their interaction and behavior. Lipids, invariably present in lesions of atherosclerosis, are taken up from the blood, processed by macrophages, and deposited in the nascent lesions [23]. The risk fac