The risk profile of patients requiring isolated CABG in the United States has changed significantly in the past decade. Patients are older, with a greater number of comorbidities, decreased LVEF, and a higher burden of atherosclerotic disease; however, early outcomes after CABG continue to improve. The STS database demonstrates that despite an increase in expected mortality from 2.6 to 3.4% (relative increase 30%) in the decade of the 1990s, the observed mortality has actually decreased from 3.9 to 3.0% (relative decrease 23%).3
Similar observations have been made using the Veterans Affairs mandatory national database, where the unadjusted mortality rate for isolated CABG fell from 4.3% in 1989 to 2.7% in the year 2000.88 In the private sector similar trends have been observed. In an analysis of outcomes of patients undergoing isolated CABG in the HCA system, a nationwide for-profit health care system involving 200 hospitals in 23 states, Mack and associates reported an ongoing decrease in unadjusted operative mortality among 51,353 patients, 80% of whom received CABG with cardiopulmonary bypass. In this study the operative mortality decreased from 2.9% in 1999 to 2.2% in 2002.89
In a multicenter prospective study performed by the Northern New England Cardiovascular Disease Study Group, 384 deaths among 8641 consecutive patients undergoing isolated CABG between 1990 and 1995 were analyzed with respect to the mode of death. The mode of death was defined as the seminal event that precipitated clinical deterioration and ultimately resulted in the patient's demise. Heart failure was judged to be the primary mode of death for 65% of the patients, followed in frequency by neurologic causes (7.3%), hemorrhage (7%), respiratory failure (5.5%), and dysrhythmia (5.5%). The greatest variability in mortality rates observed across surgeons in the study was attributable to differences in rates of heart failure.90 Cardiac causes were also identified by Sergeant and colleagues as the most common causes of death in a series 5880 patients undergoing CABG between 1983 and 1988.91
Postoperative myocardial dysfunction and cardiac failure after CABG may be related to preoperative ischemic injury, inadequate myocardial protection, incomplete revascularization, or postoperative graft failure. The spectrum of myocardial injury varies from subtle degrees of global myocardial ischemia to transmural infarction. The incidence of myocardial injury identified varies with the sensitivity of the method used for detection as well as the threshold set. Some studies have reported perioperative myocardial infarction rates as high as 10% of patients with associated worse clinical outcomes (death, MI, or revascularization).92
Some elevations of cardiac-specific enzymes are ubiquitous after CABG; however, most would agree that elevations in creatinine kinase-myocardial bound (CK-MB) greater than five times the upper limit of normal (ULN) value are considered significant. In a prospective study of 2918 patients undergoing CABG, 38% of patients had a CK-MB >5 ULN and 17% had a CK-MB >10 ULN with an incidence of new Q-wave MI of 4.7%.93 Troponin may be a more sensitive marker than CK-MB, but its role in large populations of CABG patients is still to be defined.94 Prominent elevations of CK-MB and troponin have been associated with global ischemia, MI, low cardiac output, and increased operative mortality, as well as increased midterm and long-term mortality.93,94
Transient myocardial dysfunction necessitating low-dose inotropic support for a short period of time is also common after CABG. Significant postoperative myocardial dysfunction manifest clinically as low cardiac output syndrome may be defined by the need for postoperative inotropic support or intra-aortic balloon pump support to maintain a systolic blood pressure >90 mm Hg or a cardiac index >2.2 L/min. The reported incidence of low output syndrome varies depending on the defining criteria and has a reported incidence of 4–9%.95,96 Low output syndrome has been shown to be a marker for increased operative mortality by 10- to 15-fold.97 Independent predictors of low output syndrome in order of importance include: LVEF <20%, reoperation, emergency operation, female gender, diabetes, age older than 70, left main disease, recent MI, and triple-vessel disease.96
Adverse Neurologic Outcome
Neurologic deficits after coronary surgery are divided into two types: type 1 deficits include major neurologic deficits, stupor, and coma; type 2 deficits are characterized by deterioration of intellectual function and memory. The incidence of type 1 deficits was reported to be 1.6% in a large review by the Northern New England Cardiovascular Disease Study Group with 1-, 5-, and 10-year survival rates significantly reduced in affected patients.98 Perioperative mortality is similarly increased among those with type 1 injury at over 24%.99 Type 2 deficits are more difficult to characterize and may be more related to the underlying atherosclerosis than to the bypass operation per se. In one nonrandomized study, there was no evidence that the cognitive test performance of coronary artery bypass grafting (CABG) patients differed from that of heart healthy control groups with coronary artery disease over a 1-year period.100
Predictors of neurologic deficits included advanced age (≥70 years of age), and history or presence of severe hypertension. Independent predictors of type 1 deficits included proximal aortic atherosclerosis, history of prior neurologic disease, need for IABP, diabetes, unstable angina, and perioperative hypotension. Predictors of type 2 deficits included history of alcohol consumption, dysrhythmias, prior CABG, peripheral vascular disease, congestive heart failure (CHF), and perioperative hypotension. Similar predictors of adverse neurologic outcomes have been observed in other studies.101
Deep Sternal Wound Infection
Deep sternal wound infection occurs in 1 to 4% of CABG patients and carries a mortality rate of 25%.102 Proven methods to reduce postoperative wound complications include the use of preoperative showers with chlorhexidine gluconate on the evening and morning before the procedure, prophylactic intranasal application of mupirocin given on the evening and the morning before the procedure and twice daily for 5 days postoperatively, hair clipping the morning of surgery, and administration of intravenous prophylactic antibiotics before skin incision.103–105 Application of a cyanoacrylate-based microbial skin sealant may further reduce surgical site infection.106
Obesity and diabetes are strong independent predictors of mediastinitis. Insulin-dependent diabetics are especially susceptible to deep sternal wound infection.107–109 Recent data suggest that tight glycemic control in the postoperative period decreases the risk of mediastinitis in the diabetic population.110,111 Other preoperative variables independently associated with an increased incidence of deep sternal wound infection include reoperation, longer operative times, reexploration for bleeding, and blood transfusions.108,109,112
The use of bilateral ITAs had been implicated as a risk factor for sternal would complications, especially in diabetics.113 However, this risk appears to be mitigated in part by using a skeletonized ITA harvesting technique.114 Bilateral ITA harvest should likely be avoided in obese diabetic women, in cases of repeat sternotomy, and in patients with severe COPD, because they exhibit a higher risk of deep sternal wound infection even with skeletonization of the ITA.25,115
Acute renal failure ensuing after CABG with cardiopulmonary bypass is an ominous event. In a prospective observational study conducted at 24 university centers in the United States, including data on 2222 CABG patients,116 renal dysfunction not requiring dialysis occurred in 6.3%, and renal dysfunction requiring hemodialysis developed in 1.4%. Mortality was directly related to postoperative renal function. Patients with no renal dysfunction had 0.9% mortality.116 Postoperative renal dysfunction increased mortality to 19% if no dialysis was needed and increased mortality to 63% if hemodialysis was required. Patients with large creatinine increases (≥ 50%) after CABG surgery also have higher 90-day mortality.117
Independent predictors of postoperative renal dysfunction included increasing age, CHF, reoperation, diabetes mellitus, chronic renal insufficiency, prolonged cardiopulmonary bypass time, and low cardiac output.116 These findings were confirmed in another series of 42,733 patients with similar incidence and mortality associated with postoperative renal dysfunction.118 One in four patients with preoperative chronic renal insufficiency (creatinine >1.6 mg/dL) will require renal replacement therapy post-CABG, and patients at highest risk are older than 70 years and have a baseline creatinine >2.5 mg/dL.119
Continuous infusion of low-dose recombinant human B-type natriuretic peptide (nesiritide) from the start of cardiopulmonary bypass has been evaluated as a method to effectively maintain postoperative renal function. In the prospective, randomized, NAPA Trial, 272 patients with ejection fraction ≤ 40% undergoing CABG who receive nesiritide experienced a significantly attenuated peak increase in serum creatinine and a greater urine output during the initial 24 hours after surgery. In addition, they had a shorter hospital stay and lower 180-day mortality.120 Similar renal protective results were noted in a randomized trial using human atrial natriuretic peptide in 251 patients. The treated group had fewer postoperative complications, lower serum creatinine, and higher urinary creatinine and creatinine clearance. The maximum postoperative creatinine level and percent increase of creatinine were also significantly lower in the treatment group. No patient in the natriuretic group required hemodialysis.121 We are awaiting further study before adopting natriuretic peptides in our routine CABG practice.
Long-term outcomes of surgical myocardial revascularization depend on the complex interaction of patient-related and procedure-related factors. Important patient-related factors include anatomic distribution of the CAD, the extent and severity of coronary atherosclerosis, the physiologic impact of ischemia on ventricular function at the time of the original operation, age, gender, overall health status, severity of atherosclerotic burden throughout the body, the presence and severity of associated comorbidities, development of operative complications such as stroke, and need for permanent hemodialysis. The progression rate of native coronary atherosclerosis after surgery and the development of coronary bypass graft failure are of extreme importance in the development of post-CABG angina recurrence, MI, need for reintervention, and cardiac-related mortality. Procedure-related factors that influence long-term outcomes include completeness of revascularization, myocardial protection, and selection of bypass conduits.
Sergeant and colleagues at the Gasthuiberg University Hospital of the Katholieke Universiteit (KU) Leuven, Belgium have provided several reports detailing clinical outcomes after myocardial revascularization.122–125 From 1971 to 1993, 9600 consecutive CABG patients were prospectively followed with special attention to clinical outcomes after surgical myocardial revascularization; the investigators achieved a 99.9% complete follow-up in this cohort. Clinical outcomes prospectively followed included mortality, return of angina, MI, and coronary reintervention.122
Defining the return of angina as the first occurrence of angina of any intensity or duration unless it was associated on the same day with MI or death, and recording the severity of this event, was also recorded. The overall non–risk-adjusted freedom from return of angina was 95% at 1 year, 82% at 5 years, 61% at 10 years, 38% at 15 years, and 21% at 20 years. The data suggest that if followed long enough after CABG, the return of angina is almost inevitable; by 12 years one-half of operated patients had return of angina. The initial episode of recurrent angina was rated as mild in 59% of patients.123 In the Bypass Angioplasty Revascularization Investigation (BARI) trial of 914 patients with symptomatic multivessel disease randomly assigned to receive CABG, freedom from angina was 84% at 5 and 10 years.126
The overall non–risk-adjusted freedom from MI after CABG at the KU Leuven was 97% at 30 days, 94% at 5 years, 86% at 10 years, 73% at 15 years, and 56% at 20 years.124 The overall non–risk-adjusted freedom from a coronary reintervention, either PCI or reoperative CABG, was 99.7% at 30 days, 97% at 5 years, 89% at 10 years, 72% at 15 years, and 48% at 20 years (125). In the BARI trial, freedom from subsequent coronary reintervention intervention at 10 years was 80%.126
Overall risk-unadjusted survival after CABG in the KU Leuven experience was 98% at 30 days, 92% at 5 years, 81% at 10 years, 66% at 15 years, and 51% at 20 years. Mortality after CABG was characterized by an initial period of high risk in the first month after surgery, then risk declined to its lowest at 1 year after the operation, and thereafter the mortality risk rose slowly and steadily for as long as the patient was followed. This slow and steady rise in the risk of death over time paralleled that of the general population when matched for sex, age, and ethnicity.125 In the BARI trial, survival was 89% at 5 years and 74% at 10 years.126
The occurrence of ischemic clinical events after CABG negatively influences survival. In the KU Leuven study, overall survival was lessened by return of angina, with an observed survival of 83% at 5 years and 54% at 15 years; the more intense the severity of angina at its return, the greater its influence on survival.123 The occurrence of MI after CABG has a greater negative effect on survival. Observed long-term survival after post-CABG infarction at the KU Leuven was 80% at 30 days, 65% at 5 years, 52% at 10 years, and 41% at 15 years.124
Progression of Disease in Native Coronary Arteries
Progression of atherosclerosis in the native coronary arteries continues after CABG. Bourassa and associates studied the progression of atherosclerosis in the native circulation 10 years after surgery and found that progression of CAD occurs in approximately 50% of nongrafted arteries.127 The rate of progression of disease in nongrafted arteries was no different from that of grafted arteries with patent grafts; however, progression was more frequent in grafted arteries with occluded grafts. Progression of preexisting stenoses in native coronaries was more frequent than appearance of new stenoses, and it was related to the severity of the preexisting stenosis only in nongrafted arteries.
Progression of native CAD was associated with deterioration in left ventricular function. Native coronary atherosclerosis progressed at a similar rate to that of equally diseased arteries in nonoperated patients.127 Low levels of high-density lipoprotein cholesterol and elevated levels of plasma low-density lipoprotein cholesterol correlated with native disease progression and development of new atherosclerotic lesions.128,129 Diabetes has been related to accelerated atherosclerosis. The VICTORY trial will be the first cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects of rosiglitazone is post-CABG patients with type 2 diabetes in patients 1 to 10 years after CABG.130
Although the use of the saphenous vein helped popularize coronary bypass grafting, the propensity of the saphenous vein graft to fail over time has been the limiting factor of the procedure. It has been reported that approximately 15% of vein grafts occlude in the first year after CABG, and by 6 and 10 years after surgery patency rates fall to approximately 75% and approximately 60%, respectively.18 Three entities are responsible for saphenous vein graft failure: thrombosis, intimal hyperplasia, and graft atherosclerosis
Thrombosis accounts for graft failure within the first month after CABG, and graft occlusion is found on angiography in 3 to 12% of all venous grafts. Even when performed under optimal conditions, the harvesting of venous conduits is associated with focal endothelial disruption. In particular, the high pressure distension used to overcome venospasm during harvesting causes prominent endothelial cell loss, medial damage, activation of local factors (ie, fibrinogen) influencing hemostasis. Additionally, the inherent antithrombotic properties of veins are comparatively weak. The propensity for early graft occlusion resulting from these prothrombotic effects may, on occasion, be amplified by technical factors that reduce graft flow, including intact venous valves, anastomotic stricture, or graft implantation proximal to an atheromatous segment.18
Intimal hyperplasia, defined as the accumulation of smooth muscle cells and extracellular matrix in the intimal compartment, is the major disease process in venous grafts between 1 month and 1 year after implantation. Nearly all veins implanted into the arterial circulation develop intimal thickening within 4 to 6 weeks, which may reduce the lumen by up to 25%. Intimal hyperplasia rarely produces significant stenosis per se; more importantly, however, is that it may provide the foundation for later development of graft atheroma.131
Progression of atherosclerosis in aortocoronary saphenous vein grafts is frequent and represents the predominant cause of late graft failure after CABG. Vein graft atherosclerosis may begin as early as the first year, but is fully developed only after about 5 years. Ten years after surgery, 50 to 60% of SVGs will be occluded and one-half of still patent grafts will show angiographic evidence of atherosclerosis; two-thirds of these lesions will have a luminal diameter reduction of 50% or greater. Vein graft atherosclerosis is the leading cause for reintervention following CABG, more so than progression of disease in native coronary arteries.18
Although the risk factors predisposing to vein graft atherosclerosis are broadly similar to those recognized for native coronary disease, the pathogenic effects of these risk factors are amplified by inherent deficiencies of the vein as a conduit when transposed into the coronary arterial circulation. A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification, in particular early and aggressive lipid-lowering drug therapy; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft disease at an early and fundamental level. At present, a key measure is to circumvent the problem of vein graft disease by preferential selection of arterial conduits, in particular the internal mammary arteries, for coronary bypass surgery whenever possible.18
Extended Use of Arterial Grafting
Bilateral Internal Thoracic Artery Graft
In contrast to the easily demonstrated survival benefit conferred by an ITA graft to the LAD artery, it was more difficult to demonstrate a survival benefit to a second arterial graft. Buxton and colleagues studied 1243 patients undergoing primary CABG with bilateral ITA grafts compared with 1583 patients with single ITA grafts. This group demonstrated a 15% absolute improvement in actuarial survival rates 10 years after CABG with the use of bilateral ITA grafts, as compared with the use of a single ITA graft (10-year survival for bilateral ITA was 86 ± 3% versus 71 ± 5% for a single ITA).131 Lytle and colleagues similarly demonstrated an improvement in survival at 12 years (79 versus 71%) as well as superior reoperation-free survival (77 versus 62%) among 2001 bilateral and 8123 single ITA graft patients.132 The impact of selection bias in these studies is difficult to control, however, and although some surgeons have embraced bilateral ITA grafting, it still represents a small minority of cases reported to the STS database.
Complete Arterial Revascularization
The better long-term results achieved with the use of bilateral ITAs and the well-known time-related attrition in patency of venous conduits encouraged the exclusive use of arterial conduits for myocardial revascularization. Complete arterial revascularization can be achieved by a variety of strategies, including composite grafting using exclusively ITAs or secondary arterial conduits such as the RA and the GEA. The use of sequential anastomotic techniques maximizes the utilization of arterial conduits. Although technically demanding, sequential grafting can be performed safely and with excellent long-term results with reported 96% patency rates of 7.5 years of follow-up on 1150 sequential ITA anastomoses.133
Tector has championed complete arterial revascularization using bilateral ITAs in a T configuration with end-to-side anastomosis of one ITA as a free graft to the side of the second ITA, which is left as a pedicled graft, combined with liberal use of sequential anastomoses. In his series of 897 patients overall survival was 75%, and freedom from reintervention was 92% 8 years after revascularization.134 Barner has reported similar encouraging results with composite grafting using one ITA and one RA.135 Data from randomized studies are beginning to emerge supporting improvement in early outcomes with complete arterial revascularization compared with conventional CABG. Muneretto and associates randomized 200 patients to complete arterial revascularization (left ITA to the LAD artery and composite grafts with the right ITA, RA, or both) versus conventional CABG (left ITA to the LAD artery and SVGs). In midterm follow-up (20 months) superior event-free survival (freedom from non-fatal MI, angina recurrence, graft occlusion, need for percutaneous transluminal coronary angioplasty, and late death) was demonstrable in the complete arterial revascularization patients compared to conventional CABG.136
The same group conducted a second randomized trial comparing complete arterial revascularization to conventional CABG (ITA to LAD artery and SVG) in 160 patients older than 70 years of age undergoing first time nonemergent CABG. Early mortality was similar, but at 16 ± 3 months, there were significantly fewer graft occlusions and recurrences of angina among the complete arterial revascularization group. Independent predictors of graft occlusion and angina recurrence were use of SVGs, diabetes, and dyslipidemia.137 The result of longer follow-up of these trials is still awaited.