Nosocomial infections occur in 10% to 20% of cardiac surgery patients. To prevent surgical site infections in CABG patients, a multimodality approach involving several periop- Hillis et al 2011 ACCF/AHA CABG Guideline e689 erative interventions must be considered. Preoperative inter- ventions include screening and decolonization of patients with methicillin-resistant and methicillin-sensitive S. aureus colonization and adequate preoperative preparation of the patient. Nasal carriage of S. aureus is a well-defined risk factor for subsequent infection. In proven nasal carriers of S. aureus, intranasal mupirocin reduces the rate of nosocomial S. aureus infection, but it does not reduce the rate of surgical site infection with S. aureus.928,929 Preoperative patient bath- ing, the use of topical antiseptic skin cleansers (chlorhexidine gluconate),930 932 and proper hair removal techniques (using electric clippers or depilatories rather than razors)933 937 are important measures with which to prepare the patient for surgery. Intraoperative techniques to decrease infection include strict adherence to sterile technique, minimization of operat- ing room traffic, less use of flash sterilization of surgical instruments, minimization of electrocautery933,936 and bone wax,938 use of double-gloving,938 943 and shorter operative times. identification of patients at high risk for preoperative infection allows the clinician to maximize prevention strate- gies. Superficial wound infection occurs in 2% to 6% of patients after cardiac surgery,656,944 946 and deep sternal wound infection occurs in 0.45% to 5%, with a mortality rate The etiology of deep sternal wound infection is multifac- torial. Risk factors for deep sternal wound infection are diabetes mellitus,25,27,28 obesity (body mass index 30 kg/ ),947,949,950,953,954 chronic obstructive pulmonary disease,950 prolonged CPB time, reoperation, prolonged intubation time, and surgical reexploration.945,947,955 Potentially modifiable risk factors are smoking cessation, optimized nutritional status, adequate preoperative glycemic status (with hemoglo- bin A1c 6.9%), and weight loss. The use of bilateral IMAs has been a subject of investigation as a risk factor for deep sternal wound infection. Each IMA provides sternal branches, which provide 90% of the blood supply to each hemi- sternum. As a result, IMA harvesting can compromise sternal wound healing. Although no RCTs assessing the risk of deep sternal wound infection after bilateral IMA grafting have been reported, the use of bilateral IMAs in patients with diabetes and those with other risk factors for surgical site infection increases the incidence of deep sternal wound infection.956,957 Skeletonization of the IMA may be associated with a beneficial reduction in the incidence of sternal wound complications, more evident in patients with diabetes Transfusion of homologous blood is a risk factor for adverse outcomes after cardiac surgery. Blood transfusions after CABG are correlated in a dose-related fashion to an increased risk of transfusion-related infection, postoperative infection, postoperative morbidity, and early and late death.959 962 In addition, they have been associated with a higher incidence of sternal wound infections.949,963,964 In a retrospective analysis of 15 592 cardiovascular patients, the risk of septicemia/bacteremia and Superficial and deep sternal wound infections increased incrementally with each unit of blood transfused.961 The leukocytes that are present in packed red blood cells induce the immunomodu- latory effects associated with blood transfusions. Allo- genic transfusions of blood containing leukocytes induce higher concentrations of proinflammatory mediators (such as interleukins 6 and 10) than does the transfusion of leukocyte-depleted blood.924 927,965 In patients undergoing cardiac surgery, RCTs have shown that those receiving leukocyte-filtered blood have lower rates of perioperative infection and in-hospital death than those receiving non leukocyte-filtered blood.924 927 An RCT showed that those receiving leukocyte-depleted blood had a reduced rate of ity (transfused/nonfiltered patient mortality rate, 7.8%; trans- fused/filtered at the time of donation, 3.6%; and transfused/ filtered at the time of transfusion, 3.3% [P 0.019]).927 Leukodepletion can be accomplished by the blood bank at the time of donation or at the bedside at the time of transfusion (with the use of an inexpensive in-line transfusion filter). Preoperative antibiotics reduce the risk of postoperative infection 5-fold.892 Interest has grown in administering anti- biotic prophylaxis as a single dose rather than as a multiple- dosing regimen for 24 to 48 hours, because single-dose antibiotic prophylaxis reduces the duration of prophylaxis, its cost, and the likelihood of antimicrobial resistance. Staphylococcus coagulase negative epidermidis or S. au- reus (including methicillin-resistant S. aureus) account for 50% of surgical site infections. Other organisms that are often involved are Corynebacterium and enteric gram-negative bacilli.966 968 Antibiotic prophylaxis against these organisms should be initiated 30 to 60 minutes before surgery, usually at the time of anesthetic induction, except for vancomycin, which should be started 2 hours before surgery and infused slowly to avoid the release of histamine.903,969,970 In patients without methicillin-resistant S. aureus colonization, a cepha- losporin (cefazolin, 1 g given intravenously every 6 hours, or cefuroxime, 1.5 g given intravenously every 12 hours) is the agent of choice for standard CABG.897 905 Antibiotic redosing is performed if the operation lasts 3 hours.970 Vancomycin is reserved for the patient who is allergic to cephalosporins or has known or presumed methicillin-resistant S. aureus The incidence of deep sternal wound infection has de- creased over the past 15 years despite an increased risk profile of patients undergoing cardiac surgery (ie, increased comor- bidities, obesity, diabetes mellitus, and advanced age).971 Several options are available for the treatment of deep sternal wound infection. The main treatment is surgical debridement with primary or delayed reconstruction with vascularized soft tissue (pectoral muscle or omentum).909 912,972 Conventional treatment with pectoralis flap muscle or omentum is associ- ated with procedure-related morbidities, such as destabiliza- tion of the thoracic cage, surgical trauma, and potential failure of the flap. In current practice, the vacuum-assisted closure system is often used in the treatment of mediastini- tis.913 With it, local negative pressure is applied to the open wound, accelerating granulation tissue formation and increas- ing blood supply. Such vacuum-assisted closure therapy, which is less invasive than conventional surgical treatment, has been used as standalone therapy, as a bridge to flap advancement, or as sternal preconditioning and preservation followed by titanium plate sternal osteosynthesis.913,914,973 Although several studies have suggested that vacuum- assisted closure therapy can be a successful alternative to conventional standard therapy,913 921,973 the data are from single-center retrospective studies of patients with heteroge- neous disease processes. As a result, it seems reasonable to suggest that both conventional and vacuum-assisted closure therapy can be used in the treatment of mediastinitis. 5.2.3. Renal Dysfunction: Recommendations Class IIb 1. In patients with preoperative renal dysfunction (cre- atinine clearance <60 mL/min), off-pump CABG may be reasonable to reduce the risk of acute kidney injury (AKI).974 978 (Level of Evidence: B) 2. In patients with preexisting renal dysfunction under- going on-pump CABG, maintenance of a perioper- ative hematocrit greater than 19% and mean arte- rial pressure greater than 60 mm Hg may be reasonable. (Level of Evidence: C) 3. In patients with preexisting renal dysfunction, a delay of surgery after coronary angiography may be reasonable until the effect of radiographic contrast material on renal function is assessed.979 981 (Level of Evidence: B) 4. The effectiveness of pharmacological agents to pro- vide renal protection during cardiac surgery is un- certain.982 1004 (Level of Evidence: B) See Online Data Supplements 37 to 39 for additional data on CABG and renal dysfunction. Depending on the definition used, the incidence of AKI (defined in various studies as an increase in serum creatinine concentration and/or decrease in calculated glomerular filtration rate of a certain magnitude) after isolated CABG is 2% to 3%, and the incidence of AKI requiring dialysis is 1%.1005 Risks factors for developing AKI after CABG are preoperative renal dysfunction, LV systolic dysfunction, PAD, advanced age, race, female sex, type of surgery, diabetes mellitus requiring insulin, emergency surgery, preoperative intraaortic balloon support, and congestive heart failure or shock.1005 1013 The pathogenesis of postoperative AKI is usually multi- factorial. The identification and effective management of mod- ifiable variables can minimize its occurrence. CPB can lead to renal dysfunction if renal perfusion is not adequately maintained. In addition, CPB leads to a systemic inflammatory response, with the release of 1) inflammatory cytokines (eg, kallikrein, bradykinin), 2) catecholamines, and 3) other hormones (eg, renin, aldosterone, angiotensin II, vasopressin), all of which influence renal function. The effects of hypothermia during CPB on renal function are uncertain. Two RCTs1014,1015 showed no effect of CPB temperature on renal function in patients under- going CABG, whereas a 2010 observational study1016 of 1072 subjects identified a relationship between a CPB temperature 27 C and the development of AKI (OR: 1.66; 95% CI: 1.16 to 2.39; P 0.005). Although off-pump CABG may theoretically avoid CPB-related renal injury, the cardiac manipulation that is often required to obtain adequate exposure may cause transient decreases in cardiac output, increased peripheral vasoconstric- tion, and decreased renal perfusion.1017 A meta-analysis of 6 RCTs and 16 observational studies (encompassing data from 27 806 patients) suggested a modest beneficial effect of off- pump CABG in reducing the incidence of AKI but no advantage in reducing the incidence of AKI dialysis.977 These findings were confirmed by another published RCT of 2203 patients, in which the incidence of AKI dialysis was similar among those undergoing off-pump and on-pump CABG (0.8% for off pump; 0.9% for on pump; P 0.82).61 Considering the low (approxi- mately 1%) incidence of AKI dialysis in subjects undergoing CABG, available RCTs are underpowered to detect a difference in outcome. In patients with renal dysfunction preoperatively, it might be reasonable to perform off-pump CABG to reduce the risk of AKI.974 976,978,996 During CPB, hemodilution is induced to reduce blood viscosity and plasma oncotic pressure to improve regional blood flow in the setting of hypothermia and hypoperfusion. However, an excessively low hematocrit on CPB is associated with increased adverse events and in-hospital deaths.1018 In patients undergoing isolated CABG, it has been reported that the mortality rate of patients with a single hemat- ocrit value 19% was twice that of those with a hematocrit of 25%.1019 On the basis of these data, a hematocrit 19% on CPB should be avoided. No drugs have been identified that prevent or alleviate CABG-associated AKI. N-acetylcysteine reduces proinflam- matory cytokine release, oxygen free radical generation, and reperfusion injury, but a review of 10 RCTs containing data from 1163 patients982 showed that it did not reduce the incidence of AKI and AKI dialysis.987 In several RCTs, atrial natriuretic peptide was shown to reduce peak postop- erative serum creatinine concentrations, increase urine out- put, and reduce the need for dialysis in individuals with normal renal function preoperatively, but it did not prevent AKI dialysis in patients with preexisting renal Fenoldopam, a selective dopamine D1 receptor agonist that causes vasodilatation and increases renal cortical and outer medullary blood flow, seems to exert protective renal effects in critically ill patients.994,995 A meta-analysis of the data from 1059 patients reported in 13 randomized and case-matched studies showed that fenoldopam exerts a beneficial effect on renal function. Compared with standard therapy, fenoldopam reduced the need for renal replacement therapy (5.7% versus lowered the peak value for serum creatinine concentration. Nevertheless, this beneficial effect was counterbalanced by an increased rate of hypotension and vasopressor require- P 0.008). Dopamine at low doses increases renal blood flow and blocks the tubular reabsorption of sodium. A meta-anal- ysis on the use of low-dose dopamine reported that it increased urine output and improved serum creatinine con- centrations without influencing the need for renal replace- ment therapy or the rates of adverse events or death.990 Diltiazem and mannitol have been used to prevent AKI after cardiac surgery.988 Diltiazem may inhibit the inflamma- tory response that occurs with CPB,992 whereas mannitol produces an osmotic diuresis.1000 The role of mannitol in preventing AKI is unclear.983,1004 Diltiazem does not prevent Hillis et al 2011 ACCF/AHA CABG Guideline e691 renal dysfunction.983 Contrast-induced nephropathy is a com- mon cause of AKI. It is usually self-limited and manifests its peak effect 3 to 5 days after the administration of contrast material. In patients with preoperative renal dysfunction, it is reasonable to delay surgery for several days after coronary angiography to reduce the incidence of AKI.979 981 5.2.4. Perioperative Myocardial Dysfunction: Recommendations Class IIa 1. In the absence of severe, symptomatic aorto-iliac occlusive disease or PAD, the insertion of an in- traaortic balloon is reasonable to reduce mortality rate in CABG patients who are considered to be at high risk (eg, those who are undergoing reoperation or have LVEF <30% or left main CAD).1021 1026 (Level of Evidence: B) 2. Measurement of biomarkers of myonecrosis (eg, creatine kinase-MB, troponin) is reasonable in the first 24 hours after CABG.200 (Level of Evidence: B) Intraaortic balloon counterpulsation is an established me- chanical cardiac support procedure that has been demon- strated to increase cardiac output and to improve coronary blood flow.1025,1026 In several RCTs, its preoperative initiation and perioperative use have been shown to reduce the mortal- ity rate in CABG patients who are considered to be at high risk (ie, those undergoing repeat CABG, those with an LVEF 30%, or those with left main CAD)1022 1024 despite its known associated vascular complications.1021 In contrast, its routine use in subjects who are not thought to be high risk has not been demonstrated.1027 Some myocyte necrosis often occurs during and immedi- ately after CABG, caused by cardiac manipulation, inade- quate myocardial protection, intraoperative defibrillation, or acute graft failure. A determination of the frequency and magnitude with which postoperative myonecrosis occurs has been difficult. In 2007, the European Society of Cardiology/ ACCF/AHA/World Heart Federation Task Force for the Redefinition of Myocardial Infarction stated, [B]iomarker values more than 5 times the 99th percentile of the normal reference range during the first 72 h following CABG, when associated with the appearance of new pathological Q-waves or new [left bundle branch block], or angiographically doc- umented new graft or native coronary artery occlusion, or imaging evidence of new loss of viable myocardium should be considered as diagnostic of a CABG-related myocardial infarction (type 5 myocardial infarction). 203, p. 2183 Until 2000, the conventional biomarker for myonecrosis was cre- atine kinase-MB, but at present cardiac-specific troponin is the preferred indicator of myonecrosis.198,200 The higher the serum concentrations of biomarkers after CABG, the greater the amount of myonecrosis and, therefore, the greater the likelihood of an adverse outcome. Published data from the PREVENT IV trial suggest, first, that serum biomarkers for myonecrosis are elevated postop- eratively even in roughly 10% of CABG subjects who are considered to be low risk for the procedure and, second, that short-term (30-day) and long-term (2-year) outcomes were worse in these patients than in those without a postoperative biomarker elevation. Similarly, a direct correlation has been noted between the presence and magnitude of biomarker elevations postoperatively and both intermediate- and long- term risk of death.1028 5.2.4.1. Transfusion: Recommendation Class I 1. Aggressive attempts at blood conservation are indi- cated to limit hemodilutional anemia and the need for intraoperative and perioperative allogeneic red blood cell transfusion in CABG patients.1029 1032 (Level of Evidence: B) Numerous large observational studies have identified peri- operative allogeneic red blood cell transfusion(s) as an independent risk factor for adverse outcomes, including death.1029 1032 A prospective observational study of 8004 patients demonstrated that the transfusion of allogeneic red blood cells in CABG patients was associated with an in- creased risk of low-output heart failure irrespective of the extent of hemodilutional anemia.1030 An adverse outcome may be caused by immunomodulation (known to occur with red blood cell transfusion), initiation of a systemic inflamma- tory response and its associated direct negative myocardial effects, reduced red blood cell capacity for adequate oxygen delivery1031,1032 (diphosphoglycerate function in banked blood may cause tissue hypoxia), and changes in red blood cell morphology of transfused blood. Regardless of etiology, myocardial depression is observed consistently after alloge- neic red blood cell transfusion, and this effect appears to be dose dependent. Even risk-adjusted survival rates after CABG in patients transfused with allogeneic red blood cells 5.2.5. Perioperative Dysrhythmias: Recommendations Class I 1. Beta blockers should be administered for at least 24 hours before CABG to all patients without contra- indications to reduce the incidence or clinical se- quelae of postoperative AF.604 608,608a 608c (Level of Evidence: B) 2. Beta blockers should be reinstituted as soon as possible after CABG in all patients without contra- indications to reduce the incidence or clinical se- quelae of AF.604 608,608a 608c (Level of Evidence: B) Class IIa 1. Preoperative administration of amiodarone to re- duce the incidence of postoperative AF is reasonable for patients at high risk for postoperative AF who have contraindications to beta blockers.1036 (Level of Evidence: B) 2. Digoxin and nondihydropyridine calcium channel blockers can be useful to control the ventricular rate in the setting of AF but are not indicated for prophylaxis.606,1037 1041 (Level of Evidence: B) AF immediately after CABG, occurring in 20% to 50% of patients, is often difficult to manage and is associated with a substantially increased risk of morbidity (particularly dis- abling embolic events) and mortality. A prospective observa- tional study of 1878 consecutive subjects undergoing CABG noted that post-CABG AF was associated with a 4-fold increased risk of disabling embolic stroke and a 3-fold increased risk of cardiac-related death.607 The incidence of postoperative AF is increased in the presence of advanced patient age, male sex, PAD, chronic lung disease, concomitant valvular heart disease, left atrial enlargement, previous cardiac surgery, preoperative atrial tachyarrhythmias, pericarditis, and elevated postoperative adrenergic tone. However, many subjects have none of these factors, yet they develop AF in the immediate postoperative period. Postoperative AF almost always occurs within 5 days postoperatively, with a peak incidence on the second postop- erative day.608 Numerous trials have assessed the efficacy of various pharmacologic agents in preventing post-CABG AF, including beta-adrenergic-blockers, various antiarrhythmic agents, glucocorticosteroids, hormonal agents (eg, triiodothy- ronine), and even statins. Preoperative and postoperative beta blockers (or possibly amiodarone) are most effective at reducing its incidence, with several RCTs showing that they effectively accomplish this goal. In contrast, glucocorticoste- roids, hormonal agents, and statins are not effective at decreasing its occurrence.604 606,608b,608c,1042 In subjects with- out pre-CABG AF, post-CABG AF usually resolves sponta- neously within 6 weeks of surgery. As a result, the preferred management strategy of post-CABG AF in such patients often consists of control of the ventricular rate (with beta blockers) in anticipation of spontaneous reversion to sinus rhythm within a few weeks. In addition, if the patient is considered to be at risk for a thromboembolic event while in AF, anticoagulation (with heparin and then warfarin) is warranted. For a more detailed description of the manage- ment of subjects with postoperative AF, the reader is referred to the 2011 ACCF/AHA/HRS guidelines for the Management of Patients with Atrial Fibrillation.608 5.2.6. Perioperative Bleeding/ Transfusion: Recommendations Class I 1. Lysine analogues are useful intraoperatively and postoperatively in patients undergoing on-pump CABG to reduce perioperative blood loss and trans- fusion requirements.1044 1051 (Level of Evidence: A) 2. A multimodal approach with transfusion algorithms, point-of-care testing, and a focused blood conservation strategy should be used to limit the number of trans- fusions.1052 1057 (Level of Evidence: A) 3. In patients taking thienopyridines (clopidogrel or prasugrel) or ticagrelor in whom elective CABG is planned, clopidogrel and ticagrelor should be with- held for at least 5 days520,521,523,524,531,1058 1063 (Level of Evidence: B) and prasugrel for at least 7 days533 (Level of Evidence: C) before surgery. 4. It is recommended that surgery be delayed after the administration of streptokinase, urokinase, and tissue-type plasminogen activators until hemostatic capacity is restored, if possible. The timing of rec- ommended delay should be guided by the pharma- codynamic half-life of the involved agent. (Level of Evidence: C) 5. Tirofiban or eptifibatide should be discontinued at least 2 to 4 hours before CABG and abciximab at least 12 hours before CABG.526 528,1049,1050,1064 1068 (Level of Evidence: B) Class IIa 1. It is reasonable to consider off-pump CABG to reduce perioperative bleeding and allogeneic blood transfusion.67,1069 1074 (Level of Evidence: A) See Online Data Supplements 40 to 42 for additional data on bleeding/transfusion. Approximately 10% of allogeneic blood transfusions in the United States are given to subjects undergoing cardiac sur- gery.1075 Allogeneic transfusion carries the risks of transfu- sion reactions, airborne infections, and increased hospital costs. In patients undergoing isolated CABG, transfusions are associated with reduced long-term survival and worse quality About 10% to 20% of the cardiac patients who are transfused receive roughly 80% of the transfusions that are administered.1075,1078 These high-risk patients often can be identified preoperatively to facilitate measures directed at blood conservation. Several reports have identified risk fac- tors for blood transfusions,1079 1082 including advanced age, preoperative anemia, small body size, reoperative CABG, priority of operation, duration of CPB, presence of preoper- ative coagulopathy, and preoperative antithrombotic ther- apy.1080,1083 1088 A multimodal approach that includes trans- fusion algorithms, point-of-care testing, and a focused blood conservation strategy can limit the percentage of patients requiring transfusion and the amount of blood transfusions About 60% to 70% of CABG patients are taking aspirin at the time of the procedure.536,1089,1090 Although aspirin in- creases perioperative blood loss and blood transfusion re- quirements,1091 1098 the amount of blood loss can be mini- mized by avoiding CPB1099 and by using blood conservation techniques. In a meta-analysis of data from 805 patients,1100 doses of preoperative aspirin 325 mg were associated with increased bleeding (mean difference, 230 mL), whereas those who received 325 mg preoperatively did not have a significant increase in blood loss (mean difference: 65.3 mL; 95% CI: 20.2 to 150.8; P 0.134). Some subjects undergoing CABG are receiving DAPT. Multiple studies have shown that the preoperative use of aspirin and clopidogrel is associated with increased periop- erative bleeding, transfusions, and required reexploration for bleeding.522 524,531,1058 1062,1101 1107 In a study of 350 CABG patients at 14 centers, the risk of reexploration for bleeding was increased 3-fold in patients who were exposed to clopidogrel within 5 days of surgery; half of these patients required transfusions.520 In patients taking clopidogrel in whom elective CABG is planned, the drug should be withheld Hillis et al 2011 ACCF/AHA CABG Guideline e693 for 5 to 7 days before surgery. In subjects taking DAPT because of previous placement of a DES, clopidogrel can be stopped 1 year after the most recent DES placement. If CABG cannot be postponed, some operators have suggested that the patient be hospitalized for conversion of thienopyri- dine therapy to short-acting glycoprotein IIb/IIIa inhibitors for several days before surgery497,1063,1108,1109; however, no data are available demonstrating the efficacy of such a management strategy. Streptokinase, urokinase, and tissue- type plasminogen activator should be stopped before CABG; in these individuals, the timing of CABG depends on the pharmacodynamic half-life of the agent involved.1110 The use of unfractionated heparin has not been associated with increased perioperative blood loss; it can be continued until a few hours before CABG. Low-molecular-weight heparin can be administered safely 12 hours preoperatively and does not result in excessive perioperative blood loss.1064 1068 Lysine analogues, such as epsilon-aminocaproic acid and tranexamic acid, inhibit fibrinolysis by binding to the plasminogen mole- cule. Several trials have shown that both epsilon-aminocaproic acid and tranexamic acid reduce blood loss and blood transfu- sions during cardiac surgery, but they do not reduce the rate of reexploration for bleeding.1044 1051 Both drugs appear to be safe and do not increase the risk of death.1111 Erythropoietin is a glycoprotein hormone that stimulates red blood cell production. Recombinant human erythropoietin is used in combination with iron supplementation to treat anemic patients (hemoglobin levels 13 g/dL) with renal failure and those undergoing chemotherapy. The use of erythropoietin in cardiac surgery has been studied in 12 RCTs and has been shown to be associated with significant risk reduction in allogeneic blood transfusion after cardiac sur- gery.1112 1122 However, the data from the RCTs are heteroge- neous, with different doses of erythropoietin administered for 1 to 3 weeks preoperatively; as a result, further studies are needed to define more precisely the patient subgroups who may benefit from this therapy.1123 In patients who refuse blood transfusions during cardiac surgery, a short-term course of preoperative erythropoietin, to produce a high hematocrit preoperatively, may be administered.1124,1125 Alternatively, autologous blood donation may be used, which consists of extracting 1 to 3 units during the 30 days preoperatively and then reinfusing it during or postoperatively. However, such a practice is uncommon because of the increased risk of hemodynamic instability. Off-pump CABG may avoid CPB-related coagulopathy caused by exposure of blood to artificial surfaces, mechanical trauma, alterations in temperature, and hemodilution. Some evidence suggests that off-pump CABG is associated with less bleeding and fewer blood transfusions.67,1069 1074 6. Specific Patient Subsets The term elderly in CABG patients is usually defined as 80 years of age. Compared with younger subjects, the elderly are more likely to have severe (left main or multi- vessel) CAD, LV systolic dysfunction, concomitant valvular disease, and previous sternotomy. In addition, they often have comorbid conditions, such as diabetes mellitus, hyper- tension, chronic obstructive pulmonary disease, PAD, and azotemia. As a result, the elderly have a higher perioperative risk of morbidity and mortality than do younger patients receiving CABG. The operative mortality rate among the elderly ranges from 2.6% (in a population 75 years of age) to 11% (in a population 80 years of age undergoing urgent or emergency surgery).298,1126 Retrospective studies have observed a substantially higher in-hospital mortality rate among octogenarians than among younger patients.1127 1130 A report from the National Cardiovascular Network of out- comes in 67 764 patients undergoing cardiac surgery, of whom 4743 were octogenarians, showed that the in-hospital mortality rate for the octogenarians was substantially higher Several retrospective studies of patients undergoing CABG have reported a higher incidence of neurological complica- tions, renal failure, respiratory failure, and gastrointestinal complications among octogenarians than among younger subjects.298,1127,1128 In addition, the elderly have longer lengths of stay and are less likely to be discharged home. An analysis of the New York State Department of Health Cardiac Reporting System registry revealed that length of stay after CABG was 8.5 days in patients 50 years of age and 14.1 days in those 80 years of age, with discharge-to-home rates Despite higher rates of in-hospital morbidity and mortality, the majority of octogenarians achieve functional improve- ment after CABG. Two studies of patients 80 years of age demonstrated improvements in quality of life, as assessed by the Seattle Angina Questionnaire.1131,1132 In 1 of these, angina relief and quality-of-life improvement scores after CABG did not differ between patients 75 and 75 years of age.1126 Of 136 octogenarians who underwent CABG, 81% felt that they were left with little or no disability in their daily activities, and 93% reported substantial symptomatic improvement an average of 2.1 years postoperatively.1131 Data on the influence of sex on CABG outcomes are limited. The BARI (Bypass Angioplasty Revascularization Investiga- tion) study compared the outcomes of 1829 patients with multivessel CAD randomly assigned to receive CABG or PCI; 27% were women.1133 Most information on the efficacy of CABG comes from studies done primarily in men, with extrapolation of the results to women. Although long-term outcomes with CABG in women are similar to or even better than those in men, women have higher rates of periprocedural morbidity and mortality.1133 1139 Several hypotheses have been suggested to explain this increased morbidity and mortality, including older age at presentation, more frequent need for urgent revascularization, more comorbid conditions, smaller body surface area and coronary arterial dimensions, and increased risk of bleeding. The fact that women on average are older than men at the time of CABG is thought, at least in part, to be due to the loss of the protective effects of estrogen with menopause.1134,1138,1140 1148 In studies of age-matched men and women undergoing CABG, in-hospital mortality rates were similar, even among the elderly ( 70 years of age).1149,1150 In addition to being older, women undergoing CABG are more likely than men to have ACS and cardiogenic shock1140 and, therefore, to require urgent revascularization.1138,1141 1143,1146,1148 Sex disparity in the diagnosis and treatment of CAD may contribute to the more complex and delayed presentations in women compared with men.1151 In comparison to men, women are less likely to be referred for coronary angiography and revascularization and are more likely to have refractory ischemia and repeated hospitalizations.1152 Compared with men undergoing CABG, women have more comorbid conditions, including diabetes mellitus, hy- pertension, hyperlipidemia, chronic renal insufficiency, chronic obstructive pulmonary disease, and concomitant val- vular disease.1153 In some studies, no significant difference in outcomes between women and men undergoing CABG was noted when the data were adjusted for age and comorbidi- ties,1136 1138,1154 1156 whereas in others, female sex remained an independent predictor of a worse outcome.1141,1157,1158 In a systematic review of sex differences and mortality after CABG, early mortality differences were reduced but not eliminated after adjustment for comorbidities, procedural characteristics, and body habitus.1139 Some investigators have shown that smaller body surface area, a surrogate for coro- nary arterial size, is associated with higher risk of perioper- ative mortality, whereas others have not.1140 Women use more hospital resources in the perioperative period than do men, including intra-aortic balloon counter- pulsation,1137 vasopressors, mechanical ventilation, dialysis, and blood products,1154,1159 all of which are associated with higher mortality rates.1146,1160,1161 Women are more likely to have wound complications and longer ICU and hospital stays.1162 1165 Lastly, the operative procedure itself appears to be different in women than in men, in that women are less likely to be completely revascularized1166,1167 and less likely to have IMA grafting, especially bilateral,1168 although bilat- eral IMA grafting in women is associated with low rates of in-hospital morbidity and mortality.1169 6.3. Patients With Diabetes Mellitus The prevalence of diabetes mellitus in CABG patients has increased markedly over the past 30 years. In the late 1970s, only 10% to 15% of CABG patients had diabetes1170; by 2005, the incidence had risen to 35%.308 Patients with diabetes, especially those who are insulin dependent, have higher rates of perioperative morbidity and mortality and a reduced long-term survival rate than those without diabe- tes.308,1171,1172 In the STS Registry, patients with diabetes on oral therapy had an adjusted OR of 1.15 for death within 30 days of CABG (95% CI: 1.09 to 1.21) as well as a greater likelihood of stroke, renal failure, and deep sternal wound infection than those without diabetes.308 For subjects receiv- ing insulin, the adjusted OR for death within 30 days was 1.50 (95% CI: 1.42 to 1.58), and the risks for other compli- cations were correspondingly higher. The poorer short-term outcome in patients with diabetes is only partly explained by a greater frequency of other comorbid conditions, such as obesity, hypertension, renal insufficiency, PAD, and cerebro- vascular disease. The reduced long-term survival rate after CABG in patients with diabetes is likely due to a combination of more rapid progression of atherosclerosis, a lower long- term patency rate of SVGs,1173 and a greater burden of comorbid conditions. As in patients without diabetes, long- term outcome after CABG is better when an IMA is used as a conduit than when CABG is performed with only SVGs.362 A subgroup analysis of data from the BARI trial suggested that patients with diabetes who underwent CABG with 1 arterial conduit had improved survival compared with those who underwent PCI.516 Several subsequent observational and cohort studies also showed that CABG results in better long-term outcome in patients with diabetes and multivessel CAD compared with balloon angioplasty or BMS implanta- tion.361,451,1174 A meta-analysis of 10 RCTs comparing CABG with balloon angioplasty (n 6) or BMS implantation (n 4) concluded that the mortality rate was substantially lower in patients with diabetes undergoing CABG.451 Little information is available about CABG versus PCI with DES in patients with diabetes mellitus. The results of CARDia (Coronary Artery Revascularisation in Diabetes), the first RCT comparing CABG and PCI in a population consisting entirely of subjects with diabetes, suggested that PCI with DES (used in 69% of the PCI patients) and CABG achieved similar outcomes.475 Of the 1,800 subjects enrolled in the SYNTAX trial, which compared CABG and PCI with paclitaxel-eluting stents, 452 had medically treated diabe- tes.364 At 1-year follow-up, the 2 treatments exerted a similar effect on survival, MI, and the composite endpoint of death, MI, or stroke. As in the entire SYNTAX cohort, patients with diabetes randomly assigned to receive PCI had a higher rate of repeat revascularization (20.3% after PCI versus 6.4% after CABG; P 0.001), and those with highly complex lesions (ie, SYNTAX score 33) had a higher mortality rate with PCI (13.5% versus 4.1%; P 0.04). The FREEDOM (Future Revascularization Evaluation in patients with Diabe- tes mellitus: Optimal management of Multivessel disease) trial, an ongoing randomized comparison of CABG and PCI with DES in 1900 patients with diabetes and multivessel CAD, should shed further light on the preferred therapy for Few comparisons of CABG and contemporary medical therapy in patients with diabetes mellitus are of sufficient size to allow meaningful conclusions. The largest such trial, BARI 2D, randomly assigned 2368 patients with type 2 diabetes mellitus to revascularization plus intensive medical therapy or intensive medical therapy alone,404,1176 with patients in the medical therapy group to undergo revascularization during follow-up only if such therapy were clinically indicated by the progression of angina or the development of an ACS or severe ischemia. The planned method of revascularization, PCI or CABG, was determined before randomization by the treating physicians. No significant difference in primary endpoints was evident between the PCI group and the medical therapy group. No difference in survival rate between those undergoing CABG and those receiving only medical therapy was noted. Acute MI occurred less often in those assigned to CABG plus intensive medical therapy than in those given intensive medical therapy alone (10% versus Hillis et al 2011 ACCF/AHA CABG Guideline e695 17.6%; P 0.003), and the composite endpoints of death or MI (21.1% versus 29.2%; P 0.01) and cardiac death or MI also occurred less often.1176 Compared to those selected for PCI, the CABG patients had more 3-vessel CAD (52% versus 20%), more totally occluded arteries (61% versus 32%), more proximal LAD artery stenoses 50% (19% versus 10%), and a higher myocardial jeopardy score. Elevated fasting blood glucose concentrations before CABG and persistently elevated glucose concentrations af- terward are associated with increased risk of morbidity and mortality.592,1177,1178 The complications most closely linked to postoperative hyperglycemia are infections, including deep sternal wound infection and mediastinitis. Achieving glyce- mic control perioperatively in patients with diabetes de- creases this risk.581,593 Because the risk of deep sternal wound infection in patients with diabetes is increased when both IMAs are harvested and used, bilateral IMA grafting is not recommended in this patient cohort unless the overall benefit to the patient outweighs this increased risk.957 6.4. Anomalous Coronary Arteries: Recommendations Class I 1. Coronary revascularization should be performed in patients with: a. A left main coronary artery that arises anoma- lously and then courses between the aorta and pulmonary artery.1179 1181 (Level of Evidence: B) b. A right coronary artery that arises anomalously and then courses between the aorta and pulmo- nary artery with evidence of myocardial ische- mia.1179 1182 (Level of Evidence: B) Class IIb 1. Coronary revascularization may be reasonable in patients with a LAD coronary artery that arises anomalously and then courses between the aorta and pulmonary artery. (Level of Evidence: C) Several variations and anatomic courses of anomalous coro- nary arteries have been described, some benign and others associated with sudden cardiac death. The most life- threatening variants involve anomalous origin of the left main coronary artery from the right sinus of Valsalva or of the right coronary artery from the left sinus of Valsalva, after which the anomalous artery travels to its normal area of perfusion between the ascending aorta and the main pulmonary artery. In a review of consecutive echocardiograms in 2388 asymp- tomatic children and young adolescents, the incidence of anomalous coronary arteries arising from the opposite sinus of Valsalva was 0.17%.1183 Anomalous coronary arteries (particularly those traversing between the aorta and the main pulmonary artery) are associated with exercise-related sudden death in young ( 35 years of age) athletes.1184 1190 A consecutive series of 27 young athletes with sudden death who were found to have such anomalous coronary arteries at autopsy had inducible myocardial ischemia and complained of cardiac symptoms before their demise.1179 Isolated case reports of other coronary arterial anomalies in subjects with syncope or sudden death emphasize the need for careful anatomic and functional evaluation of all individuals with anomalous coronary arteries.1191 1194 The method of revascu- larization employed in adults with anomalous coronary arter- ies has been 1) CABG or, more recently, 2) PCI with stenting.1195 When CABG is employed, consideration should be given to the presence of competitive flow in the native coronary circulation.1196 In children and some adults, an unroofing procedure or coronary arterial reimplantation may provide the best long term results.1197,1198 The risk associated with these coronary anomalies if they are left untreated and the existing operative experience make corrective surgery reasonable in these individuals.1180 6.5. Patients With Chronic Obstructive Pulmonary Disease/Respiratory Insufficiency: Recommendations Class IIa 1. Preoperative intensive inspiratory muscle training is reasonable to reduce the incidence of pulmonary complications in patients at high risk for respiratory complications after CABG.1199 (Level of Evidence: B) Class IIb 1. After CABG, noninvasive positive pressure ventila- tion may be reasonable to improve pulmonary me- chanics and to reduce the need for reintuba- tion.1200,1201 (Level of Evidence: B) 2. High thoracic epidural analgesia may be considered to improve lung function after CABG.37,1202 (Level of Evidence: B) See Online Data Supplement 43 for additional data on patients with chronic obstructive pulmonary disease/respira- tory insufficiency. In the STS Adult Cardiac Database predictive algorithms, the presence of chronic obstructive pulmonary disease pre- operatively was an independent predictor of mortality, the need for prolonged postoperative ventilator support, and renal failure.1203 Furthermore, most rehospitalizations following CABG are related to pulmonary dysfunction and/or infection or volume overload. The incidence of complications increases with patient age and the severity of chronic obstructive pulmonary disease, as measured with pulmonary function testing.1204,1205 None of these studies, however, address the relative risks and benefits of CABG in subjects with chronic obstructive pulmonary disease, thereby precluding a specific recommendation regarding the performance of CABG in these patients. In preparation for CABG, optimizing pulmo- nary function is imperative.1206 An RCT of 279 patients1199 showed that preoperative respiratory muscle training reduced postoperative pulmonary complications (including pneumo- nia) and length of stay in patients at high risk for such complications after CABG. Such muscle training is indicated in all patients before CABG, especially those with impaired baseline pulmonary function. Two prospective RCTs have shown that prophylactic nasal continuous positive airway pressure after CABG improves pulmonary function and offers protection from postoperative pulmonary complications.1200,1201 However, the applicability of these results to patients with impaired pulmonary function is uncertain, because those with severe underlying lung disease and other comorbid conditions were not enrolled. Although noninvasive positive pressure ventilation may be useful in subjects with borderline pulmonary function postoperatively, its overuse should be avoided, because it may cause gastric distention, thereby increasing the risk of vomiting and aspiration. Improved lung function has been achieved with the use of high thoracic epidural anesthesia in patients undergoing CABG,36,37 but its application has been limited by con- cerns about paraspinal and epidural hemorrhage related to epidural catheter insertion. Despite some evidence that oral corticosteroids improve pulmonary function after cardiac surgery,1207,1208 their use has not been adopted widely in subjects undergoing CABG. Finally, a consistent reduction in postoperative pulmonary complications has not been shown when off-pump (as op- posed to on-pump) CABG is performed.1209 6.6. Patients With End-Stage Renal Disease on Dialysis: Recommendations Class IIb 1. CABG to improve survival rate may be reasonable in patients with end-stage renal disease undergoing CABG for left main coronary artery stenosis of greater than or equal to 50%.479 (Level of Evidence: C) 2. CABG to improve survival rate or to relieve angina despite GDMT may be reasonable for patients with end-stage renal disease with signifi- cant stenoses (>70%) in 3 major vessels or in the proximal LAD artery plus 1 other major vessel, regardless of LV systolic function.1210 (Level of Evidence: B) Class III: HARM 1. CABG should not be performed in patients with end-stage renal disease whose life expectancy is limited by noncardiac issues. (Level of Evidence: C) Rates of cardiovascular morbidity and mortality are in- creased in patients with CKD compared with age-matched controls without CKD, and the magnitude of the increase is directly related to the severity of CKD. About half of those on maintenance dialysis die from a cardiovascular cause.476 At present, the prevalence of CKD in the general population of the United States is estimated to be 13%, with approximately 5.8% of these having Stage III V disease (ie, glomerular filtration rate 60 mL/min/1.73 To date, randomized comparisons of CABG and medical therapy in patients with CKD (irrespective of its severity) have not been reported. Observational studies have demonstrated an improved survival rate with CABG (compared with medical therapy) in patients with CKD and multivessel CAD.57,479 At the same time, these observational studies as well as other registries have demonstrated a markedly reduced long-term survival rate in patients with CKD undergoing CABG compared with non- dialysis CABG patients,1213 1216 with the magnitude of the decrease directly related to the severity of CKD. In these reports, subjects with CKD undergoing CABG had an increased inci- dence of periprocedural complications, including mediastinitis, need for blood transfusion, prolonged ventilation, reoperation, stroke, and increased length of hospital stay.1210 6.7. Patients With Concomitant Valvular Disease: Recommendations Class I 1. Patients undergoing CABG who have at least mod- erate aortic stenosis should have concomitant aortic valve replacement.1217 1220 (Level of Evidence: B) 2. Patients undergoing CABG who have severe ische- mic mitral valve regurgitation not likely to resolve with revascularization should have concomitant mi- tral valve repair or replacement at the time of CABG.1221 1226 (Level of Evidence: B) Class IIa 1. In patients undergoing CABG who have moderate ischemic mitral valve regurgitation not likely to resolve with revascularization, concomitant mitral valve repair or replacement at the time of CABG is reasonable.1221 1226 (Level of Evidence: B) Class IIb 1. Patients undergoing CABG who have mild aortic stenosis may be considered for concomitant aortic valve replacement when evidence (eg, moderate severe leaflet calcification) suggests that progression of the aortic stenosis may be rapid and the risk of the combined procedure is acceptable. (Level of Evi- dence: C) 6.8. Patients With Previous Cardiac Surgery: Recommendation Class IIa 1. In patients with a patent LIMA to the LAD artery and ischemia in the distribution of the right or left circumflex coronary arteries, it is reasonable to recommend reoperative CABG to treat angina if GDMT has failed and the coronary stenoses are not amenable to PCI.380,1227 (Level of Evidence: B) 6.8.1. Indications for Repeat CABG RCTs comparing medical therapy to CABG in subjects with SIHD demonstrated that those with specific angiographic findings, such as left main disease, 3-vessel disease, and 2-vessel disease that includes the proximal LAD artery, derive a survival benefit from CABG.318 At the same time, it is unknown if CABG provides a survival benefit compared with medical therapy in patients with these anatomic findings who have had previous CABG. It is logical to assume that subjects with previous CABG and these anatomic findings would, in fact, derive a survival benefit from repeat CABG provided that CABG could be performed with an acceptable risk. The importance of recurrent MI in the distribution of the Hillis et al 2011 ACCF/AHA CABG Guideline e697 LAD artery has been shown to be associated with a poor prognosis in patients with previous CABG. The long-term outcomes of 723 patients with diseased SVGs who did not undergo reoperation or PCI within 1 year of angiography were reviewed.1228 A stenosis of a graft to the LAD artery was associated with decreased rates of survival, reoperation- free survival, and event-free survival. On the basis of these data, these authors suggest that a 50% stenosis in a graft to the LAD artery is an indication for reoperation. In contrast, patients without ischemia in the LAD artery distribution do not derive a survival benefit from repeat CABG. In an observational study from the Cleveland Clinic, the survival rate of 4640 patients with patent LIMA grafts to the LAD artery and ischemia in the distribution of the right and/or left circumflex arteries who were treated with repeat CABG, PCI, or medical therapy was examined.380 No improvement in survival was observed in either revascularization group com- pared with those treated medically. 6.8.2. Operative Risk Because of the technical difficulty of repeat CABG and the high risk profiles of these patients, reoperative CABG is associated with higher rates of morbidity and mortality than is primary CABG.945,1229 1235 With advances in surgical tech- niques, some groups have reported a decline in mortality rate for patients undergoing repeat CABG.1233,1236 An observa- tional study suggested that the higher operative risk with reoperation is related to the higher patient risk profiles and not to the technical challenges of the operation itself, thereby suggesting that improvements in surgical techniques have neutralized the risk associated with the complexity of repeat CABG,1233 but others continue to suggest that technical issues are still important in causing the higher mortality rate in these individuals. 6.8.3. Long-Term Outcomes The survival rate after repeat CABG is lower than that after primary CABG. A multicenter study from Australia reported 1, 3, 5, and 6 year survival rates in reoperative CABG patients of results that were significantly lower than those observed after primary CABG. However, after adjusting for differences in risk profiles between primary and reoperative CABG patients, no difference in long-term survival rate was apparent. The variables associated with decreased late survival rate included advanced age, hypertension, elevated serum cholesterol, diabetes mellitus, PAD, renal failure, left main CAD, LV systolic dysfunction, and Compared with primary CABG, repeat CABG is less successful at relieving angina,1237,1238 although a 2004 quality-of-life analysis reported that repeat CABG was as effective as primary CABG in relieving angina and improv- ing functional capacity and quality of life.1239 6.9. Patients With Previous Stroke Patients with a previous stroke or TIA are at higher risk for a perioperative stroke during CABG than those without such a history. A meta-analysis of the data from several studies observed a perioperative stroke risk of 8.5% in patients with previous stroke (compared with 2.2% in those without a previous neurological event) (P 0.0001).860 When subjects with a history of stroke or TIA were analyzed separately (ie, stroke only or TIA only), the increased perioperative risk in comparison with neurologically asymptomatic patients was present in both groups. In a multivariate logistic regression analysis of 16 194 cardiac surgery patients, a history of cerebrovascular disease was identified as an independent predictor of perioperative stroke.1240 The STS National Car- diac Surgery Database demonstrated an increased risk of perioperative death, perioperative stroke, and prolonged length of stay in patients with a history of stroke who underwent isolated CABG from 2002 to 2006.308 6.10. Patients With PAD CAD and PAD, generally defined as atherosclerotic disease of the aorta, its visceral arterial branches (renal and mesen- teric), and the arteries of the lower extremities, often coexist. The presence of PAD is an independent predictor of early1241 and late death in CABG patients. In the STS National Cardiac Surgery Database, 774 881 patients underwent isolated CABG over a 5-year period, of whom 15.5% had PAD. The presence of PAD was an independent risk factor for in- hospital death or death within 30 days of CABG. In addition, PAD was an independent risk factor for perioperative stroke and subsequent need for post-CABG limb revascularization or amputation. Potential but unproven explanations for the adverse effects of PAD on long-term survival after CABG include: 1) The presence of PAD may lead to vascular events (ie, cerebrovascular events) that adversely affect post-CABG survival; 2) PAD may be a marker for more severe CAD, which may lead to an increased rate of post-CABG death from cardiac causes despite revascularization; and 3) PAD may contribute to noncardiovascular death in the long term. Revascularization of PAD before CABG is not known to improve post-CABG outcomes. 7. Economic Issues 7.1. Cost-Effectiveness of CABG and PCI In the United States, it is estimated that the annual hospital costs of CABG are approximately $10 billion.1242 Despite the increasing risk profile of CABG candidates, it nonetheless is becoming more cost-effective. Hospital charges from the Nationwide Inpatient Sample of nearly 5.5 million patients who had isolated CABG in the United States from 1988 to 2005 were examined.1243 A decrease in risk-adjusted mortal- ity rate, from 6.2% to 2.1% (P 0.0001), was noted. When hospital costs were corrected for inflation, they declined from $26 210 in 1988 to $19 196 in 2005 ($1988) (P 0.0001). Several factors tend to increase the cost of CABG, includ- ing advanced patient age, female sex, African-American ethnicity, postoperative complications, longer hospital stay, and multiple comorbidities, particularly CKD.1244 1247 The National Health Service Foundation Trust in Britain found that patients 75 years of age undergoing CABG had higher rates of postoperative complications and greater resource utilization than their younger counterparts.1244 Similarly, the Maryland Health Services Cost Review Commission reported an increased total cost and length of hospital stay with increasing age in patients undergoing CABG.1245 The same phenomenon was not present with PCI until the patients were 80 years old. In an examination of data from 12 016 subjects undergoing CABG in New York State in 2003, it was determined that older age, female sex, and African-American ethnicity were associated with higher costs.1247 Clinical char- acteristics, such as a lower LVEF, number of diseased vessels, previous open-heart operations, and numerous co- morbidities, further increased costs. Larger hospitals were associated with higher CABG discharge costs, whereas costs significantly decreased with higher CABG volumes. Not surprisingly, perioperative complications lead to in- creased costs. An examination of the Medicare Provider Analysis and Review file of data from 114 223 Medicare beneficiaries who survived CABG in 2005 showed the mean cost of hospitalization associated with CABG to be $32 201 $23 059 for a mean length of stay of 9.9 7.8 days. Those with complications (13.6% of patients) consumed significantly more hospital resources (incremental cost, $15 468) and had a longer length of stay (average additional Evidence for the role of off-pump versus on-pump CABG in decreasing costs is conflicting. In a randomized study comparing off-pump and on-pump CABG, the mean total hospitalization cost per patient was $2272 less for off-pump CABG at hospital discharge and $1955 less at 1 year.1248 Another study of 6665 patients who underwent CABG between 1999 and 2005 determined that off-pump CABG provided a small short-term gain,1249 although off-pump patients had increased long-term risks of repeat revascular- ization and major vascular events, especially if they were considered to be high risk. In the long run, in fact, off-pump patients utilized more resources. 7.1.1. Cost-Effectiveness of CABG Versus PCI Medical costs and quality of life were examined 10 to 12 years after patients were randomly assigned to receive angio- plasty or CABG in the BARI trial.1250 Although CABG costs initially were 53% higher, the gap closed to 5% by the end of 2 years. After 12 years, the average cost was $123 000 in CABG patients and $120 000 for PCI patients. Cumulative costs were significantly higher among patients with diabetes mellitus, heart failure, and comorbid conditions, and they were higher in women. CABG was deemed to be as cost- effective as PCI in patients with multivessel CAD. The cost of coronary artery revascularization in 6218 patients with and without CKD whose data were available in the Duke database was examined.1251 CABG was an economically attrac- tive alternative to PCI or medical therapy for all patients with left main or 3-vessel CAD without concomitant CKD as well as those with 2-vessel CAD with concomitant CKD. For subjects with 3-vessel CAD and concomitant CKD, 2-vessel CAD without CKD, and 1-vessel CAD regardless of renal function, medical therapy was an economically attractive strategy com- pared with CABG or PCI. This analysis concluded that CABG is most economically attractive compared with PCI and medical therapy in patients to whom it confers the greatest survival advantage and for whom the cost of alternative treatments is greatest (ie, those with the most severe CAD). Although CABG was more expensive than medical therapy for all patients, the survival benefits associated with it were of such magnitude in some subjects that it was economically attractive. The cost-effectiveness of CABG and PCI in high-risk patients was analyzed in the AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) study,446 in which costs were assessed at 3 and 5 years. After 3 years, the average total cost was $63 896 for PCI and $84 364 for CABG, a difference of $20 468. After 5 years, the average total cost was $81 790 for PCI and $100 522 for CABG, a difference of $18 732. The authors concluded that PCI was less costly and at least as effective for urgent revasculariza- tion in high-risk patients with medically refractory angina. 7.1.2. CABG Versus PCI With DES The use of DES for PCI will require a reassessment of cost- effectiveness. Although the initial procedure is considerably more expensive than the use of balloon angioplasty or BMS, equaling the cost of CABG in many patients with multivessel CAD, the cost of reintervention for restenosis may be reduced. The cost-effectiveness will depend on the pricing of stents, utilization rates of the more expensive stents, and efficacy. In a 2010 study from Japan comparing the total costs at 2 years of CABG and DES implantation in patients with left main CAD, the total costs were significantly lower for those undergoing CABG than for those receiving a DES.1252 8. Future Research Directions With improvements in percutaneous techniques and medical therapy, on-pump CABG and off-pump CABG will increas- ingly be reserved for patients with extensive CAD, many of whom have had previous PCI. The future of CABG will be directed at improving its results in high-risk patients and making CABG less invasive for elective revascularization. Minimally invasive techniques, with the use of robotics and anastomotic connectors, intraoperative imaging, hybrid pro- cedures, and protein and gene therapy, appear promising. Robotic technology in minimally invasive CABG leads to less traumatic harvesting of the LIMA for minimally invasive direct coronary artery bypass procedures compared with nonrobotic techniques.1253 The ultimate goal of robotic CABG is totally endoscopic CABG, but its use has been limited, at least partly because of a substantial learning curve, cost considerations, and few data demonstrating noninferior graft patency and outcomes compared with standard CABG. Anastomotic connectors may enable more routine applica- tion of totally endoscopic anastomoses in subjects undergoing minimally invasive CABG. Because hand-sewn anastomoses are technically challenging when performed endoscopically, consideration has been given to the concept of anatomic connectors to facilitate more reproducible and less technically demanding procedures and ultimately to allow widespread use. Both proximal and distal connectors may be used. Several options are being developed, some only available outside the United States, and the evidence base supporting their use is evolving.1254 The PAS-Port proximal device has been associated with acceptable outcomes. In two prospective studies, its angiographic graft patency 9 months after CABG was similar to that of hand-sewn anastomoses.1255,1256 With this device, the proximal anastomoses must be constructed Hillis et al 2011 ACCF/AHA CABG Guideline e699 before the distal ones. At present, only 1 distal device, the Cardica C-Port, has been approved for use in the United States. The prospective studies1257,1258 demonstrated a 6-month overall patency of 96% in 102 subjects. These devices increase the cost of the operation. Over the past 20 years, the patency rate of all graft types has improved gradually, so that the present failure rate of LIMA grafts at 1 year is about 8% and of SVGs roughly 20%.1259 Many patients being referred for CABG nowadays have far advanced CAD, which is often diffuse and exhibits poor vessel runoff. Technical issues at the time of surgery may influence graft patency, and intraoperative imaging may help to delineate technical from nontechnical issues. Because coronary angiography is rarely available intraoperatively, other techniques have been developed to assess graft integrity at this time, most often the transit-time flow and intraopera- tive fluorescence imaging. The transit-time flow is a quanti- tative volume-flow technique that cannot define the severity of graft stenosis or discriminate between the influence of the graft conduit and the coronary arteriolar bed on the mean graft flow. Intraoperative fluorescence imaging, which is based on the fluorescent properties of indocyanine green, provides a semiquantitative assessment of graft patency with images that provide some details about the quality of coronary anastomoses.1260 Although both methods are valu- able in assessing graft patency, neither is sufficiently sensi- tive or specific to allow identification of more subtle abnor- malities.1260 It is hoped that such imaging may help to reduce the occurrence of technical errors. The hybrid suite can be used as an operating room and a catheterization laboratory. It allows the performance of an angiogram after CABG so that one can identify abnormal grafts, providing the opportunity to revise them (with PCI or surgery) before leaving the operating room. Until completion angiography becomes more routine (in a hybrid suite), cardiac surgeons must rely on reasonably accurate, albeit imperfect, methods to identify problems with a recently implanted graft. 8.1. Hybrid CABG/PCI Advances in surgical techniques and the introduction of DES have provided a platform for a hybrid revascularization strategy that combines grafting the LAD artery with the LIMA and stenting the non-LAD arteries with DES (instead of bypassing them with SVGs). Although preliminary data1261 have indicated that a hybrid strategy may be a reasonable alternative in some patients with multivessel CAD, its real effect will not be known until results of RCTs are avail- able.1261 The primary purpose of performing hybrid CABG is to decrease the morbidity rate of traditional CABG in high-risk patients. Although hybrid revascularization is most often performed in a staged fashion, a simultaneous hybrid procedure can be performed in a hybrid suite, offering several potential advantages, including improving the efficiency and cost-effectiveness of therapy as well as condensing therapy into 1 patient encounter. If a staged approach is chosen, minimally invasive CABG performed first, followed days later by PCI, is probably preferable, so as to enable surgery without the unwanted effects of antiplatelet therapy as well as to enable complete angiography of the LIMA graft at the time of PCI. The major disadvantage of this approach is that if complications occur with PCI, a third procedure may be necessary. Even with a hybrid suite, one of the most substan- tive barriers to simultaneous minimally invasive CABG and PCI is the management of antiplatelet therapy. The role of hybrid CABG PCI compared with sole PCI and sole conven- tional CABG awaits the results of the ongoing observational study of hybrid coronary revascularization by the National Heart, Lung, and Blood Institute. 8.2. Protein and Gene Therapy Several proteins, such as vascular endothelial growth factor, acidic fibroblast growth factor, and basic fibroblast growth factor, induce angiogenesis1262; as a result, interest has grown in using these substances to stimulate myocardial perfusion. One RCT found that patients who were given 100 mcg of basic fibroblast growth factor became angina free, and nu- clear perfusion testing appeared to show improved perfu- sion.1262 Another RCT has suggested that the intracoronary injection of high-dose angiogenic molecules yields improve- ment in symptoms, exercise time, functional capacity, and myocardial perfusion.1263 Alternatively, gene therapy may be used to induce angiogenesis, but conceptual concerns with intravascular gene therapy, such as peripheral uptake into nontarget tissues and subsequent unintended effects, have been raised. 8.3. Teaching CABG to the Next Generation: Use of Surgical Simulators Over the past decade, pressure on hospitals and physicians to ensure high quality and safety has increased. Public reporting of outcomes, common in many states, has been endorsed by the STS. 