Some surgeons and patients wish to avoid the potential morbidity and cosmetic results of a median sternot- omy, yet the least invasive incisions usually are too small to allow hand-sewn anastomoses. To solve this problem, coro- nary connector devices have been developed for use with arterial or venous conduits to enable grafting without direct suturing. In addition, these devices have been used in subjects with diseased ascending aortas, in whom a technique that allows construction of a proximal anastomosis with minimal manipulation of the ascending aorta (typically by eliminating the need for aortic cross-clamping) may result in less embo- lization of debris, thereby reducing the occurrence of adverse neurological outcomes. In this situation, the operation is performed through a median sternotomy, and the proximal anastomoses are created with a connector (or may be hand- sewn with the assistance of a device that provides a bloodless operative field) without partial or complete clamping of the ascending aorta. 2.1.7. Intraoperative TEE: Recommendations Class I 1. Intraoperative TEE should be performed for evalu- ation of acute, persistent, and life-threatening hemo- dynamic disturbances that have not responded to treatment.137,138 (Level of Evidence: B) 2. Intraoperative TEE should be performed in patients undergoing concomitant valvular surgery.137,139 (Level of Evidence: B) Class IIa 1. Intraoperative TEE is reasonable for monitoring of hemodynamic status, ventricular function, regional wall motion, and valvular function in patients un- dergoing CABG.138,140 145 (Level of Evidence: B) The use of intraoperative TEE in patients undergoing cardiac surgery has increased steadily since its introduction in the late 1980s. Although its utility is considered to be highest in patients undergoing valvular and complex open great-vessel/ aortic surgery, it is commonly used in subjects undergoing CABG. TEE is most often used,146 although epicardial and epiaortic imaging, performed under aseptic conditions, allows visualization of imaging planes not possible with TEE.147,148 specifically, epiaortic imaging allows visualization of the blind spot of the ascending aorta (caused by interposition of the trachea with the esophagus), the site of aortic cannulation for CPB, from which dislodgement of friable atheroma, a major risk factor for perioperative stroke, may occur (Section 5.2.1). In addition, epicardial probes allow imaging when TEE is contraindicated, cannot be performed, or produces inadequate images. It can facilitate the identification of intraventricular thrombi when TEE images are equivocal. The 2003 ACC/AHA/ASE Guideline Update for the Clinical Application of Echocardiography based its recom- mendations on those reported in the 1996 American Society of Anesthesiologists/Society of Cardiovascular Anesthesiol- ogists practice guideline and considered the use of TEE in CABG patients.149 The latter document was updated in 2010.139 Because of the use of different grading methodolo- gies in the American Society of Anesthesiologists/Society of Cardiovascular Anesthesiologists guideline relative to that of the ACCF/AHA, precise comparisons are difficult. However, it is noted that TEE should be considered in subjects undergoing CABG, to confirm and refine the preoperative diagnosis, detect new or unsuspected pathology, adjust the anesthetic and surgical plan accordingly, and assess the results of surgery. The strongest recommendation is given for treatment of acute life-threatening hemodynamic instability that has not responded to conventional therapies. Observational cohort analyses and case reports have sug- gested the utility of TEE for diagnosing acute life-threatening hemodynamic or surgical problems in CABG patients, many of which are difficult or impossible to detect or treat without direct imaging. Evaluation of ventricular cross-sectional areas and ejection fraction (EF) and estimation or direct measure- ment of cardiac output by TEE may facilitate anesthetic, fluid, and inotropic/pressor management. The utility of echo- cardiography for the evaluation of LV end-diastolic area/ volume and its potential superiority over pulmonary artery occlusion or pulmonary artery diastolic pressure, particularly in the early postoperative period, has been reported150,151 (Section 4.10). In subjects without preoperative transthoracic imaging, intraoperative TEE may provide useful diagnostic information (over and above that detected during cardiac catheterization) on valvular function as well as evidence of pulmonary hypertension, intracardiac shunts, or other com- plications that may alter the planned surgery. In patients undergoing CABG, intraoperative TEE is used most often for the detection of regional wall motion abnor- malities (possibly caused by myocardial ischemia or infarc- tion) and their effect on LV function. Observational studies have suggested that regional wall motion abnormalities de- tected with TEE can guide surgical therapy, leading to revision of a failed or inadequate conduit or the placement of additional grafts not originally planned. The presence of new wall motion abnormalities after CPB correlates with adverse perioperative and long-term outcomes.143 Although the initial hope that an estimation of coronary blood flow with intramyocardial contrast enhancement visu- alized by TEE would facilitate surgical intervention has not been realized, technical advances in imaging of coronary arteries and grafts may ultimately provide reliable informa- tion. At present, the evaluation of graft flow with conven- tional nonimaging handheld Doppler probes appears adequate (Section 8). Intraoperative evaluation of mitral regurgitation may facilitate detection of myocardial ischemia and provide guidance about the need for mitral valve annuloplasty (Sec- tion 6.7). Newer technologies, including nonimaging methods for analyzing systolic and diastolic velocity and direction and timing of regional wall motion (Doppler tissue imaging and speckle tracking), as well as real-time 3-dimensional im- aging, may facilitate the diagnosis of myocardial ischemia and evaluation of ventricular function. At present, however, their cost-effectiveness has not been determined, and they are too complex for routine use.152 154 Among different centers, the rate of intraoperative TEE use in CABG patients varies from none to routine; its use is influenced by many factors, such as institutional and practi- tioner preferences, the healthcare system and reimbursement strategies, tertiary care status, and presence of training pro- grams.155 The efficacy of intraoperative TEE is likely influ- enced by the presence of 1) LV systolic and diastolic dysfunction, 2) concomitant valvular disease, 3) the planned surgical procedure (on pump versus off pump, primary versus reoperative), 4) the surgical approach (full sternotomy versus partial sternotomy versus endoscopic or robotic), 5) its acuity (elective versus emergency); and 6) physician training and The safety of intraoperative TEE in patients undergoing cardiac surgery is uncertain. Retrospective analyses of data from patients undergoing diagnostic upper gastrointestinal endoscopy, nonoperative diagnostic TEE imaging, and intra- operative imaging by skilled operators in high-volume cen- ters demonstrate a low frequency of complications related to insertion or manipulation of the probe.164,165 Nevertheless, minor (primarily pharyngeal injury from probe insertion) and major (esophageal perforation, gastric bleeding, or late me- diastinitis) complications are reported.166,167 A more indolent complication is that of acquired dysphagia and possible aspiration postoperatively. Although retrospective analyses of postoperative cardiac surgical patients with clinically mani- fest esophageal dysfunction have identified TEE use as a risk factor,168 170 such dysfunction also has been reported in subjects in whom TEE was not used.171 Advanced age, prolonged intubation, and neurological injury seem to be risk factors for its development. The significance of the incidental intraoperative detection and repair of a patent foramen ovale, a common occurrence, is controversial.172 A 2009 observa- tional analysis of 13 092 patients (25% isolated CABG; 29% CABG or other cardiac procedure), of whom 17% had a patent foramen ovale detected by TEE (28% of which were repaired), reported an increase in postoperative stroke in the patients who had patent foramen ovale repair (OR: 2.47; 95% CI: 1.02 to 6.0) with no improvement in long-term 2.1.8. Preconditioning/Management of Myocardial Ischemia: Recommendations Class I 1. Management targeted at optimizing the determinants of coronary arterial perfusion (eg, heart rate, diastolic or mean arterial pressure, and right ventricular or LV end-diastolic pressure) is recommended to reduce the risk of perioperative myocardial ischemia and infarc- tion.53,174 177 (Level of Evidence: B) Class IIa 1. Volatile-based anesthesia can be useful in reducing the risk of perioperative myocardial ischemia and infarction.178 181 (Level of Evidence: A) Class IIb 1. The effectiveness of prophylactic pharmacological therapies or controlled reperfusion strategies aimed at inducing preconditioning or attenuating the ad- verse consequences of myocardial reperfusion injury or surgically induced systemic inflammation is un- certain.182 189 (Level of Evidence: A) 2. Mechanical preconditioning might be considered to reduce the risk of perioperative myocardial ischemia and infarction in patients undergoing off-pump CABG.190 192 (Level of Evidence: B) 3. Remote ischemic preconditioning strategies using pe- ripheral-extremity occlusion/reperfusion might be con- sidered to attenuate the adverse consequences of myo- cardial reperfusion injury.193 195 (Level of Evidence: B) 4. The effectiveness of postconditioning strategies to at- tenuate the adverse consequences of myocardial reper- fusion injury is uncertain.196,197 (Level of Evidence: C) See Online Data Supplements 2 to 4 for additional data on preconditioning. Hillis et al 2011 ACCF/AHA CABG Guideline e663 Perioperative myocardial injury is associated with adverse outcomes after CABG,198 200 and available data suggest a direct correlation between the amount of myonecrosis and the likelihood of an adverse outcome198,201 204 (Section 5.2.4). The etiologies of perioperative myocardial ischemia and infarction and their complications (electrical or mechanical) range from alterations in the determinants of global or regional myocardial oxygen supply and demand to complex biochemical and microanatomic, systemic, or vascular abnor- malities, many of which are not amenable to routine diagnos- tic and therapeutic interventions. Adequate surgical reperfu- sion is important in determining outcome, even though it may initially induce reperfusion injury. Various studies delineat- ing the major mediators of reperfusion injury have focused attention on the mitochondrial permeability transition pore, the opening of which during reperfusion uncouples oxidative phosphorylation, ultimately leading to cell death.205 Although several pharmacological interventions targeting components of reperfusion injury have been tried, none has been found to be efficacious for this purpose.182,184 189,205 207 The severity of reperfusion injury is influenced by numer- ous factors, including 1) the status of the patient s coronary circulation, 2) the presence of active ongoing ischemia or infarction, 3) preexisting medical therapy (Sections 4.3 and 4.5), 4) concurrent use of mechanical assistance to improve coronary perfusion (ie, intra-aortic balloon counterpulsation), and 5) the surgical approach used (on pump or off pump). CPB with ischemic arrest is known to induce the release of cytokines and chemokines involved in cellular homeostasis, thrombosis, and coagulation; oxidative stress; adhesion of blood cell elements to the endothelium; and neuroendocrine stress responses; all of these may contribute to myocardial injury.208,209 Controlled reperfusion strategies during CPB, involving prolonged reperfusion with warm-blood cardiople- gia in conjunction with metabolic enhancers, are rarely used in lieu of more routine methods of preservation (eg, asystolic arrest, anterograde or retrograde blood cardioplegia during aortic cross-clamping). Several studies suggest that the mag- nitude of SIRS is greater with on-pump CABG than with Initial studies of preconditioning used mechanical occlusion of arterial inflow followed by reperfusion via aortic cross- clamping immediately on institution of bypass or with coronary artery occlusion proximal to the planned distal anastomosis during off-pump CABG.190,191,214 217 Because of concerns of the potential adverse cerebral effects of aortic manipulation, enthu- siasm for further study of this technique in on-pump CABG patients is limited (Section 5.2.1). Despite intense interest in the physiology of postconditioning, few data are available.197 A small 2008 study in patients undergoing valve surgery, which used repeated manipulation of the ascending aorta, reported a reduction in surrogate markers of inflammation and myo- necrosis.196 In lieu of techniques utilizing mechanical occlusion, pharmacological conditioning agents are likely to be used. An alternative approach that avoids much (but not all) of the safety concerns related to potential vascular injury is remote precondi- tioning of arterial inflow to the leg or (more commonly) the arm via blood pressure cuff occlusion.218 Two studies of patients undergoing on-pump CABG at a single center, the first of which used 2 different myocardial protection strategies and the second of which repeated the study with a standardized cold-blood cardioplegia routine, reported similar amounts of troponin re- lease during the 72 hours postoperatively, with no apparent complications.193,195 A larger trial was unable to confirm any benefits of a similar protocol, casting doubt on the utility of this Volatile halogenated anesthetics and opioids have anti- ischemic or conditioning properties,32,33,219,220 and propofol has antioxidant properties of potential value in subjects with reperfusion injury.221,222 The salutary properties of volatile anesthetics during myocardial ischemia are well known. Their negative inotropic and chronotropic effects are consid- ered to be beneficial, particularly in the setting of elevated adrenergic tone that is common with surgical stimulation. Although contemporary volatile agents demonstrate some degree of coronary arterial vasodilation (with isoflurane considered the most potent), the role of a steal phenomena in the genesis of ischemia is considered to be trivial.33 In comparison to propofol/opioid infusions, volatile agents seem to reduce troponin release, preserve myocardial function, and improve resource utilization (ie, ICU or hospital lengths of stay) and 1-year outcome.223 227 It is postulated that multiple factors that influence myocardial preservation modulate the potential impact of a specific anesthetic regimen. Observational analyses have reported an association be- tween elevated perioperative heart rates and adverse out- comes,228,229 but it is difficult to recommend a specific heart rate for all CABG patients. Instead, the heart rate may need to be adjusted up or down to maintain an adequate cardiac output.230,231 Similarly, controversy exists about management of blood pressure in the perioperative period,232 particularly with regard to systolic pressure233 and pulse pressure.234 Intraoperative hypotension is considered to be a risk factor for adverse outcomes in patients undergoing many types of surgery. Unique to CABG are unavoidable periods of hypo- tension associated with surgical manipulation, cannulation for CPB, weaning from CPB, or during suspension and stabili- zation of the heart with off-pump CABG. Minimization of such periods is desirable but is often difficult to achieve, particularly in patients who are unstable hemodynamically. 2.2. Clinical Subsets 2.2.1. CABG in Patients With Acute MI: Recommendations Class I 1. Emergency CABG is recommended in patients with acute MI in whom 1) primary PCI has failed or cannot be performed, 2) coronary anatomy is suit- able for CABG, and 3) persistent ischemia of a significant area of myocardium at rest and/or hemo- dynamic instability refractory to nonsurgical ther- apy is present.235 239 (Level of Evidence: B) 2. Emergency CABG is recommended in patients un- dergoing surgical repair of a postinfarction mechan- ical complication of MI, such as ventricular septal rupture, mitral valve insufficiency because of papil- lary muscle infarction and/or rupture, or free wall rupture.240 244 (Level of Evidence: B) 3. Emergency CABG is recommended in patients with cardiogenic shock and who are suitable for CABG irrespective of the time interval from MI to onset of shock and time from MI to CABG.238,245 247 (Level of Evidence: B) 4. Emergency CABG is recommended in patients with life-threatening ventricular arrhythmias (believed to be ischemic in origin) in the presence of left main stenosis greater than or equal to 50% and/or 3-vessel CAD.248 (Level of Evidence: C) Class IIa 1. The use of CABG is reasonable as a revasculariza- tion strategy in patients with multivessel CAD with recurrent angina or MI within the first 48 hours of STEMI presentation as an alternative to a more delayed strategy.235,237,239,249 (Level of Evidence: B) 2. Early revascularization with PCI or CABG is rea- sonable for selected patients greater than 75 years of age with ST-segment elevation or left bundle branch block who are suitable for revascularization irre- spective of the time interval from MI to onset of shock.250 254 (Level of Evidence: B) Class III: HARM 1. Emergency CABG should not be performed in pa- tients with persistent angina and a small area of viable myocardium who are stable hemodynam- ically. (Level of Evidence: C) 2. Emergency CABG should not be performed in pa- tients with noreflow (successful epicardial reperfu- sion with unsuccessful microvascular reperfusion). (Level of Evidence: C) See Online Data Supplement 5 for additional data on CABG in patients with acute myocardial infarction. With the widespread use of fibrinolytic therapy or primary PCI in subjects with STEMI, emergency CABG is now reserved for those with 1) left main and/or 3-vessel CAD, 2) ongoing ischemia after successful or failed PCI, 3) coronary anatomy not amenable to PCI, 4) a mechanical complication of STEMI,241,255,256 and 5) cardiogenic shock (defined as hypotension [systolic arterial pressure 90 mm Hg for 30 minutes or need for supportive measures to maintain a systolic pressure 90 mm Hg], evidence of end-organ hypoperfusion, cardiac index 2.2 L/min/m2 , and pulmonary capillary wedge pressure 15 mm Hg).245,247 In the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, 36% of patients randomly assigned to early revascularization therapy underwent emer- gency CABG.245 Although those who underwent emergency CABG were more likely to be diabetic and to have complex coronary anatomy than were those who had PCI, the survival rates of the 2 groups were similar.247 The outcomes of high-risk STEMI patients with cardiogenic shock undergoing emergency CABG suggest that CABG may be preferred to PCI in this patient population when complete revasculariza- tion cannot be accomplished with PCI.236,238,246 The need for emergency CABG in subjects with STEMI is relatively uncommon, ranging from 3.2% to 10.9%.257,258 Of the 1572 patients enrolled in the DANAMI-2 (Danish Mul- ticenter Randomized Study on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction) study, only 50 (3.2%) underwent CABG within 30 days (30 patients initially treated with PCI and 20 given fibrinolysis), and only 3 patients (0.2%) randomly assigned to receive primary PCI underwent emergency CABG.257 Of the 1100 patients who underwent coronary angiography in the PAMI-2 (Primary Angioplasty in Myocardial Infarction) trial, CABG was performed before hospital discharge in 120.258 The in-hospital mortality rate is higher in STEMI patients undergoing emergency CABG than in those undergoing it on a less urgent or a purely elective basis.239,257,259 264 In a study of 1181 patients undergoing CABG, the in-hospital mortality rate increased as the patients preoperative status worsened, ranging from 1.2% in those with stable angina to 26% in those with cardiogenic shock.265 Although patients requiring emergency or urgent CABG after STEMI are at higher risk than those undergoing it electively, the optimal timing of CABG after STEMI is controversial. A retrospective study performed before the widespread availability of fibrinolysis and primary PCI re- ported an overall in-hospital mortality rate of 5.2% in 440 STEMI patients undergoing CABG as primary reperfusion therapy. Those undergoing CABG 6 hours after symptom onset had a lower in-hospital and long-term (10 years) mortality rate than those undergoing CABG 6 hours after symptom onset.237 Other studies have provided conflicting results, because of, at least in part, the lack of clear delinea- tion between STEMI and NSTEMI patients in these large database reports.259,265 In an analysis of 9476 patients hospi- talized with an acute coronary syndrome (ACS) who under- went CABG during the index hospitalization, 1344 (14%) were STEMI patients with shock or intra-aortic balloon placement preoperatively.264 These individuals had a mortal- ity rate of 4% when CABG was performed on the third hospital day, which was lower than the mortality rates reported when CABG was performed earlier or later during the hospitalization.264 In studies in which the data from STEMI patients were analyzed separately with regard to the optimal timing of CABG, however, the results appear to be different. In 1 analysis of 44 365 patients who underwent CABG after MI (22 984 with STEMI; 21 381 with NSTEMI), the inhospital mortality rate was similar in the 2 groups undergoing CABG 6 hours after diagnosis (12.5% and 11.5%, respectively), but it was higher in STEMI patients than in NSTEMI patients when CABG was performed 6 to 23 hours after diagnosis (13.6% versus 6.2%; P 0.006).262 The groups had similar in-hospital mortality rates when CABG was performed at all later time points (1 to 7 days, 8 to 14 days, and 15 days after the acute event).262 Similarly, in a study of 138 subjects with STEMI unresponsive to maximal nonsurgical therapy who underwent emergency CABG, the overall mortality rate was 8.7%, but it varied according to the time interval from symptom onset to time of operation. The mortality rate was 10.8% for patients undergoing CABG within 6 hours of the onset of symptoms, 23.8% in those Hillis et al 2011 ACCF/AHA CABG Guideline e665 undergoing CABG 7 to 24 hours after symptom onset, 6.7% in patients undergoing CABG from 1 to 3 days, 4.2% in those who underwent surgery from 4 to 7 days, and 2.4% after 8 days.266 In an analysis of data from 150 patients with STEMI who did not qualify for primary PCI and required CABG, the in-hospital mortality rate increased according to the time interval between symptom onset and surgery.239 The mortal- ity rate was 6.1% for subjects who underwent CABG within 6 hours of pain onset, 50% in those who underwent CABG 7 to 23 hours after pain onset, and 7.1% in those who underwent CABG after 15 days.239 Lastly, in another study, the time interval of 6 hours was also found to be important in STEMI patients requiring CABG. The mean time from symptom onset to CABG was significantly shorter in survi- vors versus nonsurvivors (5.1 2.7 hours versus 11.4 3.2 hours; P 0.0007).235 In patients with cardiogenic shock, the benefits of early revascularization were apparent across a wide time interval between 1) MI and the onset of shock and 2) MI and CABG. Therefore, although CABG exerts its most profound salutary effect when it is performed as soon as possible after MI and the appearance of shock, the time window in which it is beneficial is quite broad. Apart from the timing of CABG, the outcomes of STEMI patients undergoing CABG depend on baseline demographic variables. Those with mechanical complications of STEMI (eg, ventricular septal rupture or mitral regurgitation caused by papillary muscle rupture) have a high operative mortality rate.240 242,244,255,267 In a study of 641 subjects with ACS, 22 with evolving STEMI and 20 with a mechanical complication of STEMI were referred for emergency CABG; the 30-day mortality rate was 0% in those with evolving STEMI and 25% in those with a mechanical complication of STEMI.268 In those with mechanical complications, several variables were predictive of death, including advanced age, female sex, cardiogenic shock, the use of intra-aortic balloon counterpul- sation preoperatively, pulmonary disease, renal insufficiency, and magnitude of elevation of the serum troponin 2.2.2. Life-Threatening Ventricular Arrhythmias: Recommendations Class I 1. CABG is recommended in patients with resuscitated sudden cardiac death or sustained ventricular tachycardia thought to be caused by significant CAD (>50% stenosis of left main coronary artery and/or >70% stenosis of 1, 2, or all 3 epicardial coronary arteries) and resultant myocardial ischemia.248,271,272 (Level of Evidence: B) Class III: HARM 1. CABG should not be performed in patients with ventricular tachycardia with scar and no evidence of ischemia. (Level of Evidence: C) See Online Data Supplement 6 for additional data on life- threatening ventricular arrhythmias. Most studies evaluating the benefits of CABG in patients with ventricular arrhythmias have examined survivors of out-of-hospital cardiac arrest as well as patients with induc- ible ventricular tachycardia or fibrillation during electro- physiological study.272 274 In general, CABG has been more effective in reducing the occurrence of ventricular fibrillation than of ventricular tachycardia, because the mechanism of the latter is usually reentry with scarred endocardium rather than ischemia. Observational studies have demonstrated a favor- able prognosis of subjects undergoing CABG for ischemic In survivors of cardiac arrest who have severe but operable CAD, CABG can suppress the appearance of arrhythmias, reduce subsequent episodes of cardiac arrest, and result in a good long-term outcome.271 273 It is particularly effective when an ischemic cause of the arrhythmia can be documented (for instance, when it occurs with exercise).275 Still, because CABG may not alleviate all the factors that predispose to ventricular arrhythmias, concomitant insertion of an implant- able cardioverter-defibrillator is often warranted.276 Simi- larly, continued inducibility or clinical recurrence of ventric- ular tachycardia after CABG usually requires an implantable cardioverter-defibrillator implantation. Patients with depressed LV systolic function, advanced age, female sex, and increased CPB time are at higher risk for life-threatening arrhythmias in the early postoperative period. Given the poor short-term prognosis of those with these arrhythmias, mechanical and ischemic causes should be considered in the postoperative setting.277 279 2.2.3. Emergency CABG After Failed PCI: Recommendations Class I 1. Emergency CABG is recommended after failed PCI in the presence of ongoing ischemia or threatened occlusion with substantial myocardium at risk.280,281 (Level of Evidence: B) 2. Emergency CABG is recommended after failed PCI for hemodynamic compromise in patients without impairment of the coagulation system and without a previous sternotomy.280,282,283 (Level of Evidence: B) Class IIa 1. Emergency CABG is reasonable after failed PCI for retrieval of a foreign body (most likely a fractured guidewire or stent) in a crucial anatomic location. (Level of Evidence: C) 2. Emergency CABG can be beneficial after failed PCI for hemodynamic compromise in patients with im- pairment of the coagulation system and without previous sternotomy. (Level of Evidence: C) Class IIb 1. Emergency CABG might be considered after failed PCI for hemodynamic compromise in patients with previous sternotomy. (Level of Evidence: C) Class III: HARM 1. Emergency CABG should not be performed after failed PCI in the absence of ischemia or threatened occlusion. (Level of Evidence: C) 2. Emergency CABG should not be performed after failed PCI if revascularization is impossible because of target anatomy or a no-reflow state. (Level of Evidence: C) See Online Data Supplement 7 for additional data on CABG after failed PCI. With widespread stent use as well as effective antiplate- let and antithrombotic therapies, emergency CABG after failed PCI is not commonly performed. In a 2009 analysis of data from almost 22 000 patients undergoing PCI at a single center, only 90 (0.4%) required CABG within 24 hours of PCI.281 A similarly low rate ( 0.8%) of emer- gency CABG after PCI has been reported by others.284 286 The indications for emergency CABG after PCI include 1) acute (or threatened) vessel closure, 2) coronary arterial dissection, 3) coronary arterial perforation,281 and 4) mal- function of PCI equipment (eg, stent dislodgement, frac- tured guidewire). Subjects most likely to require emer- gency CABG after failed PCI are those with evolving STEMI, cardiogenic shock, 3-vessel CAD, or the presence of a type C coronary arterial lesion (defined as 2 cm in length, an excessively tortuous proximal segment, an extremely angulated segment, a total occlusion 3 months in duration, or a degenerated SVG that appears to be In those in whom emergency CABG for failed PCI is performed, morbidity and mortality rates are increased com- pared with those undergoing elective CABG,287 289 resulting at least in part from the advanced age of many patients now referred for PCI, some of whom have multiple comorbid conditions and complex coronary anatomy. Several variables have been shown to be associated with increased periop- erative morbidity and mortality rates, including 1) de- multivessel CAD and complex lesion morphology,291,292 4) and 8) a prolonged time delay in transfer to the operating room.293 In patients undergoing emergency CABG for failed PCI, an off-pump procedure may be associated with a reduced incidence of renal failure, need for intra-aortic balloon use, and reoperation for bleeding.283,295 If complete revascularization is achieved with minimal delay in patients undergoing emergency CABG after failed PCI, long-term prognosis is similar to that of subjects undergoing elective CABG.280,282,296 In-hospital morbidity and mortality rates in women297 and the elderly298 undergoing emergency CABG for failed PCI are relatively high, but the long-term outcomes in these individuals are comparable to those achieved in men and younger patients. 2.2.4. CABG in Association With Other Cardiac Procedures: Recommendations Class I 1. CABG is recommended in patients undergoing non- coronary cardiac surgery with greater than or equal to 50% luminal diameter narrowing of the left main coronary artery or greater than or equal to 70% luminal diameter narrowing of other major coro- nary arteries. (Level of Evidence: C) Class IIa 1. The use of the LIMA is reasonable to bypass a signifi- cantly narrowed LAD artery in patients undergoing noncoronary cardiac surgery. (Level of Evidence: C) 2. CABG of moderately diseased coronary arteries (>50% luminal diameter narrowing) is reasonable in patients undergoing noncoronary cardiac sur- gery. (Level of Evidence: C) 3. CAD Revascularization Recommendations and text in this section are the result of extensive collaborative discussions between the PCI and CABG writing committees, as well as key members of the Stable Ischemic Heart Disease (SIHD) and UA/NSTEMI writing committees. Certain issues, such as older versus more contemporary studies, primary analyses versus subgroup analyses, and prospective versus post hoc analyses, have been carefully weighed in designating COR and LOE; they are addressed in the appropriate corresponding text. The goals of revascularization for patients with CAD are to 1) to improve survival and 2) to relieve symptoms. Revascularization recommendations in this section are predominantly based on studies of patients with symptomatic SIHD and should be interpreted in this context. As discussed later in this section, recommendations on the type of revas- cularization are, in general, applicable to patients with UA/ NSTEMI. In some cases (eg, unprotected left main CAD), specific recommendations are made for patients with UA/ NSTEMI or STEMI. Historically, most studies of revascularization have been based on and reported according to angiographic criteria. Most studies have defined a significant stenosis as 70% diameter narrowing; therefore, for revascularization decisions and recommendations in this section, a significant stenosis has been defined as 70% diameter narrowing ( 50% for left main CAD). Physiological criteria, such as an assessment of fractional flow reserve, has been used in deciding when revascularization is indicated. Thus, for recommendations on revascularization in this section, coronary stenoses with fractional flow reserve 0.80 can also be considered As noted, the revascularization recommendations have been formulated to address issues related to 1) improved survival and/or 2) improved symptoms. When one method of revascularization is preferred over the other for improved survival, this consideration, in general, takes precedence over improved symptoms. When discussing options for revascu- larization with the patient, he or she should understand when the procedure is being performed in an attempt to improve symptoms, survival, or both. Although some results from the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) study are best characterized as subgroup analyses and hypothesis generating, SYNTAX nonetheless represents the latest and most comprehensive comparison of contemporary PCI and CABG.301,302 There- Hillis et al 2011 ACCF/AHA CABG Guideline e667 fore, the results of SYNTAX have been considered appro- priately when formulating our revascularization recom- mendations. Although the limitations of using the SYNTAX score for certain revascularization recommenda- tions are recognized, the SYNTAX score is a reasonable surrogate for the extent of CAD and its complexity and serves as important information that should be considered when making revascularization decisions. Recommenda- tions that refer to SYNTAX scores use them as surrogates for the extent and complexity of CAD. Revascularization recommendations to improve survival and symptoms are given in the following text and summa- rized in Tables 2 and 3. References to studies comparing revascularization with medical therapy are presented when available for each anatomic subgroup. See Online Data Supplements 8 and 9 for additional data regarding the survival and symptomatic benefits with CABG or PCI for different anatomic subsets. 3.1. Heart Team Approach to Revascularization Decisions: Recommendations Class I 1. A Heart Team approach to revascularization is recommended in patients with unprotected left main or complex CAD.302 304 (Level of Evidence: C) Class IIa 1. Calculation of the STS and SYNTAX scores is reasonable in patients with unprotected left main and complex CAD.301,302,305 310 (Level of Evidence: B) One protocol used in RCTs302 304,311 often involves a multi- disciplinary approach referred to as the Heart Team. Com- posed of an interventional cardiologist and a cardiac surgeon, the Heart Team 1) reviews the patient s medical condition and coronary anatomy, 2) determines that PCI and/or CABG are technically feasible and reasonable, and 3) discusses revascularization options with the patient before a treatment strategy is selected. Support for using a Heart Team approach comes from reports that patients with complex CAD referred specifically for PCI or CABG in concurrent trial registries have lower mortality rates than those randomly assigned to PCI or CABG in controlled trials.303,304 The SIHD, PCI, and CABG guideline writing commit- tees endorse a Heart Team approach in patients with unprotected left main CAD and/or complex CAD in whom the optimal revascularization strategy is not straightfor- ward. A collaborative assessment of revascularization options, or the decision to treat with GDMT without revascularization, involving an interventional cardiologist, a cardiac surgeon, and (often) the patient s general cardi- ologist, followed by discussion with the patient about treatment options, is optimal. Particularly in patients with SIHD and unprotected left main and/or complex CAD for whom a revascularization strategy is not straightforward, an approach has been endorsed that involves terminating the procedure after diagnostic coronary angiography is completed; this allows a thorough discussion and affords both the interventional cardiologist and cardiac surgeon the opportunity to discuss revascularization options with the patient. Because the STS score and the SYNTAX score have been shown to predict adverse outcomes in patients undergoing CABG and PCI, respectively, calculation of these scores is often useful in making revascularization 3.2. Revascularization to Improve Survival: Recommendations Left Main CAD Revascularization Class I 1. CABG to improve survival is recommended for patients with significant (>50% diameter stenosis) left main cor- onary artery stenosis.312 318 (Level of Evidence: B) Class IIa 1. PCI to improve survival is reasonable as an alterna- tive to CABG in selected stable patients with signif- icant (>50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score [<22], ostial or trunk left main CAD); and 2) clinical characteristics that predict a significantly increased risk of adverse surgical out- comes (eg, STS-predicted risk of operative mortality >5%).301,305,307,311,319 336 (Level of Evidence: B) 2. PCI to improve survival is reasonable in patients with UA/NSTEMI when an unprotected left main coronary artery is the culprit lesion and the patient is not a candidate for CABG.301,324 327,332,333,335 337 (Level of Evidence: B) 3. PCI to improve survival is reasonable in patients with acute STEMI when an unprotected left main coronary artery is the culprit lesion, distal coronary flow is less than Thrombolysis In Myocardial Infarction grade 3, and PCI can be performed more rapidly and safely than CABG.321,338,339 (Level of Evidence: C) Class IIb 1. PCI to improve survival may be reasonable as an alter- native to CABG in selected stable patients with significant (>50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associated with a low to intermediate risk of PCI procedural complications and an intermediate to high likelihood of good long-term out- come (eg, low intermediate SYNTAX score of <33, bi- furcation left main CAD); and 2) clinical characteristics that predict an increased risk of adverse surgical out- comes (eg, moderate severe chronic obstructive pulmo- nary disease, disability from previous stroke, or previous cardiac surgery; STS-predicted risk of operative mortal- ity >2%).301,305,307,311,319 336,340 (Level of Evidence: B) Class III: HARM 1. PCI to improve survival should not be performed in stable patients with significant (>50% diameter steno- sis) unprotected left main CAD who have unfavorable Table 2. Revascularization to Improve Survival Compared With Medical Therapy Anatomic Setting COR LOE References UPLM or complex CAD CABG and PCI I Heart Team approach recommended C 302 304 CABG and PCI IIa Calculation of the STS and SYNTAX scores B 301, 302, 305 310 UPLM* CABG I B 312 318 PCI IIa For SIHD when both of the following are present Anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score of 22, ostial or trunk left main CAD) Clinical characteristics that predict a significantly increased risk of adverse surgical outcomes (eg, STS-predicted risk of operative mortality 5%) IIa For UA/NSTEMI if not a CABG candidate B 301, 324 327, 332, 333, 335 337 IIa For STEMI when distal coronary flow is TIMI flow grade 3 and PCI can be performed more rapidly and safely than CABG IIb For SIHD when both of the following are present Anatomic conditions associated with a low to intermediate risk of PCI procedural complications and intermediate to high likelihood of good long-term outcome (eg, low-intermediate SYNTAX score of 33, bifurcation left main CAD) Clinical characteristics that predict an increased risk of adverse surgical outcomes (eg, moderate-severe COPD, disability from prior stroke, or prior cardiac surgery; STS-predicted risk of operative mortality 2%) III: Harm For SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG 3-vessel disease with or without proximal LAD artery disease* IIa It is reasonable to choose CABG over PCI in patients with complex 3-vessel CAD (eg, SYNTAX 22) who are good candidates for CABG 2-vessel disease with proximal LAD artery disease* 2-vessel disease without proximal LAD artery disease* CABG IIa With extensive ischemia B 348 351 IIb Of uncertain benefit without extensive ischemia C 343 1-vessel proximal LAD artery disease CABG IIa With LIMA for long-term benefit B 87, 88, 318, 343 PCI IIb Of uncertain benefit B 314,341, 343, 370 1-vessel disease without proximal LAD artery involvement LV dysfunction CABG IIb EF 35% without significant left main CAD B 318, 352 356, 371, 372 PCI Insufficient data N/A Survivors of sudden cardiac death with presumed ischemia-mediated VT PCI I C 345 No anatomic or physiological criteria for revascularization *In patients with multivessel disease who also have diabetes, it is reasonable to choose CABG (with LIMA) over PCI350,362 369 (Class IIa/LOE: B). CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; COR, class of recommendation; EF, ejection fraction; LAD, left anterior descending; LIMA, left internal mammary artery; LOE, level of evidence; LV, left ventricular; N/A, not applicable; PCI, percutaneous coronary intervention; SIHD, stable ischemic heart disease; STEMI, ST-elevation myocardial infarction; STS, Society of Thoracic Surgeons; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TIMI, Thrombolysis in Myocardial Infarction; UA/NSTEMI, unstable angina/non ST-elevation myocardial infarction; UPLM, unprotected left main disease; and VT, ventricular tachycardia. Hillis et al 2011 ACCF/AHA CABG Guideline e669 anatomy for PCI and who are good candidates for CABG.301,305,307,312 320 (Level of Evidence: B) Non Left Main CAD Revascularization Class I 1. CABG to improve survival is beneficial in patients with significant (>70% diameter) stenoses in 3 major coronary arteries (with or without involve- ment of the proximal LAD artery) or in the proximal LAD plus 1 other major coronary artery.314,318,341 344 (Level of Evidence: B) 2. CABG or PCI to improve survival is beneficial in survivors of sudden cardiac death with presumed ischemia-mediated ventricular tachycardia caused by significant (>70% diameter) stenosis in a major coronary artery. (CABG Level of Evidence: B271,345,347; PCI Level of Evidence: C345) Class IIa 1. CABG to improve survival is reasonable in patients with significant (>70% diameter) stenoses in 2 major coronary arteries with severe or extensive myocardial ischemia (eg, high-risk criteria on stress testing, abnormal intracoronary hemodynamic eval- uation, or >20% perfusion defect by myocardial perfusion stress imaging) or target vessels supplying a large area of viable myocardium.348 351 (Level of Evidence: B) 2. CABG to improve survival is reasonable in patients with mild-moderate LV systolic dysfunction (EF 35% to 50%) and significant (>70% diameter ste- nosis) multivessel CAD or proximal LAD coronary artery stenosis, when viable myocardium is present in the region of intended revascularization.318,352 356 (Level of Evidence: B) 3. CABG with a LIMA graft to improve survival is reasonable in patients with significant (>70% diam- eter) stenosis in the proximal LAD artery and evi- dence of extensive ischemia.87,88,318,343 (Level of Evi- dence: B) 4. It is reasonable to choose CABG over PCI to im- prove survival in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery, who are good candidates for CABG.320,334,343,359 360 (Level of Evidence: B) 5. CABG is probably recommended in preference to PCI to improve survival in patients with multivessel CAD and diabetes mellitus, particularly if a LIMA graft can be anastomosed to the LAD artery.350,362 369 (Level of Evidence: B) Class IIb 1. The usefulness of CABG to improve survival is uncertain in patients with significant (>70%) steno- ses in 2 major coronary arteries not involving the proximal LAD artery and without extensive ische- mia.343 (Level of Evidence: C) 2. The usefulness of PCI to improve survival is uncer- tain in patients with 2- or 3-vessel CAD (with or without involvement of the proximal LAD artery) or 1-vessel proximal LAD disease.314,341,343,370 (Level of Evidence: B) 3. CABG might be considered with the primary or sole intent of improving survival in patients with SIHD with severe LV systolic dysfunction (EF <35%) whether or not viable myocardium is present.318,352 356,371,372 (Level of Evidence: B) 4. The usefulness of CABG or PCI to improve survival is uncertain in patients with previous CABG and extensive anterior wall ischemia on noninvasive testing.373 381 (Level of Evidence: B) Class III: HARM 1. CABG or PCI should not be performed with the primary or sole intent to improve survival in patients with SIHD with 1 or more coronary stenoses that are Table 3. Revascularization to Improve Symptoms With Significant Anatomic (>50% Left Main or >70% Non Left Main CAD) or Physiological (FFR <0.80) Coronary Artery Stenoses Clinical Setting COR LOE References 1 significant stenoses amenable to revascularization and unacceptable angina despite GDMT I CABG I PCI 1 significant stenoses and unacceptable angina in whom GDMT cannot be implemented because of medication contraindications, adverse effects, or patient preferences IIa CABG IIa PCI C N/A Previous CABG with 1 significant stenoses associated with ischemia and unacceptable angina despite GDMT IIb CABG C 381 Complex 3-vessel CAD (eg, SYNTAX score 22) with or without involvement of the proximal LAD artery and a good candidate for CABG IIa CABG preferred over PCI B 320, 343, 359 361 Viable ischemic myocardium that is perfused by coronary arteries that are not amenable to grafting IIb TMR as an adjunct to CABG B 397 401 No anatomic or physiologic criteria for revascularization III: Harm CABG III: Harm PCI C N/A CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COR, class of recommendation; FFR, fractional flow reserve; GDMT, guideline-directed medical therapy; LOE, level of evidence; N/A, not applicable; PCI, percutaneous coronary intervention; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; and TMR, transmyocardial laser revascularization. not anatomically or functionally significant (eg, <70% diameter non left main coronary artery stenosis, frac- tional flow reserve >0.80, no or only mild ischemia on noninvasive testing), involve only the left circumflex or right coronary artery, or subtend only a small area of viable myocardium.318,341,348,349,382 386 (Level of Evi- dence: B) 3.3. Revascularization to Improve Symptoms: Recommendations Class I 1. CABG or PCI to improve symptoms is beneficial in patients with 1 or more significant (>70% diameter) coronary artery stenoses amenable to revasculariza- tion and unacceptable angina despite GDMT.370,387 396 (Level of Evidence: A) Class IIa 1. CABG or PCI to improve symptoms is reasonable in patients with 1 or more significant (>70% diameter) coronary artery stenoses and unacceptable angina for whom GDMT cannot be implemented because of medication contraindications, adverse effects, or pa- tient preferences. (Level of Evidence: C) 2. PCI to improve symptoms is reasonable in patients with previous CABG, 1 or more significant (>70% diameter) coronary artery stenoses associated with ischemia, and unacceptable angina despite GDMT.374,377,380 (Level of Evidence: C) 3. It is reasonable to choose CABG over PCI to im- prove symptoms in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery, who are good candidates for CABG.320,334,343,359 360 (Level of Evidence: B) Class IIb 1. CABG to improve symptoms might be reasonable for patients with previous CABG, 1 or more signif- icant (>70% diameter) coronary artery stenoses not amenable to PCI, and unacceptable angina despite GDMT.381 (Level of Evidence: C) 2. Transmyocardial laser revascularization (TMR) performed as an adjunct to CABG to improve symptoms may be reasonable in patients with viable ischemic myocardium that is perfused by arteries that are not amenable to grafting.397 401 (Level of Evidence: B) Class III: HARM 1. CABG or PCI to improve symptoms should not be performed in patients who do not meet anatomic (>50% left main or >70% non left main stenosis) or physiological (eg, abnormal fractional flow reserve) criteria for revascularization. (Level of Evidence: C) 3.4. CABG Versus Contemporaneous Medical Therapy In the 1970s and 1980s, 3 RCTs established the survival benefit of CABG compared with contemporaneous (although minimal by current standards) medical therapy without revas- cularization in certain subjects with stable angina: the Veter- ans Affairs Cooperative Study,402 European Coronary Sur- gery Study,344 and CASS (Coronary Artery Surgery Study).403 Subsequently, a 1994 meta-analysis of 7 studies that randomized a total of 2649 patients to medical therapy for CABG318 showed that CABG offered a survival advan- tage over medical therapy for patients with left main or 3-vessel CAD. The studies also established that CABG is more effective than medical therapy at relieving anginal symptoms. These studies have been replicated only once during the past decade. In MASS II (Medicine, Angioplasty, or Surgery Study II), patients with multivessel CAD who were treated with CABG were less likely than those treated with medical therapy to have a subsequent MI, need addi- tional revascularization, or experience cardiac death in the 10 years after randomization.392 Surgical techniques and medical therapy have improved substantially during the intervening years. As a result, if CABG were to be compared with GDMT in RCTs today, the relative benefits for survival and angina relief observed several decades ago might no longer be observed. Con- versely, the concurrent administration of GDMT may sub- stantially improve long-term outcomes in patients treated with CABG in comparison with those receiving medical therapy alone. In the BARI 2D (Bypass Angioplasty Revas- cularization Investigation 2 Diabetes) trial of patients with diabetes mellitus, no significant difference in risk of mortality in the cohort of patients randomized to GDMT plus CABG or GDMT alone was observed, although the study was not powered for this endpoint, excluded patients with significant left main CAD, and included only a small percentage of patients with proximal LAD artery disease or LV ejection fraction (LVEF) 0.50.404 The PCI and CABG guideline writing committees endorse the performance of the ISCH- EMIA (International Study of Comparative Health Effective- ness with Medical and Invasive Approaches) trial, which will provide contemporary data on the optimal management strat- egy (medical therapy or revascularization with CABG or PCI) of patients with SIHD, including multivessel CAD, and moderate to severe ischemia. 3.5. PCI Versus Medical Therapy Although contemporary interventional treatments have low- ered the risk of restenosis compared with earlier techniques, meta-analyses have failed to show that the introduction of bare-metal stents (BMS) confers a survival advantage over balloon angioplasty405 407 or that the use of drug-eluting stents (DES) confers a survival advantage over BMS.407,408 No study to date has demonstrated that PCI in patients with SIHD improves survival rates.314,341,343,370,404,407,409 412 Nei- ther COURAGE (Clinical Outcomes Utilizing Revasculariza- tion and Aggressive Drug Evaluation)370 nor BARI 2D,404 which treated all patients with contemporary optimal medical therapy, demonstrated any survival advantage with PCI, although these trials were not specifically powered for this endpoint. Although 1 large analysis evaluating 17 RCTs of PCI versus medical therapy (including 5 trials of subjects with ACS) found a 20% reduction in death with PCI Hillis et al 2011 ACCF/AHA CABG Guideline e671 compared with medical therapy,411 2 other large analyses did not.407,410 An evaluation of 13 studies reporting the data from 5442 patients with nonacute CAD showed no advantage of PCI over medical therapy for the individual endpoints of all-cause death, cardiac death or MI, or nonfatal MI.412 Evaluation of 61 trials of PCI conducted over several decades shows that despite improvements in PCI technology and pharmacotherapy, PCI has not been demonstrated to reduce the risk of death or MI in patients without recent ACS.407 The findings from individual studies and systematic reviews of PCI versus medical therapy can be summarized as follows: PCI reduces the incidence of angina.370,387,392,395,396,413 PCI has not been demonstrated to improve survival in PCI may increase the short-term risk of MI.370,409,413,414 PCI does not lower the long-term risk of MI.370,404,407,409,410,414 3.6. CABG Versus PCI The results of 26 RCTs comparing CABG and PCI have been published: Of these, 9 compared CABG with balloon angio- plasty,363,393,415 429 14 compared CABG with BMS implanta- tion,376,430 447 and 3 compared CABG with DES 3.6.1. CABG Versus Balloon Angioplasty or BMS A systematic review of the 22 RCTs comparing CABG with balloon angioplasty or BMS implantation concluded the 1. Survival was similar for CABG and PCI (with balloon angioplasty or BMS) at 1 year and 5 years. Survival was similar for CABG and PCI in subjects with 1-vessel CAD (including those with disease of the proximal portion of the LAD artery) or multivessel CAD. 2. Incidence of MI was similar at 5 years after random- ization. 3. Procedural stroke occurred more commonly with CABG than with PCI (1.2% versus 0.6%). 4. Relief of angina was accomplished more effectively with CABG than with PCI 1 year after randomization and 5 years after randomization. 5. During the first year after randomization, repeat coro- nary revascularization was performed less often after CABG than after PCI (3.8% versus 26.5%). This was also demonstrated after 5 years of follow-up (9.8% versus 46.1%). This difference was more pronounced with balloon angioplasty than with BMS. A collaborative analysis of data from 10 RCTs comparing CABG with balloon angioplasty (6 trials) or with BMS implantation (4 trials)451 permitted subgroup analyses of the data from the 7812 patients. No difference was noted with regard to mortality rate 5.9 years after randomization or the composite endpoint of death or MI. Repeat revascularization and angina were noted more frequently in those treated with balloon angioplasty or BMS implantation.451 The major new observation of this analysis was that CABG was associated with better outcomes in patients with diabetes mellitus and in those 65 years old. Of interest, the relative outcomes of CABG and PCI were not influenced by other patient charac- teristics, including the number of diseased coronary arteries. The aforementioned meta-analysis and systematic re- view450,451 comparing CABG and balloon angioplasty or BMS implantation were limited in several ways. 1. Many trials did not report outcomes for other important patient subsets. For example, the available data are insufficient to determine if race, obesity, renal dysfunc- tion, peripheral artery disease (PAD), or previous cor- onary revascularization affected the comparative out- comes of CABG and PCI. 2. Most of the patients enrolled in these trials were male, and most had 1- or 2-vessel CAD and normal LV systolic function (EF 50%) subjects known to be unlikely to derive a survival benefit and less likely to experience complications after CABG.318 3. The patients enrolled in these trials represented only a small fraction (generally 5% to 10%) of those who were screened. For example, most screened patients with 1-vessel CAD and many with 3-vessel CAD were not considered for randomization. See Online Data Supplements 10 and 11 for additional data comparing CABG with PCI. 3.6.2. CABG Versus DES Although the results of 9 observational studies comparing CABG and DES implantation have been published,320,452 459 most of them had short (12 to 24 months) follow-up periods. In a meta-analysis of 24 268 patients with multivessel CAD treated with CABG or DES,460 the incidences of death and MI were similar for the 2 procedures, but the frequency with which repeat revascularization was performed was roughly 4 times higher after DES implantation. Only 1 large RCT comparing CABG and DES implantation has been published. The SYNTAX trial randomly assigned 1800 patients (of a total of 4337 who were screened) to receive DES or CABG.302,334 Major adverse cardiac events (MACE), a com- posite of death, stroke, MI, or repeat revascularization during the 3 years after randomization, occurred in 20.2% of CABG patients and 28.0% of those undergoing DES implantation (P 0.001). The rates of death and stroke were similar; however, MI (3.6% for CABG; 7.1% for DES) and repeat revascularization (10.7% for CABG; 19.7% for DES) were more likely to occur with DES implantation.334 In SYNTAX, the extent of CAD was assessed using the SYNTAX score, which is based on the location, severity, and extent of coronary stenoses, with a low score indicating less complicated anatomic CAD. In post hoc analyses, a low score was defined as 22; intermediate 23 to 32; and high, 33. The occurrence of MACE correlated with the SYNTAX score for DES patients but not for those undergoing CABG. At 12-month follow-up, the primary endpoint was similar for CABG and DES in those with a low SYNTAX score. In contrast, MACE occurred more often after DES implantation than after CABG in those with an intermediate or high SYNTAX score.302 At 3 years of follow-up, the mortality rate was greater in subjects with 3-vessel CAD treated with PCI than in those treated with CABG (6.2% versus 2.9%). The differences in MACE between those treated with PCI or CABG increased with an increasing SYN- TAX score (Figure 1).334 Although the utility of using a SYNTAX score in everyday clinical practice remains uncertain, it seems reasonable to conclude from SYNTAX and other data that outcomes of patients undergoing PCI or CABG in those with relatively uncomplicated and lesser degrees of CAD are comparable, whereas in those with complex and diffuse CAD, CABG appears to be preferable.334 See Online Data Supplements 12 and 13 for additional data comparing CABG with DES. 3.7. Left Main CAD 3.7.1. CABG or PCI Versus Medical Therapy for Left Main CAD CABG confers a survival benefit over medical therapy in patients with left main CAD. Subgroup analyses from RCTs performed 3 decades ago included 91 patients with left main CAD in the Veterans Administration Cooperative Study.316 A meta-analysis of these trials demonstrated a 66% RR reduc- tion in mortality with CABG, with the benefit extending to 10 years.318 The CASS Registry312 contained data from 1484 patients with 50% left main CAD initially treated surgically or nonsurgically. Median survival duration was 13.3 years in the surgical group and 6.6 years in the medical group. The survival benefit of CABG over medical therapy appeared to extend to 53 asymptomatic patients with left main CAD in the CASS Registry.317 Other therapies that subsequently have been shown to be associated with improved long-term out- come, such as the use of aspirin, statins, and IMA grafting, were not widely used in that era. RCTs and subgroup analyses that compare PCI with medical therapy in patients with unprotected left main CAD do not exist. 3.7.2. Studies Comparing PCI Versus CABG for Left Main CAD Of all subjects undergoing coronary angiography, approxi- mately 4% are found to have left main CAD,463 80% of whom have significant ( 70% diameter) stenoses in other epicardial coronary arteries. Published cohort studies have found that major clinical outcomes are similar with PCI or CABG 1 year after revascularization and that mortality rates are similar at 1, 2, and 5 years of follow-up; however, the risk of needing target-vessel revascularization is significantly higher with stenting than with CABG. In the SYNTAX trial, 45% of screened patients with unprotected left main CAD had complex diseases that pre- vented randomization; 89% of these underwent CABG.301,302 In addition, 705 of the 1800 patients who were randomized had revascularization for unprotected left main CAD. The majority of patients with left main CAD and a low SYNTAX score had isolated left main CAD or left main CAD plus 1-vessel CAD; the majority of those with an intermediate score had left main CAD plus 2-vessel CAD; and most of those with a high SYNTAX score had left main CAD plus 3-vessel CAD. At 1 year, rates of all-cause death and MACE were similar for the 2 groups.301 Repeat revascularization rates were higher in the PCI group than the CABG group (11.8% versus 6.5%), but stroke occurred more often in the CABG group (2.7% versus 0.3%). At 3 years of follow-up, the incidence of death in those undergoing left main CAD revascularization with low or intermediate SYNTAX scores ( 32) was 3.7% after PCI and 9.1% after CABG (P 0.03), whereas in those with a high SYNTAX score ( 33) the incidence of death after 3 years was 13.4% after PCI and 7.6% after CABG (P 0.10).334 Because the primary endpoint of SYNTAX was not met (ie, noninferiority comparison of CABG and PCI), these subgroup analyses need to be consid- ered in that context. In the LE MANS (Study of Unprotected Left Main Stenting Versus Bypass Surgery) trial,311 105 patients with left main CAD were randomized to receive PCI or CABG. Although a low proportion of patients treated with PCI received DES (35%) and a low proportion of patients treated with CABG received IMA grafts (72%), the outcomes at 30 days and 1 year were similar between the groups. In the PRECOMBAT (Premier of Randomized Comparison of By- Figure 1. Cumulative incidence of MACE in patients with 3-vessel CAD based on SYNTAX score at 3-year follow-up in the SYNTAX trial treated with either CABG or PCI. CABG indicates coronary artery bypass graft; CAD, coronary artery disease; MACE, major adverse cardiovascular event; PCI, percutaneous coronary intervention; and SYNTAX, Synergy between Percutaneous Coronary Inter- vention with TAXUS and Cardiac Surgery. Adapted with permission from Kappetein.334 Hillis et al 2011 ACCF/AHA CABG Guideline e673 pass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trial of 600 patients with left main disease, the composite endpoint of death, MI, or stroke at 2 years occurred in 4.4% of patients treated with PCI and 4.7% of patients treated with CABG, but ischemia-driven target-vessel revascularization was more often required in the patients treated with PCI The results from these 3 RCTs suggest (but do not definitively prove) that major clinical outcomes in selected patients with left main CAD are similar with CABG and PCI at 1- to 2-year follow-up, but repeat revascularization rates are higher after PCI than after CABG. RCTs with extended follow-up of 5 years are required to provide definitive conclusions about the optimal treatment of left main CAD. In a meta-analysis of 8 cohort studies and 2 RCTs,329 death, MI, and stroke occurred with similar frequency in the PCI- and CABG-treated patients at 1, 2, and 3 years of follow-up. Target-vessel revascularization was performed more often in the PCI group at 1 year (OR: 4.36), 2 years (OR: 4.20), and 3 years (OR: 3.30). See Online Data Supplements 14 to 19 for additional data comparing PCI with CABG for left main CAD. 3.7.3. Revascularization Considerations for Left Main CAD Although CABG has been considered the gold standard for unprotected left main CAD revascularization, more recently PCI has emerged as a possible alternative mode of revascu- larization in carefully selected patients. Lesion location is an important determinant when considering PCI for unprotected left main CAD. Stenting of the left main ostium or trunk is more straightforward than treating distal bifurcation or trifur- cation stenoses, which generally requires a greater degree of operator experience and expertise.464 In addition, PCI of bifurcation disease is associated with higher restenosis rates than when disease is confined to the ostium or trunk.327,465 Although lesion location influences technical success and long-term outcomes after PCI, location exerts a negligible influence on the success of CABG. In subgroup analyses, patients with left main CAD and a SYNTAX score 33 with more complex or extensive CAD had a higher mortality rate with PCI than with CABG.334 Physicians can estimate oper- ative risk for all CABG candidates by using a standard instrument, such as the risk calculator from the STS database. The above considerations are important factors when choos- ing among revascularization strategies for unprotected left main CAD and have been factored into revascularization recommendations. 