2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery
A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
- AHA Scientific Statements
- acute coronary syndromes
- antiplatelet agents
- arrhythmias, cardiac
- coronary angiography
- coronary artery revascularization interventions: stents
- drug therapy
- heart diseases
- myocardial revascularization
- platelet aggregation inhibitor
Preamble. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e654
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e656
1.1. Methodology and Evidence Review. . . . . . . .e656
1.2. Organization of the Writing Committee. . . . .e657
1.3. Document Review and Approval. . . . . . . . . . .e657
Procedural Considerations. . . . . . . . . . . . . . . . . . . .e657
2.1. Intraoperative Considerations . . . . . . . . . . . . .e657
2.1.1. Anesthetic Considerations: Recommendations. . . . . . . . . . . . . . . . .e657
2.1.2. Use of CPB . . . . . . . . . . . . . . . . . . . . .e659
2.1.3. Off-Pump CABG Versus Traditional On-Pump CABG . . . . . . . . . . . . . . . . .e659
2.1.4. Bypass Graft Conduit: Recommendations. . . . . . . . . . . . . . . . .e660
22.214.171.124. Saphenous Vein Grafts . . . . . .e661
126.96.36.199. Internal Mammary Arteries . . .e661
188.8.131.52. Radial, Gastroepiploic, and Inferior Epigastric Arteries . . .e661
2.1.5. Incisions for Cardiac Access. . . . . . . . .e661
2.1.6. Anastomotic Techniques. . . . . . . . . . . .e662
2.1.7. Intraoperative TEE: Recommendations. . . . . . . . . . . . . . . . .e662
2.1.8. Preconditioning/Management of Myocardial Ischemia: Recommendations. . . . . . . . . . . . . . . . .e663
2.2. Clinical Subsets. . . . . . . . . . . . . . . . . . . . . . . .e664
2.2.1. CABG in Patients With Acute MI: Recommendations. . . . . . . . . . . . . . . . .e664
2.2.2. Life-Threatening Ventricular Arrhythmias: Recommendations . . . . . . . . . . . . . . . . .e666
2.2.3. Emergency CABG After Failed PCI: Recommendations. . . . . . . . . . . . . . . . .e666
2.2.4. CABG in Association With Other Cardiac Procedures: Recommendations. . . . . . . . . . . . . . . . .e667
3. CAD Revascularization. . . . . . . . . . . . . . . . . . . . . .e667
3.1. Heart Team Approach to Revascularization Decisions: Recommendations . . . . . . . . . . . . .e668
3.2. Revascularization to Improve Survival: Recommendations . . . . . . . . . . . . . . . . . . . . . .e668
3.3. Revascularization to Improve Symptoms: Recommendations . . . . . . . . . . . . . . . . . . . . . .e671
3.4. CABG Versus Contemporaneous Medical Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e671
3.5. PCI Versus Medical Therapy . . . . . . . . . . . . .e671
3.6. CABG Versus PCI . . . . . . . . . . . . . . . . . . . . .e672
3.6.1. CABG Versus Balloon Angioplasty or BMS. . . . . . . . . . . . . . . . . . . . . . . . . . .e672
3.6.2. CABG Versus DES . . . . . . . . . . . . . . .e672
3.7. Left Main CAD. . . . . . . . . . . . . . . . . . . . . . . .e673
3.7.1. CABG or PCI Versus Medical Therapy for Left Main CAD . . . . . . . . . . . . . . .e673
3.7.2. Studies Comparing PCI Versus CABG for Left Main CAD. . . . . . . . . . . . . . .e673
3.7.3. Revascularization Considerations for Left Main CAD . . . . . . . . . . . . . . . . .e674
3.8. Proximal LAD Artery Disease . . . . . . . . . . .e674
3.9. Clinical Factors That May Influence the Choice of Revascularization . . . . . . . . . . . . . . . . . . .e674
3.9.1. Diabetes Mellitus . . . . . . . . . . . . . . . .e674
3.9.2. Chronic Kidney Disease . . . . . . . . . . .e675
3.9.3. Completeness of Revascularization . . . . . . . . . . . . . . . .e675
3.9.4. LV Systolic Dysfunction. . . . . . . . . . .e675
3.9.5. Previous CABG . . . . . . . . . . . . . . . . .e675
3.9.6. Unstable Angina/Non-ST-Elevation Myocardial Infarction . . . . . . . . . . . . .e676
3.9.7. DAPT Compliance and Stent Thrombosis: Recommendation . . . . . .e676
3.10. TMR as an Adjunct to CABG. . . . . . . . . . . .e676
3.11. Hybrid Coronary Revascularization: Recommendations . . . . . . . . . . . . . . . . . . . . .e676
4. Perioperative Management . . . . . . . . . . . . . . . . . . .e677
4.1. Preoperative Antiplatelet Therapy: Recommendations . . . . . . . . . . . . . . . . . . . . .e677
4.2. Postoperative Antiplatelet Therapy: Recommendations . . . . . . . . . . . . . . . . . . . . .e677
4.3. Management of Hyperlipidemia: Recommendations . . . . . . . . . . . . . . . . . . . . .e678
4.3.1. Timing of Statin Use and CABG Outcomes . . . . . . . . . . . . . . . . . . . . . .e679
184.108.40.206. Potential Adverse Effects of Perioperative Statin Therapy . . . . . . . . . . . . . . . . .e679
4.4. Hormonal Manipulation: Recommendations . . . . . . . . . . . . . . . . . . . . .e679
4.4.1. Glucose Control . . . . . . . . . . . . . . . . .e679
4.4.2. Postmenopausal Hormone Therapy. . . . . . . . . . . . . . . . . . . . . . . .e680
4.4.3. CABG in Patients With Hypothyroidism . . . . . . . . . . . . . . . . .e680
4.5. Perioperative Beta Blockers: Recommendations . . . . . . . . . . . . . . . . . . . . .e680
4.6. ACE Inhibitors/ARBs: Recommendations . . . . . . . . . . . . . . . . . . . . .e681
4.7. Smoking Cessation: Recommendations . . . . .e682
4.8. Emotional Dysfunction and Psychosocial Considerations: Recommendation . . . . . . . . .e683
4.8.1. Effects of Mood Disturbance and Anxiety on CABG Outcomes . . . . . . .e683
4.8.2. Interventions to Treat Depression in CABG Patients . . . . . . . . . . . . . . . .e683
4.9. Cardiac Rehabilitation: Recommendation. . . . . . . . . . . . . . . . . . . . . .e683
4.10. Perioperative Monitoring. . . . . . . . . . . . . . . .e684
4.10.1. Electrocardiographic Monitoring: Recommendations. . . . . . . . . . . . . . .e684
4.10.2. Pulmonary Artery Catheterization: Recommendations. . . . . . . . . . . . . . .e684
4.10.3. Central Nervous System Monitoring: Recommendations. . . . . . . . . . . . . . .e684
5. CABG-Associated Morbidity and Mortality: Occurrence and Prevention . . . . . . . . . . . . . . . . . . .e685
5.1. Public Reporting of Cardiac Surgery Outcomes: Recommendation . . . . . . . . . . . . . .e685
5.1.1. Use of Outcomes or Volume as CABG Quality Measures: Recommendations. . . . . . . . . . . . . . .e686
5.2. Adverse Events . . . . . . . . . . . . . . . . . . . . . . . .e687
5.2.1. Adverse Cerebral Outcomes . . . . . . .e687
220.127.116.11. Stroke . . . . . . . . . . . . . . . . .e687
18.104.22.168.1. Use of Epiaortic Ultrasound Imaging to Reduce Stroke Rates: Recommendation . . . . . . .e687
22.214.171.124.2. The Role of Preoperative Carotid Artery Noninvasive Screening in CABG Patients: Recommendations. . . . . . . . . . .e687
126.96.36.199. Delirium . . . . . . . . . . . . . . .e689
188.8.131.52. Postoperative Cognitive Impairment . . . . . . . . . . . . .e689
5.2.2. Mediastinitis/Perioperative Infection: Recommendations. . . . . . . . . . . . . . .e689
5.2.3. Renal Dysfunction: Recommendations. . . . . . . . . . . . . . .e691
5.2.4. Perioperative Myocardial Dysfunction: Recommendations. . . . . . . . . . . . . . .e692
184.108.40.206. Transfusion: Recommendation . . . . . . . . .e692
5.2.5. Perioperative Dysrhythmias: Recommendations. . . . . . . . . . . . . . .e692
5.2.6. Perioperative Bleeding/Transfusion: Recommendations. . . . . . . . . . . . . . .e693
6. Specific Patient Subsets . . . . . . . . . . . . . . . . . . . . .e694
6.1. Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e694
6.2. Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e694
6.3. Patients With Diabetes Mellitus . . . . . . . . . . .e695
6.4. Anomalous Coronary Arteries: Recommendations . . . . . . . . . . . . . . . . . . . . . .e696
6.5. Patients With Chronic Obstructive Pulmonary Disease/Respiratory Insufficiency: Recommendations . . . . . . . . . . . . . . . . . . . . . .e696
6.6. Patients With End-Stage Renal Disease on Dialysis: Recommendations. . . . . . . . . . . . . . .e697
6.7. Patients With Concomitant Valvular Disease: Recommendations . . . . . . . . . . . . . . . . . . . . . .e697
6.8. Patients With Previous Cardiac Surgery: Recommendation. . . . . . . . . . . . . . . . . . . . . .e697
6.8.1. Indications for Repeat CABG. . . . . . .e697
6.8.2. Operative Risk . . . . . . . . . . . . . . . . . .e698
6.8.3. Long-Term Outcomes. . . . . . . . . . . . .e698
6.9. Patients With Previous Stroke . . . . . . . . . . . .e698
6.10. Patients With PAD . . . . . . . . . . . . . . . . . . . .e698
7. Economic Issues . . . . . . . . . . . . . . . . . . . . . . . . . . .e698
7.1. Cost-Effectiveness of CABG and PCI. . . . . .e698
7.1.1. Cost-Effectiveness of CABG Versus PCI . . . . . . . . . . . . . . . . . . . . .e699
7.1.2. CABG Versus PCI With DES . . . . . .e699
8. Future Research Directions. . . . . . . . . . . . . . . . . . .e699
8.1. Hybrid CABG/PCI . . . . . . . . . . . . . . . . . . . .e700
8.2. Protein and Gene Therapy. . . . . . . . . . . . . . .e700
8.3. Teaching CABG to the Next Generation: Use of Surgical Simulators . . . . . . . . . . . . . .e700
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e701
Appendix 1. Author Relationships With Industry and Other Entities (Relevant) . . . . . . . . . . . . .e731
Appendix 2. Reviewer Relationships With Industry and Other Entitites (Relevant) . . . . . . . . .e733
Appendix 3. Abbreviation List . . . . . . . . . . . . . . . . . . .e735
The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improvement and clinical decision support tools.
The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly produced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force), charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures, directs and oversees this effort. Writing committees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patientcentric recommendations for clinical practice.
Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-specific data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing committees are asked to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and outcomes constitute the primary basis for the recommendations contained herein.
In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force.1 The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus benefits in addition to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an estimate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting each recommendation with the weight of evidence ranked as LOE A, B, or C according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized where appropriate. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by historical clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the clinicians on the writing committee is the basis for LOE C recommendations, and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate if the recommendation is determined to be of “no benefit” or is associated with “harm” to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recommendations for the comparative effectiveness of one treatment or strategy versus another have been added for COR I and IIa, LOE A or B only.
In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy (GDMT) to represent optimal medical therapy as defined by ACCF/AHA guideline–recommended therapies (primarily Class I). This new term, GDMT, will be used herein and throughout all future guidelines.
Because the ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential influence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation.
The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding the care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. As a result, situations may arise for which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas will be identified within each respective guideline when appropriate.
Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, where the benefit-to-risk ratio may be lower.
The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all such current relationships, as well as those existing 12 months previously. In December 2009, the ACCF and AHA implemented a new policy for relationships with industry and other entities (RWI) that requires the writing committee chair plus a minimum of 50% of the writing committee to have no relevant RWI (Appendix 1 for the ACCF/AHA definition of relevance). These statements are reviewed by the Task Force and all members during each conference call and meeting of the writing committee and are updated as changes occur. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the voting members. Members are not permitted to write, and must recuse themselves from voting on, any recommendation or section to which their RWI apply. Members who recused themselves from voting are indicated in the list of writing committee members, and section recusals are noted in Appendix 1. Authors' and peer reviewers' RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, writing committee members' comprehensive disclosure information—including RWI not pertinent to this document—is available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at www.cardiosource.org/ACC/About-ACC/Leadership/Guidelines-and-Documents-Task-Forces.aspx. The work of the writing committee was supported exclusively by the ACCF and AHA without commercial support. Writing committee members volunteered their time for this activity.
In an effort to maintain relevance at the point of care for practicing physicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, evidence tables (with references linked to abstracts in PubMed) have been added.
In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for Systematic Reviews and Clinical Practice Guidelines We Can Trust.2,3 It is noteworthy that the ACCF/AHA guidelines are cited as being compliant with many of the proposed standards. A thorough review of these reports and of our current methodology is under way, with further enhancements anticipated.
The recommendations in this guideline are considered current until they are superseded by a focused update or the full-text guideline is revised. Guidelines are official policy of both the ACCF and AHA.
1.1. Methodology and Evidence Review
Whenever possible, the recommendations listed in this document are evidence based. Articles reviewed in this guideline revision covered evidence from the past 10 years through January 2011, as well as selected other references through April 2011. Searches were limited to studies, reviews, and other evidence conducted in human subjects that were published in English. Key search words included but were not limited to the following: analgesia, anastomotic techniques, antiplatelet agents, automated proximal clampless anastomosis device, asymptomatic ischemia, Cardica C-port, cost effectiveness, depressed left ventricular (LV) function, distal anastomotic techniques, direct proximal anastomosis on aorta, distal anastomotic devices, emergency coronary artery bypass graft (CABG) and ST-elevation myocardial infarction (STEMI), heart failure, interrupted sutures, LV systolic dysfunction, magnetic connectors, PAS-Port automated proximal clampless anastomotic device, patency, proximal connectors, renal disease, sequential anastomosis, sternotomy, symmetry connector, symptomatic ischemia, proximal connectors, sequential anastomosis, T grafts, thoracotomy, U-clips, Ventrica Magnetic Vascular Port system, Y grafts. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative but not all-inclusive.
To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published, the absolute risk difference and number needed to treat or harm are provided in the guideline, along with confidence interval (CI) and data related to the relative treatment effects such as odds ratio (OR), relative risk (RR), hazard ratio (HR), or incidence rate ratio.
The focus of these guidelines is the safe, appropriate, and efficacious performance of CABG.
1.2. Organization of the Writing Committee
The committee was composed of acknowledged experts in CABG, interventional cardiology, general cardiology, and cardiovascular anesthesiology. The committee included representatives from the ACCF, AHA, American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons (STS).
1.3. Document Review and Approval
This document was reviewed by 2 official reviewers, each nominated by both the ACCF and the AHA, as well as 1 reviewer each from the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and STS, as well as members from the ACCF/AHA Task Force on Data Standards, ACCF/AHA Task Force on Performance Measures, ACCF Surgeons' Scientific Council, ACCF Interventional Scientific Council, and Southern Thoracic Surgical Association. All information on reviewers' RWI was distributed to the writing committee and is published in this document (Appendix 2).
This document was approved for publication by the governing bodies of the ACCF and the AHA and endorsed by the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and STS.
2. Procedural Considerations
2.1. Intraoperative Considerations
2.1.1. Anesthetic Considerations: Recommendations
Efforts are recommended to improve interdisciplinary communication and patient safety in the perioperative environment (eg, formalized checklist-guided multidisciplinary communication).12–15 (Level of Evidence: B)
A fellowship-trained cardiac anesthesiologist (or experienced board-certified practitioner) credentialed in the use of perioperative transesophageal echocardiography (TEE) is recommended to provide or supervise anesthetic care of patients who are considered to be at high risk.16–18 (Level of Evidence: C)
Class III: HARM
Routine use of early extubation strategies in facilities with limited backup for airway emergencies or advanced respiratory support is potentially harmful. (Level of Evidence: C)
See Online Data Supplement 1 for additional data on anesthetic considerations.
Anesthetic management of the CABG patient mandates a favorable balance of myocardial oxygen supply and demand to prevent or minimize myocardial injury (Section 2.1.8). Historically, the popularity of several anesthetic techniques for CABG has varied on the basis of their known or potential adverse cardiovascular effects (eg, cardiovascular depression with high doses of volatile anesthesia, lack of such depression with high-dose opioids, or coronary vasodilation and concern for a “steal” phenomenon with isoflurane) as well as concerns about interactions with preoperative medications (eg, cardiovascular depression with beta blockers or hypotension with angiotensin-converting enzyme [ACE] inhibitors and angiotensin-receptor blockers [ARBs]28–30) (Sections 2.1.8 and 4.5). Independent of these concerns, efforts to improve outcomes and to reduce costs have led to shorter periods of postoperative mechanical ventilation and even, in some patients, to prompt extubation in the operating room (“accelerated recovery protocols” or “fast-track management”).5,31
High-dose opioid anesthesia with benzodiazepine supplementation was used commonly in CABG patients in the United States in the 1970s and 1980s. Subsequently, it became clear that volatile anesthetics are protective in the setting of myocardial ischemia and reperfusion, and this, in combination with a shift to accelerated recovery or “fast-track” strategies, led to their ubiquitous use. As a result, opioids have been relegated to an adjuvant role.32,33 Despite their widespread use, volatile anesthetics have not been shown to provide a mortality rate advantage when compared with other intravenous regimens (Section 2.1.8).
Optimal anesthesia care in CABG patients should include 1) a careful preoperative evaluation and treatment of modifiable risk factors; 2) proper handling of all medications given preoperatively (Sections 4.1, 4.3, and 4.5); 3) establishment of central venous access and careful cardiovascular monitoring; 4) induction of a state of unconsciousness, analgesia, and immobility; and 5) a smooth transition to the early postoperative period, with a goal of early extubation, patient mobilization, and hospital discharge. Attention should be directed at preventing or minimizing adverse hemodynamic and hormonal alterations that may induce myocardial ischemia or exert a deleterious effect on myocardial metabolism (as may occur during cardiopulmonary bypass [CPB]) (Section 2.1.8). This requires close interaction between the anesthesiologist and surgeon, particularly when manipulation of the heart or great vessels is likely to induce hemodynamic instability. During on-pump CABG, particular care is required during vascular cannulation and weaning from CPB; with off-pump CABG, the hemodynamic alterations often caused by displacement or verticalization of the heart and application of stabilizer devices on the epicardium, with resultant changes in heart rate, cardiac output, and systemic vascular resistance, should be monitored carefully and managed appropriately.
In the United States, nearly all patients undergoing CABG receive general anesthesia with endotracheal intubation utilizing volatile halogenated general anesthetics with opioid supplementation. Intravenous benzodiazepines often are given as premedication or for induction of anesthesia, along with other agents such as propofol or etomidate. Nondepolarizing neuromuscular-blocking agents, particularly nonvagolytic agents with intermediate duration of action, are preferred to the longer-acting agent, pancuronium. Use of the latter is associated with higher intraoperative heart rates and a higher incidence of residual neuromuscular depression in the early postoperative period, with a resultant delay in extubation.23,34 In addition, low concentrations of volatile anesthetic usually are administered via the venous oxygenator during CPB, facilitating amnesia and reducing systemic vascular resistance.
Outside the United States, alternative anesthetic techniques, particularly total intravenous anesthesia via propofol and opioid infusions with benzodiazepine supplementation with or without high thoracic epidural anesthesia, are commonly used. The use of high thoracic epidural anesthesia exerts salutary effects on the coronary circulation as well as myocardial and pulmonary function, attenuates the stress response, and provides prolonged postoperative analgesia.24,25,35 In the United States, however, concerns about the potential for neuraxial bleeding (particularly in the setting of heparinization, platelet inhibitors, and CPB-induced thrombocytopenia), local anesthetic toxicity, and logistical issues related to the timing of epidural catheter insertion and management have resulted in limited use of these techniques.22 Their selective use in patients with severe pulmonary dysfunction (Section 6.5) or chronic pain syndromes may be considered. Although meta-analyses of randomized controlled trials (RCTs) of high thoracic epidural anesthesia/analgesia in CABG patients (particularly on-pump) have yielded inconsistent results on morbidity and mortality rates, it does appear to reduce time to extubation, pain, and pulmonary complications.36–38 Of interest, although none of the RCTs have reported the occurrence of epidural hematoma or abscess, these entities occur on occasion.38 Finally, the use of other regional anesthetic approaches for postoperative analgesia, such as parasternal block, has been reported.39
Over the past decade, early extubation strategies (“fast-track” anesthesia) often have been used in low- to medium-risk CABG patients. These strategies allow a shorter time to extubation, a decreased length of intensive care unit (ICU) stay, and variable effects on length of hospital stay.4–6 Immediate extubation in the operating room, with or without markedly accelerated postoperative recovery pathways (eg, “ultra-fast-tracking,” “rapid recovery protocol,” “short-stay intensive care”) have been used safely, with low rates of reintubation and no influence on quality of life.40–44 Observational data suggest that physician judgment in triaging lower-risk patients to early or immediate extubation works well, with rates of reintubation <1%.45 Certain factors appear to predict fast-track “failure,” including previous cardiac surgery, use of intra-aortic balloon counterpulsation, and possibly advanced patient age.
Provision of adequate perioperative analgesia is important in enhancing patient mobilization, preventing pulmonary complications, and improving the patient's psychological well-being.9,11 The intraoperative use of high-dose morphine (40 mg) may offer superior postoperative pain relief and enhance patient well-being compared with fentanyl (despite similar times to extubation).46
The safety of nonsteroidal anti-inflammatory agents for analgesia is controversial, with greater evidence for adverse cardiovascular events with the selective cyclooxygenase-2 inhibitors than the nonselective agents. A 2007 AHA Scientific statement presented a stepped-care approach to the management of musculoskeletal pain in patients with or at risk for coronary artery disease (CAD), with the goal of limiting the use of these agents to patients in whom safer therapies fail.47 In patients hospitalized with unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI), these agents should be discontinued promptly and reinstituted later according to the stepped-care approach.48
In the setting of cardiac surgery, nonsteroidal anti-inflammatory agents previously were used for perioperative analgesia. A meta-analysis of 20 trials of patients undergoing thoracic or cardiac surgery, which evaluated studies published before 2005, reported significant reductions in pain scores, with no increase in adverse outcomes.49 Subsequently, 2 RCTs, both studying the oral cyclooxygenase-2 inhibitor valdecoxib and its intravenous prodrug, parecoxib, reported a higher incidence of sternal infections in 1 trial and a significant increase in adverse cardiovascular events in the other.26,27 On the basis of the results of these 2 studies (as well as other nonsurgical reports of increased risk with cyclooxygenase-2–selective agents), the U.S. Food and Drug Administration in 2005 issued a “black box” warning for all nonsteroidal anti-inflammatory agents (except aspirin) immediately after CABG.50 The concurrent administration of ibuprofen with aspirin has been shown to attenuate the latter's inhibition of platelet aggregation, likely because of competitive inhibition of cyclooxygenase at the platelet-receptor binding site.51
Observational analyses in patients undergoing noncardiac surgery have shown a significant reduction in perioperative death with the use of checklists, multidisciplinary surgical care, intraoperative time-outs, postsurgical debriefings, and other communication strategies.14,15 Such methodology is being used increasingly in CABG patients.12–14
In contrast to extensive literature on the role of the surgeon in determining outcomes with CABG, limited data on the influence of the anesthesiologist are available. Of 2 such reports from single centers in the 1980s, 1 suggested that the failure to control heart rate to ≤110 beats per minute was associated with a higher mortality rate, and the other suggested that increasing duration of CPB adversely influenced outcome.52,53 Another observational analysis of data from vascular surgery patients suggested that anesthetic specialization was independently associated with a reduction in mortality rate.54
To meet the challenges of providing care for the increasingly higher-risk patients undergoing CABG, efforts have been directed at enhancing the experience of trainees, particularly in the use of newer technologies such as TEE. Cardiac anesthesiologists, in collaboration with cardiologists and surgeons, have implemented national training and certification processes for practitioners in the use of perioperative TEE (Section 2.1.7).164,165 Accreditation of cardiothoracic anesthesia fellowship programs from the Accreditation Council for Graduate Medical Education was initiated in 2004, and efforts are ongoing to obtain formal subspecialty certification.18
2.1.2. Use of CPB
Several adverse outcomes have been attributed to CPB, including 1) neurological deficits (eg, stroke, coma, postoperative neurocognitive dysfunction); 2) renal dysfunction; and 3) the Systemic inflammatory Response Syndrome (SIRS). The SIRS is manifested as generalized systemic inflammation occurring after a major morbid event, such as trauma, infection, or major surgery. It is often particularly apparent after on-pump cardiac surgery, during which surgical trauma, contact of blood with nonphysiological surfaces (eg, pump tubing, oxygenator surfaces), myocardial ischemia and reperfusion, and hypothermia combine to cause a dramatic release of cytokines (eg, interleukin [IL] 6 and IL8) and other mediators of inflammation.55 Some investigators have used serum concentrations of S100 beta as a marker of brain injury56 and have correlated increased serum levels with the number of microemboli exiting the CPB circuit during CABG. In contrast, others have noted the increased incidence of microemboli with on-pump CABG (relative to off-pump CABG) but have failed to show a corresponding worsening of neurocognitive function 1 week to 6 months postoperatively.57,58 Blood retrieved from the operative field during on-pump CABG contains lipid material and particulate matter, which have been implicated as possible causes of postoperative neurocognitive dysfunction. Although a study59 reported that CPB-associated neurocognitive dysfunction can be mitigated by the routine processing of shed blood with a cell saver before its reinfusion, another study60 failed to show such an improvement.
It has been suggested that CPB leads to an increased incidence of postoperative renal failure requiring dialysis, but a large RCT comparing on-pump and off-pump CABG showed no difference in its occurrence.61 Of interest, this study failed to show a decreased incidence of postoperative adverse neurological events (stroke, coma, or neurocognitive deficit) in those undergoing off-pump CABG.
The occurrence of SIRS in patients undergoing CPB has led to the development of strategies designed to prevent or to minimize its occurrence. Many reports have focused on the increased serum concentrations of cytokines (eg, IL-2R, IL-6, IL-8, tumor necrosis factor alpha) and other modulators of inflammation (eg, P-selectin, sE-selectin, soluble intercellular adhesion molecule-1, plasma endothelial cell adhesion molecule-1, and plasma malondialdehyde), which reflect leukocyte and platelet activation, in triggering the onset of SIRS. A study showed a greater upregulation of neutrophil CD11b expression (a marker of leukocyte activation) in patients who sustained a ≥50% increase in the serum creatinine concentration after CPB, thereby implicating activated neutrophils in the pathophysiology of SIRS and the occurrence of post-CPB renal dysfunction.62 Modulating neutrophil activation to reduce the occurrence of SIRS has been investigated; however, the results have been inconsistent. Preoperative intravenous methylprednisolone (10 mg/kg) caused a reduction in the serum concentrations of many of these cytokines after CPB, but this reduction was not associated with improved hemodynamic variables, diminished blood loss, less use of inotropic agents, shorter duration of ventilation, or shorter ICU length of stay.63 Similarly, the use of intravenous immunoglobulin G in patients with post-CPB SIRS has not been associated with decreased rates of short-term morbidity or 28-day mortality.64
Other strategies to mitigate the occurrence of SIRS after CPB have been evaluated, including the use of 1) CPB circuits (including oxygenators) coated with materials known to reduce complement and leukocyte activation; 2) CPB tubing that is covalently bonded to heparin; and 3) CPB tubing coated with polyethylene oxide polymer or Poly (2-methoxyethylacrylate). Leukocyte depletion via specialized filters in the CPB circuits has been shown to reduce the plasma concentrations of P-selectin, intercellular adhesion molecule-1, IL-8, plasma endothelial cell adhesion molecule-1, and plasma malondialdehyde after CPB.65
Finally, closed mini-circuits for CPB have been developed in an attempt to minimize the blood–air interface and blood contact with nonbiological surfaces, both of which promote cytokine elaboration, but it is uncertain if these maneuvers and techniques have a discernible effect on outcomes after CABG.
2.1.3. Off-Pump CABG Versus Traditional On-Pump CABG
Since the first CABG was performed in the late 1960s, the standard surgical approach has included the use of cardiac arrest coupled with CPB (so-called on-pump CABG), thereby optimizing the conditions for construction of vascular anastomoses to all diseased coronary arteries without cardiac motion or hemodynamic compromise. Such on-pump CABG has become the gold standard and is performed in about 80% of subjects undergoing the procedure in the United States. Despite the excellent results that have been achieved, the use of CPB and the associated manipulation of the ascending aorta are linked with certain perioperative complications, including myonecrosis during aortic occlusion, cerebrovascular accidents, generalized neurocognitive dysfunction, renal dysfunction, and SIRS. In an effort to avoid these complications, off-pump CABG was developed.58,66 Off-pump CABG is performed on the beating heart with the use of stabilizing devices (which minimize cardiac motion); in addition, it incorporates techniques to minimize myocardial ischemia and systemic hemodynamic compromise. As a result, the need for CPB is obviated. This technique does not necessarily decrease the need for manipulation of the ascending aorta during construction of the proximal anastomoses.
To date, the results of several RCTs comparing on-pump and off-pump CABG in various patient populations have been published.61,67,68 In addition, registry data and the results of meta-analyses have been used to assess the relative efficacies of the 2 techniques.69,70 In 2005, an AHA Scientific statement comparing the 2 techniques concluded that both procedures usually result in excellent outcomes and that neither technique should be considered superior to the other.71 At the same time, several differences were noted. Off-pump CABG was associated with less bleeding, less renal dysfunction, a shorter length of hospital stay, and less neurocognitive dysfunction. The incidence of perioperative stroke was similar with the 2 techniques. On-pump CABG was noted to be less technically complex and allowed better access to diseased coronary arteries in certain anatomic locations (eg, those on the lateral LV wall) as well as better long-term graft patency.
In 2009, the results of the largest RCT to date comparing on-pump CABG to off-pump CABG, the ROOBY (Randomized On/Off Bypass) trial, were published, reporting the outcomes for 2203 patients (99% men) at 18 Veterans Affairs Medical Centers.61 The primary short-term endpoint, a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) within 30 days of surgery, occurred with similar frequency (5.6% for on-pump CABG; 7.0% for off-pump CABG; P=0.19). The primary long-term endpoint, a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction (MI) within 1 year of surgery, occurred more often in those undergoing off-pump CABG (9.9%) than in those having on-pump CABG (7.4%; P=0.04). Neuropsychological outcomes and resource utilization were similar between the 2 groups. One year after surgery, graft patency was higher in the on-pump group (87.8% versus 82.6%; P<0.01). In short, the ROOBY investigators failed to show an advantage of off-pump CABG compared with on-pump CABG in a patient population considered to be at low risk. Instead, use of the on-pump technique was associated with better 1-year composite outcomes and 1-year graft patency rates, with no difference in neuropsychological outcomes or resource utilization.
Although numerous investigators have used single-center registries, the STS database, and meta-analyses in an attempt to identify patient subgroups in whom off-pump CABG is the preferred procedure, even these analyses have reached inconsistent conclusions about off-pump CABG's ability to reduce morbidity and mortality rates.69,72–83 A retrospective cohort study of 14 766 consecutive patients undergoing isolated CABG identified a mortality benefit (OR: 0.45) for off-pump CABG in patients with a predicted risk of mortality >2.5%,82 but a subsequent randomized comparison of off-pump CABG to traditional on-pump CABG in 341 high-risk patients (a Euroscore >5) showed no difference in the composite endpoint of all-cause death, acute MI, stroke, or a required reintervention procedure.78 An analysis of data from the New York State Cardiac Surgery Reporting system did not demonstrate a reduction in mortality rate with off-pump CABG in any patient subgroup, including the elderly (age >80 years) or those with cerebrovascular disease, azotemia, or an extensively calcified ascending aorta.69
Despite these results, off-pump CABG is the preferred approach by some surgeons who have extensive experience with it and therefore are comfortable with its technical nuances. Recently, published data suggested that the avoidance of aortic manipulation is the most important factor in reducing the risk of neurological complications.84,85 Patients with extensive disease of the ascending aorta pose a special challenge for on-pump CABG; for these patients, cannulation or cross-clamping of the aorta may create an unacceptably high risk of stroke. In such individuals, off-pump CABG in conjunction with avoidance of manipulation of the ascending aorta (including placement of proximal anastomoses) may be beneficial. Surgeons typically prefer an on-pump strategy in patients with hemodynamic compromise because CPB offers support for the systemic circulation. In the end, most surgeons consider either approach to be reasonable for the majority of subjects undergoing CABG.
2.1.4. Bypass Graft Conduit: Recommendations
The right internal mammary artery (IMA) is probably indicated to bypass the LAD artery when the LIMA is unavailable or unsuitable as a bypass conduit. (Level of Evidence: C)
When anatomically and clinically suitable, use of a second IMA to graft the left circumflex or right coronary artery (when critically stenosed and perfusing LV myocardium) is reasonable to improve the likelihood of survival and to decrease reintervention.90–94 (Level of Evidence: B)
Complete arterial revascularization may be reasonable in patients less than or equal to 60 years of age with few or no comorbidities. (Level of Evidence: C)
Use of a radial artery graft may be reasonable when grafting left-sided coronary arteries with severe stenoses (>70%) and right-sided arteries with critical stenoses (≥90%) that perfuse LV myocardium.96–101 (Level of Evidence: B)
Class III: HARM
An arterial graft should not be used to bypass the right coronary artery with less than a critical stenosis (<90%).89 (Level of Evidence: C)
Arteries (internal mammary, radial, gastroepiploic, and inferior epigastric) or veins (greater and lesser saphenous) may be used as conduits for CABG. The effectiveness of CABG in relieving symptoms and prolonging life is directly related to graft patency. Because arterial and venous grafts have different patency rates and modes of failure, conduit selection is important in determining the long-term efficacy of CABG.
220.127.116.11. Saphenous Vein Grafts
Reversed saphenous vein grafts (SVGs) are commonly used in patients undergoing CABG. Their disadvantage is a declining patency with time: 10% to as many as 25% of them occlude within 1 year of CABG89,102,103; an additional 1% to 2% occlude each year during the 1 to 5 years after surgery; and 4% to 5% occlude each year between 6 and 10 years postoperatively.104 Therefore, 10 years after CABG, 50% to 60% of SVGs are patent, only half of which have no angiographic evidence of atherosclerosis.104 During SVG harvesting and initial exposure to arterial pressure, the endothelium often is damaged, which, if extensive, may lead to platelet aggregation and graft thrombosis. Platelet adherence to the endothelium begins the process of intimal hyperplasia that later causes SVG atherosclerosis.103,105 After adhering to the intima, the platelets release mitogens that stimulate smooth muscle cell migration, leading to intimal proliferation and hyperplasia. Lipid is incorporated into these areas of intimal hyperplasia, resulting in atherosclerotic plaque formation.106 The perioperative administration of aspirin and dipyridamole improves early (<1 month) and 1-year SVG patency and decreases lipid accumulation in the SVG intima.103,106,107
18.104.22.168. Internal Mammary Arteries
Unlike SVGs, IMAs usually are patent for many years postoperatively (10-year patency >90%)89,95,102,108–117 because of the fact that <4% of IMAs develop atherosclerosis, and only 1% have atherosclerotic stenoses of hemodynamic significance.118–120 This resistance to the development of atherosclerosis is presumably due to 1) the nearly continuous internal elastic lamina that prevents smooth muscle cell migration and 2) the release of prostacyclin and nitric oxide, potent vasodilators and inhibitors of platelet function, by the endothelium of IMAs.119,121,122
The disadvantage of using the IMA is that it may spasm and eventually atrophy if used to bypass a coronary artery without a flow-limiting stenosis.89,95,118,123–130 Observational studies suggest an improved survival rate in patients undergoing CABG when the LIMA (rather than an SVG) is used to graft the LAD artery86–88; this survival benefit is independent of the patient's sex, age, extent of CAD, and LV systolic function.87,88 Apart from improving survival rate, LIMA grafting of the LAD artery reduces the incidence of late MI, hospitalization for cardiac events, need for reoperation, and recurrence of angina.86,88 The LIMA should be used to bypass the LAD artery provided that a contraindication to its use (eg, emergency surgery, poor LIMA blood flow, subclavian artery stenosis, radiation injury, atherosclerosis) is not present.
Because of the beneficial influence on morbidity and mortality rates of using the IMA for grafting, several centers have advocated bilateral IMA grafting in hopes of further improving CABG results.90,91,94 In fact, numerous observational studies have demonstrated improved morbidity and mortality rates when both IMAs are used. On the other hand, bilateral IMA grafting appears to be associated with an increased incidence of sternal wound infections in patients with diabetes mellitus and those who are obese (body mass index >30 kg/m2).
22.214.171.124. Radial, Gastroepiploic, and Inferior Epigastric Arteries
Ever since the observation that IMAs are superior to SVGs in decreasing the occurrence of ischemic events and prolonging survival, other arterial conduits, such as the radial, gastroepiploic, and inferior epigastric arteries, have been used in an attempt to improve the results of CABG. Information about these other arterial conduits is sparse in comparison to what is known about IMAs and SVGs, however. The radial artery is a muscular artery that is susceptible to spasm and atrophy when used to graft a coronary artery that is not severely narrowed. Radial artery graft patency is best when used to graft a left-sided coronary artery with >70% stenosis and worst when it is used to bypass the right coronary artery with a stenosis of only moderate severity.96–100
The gastroepiploic artery is most often used to bypass the right coronary artery or its branches, although it may be used to bypass the LAD artery if the length of the gastroepiploic artery is adequate. Similar to the radial artery, it is prone to spasm and therefore should only be used to bypass coronary arteries that are severely stenotic.131 The 1-, 5-, and 10-year patency rates of the gastroepiploic artery are reportedly 91%, 80%, and 62%, respectively.132
The inferior epigastric artery is only 8 to 10 centimeters in length and therefore is usually used as a “Y” or “T” graft connected to another arterial conduit. On occasion it is used as a free graft from the aorta to a high diagonal branch of the LAD artery. Because it is a muscular artery, it is prone to spasm and therefore is best used to bypass a severely stenotic coronary artery. Its reported 1-year patency is about 90%.133,134
2.1.5. Incisions for Cardiac Access
Although the time-honored incision for CABG is a median sternotomy, surgeons have begun to access the heart via several other approaches in an attempt to 1) reduce the traumatic effects often seen with full median sternotomy, 2) hasten postoperative recovery, and 3) enhance cosmesis. The utility and benefit of these smaller incisions has been evident in subjects undergoing valvular surgery, for which only limited access to the heart is required.
The most minimally invasive access incisions for CABG are seen with robotically assisted totally endoscopic CABG. A study showed that totally endoscopic CABG with robotic technology was associated with improved physical health, shorter hospital stay, and a more rapid return to the activities of daily living compared with traditional techniques. At present, direct comparisons of robotically assisted and conventional CABG are lacking.135
The use of minimally invasive cardiac access incisions for CABG is limited. The need for adequate exposure of the ascending aorta and all surfaces of the heart to accomplish full revascularization usually precludes the use of minimal access incisions, such as upper sternotomy, lower sternotomy, or anterolateral thoracotomy. Nevertheless, use of limited incisions may increase in the future with the advent of hybrid strategies that use a direct surgical approach (usually for grafting the LAD artery through a small parasternal incision) and percutaneous coronary intervention (PCI) of the other diseased coronary arteries. The benefit of hybrid revascularization and hybrid operating rooms, in which PCI and CABG can be accomplished in one procedure, is yet to be determined. In patients with certain comorbid conditions, such as severe aortic calcification, previous chest irradiation, and obesity in combination with severe diabetes mellitus, full median sternotomy may be problematic,136 and hybrid revascularization may be preferable.
2.1.6. Anastomotic Techniques
At present, most coronary bypass grafts are constructed with hand-sewn suture techniques for the proximal and distal anastomoses, a practice that has resulted in good short- and intermediate-term patency rates. Because surgeons have different preferences with regard to the technical aspects of the procedure, a wide variety of suture configurations is used. Sewing of the proximal and distal anastomoses with a continuous polypropylene suture is commonly done, but techniques with interrupted silk sutures have been used, with similar results for graft patency and adverse events.
Certain clinical scenarios have precipitated an interest in alternative techniques of constructing coronary bypass anastomoses. Some surgeons and patients wish to avoid the potential morbidity and cosmetic results of a median sternotomy, yet the least invasive incisions usually are too small to allow hand-sewn anastomoses. To solve this problem, coronary 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 embolization 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
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 recommendations on those reported in the 1996 American Society of Anesthesiologists/Society of Cardiovascular Anesthesiologists 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 methodologies 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 suggested 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 measurement of cardiac output by TEE may facilitate anesthetic, fluid, and inotropic/pressor management. The utility of echocardiography 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 complications that may alter the planned surgery.
In patients undergoing CABG, intraoperative TEE is used most often for the detection of regional wall motion abnormalities (possibly caused by myocardial ischemia or infarction) and their effect on LV function. Observational studies have suggested that regional wall motion abnormalities detected 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 visualized by TEE would facilitate surgical intervention has not been realized, technical advances in imaging of coronary arteries and grafts may ultimately provide reliable information. At present, the evaluation of graft flow with conventional 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 (Section 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 imaging, 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 practitioner preferences, the healthcare system and reimbursement strategies, tertiary care status, and presence of training programs.155 The efficacy of intraoperative TEE is likely influenced 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 experience.137,138,140–142,144,145,156–163
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 intraoperative imaging by skilled operators in high-volume centers 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 mediastinitis) 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 manifest 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 observational 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 outcome.173
2.1.8. Preconditioning/Management of Myocardial Ischemia: Recommendations
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 infarction.53,174–177 (Level of Evidence: B)
The effectiveness of prophylactic pharmacological therapies or controlled reperfusion strategies aimed at inducing preconditioning or attenuating the adverse consequences of myocardial reperfusion injury or surgically induced systemic inflammation is uncertain.182–189 (Level of Evidence: A)
Remote ischemic preconditioning strategies using peripheral-extremity occlusion/reperfusion might be considered to attenuate the adverse consequences of myocardial reperfusion injury.193–195 (Level of Evidence: B)
See Online Data Supplements 2 to 4 for additional data on preconditioning.
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 abnormalities, many of which are not amenable to routine diagnostic and therapeutic interventions. Adequate surgical reperfusion is important in determining outcome, even though it may initially induce reperfusion injury. Various studies delineating 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 numerous 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 cardioplegia 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 magnitude of SIRS is greater with on-pump CABG than with off-pump CABG.201,208,210–213
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, enthusiasm 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 preconditioning 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 release 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 approach.194
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 considered 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 between elevated perioperative heart rates and adverse outcomes,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 hypotension associated with surgical manipulation, cannulation for CPB, weaning from CPB, or during suspension and stabilization 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
Emergency CABG is recommended in patients with acute MI in whom 1) primary PCI has failed or cannot be performed, 2) coronary anatomy is suitable for CABG, and 3) persistent ischemia of a significant area of myocardium at rest and/or hemodynamic instability refractory to nonsurgical therapy is present.235–239 (Level of Evidence: B)
Emergency CABG is recommended in patients undergoing surgical repair of a postinfarction mechanical complication of MI, such as ventricular septal rupture, mitral valve insufficiency because of papillary muscle infarction and/or rupture, or free wall rupture.240–244 (Level of Evidence: B)
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)
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)
The use of CABG is reasonable as a revascularization 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)
Early revascularization with PCI or CABG is reasonable for selected patients greater than 75 years of age with ST-segment elevation or left bundle branch block who are suitable for revascularization irrespective of the time interval from MI to onset of shock.250–254 (Level of Evidence: B)
Class III: HARM
Emergency CABG should not be performed in patients with persistent angina and a small area of viable myocardium who are stable hemodynamically. (Level of Evidence: C)
Emergency CABG should not be performed in patients with noreflow (successful epicardial reperfusion 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 emergency 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 revascularization 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 Multicenter 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 reported 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 delineation between STEMI and NSTEMI patients in these large database reports.259,265 In an analysis of 9476 patients hospitalized with an acute coronary syndrome (ACS) who underwent CABG during the index hospitalization, 1344 (14%) were STEMI patients with shock or intra-aortic balloon placement preoperatively.264 These individuals had a mortality 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 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 mortality 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 survivors 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 counterpulsation preoperatively, pulmonary disease, renal insufficiency, and magnitude of elevation of the serum troponin concentration.235,239,263,265,266,269,270
2.2.2. Life-Threatening Ventricular Arrhythmias: Recommendations
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
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 inducible 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 favorable prognosis of subjects undergoing CABG for ischemic ventricular tachycardia/fibrillation.248
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 implantable cardioverter-defibrillator is often warranted.276 Similarly, continued inducibility or clinical recurrence of ventricular 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
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)
Emergency CABG can be beneficial after failed PCI for hemodynamic compromise in patients with impairment of the coagulation system and without previous sternotomy. (Level of Evidence: C)
Emergency CABG might be considered after failed PCI for hemodynamic compromise in patients with previous sternotomy. (Level of Evidence: C)
Class III: HARM
Emergency CABG should not be performed after failed PCI in the absence of ischemia or threatened occlusion. (Level of Evidence: C)
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 antiplatelet 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 emergency 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) malfunction of PCI equipment (eg, stent dislodgement, fractured guidewire). Subjects most likely to require emergency 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 friable).281
In those in whom emergency CABG for failed PCI is performed, morbidity and mortality rates are increased compared 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 perioperative morbidity and mortality rates, including 1) depressed LV systolic function,290 2) recent ACS,290,291 3) multivessel CAD and complex lesion morphology,291,292 4) cardiogenic shock,281 5) advanced patient age,293 6) absence of angiographic collaterals,293 7) previous PCI,294 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
CABG is recommended in patients undergoing noncoronary 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 coronary arteries. (Level of Evidence: C)
The use of the LIMA is reasonable to bypass a significantly narrowed LAD artery in patients undergoing noncoronary cardiac surgery. (Level of Evidence: C)
CABG of moderately diseased coronary arteries (>50% luminal diameter narrowing) is reasonable in patients undergoing noncoronary cardiac surgery. (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 revascularization 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 “significant.”299,300
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 revascularization 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 Therefore, the results of SYNTAX have been considered appropriately when formulating our revascularization recommendations. Although the limitations of using the SYNTAX score for certain revascularization recommendations 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. Recommendations 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 summarized 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
One protocol used in RCTs302–304,311 often involves a multidisciplinary approach referred to as the Heart Team. Composed 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 committees endorse a Heart Team approach in patients with unprotected left main CAD and/or complex CAD in whom the optimal revascularization strategy is not straightforward. 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 cardiologist, 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 decisions.301,302,305–310
3.2. Revascularization to Improve Survival: Recommendations
Left Main CAD Revascularization
PCI to improve survival is reasonable as an alternative to CABG in selected stable patients with significant (≥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 outcomes (eg, STS-predicted risk of operative mortality ≥5%).301,305,307,311,319–336 (Level of Evidence: B)
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)
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)
PCI to improve survival may be reasonable as an alternative 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 outcome (eg, low–intermediate SYNTAX score of <33, bifurcation left main CAD); and 2) clinical characteristics that predict an increased risk of adverse surgical outcomes (eg, moderate–severe chronic obstructive pulmonary disease, disability from previous stroke, or previous cardiac surgery; STS-predicted risk of operative mortality >2%).301,305,307,311,319–336,340 (Level of Evidence: B)
Class III: HARM
Non–Left Main CAD Revascularization
CABG to improve survival is beneficial in patients with significant (≥70% diameter) stenoses in 3 major coronary arteries (with or without involvement of the proximal LAD artery) or in the proximal LAD plus 1 other major coronary artery.314,318,341–344 (Level of Evidence: B)
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)
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 evaluation, 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)
CABG to improve survival is reasonable in patients with mild-moderate LV systolic dysfunction (EF 35% to 50%) and significant (≥70% diameter stenosis) 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)
CABG with a LIMA graft to improve survival is reasonable in patients with significant (≥70% diameter) stenosis in the proximal LAD artery and evidence of extensive ischemia.87,88,318,343 (Level of Evidence: B)
It is reasonable to choose CABG over PCI to improve 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)
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)
The usefulness of CABG to improve survival is uncertain in patients with significant (≥70%) stenoses in 2 major coronary arteries not involving the proximal LAD artery and without extensive ischemia.343 (Level of Evidence: C)
The usefulness of PCI to improve survival is uncertain 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)
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)
Class III: HARM
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 not anatomically or functionally significant (eg, <70% diameter non–left main coronary artery stenosis, fractional 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 Evidence: B)
3.3. Revascularization to Improve Symptoms: Recommendations
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 patient preferences. (Level of Evidence: C)
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)
It is reasonable to choose CABG over PCI to improve 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)
CABG to improve symptoms might be reasonable for patients with previous CABG, 1 or more significant (≥70% diameter) coronary artery stenoses not amenable to PCI, and unacceptable angina despite GDMT.381 (Level of Evidence: C)
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
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 revascularization in certain subjects with stable angina: the Veterans Affairs Cooperative Study,402 European Coronary Surgery 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 advantage 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 additional 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. Conversely, the concurrent administration of GDMT may substantially improve long-term outcomes in patients treated with CABG in comparison with those receiving medical therapy alone. In the BARI 2D (Bypass Angioplasty Revascularization 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 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, which will provide contemporary data on the optimal management strategy (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 lowered 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 Neither COURAGE (Clinical Outcomes Utilizing Revascularization 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 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:
3.6. CABG Versus PCI
The results of 26 RCTs comparing CABG and PCI have been published: Of these, 9 compared CABG with balloon angioplasty,363,393,415–429 14 compared CABG with BMS implantation,376,430–447 and 3 compared CABG with DES implantation.302,448,449
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 following450:
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.
Incidence of MI was similar at 5 years after randomization. 3. Procedural stroke occurred more commonly with CABG than with PCI (1.2% versus 0.6%).
Relief of angina was accomplished more effectively with CABG than with PCI 1 year after randomization and 5 years after randomization.
During the first year after randomization, repeat coronary 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 characteristics, including the number of diseased coronary arteries.
Many trials did not report outcomes for other important patient subsets. For example, the available data are insufficient to determine if race, obesity, renal dysfunction, peripheral artery disease (PAD), or previous coronary revascularization affected the comparative outcomes of CABG and PCI.
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
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 composite 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 SYNTAX 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 reduction 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 outcome, 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, approximately 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 prevented 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 considered 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 Bypass 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 (9.0% versus 4.2%).340
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 revascularization 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 trifurcation 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 operative 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 choosing among revascularization strategies for unprotected left main CAD and have been factored into revascularization recommendations. Use of a Heart Team approach has been recommended in cases in which the choice of revascularization is not straightforward. As discussed in Section 3.9.7, the ability of the patient to tolerate and comply with dual antiplatelet therapy (DAPT) is also an important consideration in revascularization decisions.
The 2005 PCI guidelines466 recommended routine angiographic follow-up 2 to 6 months after stenting for uprotected left main CAD. However, because angiography has limited ability to predict stent thrombosis and the results of SYNTAX suggest good intermediate-term results for PCI in subjects with left main CAD, this recommendation was removed in the 2009 STEMI/PCI focused update.467
Experts have recommended immediate PCI for unprotected left main CAD in the setting of STEMI.339 The impetus for such a strategy is greatest when the left main CAD is the site of the culprit lesion, antegrade coronary flow is diminished [eg, Thrombolysis In Myocardial Infarction flow grade 0, 1, or 2], the patient is hemodynamically unstable, and it is believed that PCI can be performed more quickly than CABG. When possible, the interventional cardiologist and cardiac surgeon should decide together on the optimal form of revascularization for these subjects, although it is recognized that these patients are usually critically ill and therefore not amenable to a prolonged deliberation or discussion of treatment options.
3.8. Proximal LAD Artery Disease
A cohort study341 and a meta-analysis318 from the 1990s suggested that CABG confers a survival advantage over contemporaneous medical therapy for patients with disease in the proximal segment of the LAD artery. Cohort studies and RCTs318,420,432,433,435,448,468–470 as well as collaborative- and meta-analyses451,471–473 showed that PCI and CABG result in similar survival rates in these patients.
See Online Data Supplement 20 for additional data regarding proximal LAD artery revascularization.
3.9. Clinical Factors That May Influence the Choice of Revascularization
3.9.1. Diabetes Mellitus
An analysis performed in 2009 of data on 7812 patients (1233 with diabetes) in 10 RCTs demonstrated a worse long-term survival rate in patients with diabetes mellitus after balloon angioplasty or BMS implantation than after CABG.451 The BARI 2D trial404 randomly assigned 2368 patients with type 2 diabetes and CAD to undergo intensive medical therapy or prompt revascularization with PCI or CABG, according to whichever was thought to be more appropriate. By study design, those with less extensive CAD more often received PCI, whereas those with more extensive CAD were more likely to be treated with CABG. The study was not designed to compare PCI with CABG. At 5-year follow-up, no difference in rates of survival or MACE between the medical therapy group and those treated with revascularization was noted. In the PCI stratum, no significant difference in MACE between medical therapy and revascularization was demonstrated (DES in 35%; BMS in 56%); in the CABG stratum, MACE occurred less often in the revascularization group. One-year follow-up data from the SYNTAX study demonstrated a higher rate of repeat revascularization in patients with diabetes mellitus treated with PCI than with CABG, driven by a tendency for higher repeat revascularization rates in those with higher SYNTAX scores undergoing PCI.364 In summary, in subjects requiring revascularization for multivessel CAD, current evidence supports diabetes mellitus as an important factor when deciding on a revascularization strategy, particularly when complex or extensive CAD is present (Figure 2).
See Online Data Supplements 21 and 22 for additional data regarding diabetes mellitus.
3.9.2. Chronic Kidney Disease
Cardiovascular morbidity and mortality rates are markedly increased in patients with chronic kidney disease (CKD) when compared with age-matched controls without CKD. The mortality rate for patients on hemodialysis is >20% per year, and approximately 50% of deaths among these patients are due to a cardiovascular cause.476,477
To date, randomized comparisons of coronary revascularization (with CABG or PCI) and medical therapy in patients with CKD have not been reported. Some, but not all, observational studies or subgroup analyses have demonstrated an improved survival rate with revascularization compared with medical therapy in patients with CKD and multivessel CAD,478–480 despite the fact that the incidence of periprocedural complications (eg, death, MI, stroke, infection, renal failure) is increased in patients with CKD compared with those without renal dysfunction. Some studies have shown that CABG is associated with a greater survival benefit than PCI among patients with severe renal dysfunction.479–485
3.9.3. Completeness of Revascularization
Most patients undergoing CABG receive complete or nearly complete revascularization, which seems to influence long-term prognosis positively.486 In contrast, complete revascularization is accomplished less often in subjects receiving PCI (eg, in <70% of patients), but the extent to which the absence of complete initial revascularization influences outcome is less clear. Rates of late survival and survival free of MI appear to be similar in patients with and without complete revascularization after PCI. Nevertheless, the need for subsequent CABG is usually higher in those whose initial revascularization procedure was incomplete (compared with those with complete revascularization) after PCI.487–489
3.9.4. LV Systolic Dysfunction
Several older studies and a meta-analysis of the data from these studies reported that patients with LV systolic dys-function (predominantly mild to moderate in severity) had better survival with CABG than with medical therapy alone.318,352–356 For patients with more severe LV systolic dysfunction, however, the evidence that CABG results in better survival compared with medical therapy is lacking. In the STICH (Surgical Treatment for Ischemic Heart Failure) trial of subjects with LVEF <35% with or without viability testing, CABG and GDMT resulted in similar rates of survival (death from any cause, the study's primary outcome) after 5 years of follow-up. For a number of secondary outcomes at this time point, including 1) death from any cause or hospitalization for heart failure, 2) death from any cause or hospitalization for cardiovascular causes, 3) death from any cause or hospitalization for any cause, or 4) death from any cause or revascularization with PCI or CABG, CABG was superior to GDMT. Although the primary outcome (death from any cause) was similar in the 2 treatment groups after an average of 5 years of follow-up, the data suggest the possibility that outcomes would differ if the follow-up were longer in duration; as a result, the study is being continued to provide follow-up for up to 10 years.371,372
Only very limited data comparing PCI with medical therapy in patients with LV systolic dysfunction are available.356 In several ways, these data are suboptimal, in that many studies compared CABG with balloon angioplasty, many were retrospective, and many were based on cohort or registry data. Some of the studies demonstrated a similar survival rate in patients having CABG and PCI,359,451,490–492 whereas others showed that those undergoing CABG had better outcomes.320 The data that exist at present on revascularization in patients with CAD and LV systolic dysfunction are more robust for CABG than for PCI, although data from contemporary RCTs in this patient population are lacking. Therefore, the choice of revascularization in patients with CAD and LV systolic dysfunction is best based on clinical variables (eg, coronary anatomy, presence of diabetes mellitus, presence of CKD), magnitude of LV systolic dysfunction, patient preferences, clinical judgment, and consultation between the interventional cardiologist and the cardiac surgeon.
3.9.5. Previous CABG
In patients with recurrent angina after CABG, repeat revascularization is most likely to improve survival in subjects at highest risk, such as those with obstruction of the proximal LAD artery and extensive anterior ischemia.373–381 Patients with ischemia in other locations and those with a patent LIMA to the LAD artery are unlikely to experience a survival benefit from repeat revascularization.380
Cohort studies comparing PCI and CABG among post-CABG patients report similar rates of mid- and long-term survival after the 2 procedures.373,376–379,381,493 In the patient with previous CABG who is referred for revascularization for medically refractory ischemia, factors that may support the choice of repeat CABG include vessels unsuitable for PCI, number of diseased bypass grafts, availability of the IMA for grafting, chronically occluded coronary arteries, and good distal targets for bypass graft placement. Factors favoring PCI over CABG include limited areas of ischemia causing symptoms, suitable PCI targets, a patent graft to the LAD artery, poor CABG targets, and comorbid conditions.
3.9.6. Unstable Angina/Non–ST-Elevation Myocardial Infarction
The main difference between management of the patient with SIHD and the patient with UA/NSTEMI is that the impetus for revascularization is stronger in the setting of UA/NSTEMI, because myocardial ischemia occurring as part of an ACS is potentially life threatening, and associated anginal symptoms are more likely to be reduced with a revascularization procedure than with GDMT.494–496 Thus, the indications for revascularization are strengthened by the acuity of presentation, the extent of ischemia, and the ability to achieve full revascularization. The choice of revascularization method is generally dictated by the same considerations used to decide on PCI or CABG for patients with SIHD.
3.9.7. DAPT Compliance and Stent Thrombosis: Recommendation
Class III: HARM
The risk of stent thrombosis is increased dramatically in patients who prematurely discontinue DAPT, and stent thrombosis is associated with a mortality rate of 20% to 45%.497 Because the risk of stent thrombosis with BMS is greatest in the first 14 to 30 days, this is the generally recommended minimum duration of DAPT therapy for these individuals. Consensus in clinical practice is to treat DES patients for at least 12 months with DAPT to avoid late (after 30 days) stent thrombosis.497,501 Therefore, the ability of the patient to tolerate and comply with at least 30 days of DAPT with BMS treatment and at least 12 months of DAPT with DES treatment is an important consideration in deciding whether to use PCI to treat patients with CAD.
3.10. TMR as an Adjunct to CABG
TMR has been used on occasion in patients with severe angina refractory to GDMT in whom complete revascularization cannot be achieved with PCI and/or CABG. Although the mechanism by which TMR might be efficacious in these patients is unknown,502,503 several RCTs of TMR as sole therapy demonstrated a reduction in anginal symptoms compared with intensive medical therapy alone.397–399,504–506 A single randomized multicenter comparison of TMR (with a holmium:YAG laser) plus CABG and CABG alone in subjects in whom some myocardial segments were perfused by arteries considered not amenable to grafting showed a significant reduction in perioperative mortality rate (1.5% versus 7.6%, respectively), and the survival benefit of the TMR–CABG combination was present after 1 year of follow-up.400 At the same time, a large retrospective analysis of data from the STS National Cardiac Database, as well as a study of 169 patients from the Washington Hospital Center who underwent combined TMR–CABG, showed no difference in adjusted mortality rate compared with CABG alone.401,507 In short, a TMR–CABG combination does not appear to improve survival compared with CABG alone. In selected patients, however, such a combination may be superior to CABG alone in relieving angina.
3.11. Hybrid Coronary Revascularization: Recommendations
Hybrid coronary revascularization (defined as the planned combination of LIMA-to-LAD artery grafting and PCI of ≥1 non-LAD coronary arteries) is reasonable in patients with 1 or more of the following508–516 (Level of Evidence: B):
Limitations to traditional CABG, such as heavily calcified proximal aorta or poor target vessels for CABG (but amenable to PCI);
Lack of suitable graft conduits;
Unfavorable LAD artery for PCI (ie, excessive vessel tortuosity or chronic total occlusion).
Hybrid coronary revascularization (defined as the planned combination of LIMA-to-LAD artery grafting and PCI of ≥1 non-LAD coronary arteries) may be reasonable as an alternative to multivessel PCI or CABG in an attempt to improve the overall risk–benefit ratio of the procedures. (Level of Evidence: C)
Hybrid coronary revascularization, defined as the planned combination of LIMA-to-LAD artery grafting and PCI of ≥1 non-LAD coronary arteries,515 is intended to combine the advantages of CABG (ie, durability of the LIMA graft) and PCI.516 Patients with multivessel CAD (eg, LAD and ≥1 non-LAD stenoses) and an indication for revascularization are potentially eligible for this approach. Hybrid revascularization is ideal in patients in whom technical or anatomic limitations to CABG or PCI alone may be present and for whom minimizing the invasiveness (and therefore the risk of morbidity and mortality) of surgical intervention is preferred510 (eg, patients with severe preexisting comorbidities, recent MI, a lack of suitable graft conduits, a heavily calcified ascending aorta, or a non-LAD coronary artery unsuitable for bypass but amenable to PCI, and situations in which PCI of the LAD artery is not feasible because of excessive tortuosity or chronic total occlusion).
Hybrid coronary revascularization may be performed in a hybrid suite in one operative setting or as a staged procedure (ie, PCI and CABG performed in 2 different operative suites, separated by hours to 2 days, but typically during the same hospital stay). Because most hospitals lack a hybrid operating room, staged procedures are usually performed. With the staged procedure, CABG before PCI is preferred, because this approach allows the interventional cardiologist to 1) verify the patency of the LIMA-to-LAD artery graft before attempting PCI of other vessels and 2) minimize the risk of perioperative bleeding that would occur if CABG were performed after PCI (ie, while the patient is receiving DAPT). Because minimally invasive CABG may be associated with lower graft patency rates compared with CABG performed through a midline sternotomy, it seems prudent to angiographically image all grafts performed through a minimally invasive approach to confirm graft patency.510
To date, no RCTs involving hybrid coronary revascularization have been published. Over the past 10 years, several small, retrospective series of hybrid revascularization using minimally invasive CABG and PCI have reported low mortality rates (0 to 2%) and event-free survival rates of 83% to 92% at 6 to 12 months of follow-up. The few series that have compared the outcomes of hybrid coronary revascularization with standard CABG report similar outcomes at 30 days and 6 months.508–514
4. Perioperative Management
4.1. Preoperative Antiplatelet Therapy: Recommendations
In patients referred for elective CABG, clopidogrel and ticagrelor should be discontinued for at least 5 days before surgery520–522 (Level of Evidence: B) and prasugrel for at least 7 days (Level of Evidence: C) to limit blood transfusions.
In patients referred for CABG, short-acting intravenous glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before surgery526,527 and abciximab for at least 12 hours beforehand528 to limit blood loss and transfusions. (Level of Evidence: B)
In patients referred for urgent CABG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontinued. (Level of Evidence: C)
Nearly all patients with UA or recent MI in whom CABG is performed will be taking aspirin; CABG can be performed safely in these individuals, with only a modest increase in bleeding risk. Preoperative aspirin use reduces operative morbidity and mortality rates.517,518
Although the use of thienopyridines (clopidogrel or prasugrel) is associated with improved outcomes in subjects with UA or NSTEMI,305,306 their use is associated with an increase in post-CABG bleeding and need for transfusions.520,522,529–533 The risk of major bleeding complications (ie, pericardial tamponade or reoperation) is increased when CABG is performed <24 hours after clopidogrel's discontinuation.524,525 Conversely, no increase in bleeding or transfusions is noted when CABG is performed >5 days after clopidogrel has been stopped.529,532 The magnitude of bleeding risk when CABG is performed 1 to 4 days after the discontinuation of clopidogrel is less certain. Although the incidence of life-threatening bleeding does not appear to be significantly increased during this time, an increase in blood transfusions is likely.523,524,529,531 Accordingly, from the perspective of blood conservation, it is reasonable to delay elective CABG for ≥5 days after discontinuing clopidogrel. For patients requiring more urgent CABG, it can be performed >24 hours after clopidogrel has been stopped with little or no increased risk of major bleeding. Approximately two thirds of clopidogrel-treated patients undergo CABG <5 days after clopidogrel discontinuation,529,532 driven largely by concerns for patient stability, resource utilization, patient preference, and the confidence of the surgical team in managing hemostasis. Little experience with CABG in patients treated with prasugrel has been reported. In the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction) trial, the incidence of CABG-related major bleeding was higher in prasugrel-treated patients than in those on clopidogrel (13.4% versus 3.2%; P<0.001).533 When possible, therefore, CABG should be delayed for ≥7 days after prasugrel is discontinued.533
Ticagrelor, an oral agent that binds reversibly to the platelet P2Y12 receptor, provides faster, more effective, and more consistent inhibition of platelet aggregation and more rapid recovery of platelet function after discontinuation than clopidogrel.534 In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 632 patients in the ticagrelor group and 629 in the clopidogrel group underwent CABG within 7 days of the last dose of study drug.521 Although the study protocol recommended waiting ≥5 days after stopping clopidogrel and 24 to 72 hours after ticagrelor, many patients underwent surgery before the recommended waiting times. The rates of major bleeding (59.3% with ticagrelor, 57.6% with clopidogrel) and transfusion requirements (55.7% with ticagrelor, 56.5% with clopidogrel) were similar. Furthermore, no difference in bleeding was noted between ticagrelor and clopidogrel with respect to time from last dose of study drug, even when CABG was performed 1, 2, or 3 days after discontinuation. On the basis of these data, it does not appear that the more rapid recovery of platelet function seen in ticagrelor pharmacokinetic studies translates to a lower risk of bleeding or less need for transfusion compared with clopidogrel when CABG is performed early (ie, <5 days) after drug discontinuation.
4.2. Postoperative Antiplatelet Therapy: Recommendations
For patients undergoing CABG, clopidogrel 75 mg daily is a reasonable alternative in patients who are intolerant of or allergic to aspirin. (Level of Evidence: C)
See Online Data Supplement 23 for additional data on postoperative antiplatelet therapy.
Aspirin significantly improves SVG patency rates, particularly during the first postoperative year. Because arterial graft patency rates are high even in the absence of antiplatelet therapy, the administration of such therapy has not shown an improvement. Aspirin administration before CABG offers no improvement in subsequent SVG patency compared with its early postoperative initiation.535 Prospective controlled trials have demonstrated a graft patency benefit when aspirin was started 1, 7, or 24 hours after operation103,537; in contrast, the benefit of postoperative aspirin on SVG patency was lost when it was initiated >48 hours after surgery.538
Dosing regimens ranging from 100 mg daily to 325 mg 3 times daily appear to be efficacious.539 As the grafted recipient's coronary arterial luminal diameter increases, SVG patency rates improve, and the relative advantage of aspirin over placebo is reduced.540 Although aspirin doses of <100 mg daily have been used for prevention of adverse events in patients with CAD, they may be less efficacious than higher doses in optimizing SVG patency.541 Enteric-coated aspirin, 75 mg, has been associated with suboptimal inhibition of platelet aggregation in 44% of patients with stable cardiovascular disease, suggesting that soluble aspirin may be preferred if low-dose aspirin is used.542 When given within 48 hours after CABG, aspirin has been shown to reduce subsequent rates of mortality, MI, stroke, renal failure, and bowel infarction.519
Although ticlopidine is efficacious at inhibiting platelet aggregation, it offers no advantage over aspirin except as an alternative in the truly aspirin-allergic patient.543 In addition, its use may be associated with potentially life-threatening neutropenia, a rare adverse effect, such that white blood cell counts should be monitored repetitively after initiating it. Dipyridamole and warfarin add nothing to the effect of aspirin on SVG patency,544,545 and use of the latter may be associated with an increased risk for bleeding compared with antiplatelet agents.546
Clopidogrel is associated with fewer adverse effects than ticlopidine. Severe leukopenia occurs very rarely.546,547 A subset analysis of CABG patients from the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events) trial suggested that clopidogrel reduced the occurrence of cardiovascular death, MI, and stroke (14.5%) compared with placebo (16.2%). This benefit occurred primarily before surgery, however, and after CABG a difference in primary endpoints between groups was not demonstrable. Clopidogrel was stopped a median of 10 days before surgery and was restarted postoperatively in 75.3% of patients assigned to receive it. All patients received aspirin, 75 mg to 325 mg daily, but the details of aspirin administration in the study groups were not described.530
4.3. Management of Hyperlipidemia: Recommendations
In patients undergoing CABG, an adequate dose of statin should be used to reduce LDL cholesterol to less than 100 mg/dL and to achieve at least a 30% lowering of LDL cholesterol.548–552 (Level of Evidence: C)
For patients undergoing urgent or emergency CABG who are not taking a statin, it is reasonable to initiate high-dose statin therapy immediately.564 (Level of Evidence: C)
Class III: HARM
See Online Data Supplement 24 for additional data on management of hyperlipidemia.
In patients with CAD, treatment of hyperlipidemia with therapeutic lifestyle changes and medications reduces the risk of nonfatal MI and death. The goal of such therapy is to reduce the LDL cholesterol level to <100 mg/dL.563 Statins are the most commonly prescribed agents for achieving this goal.563
Studies of lipid-lowering therapy in CABG patients have demonstrated that lowering LDL cholesterol with statins influences post-CABG outcomes, and “aggressive” LDL cholesterol lowering (to 60 to 85 mg/dL) is associated with a reduced rate of graft atherosclerosis and repeat revascularization compared with only “moderate” lowering (130 to 140 mg/dL).545,556 In the latter study, both groups of subjects initially received lovastatin at different doses (40 mg in the “aggressive” lowering group versus 2.5 mg in the “moderate” group), and cholestyramine was added if LDL cholesterol goals were not met with lovastatin alone. Of note, patients were maintained on therapy for ≥1 year, and as many as 11 years, after CABG.
The PROVE IT TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction) trial randomly assigned patients with ACS, a minority of whom had previous CABG, to intensive (LDL cholesterol goal <70 mg/dL) versus standard (LDL cholesterol goal <100 mg/dL) lipid-lowering therapy. The benefit of intensive therapy (a reduction in death, MI, recurrent UA, repeat revascularization, or stroke) was observed within 30 days.561 In the occasional subject who cannot take statins, alternative hypolipidemic agents, such as bile acid sequestrants, niacin, and fibrates, should be considered, in accordance with National Cholesterol Education Program: Adult Treatment Panel III guidelines.563
4.3.1. Timing of Statin Use and CABG Outcomes
As noted, the benefits of post-CABG LDL lowering with statins have been reported previously, but no prospective studies of the impact of preoperative LDL cholesterol lowering on post-CABG outcomes are available. One small randomized comparison of preoperative placebo and a statin (initiated 1 week before CABG) showed a reduction in elevated perioperative cardiac biomarkers with statin therapy.554 Several nonrandomized, retrospective studies have noted an association between preoperative statin use and reduced rates of postoperative nonfatal MI and death.553,555,557–559 In addition, preoperative statin use has been associated with reduced rates of postoperative atrial fibrillation (AF),571,572 neurological dysfunction,555,573,574 renal dysfunction,575 and infection.576 Untreated hyperlipidemic patients have been shown to have a higher risk of post-CABG events than that of treated hyperlipidemic patients and those with normal serum lipid concentrations.567 In patients undergoing CABG who are not on statin therapy or at LDL goal, it seems reasonable to initiate intensive statin therapy preoperatively (ie, no later than 1 week before surgery).
Postoperatively, statin use should be resumed when the patient is able to take oral medications and should be continued indefinitely. Patients in whom statins were discontinued after CABG have been shown to have a higher mortality rate than those in whom statins were continued postoperatively.566
126.96.36.199. Potential Adverse Effects of Perioperative Statin Therapy
The most common adverse effects reported with statin use are myopathy and hepatotoxicity. Muscle aches have been reported in about 5% of patients treated with statins, although several pooled analyses of RCTs have shown a similar rate of muscle aches with placebo.577 Myositis, defined as muscle pain with a serum creatine kinase >10 times the upper limit of normal, occurs in 0.1% to 0.2% of statin users, and rhabdomyolysis occurs in 0.02%.578,579 In addition, approximately 2% of patients are observed to have elevated liver enzymes (ie, alanine and aspartate transaminases) in the weeks to months after statin initiation, but no data are available to suggest that these elevations are associated with permanent hepatotoxicity or an increased risk of hepatitis. Nonetheless, the presence of active or chronic liver disease is a contraindication to statin use, and patients initiated on a statin should be monitored for the development of myositis or rhabdomyolosis, either of which would mandate its discontinuation.580
4.4. Hormonal Manipulation: Recommendations
Use of continuous intravenous insulin to achieve and maintain an early postoperative blood glucose concentration less than or equal to 180 mg/dL while avoiding hypoglycemia is indicated to reduce the incidence of adverse events, including deep sternal wound infection, after CABG.581–583 (Level of Evidence: B)
Class III: HARM
4.4.1. Glucose Control
Hyperglycemia often occurs during and after CABG, particularly when CABG is performed on pump. Intraoperative hyperglycemia is associated with an increased morbidity rate in patients with diabetes590 and with excess mortality in patients with and without diabetes.591 Hyperglycemia during CPB is an independent risk factor for death in patients undergoing cardiac surgery. A retrospective observational study of 409 cardiac surgical patients identified intraoperative hyperglycemia as an independent risk factor for perioperative complications, including death, and calculated a 34% increased likelihood of postoperative complications for every 20-mg/dL increase in blood glucose concentration >100 mg/dL during surgery.592 An RCT of critically ill patients, many of whom had high-risk cardiac surgery, found reduced morbidity and mortality rates in those whose blood glucose was tightly controlled,583 and follow-up of these subjects showed that this benefit persisted for up to 4 years.582
The Portland Diabetes Project, begun in 1992, was the first large study to elucidate the detrimental effects of hyperglycemia in relation to CABG outcomes. This prospective observational study described the evolution in management of cardiac surgical patients with diabetes mellitus from a strategy of intermittent subcutaneous injections of insulin to one of continuous intravenous insulin infusion with decreasing target glucose concentrations. As this management strategy evolved, the upper target serum glucose concentrations declined from 200 mg/dL to 110 mg/dL, with which significant reductions in operative and cardiac-related death (arrhythmias and acute ventricular failure) were noted.581 In addition, continuous intravenous insulin to maintain a serum glucose concentration of 120 mg/dL to 160 mg/dL resulted in a reduced incidence of deep sternal wound infection.593,594 As a result, most centers now emphasize tight glucose control (target serum glucose concentration ≤180 mg/dL, accomplished with a continuous intravenous insulin infusion) during surgery and until the morning of the third postoperative day.
Whether extremely tight intraoperative glucose control can further reduce morbidity or mortality rate is controversial. A prospective trial from the Mayo Clinic randomly assigned 400 patients to intensive treatment (continuous insulin infusion during surgery) or conventional treatment (insulin given only for a glucose concentration >200 mg/dL).586 Postoperative ICU management was similar in the 2 groups. Although no difference was noted between groups in a composite endpoint of death, deep sternal wound infection, prolonged ventilation, cardiac arrhythmias, stroke, or renal failure within 30 days of surgery, intensive treatment caused an increased incidence of death and stroke, thereby raising concerns about this intervention.586 In a prospective RCT in 381 CABG patients without diabetes, those with an intraoperative blood glucose concentration >100 mg/dL were assigned to an insulin infusion or no treatment.584 Those receiving insulin had lower intraoperative glucose concentrations, but no difference between groups was observed in the occurrence of new neurological, neuro-ophthalmologic, or neurobehavioral deficits or neurology-related deaths. Of note, no difference in need for inotropic support, hospital length of stay, or operative mortality rate was seen between the groups.584 A retrospective analysis of intraoperative and postoperative ICU glucose concentrations in >4300 patients undergoing cardiac surgery at the Cleveland Clinic observed that a blood glucose concentration >200 mg/dL in the operating room or ICU was associated with worse outcomes, but intraoperative glucose concentrations ≤140 mg/dL were not associated with improved outcomes compared with severe hyperglycemia, despite infrequent hypoglycemia. Diabetic status did not influence the effects of hyperglycemia.585 In short, until additional information is available, extremely tight intraoperative glucose control is not recommended.
Although the management of blood glucose before surgery in patients with and without diabetes mellitus is not well studied, an increased incidence of adverse outcomes has been noted in patients with poor preoperative glycemic control.593,595 As a result, most centers now attempt to optimize glucose control before surgery, attempting to achieve a target glucose concentration ≤180 mg/dL with continuous intravenous insulin. Measuring preoperative hemoglobin A1c concentrations may be helpful in assessing the adequacy of preoperative glycemic control and identifying patients at risk for postoperative hyperglycemia.596
4.4.2. Postmenopausal Hormone Therapy
Postmenopausal hormone therapy was shown previously to reduce the risk of cardiac-related death. However, more contemporary published RCTs have suggested that it may have adverse cardiovascular effects. The Women's Health Initiative randomly assigned >16 000 healthy postmenopausal women to placebo or continuous combined estrogen–progestin therapy. Hormone therapy was discontinued early because of an increased risk of breast cancer in those receiving it. Additionally, subjects receiving it had an increased incidence of cardiac ischemic events (29% increase, mainly nonfatal MI), stroke, and venous thromboembolism.588 A secondary prevention trial, HERS (Heart and Estrogen/Progestin Replacement Study), randomly assigned 2763 postmenopausal women with known CAD to continuous estrogen/progestin or placebo, after which they were followed up for a mean of 4.1 years.587 No difference in the primary endpoints of nonfatal MI and CAD death was noted, but those receiving hormone therapy had a greater incidence of deep venous thrombosis and other thromboembolic events. This predisposition to thrombosis has raised concerns that hormone therapy may cause adverse events at the time of CABG. A prospective RCT comparing hormone therapy to placebo in postmenopausal women after CABG was initiated in 1998 but was stopped when the Women's Health Initiative trial results were reported.589 Eighty-three subjects were enrolled, and 45 underwent angiographic follow-up at 42 months. Angiographic progression of CAD in nonbypassed coronary arteries was greater in patients receiving hormone therapy, although less progression of disease was observed in SVGs. Postoperative angioplasty was performed in 8 hormone therapy patients and only 1 placebo subject (P<0.05). On the basis of these data, it is not recommended that post-menopausal hormone therapy be initiated in women undergoing CABG, and it may be reasonable to discontinue it in those scheduled for elective CABG.
4.4.3. CABG in Patients With Hypothyroidism
Subclinical hypothyroidism (thyroid-stimulating hormone concentration, 4.50 mIU/L to 19.9 mIU/L) occurs commonly in patients with CAD. In a meta-analysis of >55 000 subjects with CAD, those with subclinical hypothyroidism did not have an increase in total deaths, but the CAD mortality rate was increased, particularly in those with thyroid-stimulating hormone concentrations >10 mIU/L.597
The risks of CABG in hypothyroid patients are poorly defined. A retrospective study of hypothyroid patients undergoing CABG had a higher incidence of heart failure and gastrointestinal complications and a lower incidence of postoperative fever than did members of a matched euthyroid group.598 Patients with subclinical hypothyroidism may be at increased risk for developing AF after CABG,599 and 1 study even suggested that triiodothyronine supplementation in patients undergoing CABG (including those who are euthyroid) decreased the incidence of postoperative AF.600 Conversely, controlled studies of triiodothyronine in subjects undergoing CABG have shown no benefit.601,602 Rarely, patients may develop severe hypothyroidism after CABG, which manifests as lethargy, prolonged required ventilation, and hypotension.603 Thyroid replacement is indicated in these individuals.
4.5. Perioperative Beta Blockers: Recommendations
Beta blockers should be administered for at least 24 hours before CABG to all patients without contraindications to reduce the incidence or clinical sequelae of postoperative AF.604–608,608a–608c (Level of Evidence: B)
Beta blockers should be reinstituted as soon as possible after CABG in all patients without contraindications to reduce the incidence or clinical sequelae of AF.604–608,608a–608c (Level of Evidence: B)
Beta blockers should be prescribed to all CABG patients without contraindications at the time of hospital discharge. (Level of Evidence: C)
Preoperative use of beta blockers in patients without contraindications, particularly in those with an LVEF greater than 30%, can be effective in reducing the risk of in-hospital mortality.609–611 (Level of Evidence: B)
Intravenous administration of beta blockers in clinically stable patients unable to take oral medications is reasonable in the early postoperative period.616 (Level of Evidence: B)
See Online Data Supplement 25 for additional data on beta blockers.
Because beta blockers have been shown to reduce the incidence of postoperative AF in CABG patients who are receiving them preoperatively604,605,608 (Section 5.2.5), the STS and AHA recommend that they be administered preoperatively to all patients without contraindications and then be continued postoperatively.618,619 Despite this recommendation, uncertainty exists about their efficacy in subjects not receiving them preoperatively; in this patient population, their use appears to lengthen hospital stay and not to reduce the incidence of postoperative AF.604,607 Their efficacy in preventing or treating perioperative myocardial ischemia is supported by the results of observational studies and small RCTs.612–614 Although a meta-analysis of available data did not show an improvement in outcomes with perioperative beta blockers,615 observational analyses suggest that preoperative beta-blocker use is associated with a reduction in perioperative deaths.609–611 Another analysis of data from 629 877 patients reported a mortality rate of 2.8% in those receiving beta blockers versus 3.4% in those not receiving them.609
Few data are available on the pharmacokinetic disposition of beta blockers in the early postoperative period, when an alteration in gastrointestinal perfusion may adversely affect their absorption after oral administration. An RCT demonstrated a significant reduction in the incidence of postoperative AF when a continuous intravenous infusion of metoprolol was used rather than oral administration.616
The efficacy of beta-blocker use in CABG patients after hospital discharge is uncertain, as data from 2 RCTs and 1 large detailed observational analysis suggest that they exert no benefit over 2 years postoperatively.621–623 In contrast, some observational analyses have reported that they are, in fact, efficacious in high-risk subgroups (eg, those with perioperative myocardial ischemia or elderly subjects with heart failure).624 A contemporary analysis of prescription data from 3,102 Canadian patients, 83% of whom were prescribed a beta blocker at the time of discharge, reported that those receiving beta blockers had a reduced mortality rate during a mean follow-up of 75 months.625 Of note, improved survival was noted in all patient subgroups receiving beta blockers, even including those without perioperative myocardial ischemia or heart failure.
4.6. ACE Inhibitors/ARBs: Recommendations
ACE inhibitors or ARBs should be initiated postoperatively and continued indefinitely in CABG patients who were not receiving them preoperatively, who are stable, and who have an LVEF less than or equal to 40%, hypertension, diabetes mellitus, or CKD, unless contraindicated.622,627,627a,627b (Level of Evidence: A)
It is reasonable to initiate ACE inhibitors or ARBs postoperatively and to continue them indefinitely in all CABG patients who were not receiving them preoperatively and are considered to be at low risk (ie, those with a normal LVEF in whom cardiovascular risk factors are well controlled), unless contraindicated.622,627–630 (Level of Evidence: B)
See Online Data Supplements 26 and 27 for additional data on ACE inhibitors.
ACE inhibitors and ARBs are known to exert cardiovasculoprotective actions, particularly in subjects with LV systolic dysfunction, hypertension, diabetes mellitus, or chronic renal insufficiency.626 Nonetheless, the safety and effectiveness of preoperative ACE inhibitors and ARBs in patients undergoing cardiac or noncardiac surgery is uncertain638 because their administration has been associated with intraoperative hypotension as well as a blunted response to pressors and inotropic agents after induction of anesthesia. Of particular concern during cardiac surgery is their reported association with severe hypotension after CPB (so-called vasoplegia syndrome) and postoperative renal dysfunction.631,639
Although it has been postulated that these agents may protect against the development of postoperative AF, published studies have reached conflicting conclusions in this regard.634,636 The safety and efficacy of ACE inhibitors and ARBs after CABG in previously naïve low- to moderate-risk patients (ie, subjects without diabetes mellitus or renal insufficiency and with or without asymptomatic moderate LV systolic dysfunction) are uncertain; furthermore, ACE inhibitors and ARBs must be used with caution in these subjects. They should not be instituted in the immediate postoperative period if the systolic arterial pressure is <100 mm Hg or if the patient develops hypotension in the hospital after receiving them. The IMAGINE (Ischemia Management With Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme) study failed to show a beneficial effect of postoperative ACE inhibitor therapy 3 years after CABG, instead noting an increase in adverse events, particularly recurrent angina in the first 3 months of therapy.630 A subanalysis of the data from patients enrolled in EUROPA (European Trial on the Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) with previous revascularization (CABG or PCI no sooner than 6 months before enrollment) suggested a primary and secondary prevention benefit over a 4.2-year follow-up period; however, an analysis of the data from almost 3000 patients in the PREVENT IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection) trial, all of whom were taking either ACE inhibitors or ARBs at the time of hospital discharge, failed to demonstrate a significant reduction in death or MI after 2 years of follow-up in “ideal” candidates (based on ACCF/AHA/HRS guidelines) (HR: 0.87; 95% CI: 0.52 to 1.45; P=NS), whereas significance was achieved in “non-ideal” candidates (HR: 1.64; 95% CI: 1.00 to 2.68; P=0.05).608,622,628,640
4.7. Smoking Cessation: Recommendations
The effectiveness of pharmacological therapy for smoking cessation offered to patients before hospital discharge is uncertain. (Level of Evidence: C)
See Online Data Supplement 28 for additional data on smoking cessation.
Smoking cessation after CABG is associated with a substantial reduction in subsequent MACE, including MI and death. Data from the randomized portion of the CASS study showed 10-year survival rates of 82% among the 468 patients who quit smoking after CABG and only 77% in the 312 who continued to smoke (P=0.025).645 Those who continued to smoke were more likely to have recurrent angina and to require repeat hospitalization. Data from the CASS registry demonstrated 5-year mortality rates of 22% for those who continued to smoke and only 15% for those who successfully quit smoking after CABG (RR: 1.55; 95% CI: 1.29 to 1.85).646 Similar favorable outcomes with smoking cessation were reported from the MRFIT (Multiple Risk Factor Intervention Trial), in which the impact of smoking cessation on MACE was assessed after 10.5 years of follow-up in 12 866 men; the risk of death was greater among smokers than nonsmokers (RR: 1.57).647 Notably, the risk of dying from cardiac causes was lower for those who successfully quit than for nonquitters after only 1 year of smoking cessation (RR: 0.63), and it remained so in those who quit for at least the first 3 years of the study (RR: 0.38).647 The beneficial effects of smoking cessation after CABG seem to be durable during long-term follow-up (ie, even 30 years postoperatively).648–650 In fact, smoking cessation was associated with a reduction in mortality rate of greater magnitude than that resulting from any other treatment or intervention after CABG.649 In these long-term follow-up studies, patients who continued to smoke had significantly higher rates of MI, reoperation, and death.
Smoking is a powerful independent predictor of sudden cardiac death in patients with CAD (HR: 2.47; 95% CI: 1.46 to 4.19). It has been associated with accelerated disease and occlusion of SVGs as well as endothelial dysfunction of arterial grafts.651–653 Compared with nonsmokers, subjects who are smoking at the time of CABG more often have pulmonary complications that require prolonged postoperative intubation and a longer ICU stay as well as postoperative infections.654–656 Even smokers who quit just before CABG have fewer postoperative complications than those who continued to smoke.654 As a result, all smokers referred for CABG should be counseled to quit smoking before surgery.
Smoking cessation seems to be especially beneficial for patients hospitalized with ACS who then require CABG.644,657 Independent predictors of continued nonsmoking 1 year after CABG included <3 previous attempts to quit (OR: 7.4; 95% CI: 1.9 to 29.1), >1 week of preoperative nonsmoking (OR: 10.0; 95% CI: 2.0 to 50), a definite intention to quit smoking (OR: 12.0; 95% CI: 2.6 to 55.1), and no difficulty with smoking cessation while in the hospital (OR: 9.6; 95% CI: 1.8 to 52.2).658 Aggressive smoking cessation intervention directed at patients early after post-CABG discharge appears to be more effective than a conservative approach.642 In a systematic review of 33 trials of smoking cessation, counseling that began during hospitalization and included supportive contacts for >1 month after hospital discharge increased the rates of smoking cessation (OR: 1.65; 95% CI: 1.44 to 1.90), whereas the use of pharmacotherapy did not improve abstinence rates.643 These findings are supported by a 2009 RCT comparing intensive or minimal smoking cessation intervention in patients hospitalized for CABG or acute MI.644 In this trial, the 12-month self-reported rate of abstinence was 62% among patients randomly assigned to the intensive program and 46% among those randomly allocated to the minimal intervention (OR: 2.0; 95% CI: 1.2 to 3.1). Overall, a higher rate of continuous abstinence was observed in patients undergoing CABG than in those who had sustained an MI. Interestingly, the rates of abstinence were lower in subjects who used pharmacotherapy regardless of the intervention group (OR: 0.3; 95% CI: 0.2 to 0.5).644
Seven first-line pharmacological treatments are available for smoking cessation therapy, including 5 nicotine-replacement therapies; the antidepressant bupropion; and varenicline, a partial agonist of the α4β2 subtype of the nicotinic acetylcholine receptor.659–661 The data supporting the use and timing of nicotine-replacement therapy after CABG are unclear. One study from a large general practice database reported no increased risk of MI, stroke, or death with nicotine-replacement therapy,662 whereas a retrospective case–control study of critically ill patients reported a higher in-hospital mortality rate in those receiving nicotine replacement (20% versus 7%; P=0.0085). Despite adjusting for the severity of illness, nicotine-replacement therapy was an independent predictor of inhospital mortality (OR: 24.6; 95% CI: 3.6 to 167.6; P=0.0011).663 Similarly, in a cohort study of post-CABG patients, nicotine-replacement therapy was shown to be an independent predictor of in-hospital mortality after adjusting for baseline characteristics (OR: 6.06; 95% CI: 1.65 to 22.21).663,664 Additional studies are needed to determine the safety of nicotine-replacement therapy in smokers undergoing CABG as well as the optimal time at which to begin such therapy postoperatively.
4.8. Emotional Dysfunction and Psychosocial Considerations: Recommendation
The negative impact of emotional dysfunction on risk of morbidity and mortality after CABG is well recognized. In a multivariate analysis of elderly patients after CABG, the 2 most important predictors of death were a lack of social participation and a lack of religious strength.670 Social isolation is associated with increased risk of death in patients with CAD,671 and treatment may improve outcomes.672 The most carefully studied mood disorder, depression, occurs commonly after CABG. Several studies have shown that the primary predictor of depression after CABG is its presence before CABG and that only rarely does CABG cause depression in patients who were not depressed beforehand. In 1 report, half the patients who were depressed before CABG were not depressed afterward, and only 9% of subjects who were not depressed before CABG developed depression postoperatively.673 The prevalence of depression at 1 year after CABG was 33%, which is similar to the prevalence in those undergoing other major operations. Patients with stronger perceptions of control of their illness were less likely to be depressed or anxious after CABG.674 No difference in the incidence of mood disturbances was noted when off-pump and on-pump CABG were compared.675
4.8.1. Effects of Mood Disturbance and Anxiety on CABG Outcomes
Depression is an important risk factor for the development and progression of CAD. In fact, it is a more important predictor of the success of cardiac rehabilitation than many other functional cardiac variables.676 Both the presence of depressive symptoms before CABG and the postoperative worsening of these symptoms correlate with poorer physical and psychosocial functioning and poorer quality of life after CABG.677 In a study of 440 patients who underwent CABG, the effects of both preoperative anxiety and depression (as defined by the Depression Anxiety and Stress Scale) on mortality rate were assessed for a median of 5 years postoperatively.678 Interestingly, preoperative anxiety was associated with a significantly increased risk of death (HR: 1.88; 95% CI: 1.12 to 3.37; P=0.02), whereas preoperative depression was not.678 In a multivariate analysis of 817 patients at Duke University Medical Center, severe depression (assessed using the Center for Epidemiological Studies–Depression scale before surgery and 6 months postoperatively665 was associated with increased risk of death (HR: 2.4; 95% CI: 1.4 to 4.0), as was mild or moderate depression that persisted at 6 months (HR: 2.2; 95% CI: 1.2 to 4.2). In another study of 309 subjects followed up for ≤1 year after CABG, those with diagnostic criteria for a major depressive disorder before discharge were nearly 3 times as likely to have a cardiac event, such as heart failure requiring hospitalization, MI, cardiac arrest, PCI, repeat CABG, or cardiac death.666 Finally, depression after CABG is an important predictor of the recurrence of angina during the first 5 postoperative years.666,673
4.8.2. Interventions to Treat Depression in CABG Patients
The Bypassing the Blues investigators identified 302 patients who were depressed before CABG and 2 weeks after discharge.668 They were randomly assigned to 8 months of telephone-delivered collaborative care (150 patients) or “usual care” (152 patients). The 2 groups were compared with each other and also to another group of 151 randomly selected nondepressed post-CABG patients. At 8 month follow-up, the collaborative care group showed an improvement in qu