I. Surgical Revascularization with CABG: What every physician needs to know.

At the age of 50 years, the procedure of coronary artery bypass grafting (CABG) has now the most solid evidence supporting its role in revascularization for stable ischemic heart disease (SIHD) in its history. In many respects, this interventional procedure is the most studied in the history of medicine, and therefore a considerable volume of information helps to define the short- and long-term outcomes of CABG as an individual therapeutic option for SIHD. More recently, comparative effectiveness studies between medical therapy, percutaneous cardiovascular intervention (PCI), and CABG have been performed, and the importance of CABG as a definitive therapeutic revascularization option in these patients has been augmented by the findings from these studies.

This chapter characterizes the information sources and data that describe the current outcomes of surgical intervention for coronary artery disease.

II. Diagnostic Classification: What Clinical Conditions might indicate CABG ?

Acute coronary syndrome vs. stable ischemic heart disease

The diagnostic confirmation for surgical intervention has, for this 50-year interval, been a complex and evolving dynamic, that includes (1) the evolution of the operative procedure itself, and (2) the medical environment that surrounds the procedure.

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Currently, ischemic heart disease is most usefully divided into acute coronary syndromes (ACS) and SIHD. This categorization has important implications for the diagnostic appropriateness for surgical intervention.

As discussed elsewhere, remarkable advances in pharmacologic and interventional percutaneous therapies for ACS have redefined ACS care over the past 5 years. Likewise, the number of patients in whom a technical issue arises in the catheterization laboratory has decreased, likely due to more defined indications for diagnostic cardiac catheterization, and more appropriate use of PCI.

Because of both of these influences, the role of surgical intervention in ACS is now limited to ACS patients who can be surgically revascularized within an appropriate 4-hour window, and patients who need to be taken directly from the catheter lab to the operating room for acute ischemia not controlled by maximal medical therapy, usually for a catheter-induced dissection of a coronary artery.

Patients with SIHD are more complicated in terms of their diagnostic confirmation for CABG, as discussed in the next section.

Anatomy as the basis for CABG

The advent of selective coronary angiography in 1963 quickly established coronary anatomy as the basis for defining surgical revascularization, both the indications in patients with ischemic heart disease and the technical principles of the procedure.

For the 50 years, the conceptual and practical basis of surgical revascularization with CABG has been the underlying coronary anatomy, with the accompanying atherosclerotic stenotic plaque and/or thrombotic occlusion of the target vessel epicardial coronary artery (TVECA). Early on, incomplete revascularization based on this anatomy-derived construct for revascularization was associated with a 15% reduction in the 5-year survival rate, and the principle of complete anatomic revascularization became linked to these anatomic stenotic triggers.

Over time, this anatomic construct was divided into Left Main disease (>50% obstruction at angiography), and 1-, 2- and 3-vessel disease (either >50 or >70% stenoses at angiography), depending upon the anatomic extent of stenoses in major TVECAs. These can be understood to supply the anterior (left anterior descending coronary artery), lateral (circumflex coronary artery), and inferior (right coronary artery in patients with a right-dominant anatomy, the distal circumflex in patients with a left-dominant anatomy) areas of myocardium of the heart. Frequently, in addition to these TVECAs, branches also have anatomic stenoses suitable for bypass grafting by anatomic criteria.

The emerging importance of functionality

More recently, as a result of advances in our understanding of SIHD and the importance of functionality in percutaneous revascularization, this anatomic construct in surgery has begun to be challenged. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial established the importance of Optimal Medical Therapy in SIHD, and as importantly a substudy of COURAGE established the importance of >10% myocardial ischemia as a threshold for successful PCI intervention.

This finding mirrored studies by Hachamovitch, documenting that interventions (other than medical therapy) in patients with less than 10% ischemia had a negative risk/benefit profile.

In PCI-based revascularization, the fractional flow reserve (FFR) versus angiography for multivessel disease Fractional Flow Reserve vs. Angiography for Multivessel Evaluation (FAME) 1 and 2 studies have created a paradigm shift from anatomy to “functional anatomy” as the basis for PCI. FFR is measured as a pressure drop across an anatomic stenosis at maximal coronary vasodilation, where a drop of >20% (FFR < 0.8) is considered clinically significant as indicating a perfusion deficit and/or ischemia in the myocardium supplied by the TVECA with the anatomic stenosis.

These studies demonstrated that intervention on anatomic stenoses without functionality was associated with poorer clinical outcomes and increased health care costs.

Whether this paradigm shift is applicable to surgical intervention is a matter of considerable controversy at present. There are several important factors that are influencing this controversy. First, the concept of functionality brings the acute physiology of blood flow and perfusion directly into the CABG procedure, but this is difficult for surgeons to envision in the setting of CABG with cardioplegic arrest.

Stopping the heart creates a bloodless field and motionless heart, but creates a conceptual gap related to the direct impact of revascularization on the myocardium. A second consequence of this approach is the failure to appreciate the remarkable ability of the heart to move blood from one area to another, based on local demand. Most patients coming to surgery have an extensive duration of SIHD, with the formation of extensive collateral vasculature, but this fact is not readily appreciated with an anatomic-based, arrested-heart approach to revascularization.

The experience with beating-heart revascularization without cardiopulmonary bypass known as off-pump CABG (OPCAB) has been very important in understanding these factors, and creates the opportunity to understand in real time the physiology of blood flow and perfusion in CABG. However, the absence of accurate techniques to assess blood flow and perfusion intraoperatively has been the second important factor in this controversy.

Recently, real-time imaging at the time of CABG has created the very new opportunity to better understand the acute physiology of revascularization on a per graft basis. As illustrated below, these new findings will impact on determining what the overall impact of “functional anatomy” is on surgical revascularization.

The intersection of anatomy and functionality in CABG

Using anatomy as the basis for the surgical intervention strategy, intraoperative imaging at the time of OPCAB has documented that 75% to 80% of bypass grafts for TVECAs increase perfusion to the surrounding myocardium, but perhaps surprisingly 20% to 25% do not, despite wide angiographic patency documented with imaging.

This incidence is remarkably similar to the 20% of anatomic stenoses between 71% and 90% in FAME 1 that were not associated with functionality, and the number of saphenous vein bypass grafts (SVGs) in the Project of Ex-Vivo Vein Graft Engineering via Transfection (PREVENT IV) trial found occluded at protocol-specified angiography at 12 to 18 months postoperatively (26%). Long-term follow-up of these patients with occluded SVGs demonstrated no increased incidence of MIs or death at 5 years compared to patients in the trial without occluded SVGs, suggesting that the graft occlusion had no associated functionality.

Botman et al demonstrated in an early study prospectively applying FFR to pre-CABG patients, that the 1-year graft patency rate was directly associated to the functionality of the anatomic stenosis; the surgeon was blinded to this functional information, and used a traditional anatomic strategy for revascularization.

Thus an accumulating body of evidence suggests that functionality of anatomic stenoses has importance in CABG related to the physiologic consequences of revascularization on a per graft basis.

Evidence for outcomes in CABG: observational studies

CABG is perhaps unique in medicine with the volume of short-term and long-term outcomes data accumulated over the years. In 1988 the Society of Thoracic Surgeons database was started to assess short-term (30-day) mortality outcomes for CABG in response to nonrisk adjusted mortality being reported in local papers by Medicare.

This database effort has become the flagship clinical database program in medicine; currently, >95% of all hospitals in which open heart surgery is performed currently participate in this database. Over 150 observational analyses manuscripts have been published from this database program.

At a national level, these studies have documented the remarkable decline in 30-day mortality and, to a lesser extent, morbidity in the face of a relentless increase in the preoperative risk status of the patients coming to CABG. These studies have also documented, through a series of quality improvement studies funded by the Agency for Healthcare Research and Quality, the importance of preoperative beta-blocker use and internal mammary artery use on acute mortality, as well as the opportunity and importance of secondary prevention medications following isolated CABG.

Over the past several years, these national data have also documented that mortality for CABG has reached an asymptote of 1.8% to 2.0% nationally by Society of Thoracic Surgeons National Database data. Not surprisingly, at this level of infrequency of outcomes, additional improvements will be more difficult to achieve, perhaps requiring developments that change CABG in a paradigm-shifting manner.

Other critically important information has been generated from regional database activities, beginning with the Northern New England Cardiac Surgery studies, and including the New York State database analyses. Other studies from the Virginia Cardiac Surgery Quality Improvement project, the Michigan Society of Thoracic and Cardiovascular Surgery, and the Washington State COAP program have generated additional considerable observational evidence about the processes and outcomes of CABG.

Importantly, these national/regional observational analyses were limited in that most didn’t capture long-term outcome data. The NY State databases for PCI and CABG allowed for long-term follow-up analysis of the comparison of these two procedures, which suggested a long-term survival benefit with CABG vs. PCI. Two reports from the Duke University Clinical Cardiology database over 25 years both suggested improved survival with CABG vs. PCI or medical therapy in patients with more severe anatomic disease.

Evidence for outcomes in CABG: randomized trials

The limitations of observational dataset analyses are inherent site and selection confounding bias that cannot be addressed without the rigor of a randomized design. As PCI emerged as an alternative therapy to CABG for ischemic heart disease, a number of inferiority-design trials in low-risk surgical patients documented equivalent short-term outcomes. Several of these trials, such as the ARTS trial, had longer term outcomes reported as well. Overall, however, these trials mostly excluded patients with more severe disease by anatomic classification, while including patients with lower predicted surgical risk.

To address these trial design issues, the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) and Future Revascularization Evaluation in Patients with Diabetes (FREEDOM) trials were designed and executed over the past 5 to 7 years. In SYNTAX, the anatomic construct for revascularization reached its apogee with the development and use of the SYNTAX score to classify patient’s SIHD based on anatomic severity. In FREEDOM, 83% of patients had at least moderately severe 3-vessel disease in both arms of the trial.

Both trials have recently reported 5-year results, with important and perhaps surprisingly consistent results regarding late outcomes from CABG vs. PCI in “real world” and diabetic patients. There was a demonstrated long-term survival benefit seen in both SYNTAX and FREEDOM, statistically favoring CABG.

In SYNTAX, this freedom from mortality was seen in patients with more severe anatomic disease, as indicated in the intermediate and high SYNTAX terciles. In FREEDOM, the mortality benefit was seen across all three SYNTAX terciles, probably because of the underlying severity of anatomic disease present in these patients. In both SYNTAX and FREEDOM, at 5 years there was a decreased incidence of myocardial infarction in the CABG arms, as well.

These two seminal RCTs have firmly established late freedom from death and MI as critical outcomes in considering revascularization strategies for SIHD.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Current patient evaluation for CABG

Patient evaluation for a CABG includes an accurate history and physical examination to account for comorbidities that can contribute to the predicted risk for adverse outcomes. In this current era, where patients with SIHD are evaluated between Optimal Medical Therapy and intervention, documentation of sufficient ischemia by imaging studies is very important prior to defining the coronary anatomy, because the oculostenotic reflex is now known to lead to inappropriate intervention.

Definition of clinical ischemia by cardiac MRI, stress echocardiography, or nuclear evaluation, coupled with the definition of coronary anatomy by diagnostic angiography, and supplemented by FFR evaluation of all intermediate or uncertain lesions, allows for a complete “functional anatomic” construct that, if the degree of ischemia warrants it, helps drive the interventional decisions for individual patients.

For most patients, this process should involve the heart team at the treatment center, compromised of interventional cardiology, cardiac surgery, general cardiology, and other care providers engaged with that patient to arrive at the treatment strategy that is best for the individual patient. Included in this shared decision-making process would be features of appropriateness criteria; the anatomic nature and extent of disease; the correlation between anatomy and functionality; the patient’s comorbidities; the calculated predicted risks for, where appropriate, OMT vs. PCI vs. CABG; and most importantly long-term outcomes as part of the discussion.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Figure 1shows a coronary angiogram from a patient with severe 2-vessel disease who underwent surgical revascularization. This angiogram can be characterized by anatomy, as depicted by the SYNTAX score of 29 (Figure 2), but also by a “functional SYNTAX” classification because the LAD had a highly functional FFR value of 0.63 (Figure 3).

Figure 1.
Conventional angiogram of CABG patient.

Figure 2.
SYNTAX evaluation of angiogram in Figure 1.

Figure 3.
Functional SYNTAX evaluation of angiogram in Figure 1.

Near-infrared imaging at the time of surgical revascularization can be used to assess the angiographic quality of the bypass conduit (Figure 4), and to quantify the change in regional myocardial perfusion surrounding the TVECA as a result of bypass grafting (Figure 5). The increase in perfusion documented at surgery directly mirrors the preprocedural documentation of perfusion deficit/ischemia seen in Figure 6.

Figure 4.
Intraoperative near-infrared fluorescence angiogram of skeletonized IMA graft to the LAD and anterior wall of the heart.

Figure 5.
From the same intraoperative angiogram as Figure 4, illustration of the perfusion to the myocardium supplied by the LAD. This perfusion image can be quantified to determine the magnitude of perfusion change to the myocardium as a result of the bypass graft, which is demonstrated to be widely patent angiographically.

Figure 6.
2012 STS Benchmark data, illustrating current clinical characteristics of isolated CABG patients.

III. Management.

The synthesis of the traditional tenets of CABG (complete revascularization, IMA grafting to the LAD), anatomy as defined at catheterization, surgical technical issues (multiple arterial grafting, OPCAB vs. conventional CABG), the importance of the functional nature of stenoses on grafting and graft failure, the preoperative and postoperative pharmacologic and secondary prevention therapies of demonstrated benefit on short- and long-term outcomes, comprise the milieu around CABG management today.

A. Immediate management.

Less than 20% of isolated CABG procedures in the U.S. are done using the OPCAB approach, in contrast to most places outside the U.S. Despite considerable evidence supporting the long-term mortality benefits of multiple arterial grafting, the incidence of bilateral IMA grafting in the US remains quite low, below 7% to 8%. With the emerging importance of functionality (and therefore physiology) and long-term outcomes in CABG, perhaps the incidence of OPCAB and multiple IMA use will increase in the future.

Perioperative care has improved dramatically over the past several decades, and the STS database has defined multiple major comorbidities following isolated CABG. As patient age continues to increase, the most serious of these continues to be postoperative CVA. The use of epiaortic ultrasound evaluation of the ascending aorta, avoidance of a partial occlusion clamp application, and avoidance of severe hemodilution on CPB have been shown to decrease the incidence of CVA. Given the low risk-adjusted mortality outcomes, focusing on specific strategies to reduce these major morbidity complications (perioperative MI, CVA, acute renal failure, prolonged ventilation, infection, or reexploration for any cause) is an area of ongoing quality investigation.

Secondary prevention of CAD following CABG

The importance of secondary prevention following CABG has been firmly established. The circumstance of hospitalization for CABG is an ideal “teachable moment” for implementing secondary prevention medications, the clinical benefit of which has been demonstrated within CABG patients and/or extrapolated from other populations with SIHD.

This teachable moment was tested and validated in an AHRQ-funded grant to the STS, where efforts to improve adherence with secondary prevention medications at discharge was validated through the STS database mechanism.

Adherence to secondary prevention medications at discharge is part of the 21-metric National Quality Forum Cardiac Surgery Quality Set, and part of the STS Star Rating system.

C. Long-term management.

Now that late mortality is an important metric is evaluating therapies for SIHD patients, additional efforts to improve the long-term benefits of CABG are critical. Modification of known risk factors such as diabetes, smoking, hypertension, obesity, and poor exercise tolerance is critically important; the surgical team has the opportunity to address these issues directly and emphatically in the perioperative period.

Multiple arterial grafting has been shown to have a positive late mortality benefit compared to single arterial grafting. OPCAB vs. conventional CABG has been shown to have an acute benefit in patients with higher Predicted Risk of Mortality (PROM), with equivalent long-term outcomes.

Early in life, the supply of blood to the heart exceeds greatly the demand required. As SIHD progresses, the supply/demand balance becomes more and more unfavorable. The procedure of CABG acts to significantly augment supply again, with the new grafts supplying new and excess flow and perfusion to the myocardium, which will be sustained as long as the bypass grafts remain patent and the myocardial demand is not met by the native circulation. In addition to strategic and pharmacologic efforts to keep grafts patent long-term, reducing the progression of the native coronary artery disease is critical, through secondary prevention medications and risk factor modification both short- and long-term.

IV. Management with Co-Morbidities

Figure 6 data are from the STS database, illustrating the principal comorbidities that patients presenting for CABG have, along with their relative incidences. Tight perioperative glucose control has been shown to be beneficial, although more recently this has been brought into question.

Screening of patients with moderate to severe central and peripheral vascular disease (with epiaortic ultrasound, and with carotid Doppler evaluation in patients with known cerebrovascular disease) is also important. Careful perioperative management of patients with preexisting chronic renal insufficiency, including patients on dialysis, is important in this very high-risk subset of patients. The development of the complication of irreversible postoperative renal insufficiency is associated with the highest risk of postoperative mortality.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The importance of secondary prevention medications, and risk factor modifications, is discussed above.

With isolated CABG, the most common causes for readmission are acute heart failure, arrhythmias, and infection. Acute heart failure is usually a result of volume overload and inadequate postdischarge diuretic therapy.

Atrial fibrillation/flutter is the most common postoperative arrhythmia, which can sometimes revert after discharge in sinus rhythm. In a well-controlled study by the National Heart, Lung, and Blood Institute Cardiac Surgery Network, pneumonia was the most common postoperative infection; the incidence of deep sternal wound infection was actually quite low in this group of patients following multiple types of open heart surgery.

B. What’s the evidence for specific management and treatment recommendations?

Major international cardiovascular organizations have recently published revisions to Guidelines for CABG, including the European Guidelines and the AHA/ACC guidelines. Also, the AHA/ACC/STS/AATS/SCAI Appropriateness for Revascularization Intervention in Stable Ischemic Heart Disease were published in 2012, and are currently in the process of being revised. Each of these documents has extensive evidence, and rating of the weight of the evidence.

“2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease: Executive Summary”. JACC. vol. 60. 2012. pp. 2564-603. (This guideline includes detailed algorithms for diagnosis, risk assessment, medical therapy, and revascularization to improve symptoms and, in some circumstances, prolong life.)

“2011 ACCF/AHA guideline for coronary artery bypass graft surgery: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines”. J Thorac Cardiovasc Surg. vol. 143. 2012. pp. 4-34. (This is the latest multispecialty consensus document on CABG in the U.S., an excellent compilation of data up to the 5-year SYNTAX and FREEDOM trial data.)

Head, SJ, Kaul, S, Mack, MJ, Serruys, PW, Taggart, DP, Holmes, DR, Leon, MB, Marco, J, Bogers, AJJC, Kappetein, AP. ” The rationale for Heart Team decision-making for patients with stable complex coronary artery disease”. Eur Heart J. (Excellent discussion on the merits of the Heart Team and the influence this approach has on care delivery in cardiovascular disease.)

“ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 2012 appropriate use criteria for coronary revascularization focused update: A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, American Society of Nuclear Cardiology, and the Society of Cardiovascular Computed Tomography”. J Thorac Cardiovasc Surg. vol. 143. 2012. pp. 780-803. (Controversial document introducing the consensus opinion for the appropriateness of revascularization, or the lack of appropriateness for revascularization, under a variety of clinical circumstances.)

“Guidelines on myocardial revascularization. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)”. Eur Heart J. vol. 31. 2010. pp. 2501-2555. (Very important multidisciplinary document from Europe that paved the way for moving in the same direction in the U.S.)

Ferguson, TB, Chen, C, Babb, JD, Efird, JD, Daggubati, R, Cahill, J. ” FFR-Guided CABG: Can Intraoperative Physiologic Imaging Guide the Decision-Making ?”. J Thoracic Cardiovasc Surg. 2013. (The introduction of physiologic evaluation, through novel imaging technology and analysis, into CABG has raised questions about a number of long-standing assumptions about surgical revascularization.)

Hachamovitch, R, Rozanski, A, Hayes, SW, Thomson, LEJ, Germano, G, Friedman, JD, Cohen, I, Berman, DS. ” Predicting therapeutic benefit from myocardial revascularization procedures: Are measurements of both resting left ventricular ejection fraction and stress-induced myocardial ischemia necessary?”. J Nuc Cardiol. vol. 13. 2006. pp. 768-78. (Important observational study identifying >10% myocardial ischemia as the predictive cutoff for revascularization benefit.)

Botman, CJ, Schonberger, J, Koolen, S, Penn, O, Botman, H, Dib, N, Eeckhout, E, Pijls, N. ” Does stenosis severity of native vessels influence bypass graft patency? A prospective fractional flow reserve-guided study”. Ann Thorac Surg. vol. 83. 2007. pp. 2093-7. (Overlooked initially, this study is emerging as an important first benchmark into the concept of “FFR-guided CABG.”)