2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Health disparities by sex and race are evident across the spectrum of CVD in the United States,^7,9,13-15 and mounting evidence demonstrates that social factors are strongly associated with cardiovascular health outcomes.^{16, 17} Differences in access to care, cardiovascular treatment, mortality rate, and readmission outcomes persist by important sociodemographic characteristics that include but are not limited to socioeconomic status, race, and ethnicity.^18-22 African Americans,^23-25 Hispanics,²⁴ and South Asians²⁶ (with substantial heterogeneity within Asian subgroups) have a higher prevalence of cardiovascular risk factors and crude mortality.¹⁶ Although access to health care remains a problem, even after entering into the health care system, women and non-White patients are less likely to receive reperfusion therapy, an invasive strategy, or revascularization^9,13,27-37 and more likely to have worse outcomes.^37-40 As compared with White male patients, women and Black patients with acute coronary syndrome (ACS) receive less guideline-based therapy in hospital and at discharge.^27,32,41,42 Differences in comorbidities, health education, presentation, socioeconomic status, regional hospital capability and quality, and insurance and health care access^{15,28,29,35,37,43-48} contribute to the problem, but disparities can persist despite adjustment for these factors.^{7,30-32,49,50} In a study of patients with cardiac symptoms, clinicians were less likely to recommend cardiac catheterization to women and non-White patients than to White male patients, despite being given the exact same clinical vignette for White male patients.⁵¹ Continued vigilance against conscious and unconscious gender, racial, and ethnic discrimination and purposeful efforts to increase the implementation of guideline-based therapy for all patients, regardless of sex, race, or ethnicity, are needed.

After controlling for greater baseline comorbidities among patients undergoing revascularization, several observational studies have demonstrated that Black,^28,52-54 Hispanic,^24,50 and Asian^55,56 patients have outcomes similar to those of White patients. Similarly, after controlling for baseline comorbidities and treatment strategy, most studies demonstrate similar outcomes in women and men.^1-6 Post hoc analyses of randomized trials evaluating revascularization provide compelling evidence, inasmuch as enrolled patients are more similar and the decision to revascularize is protocol driven. In the SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, revascularization rates were lowest and mortality rates highest for Hispanics and African Americans, but there was no interaction between race and the mortality benefit of revascularization.⁹ Similar results have been reported for women with shock in the CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock trial.⁵⁷ In the TACTICS-TIMI 18 (Treat Angina With Aggrastat and Determine Cost of Therapy With Invasive or Conservative Strategy—Thrombolysis In Myocardial Infarction 18) trial, evaluating patients with NSTE-ACS, non-White patients and female patients had more comorbidity and more major adverse cardiovascular event (MACE) outcomes than White and male patients but were revascularized at the same rate. After adjustment for baseline characteristics, the invasive strategy was equally beneficial for all patients, without evidence of racial differences.¹⁰ A meta-analysis of RCT of invasive vs conservative strategies in women and men with NSTE-ACS reported a similar proportional benefit of an invasive strategy in women and men, (although low risk women with biomarker negative ACS did not derive a benefit to an early invasive strategy).¹ Additionally, studies have shown similar relative benefits of primary PCI³ and revascularization in SIHD.^5,6 for women and men. In view of these findings, the decision to offer revascularization should be made on the basis of a patient’s clinical characteristics, and preferences and should be the same for all patients, regardless of sex, race, or ethnicity.

Shared decision-making (Figure 1) is a collaborative approach that provides patients with unbiased, evidence-based information on treatment choices and encourages a dialogue between patients and providers, with the aim of making decisions that use scientific evidence and align with the patient’s values and preferences.^3,4,6 It is essential that the clinician use terminology that the patient understands to allow effective processing of health information and to foster the patient’s participation in treatment decisions.⁷ The use of online modules, decision aids, or videos about treatment options can help patients better understand the risks and benefits of various therapies. Patients are interested in how a recommended treatment might impact their prognosis and quality of life.⁸ In the treatment decision-making process, the patient’s best interest should be placed first, and the active participation of the patient and significant others should be engaged. The contributions of social determinants of health to CVD are poorly understood.^9,10 but may impact a patient’s decision with regard to treatments. In high-income countries, 4 socioeconomic status metrics have been associated with CVD: income level, educational attainment, employment status, and environmental factors.^11-13

The multidisciplinary Heart Team, which involves the cardiologist, cardiac surgeon, and other specialists, has become a critical component of the revascularization decision. Initially, the Heart Team approach to decision-making for coronary disease arose within the context of randomized trials comparing PCI with CABG to ensure selected patients were equally suited for either strategy before randomization.⁸ Subsequently, the Heart Team has become an important paradigm in clinical practice, emphasizing the importance of team consensus on the optimal approach to revascularization. Ideal situations for Heart Team consideration include patients with complex coronary disease, comorbid conditions that could impact the success of the revascularization strategy, and other clinical or social situations that may impact outcomes (Figure 2 and Table 4). The Heart Team process should rest on the principles of collegiality, mutual respect, and commitment to excellence. The logistics of convening the Heart Team should depend on local resources and workflows. Models include daily to weekly scheduled meetings and ad hoc activation.^1,2,4,6,9 Remote conferences have also been advocated.⁹ Additionally, there should be a process for rapid activation of the Heart Team for urgent or emergency clinical situations.

The STS risk score is designed to predict adverse outcomes in patients undergoing CABG, including the risk of death, renal failure, permanent stroke, prolonged ventilation, deep sternal wound infection, reoperation, and prolonged length of stay. The STS risk score is derived from data on patients undergoing CABG in the United States. The STS score is periodically updated to reflect new risk models for CABG, with the most recent update in 2018 based on the Adult Cardiac Surgery Database from 2011–2014.^3,4 Similar to the STS score, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, developed in 2011, is designed to predict adverse outcomes in patients undergoing isolated CABG.⁵

The anatomic complexity of lesions, expected completeness of revascularization, predicted risk of death, and other adverse outcomes are important factors to consider for determining the type of revascularization for patients with CAD. Many factors contribute to the estimation of the complexity of CAD (Table 6). The SYNTAX score was prospectively derived from the SYNTAX trial to aid in this decision-making process by providing an objective measure to grade the anatomic complexity of CAD in patients with multivessel disease.¹ Its value as an independent predictor of long-term major adverse cardiac and cerebrovascular events and death was established in the SYNTAX trial cohort and subsequently validated in external studies of patients treated with PCI but not CABG.^2-4 The SYNTAX II score and the revised SYNTAX Score II 2020 was retrospectively developed from the SYNTAX trial cohort.^5,6 to incorporate clinical variables in addition to the anatomic variables. These scores demonstrate modest discrimination in predicting adverse clinical events after revascularization.⁶

FFR and iFR are 2 of the most commonly used physiological methods of assessing lesion significance. FFR is defined as the ratio of maximal blood flow in a region distal to a lesion compared with the normal maximal blood flow of an artery. iFR, an index of lesion severity, is the instantaneous wave-free ratio (in diastole) of coronary pressure distal to the coronary lesion (Pd) to the aortic pressure (Pa) The potential advantage of iFR, which is a resting physiological index, is that it obviates the use of adenosine because it does not require a state of maximal hyperemia. These 2 measures—FFR and iFR—have been studied in randomized trials with clinical endpoints of death, myocardial infarction (MI), or repeat revascularization.^1-5 There are other resting indices that have been compared with iFR or FFR in observational studies.^9,10 These resting indices have varying degrees of accuracy relative to FFR and iFR but have not been studied in randomized trials with clinical endpoints. The FAME 2 (Fractional Flow-Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease) trial² tested a strategy of PCI for all lesions with abnormal FFR compared with optimal medical therapy alone. Recruitment into the trial was stopped early because of a significant benefit of PCI over medical therapy in patients with an abnormal FFR with respect to death, MI, or urgent revascularization, with the benefit derived largely from a reduction in ischemia-driven revascularization.

The role of FFR in guiding surgical revascularization is uncertain. Multiple small observational studies, as well as RCTs and meta-analyses of these trials, suggest that fewer distal anastomoses are performed, and off-pump CABG is more often chosen in patients undergoing CABG with FFR-guided revascularization than in those undergoing CABG with angiogram-guided revascularization.^11-14 However, in these studies, no differences were found in clinical outcomes in patients undergoing CABG with FFR guidance compared with patients undergoing CABG with angiogram guidance.^11-14 Additionally, not all studies included an angiogram-guided comparison group. Large, randomized trials that are appropriately powered are warranted to guide the use of FFR in patients undergoing surgical revascularization.

IVUS can offer important anatomic information beyond what is seen on coronary angiography. IVUS is particularly useful in lesions involving the left main artery where there may be limitations in coronary angiography due to overlapping vessels or foreshortening. IVUS offers significantly greater spatial resolution than angiography alone (IVUS axial resolution is 100 to 150 μm, and coronary angiography axial resolution is 300 μm). Detailed cross-sectional images provide accurate evaluation of lesion characteristics, including lumen dimensions, lesion length, plaque morphology and location, thrombus, dissection, and stent apposition and expansion. Additionally, minimal lumen area on IVUS has been shown to correlate with physiological indices.⁶

Immediate reperfusion therapy for patients with STEMI improves mortality rate, and primary PCI has been shown to be superior to fibrinolytic therapy¹ (Figure 3).^6,23,27-29 Fibrinolytic therapy is recommended only in cases in which primary PCI is not immediately available and the delay from hospital presentation to PCI is anticipated to be >120 minutes.³⁰ Because approximately 35% of patients treated with fibrinolysis do not achieve reperfusion,³¹ and an additional 10% have ineffective reperfusion (TIMI [Thrombolysis In Myocardial Infarction] flow grade <3),¹ early transfer of patients to centers capable of performing PCI will facilitate early catheterization and/or PCI.^15-17,19 CABG has a limited role in the acute phase of STEMI, and its use in this setting continues to decrease.²³ Older case series have highlighted a potential excess mortality risk when CABG is performed early after STEMI.³² However, contemporary modifications to the standard operative approach, improved anesthesia and monitoring, improved technical methods, and adjunctive temporary mechanical circulatory support devices may lead to improved rates of survival after CABG (Figure 3).

A Heart Team approach is utilized to determine optimal revascularization strategy in patients with STEMI and multivessel CAD. Revascularization strategies (Figure 4) for patients with STEMI and multivessel disease include multivessel PCI at the time of primary PCI, PCI of the infarct artery only followed by staged PCI of a non-infarct artery, PCI of the infarct artery only with an ischemia-guided approach to treatment of a non-infarct artery, or PCI of the infarct artery only with elective CABG. Observational studies and meta-analyses have reported conflicting results for the superiority of one approach over another.¹¹ Recent randomized trials of PCI in STEMI support the safety and efficacy of multivessel PCI in selected patients with STEMI.^2-4,6,7 The data are strongest for patients undergoing staged PCI.⁴ It should be noted that only one-third of enrolled patients in these trials had triple-vessel disease, and most of these trials excluded patients with left main disease, chronic total occlusion (CTO) of the non-infarct artery, or complex non-infarct artery disease. For this reason, CABG remains a reasonable option in patients with residual complex non-infarct artery disease. Ideal patients who may benefit from revascularization of non-infarct arteries include those with a large area of myocardium at risk and those without significant comorbidities that would increase the risk of revascularization.

A routine invasive approach for patients with NSTE-ACS is associated with improved outcomes.^1-4,20,21 Risk stratification with a validated score (ie, GRACE or TIMI) has been recommended to guide the timing of coronary angiography.^22,23 The GRACE score has been used in most clinical trials to identify patients who were at high risk of death or MI. It enables a direct estimation of the mortality risk during hospitalization and at longer term followup.²⁴ Traditionally, a GRACE score of >140 had been used to denote a patient at higher risk of in-hospital clinical events. Other factors associated with higher risk include older age (≥75 years), elevated TIMI risk score (https://timi.org/calculators/timi-risk-score-calculator-for-ua-nstemi/),²⁵ and elevated cardiac markers.^11,26 Factors indicating a need for an urgent revascularization (Table 7) with either PCI or CABG include threatening anatomy, ongoing ischemia, or hemodynamic compromise. In such patients and in those with complex CAD, treatment should be individualized and involve a Heart Team discussion.

Studies have shown that CABG confers a survival benefit over medical therapy in multiple subsets of patients, including those with left main CAD (Figure 6),^9-12 triple-vessel CAD,¹³ and ischemic cardiomyopathy.^1,3-7,31-33 Many of these studies were conducted before the widespread use of antiplatelet and statin therapies and before the broad recognition of benefit from beta-blockers and ACE inhibitors/ARBs. There are no RCTs that have demonstrated a survival advantage of PCI over medical therapy in patients with SIHD.^14,17,34-38 There may be an advantage of PCI over medical therapy in patients who have a clinical indication for CABG but are deemed prohibitive surgical risk. For this reason, the Heart Team must weigh the risks and benefits of PCI as compared to medical therapy in such patients. The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with SIHD and moderate-to-severe ischemia on stress testing to an initial invasive strategy versus an initial conservative strategy. Patients with left main disease or an ejection fraction <35% were excluded from enrollment. As compared with a strategy of medical therapy alone, an invasive strategy including revascularization with PCI or CABG was not associated with improved outcomes.¹⁴

Clinical practice guidelines have traditionally included recommendations for revascularization in patients with SIHD based on the ability of CABG or PCI to improve overall survival (Section 7.1.) or to reduce ischemic symptoms (Section 7.3.), as compared with medical therapy alone. However, there are other clinical events that can affect a patient’s overall prognosis, and that remain important considerations for patients. Several studies suggest that revascularization with CABG or PCI lowers the risk of adverse events such as cardiac death, MI, or urgent revascularization compared with medical therapy alone.^2,5,6,9,10

Cardiac death may be related to the occurrence of MI after revascularization.¹² The relative prognostic importance of procedural MIs versus that of late spontaneous MIs remains uncertain.¹³ In the ISCHEMIA trial,¹ the incidence of procedural type 4a or type 5 MIs was increased with revascularization, but the incidence of late MI (spontaneous MI [type 1], demand-induced MI [type 2], or MIs associated with stent thrombosis [type 4b] or with restenosis [type 4c]) was reduced. A preplanned analysis of the MI patterns in the ISCHEMIA trial⁴ found that all-cause death was increased with spontaneous MIs but not with procedural MIs. A large network meta-analysis found that spontaneous MI was reduced by revascularization compared with medical therapy alone.³ However, a concurrent analysis found an increased rate of procedural MI, a reduced rate of nonprocedural MI, and no difference in overall MI.¹¹ On the contrary, another meta-analysis of stable patients, did not show a reduction in MI with revascularization,¹⁰ and 1 other study reported reduction in MI with CABG but not with PCI.⁹ Revascularization with CABG or PCI may reduce the need for subsequent urgent revascularization or hospitalization for acute coronary events.^5-8

One of the main goals of coronary revascularization with either PCI or CABG surgery is to improve symptoms (Figure 6). In the treatment of patients with SIHD, medical therapy can often be an effective option. However, studies have shown that revascularization results in a greater improvement in angina or quality of life than does medical therapy alone.^1-6 Additionally, some patients may be intolerant of or unwilling to take anti-anginal medications. For these reasons, revascularization is frequently used to provide symptom relief.

Revascularization with either CABG or PCI is indicated to treat symptoms or improve outcomes in specific subsets of patients. However, CABG and PCI are inherently different in the mechanisms by which they improve blood flow to the jeopardized myocardium. PCI will directly relieve a discrete obstruction and increase the arterial lumen in the stented area but will have no effect on preventing plaque progression or rupture in other diseased segments within the artery. In contrast, bypass of a coronary artery will improve blood flow to the jeopardized myocardium supplied by the diseased artery and will also protect the distal myocardial beds from future ischemic insult caused by proximal plaque progression or rupture. Although most studies comparing CABG and PCI have reported similar survival,^1,3,5-17 certain subgroups of patients have been shown to derive a survival benefit from CABG compared with PCI.^1,2,4,18 Additionally, compared with PCI, CABG may be more effective at reducing the risk of late spontaneous MI.^11,19

Revascularization decisions in patients with diabetes and multivessel CAD are complex and are optimized via a Heart Team approach, with consideration of left ventricular function, patient preferences, symptoms, clinical presentation, comorbidities, and expected survival.^1,12-14 Diabetes is associated with 2- to 4-fold increased mortality risk from heart disease, and patients with diabetes have more aggressive atherosclerosis, more diffuse coronary lesions, smaller coronary vessels, and more extensive disease. After coronary revascularization, patients with diabetes experience a higher mortality rate and greater need for repeat revascularization procedures.¹⁵ Clinical trials of patients with diabetes and multivessel CAD have demonstrated that PCI is associated with a higher mortality rate at 5 years than that associated with CABG. The survival advantage of CABG becomes evident after 2 years and attenuates after 8 years, as patients treated with CABG experience a late mortality catch-up.^2,16 Of note, CABG is associated with an increased risk of stroke that persists up to 5 years.¹⁷ The need for repeat revascularization is higher after PCI, regardless of the use of latest-generation DES.^1,4-8

A Heart Team approach and shared decision-making are important in patients who require repeat revascularization after CABG. There are no randomized trials comparing medical therapy with revascularization in patients with previous CABG. PCI and repeat CABG in patients with previous CABG are associated with higher rates of procedural failure and complications^5,6 and worse outcomes than those of patients without previous CABG.^6-8 The need for any repeat revascularization after PCI or CABG is itself an independent predictor of higher mortality risk.⁹ Factors that influence the choice of revascularization modality include the availability of the IMA for grafting, a patent graft to the LAD, comorbid conditions, patient factors and preferences, the quality of the target vessels, anatomic complexity of the native and graft disease, and the feasibility and risks of the revascularization method.

In patients undergoing coronary revascularization, careful consideration should be given to factors that may affect adherence to medications, including patient preferences and comorbidities, socioeconomic status, and lifestyle factors. Premature cessation of DAPT after PCI is associated with stent thrombosis and poor outcomes, including death.^1-10 Therefore, PCI is not favored as the mode of revascularization among patients manifesting risk factors for poor adherence.

In pregnant patients, an expanded, multidisciplinary Heart Team approach is often used to determine the appropriate coronary revascularization treatment, with consideration of patient preferences, comorbidities, and clinical status. Decisions in pregnant patients are often difficult and must include consideration of the risk to the unborn fetus, as well as the risks and benefits to the mother. Pregnant women are generally excluded from clinical trials, and therefore there is limited evidence regarding the safety of antiplatelet agents during pregnancy, especially during the third trimester. Low-dose aspirin is generally felt to be safe throughout pregnancy. If clopidogrel is needed, it should be used for the shortest duration possible^3,4 with close monitoring. In a recent systematic review of 39 publications with 42 live births, the outcomes for both mothers and neonates when exposed to clopidogrel at varying durations throughout gestation, did not suggest higher than acceptable risk, with a congenital anomaly rate comparable to background risk. The evidence regarding the use of other antiplatelet agents remains limited.⁴

Although the terms “elderly” or “older” have been used to describe various patient-age subgroups in the literature, most clinical trials have defined older patients as those ≥75 years of age.³ Older patients form a vulnerable subset of patients undergoing coronary revascularization because of their more complex presentations and higher prevalence of comorbidities.^4,5 In addition, they have an increased risk of bleeding complications and stroke after PCI.^3,6-8 However, the optimal treatment for older patients with an indication for revascularization remains poorly defined because most studies have excluded older patients and included only low-risk populations.⁹

Patients with CKD constitute a growing subset of the population^7,8 and have been found to have worse outcomes after AMI or PCI.^9,10 Risk of cardiovascular death has been shown to be inversely proportional to estimated glomerular filtration rate, with impaired renal function being an independent predictor of cardiovascular risk.^11,12 Although about 30% to 40% of all patients undergoing PCI have concomitant CKD,^13,14 data on optimal treatment strategies in this population remain scarce because most RCTs have traditionally excluded patients with severe CKD. Patients with CKD who present with ACS are less likely to receive GDMT or invasive angiography than are patients with normal renal function, and the likelihood of undergoing cardiovascular interventions decreases with increasing severity of CKD.^9,15-17 Before coronary angiography is performed, the risks of AKI and the benefits of obtaining diagnostic information should be carefully considered. Preexisting CKD is the strongest independent risk factor for the development of AKI, with a higher stage of CKD associated with incrementally higher risk.^6,7

Patients with significant CAD who are undergoing high-risk surgery, such as solid organ transplantation² or vascular surgery,³ have an increased incidence of perioperative cardiovascular events. Routine prophylactic revascularization does not reduce the risk of death or cardiovascular events.¹ Clinical studies have excluded or randomized few patients with high-risk coronary anatomy such as unprotected left main and multivessel CAD. Additionally, these studies did not include patients referred for solid organ transplantation. In such patients, a Heart Team approach would be used to determine the risks and benefits of revascularization. In symptomatic patients or patients with other clinical indications for revascularization, coronary revascularization should be considered in accordance with the recommendations otherwise provided for such situations, but revascularization should not be done for the sole purpose of reducing perioperative complications.

In patients with ventricular arrhythmias, the evaluation for potential ischemic CAD will guide appropriate treatment, including coronary revascularization.^10,11 The “2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death” describes situations in which CABG or PCI may benefit patients with ischemic CAD.¹² Observational studies have shown that revascularization in patients with life-threatening ventricular arrhythmias^2,13 and in survivors of cardiac arrest¹⁴ is associated with arrhythmia reduction and improved survival. Monomorphic VT may be seen in patients with large AMIs; however, it is often attributable to reentrant rhythms from scar and not acute ischemia. Therefore, revascularization alone has not been shown to improve patient outcomes.¹⁵

SCAD is characterized by the interruption of the coronary artery intimal layer and intramural hematoma, causing vessel compression, and typically presenting as an ACS. Although most dissections will heal without intervention, a notable subset is associated with ongoing symptomatic ischemia, which can progress to complete occlusion. Treatment of patients with SCAD is challenging, and guidance from randomized trials is lacking. Observational studies indicate that most conservatively managed patients recover without further intervention. In patients with ongoing ischemia, vessel occlusion, or patient instability, selective revascularization may be necessary. However, unlike other forms of ACS, routine revascularization for patients with SCAD may not confer the same benefit. PCI wires may propagate the dissection, and balloons and stents can extend the hematoma and lead to vessel occlusion. CABG onto a dissected vessel or one with a propensity to dissect is challenging, and as many as 30% of patients have acute graft closure.⁵ The current state of the science and best practices for treating SCAD are described in the AHA scientific statement, which is based on an evaluation of retrospective studies and expert opinion.⁶

In patients after orthotopic heart transplantation, the onset of allograft vasculopathy presents a challenging treatment dilemma. Cardiac allograft vasculopathy is a major cause of death after the first year following orthotopic heart transplantation.^3-5 Cardiac allograft vasculopathy is often diffuse and characterized by concentric and rapidly progressive intimal hyperplasia.^6,7 Multiple immunologic and nonimmunologic risk factors have been linked to the accelerated progression of disease.^8,9 Treatment options are limited, with retransplantation being the only definitive therapy for cardiac allograft vasculopathy.¹⁰ However, the scarcity of donor organs and worse outcomes, compared with initial transplantation, remain important limitations.^11,12 Revascularization with PCI serves as a palliative treatment option in patients with focal disease.^2,13 Studies have demonstrated lower periprocedural and intermediate-term mortality rates with stent implantation than with balloon angioplasty.⁹

Recommendations for revascularization in patients before TAVR should be accessed in the 2020 valvular heart disease guideline.¹

Over the past decade, the proportion of patients undergoing radial artery catheterization and PCI has increased exponentially.⁸ Patients prefer the transradial approach,⁹ and this approach offers the advantage of earlier time to ambulation, lower rate of vascular and bleeding complications, and improved cardiovascular outcomes in patients with ACS.⁴ An important caveat to radial access trials^1,2,9 is that the treating physicians were required to have experience in radial artery access, and therefore, it is not surprising that femoral crossover rates were notably low among patients assigned to radial access.^1-4 For this reason, it is encouraged that all operators gain experience in radial artery access so that they may ultimately acquire the skills needed to have expertise with this approach. The decision to use the transradial approach should be tempered with the possibility that the radial artery may be needed for bypass grafting in the future. In patients for whom there is a high likelihood of future CABG, the choice of vascular access may require discussion with the patient and the cardiac surgeon. In centers where expertise in the transradial approach is unavailable, or in those patients who are unable to get radial artery catheterization because of anatomic or clinical limitations, femoral artery access remains the default strategy.

Earlier studies comparing outcomes with first-generation DES and BMS reported an increase in late stent thrombosis and increased mortality rate with DES.^5-8 Over the past 2 decades, there has been a significant evolution in DES technology, including the optimization of drug, polymer, and stent design, which has supported the safety as well as the efficacy of newer DES. To make sense of the small absolute differences between stent types, several large meta-analyses have been completed^1-4 and have suggested that the currently available DES have higher efficacy and safety and lower restenosis rates than both first-generation DES and BMS.^1-4

Because of limitations in angiography, intracoronary imaging can be a useful tool to guide coronary stent implantation, particularly in cases involving the left main artery or complex lesions. IVUS enables full-thickness visibility of the vessel wall, enabling pre-PCI assessment of plaque burden, extent of calcification, lesion length, and external elastic lamina diameter for stent sizing and post-PCI assessment of minimum stent area, malapposition, underexpansion, tissue protrusion, edge disease, and edge dissection.^18,19 OCT uses infrared light to generate high-resolution images of the vessel wall, with particular advantages in assessing calcium thickness, lipid, thrombus, fibroatheroma, and plaque rupture, as well as stent strut neointimal thickness and apposition, and edge dissections.²⁰ However, OCT has more limited depth of imaging. It also requires blood clearance through the use of contrast injection, which diminishes its use in ostial left main disease. IVUS and OCT can assist with assessing the need for lesion preparation, stent sizing, minimizing geographic miss, verifying stent expansion, evaluating complications, and identifying causes of stent failure.²⁰

Many patients with STEMI will have thrombotic occlusion of the infarct artery on the initial angiogram. Therefore, it is natural to consider the use of a device that would decrease thrombus burden to decrease the risk of distal embolization and the no-reflow phenomenon. However, patients in trials with STEMI undergoing primary PCI did not derive any clinical benefit from routine rheolytic thrombectomy.^6,7 Additionally, although the initial studies of aspiration thrombectomy in STEMI demonstrated an improvement in myocardial blush grades and rates of ST-segment–elevation resolution,^8-10 larger studies have not demonstrated improved cardiovascular outcomes with thrombus aspiration.^1-5

Fibrotic or heavily calcified lesions can hinder stent expansion. The presence of calcium deposits thicker than 500 μm or calcium involving an arc of the vessel >270° on intravascular imaging predicts the need for lesion modification to facilitate stent delivery.⁹ Lesions can be modified by using rotational atherectomy, orbital atherectomy, cutting balloon atherotomy, intracoronary lithotripsy, or excimer laser angioplasty. Despite promising results from hundreds of small mechanistic studies, dozens of large, randomized trials have shown that the routine use of atheroablative devices does not improve clinical or angiographic outcomes.^1-3,10 However, the use of atheroablative devices may enhance procedural success in specific circumstances.

In patients with previous CABG undergoing PCI of an SVG, the incidence of MACE is significantly higher than those with native coronary artery PCI because of the higher risk of procedural complications, including the no-reflow phenomenon and periprocedural MI.⁶ Compared with native coronary arteries, atherosclerotic plaques in SVGs are more diffuse, with thinner, more friable fibrous caps that increase the risk of distal debris embolization during PCI.⁹ In several large prospective registries, patients who underwent SVG PCI were more likely to have no-reflow,⁵ stent thrombosis, ischemia-driven target-vessel revascularization, increased overall adjusted MACE, and increased risk of death^4,5,10 in long-term follow-up than were those who underwent non-SVG PCI.

A CTO is found in approximately one-quarter of patients undergoing coronary angiography.^5,6 Considerable progress in the technical aspects of interventional revascularization has yielded success rates in excess of 80% in the hands of skilled operators.⁷ However, the 30-day mortality rate after CTO PCI is 1.3%, and perforations occur in 4.8% of cases.⁸ Enthusiasm for treating these lesions was fueled by retrospective data suggesting improved clinical outcomes for those patients who underwent successful recanalization compared with those who had failed.⁹ However, RCTs have not demonstrated improved function^4,10 and have been equivocal with regard to symptoms.^1,2 For this reason, shared decision-making should inform the treatment of patients with refractory angina despite GDMT with remaining CTO coronary lesion, with careful discussions of the limitations of treating these lesions, as well as the potential benefits.

The increasing use of newer-generation DES has led to a significant reduction in the risk of ISR and subsequent target-lesion revascularization compared with BMS and first-generation DES.^6-8 Nevertheless, ISR is still reported in 5% to 10% of patients undergoing PCI.^9,10 The primary mechanism of ISR after stent implantation is neointimal hyperplasia, with angiographic and histopathological studies demonstrating considerable differences in tissue characteristics based on the type of stent.^11-14 The risk of restenosis is also linked to clinical presentation, patient profile, lesion location, and procedural characteristics.^15,16 Numerous approaches to the treatment of restenosis have been explored and include balloon angioplasty, DES, drug-coated balloons, scoring or cutting balloons, vascular brachytherapy, atheroablative therapies, and CABG. Compared with other therapies, DES appears to provide the most benefit. However, the type of ISR (ie, focal versus diffuse) may also affect the decision to treat with one modality over another and, therefore, treatment of ISR should be individualized. Importantly, intensive medical therapy is also vital in these patients.

Patients undergoing complex PCI are at risk of hypotension, decompensated heart failure, shock, or arrhythmias that may lead to rapid hemodynamic deterioration or death. Intra-aortic balloon pump counterpulsation provides minimal hemodynamic support for PCI but improves coronary and cerebral perfusion. Its use is limited in patients with severe peripheral artery or aortic disease. Its advantages are ease of use and smaller catheter diameter, leading to lower rates of vascular access site complications. The Impella percutaneous left ventricular–assist devices (Abiomed, Danvers, MA) provide greater left ventricular support. The use of the Impella support devices is limited in patients with left ventricular thrombus, aortic stenosis, peripheral artery disease, or aortic disease. Extracorporeal membrane oxygenation and the TandemHeart (CardiacAssist, Inc, Pittsburgh, PA) devices are rarely used to support complex PCI. New hemodynamic support devices are undergoing evaluation in clinical trials.

DAPT with aspirin and oral P2Y12 inhibitors remains the cornerstone of therapy for the prevention of thrombotic complications with PCI. In the early days of PCI, aspirin was found to be effective at decreasing coronary thrombosis with balloon angioplasty,¹ and since that time, aspirin has remained a key agent for patients with chronic vascular disease.^2-4 The contemporary oral P2Y12 inhibitors used in PCI include clopidogrel, ticagrelor, and prasugrel. Patients should be treated with a loading dose of these agents, either before PCI or otherwise at the time of PCI (Table 9). Clopidogrel is the least potent agent, requiring longer time to platelet inhibition after a loading dose. In patients with stable angina, there is no compelling evidence to support routine pretreatment with a P2Y12 inhibitor before coronary angiography when the coronary anatomy is not known.²² This is especially important because the need for CABG still occurs in a nonnegligible proportion of patients referred for angiography, and pretreatment can result in postponement of surgery.¹⁸ The duration of treatment with DAPT is discussed in Section 14.

Cangrelor is a potent, direct, reversible, short-acting intravenous P2Y12 inhibitor with rapid onset of platelet inhibition and restoration of platelet function within 1 hour of discontinuation. Cangrelor thus provides rapid, predictable, and profound inhibition of platelets. It can be efficacious in preventing stent thrombosis and may be considered in patients who have not been pretreated with a P2Y12 inhibitor, in patients whose absorption of oral medications may be inhibited, or in patients who are unable to take oral medications. Cangrelor has been investigated within the CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program and compared with a loading dose of clopidogrel given at the time of PCI in 3 large-scale clinical trials.^1,2,4 There are no studies comparing cangrelor with a loading dose of ticagrelor or prasugrel given at the time of PCI.

Glycoprotein IIb/IIIa receptor inhibitors are direct-acting antiplatelet agents targeting the glycoprotein IIb/IIIa platelet receptor. Many of the trials of glycoprotein IIb/IIIa inhibitors in the setting of ACS were conducted in an era before the use of potent P2Y12 inhibitors or before routine stenting.^2,6 Additionally, in the earlier trials, the time from presentation to coronary angiography was often prolonged. In the contemporary era of shorter revascularization times and use of potent DAPT, the benefit of glycoprotein IIb/IIIa receptor inhibitor agents is diminished.^2,7

Antithrombotic therapy is a mainstay of treatment in patients undergoing PCI. Currently, there are 3 antithrombotic agents that have been studied in PCI. These are UFH, bivalirudin, and enoxaparin. Fondaparinux is no longer recommended as the only anticoagulant in PCI because of a higher incidence of guiding-catheter thrombosis.^20,21 Consideration of the patient’s clinical presentation (eg, stable disease, NSTE-ACS, or STEMI) and bleeding risk profile²² may influence selection of the optimal anticoagulant type. Suggested dosing regimens of parenteral agents are shown in Table 10.

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Previous recommendations with regard to perioperative management assessed the role of certain monitoring modalities to guide intraoperative and postoperative decision-making and also emphasized the use of fast-track cardiac anesthesia, which uses short-acting anesthetic agents to improve outcomes after CABG.⁴ More recently, cardiac surgical service lines have been encouraged to expand the scope of these efforts to develop multidisciplinary perioperative programs that incorporate bundled evidence-based surgical, anesthetic, and nursing interventions, including the targeted use of appropriate monitoring modalities, to optimize care and improve patient recovery.

In the choice of conduits for CABG, both clinical and technical factors (eg, life expectancy, presence of diabetes, presence of CKD, degree of target stenosis) are considered (Table 12). Decades of data have supported the use of the LIMA to graft the LAD to prolong survival. These data are from observational studies and, for the most part, were derived before the introduction of current optimal medical therapy. The LIMA is preferable unless specific contraindications are present. The right IMA can be used to graft the LAD if the LIMA is unusable, or the right IMA can be used in conjunction with the LIMA (BIMA grafting). Several randomized trials and meta-analyses have demonstrated better mid- and long-term patency rates for the radial artery than for the saphenous vein. A pooled analysis of 6 randomized trials has shown improved clinical outcomes at 10 years’ follow-up.¹³

The right IMA is biologically equivalent to the LIMA, and BIMA grafting has shown a survival advantage compared with CABG with a single IMA in observational studies. The extensive use of arterial conduits (>2) instead of SVGs for multivessel CABG may provide an additional late mortality benefit compared with CABG with 2 arterial grafts.

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The decision to add CABG to another planned cardiac surgery in patients with significant CAD is multifactorial. Considerations include but are not limited to comorbidities, technical feasibility of CABG, extent of the jeopardized myocardium, availability of conduit, left ventricular ejection fraction, and the additional time needed to construct the coronary bypass while on cardiopulmonary bypass. A multidisciplinary discussion with a Heart Team can help weigh the risks and benefits of adding CABG to the index cardiac operation. Age does not appear to be a prohibitive risk factor for the addition of CABG to other cardiac surgery in patients between the ages of 75 and 84 years,^1,2,4 but risk increases in patients ≥85 years of age.¹² The available evidence supporting CABG at the time of cardiac surgery performed for another primary indication (ie, valve, aortic, or other cardiac surgery) is limited and complicated because many studies include patients with CAD defined as at least 1 vessel with stenosis ≥50%, thus including both intermediate and significant CAD. The knowledge that incomplete revascularization is associated with reduced long-term survival rates after surgery compared with patients who receive complete revascularization may inform decisions about adding CABG to other cardiac surgery.^5,10 Additionally, it has become standard practice to bypass significant coronary artery stenoses in patients undergoing other cardiac surgery.

Atherosclerotic disease of the aorta is common in patients who undergo CABG surgery, with a reported prevalence that varies between 19% and 90%, depending on the patient population and modality of examination.^2,11-16 There has been a clear association between aortic atherosclerosis and stroke,¹⁷ especially in patients undergoing CABG.^11,12,18-21 Epiaortic ultrasound has been demonstrated to be far superior to either surgical digital palpation or transesophageal echocardiography for defining the presence and extent of disease and has come to be recognized as the “gold standard” for the detection of aortic atherosclerosis.^13-15,22-24 There has been considerable variability in the extent to which epiaortic ultrasound has changed operative strategy, varying from 4% to 22%.^1,2,6,9,16

When the operative strategy for CABG for a patient is being planned, it may be determined that the risks of aortic manipulation preclude the safe use of a cross-clamp or cannulation of the ascending aorta, and significant pulmonary disease may increase risk of cardiopulmonary bypass. In such cases, the risks and benefits of alternative operative strategies (off-pump or beating heart) are considered, along with surgeon experience with such strategies. Excellent surgical results can be achieved by surgeons experienced in off-pump techniques with either on-pump or off-pump CABG.^2,4-15 The major concerns with the off-pump approach relate to the technical difficulty of bypassing coronary arteries in the circumflex distribution, as well as the small and intramyocardial segments. These issues have resulted in a tendency toward fewer grafts per patient,^2,16,17 a potential for incomplete revascularization,^2,15 and a concern about long-term graft patency.^17-20

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Sternal wound infection has become less common in CABG surgery, with current rates reported to be <1%.¹⁶ However, the associated risk of death may increase several-fold,¹⁷ while the associated morbidity and expense can be considerable.⁷ Management of hyperglycemia with perioperative insulin infusion to maintain a glucose level <180 mg/dL, both in patients with known diabetes and in patients with stress hyperglycemia, has emerged as an important strategy to prevent infection, as well as to improve survival and reduce recurrent ischemic events.^1-3,18,19 Continuous intravenous insulin infusion after CABG reduces postoperative complications, such as mediastinitis, cardiac arrhythmias, deep sternal would infections, renal failure, and length of stay.^3,5,6 In addition to standard antibiotic prophylaxis, several other strategies have emerged as best practices to reduce the risk of sternal infection (Table 13).

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The use of aspirin and antiplatelet agents in patients undergoing CABG is discussed with the Heart Team to determine the optimal treatment for each patient, with careful consideration of the risk of myocardial ischemia, significant bleeding, reoperation, and transfusion. The present recommendations are based on the severity of the patient’s condition and the associated surgical necessity. When the various therapies are considered, the urgency of the planned surgery should be determined, as outlined in Table 7 (Section 5.2).^26,27

In patients undergoing elective CABG, the risks and benefits of beta-blocker and amiodarone administration before surgery should be carefully considered. Although preoperative beta blockers are associated with reduced incidence of postoperative atrial fibrillation, recent data, including meta-analyses of RCTs and several large observational trials, have yielded conflicting results with regard to their impact on other outcomes, including death, MACE, and other arrhythmias.

After PCI, the use of DAPT prevents stent thrombosis and reduces ischemic events at the cost of increased bleeding.⁵ Pooled data have demonstrated less bleeding with shorter-term DAPT (3–6 months) and fewer ischemic events (including stent thrombosis) with longer-term DAPT (>12 months)⁵ (Figure 7). The 2016 guideline focused update on duration of DAPT⁶ highlights the importance of balancing ischemic and bleeding risk when DAPT is considered and provides recommendations for short and prolonged DAPT followed by aspirin monotherapy after revascularization. Since the release of those guidelines, more recent trials have been published.^1-4,7 For this reason, additional recommendations for DAPT are provided. These recommendations should act as a supplement to the prior guideline focused update. Given the multiplicity of possible antiplatelet regimens available for use after revascularization, clinicians should weigh the risks of bleeding and recurrent ischemia when determining the choice of DAPT.

The mechanisms warranting DAPT therapy in patients who have undergone CABG are distinct from those in patients who have had ACS and have undergone PCI. The pathophysiology of vein graft occlusion involves a different mechanism from that of native vessel disease with atherosclerosis, plaque rupture, or stent thrombosis. Additionally, a larger percentage of the coronary tree is bypassed with CABG in contrast to the focal lesions treated with PCI. Finally, surgical bleeding is more of a concern in the perioperative and immediate postoperative period following CABG. Observational and small randomized trials and meta-analyses of these studies support that DAPT after CABG improves vein graft patency, primarily among patients undergoing off-pump surgery and those with higher SYNTAX scores. The role of DAPT in patients who undergo CABG after ACS is addressed in the DAPT guideline.¹¹ The role of prolonged DAPT for general secondary prevention in patients with a distant history of CABG is not well established.

In patients who have undergone revascularization, the risks and benefits of beta blockers should be considered before the initiation of therapy. The benefit of beta blockers for secondary prevention after acute infarction or for those with left ventricular dysfunction has been clearly reported in clinical trials examining these subgroups, and recommendations based on this evidence are outlined in previous guidelines.^7,8 However, in patients without acute infarction or left ventricular dysfunction, there is a paucity of data to support a benefit of the routine use of beta blockers after revascularization, especially in patients without residual disease. Further risk reduction may not be useful in patients after MI with normal left ventricular ejection fraction in the presence of GDMT with antiplatelet treatment, statins, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Thus, in the absence of new data to guide current therapy, clinicians will need to make decisions on an individualized basis.

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New-onset postoperative atrial fibrillation occurs in about 18% of patients after CABG and is associated with a 4-fold increased risk of stroke and a 3-fold increase in all-cause mortality rate.^8,9 Postoperative atrial fibrillation after CABG can be challenging to prevent and treat.

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Patients undergoing PCI frequently have or develop concomitant indications for anticoagulant therapy, including atrial fibrillation, venous thromboembolism, and prosthetic heart valves. The most robust evidence for anticoagulant management in such patients comes from trials in patients with atrial fibrillation. The 2019 focused update of the atrial fibrillation guidelines⁸ gave a Class 2a recommendation to a P2Y12 inhibitor with a non–vitamin K oral anticoagulant (rivaroxaban or dabigatran) or a vitamin K antagonist (warfarin) rather than triple therapy with an anticoagulant and DAPT. Since the publication of this guideline focused update, there have been 2 additional trials^1,4 examining the benefits of dual anticoagulant therapy after PCI in patients with atrial fibrillation. On the basis of analyses of these trials, the recommendations for antiplatelet and anticoagulant therapy after PCI in patients with atrial fibrillation have been updated.

Cardiac rehabilitation is an evidence-based intervention comprising patient education, behavior modification, and exercise training to improve secondary prevention outcomes in patients with CVD.⁸ Cardiac rehabilitation assists patients with adherence to healthy lifestyle habits; addresses comorbid conditions (eg, diabetes); monitors for safety issues, including new or recurrent symptoms; and facilitates adherence to evidence-based medical therapies.⁹ Cardiac rehabilitation may include a center-based cardiac rehabilitation program that incorporates face-to-face supervised exercise or an alternative cardiac rehabilitation delivery model that meets criteria for safety and effectiveness, as specified by the cardiac rehabilitation guidelines of the American Association of Cardiovascular and Pulmonary Rehabilitation.¹⁰

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Tobacco use, especially cigarette smoking, is a major risk factor for cardiovascular morbidity and mortality and is the leading preventable cause of death worldwide.^6,7 Among patients with coronary heart disease, continued cigarette smoking after revascularization is associated with adverse clinical outcomes,⁸ particularly stent thrombosis.⁹ Electronic nicotine delivery systems or e-cigarettes¹⁰ are a class of tobacco product that emit aerosol containing fine and ultrafine particulates, nicotine, and toxic gases that may increase risk of CVD and pulmonary disease.^11-13 The dominant pattern of e-cigarette use in adults is dual use of both combustible cigarettes and e-cigarettes.^14,15 When patients are counseled about risk factor management after revascularization, the topic of tobacco abuse is paramount and timely, because patients who are hospitalized after revascularization are often at their most attentive state. The recommendations for smoking cessation counseling and treatment are outlined in the “2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease”¹⁶ and are also applicable to the secondary prevention of patients after coronary artery revascularization.

Cardiac events and coronary revascularization can be distressing life events that lead to psychosocial morbidity.^10-13 Anxiety, depression, and stress are associated with poor adherence to healthy behaviors and prescribed medications, compromised quality of life, increased health care costs, and increased recurrent cardiac events^12,14-18 and are independent risk factors for CVD morbidity and mortality^19-24 (Figure 8). Presurgery estimates of depression in patients undergoing CABG range from 14% to 43%,^23,25-27 and depression increases length of hospital stay²⁸ and mortality rate.^14,23,29 About 20% of patients who undergo CABG remain depressed postoperatively.³⁰ Several psychological therapies have been used as part of secondary prevention to improve psychological outcomes. These include relaxation and stress management, enhancement of coping skills, and cognitive behavioral therapy, many of which are incorporated into cardiac rehabilitation programs.^3,31

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Centers that provide coronary revascularization should participate in clinical data registries with the intent to review and continuously improve patient outcomes. Comparison of outcomes through the use of national databases allows individual- and program-level assessment of the care provided and the opportunity to enhance care with quality improvement initiatives. Collaboration with other centers allows peer review and discussion, as well as sharing and adoption of effective quality improvement measures.

Despite advances in the identification of risk factors for CVD and the widespread use of evidence-based strategies to manage CVD, there are persistent sex, racial, and ethnic disparities in the delivery of care and in morbidity and mortality.^1-8 Studies have shown that Black patients and patients of South Asian descent with CAD have worse outcomes than do White patients.^2,4 Additionally, studies have reported worse outcomes in women than in men, although this finding is largely attenuated after adjustment for differences in baseline presentation and treatment.⁹ Recommendations for care in patients with CAD are often derived from RCT data with an unequal representation of women and racial and ethnic groups.¹⁰ Although a study’s findings might be extrapolated to such populations, it is unclear whether similar outcomes can be assumed from the reported trial results across all populations of patients. For this reason, in the planning of clinical trials, measures to ensure the enrollment of underrepresented racial and ethnic groups should be implemented to inform better care of patients.¹¹

RCT data support the use of CABG for the treatment of patients with coronary heart disease and left ventricular dysfunction to improve survival.^12-14 Although the STICH trial reported improved outcomes with CABG compared with medical therapy, the advantage of CABG over medical therapy was independent of the presence or absence of myocardial viability.^15-17 Critics have argued that the lack of a relative benefit of myocardial viability in predicting outcome with CABG was largely a result of the type of testing used.¹⁸ Many surgeons still use viability testing to guide decisions about revascularization in patients with severe left ventricular dysfunction. Nevertheless, in view of the lack of association of myocardial viability with derived benefit from revascularization, it remains unclear whether viability studies should be used to inform clinical practice, and if they are used, it remains unclear which method of assessment provides the most useful information.

There are currently insufficient data on the role of PCI in patients with left ventricular dysfunction to improve survival or cardiovascular outcomes. To address this gap in evidence, the ongoing REVIVED-BCIS2 (Percutaneous Revascularization for Ischemic Ventricular Dysfunction)¹⁹ study will evaluate the benefits of PCI versus medical therapy in reducing the combined endpoint of death or hospitalization for heart failure at 2 years’ follow-up. Additional studies are also currently under way, including the ISCHEMIA–Heart Failure Planning Study,²⁰ which is expected to pave the way for a larger phase 3 trial of PCI in patients with systolic heart failure.

SCAD is increasingly recognized as a cause of ACS in young patients, particularly women, and is present in roughly one-fourth of women ≤50 years of age presenting with AMI.²¹ The management of SCAD has evolved over the years toward a more cautious use of PCI after various case series demonstrated low success rates and higher rates of complications with PCI for SCAD, as well as good long-term outcomes in conservatively treated patients.²² For this reason, expert consensus statements emphasize conservative care in most patients.²³ However, managing patients with SCAD who have ongoing symptoms, hemodynamic instability, or severely compromised blood flow of an artery subtending a large amount of myocardium (ie, the proximal LAD or left main lesions) is particularly problematic, as conservative care may not be a good option. Further investigation therefore is needed to understand the ideal scenarios for proceeding with revascularization and the optimal techniques for revascularization in SCAD.

Coronary artery aneurysms and fistulas are uncommon findings on coronary angiography, with a reported prevalence of 0.02% to 0.2%.^24,25 Most patients with coronary artery aneurysms are asymptomatic, but coronary artery aneurysms can lead to ischemia, vessel thrombosis, fistula formation, or rupture.^24-27 There are no randomized studies evaluating the most effective therapy for these patients. Case reports and case series have described various methods for repair of aneurysms or fistulas, including covered stenting, coil embolization, Amplatzer device implantation, and surgical bypass with exclusion of the aneurysm.^24-27 Because many patients remain asymptomatic and treatments for aneurysms or fistulas are not well defined, information on the timing of intervention (with respect to size and/or symptoms) and the ideal approach to treatment (surgical excision versus percutaneous therapies) is strongly needed.

Myocardial bridging occurs when there is systolic compression of a coronary artery because of a segmental intramyocardial course of the vessel, and it is seen in up to 25% of patients undergoing coronary angiography.²⁸ Although most myocardial bridging is clinically insignificant, severe bridging has been inferred to produce myocardial ischemia, coronary thrombosis, AMI, and stress cardiomyopathy.²⁸ In patients with ischemic pain and a myocardial bridge, provocative testing can be performed by measuring FFR under baseline conditions and during dobutamine stress or by obtaining positron emission tomographic imaging during adenosine vasodilator challenge.²⁹ If a patient has evidence of severe ischemia and a significant myocardial bridge, surgical approaches are available; small studies have reported subsequent improvement in angina, as documented by the Seattle Angina Questionnaire.³⁰ Although these data appear promising, the long-term risks and benefits of surgery for myocardial bridging are uncertain, and larger studies are needed to define best practices in these circumstances.

Robust data are also lacking for recommendations for clinical situations that include acute graft failure after CABG, the percutaneous treatment of significant arterial graft disease after CABG, and percutaneous interventions via an arterial graft after CABG. Such circumstances warrant discussion with a Heart Team and further investigation.

Although antiplatelet therapy in patients with atrial fibrillation who are on anticoagulation after PCI is detailed in Section 14.5., there are no data to inform the treatment of patients after ACS who undergo CABG and also have an indication for anticoagulation (atrial fibrillation or mechanical valve). Care in such patients requires further study and careful consideration of bleeding risks, recurrent ischemic events, graft patency, and risk of thromboembolic events.

The number of patients undergoing radial artery catheterization has increased exponentially over the years.³¹ Some patients undergoing radial artery catheterization will ultimately require CABG. In patients undergoing CABG, the radial artery is the preferred conduit after the use of the LIMA.³² However, if the radial artery has been manipulated (eg, for access to perform coronary angiography or intervention), there is informal agreement among surgeons to generally avoid the use of this artery as a conduit for grafting, because of the findings of reduced acute and long-term graft patency in such patients.^33,34 Intimal tears, medial dissections, and increased intimal thickness are frequently found after radial artery catheterization,³⁵ and greater intimal hyperplasia was noted in the radial artery in pathology studies after radial artery catheterization.³⁴ The studies, which evaluated the integrity of the radial artery early after radial artery catheterization, were generally performed within 6 weeks of the radial artery procedure. The persistence of these abnormal findings in the radial artery in longer-term follow-up is uncertain. Given the increase in the use of radial access for coronary angiography and intervention, it would be important to know whether these pathological findings remain over time. Further research is needed to determine whether there is healing of the radial artery and, if so, whether the radial artery might be considered suitable for graft harvesting after a prespecified period of time that allows for resumption of normal endothelial integrity.

In patients with multivessel disease, when feasible, operators often attempt to treat all vessels to allow for a complete revascularization. There are no randomized studies prospectively comparing planned complete versus incomplete revascularization in SIHD, but several observational studies have concluded that patients who undergo CABG or PCI have worse outcomes if major epicardial vessels with significant stenoses are not revascularized during the index procedure.^36-41 In the SYNTAX trial, in which complete revascularization was attempted in all patients, patients who underwent CABG or PCI with incomplete revascularization had worse cardiovascular outcomes at long-term follow-up.⁴² Nevertheless, patients who have incomplete revascularization are more likely to have a greater burden of comorbidities, including older age, diabetes, renal failure, previous MI, lower left ventricular function, and more extensive and complex coronary anatomy, that may also impact the completeness of revascularization. The observational studies comparing patients who receive complete or incomplete revascularization cannot fully account for the underlying reasons why an operator might choose to revascularize only a limited area. It is reasonable to rationalize that complete revascularization to improve perfusion of as large an amount of myocardium as possible is a good strategy and likely improves patient outcomes. Nevertheless, the ISCHEMIA trial, which encouraged complete revascularization (especially if the arteries supplied areas in which there was ischemia on stress testing), did not demonstrate improved cardiovascular outcomes with revascularization. As such, when considering multivessel PCI or additional bypass grafting during a CABG procedure, one must be mindful of the theoretical benefits of complete revascularization for the individual patient. RCTs are needed to examine the benefits of complete revascularization in SIHD, with trial designs that mimic the trials performed on patients with STEMI and multivessel disease.⁴³

The hybrid approach to coronary revascularization (which combines minimally invasive off-pump grafting of the LIMA to the LAD, with PCI of the remaining vessels) has gained increasing popularity in recent years, although it is still performed by few select centers in the United States.⁴⁴ Small RCTs and observational studies with propensity-matching of hybrid revascularization versus conventional CABG^45-47 have found similar rates of death, MI, stroke, and repeat revascularization. Unfortunately, the Hybrid Coronary Revascularization trial, a phase 3, large-scale, randomized trial designed to compare multivessel PCI with hybrid coronary surgery in patients with disease of the LAD and ≥1 additional stenoses, was terminated early because of low enrollment (ClinicalTrials.gov identifier: NCT03089398). For this reason, the role of hybrid surgery as an alternative to multivessel PCI for patients with multivessel disease involving the LAD remains unclear. Furthermore, the Hybrid Coronary Revascularization trial did not compare hybrid surgery as an alternative to traditional CABG and, as such, additional studies to evaluate the use of hybrid surgery in these circumstances are needed. Other areas in need of further research include the use of non-sternotomy coronary artery revascularization.

The presence of CAD in patients referred for TAVR is variable, with 15% to 81% of patients enrolled in the landmark trials of TAVR having obstructive CAD.⁴⁸ Although the presence of CAD, particularly complex CAD, is associated with worse outcomes after TAVR,⁴⁹ observational studies have not demonstrated improved outcomes when PCI is performed before TAVR.⁵⁰ The RCT that evaluated TAVR versus surgical AVR advised that PCI be performed before TAVR in patients with proximal obstruction of large vessels.⁵¹ For this reason, PCI is often planned before valve procedures, and guidelines indicate that PCI may be reasonable in patients with severe disease of the proximal arteries.⁵² Nevertheless, this recommendation is based on limited data, and therefore, further research is needed to determine whether the routine use of PCI before percutaneous valve procedures improves outcomes.

There are currently no RCTs evaluating the role of revascularization before solid organ transplantation, although the RCT of revascularization before vascular surgery did not report improved outcomes with PCI.⁵³ Nonetheless, because of the increased risk of cardiovascular events among renal transplant recipients,⁵⁴ routine risk assessment is often performed before consideration for transplantation. When obstructive CAD is noted, many transplantation surgeons are hesitant to proceed with surgery in this complex group of patients without revascularization; therefore, it is common for a patient to be referred for revascularization in preparation for organ transplantation. In the Ischemia CKD trial, there were no differences in outcomes with routine revascularization even in the presence of severe ischemia, although only about 10% of enrolled patients were on the waitlist for transplantation. Even less is known about revascularization before liver transplantation. For this reason, it remains unclear whether revascularization before organ transplantation imparts a better outcome, and RCTs are needed to further inform care in this complex group of patients.