A 62-year-old man presented with acute chest pain that started with mild physical activity and lasted for more than 45 minutes after rest. His past medical history includes advanced coronary artery disease status post coronary artery bypass graft (CABG) surgery 6 years earlier. The grafts included an internal mammary graft to his anterior descending artery and saphenous vein grafts (SVGs) to the marginal branch of the circumflex artery and the posterior descending branch of the right coronary artery. His cardiovascular risk factors included hyperlipidemia, diabetes mellitus, and continued heavy smoking.

His initial blood work and electrocardiogram revealed elevated cardiac enzymes with ST-segment depression in inferior and lateral leads (II, III, V₅, and V₆). He was stabilized medically using antiplatelet and anticoagulant therapy before undergoing coronary angiography. Selective bypass graft angiography revealed a subtotal thrombotic occlusion in the body of SVG to the marginal branch of the circumflex artery (Figure 13-1). The lesion was considered the culprit lesion underlying his acute coronary syndrome and was treated percutaneously using a drug-eluting stent. The procedure was uncomplicated, and the patient was discharged the following day with aggressive secondary prevention measures and on dual antiplatelet therapy.

Acute coronary syndrome (ACS) secondary to SVG failure is similar in presentation to native coronary artery failure. Patients most commonly present with angina or pressure-type retrosternal chest pain that typically occurs with exertion but can also occur at rest. Chest pain can radiate to the arms, neck, or jaw with additional symptoms such as diaphoresis, dyspnea, nausea, abdominal pain, or syncope. Typically, although not necessarily, patients with a history of CABG surgery are older with multiple risk factors (eg, diabetes, hypertension, dyslipidemia, and tobacco use) that have resulted in the initial multivessel disease. The physical examination for ACS patients can be unremarkable, but manifestations of cardiogenic shock, acute heart failure (eg, tachycardia, hypotension, and/or elevated venous pressure), or new murmurs carry important diagnostic and prognostic implications.

Patients with SVG disease can also present with stable ischemic syndromes. SVG lesions can develop insidiously and lead to severe stenosis and even total occlusion over time. Collateral filling from ipsilateral or contralateral vessels can preserve myocardial viability, but it is often inadequate to prevent exertional angina. The clinical significance or degree of angina is determined by the patient’s level of activity, amount of myocardium subtended by the diseased graft, and the efficacy of the collateral circulation providing for that myocardial territory.

Over the past decade, the total number of coronary revascularization procedures, both percutaneous and surgical, have steadily declined.¹ In 2010, approximately 395,000 CABG surgeries were performed in the United States.² In addition to at least 1 arterial graft, the use of SVGs is common in the surgical revascularization of coronary artery disease since its introduction in the 1960s.^3,4 In contrast to arterial conduits, SVGs are more susceptible to degeneration, with a patency rate of 50% to 60% at 10 years, compared to 85% to 95% for arterial conduits.^5-9 The degenerative process and the limited life span of SVGs frequently lead to significant increase in major adverse cardiovascular events, including death, myocardial infarction (MI), and need for repeat revascularization.^10,11 In patients with previous CABG, ACSs are attributed to SVG lesions in up to 80% of cases.^12-14

Three main mechanisms have been described for SVG failure, each with a predilection for a specific time window in the life of the graft. Failure of SVG conduits during the early postoperative period (first month) is not rare, ranging from 3% to 12%.^6,7 At its early stage, SVG failure is primarily driven by thrombosis. The prothrombotic effects from endothelial injury and inflammatory cytokines during surgery are often augmented by other factors that reduce graft flow and precipitate thrombotic occlusion.^15-27 These factors include poor run-off due to severe distal native coronary atherosclerosis, nonobstructive proximal native artery disease, intrinsic saphenous vein disease, and surgical factors such as graft malpositioning or distal arterial dissection.^15,16 Between 1 and 12 months after surgery, SVG failure is more commonly due to platelet adherence and intimal hyperplasia after the vein graft’s adaptation to higher arterial pressures with concomitant loss of endothelial inhibition and increased smooth muscle proliferation (Figure 13-2).^{15,17,19,20,23,27-32} After the first year, following arterialization of the conduit, accelerated atherosclerosis by lipid incorporation into the intima is thought to be the main cause for graft stenosis and occlusion.¹⁵ Analysis of SVG lesions underlying ACS demonstrates similar morphologic characteristics to native coronary culprit lesions. However, SVG atheromas are bulkier, with poorly developed fibrous caps making them more vulnerable to acute rupture and subsequent thrombotic occlusions (Figures 13-2 and 13-3).^12,15,33-39

The accelerated degenerative and atherosclerotic processes predispose SVGs to extensive plaque and thrombus burden, which increases the risk of distal embolization (Figure 13-4). This feature is the principal mechanism that increases the risk of SVG coronary interventions: propensity for downstream embolization and the no-reflow phenomenon. More importantly, despite the high rate of early success, the diffuse and progressive nature of degenerative processes in vein grafts limits the therapeutic benefit of percutaneous treatment, which only relieves obstruction in a short segment of the graft.

Intimal hyperplasia is a different but common cause of stenosis at both aortic and native coronary anastomotic locations (Figure 13-5).⁴⁰ The luminal compromise is caused by progressive accumulation of neointima, which is an injury response initiated by the trauma of suture anastomosis to the aorta proximally and/or the native coronary artery distally.

Several clinical and angiographic characteristics have been identified as predictors of accelerated atherosclerosis in SVGs (Table 13-1). Clinical variables predicting SVG disease progression include male sex, tobacco use, hypertension, and dyslipidemia.⁴¹ Angiographically, small target vessel diameter and presence of moderate SVG lesions have been associated with earlier graft failure.^15,42 When examining the long-term patency of SVGs, grafting into the left anterior descending artery or recipient vessels with a diameter greater than 2 mm predicted higher rates of patency.⁸ In the Post Coronary Artery Bypass Graft Trial, the SVG maximum percent stenosis at baseline was found to be the most important predictor of disease progression.⁴¹ The incidence of death or MI in patients with moderate SVG lesions was high as 17% to 25% at 2- to 3-year follow-up. This is considerably higher than that observed in patients with moderate lesions in native coronary arteries.^41,43-46

The principles of management for patients with SVG lesions are similar to those of patients with native coronary disease. The clinical presentation, the severity of obstruction, and the distribution of disease play a critical role in decision making. In all cases, optimal medical therapy should be employed. This encompasses antianginal medications as well as pharmacologic and nonpharmacologic secondary prevention measures. In patients with stable symptoms, this may suffice for symptom control. However, for patients with refractory angina or ACS, revascularization is frequently indicated. Typically, percutaneous interventions are preferred due to the increased risk of morbidity and mortality of repeat bypass surgery. Whether the patients undergo repeat revascularization or not, aggressive pharmacologic and nonpharmacologic secondary prevention are strongly indicated.

OPTIMAL MEDICAL THERAPY

These strategies should represent the first-line and background therapy of all patients with a history of coronary artery disease (CAD) and/or CABG. The goals of therapy include (1) control of symptoms, (2) prevention of acute events, and (3) prevention of disease progression.

In stable ischemic presentations, angina can frequently be controlled using β-blockers, calcium channel blockers, and/or long-acting nitrates. Revascularization should be considered when symptoms are intractable. As discussed later, aspirin is the main antiplatelet therapy and is recommended for patients with CAD to reduce risk of death and acute ischemic events. Prevention of disease progression primarily depends on control of risk factors, namely statin therapy and cessation of tobacco use.

REVASCULARIZATION

Compared to primary CABG, re-do bypass surgery is associated with increased morbidity and mortality. Therefore, percutaneous coronary intervention (PCI) is often the preferred revascularization approach for bypass graft lesions. Repeat CABG is reserved for those in whom percutaneous approaches are not feasible.^47-50 In comparison to native artery PCI, SVG PCI procedures are considered high risk due to concerns of distal embolization with subsequent slow-flow or no-reflow phenomenon and periprocedural MI. The following discussion focuses on the unique features, risks, and technical considerations related to SVG PCI and the impact on patient outcomes.

EVOLUTION OF STENTS FOR SVG PCI

The Saphenous Vein De Novo (SAVED) trial established the value of using bare metal stents (BMS) compared to balloon angioplasty in SVG lesions. Compared to balloon angioplasty, BMS implantation was associated with higher procedural success (92% vs. 69%, P <.001) and a significant reduction in the composite outcome of freedom from death, MI, repeat CABG, and target lesion revascularization (73% vs. 58%, P = .03).⁵¹ Interestingly, the reduction in restenosis was less than expected when compared to native coronary PCI trials.⁵¹

For native artery lesions, drug-eluting stents (DES) are now accepted as the mainstay for PCI due to the established superiority over BMS in reducing major adverse cardiac events (MACE), primarily by reducing restenosis and need for target vessel revascularization (TVR). Subsequently, small observational and randomized trials demonstrated the safety and efficacy of DES in SVG PCI, primarily by reducing need for repeat revascularization.^52-61 In a systematic review and meta-analysis comparing use of DES with BMS in SVG lesions, DES use was associated with a 25% reduction in mortality and over 40% reduction in TVR. There was no significant difference in the incidence of MI or stent thrombosis.⁶² In a more recent randomized superiority trial, the ISAR-CABG (Is Drug-Eluting Stenting Associated with Improved Results in Coronary Artery Bypass Grafts?) study showed that DES reduced the incidence of the primary end point (combined incidence of death, MI, and need for revascularization) when compared with BMS (15.4% vs. 22.1%, P = .03; Figure 13-6).⁶³ This clinical benefit was primarily driven by the lower rate of repeat procedures in patients treated with DES (7.2% vs. 13.1%, P = .02), with no significant advantage in all-cause mortality, MI, or stent thrombosis. Furthermore, in a recent large observational study, there was no evidence of increased risk of death, MI, or urgent revascularization after DES use in SVG lesions compared to BMS.⁶⁴ Given these results, in the absence of contraindications, DES use in SVG PCI is strongly recommended in national practice guidelines.⁶⁵

Despite potential benefits of revascularization, for chronic total SVG occlusions, successful recanalization with stent implantation has poor short-term and long-term results and is not generally recommended.⁶⁶

NO-REFLOW PHENOMENON

The bulky and friable atheromas typically encountered in SVG disease increase the risk of complications during SVG PCI. “No-reflow” or “slow-flow” is a phenomenon characterized by absent or poor antegrade coronary flow without evidence of dissection, thrombus, or vessel closure. It occurs in up to 15% of patients undergoing higher risk procedures, such as SVG intervention, and is associated with an increased risk of death and MI.⁶⁷ Although the exact mechanism remains unknown, it is thought to be precipitated by embolism into the distal capillary beds, which in turn is associated with endothelial swelling, neutrophil infiltration, and platelet aggregation, leading to obstruction and spasm.⁶⁸ Clinical and angiographic predictors of no-flow phenomenon include ACS, degenerated SVG, lesion ulcerations, and angiographic evidence of thrombus in the graft.⁶⁹ In attempt to decrease complications of SVG PCI, various pharmacologic and percutaneous device strategies have been examined. Although the use of glycoprotein IIb/IIIa inhibitors and vasodilators demonstrated limited success, embolism protection devices (EPDs) were associated with reduced periprocedural MIs and no-reflow, which translated into reduction in MACE.

EMBOLIC PROTECTION DEVICES

Mechanical embolic protection devices were developed primarily to reduce the risk of distal embolization during SVG PCI (Figure 13-7). These devices proved to be the first treatment modality to reduce death and periprocedural MI during SVG PCI. Distal EPDs include the distal balloon occlusion/aspiration system and the distal filter system. The distal occlusion and aspiration system, PercuSurge GuardWire system (Medtronic, Minneapolis, MN), occludes the vessel distal to the target lesion in order to provide myocardial protection from embolization. Following balloon inflation and stent deployment, the aspiration device removes the debris before balloon deflation and restoration of antegrade blood flow. In the Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) trial, the GuardWire distal occlusion and aspiration system showed a 42% reduction in 30-day MACE (9.6% vs. 16.5%, P = .004), primarily driven by reduction in periprocedural MIs (8.6% vs. 14.7%, P = .008) and decrease in no-flow phenomenon (3% vs. 9%, P = .02).⁷⁰ In the FilterWire EX Randomized Evaluation (FIRE) study, the distal filtration Filter Wire EX System (Boston Scientific, Marlborough, MA) demonstrated noninferiority to the GuardWire balloon distal occlusion and aspiration system (Figure 13-8).⁷¹ New-generation distal filtration systems, such as the second-generation FilterWire EX, Spider Rx (Medtronic), and Interceptor PLUS (Medtronic), showed similar results in its utility to treat SVG lesions.⁷²