**10. Percutaneous coronary intervention**

Implantation of coronary stents has become the preferred revascularization strategy for treatment of graft lesions, because redo CABG is associated with an increased morbidity and mortality. [17,124-129] Compared to native vessel stenting, stenting of graft lesions is associ‐ ated with higher rates of periprocedural events as well as cardiac events at follow-up, due to distal embolization and subsequent no-reflow and higher percentages of restenosis. [124,125, 130,131] This increased risk is mainly attributed to the friable, degenerated atheromatous and thrombotic debris that develop when SVGs deteriorate. [132] Moreover, patients with graft intervention often have a higher generalized atherosclerotic burden and more comorbidities. [130,131] To date, SVG graft intervention accounts approximately for 5% to 10% of all PCI.

*Early graft failure -* The incidence of early graft failure within 24 h after CABG is about 1% to 3%. [133] Perioperative graft failure following CABG may result in acute myocardial ischemia which may necessitate acute secondary revascularization procedure to salvage myocardium, preserve left ventricular function and improve patient outcome. Perioperative MI and rise in cardiac markers after CABG is associated with a substantially increased in-hospital morbidity and mortality. [134-136] The most common graft-related causes of myocardial ischemia after CABG are graft occlusion due to acute graft thrombosis, graft kinking or overstretching, postoperative graft spasm and subtotal or hemodynamic relevant anastomotic stenosis. [137,138] Nongraft-related causes for myocardial ischemia after CABG are surgery-related possibly due to surgical manipulation on pre-existing microembolizing and disintegrating unstable plaque and include inadequate cardioplegic perfusion and myocardial protection, incomplete revascularization, or distal coronary microembolization. [139-141] Rapid identifi‐ cation of early graft failure after CABG and diagnostic discrimination from other causes enables an adequate reintervention strategy for re-revascularization, i.e. redo CABG or PCI, and may prevent irreversible myocardial ischemia. Thus far, limited non-randomized data is available showing that in patients with acute perioperative myocardial ischemia due to early graft failure following CABG, emergency PCI may limit the extent of myocardial cellular damage compared with redo CABG. [133] A nonsignifiant numerical difference was observed in in-hospital and 1-year mortality between the PCI group or redo CABG (12.0% and 20.0% in PCI group versus 20.0% and 27% in redo CABG group). Moreover, compared to acute redo-CABG, emergency PCI is quicker and less invasive. Importantly, in this study patent grafts were observed in 25% to 34% of the patients, therefore repeat coronary angiography should be applied when myocardial ischemia due to acute graft failure is suspected. Regarding the type of bypass graft, LIMA graft failure may be responsible for acute ischemic complications after CABG in at least a third up to half of the cases. [133,138,142]

Society for Cardiovascular Angiography and Interventions (SCAI), Society of Thoracic Surgeons (STS), American Association for Thoracic Surgery (AATS), American Heart Associ‐ ation (AHA), and the American Society of Nuclear Cardiology (ASNC) it is stated that in patients with prior CABG, the presence of high-risk findings on noninvasive testing, higher severity of symptoms, or an increasing burden of disease in either the bypass grafts or native coronaries tended to increase the likelihood of an appropriate rating. [119] In patients with prior CABG receiving no or minimal anti-ischemic therapy or having low-risk findings on noninvasive testing revascularization was considered inappropriate. No specific recommenda‐ tions are provided on the strategy for revascularization, performing redo CABG or PCI.

Both the ESC/EACTS guidelines on myocardial revascularization and the ACCF/SCAI/STS/ AATS/AHA/ASNC/HFSA/SCCT 2012 appropriate use criteria for coronary revascularization focused update do not provide recommendations for patients with prior CABG presenting

Implantation of coronary stents has become the preferred revascularization strategy for treatment of graft lesions, because redo CABG is associated with an increased morbidity and mortality. [17,124-129] Compared to native vessel stenting, stenting of graft lesions is associ‐ ated with higher rates of periprocedural events as well as cardiac events at follow-up, due to distal embolization and subsequent no-reflow and higher percentages of restenosis. [124,125, 130,131] This increased risk is mainly attributed to the friable, degenerated atheromatous and thrombotic debris that develop when SVGs deteriorate. [132] Moreover, patients with graft intervention often have a higher generalized atherosclerotic burden and more comorbidities. [130,131] To date, SVG graft intervention accounts approximately for 5% to 10% of all PCI.

*Early graft failure -* The incidence of early graft failure within 24 h after CABG is about 1% to 3%. [133] Perioperative graft failure following CABG may result in acute myocardial ischemia which may necessitate acute secondary revascularization procedure to salvage myocardium, preserve left ventricular function and improve patient outcome. Perioperative MI and rise in cardiac markers after CABG is associated with a substantially increased in-hospital morbidity and mortality. [134-136] The most common graft-related causes of myocardial ischemia after CABG are graft occlusion due to acute graft thrombosis, graft kinking or overstretching, postoperative graft spasm and subtotal or hemodynamic relevant anastomotic stenosis. [137,138] Nongraft-related causes for myocardial ischemia after CABG are surgery-related possibly due to surgical manipulation on pre-existing microembolizing and disintegrating unstable plaque and include inadequate cardioplegic perfusion and myocardial protection, incomplete revascularization, or distal coronary microembolization. [139-141] Rapid identifi‐ cation of early graft failure after CABG and diagnostic discrimination from other causes enables an adequate reintervention strategy for re-revascularization, i.e. redo CABG or PCI, and may prevent irreversible myocardial ischemia. Thus far, limited non-randomized data is available showing that in patients with acute perioperative myocardial ischemia due to early

with (non) ST segment elevation myocardial infarction (STEMI) or ACS.

**10. Percutaneous coronary intervention**

204 Artery Bypass

Recurrent angina during the early postoperative period is usually due to a technical problem with a graft or with early graft closure and there is an indication for prompt coronary angiog‐ raphy with percutaneous revascularization. The feasibility of PCI in patients presenting with clinical evidence of ischemia within 90 days of CABG was evaluated in 2 registries. Most patients presented with ACS and the most common cause of graft failure was occlusion or thrombosis. Both registries showed that patients with graft failure can undergo PCI with a relatively low risk for in-hospital mortality or nonfatal major complications. [143,144]

*SVG failure -* Recurrent angina after the first few months after CABG is caused by both graft disease and by progression of atherosclerosis in non-bypassed vessels. Percutaneous inter‐ vention in SVG lesions was evaluated in several randomized studies. The SAVED (Saphenous Vein de Novo) study randomized 200 patients with SVG lesions to placement of Palmaz-Schatz bare metal stent (BMS) or standard balloon angioplasty (BA) and demonstrated that compared to BA, bare metal stents (BMS) were associated with a higher procedural success (92% vs. 69%, p<0.001) but they had more frequent hemorrhagic complications (17% vs. 5 %, p<0.01). [145] At 6 months, a non-significant reduction in angiographic restenosis was observed (36% vs. 47%, p=0.11) and clinical follow-up at 9 months showed that freedom from death, MI, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73% vs. 58 %, P = 0.03). Based on the results of the SAVED study, the majority of patients with SVG stenosis are treated with stenting. To prevent distal embolization form friable atheroemboli, and in addition may serve as a smooth-muscle cell barrier to decrease restenosis, stents covered with a mesh, most commonly polytetrafluorethylene (PTFE), were evaluated. However, 3 prospective randomized trails have not shown benefit with covered stents with respect to major adverse cardiac events nor in preventing restenosis. [146-148]

In native coronary arteries, drug-eluting stents (DES) have demonstrated a marked reduction in in-stent restenosis compared to BMS in the treatment of coronary artery disease. Several DES with different stent platforms, polymers or drugs are available. In the RRISC (Reduction of Restenosis in Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent) trial, 75 patients were randomized to sirolimus-eluting stent (SES) or BMS. [149] At 6 months follow-up, instent late loss was significantly reduced in SES (0.38 ± 0.51 mm vs. 0.79 ± 0.66 mm in BMS). Target lesion revascularization rate was also significantly reduced (5.3% vs. 21.6%) but no difference in death and MI was observed. Howbeit, a post hoc analysis of RRISC trial at 3 years reported similar rates of target vessel revascularization and while statistically underpowered for clinical outcomes, significantly higher all-cause mortality was reported with SES compared with BMS. [150] The SOS (Stenting of Saphenous Vein Grafts) trial randomized 80 patients to either paclitaxel-eluting stent (PES) or BMS and showed significant reduction in primary end point, binary angiographic restenosis at 12 months (9% vs. 51%). [151] At 1.5 years clinical follow-up the PES patients had a significant reduction in target lesion revascularization (5% vs. 28%), target vessel failure (22% vs. 46%) and a trend towards less MI (15% vs. 31%) but increased mortality (12% vs. 5%). In contrast to the long-term results of the RRISC study, at a median follow-up of 35 months PES treated-patients had a significantly lower incidence of MI (17% vs. 46%), target lesion revascularization (10% vs. 41%), and target vessel failure (34% vs. 72%) as well as a trend toward less definite or probable stent thrombosis (2% vs. 15%). Allcause mortality (24% vs. 13%) and cardiac mortality (7% vs. 13%) did not differ between groups. [152] More evidence was provided in the ISAR-CABG (Prospective, Randomized Trial of Drug-Eluting Stents Versus Bare Metal Stents for the Reduction of Restenosis in Bypass Grafts). In this study, 610 patients with diseased SVGs were randomized to DES and BMS and the combined incidence of death, MI, and target lesion revascularisation at 1 year was significantly lower in the DES group than in the BMS group (15.4% vs. 22.1%) which was mainly driven by a nearly 50% relative reduction in the risk of target lesion revascularization (7.2% vs. 13.1%), with non-significant differences in mortality. [153] Consistent results of improved efficacy with DES and no significant safety hazard were reported in different metaanalyses which also included non randomized trails. [154-157] The RRISC, SOS and ISAR CABG all compared first-generation DES to BMS. The SOS-Xience V (Stenting of Saphenous Grafts-Xience V) prospectively examined the frequency of angiographic in-stent restenosis in SVG lesions 12 months after implantation of everolimus-eluting stent (EES), a second gener‐ ation DES. Use of EES in SVGs is associated with high rates of stent strut coverage and high malapposition rates at 12 months post implantation as assessed by optical coherence tomog‐ raphy, however, clinical results are to be waited. [158] Finally, in a multicenter analysis no difference was observed in real-world patients comparing first-generation DES to BMS. [159] In a meta-analysis including 29 studies (3 randomized controlled trials (RCT)) involving over 7500 patients, the authors stated that DES may decrease TVR rate in treatment of SVG stenoses but no differences in reinfarction rate, stent thrombosis or mortality was found between the DES and BMS groups in the RCT's. [160] In contrast, the observational data showed lower risk for MI, stent thrombosis and death in the DES group. This may be a result of patient selection bias in the observational studies or represent a true finding that was not detected in the RCT analysis due to limited statistical power.

associated with a lower CK-MB release and fewer non-Q-wave MI. [162] These results needs

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After PCI of SVG, progression of disease outside the stented segment can lead to high rates of restenosis. Therefore, treatment of native coronary artery lesions is preferred to treatment of degenerated SVG if feasible. In addition, in patients with prior CABG, early diagnostic angiography can be important as there is a high success rate of percutaneous coronary intervention (PCI) at the time of subtotal occlusion; and the substantial consequences of the loss of a bypass graft through total occlusion (e.g, low success and high complication rates of

A numerous of predictors for worse outcome after percutaneous SVG intervention have been identified. Multivariate analysis revealed that major CK-MB release after SVG intervention and renal insufficiency are powerful independent predictor of all-cause mortality. [163-165] Lesion length, greater angiographic degeneration of SVG, and larger estimated plaque volume which may result in a greater likelihood of distal embolization and myocardial necrosis after intervention, have been identified as predictors of 30-day major adverse cardiac events after SVG intervention. [166,167] Sexe also appeared to be a predictor as women have a significantly higher 30-day cumulative mortality rate compared with men (4.4% vs. 1.9%), a higher incidence of vascular complications (12% vs. 7.3%), and postprocedural acute renal failure (8.1% vs. 4%). [168] Whether specific stent platforms, polymers or drugs are more appropriate

*Arterial graft failure -* Due to the superior long-term patency of arterial grafts, in specific the IMA, they are the vascular conduit of choice for patients undergoing CABG and the increasing frequency of their use has resulted in a small but increasing need for revascularization. In arterial graft failure, ostial stenoses are the least common and the pathogenesis of ostial stenoses may be affected by its proximity to the aorta and potential extension of atherosclerosis

Anastomosis of IMA to the native coronary is the most frequent site of a target lesion. The particular anatomical feature of the IMA-to-LAD anastomosis is subjected to continuous mechanical stress, owing to the asynchronous motion of heart, lungs and bypass. Moreover, it has been suggested that this predilection reflects scar tissue induced by injury during surgical

Published reports have demonstrated that BA of the IMA can be performed safely with high procedural success and a low incidence of clinical restenosis. [170-175] The use of BMS compared to BA alone for percutaneous revascularization of the IMA graft was investigated in several studies. In a large cohort of 174 patients who underwent BA or BMS placement, anastomotic lesions were more evident, 63% of al cases. [169] These lesions were more commonly treated with BA (91%), whereas lesions located at the ostium (8%) were more frequently treated with stents (69%). Patients who underwent stenting had a target lesion revascularization rate of 15.4% and those who underwent BA had a rate of 5.4%. In a retro‐ spective analysis patients undergoing BMS implantation for the treatment of IMA graft stenosis were compared to patients treated with BA. [176] The minority of patients were treated

to be confirmed in a prospective randomized trial.

PCI for totally occluded SVG, and difficult to control angina).

in SVG and arterial graft lesions has not been addressed at this time.

from that vessel.

manipulation. [169]

Stents are effective as treatment for focal lesions, however, the optimal treatment strategy for a diffusely degenerated SVG is uncertain. Endoluminal reconstruction with stent omplantation has been suggested as a treatment for diffuse lesions. This was evaluated in a study including 126 patients with diffusely degenerated stenosed or occluded SVG treated with stents. [161] At 3 year follow-up, survival free of death, infarction, or revascularization was only 43%.

Regarding stenting technique in SVG lesions, it has been suggested that direct stenting, compared to predilatation with balloon angioplasty, may be beneficial as trapping of debris could decrease distal embolization that may occur from repeated balloon inflations. Registry data showed that in unselected patients who underwent SVG intervention direct stenting was associated with a lower CK-MB release and fewer non-Q-wave MI. [162] These results needs to be confirmed in a prospective randomized trial.

with BMS. [150] The SOS (Stenting of Saphenous Vein Grafts) trial randomized 80 patients to either paclitaxel-eluting stent (PES) or BMS and showed significant reduction in primary end point, binary angiographic restenosis at 12 months (9% vs. 51%). [151] At 1.5 years clinical follow-up the PES patients had a significant reduction in target lesion revascularization (5% vs. 28%), target vessel failure (22% vs. 46%) and a trend towards less MI (15% vs. 31%) but increased mortality (12% vs. 5%). In contrast to the long-term results of the RRISC study, at a median follow-up of 35 months PES treated-patients had a significantly lower incidence of MI (17% vs. 46%), target lesion revascularization (10% vs. 41%), and target vessel failure (34% vs. 72%) as well as a trend toward less definite or probable stent thrombosis (2% vs. 15%). Allcause mortality (24% vs. 13%) and cardiac mortality (7% vs. 13%) did not differ between groups. [152] More evidence was provided in the ISAR-CABG (Prospective, Randomized Trial of Drug-Eluting Stents Versus Bare Metal Stents for the Reduction of Restenosis in Bypass Grafts). In this study, 610 patients with diseased SVGs were randomized to DES and BMS and the combined incidence of death, MI, and target lesion revascularisation at 1 year was significantly lower in the DES group than in the BMS group (15.4% vs. 22.1%) which was mainly driven by a nearly 50% relative reduction in the risk of target lesion revascularization (7.2% vs. 13.1%), with non-significant differences in mortality. [153] Consistent results of improved efficacy with DES and no significant safety hazard were reported in different metaanalyses which also included non randomized trails. [154-157] The RRISC, SOS and ISAR CABG all compared first-generation DES to BMS. The SOS-Xience V (Stenting of Saphenous Grafts-Xience V) prospectively examined the frequency of angiographic in-stent restenosis in SVG lesions 12 months after implantation of everolimus-eluting stent (EES), a second gener‐ ation DES. Use of EES in SVGs is associated with high rates of stent strut coverage and high malapposition rates at 12 months post implantation as assessed by optical coherence tomog‐ raphy, however, clinical results are to be waited. [158] Finally, in a multicenter analysis no difference was observed in real-world patients comparing first-generation DES to BMS. [159] In a meta-analysis including 29 studies (3 randomized controlled trials (RCT)) involving over 7500 patients, the authors stated that DES may decrease TVR rate in treatment of SVG stenoses but no differences in reinfarction rate, stent thrombosis or mortality was found between the DES and BMS groups in the RCT's. [160] In contrast, the observational data showed lower risk for MI, stent thrombosis and death in the DES group. This may be a result of patient selection bias in the observational studies or represent a true finding that was not detected in the RCT

Stents are effective as treatment for focal lesions, however, the optimal treatment strategy for a diffusely degenerated SVG is uncertain. Endoluminal reconstruction with stent omplantation has been suggested as a treatment for diffuse lesions. This was evaluated in a study including 126 patients with diffusely degenerated stenosed or occluded SVG treated with stents. [161] At 3 year follow-up, survival free of death, infarction, or revascularization was only 43%.

Regarding stenting technique in SVG lesions, it has been suggested that direct stenting, compared to predilatation with balloon angioplasty, may be beneficial as trapping of debris could decrease distal embolization that may occur from repeated balloon inflations. Registry data showed that in unselected patients who underwent SVG intervention direct stenting was

analysis due to limited statistical power.

206 Artery Bypass

After PCI of SVG, progression of disease outside the stented segment can lead to high rates of restenosis. Therefore, treatment of native coronary artery lesions is preferred to treatment of degenerated SVG if feasible. In addition, in patients with prior CABG, early diagnostic angiography can be important as there is a high success rate of percutaneous coronary intervention (PCI) at the time of subtotal occlusion; and the substantial consequences of the loss of a bypass graft through total occlusion (e.g, low success and high complication rates of PCI for totally occluded SVG, and difficult to control angina).

A numerous of predictors for worse outcome after percutaneous SVG intervention have been identified. Multivariate analysis revealed that major CK-MB release after SVG intervention and renal insufficiency are powerful independent predictor of all-cause mortality. [163-165] Lesion length, greater angiographic degeneration of SVG, and larger estimated plaque volume which may result in a greater likelihood of distal embolization and myocardial necrosis after intervention, have been identified as predictors of 30-day major adverse cardiac events after SVG intervention. [166,167] Sexe also appeared to be a predictor as women have a significantly higher 30-day cumulative mortality rate compared with men (4.4% vs. 1.9%), a higher incidence of vascular complications (12% vs. 7.3%), and postprocedural acute renal failure (8.1% vs. 4%). [168] Whether specific stent platforms, polymers or drugs are more appropriate in SVG and arterial graft lesions has not been addressed at this time.

*Arterial graft failure -* Due to the superior long-term patency of arterial grafts, in specific the IMA, they are the vascular conduit of choice for patients undergoing CABG and the increasing frequency of their use has resulted in a small but increasing need for revascularization. In arterial graft failure, ostial stenoses are the least common and the pathogenesis of ostial stenoses may be affected by its proximity to the aorta and potential extension of atherosclerosis from that vessel.

Anastomosis of IMA to the native coronary is the most frequent site of a target lesion. The particular anatomical feature of the IMA-to-LAD anastomosis is subjected to continuous mechanical stress, owing to the asynchronous motion of heart, lungs and bypass. Moreover, it has been suggested that this predilection reflects scar tissue induced by injury during surgical manipulation. [169]

Published reports have demonstrated that BA of the IMA can be performed safely with high procedural success and a low incidence of clinical restenosis. [170-175] The use of BMS compared to BA alone for percutaneous revascularization of the IMA graft was investigated in several studies. In a large cohort of 174 patients who underwent BA or BMS placement, anastomotic lesions were more evident, 63% of al cases. [169] These lesions were more commonly treated with BA (91%), whereas lesions located at the ostium (8%) were more frequently treated with stents (69%). Patients who underwent stenting had a target lesion revascularization rate of 15.4% and those who underwent BA had a rate of 5.4%. In a retro‐ spective analysis patients undergoing BMS implantation for the treatment of IMA graft stenosis were compared to patients treated with BA. [176] The minority of patients were treated with BMS (26.4%) and received at least either ticlopidine or clopidogrel for 4 weeks post PCI. Angiographic success after stenting was high, 92%. At 1 year follow-up, target lesion revas‐ cularization rates were significantly higher in the stented lesions than lesions treated with BA alone (19.2% vs. 4.9%) and the higher rate in stented lesions was most apparent at the anasto‐ motic site (25.0% vs. 4.2%). Moreover, a significant difference was observed between 1-year all-cause mortality between stented lesions and lesions treated with BA alone (13.6% vs. 4.4%), no difference was observed for MI. In a multivariate analysis including all available baseline factors contributing to target lesion revascularization, indicated that stent use was an inde‐ pendent predictor. In this observational study selection bias may have resulted in more lesions at high risk of restenosis being chosen for stenting, as stenting was at the discretion of the operator.

Failure of the RA graft is most frequently a complete occlusion and less often a string-like

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RA graft stenosis treated by percutaneous intervention was evaluated in a small study including 18 patients. [184] The location of the RA stenosis was proximal (n = 2), shaft (n = 11) or distal anastomosis (n = 5). BA alone was performed on nine RA grafts at 1.7 years after surgery and stenting (3 BMS, 6 DES) of nine RA grafts was achieved at 9.2 years after surgery. At 5.8 years, clinical follow-up showed heart failure (n = 2) and recurrent angina (n = 3), all after balloon dilatation. At 4.5 years, 1 RA graft was occluded due to competitive flow from the native coronary vessel and 2 RA restenoses following BA were treated by stenting. Intrastent RA stenosis was noted in 1 patient. PCI with BA should be restricted to the early postoperative period during which spasm is difficult to exclude. Stenting showed excellent and durable results and is preferred in most cases. There are no large studies on other arterial

appearance. However, on rare occasions, focal stenoses of the RA graft can occur.

grafts to draw definite conclusions for the treatment with PCI by BA, BMS or DES.

diseased SVG, and lesion ulceration.

*Antithrombotic therapy during graft intervention -* The preferred parenteral antithrombotic therapy during graft intervention remains to be explored. The role of glycoprotein IIb/IIIa antagonists in graft intervention is limited as they failed to demonstrate a reduction in periprocedural MI. [185-187] Similarly, no reduction in MACE at 30 days was observed in a post hoc analysis when glycoprotein IIb/IIIa antagonists were used in conjunction with filterbased embolic protection, although there was a trend toward improved procedural success. [188] In contrast, bivalirudin as compared with unfractionated heparin may have beneficial effects on biochemical and clinical outcomes as it was associated with a significant reduction in CK-MB elevation and a trend toward lower in-hospital non–Q-wave MI, repeat revascula‐ rization, and vascular complications. [189] Moreover, bivalirudin may offer a safety advantage over heparin plus a glycoprotein IIb/IIIa anatagonist as minor bleeding complications were lower with bivalirudin alone (26% vs. 38%) with equal or greater suppression of adverse ischemic events. [190] Pharmacological treatment of slow or no-reflow is targeted at micro‐ vascular flow with intragraft administration of vasodilators and delivery of pharmaceutical agents to the distal microvasculature and can be maximized with a microcatheter like an aspiration thrombectomy catheter. Adenosine is an endogenous purine nucleoside, a vasodi‐ lator of arteries and arterioles, and inhibits platelet activation and aggregation. A high dose of intragraft adenosine (≥5 boluses of 24 μg each) can result in reversal of slow or no-reflow and improve final Thrombolysis In Myocardial Infarction (TIMI) flow grade. However, the use of adenosine is limited because severe bradycardia may occur due to its effect on sinoatrial and atrioventricular nodal conduction and the half-life of adenosine is very short. Intracoronary administration of nitroprusside, a direct donor of NO, results in a rapid improvement in both angiographic flow and blood flow velocity. Caution is warranted in patients who are volume depleted or hypotensive at baseline because profound hypotension may occur. Prophylactic intragraft administration of verapamil (100 to 500 μg) can reduce the occurrence of no-reflow and improve TIMI myocardial perfusion grade. Prophylactic intragraft administration of nicardipine, a potent arteriolar vasodilator, may reduce CK-MB elevation. Independent predictors for slow flow or no-reflow are probable patients treated for ACS, stent thrombosis,

Comparison of BMS and DES for percutaneous revascularization of IMA Grafts, have reported conflicting results. In a retrospective study, outomes after BMS and DES treatment in IMA grafts were evaluated. [177] Baseline characteristics were comparable between the 2 groups, except for a trend toward longer stent lengths in the DES group (DES 20.2±7.7 mm vs. BMS 14.8±3.5 mm). No significant differences were present in in-hospital and 1- or 6-month outcomes between the 2 groups, including target lesion revascularization with DES (DES 3.33% vs. BMS 10%). Contrastingly, 2 small studies did not show improved clinical impact of DES compared to BMS. At 1-year clinical follow-up, no differences were detected in target lesion revascularization rates after treatment with BMS and PES (26.6% vs. 25%). [178] In the PES group, 2 late stent thromboses were observed. In addition, in a small study the long-term outcomes of 41 patients undergoing PCI of the IMA anastomosis BMS or SES were compared. [179] At a median follow-up of 29.2 months (interquartile range, 11.1-77.7 months) target lesion revascularization was 47.8% with SES and 7.1% with BMS. Patients who underwent repeat revascularization were more likely to have longer stents than those who did not (18.2 mm vs 14.2 mm).

The favourable results of BA compared to stenting in IMA graft intervention is in contrast with native coronary artery intervention. This might be explained by the fact that: 1) the proliferative response to BA in IMA may be less aggressive than that in native coronary arteries; 2) in native coronary arteries as compared to BA, stenting leads to more pronounced arterial injury, greater inflammatory response, and enhanced neointimal formation; 3) in small native coronary arteries, the high stent-to-wall ratio might predispose restenosis more frequently; and 4) stents are known to be thrombogenic and lead to neointimal formation and restenosis. [180-183]

Percutaneous treatment of ostial stenosis, presents technical challenges for the intervention‐ alist whereas lesions in the shaft are most similar to routine intervention in a native coronary arteries. Stenting of the anastomotic site takes carefully positioning of the stent to achieve apposition to the arterial wall given the acute angle at which IMA meets the native coronary artery. In one observational study a difference in 1-year target lesion revascularization rates was present at the ostial, shaft, and anastomotic sites (30.8%, 5.0%, and 7.2%, respectively). [176] The anastomosis experiences a bending of the stent with strut shrinkage and might cause stent fracture or in DES might limit elution of drug to vessel wall.

Failure of the RA graft is most frequently a complete occlusion and less often a string-like appearance. However, on rare occasions, focal stenoses of the RA graft can occur.

with BMS (26.4%) and received at least either ticlopidine or clopidogrel for 4 weeks post PCI. Angiographic success after stenting was high, 92%. At 1 year follow-up, target lesion revas‐ cularization rates were significantly higher in the stented lesions than lesions treated with BA alone (19.2% vs. 4.9%) and the higher rate in stented lesions was most apparent at the anasto‐ motic site (25.0% vs. 4.2%). Moreover, a significant difference was observed between 1-year all-cause mortality between stented lesions and lesions treated with BA alone (13.6% vs. 4.4%), no difference was observed for MI. In a multivariate analysis including all available baseline factors contributing to target lesion revascularization, indicated that stent use was an inde‐ pendent predictor. In this observational study selection bias may have resulted in more lesions at high risk of restenosis being chosen for stenting, as stenting was at the discretion of the

Comparison of BMS and DES for percutaneous revascularization of IMA Grafts, have reported conflicting results. In a retrospective study, outomes after BMS and DES treatment in IMA grafts were evaluated. [177] Baseline characteristics were comparable between the 2 groups, except for a trend toward longer stent lengths in the DES group (DES 20.2±7.7 mm vs. BMS 14.8±3.5 mm). No significant differences were present in in-hospital and 1- or 6-month outcomes between the 2 groups, including target lesion revascularization with DES (DES 3.33% vs. BMS 10%). Contrastingly, 2 small studies did not show improved clinical impact of DES compared to BMS. At 1-year clinical follow-up, no differences were detected in target lesion revascularization rates after treatment with BMS and PES (26.6% vs. 25%). [178] In the PES group, 2 late stent thromboses were observed. In addition, in a small study the long-term outcomes of 41 patients undergoing PCI of the IMA anastomosis BMS or SES were compared. [179] At a median follow-up of 29.2 months (interquartile range, 11.1-77.7 months) target lesion revascularization was 47.8% with SES and 7.1% with BMS. Patients who underwent repeat revascularization were more likely to have longer stents than those who did not (18.2 mm vs

The favourable results of BA compared to stenting in IMA graft intervention is in contrast with native coronary artery intervention. This might be explained by the fact that: 1) the proliferative response to BA in IMA may be less aggressive than that in native coronary arteries; 2) in native coronary arteries as compared to BA, stenting leads to more pronounced arterial injury, greater inflammatory response, and enhanced neointimal formation; 3) in small native coronary arteries, the high stent-to-wall ratio might predispose restenosis more frequently; and 4) stents are known to be thrombogenic and lead to neointimal formation and restenosis. [180-183]

Percutaneous treatment of ostial stenosis, presents technical challenges for the intervention‐ alist whereas lesions in the shaft are most similar to routine intervention in a native coronary arteries. Stenting of the anastomotic site takes carefully positioning of the stent to achieve apposition to the arterial wall given the acute angle at which IMA meets the native coronary artery. In one observational study a difference in 1-year target lesion revascularization rates was present at the ostial, shaft, and anastomotic sites (30.8%, 5.0%, and 7.2%, respectively). [176] The anastomosis experiences a bending of the stent with strut shrinkage and might cause

stent fracture or in DES might limit elution of drug to vessel wall.

operator.

208 Artery Bypass

14.2 mm).

RA graft stenosis treated by percutaneous intervention was evaluated in a small study including 18 patients. [184] The location of the RA stenosis was proximal (n = 2), shaft (n = 11) or distal anastomosis (n = 5). BA alone was performed on nine RA grafts at 1.7 years after surgery and stenting (3 BMS, 6 DES) of nine RA grafts was achieved at 9.2 years after surgery. At 5.8 years, clinical follow-up showed heart failure (n = 2) and recurrent angina (n = 3), all after balloon dilatation. At 4.5 years, 1 RA graft was occluded due to competitive flow from the native coronary vessel and 2 RA restenoses following BA were treated by stenting. Intrastent RA stenosis was noted in 1 patient. PCI with BA should be restricted to the early postoperative period during which spasm is difficult to exclude. Stenting showed excellent and durable results and is preferred in most cases. There are no large studies on other arterial grafts to draw definite conclusions for the treatment with PCI by BA, BMS or DES.

*Antithrombotic therapy during graft intervention -* The preferred parenteral antithrombotic therapy during graft intervention remains to be explored. The role of glycoprotein IIb/IIIa antagonists in graft intervention is limited as they failed to demonstrate a reduction in periprocedural MI. [185-187] Similarly, no reduction in MACE at 30 days was observed in a post hoc analysis when glycoprotein IIb/IIIa antagonists were used in conjunction with filterbased embolic protection, although there was a trend toward improved procedural success. [188] In contrast, bivalirudin as compared with unfractionated heparin may have beneficial effects on biochemical and clinical outcomes as it was associated with a significant reduction in CK-MB elevation and a trend toward lower in-hospital non–Q-wave MI, repeat revascula‐ rization, and vascular complications. [189] Moreover, bivalirudin may offer a safety advantage over heparin plus a glycoprotein IIb/IIIa anatagonist as minor bleeding complications were lower with bivalirudin alone (26% vs. 38%) with equal or greater suppression of adverse ischemic events. [190] Pharmacological treatment of slow or no-reflow is targeted at micro‐ vascular flow with intragraft administration of vasodilators and delivery of pharmaceutical agents to the distal microvasculature and can be maximized with a microcatheter like an aspiration thrombectomy catheter. Adenosine is an endogenous purine nucleoside, a vasodi‐ lator of arteries and arterioles, and inhibits platelet activation and aggregation. A high dose of intragraft adenosine (≥5 boluses of 24 μg each) can result in reversal of slow or no-reflow and improve final Thrombolysis In Myocardial Infarction (TIMI) flow grade. However, the use of adenosine is limited because severe bradycardia may occur due to its effect on sinoatrial and atrioventricular nodal conduction and the half-life of adenosine is very short. Intracoronary administration of nitroprusside, a direct donor of NO, results in a rapid improvement in both angiographic flow and blood flow velocity. Caution is warranted in patients who are volume depleted or hypotensive at baseline because profound hypotension may occur. Prophylactic intragraft administration of verapamil (100 to 500 μg) can reduce the occurrence of no-reflow and improve TIMI myocardial perfusion grade. Prophylactic intragraft administration of nicardipine, a potent arteriolar vasodilator, may reduce CK-MB elevation. Independent predictors for slow flow or no-reflow are probable patients treated for ACS, stent thrombosis, diseased SVG, and lesion ulceration.

*Embolic protection Devices -* Graft intervention, in particular SVG, can be complicated by distal embolization of atheroembolic debris leading to decreased epicardial and microvascular perfusion due to capillary plugging and vasospasm from the release of neurohumoral factors. Distal embolization may result in the slow or no-reflow and is associated with periprocedural myocardial necrosis and increased in-hospital mortality. However, distal embolization remains difficult to predict. Several embolic protection devices are available to prevent distal embolization and in SVG intervention it is recommended a class I according to the ACC/AHA guideline. [191] Distal balloon systems provide occlusion beyond the lesion securing the blood and may prevent plaque embolization into the myocardial bed. Hereafter, the blood with contained debris can be aspirated before occlusive balloon deflation. Advantages are the low crossing profile and entrapment of debris of all sizes as well as neurohumoral mediators such as serotonin and thromboxane that may have an adverse effect on the distal microvasculature. However, disadvantages are: 1) the need to cross the lesion before adequate protection, possibly liberating friable material before balloon occlusion; 2) temporary cessation of blood flow leading to ischemia and possible hemodynamic instability, as well as limiting visualiza‐ tion making accurate stent placement difficult; 3) inability to obtain full evacuation, especially near the occlusion balloon; 4) possible traumatic injury to the SVG during balloon occlusion, and 5) the need for a relatively disease-free landing zone of approximately 3 cm distal to the lesion for placement of the occlusion balloon. [192] The PercuSurge GuardWire (Medtronic, Minneapolis, Minnesota) and the TriActiv embolic protection system (Kensey Nash Corpora‐ tion, Exton, Pennsylvania) both demonstrated a significant decrease the incidence of no-reflow and improved 30-day clinical outcome but the latter was associated with more vascular complications and the need for blood transfusion. [193,194]

downstream into the microvasculature. After the intervention, the blood with the debris can be aspirated with a suction catheter before deflating the balloon. The advantages are that protection from distal embolization of atheromatous debris can be established before crossing the lesion, side branches can be protected, and distal lesions that are not amenable to distal embolic protection because of lack of a landing zone can be treated. The device can not be used in ostial or very proximal lesions as approximately 15 mm of landing zone is required, and the device causes cessation of antegrade perfusion resulting in myocardial ischemia. The multi‐ center prospective randomized PROXIMAL trial determined outcomes of the Proxis embolic protection device compared to distal protection devices during stenting of degenerated SVG. [196] In a subset of 410 patients with lesions amenable to treatment with either proximal or distal protection devices the primary composite end point, death, MI, or target vessel revas‐ cularization at 30 days, occurred in 12.2% of distal protection patients and 7.4% of proximal

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The decision regarding whether or not to intervene in a diseased graft should be guided by the patient's symptoms, angiographic evidence of a significant stenosis, and noninvasive evidence of myocardial ischemia in the region subtended by the bypass graft. Fractional flow reserve (FFR) measurement to assess the significance of stenosis in a bypass graft can be performed in a similar fashion as in a native coronary vessel and guide decision making.

Moreover, risk-scoring models are considered to be valuable in predicting outcomes and guiding to appropriate treatment strategies for patients undergoing PCI. Although, the SYNTAX score, developed to characterize angiographic complexity, has been proposed to predict outcomes and select an optimal treatment strategy for patients with coronary artery disease, the score is complex and does not take into account patients with coronary bypass graft lesions. [197-199] The Duke myocardial jeopardy score was developed in the 1980s as a simple method to estimate the amount of myocardium at risk for ischemia on the basis of the location of a coronary lesion in non-surgically managed patients with coronary artery disease. [200] Recently, an adjustment was suggested to this score to include left main disease as well as the protective properties of patent bypass grafts, the modified Duke jeopardy score (Figure 1). [201] The same assumptions are used as in the original score, assigning greater prognostic significance to more proximal lesions than more distal lesions in the same vessel. Noteworthy,

*Acute coronary syndrome -* After CABG, progression of atherosclerosis occurs both in grafts and native coronary arteries, resulting in significant morbidity and mortality, especially in patients who present with acute ACS. Estimates from the Coronary Artery Surgery Study and Veteran's Affairs Cooperative Study of Coronary Bypass indicate a rate of MI of approximately 2% to 3% per year over the first 5 years after CABG, with recurrent infarction in as many as 36% of patients at 10 years and even higher rates of hospitalization for recurrent ischemia. [202-204] Although primary PCI is the preferred strategy for STEMI patients, current guidelines do not provide specific recommendations on the optimal reperfusion strategy in patients with prior CABG. [205] Compared to patient without prior CABG, patients with prior CABG presenting with ACS are older, have more cardiovascular risk factors, more frequent comorbidities, higher

the modified Duke jeopardy score has not been validated yet.

protection patients.

Distal filter systems, composed of a tightly wrapped filter attached to a guidewire and sheathed within a delivery catheter for placement distal to the target lesion, can trap debris that embolize while the intervention is performed over the guidewire. After the intervention, a retrieval catheter is advanced over the guidewire to collapse the filter and remove it along with retained contents. It is ease-of-use and antegrade blood flow during intervention is maintained to avoid ischemia allowing the ability to inject contrast media to facilitate accurate balloon inflation or stent placement. Distal filter systems may be preferred in high-risk patients who are at increased risk for hemodynamic instability such as patients with severe left ventricular dysfunction or last remaining conduit. These systems do need a high crossing profile (large diameter sheath approximately 3- to 4-F) and the maneuverability is poor. Moreover, the inability to completely entrap microparticles, possible occlusion of the filter due to large amounts of debris, and inability to use in very distal lesions because of the need for a landing zone to deploy the filter are some other disadvanteges. The FilterWire EX (Boston Scientific) and the FilterWire EX (Boston Scientific) both showed noninferiority to distal balloon occlusion devices. [195]

The Proxis embolic protection system (St. Jude Medical, Maple Groves, Minnesota), a proximal balloon occlusion device, employs a distal balloon to seals the SVG while a proximal balloon seals the inside of the guiding catheter. This secures the blood with debris from embolizing downstream into the microvasculature. After the intervention, the blood with the debris can be aspirated with a suction catheter before deflating the balloon. The advantages are that protection from distal embolization of atheromatous debris can be established before crossing the lesion, side branches can be protected, and distal lesions that are not amenable to distal embolic protection because of lack of a landing zone can be treated. The device can not be used in ostial or very proximal lesions as approximately 15 mm of landing zone is required, and the device causes cessation of antegrade perfusion resulting in myocardial ischemia. The multi‐ center prospective randomized PROXIMAL trial determined outcomes of the Proxis embolic protection device compared to distal protection devices during stenting of degenerated SVG. [196] In a subset of 410 patients with lesions amenable to treatment with either proximal or distal protection devices the primary composite end point, death, MI, or target vessel revas‐ cularization at 30 days, occurred in 12.2% of distal protection patients and 7.4% of proximal protection patients.

*Embolic protection Devices -* Graft intervention, in particular SVG, can be complicated by distal embolization of atheroembolic debris leading to decreased epicardial and microvascular perfusion due to capillary plugging and vasospasm from the release of neurohumoral factors. Distal embolization may result in the slow or no-reflow and is associated with periprocedural myocardial necrosis and increased in-hospital mortality. However, distal embolization remains difficult to predict. Several embolic protection devices are available to prevent distal embolization and in SVG intervention it is recommended a class I according to the ACC/AHA guideline. [191] Distal balloon systems provide occlusion beyond the lesion securing the blood and may prevent plaque embolization into the myocardial bed. Hereafter, the blood with contained debris can be aspirated before occlusive balloon deflation. Advantages are the low crossing profile and entrapment of debris of all sizes as well as neurohumoral mediators such as serotonin and thromboxane that may have an adverse effect on the distal microvasculature. However, disadvantages are: 1) the need to cross the lesion before adequate protection, possibly liberating friable material before balloon occlusion; 2) temporary cessation of blood flow leading to ischemia and possible hemodynamic instability, as well as limiting visualiza‐ tion making accurate stent placement difficult; 3) inability to obtain full evacuation, especially near the occlusion balloon; 4) possible traumatic injury to the SVG during balloon occlusion, and 5) the need for a relatively disease-free landing zone of approximately 3 cm distal to the lesion for placement of the occlusion balloon. [192] The PercuSurge GuardWire (Medtronic, Minneapolis, Minnesota) and the TriActiv embolic protection system (Kensey Nash Corpora‐ tion, Exton, Pennsylvania) both demonstrated a significant decrease the incidence of no-reflow and improved 30-day clinical outcome but the latter was associated with more vascular

Distal filter systems, composed of a tightly wrapped filter attached to a guidewire and sheathed within a delivery catheter for placement distal to the target lesion, can trap debris that embolize while the intervention is performed over the guidewire. After the intervention, a retrieval catheter is advanced over the guidewire to collapse the filter and remove it along with retained contents. It is ease-of-use and antegrade blood flow during intervention is maintained to avoid ischemia allowing the ability to inject contrast media to facilitate accurate balloon inflation or stent placement. Distal filter systems may be preferred in high-risk patients who are at increased risk for hemodynamic instability such as patients with severe left ventricular dysfunction or last remaining conduit. These systems do need a high crossing profile (large diameter sheath approximately 3- to 4-F) and the maneuverability is poor. Moreover, the inability to completely entrap microparticles, possible occlusion of the filter due to large amounts of debris, and inability to use in very distal lesions because of the need for a landing zone to deploy the filter are some other disadvanteges. The FilterWire EX (Boston Scientific) and the FilterWire EX (Boston Scientific) both showed noninferiority to distal balloon occlusion

The Proxis embolic protection system (St. Jude Medical, Maple Groves, Minnesota), a proximal balloon occlusion device, employs a distal balloon to seals the SVG while a proximal balloon seals the inside of the guiding catheter. This secures the blood with debris from embolizing

complications and the need for blood transfusion. [193,194]

devices. [195]

210 Artery Bypass

The decision regarding whether or not to intervene in a diseased graft should be guided by the patient's symptoms, angiographic evidence of a significant stenosis, and noninvasive evidence of myocardial ischemia in the region subtended by the bypass graft. Fractional flow reserve (FFR) measurement to assess the significance of stenosis in a bypass graft can be performed in a similar fashion as in a native coronary vessel and guide decision making.

Moreover, risk-scoring models are considered to be valuable in predicting outcomes and guiding to appropriate treatment strategies for patients undergoing PCI. Although, the SYNTAX score, developed to characterize angiographic complexity, has been proposed to predict outcomes and select an optimal treatment strategy for patients with coronary artery disease, the score is complex and does not take into account patients with coronary bypass graft lesions. [197-199] The Duke myocardial jeopardy score was developed in the 1980s as a simple method to estimate the amount of myocardium at risk for ischemia on the basis of the location of a coronary lesion in non-surgically managed patients with coronary artery disease. [200] Recently, an adjustment was suggested to this score to include left main disease as well as the protective properties of patent bypass grafts, the modified Duke jeopardy score (Figure 1). [201] The same assumptions are used as in the original score, assigning greater prognostic significance to more proximal lesions than more distal lesions in the same vessel. Noteworthy, the modified Duke jeopardy score has not been validated yet.

*Acute coronary syndrome -* After CABG, progression of atherosclerosis occurs both in grafts and native coronary arteries, resulting in significant morbidity and mortality, especially in patients who present with acute ACS. Estimates from the Coronary Artery Surgery Study and Veteran's Affairs Cooperative Study of Coronary Bypass indicate a rate of MI of approximately 2% to 3% per year over the first 5 years after CABG, with recurrent infarction in as many as 36% of patients at 10 years and even higher rates of hospitalization for recurrent ischemia. [202-204] Although primary PCI is the preferred strategy for STEMI patients, current guidelines do not provide specific recommendations on the optimal reperfusion strategy in patients with prior CABG. [205] Compared to patient without prior CABG, patients with prior CABG presenting with ACS are older, have more cardiovascular risk factors, more frequent comorbidities, higher



improve short-term or long-term prognoses in ACS patients with prior CABG. Currently, the optimal antithrombotic therapy for patients with prior CABG presenting with ACS is not

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As the non-invasive treatment did not significantly improve outcomes in patients with prior CABG presenting with ACS a percutaneous strategy was investigated. Invasive versus noninvasive treatment in ACS and prior CABG was evaluated in the GRACE (Global Registry of Acute Coronary Events), and 6-month mortality was lower in patients revascularized versus those treated medically by univariate but not by multivariable analysis. [211] Similarly, in a large Swedish registry of 10,837 patients with previous CABG, 1-year adjusted mortality was

Long-term clinical follow-up of ACS patients with prior CABG treated with PCI has been assessed in several studies. In a small study, 34 consecutive patients with ACS who underwent PCI with DES for occluded SVG, showed a procedural success rate of 81%. [213] At 3-year follow-up mortality was 42%, recurrent ACS was 41% and repeat intervention was 38%. In a recently published retrospective analysis, the outcomes after PCI with BMS or DES for ACS due to graft failure were evaluated. [214] Although the majority of the 92 patients included were treated with BMS (84%), the groups were comparable for baseline clinical and angio‐ graphic characteristics. Graft failure occurred mainly in the SVG (90%), but also arterial grafts (LIMA and RIMA) were treated (8.7%). The initial restoration of normal blood flow was approximately 80%. The primary endpoint of death, MI, target vessel revascularization at 5 year follow-up was 65.9% in the BMS group and 43.4% in the DES group, this difference did not reach statistical significance. Individual endpoints at 5 years were also comparable between BMS and DES groups (death 46% vs. 43%, MI 36% vs. 33%, target lesion revascularization 26% vs. 15%, respectively). Predictors for the composite endpoint were cardiac shock (HR= 6.13; 95%-CI:3.12-12.01), creatinin (HR=1.006; 95%-CI:1.001-1.011), and multi-vessel disease (HR=

reduced with 50% with revascularization compared with medical management. [212]

4.64; 95%-CI:1.40-15.41). Cardiac shock and creatinin also predicted for death.

myocardial ischemia, although patients favoured PCI. [215]

The beneficial effect of redo CABG over PCI was examined in the randomized AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) trial in which 3-year survival and freedom from recurrent ACS was similar among patients with prior CABG and refractory

Patients with an acute MI / STEMI from a SVG culprit undergoing PCI are a high-risk subset of an already high-risk population. In the PAMI-2 (Second Primary Angioplasty in Myocardial Infarction) trial demonstrated lower angiographic success rates and higher mortality rates after BA in 58 patients with prior CABG compared with the 1068 patients without prior CABG. Primary PCI in patients with acute MI and prior CABG showed that patients treated with BA or BMS in SVG grafts compared to patients in whom a native vessel was treated had more noreflow at initial treatment (8.9% vs. 1.6%) and significantly more MI at 1 year follow-up (26% vs. 11%). [130] In another study, outcomes of 192 patients with acute MI from a SVG culprit undergoing PCI were compared to patients with a native culprit. [216] After multivariable adjustment, SVG culprit remained significantly associated with lower levels of peak troponin. The likelihood of MACE was higher in SVG vs. native culprits in patients with small to modest

known, and existing data are conflicting.


TIMI risk score, lower left ventricular ejection fraction, had higher prevalence of previous treatment with evidence-based medications, were less likely to have ST-segment deviation or positive cardiac biomarker on presentation. [206-209] During hospitalization prior CABG patients experienced larger infarct size, were less likely to receive reperfusion therapy, early invasive therapy and were more likely to be managed medically when compared to non-CABG patients. [207,209] However, the efficacy of reperfusion therapy in patients with previous CABG is less well characterized. Given the large amount of atherosclerotic material and thrombus burden with limited runoff found in occluded SVG, it is suggested that reperfusion success rate is reduced. In the GUSTO-1 (Global Utilization of Streptokinase and TPA for Occluded Arteries I) trial a significantly increase in 30-day mortality was observed following reperfusion with tissue-type plasminogen activator in prior CABG patients compared to those without prior CABG (10.7% vs. 6.7%). [210] In addition, the prior CABG group also suffered more pulmonary edema, hypotension, or cardiogenic shock and a lower TIMI flow grade 3 rate was achieved (31% vs. 49.2%). In the PERSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial the efficacy of eptifibatide, a Glycoprotein IIb/IIIa antagonist, in patients with ACS was compared in patients with or without prior CABG. [88] After adjusting for differences in baseline characteristics and treatment, patients with prior CABG had a significantly higher mortality rates at 6 months. At 30 days, there was a similar effect on the primary end point of death or MI in the eptifibatide group versus the placebo group in prior CABG patients and in patients without a history of CABG. Finally, in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial patients with prior CABG presenting with ACS were randomized to bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor. [209] Bivalirudin monotherapy did not

**Figure 1.** Modified Duke Jeopardy Score

improve short-term or long-term prognoses in ACS patients with prior CABG. Currently, the optimal antithrombotic therapy for patients with prior CABG presenting with ACS is not known, and existing data are conflicting.

As the non-invasive treatment did not significantly improve outcomes in patients with prior CABG presenting with ACS a percutaneous strategy was investigated. Invasive versus noninvasive treatment in ACS and prior CABG was evaluated in the GRACE (Global Registry of Acute Coronary Events), and 6-month mortality was lower in patients revascularized versus those treated medically by univariate but not by multivariable analysis. [211] Similarly, in a large Swedish registry of 10,837 patients with previous CABG, 1-year adjusted mortality was reduced with 50% with revascularization compared with medical management. [212]

Long-term clinical follow-up of ACS patients with prior CABG treated with PCI has been assessed in several studies. In a small study, 34 consecutive patients with ACS who underwent PCI with DES for occluded SVG, showed a procedural success rate of 81%. [213] At 3-year follow-up mortality was 42%, recurrent ACS was 41% and repeat intervention was 38%. In a recently published retrospective analysis, the outcomes after PCI with BMS or DES for ACS due to graft failure were evaluated. [214] Although the majority of the 92 patients included were treated with BMS (84%), the groups were comparable for baseline clinical and angio‐ graphic characteristics. Graft failure occurred mainly in the SVG (90%), but also arterial grafts (LIMA and RIMA) were treated (8.7%). The initial restoration of normal blood flow was approximately 80%. The primary endpoint of death, MI, target vessel revascularization at 5 year follow-up was 65.9% in the BMS group and 43.4% in the DES group, this difference did not reach statistical significance. Individual endpoints at 5 years were also comparable between BMS and DES groups (death 46% vs. 43%, MI 36% vs. 33%, target lesion revascularization 26% vs. 15%, respectively). Predictors for the composite endpoint were cardiac shock (HR= 6.13; 95%-CI:3.12-12.01), creatinin (HR=1.006; 95%-CI:1.001-1.011), and multi-vessel disease (HR= 4.64; 95%-CI:1.40-15.41). Cardiac shock and creatinin also predicted for death.

TIMI risk score, lower left ventricular ejection fraction, had higher prevalence of previous treatment with evidence-based medications, were less likely to have ST-segment deviation or positive cardiac biomarker on presentation. [206-209] During hospitalization prior CABG patients experienced larger infarct size, were less likely to receive reperfusion therapy, early invasive therapy and were more likely to be managed medically when compared to non-CABG patients. [207,209] However, the efficacy of reperfusion therapy in patients with previous CABG is less well characterized. Given the large amount of atherosclerotic material and thrombus burden with limited runoff found in occluded SVG, it is suggested that reperfusion success rate is reduced. In the GUSTO-1 (Global Utilization of Streptokinase and TPA for Occluded Arteries I) trial a significantly increase in 30-day mortality was observed following reperfusion with tissue-type plasminogen activator in prior CABG patients compared to those without prior CABG (10.7% vs. 6.7%). [210] In addition, the prior CABG group also suffered more pulmonary edema, hypotension, or cardiogenic shock and a lower TIMI flow grade 3 rate was achieved (31% vs. 49.2%). In the PERSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial the efficacy of eptifibatide, a Glycoprotein IIb/IIIa antagonist, in patients with ACS was compared in patients with or without prior CABG. [88] After adjusting for differences in baseline characteristics and treatment, patients with prior CABG had a significantly higher mortality rates at 6 months. At 30 days, there was a similar effect on the primary end point of death or MI in the eptifibatide group versus the placebo group in prior CABG patients and in patients without a history of CABG. Finally, in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) Trial patients with prior CABG presenting with ACS were randomized to bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor. [209] Bivalirudin monotherapy did not

**Figure 1.** Modified Duke Jeopardy Score

212 Artery Bypass

The beneficial effect of redo CABG over PCI was examined in the randomized AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) trial in which 3-year survival and freedom from recurrent ACS was similar among patients with prior CABG and refractory myocardial ischemia, although patients favoured PCI. [215]

Patients with an acute MI / STEMI from a SVG culprit undergoing PCI are a high-risk subset of an already high-risk population. In the PAMI-2 (Second Primary Angioplasty in Myocardial Infarction) trial demonstrated lower angiographic success rates and higher mortality rates after BA in 58 patients with prior CABG compared with the 1068 patients without prior CABG. Primary PCI in patients with acute MI and prior CABG showed that patients treated with BA or BMS in SVG grafts compared to patients in whom a native vessel was treated had more noreflow at initial treatment (8.9% vs. 1.6%) and significantly more MI at 1 year follow-up (26% vs. 11%). [130] In another study, outcomes of 192 patients with acute MI from a SVG culprit undergoing PCI were compared to patients with a native culprit. [216] After multivariable adjustment, SVG culprit remained significantly associated with lower levels of peak troponin. The likelihood of MACE was higher in SVG vs. native culprits in patients with small to modest troponin elevations. Patients with a SVG culprit also suffered higher rates of mortality at 30 days (14.3% vs. 8.4%) and MACE at 1 year (36.8% vs. 24.5%). Finally, in the APEX-AMI trial, STEMI patients with prior CABG exhibited a smaller baseline territory at risk as measured by 12-lead ECG and had less myocardial necrosis. Moreover, in these patients receiving primary PCI, TIMI flow grade 3 was less frequently achieved and ST-segment resolution was less common but they have more frequent clinical comorbidities and increased 90-day clinical events including mortality. Risk factors for mortality were prior heart failure and age.

cantly due to the large number of options for proximal as well as distal anastomosis sites. Careful review of the coronary angiogram or even cardiac/thoracic imaging to assess the relationship to the sternum and other anatomic structures is therefore warranted. Other structures at risk for injury during sternal re-entry include perforation of the right ventricle, and innominate vein. This is particularly true in patients where the pericardium was not closed. After sternal access, subsequent exposure of the heart can be completed by fibrosis which can be significant especially after pericarditis or radiation exposure. In patients requiring posterior vessel bypass, the entire heart should be cleared of fibrosis to allow surgical

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After sternal entry and inspection of the coronary vessels and branches, the second challenge is to assure adequate revascularization. Diffuse coronary artery disease poses a major problem in finding a suitable and satisfactory area for anastomosis. Thick plaque build-up and calcified coronary artery branches as well as calcification of the aortic arch make distal and proximal anastomosis of coronary bypass grafts hard and increase the chances of graft failure. [219] Additionally, the lack of satisfactory bypass conduits is common, because many patients undergoing redo CABG have very thin and dilated varicose veins, and small and calcified radial arteries. Risk factors for poor saphenous vein quality are age, obesity and diabetes, which are all more prominent in patients requiring redo CABG. In those patients the IMA may

Inadequate myocardial protection is an important cause of failure to wean patients off cardiopulmonary bypass. In the presence of degenerative old vein grafts, delivery of cardio‐ plegia solution is considered safer through retrograde coronary sinus perfusion than anterog‐ rade delivery of cardioplegic solution because of the risk of atheromatous embolization from atherosclerotic vein grafts which can lead to acute occlusion of coronary artery branches. [222] Additional measures include a no touch approach regarding diseased vein grafts to minimalize the chance of distal embolization due to manipulation. [223] To assure a constant temperature in an attempt to minimize haematological abnormalities and tissue edema, some surgeons also occlude the IMA with a bulldog clamp to prevent the delivery of warm blood into the myocardium. In such a way, the entire myocardium is provided with continuous, cold cardioplegic solution through coronary sinus perfusion. [224,225] After placement of newly constructed coronary artery bypass grafts, anterograde cardioplegic solution can also be given.

Neurological complications and bleedings are common following redo CABG. Several techniques are used to decrease the risk of neurological complications. Most common are ischemic stroke or TIA due to cerebral embolization from a calcified ascending aorta, athe‐ romatous plaques on the ascending aorta, and embolization from a jet phenomenon from aortic cannulation. Other causes for cerebal dysfunction are systemic inflammatory processes in response to cardiopulmonary bypass and gaseous microemboli. [226] Soft flow aortic cannu‐ lae, heparin-coated circuits, and administration of adenosine have proposed as techniques to lower neurological complications, but adequate studies and therefore evidence are lacking. [227-229] Bleeding is associated with an increased morbidity and mortality. Bleedings can be largely avoided by meticulous surgical dissection and careful catherization. Some studies using the application of fibrin glue suggest that this may help minimize peri-operative

manipulation.

be small or even atherosclerotic.

In conclusion, in patients with prior CABG presenting with ACS, PCI improves clinical outcomes compared to medical therapy alone. Redo CABG does not seem to further improve clinical outcomes.
