**Percutaneous Intervention Post Coronary Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art**

R. Ernesto Oqueli *Ballarat Health Services, Victoria Australia* 

#### **1. Introduction**

94 Coronary Interventions

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of dobutamine for treating post-resuscitation left ventricular dysfunction.

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Losert H. (2011). Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms.

weak aspects of an established post-resuscitation treatment protocol-A five-year

AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). (2008). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and management of Acute Pulmonary Embolism of the European Society of Cardiology

hypothermia on pharmacokinetics and pharmacodynamics: a systematic review of

Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Silber S, Aguirre FV, Al-Attar N, Alegria E, Andreotti F, Benzer W, Breithardt O, Danchin N, Di Mario C, Dudek D, Gulba D, Halvorsen S, Kaufmann P, Kornowski R, Lip GY, Rutten F. (2008). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of The success of coronary artery bypass grafting, although the gold standard for the treatment of multivessel coronary artery disease is limited by poor long-term vein graft patency. Despite the superiority of arterial graft patency over that of vein grafts, the multivessel nature of coronary artery disease and ready availability of saphenous veins still result in its use in over 70% of coronary artery bypass graft procedures (Murphy & Angelini, 2004). These thin walled grafts promptly begin to fail with intimal hyperplasia, thrombosis and progressive atherosclerosis when exposed to an abrupt increase in wall stress imparted by systemic arterial pressure (Hiscock et al., 2007).

Recurrent ischaemia in patients who have had previous saphenous bypass surgery occurs not only because of attrition of the saphenous vein grafts but also because of progression of coronary artery disease in the native coronary arteries (de Feyter et al., 1993).

During the first year after bypass surgery up to 15% of venous grafts occlude, between 1 and 6 years the graft attrition rate is 1% to 2% per year, and between 6 and 10 years it is 4% per year. By 10 years after surgery only 60% of vein grafts are patent and only 50% of patent vein grafts are free of significant stenosis. In addition, native coronary artery disease progresses in approximately 5% of patients annually (Motwani & Topol, 1998).

Reflecting this graft and native vessel attrition, angina recurs in up to 20% of patients during the first year after saphenous vein grafting and in approximately 4% of patients annually during the ensuing 5 years (Motwani & Topol 1998).

Angiographic studies have shown that 70% to 80% of bypass surgery patients who present with acute coronary syndrome have their culprit lesion located in the saphenous vein graft (Pregowski J et al., 2005).

Further revascularisation, either reoperative bypass surgery or percutaneous intervention, is required in approximately 4% of patients by 5 years, 19% of patients by 10 years, and 31% of patients by 12 years after initial bypass surgery.

Both surgical and percutaneous forms of repeat revascularisation have considerable limitations. As compared with initial surgery, reoperation carries a higher mortality rate (3%

Percutaneous Intervention Post Coronary

with thrombus. (Nguyen T et al., 2004)

**2.3 Late postoperative ischaemia (>3 years after surgery)** 

Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 97

fibrointimal hyperplasia (Nguyen T et al., 2004). These occlusions are predominantly focal, not associated with diffuse vein graft disease, and usually the thrombotic component of the occlusion is not extensive (de Feyter et al., 1993). Recurrence of angina at about 3 months postoperatively is highly suggestive of a distal graft anastomotic lesion and should, in most cases lead to evaluation for percutaneous coronary intervention. (Nguyen T et al., 2004)

At this stage, the most common cause of ischaemia is due to formation in vein grafts of new atherosclerotic plaque, which contains foam cells, cholesterol crystals, blood elements, and necrotic debris as in native vessels, however, these plaques have less fibrocollagenous tissue and calcification, so they are softer, more friable, of larger size, and frequently associated

The optimal revascularization strategy in patients with symptomatic multivessel coronary

Brener et al evaluated 2191 consecutive patients with previous coronary artery bypass graft surgery undergoing isolated, non-emergency multivessel revascularization (1487 with reoperation and 704 with percutaneous coronary intervention) between 1 January 1995 and 31 December 2000. The analysis concentrated on the independent predictors of the revascularization method, as well as on long-term mortality and its predictors, after

These authors concluded that in the absence of a dedicated, randomized controlled trial to guide multivessel revascularization in post-coronary artery bypass graft patients, clinical practice appears to favour reoperation over percutaneous coronary intervention for patients at higher risk, with fewer functional grafts, more chronic total occlusions, and impaired systolic function, whereas percutaneous coronary intervention is favoured in those with

In their study long-term mortality was mostly affected by age and ejection fraction, while the choice of revascularization had a modest impact. Percutaneous coronary intervention appeared to be related to a slight excess in long-term mortality (despite better 30-day outcome) compared with reoperation, an effect markedly attenuated by risk adjustment.

The effect of drug-eluting stents, higher success in percutaneous recanalization of chronic total occlusions and improvements in surgical techniques and overall medical care needs to be evaluated prospectively, particularly in high-risk subsets defined by advanced age and systolic dysfunction, before a definitive recommendation can be made for this important

**4. Balloon angioplasty for the treatment of saphenous vein graft disease** 

Percutaneous treatment of saphenous vein grafts was attempted in the early days of balloon

**3. Selection of revascularisation strategy in patients who experience** 

artery disease and previous coronary artery bypass grafting remains unknown.

**recurrence of ischaemia after coronary artery bypass surgery** 

calculating a propensity score for the method of revascularization.

patent left internal mammary artery and amenable anatomy.

segment of the coronary artery disease population (Brener et al., 2006).

angioplasty.

to 7%) with a high rate of perioperative myocardial infarction (4% to 11.5%). Coronary atheroembolism from diseased vein grafts is a major cause of the morbidity and mortality associated with reoperation. Redo surgery is also associated with less complete relief of angina and with reduction in saphenous vein graft patency as compared with initial bypass surgery. As increasing numbers of patients undergo second and third reoperations, the perioperative morbidity and mortality escalates further and the clinical benefit diminishes (Motwani & Topol, 1998). Thus, currently percutaneous coronary intervention is the preferred treatment for saphenous vein graft lesions (Vermeersh et al., 2006).

Percutaneous treatment of soft and friable, degenerated saphenous vein graft lesions provides unique challenges to the interventionalist due to the tendency for distal embolisation to result in slow or no-reflow phenomena with peri-procedural myocardial infarction and the relatively frequent association of superimposed thrombus on critical graft stenoses. This has sprawled a number of pharmaceutical and device-based approaches that may afford distal protection during percutaneous intervention. Nonetheless, there remains a disappointingly high long-term recurrence rate due to restenosis and the emergence of new lesions resulting in target vessel failure (Hiscock et al., 2007).

## **2. Mechanisms of saphenous vein graft ischaemia**

The mechanisms of saphenous vein graft related ischaemia vary with the time that has elapsed since the surgery.

Early, 1-year and late graft failure may be due to thrombosis, fibrointimal hyperplasia and atherosclerosis respectively. There is general agreement that vein graft atherosclerosis differs from arterial lesions in terms of temporal and histological changes. Vein graft atherosclerosis is more rapid, with diffuse concentric changes and a less noticeable fibrous cap, making venous plaques more vulnerable to rupture and subsequent thrombus formation (Hassantash et al., 2008).

#### **2.1 Early postoperative ischaemia (<1month)**

The most common cause of ischaemia within hours or days of surgery is acute vein graft thrombosis (60%) (Nguyen T et al., 2004), possibly attributed to harvesting and handling of the vein, to failure of surgical techniques at sites of anastomosis such as surgical failure to carry the graft distal to obstructive points indicated by angiography (Vlodaver & Edwards, 1973) or to poor distal runoff due to severely diseased native arteries (de Feyter et al., 1993). Other causes are incomplete surgical revascularisation (10%), kinked grafts, and focal stenosis distal to the insertion site and at the proximal or distal anastomotic sites, spasm or injury, insertion of graft to a vein causing AV fistulae, or bypass of the wrong vessel. The patients at increased risk for early postoperative ischaemia include those undergoing technically demanding minimally invasive and "off bypass" techniques. (Nguyen T et al., 2004)

#### **2.2 Early postoperative ischaemia (1 month -1 year)**

Recurrent angina between 1 month and 1 year after the surgery is most often due to perianastomotic stenosis, graft occlusion or mid saphenous vein graft stenosis from fibrointimal hyperplasia (Nguyen T et al., 2004). These occlusions are predominantly focal, not associated with diffuse vein graft disease, and usually the thrombotic component of the occlusion is not extensive (de Feyter et al., 1993). Recurrence of angina at about 3 months postoperatively is highly suggestive of a distal graft anastomotic lesion and should, in most cases lead to evaluation for percutaneous coronary intervention. (Nguyen T et al., 2004)

#### **2.3 Late postoperative ischaemia (>3 years after surgery)**

96 Coronary Interventions

to 7%) with a high rate of perioperative myocardial infarction (4% to 11.5%). Coronary atheroembolism from diseased vein grafts is a major cause of the morbidity and mortality associated with reoperation. Redo surgery is also associated with less complete relief of angina and with reduction in saphenous vein graft patency as compared with initial bypass surgery. As increasing numbers of patients undergo second and third reoperations, the perioperative morbidity and mortality escalates further and the clinical benefit diminishes (Motwani & Topol, 1998). Thus, currently percutaneous coronary intervention is the

Percutaneous treatment of soft and friable, degenerated saphenous vein graft lesions provides unique challenges to the interventionalist due to the tendency for distal embolisation to result in slow or no-reflow phenomena with peri-procedural myocardial infarction and the relatively frequent association of superimposed thrombus on critical graft stenoses. This has sprawled a number of pharmaceutical and device-based approaches that may afford distal protection during percutaneous intervention. Nonetheless, there remains a disappointingly high long-term recurrence rate due to restenosis and the emergence of new

The mechanisms of saphenous vein graft related ischaemia vary with the time that has

Early, 1-year and late graft failure may be due to thrombosis, fibrointimal hyperplasia and atherosclerosis respectively. There is general agreement that vein graft atherosclerosis differs from arterial lesions in terms of temporal and histological changes. Vein graft atherosclerosis is more rapid, with diffuse concentric changes and a less noticeable fibrous cap, making venous plaques more vulnerable to rupture and subsequent thrombus

The most common cause of ischaemia within hours or days of surgery is acute vein graft thrombosis (60%) (Nguyen T et al., 2004), possibly attributed to harvesting and handling of the vein, to failure of surgical techniques at sites of anastomosis such as surgical failure to carry the graft distal to obstructive points indicated by angiography (Vlodaver & Edwards, 1973) or to poor distal runoff due to severely diseased native arteries (de Feyter et al., 1993). Other causes are incomplete surgical revascularisation (10%), kinked grafts, and focal stenosis distal to the insertion site and at the proximal or distal anastomotic sites, spasm or injury, insertion of graft to a vein causing AV fistulae, or bypass of the wrong vessel. The patients at increased risk for early postoperative ischaemia include those undergoing technically demanding minimally invasive and "off bypass" techniques. (Nguyen T et al.,

Recurrent angina between 1 month and 1 year after the surgery is most often due to perianastomotic stenosis, graft occlusion or mid saphenous vein graft stenosis from

preferred treatment for saphenous vein graft lesions (Vermeersh et al., 2006).

lesions resulting in target vessel failure (Hiscock et al., 2007).

**2. Mechanisms of saphenous vein graft ischaemia** 

elapsed since the surgery.

2004)

formation (Hassantash et al., 2008).

**2.1 Early postoperative ischaemia (<1month)** 

**2.2 Early postoperative ischaemia (1 month -1 year)** 

At this stage, the most common cause of ischaemia is due to formation in vein grafts of new atherosclerotic plaque, which contains foam cells, cholesterol crystals, blood elements, and necrotic debris as in native vessels, however, these plaques have less fibrocollagenous tissue and calcification, so they are softer, more friable, of larger size, and frequently associated with thrombus. (Nguyen T et al., 2004)

#### **3. Selection of revascularisation strategy in patients who experience recurrence of ischaemia after coronary artery bypass surgery**

The optimal revascularization strategy in patients with symptomatic multivessel coronary artery disease and previous coronary artery bypass grafting remains unknown.

Brener et al evaluated 2191 consecutive patients with previous coronary artery bypass graft surgery undergoing isolated, non-emergency multivessel revascularization (1487 with reoperation and 704 with percutaneous coronary intervention) between 1 January 1995 and 31 December 2000. The analysis concentrated on the independent predictors of the revascularization method, as well as on long-term mortality and its predictors, after calculating a propensity score for the method of revascularization.

These authors concluded that in the absence of a dedicated, randomized controlled trial to guide multivessel revascularization in post-coronary artery bypass graft patients, clinical practice appears to favour reoperation over percutaneous coronary intervention for patients at higher risk, with fewer functional grafts, more chronic total occlusions, and impaired systolic function, whereas percutaneous coronary intervention is favoured in those with patent left internal mammary artery and amenable anatomy.

In their study long-term mortality was mostly affected by age and ejection fraction, while the choice of revascularization had a modest impact. Percutaneous coronary intervention appeared to be related to a slight excess in long-term mortality (despite better 30-day outcome) compared with reoperation, an effect markedly attenuated by risk adjustment.

The effect of drug-eluting stents, higher success in percutaneous recanalization of chronic total occlusions and improvements in surgical techniques and overall medical care needs to be evaluated prospectively, particularly in high-risk subsets defined by advanced age and systolic dysfunction, before a definitive recommendation can be made for this important segment of the coronary artery disease population (Brener et al., 2006).

### **4. Balloon angioplasty for the treatment of saphenous vein graft disease**

Percutaneous treatment of saphenous vein grafts was attempted in the early days of balloon angioplasty.

Percutaneous Intervention Post Coronary

of the graft (de Feyter et al., 1993).

(Hanekamp et al., 2003).

(Savage et al., 1997).

saphenous vein grafts (Morrison et al., 1994).

a serious limitation of balloon angioplasty (de Feyter et al., 1993).

**5. Bare metal stents in the treatment of saphenous vein grafts** 

disease stent implantation was suggested as an alternative therapeutic approach.

restenosis, defined as stenosis of 50% or more of the luminal diameter at follow-up.

Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 99

length of stenosis grater than 10mm; and 5) dilation of lesion at the proximal site and body

Some authors advocated the use of aggressive adjunctive pharmacotherapy with intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin, calcium channel blocking agents and Coumadin for patients undergoing balloon angioplasty of

Balloon angioplasty of saphenous vein grafts is a palliative procedure, not a long-term solution in patients with previous coronary bypass graft surgery. The high restenosis rate is

Given the limitations of balloon angioplasty for the treatment of saphenous vein graft

Initial observational studies with balloon-expandable stent implantation in saphenous vein graft lesions had claimed a high procedural success rate, low early complication rate, and more favourable long-term outcome than previously reported for balloon angioplasty alone

The SAVED (Saphenous Vein De Novo) trial was the first multicentre, prospective, randomized trial of saphenous vein graft stenting. This study compared the placement of Palmaz-Schatz stents (Johnson & Johnson Interventional Systems, Warren, N.J.) with standard balloon angioplasty in 220 patients with relatively focal de-novo lesions in aortocoronary-venous bypass grafts. The primary angiographic end point of this trial was

Patients assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50% of the vessel diameter without a major cardiac complication (92% versus 69%, P<0.001). Bleeding and vascular complications were significantly more common in the stent group (17 % versus 5%, P<0.01) probably related to the intense anticoagulation protocol used in this trial. Patients in the stent group had a larger mean increase in luminal diameter immediately after the procedure (1.92 ± 0.3 mm versus 1.21 ± 0.37 mm) and a greater mean net gain in luminal diameter at six months (0.85 ± 0.96 mm versus 0.54 ± 0.91 mm). The rate of event free survival (freedom from death, myocardial infarction, repeated bypass surgery and revascularisation of the target lesion) at 240 days was significantly greater for patients assigned to stenting than for patients assigned to balloon angioplasty (73% versus 58%, P=0.03). When the results were analysed according to intention-to-treat principles, restenosis was found in 37% of the patients in the stent group and in 46% of the patients in the angioplasty group, p=0.24

These authors concluded that as compared with conventional angioplasty, stent placement in new vein-graft lesions was associated with better initial angiographic results and higher rates of procedural success. Although the luminal diameter at six months was larger in the stent group, there was no significant difference in the rate of restenosis. However, major

cardiac events occurred less frequently in the stent group (Savage et al., 1997).

#### **4.1 Initial results of balloon angioplasty of saphenous vein bypass grafts**

In carefully selected patients the initial success rate of balloon angioplasty for saphenous vein grafts varied from 75% to 94%, with a combined overall success rate of 88%. The initial success rate was dependent on the site of dilatation. The overall combined initial result of dilatation of the proximal site was 87%, of the graft body 94% and of the distal site 90%.

The procedure related death rate was <1%, the myocardial infarction rate was approximately 4% and the need for coronary bypass surgery was <2%. These results reflected the careful selection of patients and probably the exclusion of complex lesions (de Feyter et al., 1993).

#### **4.2 Restenosis after successful balloon angioplasty of saphenous vein bypass grafts**

The restenosis rate was also dependent on the site of dilatation within the graft. Ostial or very proximal graft lesions had very high restenosis rate (58% on average), the restenosis rate of the body of the graft was 52% and the restenosis rate in the distal anastomotic part of the graft was 28%. The overall combined restenosis rate was 42%(de Feyter et al., 1993).

It was suggested that the interval to restenosis after angioplasty of a saphenous vein graft was longer than the usual 6 months interval after angioplasty in native coronary arteries. In a series published by Douglas, the restenosis rate was 32% at six months, but it rose to 43%, 61% and 64% after 6-12 months, 1-5 years, and 5 years respectively. (Douglas, 1994). The reason for this late pattern according to some authors, could be the larger reference diameter, which means more time would be required to reach a minimum luminal diameter small enough to yield clinical findings. (Hong et al., 2000; Lozano et al., 2005)

#### **4.3 Long term outcome after balloon angioplasty of saphenous vein bypass grafts**

The 5-year follow-up was poor, and although 74% of the patients were still alive, only 26% were event free with no myocardial infarction or repeat revascularisation (de Feyter, 2003). The interval between balloon angioplasty and bypass surgery was a significant predictor for 5 year-event free survival.

#### **4.4 Risk factors predictive of unfavourable outcome after balloon angioplasty of saphenous vein bypass grafts**

Several variables predictive of unfavourable outcome after balloon angioplasty of saphenous vein graft were identified.

Factors that predicted a poor initial result included 1) diffuseness of saphenous vein graft disease; 2) attempted angioplasty of stenoses in grafts more than 4 to 6 years old; 3) chronic totally occluded grafts; and 4) the presence of intravein graft thrombus. The presence of one or more of those variables was associated with a high frequency of major complications, often due to embolization of friable material into the coronary circulation or the occurrence of abrupt occlusion with thrombosis formation.

Variables predictive of late restenosis after balloon angioplasty of saphenous vein grafts included 1) lesions in old (more than 36 months) grafts; 2) multiple lesions, diffuse graft disease and total occlusion; 3) small diameter (<2.2 mm) of the grafted coronary artery; 4)

In carefully selected patients the initial success rate of balloon angioplasty for saphenous vein grafts varied from 75% to 94%, with a combined overall success rate of 88%. The initial success rate was dependent on the site of dilatation. The overall combined initial result of dilatation of the proximal site was 87%, of the graft body 94% and of the distal site 90%.

The procedure related death rate was <1%, the myocardial infarction rate was approximately 4% and the need for coronary bypass surgery was <2%. These results reflected the careful selection of patients and probably the exclusion of complex lesions (de

**4.2 Restenosis after successful balloon angioplasty of saphenous vein bypass grafts**  The restenosis rate was also dependent on the site of dilatation within the graft. Ostial or very proximal graft lesions had very high restenosis rate (58% on average), the restenosis rate of the body of the graft was 52% and the restenosis rate in the distal anastomotic part of the graft was 28%. The overall combined restenosis rate was 42%(de Feyter et al., 1993).

It was suggested that the interval to restenosis after angioplasty of a saphenous vein graft was longer than the usual 6 months interval after angioplasty in native coronary arteries. In a series published by Douglas, the restenosis rate was 32% at six months, but it rose to 43%, 61% and 64% after 6-12 months, 1-5 years, and 5 years respectively. (Douglas, 1994). The reason for this late pattern according to some authors, could be the larger reference diameter, which means more time would be required to reach a minimum luminal diameter

small enough to yield clinical findings. (Hong et al., 2000; Lozano et al., 2005)

**4.3 Long term outcome after balloon angioplasty of saphenous vein bypass grafts** 

**4.4 Risk factors predictive of unfavourable outcome after balloon angioplasty of** 

The 5-year follow-up was poor, and although 74% of the patients were still alive, only 26% were event free with no myocardial infarction or repeat revascularisation (de Feyter, 2003). The interval between balloon angioplasty and bypass surgery was a significant predictor for

Several variables predictive of unfavourable outcome after balloon angioplasty of

Factors that predicted a poor initial result included 1) diffuseness of saphenous vein graft disease; 2) attempted angioplasty of stenoses in grafts more than 4 to 6 years old; 3) chronic totally occluded grafts; and 4) the presence of intravein graft thrombus. The presence of one or more of those variables was associated with a high frequency of major complications, often due to embolization of friable material into the coronary circulation or the occurrence

Variables predictive of late restenosis after balloon angioplasty of saphenous vein grafts included 1) lesions in old (more than 36 months) grafts; 2) multiple lesions, diffuse graft disease and total occlusion; 3) small diameter (<2.2 mm) of the grafted coronary artery; 4)

**4.1 Initial results of balloon angioplasty of saphenous vein bypass grafts** 

Feyter et al., 1993).

5 year-event free survival.

**saphenous vein bypass grafts** 

saphenous vein graft were identified.

of abrupt occlusion with thrombosis formation.

length of stenosis grater than 10mm; and 5) dilation of lesion at the proximal site and body of the graft (de Feyter et al., 1993).

Some authors advocated the use of aggressive adjunctive pharmacotherapy with intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin, calcium channel blocking agents and Coumadin for patients undergoing balloon angioplasty of saphenous vein grafts (Morrison et al., 1994).

Balloon angioplasty of saphenous vein grafts is a palliative procedure, not a long-term solution in patients with previous coronary bypass graft surgery. The high restenosis rate is a serious limitation of balloon angioplasty (de Feyter et al., 1993).
