**10. Embolic protection devices during saphenous vein graft interventions**

There are two types of embolic protection devices: balloon occlusion-aspiration (proximal or distal) and filter devices. These systems have different characteristics and to date none has demonstrated enough advantages over the other mechanism to be ideally recommended universally (Morís et al., 2009).

#### **10.1 Distal balloon occlusion devices**

The Guard-Wire (Medtronic, Minneapolis, MN) temporary occlusion-aspiration system, consist of a wire with a central lumen that inflates an elastomeric balloon at the distal tip of the wire. The lesion is crossed with the Guard-Wire. Once the balloon is inflated (2.5 to 5.0 mm or 3.0 to 6.0 mm in diameter) with diluted contrast using an adaptor device, it occludes flow distal to the target lesion. The procedure (angioplasty and stenting) is then performed over the Guard-Wire shaft instead of using a standard angioplasty guidewire. Liberated plaque and thrombotic debris trapped proximal to the balloon are then aspirated through a 5 French monorail Export aspiration catheter. The balloon is then deflated with restoration of antegrade flow (Figure 2).

The SAFER (Saphenous vein graft Angioplasty Free of Emboli Randomized) trial enrolled 801 patients with signs of myocardial ischemia resulting from a target lesion > 50% diameter stenosis located in the mid-portion of a saphenous vein graft, with a reference vessel

Percutaneous Intervention Post Coronary

Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 115

which is poorly tolerated by some patients. Sixty one percent of patients in the SAFE trial developed angina during balloon inflation; however, in no patient was ischaemia so severe as to prompt premature deflation of the occlusion balloon. Additionally, balloon-induced injury may occur if they are not used carefully and it is difficult to get adequate imaging

during the procedure while the distal vessel is occluded (Morís et al., 2009).

Fig. 3. Aspirated debris from a saphenous vein graft. Courtesy of Medtronic.

A second-generation distal balloon occlusion device, TriActiv (Kensey Nash Corp., Exton, PA), has 4 principal components: a balloon guidewire consisting of a 0.014" hypotube with a carbon dioxide–inflated compliant occlusion balloon on the wire (balloon diameter 3-5 mm), a modified syringe filled with sterile carbon dioxide used to inflate the occlusion balloon, a 4F side-attachable flush catheter, and a drive console with mechanical pumps for infusion and extraction. The lesion is crossed with the balloon guidewire and the occlusion balloon is positioned at least 20 mm beyond the distal edge of the target lesion. The occlusion balloon is inflated with carbon dioxide. A stent is delivered over the Balloon Guidewire and deployed at the lesion. The flush catheter is advanced over the balloon guidewire and saline is infused via holes in the distal end. Extraction of fluid and debris is performed through the guiding

catheter. The occlusion balloon is deflated and flow is restored (Carrozza et al., 2005a).

without embolic protection could not be made.

The PRIDE (Protection During Saphenous Vein Graft Intervention to Prevent Distal Embolization) study was a prospective randomized trial, which enrolled patients with coronary ischemia and lesions in saphenous vein grafts in two cohorts. Cohort I randomized patients to protection with the TriActiv System versus percutaneous coronary intervention without embolic protection, to demonstrate superiority of the TriActiv System compared with an "unprotected" group. Given the small number of patients in Cohort I, meaningful conclusions regarding the superiority of TriActiv to saphenous vein graft intervention

Cohort II randomized 631 patients to embolic protection with the TriActiv System or control group (Guardwire System [Medtronic] or Filterwire EX [Boston Scientific]) to establish noninferiority to other distal protection devices. The incidence of major adverse cardiac events at 30 days was 11.2% for the TriActiv group and 10.1% for the control group (relative risk = 1.1%; 95% confidence interval 0.67 to 1.76; p = 0.65; p = 0.02 for non-inferiority). Safety and efficacy end points were similar between groups except that patients randomized to the TriActiv System had more hemorrhagic complications (10.9% vs. 5.4%; p = 0.01). Patients in the TriActiv group were more likely to require blood transfusion. Sub-group analysis indicated that the higher rate of transfusion in the TriActiv cohort was associated with an early design of the haemostatic valve in combination with 8-F guiding catheters. The

diameter between 3 and 6 mm. Four hundred and six patients were randomized to stent placement over the shaft of the distal protection device and 395 were assigned to stent placement over a conventional angioplasty guidewire (control group). There was a 6.9% absolute (42% relative) reduction in the 30-day primary end point - a composite of death, myocardial infarction, emergency bypass, or target lesion revascularisation – 9.6% for GuardWire patients versus 16.5% for control patients; p = 0.004. The reduction in major adverse cardiac events was driven by a reduction in myocardial infarction of all magnitudes (8.6% versus 14.7%, p= 0.008). In addition, rates of TIMI grade 3 flow were higher for the GuardWire arm (98%) compared with the control arm (95%; p = 0.04) and the incidence of clinically evident no-reflow was reduced (3% versus 9%; p = 0.001). A per-protocol analysis on the patients with technically successful use of the GuardWire (90.1%) showed an even lower incidence of myocardial infarction (7.9%) and no-reflow phenomenon (2.4%). The rates of the primary end point and no-reflow in patients with technical failure of Guard-wire arm were similar to the control arm (Baim et al., 2002).

Fig. 2. Diagram of the GuardWire temporary occlusion and aspiration system. A) The lesion is crossed with the GuardWire. The distal occlusion balloon is positioned proximal to anastomosis. The stent/balloon is advanced to the tip of the guide catheter. B) The compliant occlusion balloon at the GuardWire tip is inflated to occlude flow before the stent is deployed. C) After stent deployment, an Export catheter is advanced over the GuardWire and aspiration is performed to remove the stagnant column of blood with suspended embolic debris. D) The GuardWire balloon is deflated to restore antegrade blood flow. Courtesy of Medtronic.

A morphometric and histological analysis of aspirated debris in the SAFE (Saphenous Vein Graft Angioplasty Free of Emboli) trial, using the GuardWire, showed grossly visible red and/or yellow debris extracted from 91% of the patients (Figure 3). Scanning electron microscopy documented particles ranging from 17 to 807 µm in diameter, with 81% of the aspirated particle size smaller than 96 microns (Grube et al., 2020). This is of particular consideration when one considers that the FilterWire (Boston Scientific, Natic, MA) has an 80 µm diameter pore size (Carter et al., 2007).

Despite these results there are some disadvantages with the use of these devices. The resulting absence of antegrade flow during balloon inflation may result in distal ischaemia,

diameter between 3 and 6 mm. Four hundred and six patients were randomized to stent placement over the shaft of the distal protection device and 395 were assigned to stent placement over a conventional angioplasty guidewire (control group). There was a 6.9% absolute (42% relative) reduction in the 30-day primary end point - a composite of death, myocardial infarction, emergency bypass, or target lesion revascularisation – 9.6% for GuardWire patients versus 16.5% for control patients; p = 0.004. The reduction in major adverse cardiac events was driven by a reduction in myocardial infarction of all magnitudes (8.6% versus 14.7%, p= 0.008). In addition, rates of TIMI grade 3 flow were higher for the GuardWire arm (98%) compared with the control arm (95%; p = 0.04) and the incidence of clinically evident no-reflow was reduced (3% versus 9%; p = 0.001). A per-protocol analysis on the patients with technically successful use of the GuardWire (90.1%) showed an even lower incidence of myocardial infarction (7.9%) and no-reflow phenomenon (2.4%). The rates of the primary end point and no-reflow in patients with technical failure of Guard-wire

Fig. 2. Diagram of the GuardWire temporary occlusion and aspiration system. A) The lesion is crossed with the GuardWire. The distal occlusion balloon is positioned proximal to anastomosis. The stent/balloon is advanced to the tip of the guide catheter. B) The

compliant occlusion balloon at the GuardWire tip is inflated to occlude flow before the stent is deployed. C) After stent deployment, an Export catheter is advanced over the GuardWire and aspiration is performed to remove the stagnant column of blood with suspended embolic debris. D) The GuardWire balloon is deflated to restore antegrade blood flow.

A morphometric and histological analysis of aspirated debris in the SAFE (Saphenous Vein Graft Angioplasty Free of Emboli) trial, using the GuardWire, showed grossly visible red and/or yellow debris extracted from 91% of the patients (Figure 3). Scanning electron microscopy documented particles ranging from 17 to 807 µm in diameter, with 81% of the aspirated particle size smaller than 96 microns (Grube et al., 2020). This is of particular consideration when one considers that the FilterWire (Boston Scientific, Natic, MA) has an

Despite these results there are some disadvantages with the use of these devices. The resulting absence of antegrade flow during balloon inflation may result in distal ischaemia,

arm were similar to the control arm (Baim et al., 2002).

Courtesy of Medtronic.

80 µm diameter pore size (Carter et al., 2007).

which is poorly tolerated by some patients. Sixty one percent of patients in the SAFE trial developed angina during balloon inflation; however, in no patient was ischaemia so severe as to prompt premature deflation of the occlusion balloon. Additionally, balloon-induced injury may occur if they are not used carefully and it is difficult to get adequate imaging during the procedure while the distal vessel is occluded (Morís et al., 2009).

Fig. 3. Aspirated debris from a saphenous vein graft. Courtesy of Medtronic.

A second-generation distal balloon occlusion device, TriActiv (Kensey Nash Corp., Exton, PA), has 4 principal components: a balloon guidewire consisting of a 0.014" hypotube with a carbon dioxide–inflated compliant occlusion balloon on the wire (balloon diameter 3-5 mm), a modified syringe filled with sterile carbon dioxide used to inflate the occlusion balloon, a 4F side-attachable flush catheter, and a drive console with mechanical pumps for infusion and extraction. The lesion is crossed with the balloon guidewire and the occlusion balloon is positioned at least 20 mm beyond the distal edge of the target lesion. The occlusion balloon is inflated with carbon dioxide. A stent is delivered over the Balloon Guidewire and deployed at the lesion. The flush catheter is advanced over the balloon guidewire and saline is infused via holes in the distal end. Extraction of fluid and debris is performed through the guiding catheter. The occlusion balloon is deflated and flow is restored (Carrozza et al., 2005a).

The PRIDE (Protection During Saphenous Vein Graft Intervention to Prevent Distal Embolization) study was a prospective randomized trial, which enrolled patients with coronary ischemia and lesions in saphenous vein grafts in two cohorts. Cohort I randomized patients to protection with the TriActiv System versus percutaneous coronary intervention without embolic protection, to demonstrate superiority of the TriActiv System compared with an "unprotected" group. Given the small number of patients in Cohort I, meaningful conclusions regarding the superiority of TriActiv to saphenous vein graft intervention without embolic protection could not be made.

Cohort II randomized 631 patients to embolic protection with the TriActiv System or control group (Guardwire System [Medtronic] or Filterwire EX [Boston Scientific]) to establish noninferiority to other distal protection devices. The incidence of major adverse cardiac events at 30 days was 11.2% for the TriActiv group and 10.1% for the control group (relative risk = 1.1%; 95% confidence interval 0.67 to 1.76; p = 0.65; p = 0.02 for non-inferiority). Safety and efficacy end points were similar between groups except that patients randomized to the TriActiv System had more hemorrhagic complications (10.9% vs. 5.4%; p = 0.01). Patients in the TriActiv group were more likely to require blood transfusion. Sub-group analysis indicated that the higher rate of transfusion in the TriActiv cohort was associated with an early design of the haemostatic valve in combination with 8-F guiding catheters. The

Percutaneous Intervention Post Coronary

**10.3 Filter devices** 

2009).

5.5 mm.

Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 117

Unfortunately, this device also has limitations: there is no antegrade flow with the subsequent possibility of myocardial ischaemia during the procedure, its utilization is more complex than the distal filters and they can not be used in ostial disease (Morís et al., 2009).

Distal embolic filter devices maintain distal perfusion and allow injection of contrast medium during PCI while trapping most particulate debris. The advantages are that they preserve antegrade flow, contrast imaging is possible throughout the procedure and they are very simple to use. However, they are associated with limitations such as the fact that may not be able to capture all the debris, it may also be difficult to evaluate retrieval of the debris during the procedure, delivery catheters may cause embolization before filter deployment and the possibility of snagging of the retrieval sheath on the stent (Morís et al.,

The FilterWire EZ (Boston Scientific) consists of a distal polyurethane filter with a 110 µm pore size mounted on a 0.014-inch guidewire. The latest version has a 100 µm pore size. The system consists of a protection wire, a delivery sheath, a retrieval sheath and accessories (Figures 5 and 6). When deployed, the protection wire's filter bag is designed to capture and recover emboli that may be released during the procedure. The protection wire is used as the primary guidewire during the procedure. The floppy tip of the protection wire and the filter loop are radiopaque to enable visual guidance during placement. At the completion of the procedure, the filter is captured using the retrieval sheath and then removed from the patient (Figure 7). The loop of the device is designed to appose vessels ranging from 3.5 to

The FIRE (FilterWire EX Randomized Evaluation) trial was a multicenter randomized trial designed to evaluate the safety and efficacy of distal microcirculatory protection with the FilterWire EX compared with the GuardWire balloon occlusion and aspiration device during percutaneous intervention of diseased saphenous vein grafts. Six hundred and fifty one patients undergoing stent implantation in 682 de novo lesions in saphenous vein grafts with a reference diameter between 3.5 to 5.5 mm were randomized. Device success (defined as the ability to deliver, deploy and retract a device at and from the target location for FilterWire and the ability to deliver a device to the target, obtain distal occlusion and perform aspiration without loss of occlusion attributable to leak or rupture for GuardWire) was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (p= 0.25).

Fig. 5. Image of the FilterWire EZ. Courtesy of Boston Scientific.

TriActiv System was shown to be not inferior to approved embolic protection devices for the treatment of diseased saphenous vein grafts (Carrozza et al., 2005b).

#### **10.2 Proximal balloon occlusion devices**

The Proxis Embolic Protection System (St. Jude Medical, Maple Grove, Minnesota) is a unique single-operator catheter that is deployed proximal to the target lesion before crossing. Inflation of the sealing balloon interrupts antegrade flow during the period of lesion intervention. Stagnated blood and emboli liberated during intervention is then retrieved by gentle aspiration or via ancillary flushing of the vessel (Figure 4).

Fig. 4. Image of the Proxis embolic protection system. Courtesy of St. Jude Medical.

The PROXIMAL (Proximal Protection During Saphenous Vein Graft Intervention) trial was a multicenter prospective randomized trial, which compared 2 treatment strategies in a noninferiority format. Patients with saphenous vein graft stenosis were randomized to 1 of 2 treatment strategies: a current-care control arm (distal embolic protection device with FilterWire or GuardWire whenever possible, and no embolic protection when not) or a test arm (proximal protection with the Proxis system whenever possible and distal embolic protection when anatomy precluded proximal protection).

A total of 594 patients undergoing stenting of 639 saphenous vein grafts were prospectively randomized. The primary composite end point of death, myocardial infarction, or target vessel revascularization at 30 days by intention to treat analysis occurred in 10.0% of control and 9.2% of test patients; difference = -0.8% (95% confidence interval [CI] -5.5% to 4.0%); p for noninferiority= 0.0061. In device specific analysis, this composite end point occurred in 11.7% of distal protection patients and 7.1% of proximal protection patients (difference = - 4.6% [95% CI -9.6% to 0.3%]; p for superiority = 0.10, p for noninferiority = 0.001). Finally, in the subset of patients with lesions amenable to treatment with either proximal or distal protection devices (n = 410), the primary composite end point occurred in 12.2% of distal protection patients and 7.4% of proximal protection patients; p for superiority = 0.14, p for noninferiority = 0.001.

This study concluded that using proximal embolic protection whenever possible during treatment of diseased saphenous vein grafts produced outcomes similar to those with distal embolic protection (Mauri et al., 2007).

Unfortunately, this device also has limitations: there is no antegrade flow with the subsequent possibility of myocardial ischaemia during the procedure, its utilization is more complex than the distal filters and they can not be used in ostial disease (Morís et al., 2009).

#### **10.3 Filter devices**

116 Coronary Interventions

TriActiv System was shown to be not inferior to approved embolic protection devices for the

The Proxis Embolic Protection System (St. Jude Medical, Maple Grove, Minnesota) is a unique single-operator catheter that is deployed proximal to the target lesion before crossing. Inflation of the sealing balloon interrupts antegrade flow during the period of lesion intervention. Stagnated blood and emboli liberated during intervention is then

treatment of diseased saphenous vein grafts (Carrozza et al., 2005b).

retrieved by gentle aspiration or via ancillary flushing of the vessel (Figure 4).

Fig. 4. Image of the Proxis embolic protection system. Courtesy of St. Jude Medical.

protection when anatomy precluded proximal protection).

noninferiority = 0.001.

embolic protection (Mauri et al., 2007).

The PROXIMAL (Proximal Protection During Saphenous Vein Graft Intervention) trial was a multicenter prospective randomized trial, which compared 2 treatment strategies in a noninferiority format. Patients with saphenous vein graft stenosis were randomized to 1 of 2 treatment strategies: a current-care control arm (distal embolic protection device with FilterWire or GuardWire whenever possible, and no embolic protection when not) or a test arm (proximal protection with the Proxis system whenever possible and distal embolic

A total of 594 patients undergoing stenting of 639 saphenous vein grafts were prospectively randomized. The primary composite end point of death, myocardial infarction, or target vessel revascularization at 30 days by intention to treat analysis occurred in 10.0% of control and 9.2% of test patients; difference = -0.8% (95% confidence interval [CI] -5.5% to 4.0%); p for noninferiority= 0.0061. In device specific analysis, this composite end point occurred in 11.7% of distal protection patients and 7.1% of proximal protection patients (difference = - 4.6% [95% CI -9.6% to 0.3%]; p for superiority = 0.10, p for noninferiority = 0.001). Finally, in the subset of patients with lesions amenable to treatment with either proximal or distal protection devices (n = 410), the primary composite end point occurred in 12.2% of distal protection patients and 7.4% of proximal protection patients; p for superiority = 0.14, p for

This study concluded that using proximal embolic protection whenever possible during treatment of diseased saphenous vein grafts produced outcomes similar to those with distal

**10.2 Proximal balloon occlusion devices** 

Distal embolic filter devices maintain distal perfusion and allow injection of contrast medium during PCI while trapping most particulate debris. The advantages are that they preserve antegrade flow, contrast imaging is possible throughout the procedure and they are very simple to use. However, they are associated with limitations such as the fact that may not be able to capture all the debris, it may also be difficult to evaluate retrieval of the debris during the procedure, delivery catheters may cause embolization before filter deployment and the possibility of snagging of the retrieval sheath on the stent (Morís et al., 2009).

The FilterWire EZ (Boston Scientific) consists of a distal polyurethane filter with a 110 µm pore size mounted on a 0.014-inch guidewire. The latest version has a 100 µm pore size. The system consists of a protection wire, a delivery sheath, a retrieval sheath and accessories (Figures 5 and 6). When deployed, the protection wire's filter bag is designed to capture and recover emboli that may be released during the procedure. The protection wire is used as the primary guidewire during the procedure. The floppy tip of the protection wire and the filter loop are radiopaque to enable visual guidance during placement. At the completion of the procedure, the filter is captured using the retrieval sheath and then removed from the patient (Figure 7). The loop of the device is designed to appose vessels ranging from 3.5 to 5.5 mm.

Fig. 5. Image of the FilterWire EZ. Courtesy of Boston Scientific.

The FIRE (FilterWire EX Randomized Evaluation) trial was a multicenter randomized trial designed to evaluate the safety and efficacy of distal microcirculatory protection with the FilterWire EX compared with the GuardWire balloon occlusion and aspiration device during percutaneous intervention of diseased saphenous vein grafts. Six hundred and fifty one patients undergoing stent implantation in 682 de novo lesions in saphenous vein grafts with a reference diameter between 3.5 to 5.5 mm were randomized. Device success (defined as the ability to deliver, deploy and retract a device at and from the target location for FilterWire and the ability to deliver a device to the target, obtain distal occlusion and perform aspiration without loss of occlusion attributable to leak or rupture for GuardWire) was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (p= 0.25).

Percutaneous Intervention Post Coronary

measures in this population (Halkin et al., 2006).

C) End result after removing the FilterWire.

**11. Conclusions** 

Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 119

Although, as has been mentioned above, none of these devices has demonstrated more efficacy than others in a randomized trial, some recommendations can be made based on anatomical considerations and tolerance of absence of antegrade flow: distal occlusion may be the preferred choice in cases of proximal disease with high plaque or thrombus burden; filters may be proposed in cases of poor tolerance for ischaemia or single remaining grafts without distal disease and proximal occlusion devices would be indicated in grafts with

Distal protection devices have been shown to enhance procedural success rates, reduce the occurrence of no reflow, and prevent large as well as small periprocedural infarctions; the former of which is clearly prognostically relevant. These results thus support the general recommendation for routine use of distal protection devices during saphenous vein graft intervention when possible. However, it should be recognised that the long-term course after intervention in diseased saphenous vein grafts is not benign even when distal protection is used. Periprocedural major adverse events still occur in approximately 10% of patients, and the rates of death, myocardial infarction and repeat revascularisation procedures are relatively high compared with percutaneous coronary interventions in native coronary arteries, due not only to restenosis at the target site but also to disease progression in sites remote from that of the index intervention. These observations underscore the need for intensive post-discharge surveillance and secondary prevention

Fig. 7. Percutaneous intervention in a saphenous vein graft using a FilterWire embolic protection device. A) Saphenous vein graft stenosis with superimposed thrombus (arrows). B) Particulate debris trapped within the FilterWire embolic protection device (arrow).

Saphenous vein graft disease represents the "Achilles heel" of coronary artery bypass surgery

Stenosed saphenous vein grafts can be treated by percutaneous intervention or a second coronary artery bypass surgery; however, a repeated bypass surgery is burdened by a

interventions, due to the high failure rate of saphenous vein grafts (Lupi et al., 2011).

higher risk of death and provides less symptomatic improvement (Lupi et al., 2011).

distal disease, especially in relatively straight vessels (Morís et al., 2009).

Postprocedural measures of epicardial flow, angiographic complications and the extent of myonecrosis were similar between the 2 groups. The primary end point of the study, the composite occurrence of major adverse cardiac events, including death, myocardial infarction or target vessel revascularization at 30-days occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% confidence interval] = -1.7% [- 6.4%, 3.1%]; p for superiority = 0.53, p for noninferiority = 0.0008). This was driven primarily by non-Q wave myocardial infarction. Although exploratory subgroup analyses demonstrated a possible benefit of the FilterWire EX compared with the GuardWire in smaller vessels and eccentric lesions, the mechanistic explanation for these observations is uncertain, and these findings may be attributable to chance. It is important to note that, event rates were very low in both groups when only one stent was implanted or the total length of stents was limited. Conversely, the longer the lesion and the greater the number and length of stents implanted, the higher the event rate with both protection devices. Periprocedural adverse event rates were also increased in thrombotic lesions and degenerated vein grafts (Stone et al., 2003). By 6 months, the outcomes of the FIRE trial showed similar major adverse cardiac event increases to 19.3% in the FilterWire EX and to 21.9% in the GuardWire groups (p= 0.44) (Halkin et al., 2006).

Fig. 6. Image of the FilterWire EZ. Courtesy of Boston Scientific.

The SpiderRX embolic protection device (eV3, Plymouth, MN) is a nitinol mesh filter system. One major innovation of this filter is the ability to cross the lesion with a conventional 0.014-inch guidewire, then deploying the filter via monorail delivery catheter (Carter et al., 2007). This device was assessed in the Spider trial, which randomized 732 patients to saphenous vein intervention using either the Spider device or a control arm of distal protection with the GuardWire or the FilterWire. Major adverse cardiac event rates were statistically similar between both groups after 30 days. Compared with controls, the SpiderRX showed non-inferiority in terms of all secondary end points, including device success, in-hospital major adverse cardiac events, clinical success and procedural success (Carter et al., 2007 & White, 2006).

One concern regarding the use of filter based systems versus balloon occlusion systems has been the functional limitations of the pore size and retrieved particulate debris. This concern however, has not been substantiated by the outcomes of the clinical trials. In fact, one analysis of retrieved particles using a filter device and the GuardWire showed retrieval of particles well less than 100 µm. It is possible that deposition of platelets and debris reduces the functional pore size (Carter et al., 2007).

Although, as has been mentioned above, none of these devices has demonstrated more efficacy than others in a randomized trial, some recommendations can be made based on anatomical considerations and tolerance of absence of antegrade flow: distal occlusion may be the preferred choice in cases of proximal disease with high plaque or thrombus burden; filters may be proposed in cases of poor tolerance for ischaemia or single remaining grafts without distal disease and proximal occlusion devices would be indicated in grafts with distal disease, especially in relatively straight vessels (Morís et al., 2009).

Distal protection devices have been shown to enhance procedural success rates, reduce the occurrence of no reflow, and prevent large as well as small periprocedural infarctions; the former of which is clearly prognostically relevant. These results thus support the general recommendation for routine use of distal protection devices during saphenous vein graft intervention when possible. However, it should be recognised that the long-term course after intervention in diseased saphenous vein grafts is not benign even when distal protection is used. Periprocedural major adverse events still occur in approximately 10% of patients, and the rates of death, myocardial infarction and repeat revascularisation procedures are relatively high compared with percutaneous coronary interventions in native coronary arteries, due not only to restenosis at the target site but also to disease progression in sites remote from that of the index intervention. These observations underscore the need for intensive post-discharge surveillance and secondary prevention measures in this population (Halkin et al., 2006).

Fig. 7. Percutaneous intervention in a saphenous vein graft using a FilterWire embolic protection device. A) Saphenous vein graft stenosis with superimposed thrombus (arrows). B) Particulate debris trapped within the FilterWire embolic protection device (arrow). C) End result after removing the FilterWire.

### **11. Conclusions**

118 Coronary Interventions

Postprocedural measures of epicardial flow, angiographic complications and the extent of myonecrosis were similar between the 2 groups. The primary end point of the study, the composite occurrence of major adverse cardiac events, including death, myocardial infarction or target vessel revascularization at 30-days occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% confidence interval] = -1.7% [- 6.4%, 3.1%]; p for superiority = 0.53, p for noninferiority = 0.0008). This was driven primarily by non-Q wave myocardial infarction. Although exploratory subgroup analyses demonstrated a possible benefit of the FilterWire EX compared with the GuardWire in smaller vessels and eccentric lesions, the mechanistic explanation for these observations is uncertain, and these findings may be attributable to chance. It is important to note that, event rates were very low in both groups when only one stent was implanted or the total length of stents was limited. Conversely, the longer the lesion and the greater the number and length of stents implanted, the higher the event rate with both protection devices. Periprocedural adverse event rates were also increased in thrombotic lesions and degenerated vein grafts (Stone et al., 2003). By 6 months, the outcomes of the FIRE trial showed similar major adverse cardiac event increases to 19.3% in the FilterWire EX and to

21.9% in the GuardWire groups (p= 0.44) (Halkin et al., 2006).

Fig. 6. Image of the FilterWire EZ. Courtesy of Boston Scientific.

(Carter et al., 2007 & White, 2006).

the functional pore size (Carter et al., 2007).

The SpiderRX embolic protection device (eV3, Plymouth, MN) is a nitinol mesh filter system. One major innovation of this filter is the ability to cross the lesion with a conventional 0.014-inch guidewire, then deploying the filter via monorail delivery catheter (Carter et al., 2007). This device was assessed in the Spider trial, which randomized 732 patients to saphenous vein intervention using either the Spider device or a control arm of distal protection with the GuardWire or the FilterWire. Major adverse cardiac event rates were statistically similar between both groups after 30 days. Compared with controls, the SpiderRX showed non-inferiority in terms of all secondary end points, including device success, in-hospital major adverse cardiac events, clinical success and procedural success

One concern regarding the use of filter based systems versus balloon occlusion systems has been the functional limitations of the pore size and retrieved particulate debris. This concern however, has not been substantiated by the outcomes of the clinical trials. In fact, one analysis of retrieved particles using a filter device and the GuardWire showed retrieval of particles well less than 100 µm. It is possible that deposition of platelets and debris reduces

Saphenous vein graft disease represents the "Achilles heel" of coronary artery bypass surgery interventions, due to the high failure rate of saphenous vein grafts (Lupi et al., 2011).

Stenosed saphenous vein grafts can be treated by percutaneous intervention or a second coronary artery bypass surgery; however, a repeated bypass surgery is burdened by a higher risk of death and provides less symptomatic improvement (Lupi et al., 2011).

Percutaneous Intervention Post Coronary

**12. References** 

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Artery Graft Surgery in Patients with Saphenous Vein Graft Disease – State of the Art 121

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Baim D.S.; Wahr, D.; George B.; Leon, M.B.; Greenberg, J.; Cutlip, D.E.; Kaya, U.; Popma, J.J.;

Baim, D. (2003). Percutaneous treatment of saphenous vein graft disease: the ongoing challenge. *J Am Coll Cardiol*, Vol 42, No. 8 (October 2003), pp. 1370-1372. Baldus, S.; Köster, R.; Elsner, M.; Walter, D.H.; Arnold, R.; Auch-Schwelk, W.; Berger, J.;

surveillance trial. *Circulation*, Vol 102, No.17, (October 2000), pp. 2024-2027. Bittl, J.A. (2009). Drug-eluting stents for saphenous vein graft lesions. The limits of evidence.

Brener, S.J.; Lytle, B.W.; Casserly, I.P.; Ellis, S.G.; Topol, E.J. & Lauer, M.S. (2006). Predictors

Brilakis, E.S. & Berger, P.B. (2008). Should bare metal or drug-eluting stents be used during

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Carrozza, J.P.; Caussin, C.; Braden, G.; Braun, P.; Hansell, F.; Fatzinger, R.; Walters, G.;

Carrozza, J.P.; Mumma, M.; Breall, J.A.; Fernandez, A.; Heyman, E. & Metzger, C. for the

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potentially favourable milieu such as that in saphenous vein graft disease.

Attempts at percutaneous revascularisation in saphenous vein graft lesions with balloon angioplasty were limited by a relatively low procedural success rate and a high incidence of angiographic recurrence.

Stent implantation in patients with focal saphenous vein graft lesions improved procedural success and clinical outcome compared with balloon angioplasty. However, even with the use of stents treatment of saphenous vein graft lesions is associated with a high incidence of acute complications, principally distal embolisation and periprocedural myocardial infarction, because of the more friable atherosclerotic or thrombotic components of the saphenous vein graft lesions (Stankovic et al., 2003). Besides, the results of bare metal stents in saphenous vein grafts are less favourable than those in native vessels, with restenosis rates exceeding 30% (Savage et al., 1997; Silber et al., 2005). In fact some authors recommend carrying out percutaneous coronary intervention in native vessels whenever possible even when there is complete obstruction or to consider the possibility of new revascularisation surgery rather than percutaneous saphenous vein graft intervention (Lozano et al., 2005).

In an attempt to improve the outcome of intervention in stenotic vein grafts, several approaches and adjunctive pharmacological regimens have been studied, but with the exception of distal protection devices, none showed a clear benefit in reducing the incidence of distal embolisation, especially in complex lesions (Stankovic et al., 2003). However, despite the existence of successful proximal and distal filters and balloons, 30-day major adverse cardiac event rates still hover between 8% and 10%. A logical approach to assess a potential reduction in the incidence of no-reflow phenomenon and its deleterious consequences would be to conduct prospective, randomised, controlled trials assessing the combination of distal filter protection devices, glycoprotein IIb/IIIa inhibitors and pretreatment with intra-graft administration of vasodilators, particularly nicardipine.

Drug-eluting stents have been shown to reduce restenosis in many lesion types and clinical syndromes. However, there is a paucity of prospective data on drug-eluting stents in saphenous vein graft intervention (Brilakis et al., 2009). Most meta-analysis of randomised trials and observational studies comparing drug-eluting stents and bare metal stents in saphenous vein graft percutaneous intervention suggest that drug-eluting stent use in saphenous vein graft is safe and reduces target vessel revascularisation.

Patients with previous coronary artery bypass graft surgery suffer from diffuse atherosclerosis of native coronary arteries as well as rapid saphenous vein graft degeneration, thus the benefit from drug-eluting stents could be largely diluted by acute coronary syndromes arising from other previously untreated coronary lesions (Lupi et al., 2011).

In addition, it is well established that the long-term prognosis of patients with diseased saphenous vein grafts is mainly impacted by progression of disease in the nonintervened saphenous vein grafts segments (Ellis et al., 1997 & Keeley et al., 2001).

Large, prospective, multicenter, randomised-controlled clinical trials that use a clinical rather than angiographic end point are needed to confirm the beneficial role of drug-eluting stents in saphenous vein graft lesions (Brilakis & Berger, 2008). Additionally, longer-term follow-up of at least 3 to 5 years is essential for randomised trials involving the use of drugeluting stents in saphenous vein grafts to address two potentially harmful events. First, the possibility of late restenosis catch-up with drug-eluting stents in saphenous vein graft disease, considering their higher restenosis rate and more delayed restenosis process than in native vessels. Second, the possible risk of late stent thrombosis, which has been already shown for native coronary arteries (Mc Fadden et al., 2004; & Ong et al., 2005), in a potentially favourable milieu such as that in saphenous vein graft disease.
