**5. Endovascular intervention to correct dialysis vascular access malfunction**

The initial treatment recommended for stenotic lesions in both nAVF and AVG is endovascular intervention, primarily angioplasty. Endovascular intervention is employed to maintain or even rescue AV access [32].

The recommendation within the K/DOQI guidelines is to treat hemodialysis access stenosis of more than 50% of the vessel lumen, if those are related with reduced flow rate and high venous pressure. PTA is considered a standard of care in failing hemodialysis access due to its high rates of success and satisfactory patency rate [33].

#### **5.1 Stenosis location**

The stenotic lesions in an AV fistula can occur in any location of the access system, with a higher incidence in specific spots for each type of VA. This is the case of stenosis at the proximal "swing segment" (the vein segment immediately after the arteriovenous anastomosis of a nAVF, which was dissected and brought close to the artery to create the anastomosis) either in the upper arm in transposed brachio-basilic fistulas, or in the lower forearm, in radio-cephalic fistulas, which are relatively more frequent than lesions at any other site [34]. Another example is the cephalic arch region, in patients with brachiocephalic fistulas [32].

Below we describe some types of stenosis of the vascular circuit, selected for their particularities, namely, their frequency, risk of restenosis, and predictable danger of VA failure.

#### **5.2 Cephalic arch stenosis**

The proximal cephalic vein is characterized by a curved shape, which occurs as the cephalic arch passes though the coracoclavicular ligament, just before joining the subclavian vein.

Several reasons have been put forward to justify the development of cephalic arch stenosis, such as increased blood flow rates, hemodynamic factors associated with the vessel shape, external compression by the outer structures surrounding the vein, and hypertrophy of valves that are often present in the cephalic arch.

**189**

**Figure 1.**

*Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction*

Although angioplasty is the accepted initial treatment of cephalic arch stenosis, it can be problematic because lesions in that location are more resistant to dilatation. When dealing with resistant stenotic lesions, it is shown that employing cutting balloons (see below) may improve outcomes. On the other hand, complications are more likely (vein rupture), and patency is reduced compared with other vein location. Stent placement in the arch is a delicate task because the stent should invade the subclavian vein lumen, which can result in its partial or total occlusion, impeding the future creation of an AVF or AVG using the basilic or axillary vein, thereby consuming vascular patrimony. In view of the recurrent problems with angioplasty of the cephalic arch, the stent placement can be an alternative to rescue the vascular access (**Figure 1**). For several reasons, it is not possible to make any evidence-based recommendations on best practices for management of CAS (endovascular or surgical). There is profound heterogeneity in the studies retrieved, from their initial design to their presentation of data. Few studies were prospective, few studies involved more than one or two centers, and the lack of uniformity of outcomes is another weakness of current published studies. CAS is often managed alternatively by interventionists

The prior placement of a central venous catheter is by far the most common cause of central vein stenosis (CVS) in dialysis patients. Transvenous wires of cardiac rhythm devices are more and more related with central veins stenosis in this population of high cardiovascular morbidity. Hemodialysis patients are, therefore, primary candidates for new wireless pacemakers or epicardial pacemaker leads. The surgical approach to central vein stenosis is difficult because they can hide behind the bone structure. Therefore, endovascular intervention with angioplasty and/or stent placement becomes a logistically more receptive proposal for treatment of CVS. Still, anatomically and functionally, central veins have several specific characteristics including the diameter, angle, and elasticity that make treatment

Some central vein stenoses are not symptomatic. Asymptomatic central veins stenosis, involving less than 50% of the vessel lumen, does not require treatment

Angioplasty with or without stent placement has been the recommended preferred approach to CVS. The guideline 20 NKF-K/DOQI suggests that the percutaneous intervention with transluminal angioplasty is the preferred treatment for CVS [36]. PTA has very high initial technical success rates, ranging from 70 to 90% [37, 38]. Primary and cumulative patency rates are widely variable and can

*(a) and (b). Stenosis affecting cephalic arch; this lesion responded well to balloon angioplasty.*

*DOI: http://dx.doi.org/10.5772/intechopen.92631*

and surgeons, in our experience with identical success.

and maintenance of their patency after intervention difficult.

and is best managed by simple supervision [35].

**5.3 Central vein stenosis**

#### *Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction DOI: http://dx.doi.org/10.5772/intechopen.92631*

Although angioplasty is the accepted initial treatment of cephalic arch stenosis, it can be problematic because lesions in that location are more resistant to dilatation. When dealing with resistant stenotic lesions, it is shown that employing cutting balloons (see below) may improve outcomes. On the other hand, complications are more likely (vein rupture), and patency is reduced compared with other vein location. Stent placement in the arch is a delicate task because the stent should invade the subclavian vein lumen, which can result in its partial or total occlusion, impeding the future creation of an AVF or AVG using the basilic or axillary vein, thereby consuming vascular patrimony. In view of the recurrent problems with angioplasty of the cephalic arch, the stent placement can be an alternative to rescue the vascular access (**Figure 1**).

For several reasons, it is not possible to make any evidence-based recommendations on best practices for management of CAS (endovascular or surgical). There is profound heterogeneity in the studies retrieved, from their initial design to their presentation of data. Few studies were prospective, few studies involved more than one or two centers, and the lack of uniformity of outcomes is another weakness of current published studies. CAS is often managed alternatively by interventionists and surgeons, in our experience with identical success.

## **5.3 Central vein stenosis**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

In our unit, prospective results of 1-year follow-up in 71 new AV grafts with

a.A Qa < 600 ml/min had the same predictive value with that ΔQa of 25%, and

b.After 1 year only 35% of PTFEs did not need any kind of intervention. We demonstrated then a sensitivity of 82% and a specificity of 90% to detect

d.A sensitivity of 39% and a specificity of 21% to detect thrombosis.

**5. Endovascular intervention to correct dialysis vascular access** 

alysis access due to its high rates of success and satisfactory patency rate [33].

cephalic arch region, in patients with brachiocephalic fistulas [32].

The stenotic lesions in an AV fistula can occur in any location of the access system, with a higher incidence in specific spots for each type of VA. This is the case of stenosis at the proximal "swing segment" (the vein segment immediately after the arteriovenous anastomosis of a nAVF, which was dissected and brought close to the artery to create the anastomosis) either in the upper arm in transposed brachio-basilic fistulas, or in the lower forearm, in radio-cephalic fistulas, which are relatively more frequent than lesions at any other site [34]. Another example is the

Below we describe some types of stenosis of the vascular circuit, selected for their particularities, namely, their frequency, risk of restenosis, and predictable

The proximal cephalic vein is characterized by a curved shape, which occurs as the cephalic arch passes though the coracoclavicular ligament, just before joining the

Several reasons have been put forward to justify the development of cephalic arch stenosis, such as increased blood flow rates, hemodynamic factors associated with the vessel shape, external compression by the outer structures surrounding the

vein, and hypertrophy of valves that are often present in the cephalic arch.

The initial treatment recommended for stenotic lesions in both nAVF and AVG is endovascular intervention, primarily angioplasty. Endovascular intervention is

The recommendation within the K/DOQI guidelines is to treat hemodialysis access stenosis of more than 50% of the vessel lumen, if those are related with reduced flow rate and high venous pressure. PTA is considered a standard of care in failing hemodi-

monthly surveillance revealed the following:

dynamic venous pressure was useless.

e.A thrombosis rate—0.46 thru/pt. year.

c. "Successful" PTA in 91% and Qa↑ on average 142%.

f. In 60% of cases, previous monitoring was normal.

employed to maintain or even rescue AV access [32].

stenosis.

**malfunction**

**5.1 Stenosis location**

danger of VA failure.

subclavian vein.

**5.2 Cephalic arch stenosis**

**188**

The prior placement of a central venous catheter is by far the most common cause of central vein stenosis (CVS) in dialysis patients. Transvenous wires of cardiac rhythm devices are more and more related with central veins stenosis in this population of high cardiovascular morbidity. Hemodialysis patients are, therefore, primary candidates for new wireless pacemakers or epicardial pacemaker leads.

The surgical approach to central vein stenosis is difficult because they can hide behind the bone structure. Therefore, endovascular intervention with angioplasty and/or stent placement becomes a logistically more receptive proposal for treatment of CVS. Still, anatomically and functionally, central veins have several specific characteristics including the diameter, angle, and elasticity that make treatment and maintenance of their patency after intervention difficult.

Some central vein stenoses are not symptomatic. Asymptomatic central veins stenosis, involving less than 50% of the vessel lumen, does not require treatment and is best managed by simple supervision [35].

Angioplasty with or without stent placement has been the recommended preferred approach to CVS. The guideline 20 NKF-K/DOQI suggests that the percutaneous intervention with transluminal angioplasty is the preferred treatment for CVS [36]. PTA has very high initial technical success rates, ranging from 70 to 90% [37, 38]. Primary and cumulative patency rates are widely variable and can

**191**

ment [49, 50].

*Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction*

range between 23 and 63% at 6 months and 12 and 50% at 12 months in the case of primary patency rate, as well as 29 and 100% at 6 months and 13 and 100% at

Our cumulative experience shows that angioplasty and stent placement is undermined by frequent and rapid recurrence. It can also happen that an asymptomatic lesion can become symptomatic upon intervention. Indeed, one study showed that stenosis can progress faster after intervention [37]. The venous response may be worsening, and the stenosis process can be accelerated due to angioplasty.

Correction of CVS with endovascular approaches remains therefore limited and suboptimal and may even be harmful in certain cases. After angioplasty, more aggressive neointimal hyperplasia and proliferative lesions were found in restenosis

A major problem with lesions in the central veins is that many are quite elastic. For this reason, endovascular stents are used more frequently for central veins stenosis than for other types of dialysis access lesions. Cost considerations are highly relevant and also the fact that we are left without any option to treat effectively a restenosis inside a stent. Even if we extend 100% the half-life of a recurrent stenotic access (from a procedure every 3 months to every 6 months), it may look as an

The vein immediately adjacent to the arteriovenous anastomosis (commonly referred to as juxta-anastomosis) is a common location of stenosis. This is in part due to injury, which occurred while "swinging" the vein to form the AV anastomosis. Some studies demonstrate that the frequency of juxta-anastomotic stenosis may

Angioplasty and surgery are two treatment options. Percutaneous angioplasty has 1-year patency rates of 44–79% [44–46]. For surgery, 1-year patency rates are between 64 and 88% [45–47]. In this location, we usually need very high-pressure balloons to deal with very hard lesions. If we elect a surgical solution, we get better results at the expense of a few more centimeters of vascular territory. Regrettably, randomized studies comparing endovascular treatment and surgery for this lesion

There are several types of balloons that we can use in angioplasty: (i) "highpressure," (ii) "ultrahigh-pressure (UHP)," (iii) "cutting," and (iv) "drug-eluting."

High-pressure, noncompliant balloons (e.g., Conquest from Bard Peripheral Vascular Inc., Tempe, Arizona) have rated burst pressures of 20 to 24 atm and are

Venous stenosis is characterized by extensive fibrosis and the need for ultrahighpressure balloon inflations [48] or cutting balloon atherotomy for optimal treat-

12 months in the case of cumulative patency rate (**Figure 2**) [36, 39–42].

*DOI: http://dx.doi.org/10.5772/intechopen.92631*

areas than in the original stenotic lesions [38].

**5.4 Juxta-anastomotic location**

be up to 55% [43].

are not available (**Figure 3**).

*5.5.1 High-pressure balloons*

*5.5.2 Ultrahigh-pressure balloons*

**5.5 Type of angioplasty balloons**

used to treat dialysis vascular access stenosis.

impressive achievement, but with little clinical relevance.

#### *Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction DOI: http://dx.doi.org/10.5772/intechopen.92631*

range between 23 and 63% at 6 months and 12 and 50% at 12 months in the case of primary patency rate, as well as 29 and 100% at 6 months and 13 and 100% at 12 months in the case of cumulative patency rate (**Figure 2**) [36, 39–42].

Our cumulative experience shows that angioplasty and stent placement is undermined by frequent and rapid recurrence. It can also happen that an asymptomatic lesion can become symptomatic upon intervention. Indeed, one study showed that stenosis can progress faster after intervention [37]. The venous response may be worsening, and the stenosis process can be accelerated due to angioplasty.

Correction of CVS with endovascular approaches remains therefore limited and suboptimal and may even be harmful in certain cases. After angioplasty, more aggressive neointimal hyperplasia and proliferative lesions were found in restenosis areas than in the original stenotic lesions [38].

A major problem with lesions in the central veins is that many are quite elastic. For this reason, endovascular stents are used more frequently for central veins stenosis than for other types of dialysis access lesions. Cost considerations are highly relevant and also the fact that we are left without any option to treat effectively a restenosis inside a stent. Even if we extend 100% the half-life of a recurrent stenotic access (from a procedure every 3 months to every 6 months), it may look as an impressive achievement, but with little clinical relevance.

### **5.4 Juxta-anastomotic location**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

*(a) Right brachiocephalic trunk stop flow. (b) PTA of stenosis with 12 mm balloon. (c) Final angiogram result.*

**190**

**Figure 2.**

The vein immediately adjacent to the arteriovenous anastomosis (commonly referred to as juxta-anastomosis) is a common location of stenosis. This is in part due to injury, which occurred while "swinging" the vein to form the AV anastomosis. Some studies demonstrate that the frequency of juxta-anastomotic stenosis may be up to 55% [43].

Angioplasty and surgery are two treatment options. Percutaneous angioplasty has 1-year patency rates of 44–79% [44–46]. For surgery, 1-year patency rates are between 64 and 88% [45–47]. In this location, we usually need very high-pressure balloons to deal with very hard lesions. If we elect a surgical solution, we get better results at the expense of a few more centimeters of vascular territory. Regrettably, randomized studies comparing endovascular treatment and surgery for this lesion are not available (**Figure 3**).

#### **5.5 Type of angioplasty balloons**

There are several types of balloons that we can use in angioplasty: (i) "highpressure," (ii) "ultrahigh-pressure (UHP)," (iii) "cutting," and (iv) "drug-eluting."

#### *5.5.1 High-pressure balloons*

High-pressure, noncompliant balloons (e.g., Conquest from Bard Peripheral Vascular Inc., Tempe, Arizona) have rated burst pressures of 20 to 24 atm and are used to treat dialysis vascular access stenosis.

#### *5.5.2 Ultrahigh-pressure balloons*

Venous stenosis is characterized by extensive fibrosis and the need for ultrahighpressure balloon inflations [48] or cutting balloon atherotomy for optimal treatment [49, 50].

**Figure 3.**

*(a) Severe stenosis in juxta-anastomotic radio-cephalic fistula. (b) Angiogram result after angioplasty with 7 mm PTA balloon.*

An UHP balloon is certified for a burst pressure of 27 atm, but higher inflation pressures are possible. Although those balloons do not provide better results in terms of permeability, when compared to conventional ones, it has been suggested that such devices may achieve better patency rates than traditional HP angioplasty balloons [51]. Its use is indicated in the treatment of symptomatic stenosis not responding to conventional high-pressure balloon. The high price of UHP balloon, the need for use thicker inserts, the difficulty of emptying, and its lower compliance and flexibility make it advisable that UHP balloons should not be a first choice in stenosis treatment.

Despite that, ultrahigh-pressure balloons have significantly reduced the incidence of "resistant" lesions [52].

#### *5.5.3 Cutting balloons*

The cutting balloons are special angioplasty balloons with three or four cutting edges (atherotomes) fixed longitudinally to its surface. The atherotomes expand radially with balloon inflation and provide longitudinal incisions into the lesion cutting into tenacious neointima. Using cutting balloons has the advantage that disruption of the lesion occurs in a more controlled manner and at lower balloon inflation pressure than with conventional angioplasty.

The use of a cutting angioplasty balloon (CAB) to treat resistant lesions can be found in several reports [49, 51]. Most of these reports are constrained because they are retrospective, lack control, or the size is too small to allow meaningful

**193**

*Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction*

conclusions. Taking into account the data reported in the literature and also considering the authors experience, it can be stated that angioplasty with a cutting balloon is safe and can be considered as an alternative treatment for stenosis of hemodialy-

There are serious methodologic limitations in the published reports describing the use of cutting balloon angioplasty to treat hemodialysis vascular access stenosis [53–56]. Studies include the concurrent use of cutting and conventional balloon angioplasty, the use of a high-pressure balloon, or a combination with placement of a stent after cutting balloon angioplasty. In other studies, cutting PTA was used only after the failure of high-pressure balloon angioplasty. In these reports, the long-term patency rate does not reflect the results obtainable with cutting balloon angioplasty as a primary, stand-alone treatment. The cutting balloon was designed primarily to reduce vascular trauma, thereby diminishing neointimal hyperplasia, thereby improving hemodialysis access long-term patency. It should be noted that studies comparing cutting balloon and conventional balloon angioplasty in the treatment of vascular access stenosis are fraught

Good results have been obtained with drug-coated balloon (DCB) angioplasty used to prevent restenosis in the treatment of arterial stenosis. This approach (using paclitaxel-coated balloons) was extended to the treatment of stenosis associated

Drug-coated balloon endovascular technology merges the dilating properties of angioplasty with local drug delivery. Balloon surface excipients enable drugeluting within the vessel wall, inhibiting cell proliferation, and reducing neointimal

DCB angioplasty of vascular access stenosis seem to be safe and effective, providing superior reintervention-free intervals compared to conventional plain balloon angioplasty [58–60]. Recently, Yan and others published a meta-analysis that reveals that DCB is an effective and safe method that can significantly prolong 6-month and 1-year target lesion primary patency for failing hemodialysis access, as compared to conventional plain balloon angioplasty. However, their study was limited by the small number of patients enrolled in each trial, the diversity characteristics of the lesions, the vintage of the dialysis access, and the formulations of paclitaxel (different dose or excipients

The reported number of dialysis patients treated with DCBs is low, and several concerns remain unanswered. First of all, it is uncertain which lesions will benefit from the use of this balloon device. Lesion preparation is another issue that deserves further investigation. Manufacturing companies suggest pre-dilation with a shorter balloon, with the same diameter, to promote drug diffusion within the deeper layers of the vessel wall and to improve the restenosis rate. However, in some RCTs published, pre-dilation was not even performed. Last but not least, although the long-term safety of PCBs in dialysis access treatment has been proven, preclinical and experimental studies in animal models are lacking; consequently, we have no available information on the posttreatment lesion pathology, degree of drug

*DOI: http://dx.doi.org/10.5772/intechopen.92631*

with conflicting results.

**5.6 Drug-coated balloons**

sis AVFs that do not respond to conventional balloons.

with hemodialysis AV access, with mixed results [57].

hyperplasia, while avoiding the use of permanent metal stents.

used). A very heterogeneous group of studies lumped together [61].

diffusion, and the extent of paclitaxel fixation within the venous wall.

It should be noted that the use of drug-eluting balloons is a novel medical device that aims to decrease the trauma in the endothelium of the vascular wall of a fistula. Although more expensive than the conventional balloon, it is much cheaper than a bare metal stent, and repeated procedures can be performed in case of

#### *Early Detection and Endovascular Intervention to Correct Dialysis Vascular Access Malfunction DOI: http://dx.doi.org/10.5772/intechopen.92631*

conclusions. Taking into account the data reported in the literature and also considering the authors experience, it can be stated that angioplasty with a cutting balloon is safe and can be considered as an alternative treatment for stenosis of hemodialysis AVFs that do not respond to conventional balloons.

There are serious methodologic limitations in the published reports describing the use of cutting balloon angioplasty to treat hemodialysis vascular access stenosis [53–56]. Studies include the concurrent use of cutting and conventional balloon angioplasty, the use of a high-pressure balloon, or a combination with placement of a stent after cutting balloon angioplasty. In other studies, cutting PTA was used only after the failure of high-pressure balloon angioplasty. In these reports, the long-term patency rate does not reflect the results obtainable with cutting balloon angioplasty as a primary, stand-alone treatment. The cutting balloon was designed primarily to reduce vascular trauma, thereby diminishing neointimal hyperplasia, thereby improving hemodialysis access long-term patency. It should be noted that studies comparing cutting balloon and conventional balloon angioplasty in the treatment of vascular access stenosis are fraught with conflicting results.

### **5.6 Drug-coated balloons**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

An UHP balloon is certified for a burst pressure of 27 atm, but higher inflation pressures are possible. Although those balloons do not provide better results in terms of permeability, when compared to conventional ones, it has been suggested that such devices may achieve better patency rates than traditional HP angioplasty balloons [51]. Its use is indicated in the treatment of symptomatic stenosis not responding to conventional high-pressure balloon. The high price of UHP balloon, the need for use thicker inserts, the difficulty of emptying, and its lower compliance and flexibility make it advisable that UHP balloons should not be a first choice in stenosis

*(a) Severe stenosis in juxta-anastomotic radio-cephalic fistula. (b) Angiogram result after angioplasty with* 

Despite that, ultrahigh-pressure balloons have significantly reduced the inci-

The cutting balloons are special angioplasty balloons with three or four cutting edges (atherotomes) fixed longitudinally to its surface. The atherotomes expand radially with balloon inflation and provide longitudinal incisions into the lesion cutting into tenacious neointima. Using cutting balloons has the advantage that disruption of the lesion occurs in a more controlled manner and at lower balloon

The use of a cutting angioplasty balloon (CAB) to treat resistant lesions can be found in several reports [49, 51]. Most of these reports are constrained because they are retrospective, lack control, or the size is too small to allow meaningful

**192**

treatment.

**Figure 3.**

*7 mm PTA balloon.*

dence of "resistant" lesions [52].

inflation pressure than with conventional angioplasty.

*5.5.3 Cutting balloons*

Good results have been obtained with drug-coated balloon (DCB) angioplasty used to prevent restenosis in the treatment of arterial stenosis. This approach (using paclitaxel-coated balloons) was extended to the treatment of stenosis associated with hemodialysis AV access, with mixed results [57].

Drug-coated balloon endovascular technology merges the dilating properties of angioplasty with local drug delivery. Balloon surface excipients enable drugeluting within the vessel wall, inhibiting cell proliferation, and reducing neointimal hyperplasia, while avoiding the use of permanent metal stents.

DCB angioplasty of vascular access stenosis seem to be safe and effective, providing superior reintervention-free intervals compared to conventional plain balloon angioplasty [58–60]. Recently, Yan and others published a meta-analysis that reveals that DCB is an effective and safe method that can significantly prolong 6-month and 1-year target lesion primary patency for failing hemodialysis access, as compared to conventional plain balloon angioplasty. However, their study was limited by the small number of patients enrolled in each trial, the diversity characteristics of the lesions, the vintage of the dialysis access, and the formulations of paclitaxel (different dose or excipients used). A very heterogeneous group of studies lumped together [61].

The reported number of dialysis patients treated with DCBs is low, and several concerns remain unanswered. First of all, it is uncertain which lesions will benefit from the use of this balloon device. Lesion preparation is another issue that deserves further investigation. Manufacturing companies suggest pre-dilation with a shorter balloon, with the same diameter, to promote drug diffusion within the deeper layers of the vessel wall and to improve the restenosis rate. However, in some RCTs published, pre-dilation was not even performed. Last but not least, although the long-term safety of PCBs in dialysis access treatment has been proven, preclinical and experimental studies in animal models are lacking; consequently, we have no available information on the posttreatment lesion pathology, degree of drug diffusion, and the extent of paclitaxel fixation within the venous wall.

It should be noted that the use of drug-eluting balloons is a novel medical device that aims to decrease the trauma in the endothelium of the vascular wall of a fistula. Although more expensive than the conventional balloon, it is much cheaper than a bare metal stent, and repeated procedures can be performed in case of

recurrences. More trials are needed to find out if this more expensive material can really increase the patency of venous lesions.
