Choosing the Right Guidewire: The Key for a Successful Revascularization

*Daniel Brandão*

## **Abstract**

Even though frequently less considered, the guidewires are the most fundamental tools to track throughout the vessels, to cross stenoses or occlusions, and to be able to deliver the desired therapy to the selected vessel. In this chapter entitled "Choosing the Right Guidewire: The Key for a Successful Revascularization," the following issues will be thoroughly described: how the guidewires are built and why it is so important to be aware of it; why are there so many different guidewires; what are the possible applications for each guidewire; how to choose the right guidewire in every situation; techniques to cross a stenosis and a chronic total occlusion.

**Keywords:** guidewire, core, tip, stenosis, occlusion

## **1. Introduction**

Even though frequently less considered, the guidewires are the most fundamental tools to track throughout the vessels, to cross stenoses or occlusions, and to be able to deliver the desired therapy to the target lesion of a given vessel. A thorough knowledge of how they are built and in what way this impacts on their specific characteristics and applications is crucial for any vascular specialist who wishes to succeed. In fact, considering the vast number of options, a correct choice and utilization of a guidewire can frequently be the difference between success and failure of a revascularization, avoiding many possible complications that can jeopardize the final result.

## **2. General characteristics**

#### **2.1 Length**

The selection of a guidewire with a correct length can be very relevant to adequately reach and treat the target vessel. For this decision, distance from the access to the vessel to be treated and the shaft length of the sheaths and catheters to be used (either if it is a diagnostic catheter, a balloon catheter, or a delivery device of a stent or a stent graft) needs to be considered. In fact, this apparently less relevant subject may threaten the entire procedure.

Depending on the manufacturer, guidewires can range from 80 to 450 cm. Additionally, some guidewires may allow the connection of an extension during the procedure. This is particularly the case when a coronary guidewire is used as it is designed for rapid exchange devices.

There is a trick that can help in extreme circumstances and as bailout option only. During the removal of a catheter from inside the patient, it is possible to connect an inflation syringe device to the guidewire port of the catheter, just after losing the guidewire, and inflate inside the port, which will keep the guidewire in place. It is crucial to perform this maneuver under fluoroscopy as the guidewire may move forward and the external tip can even migrate and be lost inside the patient.

## **2.2 Diameter**

Even if there are several diameters available, the most commonly used guidewires to cross stenoses and occlusions in peripheral arteries have 0.014″, 0.018″, or 0.035″ in diameter. At this point, it will be relevant to recall the relation between the different units used in endovascular devices, as so: 1 French (F) = 1/3 millimeter = 0.013 inches. It is quite obvious that the thicker the guidewire, the stiffer it is and the more support it allows, even if the core material of it is also very relevant for those properties.

They are several factors that someone should keep in mind when choosing the diameter of a guidewire:


*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

#### **Figure 1.**

*A, B—Anterior tibial artery with very calcified and tight stenoses. C—Posterior tibial artery of the same patient (diabetic and on hemodialysis). The stenoses were successfully crossed and treated with angioplasty with a 0.014*″ *guidewire.*

#### **2.3 Stiffness**

There is no clearly accepted nomenclature that can reproductively relate a word or a group of words to the stiffness of a guidewire. As so, it is possible to find several guidewires with the label stiff, extra stiff, super stiff, or even ultra-stiff, without any objective information of its real stiffness. Flexural modulus is an engineering parameter related to a wire's resistance to bending (**Figure 2**). This measure is rarely displayed on the guidewire packaging or within the catalog [1]. Yet, it represents an objective method to quantify the stiffness of a guidewire.

This property is more frequently used to describe the body of the guidewire, but its use in the description of the tip of the guidewire can be very useful too. The stiffer the body of a guidewire is, the more support it will allow to deliver the intended endovascular devices to the target vessel. On the other end, a higher stiffness of the body reduces the ability of the guidewire to track the vessel tree. Concerning the tip, a higher stiffness increases the penetration capacity, but also turns the tip more aggressive to vessel wall increasing the risk of dissection or perforation.

#### **Figure 2.**

*Generically, the guidewire is supported at two points that are equidistant to a third point where a vertical force is applied. The force needed to bend the guidewire to a given extent determines its stiffness.*

## **2.4 Trackability**

It represents the capacity of a guidewire to navigate through the arterial tree, especially through curves of tortuous vessels. As so, floppier guidewires have a better trackability than stiffer guidewires.

## **2.5 Crossability**

It characterizes the ability of a guidewire to easily cross a lesion without buckling or kinking. Several features of the guidewire can optimize this capacity, depending on whether it is a stenosis or a chronic total occlusion.

#### **2.6 Pushability**

Pushability can be defined by the percentage or amount of a given forward force applied to the proximal end of the guidewire that is transmitted to the distal end of the guidewire. Usually, the stiffer and broader the guidewire, the more pushability it gives. This characteristic is particularly relevant in crossing long and/or calcified chronic total occlusions, either in an intraluminal or subintimal way.

### **2.7 Torqueability**

Torqueability represents the ability to apply a given rotational force at the proximal end of the guidewire and have that force transmitted efficiently and with the less delay possible, to achieve proper control of the distal tip. This feature is very relevant to determine the path of the guidewire and, consequently, to navigate inside the arterial tree (for instance, to go from the popliteal artery to the anterior tibial artery without a curved catheter) or to cross lesions. Torqueability is very dependent on the material used in the core and the distance from the access to the tip of the guidewire. As an example, guidewires with a stainless-steel core lose most their torqueability when used in a crossover fashion.

## **3. Composition**

A basic knowledge of the engineering aspects of the guidewire technology is quite relevant to understand more thoroughly how a given guidewire is expected to behave in different conditions.

A guidewire has essentially four major components (**Figures 3** and **4**):


#### **3.1 Core**

A guidewire has a core that goes all the way through the body and finishes at the tip, where it may or may not reach the end of the guidewire (**Figure 5**). The core can be made of nitinol (alloy of nickel and titanium), stainless steel, or another metallic alloy. Nitinol allows more flexibility, memory (ability to maintain the original shape), and resistance to bending. Stainless steel increases the stiffness of the

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

**Figure 4.**

*A—Spring coils design. B—Guidewire with a complete polymer jacket and coating. C—Hybrid covering.*

**Figure 5.**

*A, B, C—Core-to-tip design. The core taper is longer and segmented in B and C. D – Shaping ribbon design.*

guidewire, but is less resistant to bending, so it is easier to irreversibly kink a guidewire with a stainless-steel core than a guidewire with a nitinol core. Other alloys will provide intermediate characteristics. Some guidewires may also have hybrid cores

with stainless steel in the body and nitinol in the tip. In addition to its composition, its thickness straightforwardly corresponds to its stiffness: the thicker the core, the greater the stiffness and support. Therefore, the core is decisive for the behavior of the guidewire concerning its stiffness, torqueability, pushability, and trackability.

### **3.2 Tip**

There are essentially two main inner designs concerning the tip (**Figure 5**): the core finishes at the end of the tip in a variable tapered format (core-to-tip design) [2]. In this configuration, the tip has more pushability and torque, a higher penetration capacity, and a better tactile feel (see below). On the other hand, the tip is more prone to inadvertently perforate a vessel, to prolapse to an undesired vessel during tracking the arterial tree (**Figure 6A**) and to be irreversibly damaged (especially if the core is made of stainless steel). The length of the core taper and its configuration in a continuous or segmented design will enhance or attenuate the enumerated characteristics (**Figure 5A–C**).

The core does not reach the end of the tip (shaping ribbon design) [2]. With this configuration, the end of the tip is wrapped in a small flexible metal ribbon, providing the continuity of the guidewire (**Figure 5D**). This design provides a less aggressive and flexible tip, less prone to prolapse (**Figure 6B**), easier to shape, though at the cost of a less tip torque control.

The outer diameter of conventional guidewires is usually the same throughout its length. However, in more dedicated devices, the tip has a progressive reduction of the diameter (tapered tip design—**Figure 7**), going, for instance, from 0.014″ to 0.009″ [2]. This characteristic increases the penetration capacity but turns the tip much more aggressive and prone to vessel perforation. These guidewires are almost exclusively utilized in chronic total occlusions and should be handled with extreme care.

#### **Figure 6.**

*A—A guidewire with a core-to-tip design has more difficulties in tracking the arterial tree and can prolapse to an undesired vessel. B—A guidewire with a shaping ribbon design tracks the intended vessel much more easily. Arrows indicate the natural direction of each guidewire.*

#### **Figure 7.** *An example of a tapered tip design.*

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

## **3.3 Cover**

The core of the guidewire is usually covered either by coils or by a polymer component (**Figure 4**). When all the core is surrounded only by spring coils (spring coils design), it enhances tactile feel (see below), but adds friction when navigating the arterial tree, reducing trackability. However, this additional friction tends to stabilize the wire distally to the target lesion, making the guidewire less prone to move backward or forward. On the other hand, a polymer jacket along all the guidewire including the tip provides a very smooth surface improving trackability at the cost of losing tactile feel. Some guidewires have a hybrid covering or polymer covering all the body but leaving the coils of the tip naked, also referred to as "sleeves" [3]. This configuration allows good trackability of the body maintaining tactile feel mostly intact.

#### **3.4 Coating**

Most of contemporary guidewires have a thin hydrophilic or hydrophobic coating applied at the final manufacturing process (**Figure 4**). Hydrophilic coating (e.g., polyethylene oxide or polyvinyl pyrolidone) needs water to be activated and to become slippery, but once wet, it allows an extremely low coefficient of friction [4]. As a result, it makes vessels easier to track and stenoses simpler to cross but leads to a decreased tactile feel, increasing the risk of dissection or perforation. Paradoxically, if a guidewire with hydrophilic coating gets dry, it loses lubricity and can get stuck, for instance, inside a catheter. Conversely, hydrophobic coatings (e.g., polytetrafluoroethylene or silicones) do not require water for activation [4]. As their name indicates, they repel water and create a smooth, "wax-like" surface [3]. Hydrophobic coating reduces friction but leads to a less slippery guidewire with enhanced tactile feel. Frequently, hydrophobic coatings are applied to guidewire bodies to facilitate movement inside plastic catheters [4]. Nevertheless, both coatings can coexist in a single guidewire, allowing their respective specific characteristics to be present either at the tip or throughout the body. In some configurations, even the tip can have both coatings, for instance, hydrophobic at the end for tactile feel and tip control purposes and hydrophilic intermediate segment for smooth crossing. Moreover, both hydrophilic and hydrophobic coatings may chafe or degrade with use [4]. This can account for the deterioration in wire performance at times noted during long procedures, particularly when wires are working through areas of severe tortuosity and friction or after numerous device exchanges [4]. This can even lead the guidewire to get fixed inside the catheter, forcing both devices to be removed as one piece, jeopardizing the therapy of the targeted vessel.

## **4. Specific characteristics**

Even though, they are common to all guidewires used in endovascular procedures, the characteristics that will be discussed here are much more relevant in the 0.014″ and 0.018″ guidewires.

#### **4.1 Tactile feel**

It reports to the ability of a guidewire in transmitting tactile information from its tip to the hands of the interventionist. Even though it is a relatively subjective property, the possibility of the interventionist to feel the behavior of the tip when tracking vessels or crossing lesions (e.g., the tip goes freely or finds resistance) can help avoiding complications and improving results.

**Figure 8.** *Components combination influencing the relationship between lubricity and tactile feel.*

There is an inverse relationship between lubricity and tactile feel (**Figure 8**). Moreover, specific features can enhance tactile feel such as the core-to-tip design and the spring coil design.

## **4.2 Tip load**

The tip load represents the stiffness of the tip and is defined by the force needed to deflect to bend the tip 2 mm when the wire is fixed 10 mm above its end (**Figure 9**). It is a quite well-defined and reproducible parameter and therefore a comparable property. But as it is expressed in grams, it can generate confusion making some to think that the guidewire has effectively added weights at the tip. The tip load of the 0.014″ and 0.018″ guidewires utilized in peripheral interventions can range from 0.5 up to 35 g or more. The higher the tip load, the more aggressive the tip is. The lower it is, the softer and atraumatic it is.

**Figure 9.** *Tip load test.*

## **4.3 Penetration capacity**

The penetration capacity can be defined by the perpendicular force exerted over a defined area (i.e., pressure). It will depend on the tip load and the profile of the tip. For the same tip load, a guidewire that has a tapered tip will have a much higher penetration capacity than a more conventional nontapered tip. Additionally, adding a catheter (either a balloon catheter or a support catheter) very close to the end of the tip also adds penetration capacity as it prevents the tip to bend.

## **4.4 Shape, shapeability, and shape retention**

Most of the 0.035″ guidewires used in peripheral interventions come in a preshaped format from the manufacturer. The more common available shapes are straight, angled, and J-shaped. The latter is the least traumatic. As so, it can be the best guidewire to use to deliver the intended devices to a target vessel. It can also be quite useful in tracking throughout a previously placed patent stent because the tip will not get stuck in the struts of the stent, neither will go between the stent and the vessel wall. Straight tips are more adequate to cross occlusions and angled tips to track vessels and to cross stenoses.

On the other hand, the vast majority of the 0.014″ and 0.018″ guidewires available for peripheral purposes comes in a straight shape and needs to be shaped. As so, shapeability characterizes the capacity of the guidewire tip to be angulated and shaped by the interventionist and shape retention represents its ability to maintain the intended shape over time [3]. These properties depend on the tip design and materials. Accordingly, a core-to-tip design with a core made of stainless steel is particularly easy and accurate to be shaped, but almost impossible to be reshaped. Conversely, nitinol core makes the tip more difficult to be shaped because it tends to return to its original form (memory) but is more reshapeable.

The tip of the GW can be shaped using the puncture needle (for moderately angulated curves), with the non-cutting edge of the blade (for sharp angulations) or with the inserter (for both) (Videos 1 and 2, https://bit.ly/3jPF7aj).

The desired shape depends on the primary purpose the guidewire will be used (**Figure 10**). Moderately angled continuous curves are very useful to track throughout the artery tree or to select a target vessel (**Figure 10A**). Several sharp angulations may help in selecting arteries with an acute takeoff such as the anterior tibial artery

**Figure 10.**

*Tip shaping. A—Moderately angled continuous curve. B—Two sharp angles. C—Very short sharply angled curve.*

(**Figure 10B**). A very short sharply angled curve (usually no more than 1 mm) is intended to perform forceful and well-controllable drilling (**Figure 10C**).

## **5. Guidewire selection**

An accurate knowledge of the discussed characteristics of each guidewire will permit the proper choice for every specific situation and also to create an adequate local laboratory portfolio. In practice, a vascular interventionist will rather need to thoroughly master a relatively small number of guidewires, instead of scarcely knowing many.

The purpose of guidewires in a peripheral procedure can be summarized as:


Most of the interventionists have one or two "workhorse" guidewires, which are the guidewires that will be chosen to initiate the procedure and get to the target vessel. Their common characteristics are: good trackability and torqueability to navigate throughout the arterial tree, correct body stiffness to deliver catheters and sheaths to the intended vessel, and a tip as atraumatic as possible. They can also be used as an initial approach to the target lesion.

One additional aspect to take into account when choosing a guidewire is the catheter that will be also used. As such, for stenoses and some occlusions in larger vessels, such as the iliac arteries, an angled diagnostic or support catheter can be preferred to guide the tip of the guidewire to the center of the vessel, avoiding a subintimal track. Meanwhile, a straight support catheter or a balloon catheter would be the primary option for most of the stenoses and for occlusions in smaller vessels such as the tibial arteries.

#### **5.1 Basic rules for guidewire manipulation**

One of the best friends of a vascular interventionist is the torquer (**Figure 11**). It is the most proper manner to control the orientation of the guidewire tip. Therefore, its utilization is of utmost relevance in tracking difficult anatomies or in crossing challenging lesions (for instance, if the drilling technique is to be employed).

After having crossed the target lesion, the guidewire should be advanced very smoothly to the distal segment of the vessel. Confirmation through contrast injection that the true lumen has been reached after crossing the lesion is a basic but essential

**Figure 11.** *Example of a torquer.*

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

step. If a guidewire with a very aggressive tip was used to cross the lesion, it should be replaced by a much safer guidewire with good body stiffness for support (frequently the initial workhorse guidewire is adequate for this intent), sometimes after having shaped the tip as a loop (J-shaped like). During the delivery of the intended devices to the target lesion, it is of paramount importance to avoid inadvertent retraction of the guidewire, particularly after a complex crossing step and to prevent back and forth or shaking motion of the guidewire. That is why the tip of the guidewire should be on sight at almost all times. In summary, the two goals are: to secure the access to the target vessel and lesion; to avoid any trauma to the distal intact vessels.

#### **5.2 Crossing the target lesion**

The opening "workhorse" guidewire can be used in an initial attempt to cross the target lesion. Nevertheless, in many circumstances, a more dedicated guidewire will be required.

### *5.2.1 Crossing a stenosis*

To cross a stenosis, it is perceptibly fundamental to stay intraluminal. For that purpose, the guidewire does not need to have increased stiffness, pushability, or penetration capacity. The tip should probably be hydrophilic as tactile feel is less relevant in those situations, and this can also improve the crossability of the guidewire. The tip is typically shaped in soft curve (**Figure 10A**), to be directed to the opposite direction of the stenosis. Specifically in tibial vessels, a 0.014″ guidewire can be preferable as in the case showed in **Figure 1**.

#### *5.2.2 Crossing a chronic total occlusion*

A chronic total occlusion is generally defined as an occluded artery of 3 months duration or longer [5]. When the vascular interventionist faces a chronic total occlusion, the best guidewire is obviously the one that successfully crosses the lesion. Nevertheless, there are several issues to consider in an attempt to cross a chronic total occlusion:


very poor collateralization, it may not be initially adequately outlined and only appears after having crossed the occlusion.

## *5.2.3 Sliding technique*

This technique is particularly indicated for engaging softer chronic total occlusions with microchannels [6]. It is frequently the first approach. For that intent, the initial "workhorse" guidewire with a soft hydrophilic tip and a body with some stiffness can be the option as reduced surface friction enhances passage through the chronic total occlusion core. The tip should initially be shaped in a single, long shallow bend (**Figure 10A**), and movement consists of simultaneous smooth tip rotation and gentle probing. But during the crossing, the interventionist should stay vigilant, as the guidewire has reduced tactile feel and typically advances with minimal resistance, frequently resulting in inadvertent entry to the subintimal space [7].

## *5.2.4 Drilling technique*

If the sliding technique fails after a few attempts (one should not insist on this technique as it is easy to create several subintimal tracks that will jeopardize a desirable intra-luminal crossing), then the drilling technique should be tried. In this technique, a guidewire with a core-to-tip design with an uncovered tip should be preferred to enhance tactile feel. The tip is bended in a very short extension (**Figure 10C**) and clockwise and counterclockwise rotations of the guidewire are performed while the tip is pushed modestly against the chronic total occlusion (**Figure 12**). The important issue in this technique is that one does not push the guidewire very hard. Placing the balloon or the support catheter very close to the tip increases the penetration capacity. If the tip of the guidewire does not advance any more with gentle pushing, it is by far better to exchange for a stiffer tip and body guidewire, rather than continue pushing. If one pushes the wire hard, it will easily go into the subintimal space. Yet, when a stiffer guidewire is used, it may be difficult to perceive whether the tip has been engaged in the true or in a false lumen inside the chronic total occlusion. The movement of the tip may help in distinguishing one from the other. Typically, when the guidewire is in the subadventitial space, the tip budges markedly. Tactile feel from the guidewire during pullback can also aid as true lumen usually offers higher resistance. This technique has an increased risk of perforation, especially when using stiff tips guidewires [7].

**Figure 12.** *Drilling technique. Adapted from [7].*

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

**Figure 13.** *Penetrating technique. Adapted from [7].*

### *5.2.5 Penetrating technique*

The penetration technique comes next if the drilling technique does not succeed or when the interventionist has a chronic total occlusion with very calcified cap. In this technique, the preferred guidewires have a very aggressive tip (core to-tip design, uncovered tapered tip, with increased tip load, and a subsequent high penetration capacity) and a relatively stiff body. The tip shape is essentially straight, and a less rotational tip motion and a more direct forward probing is used in comparison to the drilling technique (**Figure 13**). Again, placing the balloon or the support catheter very close to the tip increases the penetration capacity and reduces the propensity of the tip to bend. Additionally, the distal target must be clearly identified and careful monitoring of the progressive guidewire advancement should be done. The guidewires employed in this technique should not be used to deliver the intended devices to the target lesion as the tip can easily damage the distally intact vessels. It is a technique with a particularly augmented risk of complications [7].

#### *5.2.6 Subintimal technique*

It is usually the last technique to be employed, even if it can be a first option in specific situations such as very long chronic total occlusions. For this technique, a guidewire with a stiff body and a soft short tip with hydrophilic coating is usually preferable. The short tip allows a short loop. After having created the loop, the guidewire is advanced to the end of the occlusion. To reenter into the true lumen, the loop has to be undone. Sometimes, the guidewire needed to be exchanged to a guidewire with a reduced diameter (if the initial guidewire was not a 0.014″ guidewire), with an uncovered tip (to increase the tactile feel and reduce the tendency to stay in the subintimal space that a hydrophilic tips has), a good torqueability, and an angled shaped tip (to be able to direct this one to the true lumen). Sometimes moving the balloon or the support catheter and the guidewire as one can be very useful (Video 3, https://bit.ly/3jPF7aj and **Figure 14**). If the loop, during the crossing, becomes too large, it means that most certainly, a perforation has occurred. In these situations, the guidewire should be retracted and an another subintimal track should be pursued.

#### *5.2.7 Retrograde access*

When the antegrade approach is not successful, a retrograde puncture may be required. Retrograde puncture of the popliteal artery is usually not a big issue. However, at below-the-knee level, since arteries are quite small and fragile and

#### **Figure 14.**

*A, B—Initial angiogram showing a long occlusion of the anterior tibial artery. C—Confirmation that the true lumen has been reached after a subintimal crossing of the occlusion (Video 3, https://bit.ly/3jPF7aj). D—Final result.*

frequently the tibial or peroneal artery to be punctured is the unique artery to the foot, extreme care must be the rule. As so, after having performed the puncture with a 21G needle (either guided by ultrasound or by X-ray), a guidewire is to be engaged inside the artery. To avoid additional injury to the artery, the devices introduced in it should be kept at the strict minimum. That why usually it is most preferable to initially advance only the guidewire without any catheter or sheath (**Figure 15**). Therefore, the guidewire to be chosen needs to have a hydrophilic stiff body due to the lack of a sheath, the relevance of having adequate torqueability to guide the tip and to perform the snaring of the guidewire, and a potential need for an additional catheter if the guidewire does not reach the true lumen or the same subintimal track made anterogradely. A 0.018″ diameter guidewire is probably the best option as it is still a delicate guidewire, but with more support than a 0.014″ guidewire. The tip should be soft and most probably hydrophilic to track easily the punctured vessel retrogradely. As no sheath should usually be introduced, hard push on the guidewire can lead to irreversible kinging of its body, which can jeopardize the intervention.

#### *5.2.8 Pedal plantar loop technique*

This technique consists in creating a loop with the guidewire from the anterior tibial artery to the posterior tibial artery, or the reverse, through the foot vessels [8, 9]. The most common pathway is through dorsalis pedis artery, deep plantar artery, deep plantar arterial arch, lateral plantar artery, and posterior tibial artery. Indications for this technique are similar to the retrograde access. However, it can be performed when no distal vessels are available for puncture, being also less invasive. Moreover, this technique can improve the outflow for tibial arteries.

However, complications related to foot vessels manipulation can precipitate a serious worsening of the ischemic condition. Taking this into account, the guidewire to be chosen to this technique needs to have a soft hydrophilic tip to easily

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

**Figure 15.**

*After a retrograde puncture of the peroneal artery, a guidewire was inserted in it lumen, without any sheath or catheter.*

track through tortuous foots vessels without damaging them. The body should also have reduced stiffness to track across the created loop, that's why usually a 0.014″ guidewire is preferred.

## **6. Potential guidewire-related complications**

The manipulation with a guidewire of smaller vessels such as the tibial and foot arteries can precipitate vasospasm. This can be quite common in young patients or in vessels with no calcification. It is very relevant to be able to recognize it and consequently avoid the confusion with atherosclerotic stenoses and perform angioplasty on those arteries, which can lead to dissection or even rupture (**Figure 16**). Several drugs can be administered intra-arterially to solve the issue. Agents commonly used for this purpose are nitroglycerin, verapamil, or papaverine. The dose to be injected should consider the blood pressure of the patient. The hemodynamic status of the patient should also be closely checked after the administration. They ideally should be given selectively through a diagnostic catheter to the target vessel. The guidewire can be gently withdrawn to a more proximal segment of the vessel, but without losing the ostium and consequently the access to the vessel.

A perforation or an arteriovenous fistula that occurs while attempting to cross a chronic total occlusion is rarely of any clinical significance as it will almost constantly closes within few minutes when only a guidewire or a low-profile catheter has passed extraluminally [10] (**Figures 17** and **18**). Thus, one should be sure to be inside the vessel before inflating a balloon. Removing the devices to above the proximal cap of the chronic total occlusion and reattempting to cross the lesion from the top, may allow successful path and aid in solving the perforation or the arteriovenous fistula. When those complications do not auto-resolve, external compression guided by angiography or temporary vessel occlusion with a balloon can be attempted. Sometimes a covered stent may be needed. In very rare situations, coil embolization must be envisaged.

An unintended wall dissection or perforation of an intact vessel distally after having crossed the target lesion can be quite challenging to solve and can threaten the success of the procedure or even worsen the ischemic condition of the patient.

#### **Figure 16.**

*A—Initial angiogram showing an occlusion of the tibioperoneal trunk and a quite healthy posterior tibial artery. B—After having crossed the occlusion, a 0.018*″ *guidewire was advanced inside the posterior tibial artery causing diffuse spasm of the artery (string of beads appearance). C—Few minutes after having selectively administrated 200 μg of nitroglycerin, the posterior tibial artery is widely open again.*

#### **Figure 17.**

*A—Perforation of the lateral plantar artery; extraluminal contrast is easily noticed. B—Peroneal arteriovenous fistula. Adapted from [7].*

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

**Figure 18.**

*A—Occlusion of the popliteal artery, tibio-peroneal trunk, and proximal segment of peroneal artery. B— Perforation occurred while trying to cross the occlusion through the initial antegrade approach. C & D—Final result after a retrograde puncture of the peroneal artery and successful crossing of the occlusion.*

Therefore, the most relevant concerning this issue is to adopt correct guidewire choices and strategies to avoid it.

## **7. Future perspectives**

X-ray fluoroscopy is still the gold standard imaging technique for the vast majority of endovascular procedures currently performed. Therefore, most of the endovascular devices, guidewires included, are designed to optimally perform under X-ray. However, its inherent ionizing radiation leads to safety concerns not only to the healthcare professionals, but also to the patients. As a result, recent advancements have been made toward magnetic resonance guided endovascular interventions [11]. Magnetic resonance imaging is a noninvasive, radiation-free imaging technique that can provide not only morphologic but also functional information (e.g., blood flow, tissue oxygenation, diffusion, or perfusion), which can potentially influence decisions during a procedure [11]. Yet, magnetic resonance guided interventions face a major challenge due to the presence of a large magnetic field, which limits the utilization of the currently available materials, including guidewires. Despite these challenges, significant progress has been recently made in the development of biocompatible, magnetic resonance safe, and visible interventional devices [11]. The guidewires presently used in the endovascular field have a long metallic core. In a magnetic resonance environment, it can create artifacts and can also induce thermal injury. As a result, new dedicated guidewires have been designed with the metallic core replaced by polymers reinforced by glass fibers or fiber composites. Those guidewires demonstrated to have improved stiffness and kink resistance [11]. Further research and development regarding magnetic resonance compatible devices and magnetic resonance imaging techniques will probably lead to a shift in the future standards of endovascular procedures.

## **8. Conclusions**

Guidewires are the cornerstone of any endovascular revascularization. Therefore, a correct knowledge of the engineering aspects of wire technology can be the difference between failure and success as it allows an adequate guidewire choice in any situation and for each specific crossing technique. A vascular interventionist should subsequently master a relatively small number of guidewires to be able to fully translate in practice his theoretical knowledge on guidewire design.

## **Video materials**

Video materials referenced in this chapter are available at: https://bit.ly/3jPF7aj.

## **Author details**

Daniel Brandão1,2

1 Angiology and Vascular Surgery Department, Vila Nova de Gaia/Espinho Hospital Center, Portugal

2 Angiology and Vascular Surgery Unit, Faculty of Medicine of the University of Porto, Portugal

\*Address all correspondence to: jdanielbrandao@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Choosing the Right Guidewire: The Key for a Successful Revascularization DOI: http://dx.doi.org/10.5772/intechopen.104484*

## **References**

[1] Harrison GJ, How TV, Vallabhaneni SR, Brennan JA, Fisher RK, Naik JB, et al. Guidewire stiffness: What's in a name? Journal of Endovascular Therapy. 2011;**18**(6):797-801

[2] Lorenzoni R, Ferraresi R, Manzi M, Roffi M. Guidewires for lower extremity artery angioplasty: A review. EuroIntervention. 2015;**11**(7):799-807

[3] Lanzer P. Textbook of Catheter-Based Cardiovascular Interventions: A Knowledge-Based Approach. 2nd ed. Cham: Springer International Publishing; 2018

[4] Buller C. Coronary guidewires for chronic total occlusion procedures: Function and design. Interventional Cardiology. 2013;**5**(5):533-540

[5] Stone GW, Kandzari DE, Mehran R, Colombo A, Schwartz RS, Bailey S, et al. Percutaneous recanalization of chronically occluded coronary arteries: A consensus document: Part I. Circulation. 2005;**112**(15):2364-2372

[6] Godino C, Sharp AS, Carlino M, Colombo A. Crossing CTOs-the tips, tricks, and specialist kit that can mean the difference between success and failure. Catheterization and Cardiovascular Interventions. 2009;**74**(7):1019-1046

[7] Forbes T. Angioplasty, Various Techniques and Challenges in Treatment of Congenital and Acquired Vascular Stenoses. London: InTech; 2012

[8] Fusaro M, Dalla Paola L, Biondi-Zoccai G. Pedal-plantar loop technique for a challenging below-theknee chronic total occlusion: A novel approach to percutaneous revascularization in critical lower limb ischemia. The Journal of Invasive Cardiology. 2007;**19**(2):E34-E37

[9] Manzi M, Fusaro M, Ceccacci T, Erente G, Dalla Paola L, Brocco E. Clinical results of below-the knee intervention using pedal-plantar loop technique for the revascularization of foot arteries. The Journal of Cardiovascular Surgery. 2009;**50**(3):331-337

[10] Lyden SP. Techniques and outcomes for endovascular treatment in the tibial arteries. Journal of Vascular Surgery. 2009;**50**(5):1219-1223

[11] Abdelaziz MEMK, Tian L, Hamady M, Yang G-Z, Temelkuran B. X-ray to MR: The progress of flexible instruments for endovascular navigation. Progress in Biomedical Engineering. 2021;**3**(3):032004

## **Chapter 5**

## Revascularization Strategies in Liver Transplantation

*Flavia H. Feier, Melina U. Melere, Alex Horbe and Antonio N. Kalil*

## **Abstract**

Vascular complications following liver transplantation chan jeopardize the liver graft and recipient survival. Aggressive strategies to diagnose and treat these complications may avoid patient and graft loss. With the evolving knowledge and novel therapies, less invasive strategies are gaining importance in the treatment of post liver transplant vascular complications. Portal, hepatic, and arterial thrombosis may be managed with systemic therapies, endovascular approaches, surgical and lastly with retransplantation. The timing between the diagnosis and the directed treatment is paramount for the success. Revascularization by means of interventional radiology plays an important role in the resolution and long-term patency of arterial and venous complications. This chapter will lead the reader into the most up-to-date treatments of post liver transplant vascular complications.

**Keywords:** hepatic artery thrombosis, portal thrombosis, heparin, alteplase

#### **1. Introduction**

Liver transplantation (LT) is the last resource for patients with end-stage liver failure. Currently, the excellent posttransplant survival rates shift the attention to improved patient care, quality of life, and diminishing posttransplant complications. LT can be performed with deceased donors or living donors. Also, the liver can be implanted as the hole organ, as in orthotopic liver transplantation (OLT) (**Figure 1**), or partial liver (left lobe, right lobe, left lateral segment) (**Figure 2**). Technical variant grafts include partial liver grafts from living donors, split liver, and reduced grafts and have historically been associated with higher risk of posttransplant vascular complications. The indications for LT and the techniques vary according to the age of the recipient, but basically involve a total liver resection with a graft implantation that requires three vascular anastomosis [hepatic vein (HV), portal vein (PV), and hepatic artery (HA)], and a biliary anastomosis. Each of the vascular anastomosis has a potential to suffer thrombosis and/or stenosis. The early diagnosis and intervention will determine the graft and patient survival, since any one of these may be fatal [1, 2].

In the following paragraphs, a detailed review of the pathogenesis of each vascular complication and current available treatment options will be presented.

#### **Figure 1.**

*Whole-liver transplant with related surgical anastomosis sites. 1= hepatic vein anastomosis using the recipients three hepatic veins and the common stump of the recipient hepatic veins by the piggyback technique; 2 = biliary anastomosis with choledochojejunostomy; 3 = HA reconstruction; and 4 = PV anastomosis [1].*

#### **Figure 2.**

*Living-donor liver transplant, with left lateral liver graft with surgical anastomoses of the hepatic veins by using the piggyback technique (1), hepaticojejunostomy (2), HA reconstruction with two anastomoses (double HA technique) (3), and PV anastomosis (4) [1].*

## **2. Hepatic vein thrombosis/stenosis**

## **2.1 Pathogenesis and diagnosis**

Hepatic vein anastomosis can be complicated by the development of stenosis and thrombosis. When venous drainage from the liver is compromised, liver parenchyma gets congested, causing impairment in the liver function, including a sluggish portal flow, and is called hepatic venous outflow obstruction (HVOO). Clinical manifestations of HVOO are nonspecific but may include abnormal liver function, hepatomegaly, ascites, pleural effusion, and lower-extremity edema. If it occurs in the immediate postoperative period, it can cause refractory graft dysfunction from liver congestion and graft loss. The mortality can be as high as 17–24% [3].

The incidence of HVOO after OLT varies from 0.5 to 9.5%. This incidence can be a little higher (3.9–16%) in living donor liver transplantation (LDLT) [4].

Routine Doppler ultrasound (DUS) performed in the immediate posttransplant period can identify signs of HVOO, such as dilated hepatic veins and dampened phasicity (pulsatility index less than 0.45) as lack of transmission of the right atrial waveform into the hepatic veins. In addition, the flow at the anastomosis often shows turbulence [5]. A computed tomography (CT) scan shows better sensitivity (97% vs. 87%) and specificity (86% vs. 68%) than DUS and allows the observation of parenchymal changes such as hypoattenuation during the portal venous phase or the delayed phase, which could suggest venous congestion [6]. The confirmation of this diagnosis is made by hepatic venography and manometry and is defined as stasis of the contrast medium from anastomotic obstruction on venography or a pressure gradient across the stenosis between the distal hepatic vein and the right atrium >5 mmHg. A pressure gradient of >5–6mmHg is widely accepted as the threshold for induction of symptoms [4].

Early complications (<30 days) are thought to be caused by technical factors such as a tight suture line, venous size match, kinking, and compression from a large graft. On the other hand, chronic (>30 days) obstructions are thought to result from fibrosis around the anastomotic site, intimal hyperplasia, twisting, or compression of the anastomosis from a hypertrophic graft [7].

Particular attention to anastomotic techniques is important such as performing a wide triangulated anastomosis, avoiding rotation of graft at the hepatocaval junction, and stabilization of the graft in an anatomical position [8]. Hepatic vein reconstruction is of particular challenge in right lobe grafts, in adult LDLT. Multiple middle hepatic vein tributaries draining the segment 5 vein (V5) are commonly found in donor hepatectomy using conventional modified right lobe grafts, leading to the performance of multiple anastomosis, including the use of vascular grafts to ensure adequate liver parenchymal drainage [4].

#### **2.2 Revascularization and outcomes**

Treatment of HVOO depends on the time of presentation and the cause (**Figure 3**). Most patients can be managed by interventional radiology (IR), performing a balloon angioplasty, with or without stent placement (**Figure 4**). During the early postoperative period, given the mechanism of HVOO, there is a high chance of restenosis if angioplasty alone is done. Stent is therefore indicated, also because balloon dilatation carries a risk of anastomosis disruption in the first days. Primary stent placement may be an effective treatment modality with an acceptable long-term patency to manage

*Art and Challenges Involved in the Treatment of Ischaemic Damage*

**Figure 3.**

*Algorithm for the management of HVOO. HVOO: hepatic venous outflow obstruction; and IR: interventional radiology.*

#### **Figure 4.**

*Hepatic vein stenosis treated with balloon angioplasty. (a) Left hepatic vein stenosis with evidence of collateral veins. (b) Trans-hepatic access and balloon positioning in the stenosis site. (c) Final aspect after balloon dilatation with resolution of collateral veins.*

early posttransplant HVOO. Jang et al reported a technical success rate of 96% and 3-year patency rate of 80% in 21 adult LDLT recipients with HVOO treated with IR [4].

Surgical options should be considered if HVOO is evident at the initial operation, which can be assessed by a transoperative DUS or in the early postoperative period. Surgery is also preferred if there is thrombosis of the hepatic veins because of the high chance of pulmonary embolism with IR treatment [5]. Retransplantation is considered as a last resource, when recanalization fails after these previous attempts.

## **3. Portal vein thrombosis/stenosis**

## **3.1 Pathogenesis and diagnosis**

The incidence of portal vein complications (PVCs) varies according to the recipient (children vs. adult), the LT modality (LDLT vs. OLT), and the preexistence of portal vein thrombosis (PVT). Untreated, it can lead to retransplantation, which happens in almost half of the recipients with PVT [9, 10].

The incidence of PVT after OLT can be up to 3–7%, 4% after LDLT [10], and up to 30% in children [11]. LT in children can present with additional difficulties related to portal vein reconstruction (short vascular stumps, size discrepancy between the donor's and the recipient's vascular structures, anastomotic misalignment, stenosis, anastomotic kinks, low portal flow (<7 cm/s), small portal veins (<4 mm), and use of interposition vascular grafts) that can justify the higher incidence of portal vein complications [12].

The diagnosis of PVT can be made by the detection of clinical signs (fever, abdominal pain, intractable ascites, gastrointestinal bleeding, or encephalopathy) and/or laboratory abnormalities (elevated liver enzymes, elevated ammonia levels, and/or thrombocytopenia), or detected during routine posttransplant DUS examination. Some signs present in DUS can indicate a portal vein complication: decreased or absent PV blood flow, acceleration of blood flow at the PV anastomosis, and postanastomotic jet flow. Any of these findings should prompt a CT scan. A decrease in more than 50% in PV diameter in CT scan is a sign of portal vein stenosis (PVS) even though recipient/donor mismatch should always be considered in cases of LDLT and pediatric recipients. PVT appears in the CT scan as the absence of visible lumen at the site of a thrombus [10–12].

PVT can be classified into four grades according to Yerdel [13]: Grade I: thrombus at main PV affecting less than 50% of the lumen with or without minimal extension into superior mesenteric vein (SMV); Grade II: thrombus at PV affecting more than 50%, including complete thrombosis, with or without minimal extension into the SMV; Grade III: complete PVT plus thrombosis extending to the proximal SMV with patent distal SMV; Grade IV: complete PVT plus complete thrombosis of the SMV (proximal and distal).

## **3.2 Revascularization and outcomes**

Revascularization options for patients with PVT after LT will depend on the extension of the thrombosis and the time of onset/diagnosis. Surgical revision, systemic anticoagulation, catheter-based thrombolytic therapy, balloon angioplasty and stenting, portosystemic shunting compose the usual algorithm. Retransplantation remains as the last resource when everything else has failed [10].

Early complications (from 24 h to 1 week after LT) are usually associated with technical issues and tend to benefit from surgical revision (redo anastomosis, kinking, liver graft repositioning) (**Figure 5**). However, IR may play an important role as a salvage treatment when surgical revision of PV anastomoses fails. In contrast to early PVCs, late complications (>30 days), as well as grades 2–4 PVT, are associated with less favorable prognoses [11, 14].

Patients with grade 1 PVT without liver graft impairment can be treated with full heparinization [unfractioned or low-molecular-weight heparin (LMWH)] and then maintained anticoagulated with warfarin or rivaroxaban for 3–6 months.

#### **Figure 5.**

*Algorithm for the management of e-PVT. e-PVT: early portal vein thrombosis; LFT: liver function tests; and PV: portal vein.*

IR treatment is the first choice for patients with higher grades of PVT (2–4), portal vein occlusion, failed surgical revascularization, or failed recanalization with systemic anticoagulation (**Figure 6**). Balloon angioplasty with stent placement has high rates of success and low PVT recurrence [10, 11]. The PV access can be made percutaneously (trans-hepatic or trans-splenic) or via mini-laparotomy for a direct catheterization of the portal venous system through ileo-colic or mesenteric venous branches [10].

The trans-hepatic approach is usually chosen for the first attempt; however, in patients with chronic PVT, recanalization can be difficult, precluding venoplasty [15]. The ileo-colic approach involves a mini-laparotomy, followed by a catheterization of a venous branch, introduction of a 7 F sheath, and performance of the portography. This approach has advantages in terms of the certainty of portal catheterization [10]. Another option is the trans-splenic access, which is less injurious to the transplanted liver graft (**Figure 7**) [11].

Despite the chosen access, IR protocols for PVT revascularization usually include catheterization, passage of the guidewire through the thrombosed segment, balloon angioplasty, and stent placement (**Figure 7**). A thrombolysis may be performed in order to facilitate the aspiration of the thrombus. The catheter is placed inside the thrombus and the thrombolytic agent infused. If the first treatment is considered ineffective, the catheter may be left and a continuous infusion of the thrombolytic agent maintained, from a period of 10 days to 30 days [10]. Patients are left anticoagulated after the procedure, at least for 3 months. Sanada et al. recommended

*Revascularization Strategies in Liver Transplantation DOI: http://dx.doi.org/10.5772/intechopen.104708*

#### **Figure 6.**

*Algorithm for the management of late PVC. PVC: portal vein complication; PVS: portal vein stenosis; PVT: portal vein thrombosis; and IR: interventional radiology.*

#### **Figure 7.**

*Portal vein thrombosis treated with balloon angioplasty and stent. (a) Trans-splenic access and portography; (b) Passage of the guidewire through the site of thrombosis; (c) Balloon dilatation; and (d) Final aspect after stent positioning.*

the use of a three-agent anticoagulant therapy that combines low-molecular-weight heparin, warfarin, and aspirin for 3 months following balloon dilation for portal vein stenosis (PVS) in pediatric liver transplantation. Recurrence of PVS reduced from 55.6 to 0% in the long-term follow-up [16].

High rate of technical success can be achieved, and recent studies focus on LDLT. In adults, a rate of 80% was achieved with long-term patency in approximately 50–60% of cases [10]. Cavalcante et al reported on pediatric LDLT recipients with chronic PVT who underwent IR with stent placement using a trans-mesenteric approach. The technical success was of 78.6%; and 31.8% developed restenosis/thrombosis and attempted a new dilatation via transhepatic access. Most of the patients (78.5%) had less than 1 year of PVT, with an 81.8% technical success rate in this group, compared with a rate of 66.7% in patients with more than 1 year of PVT [11].

In cases of PVS, balloon angioplasty is considered the first line of treatment and has produced highly successful results (**Figure 8**). However, 28–50% of these patients may develop recurrent stenosis. There is no minimal time one should wait to perform an angioplasty, even though some groups are concerned about the risk of rupture of the suture. Some cases of PVS induced by chronic PVT are not resolved with balloon angioplasty, because the wall flexibility induces easy expansion and reversion of the PV wall by inflation and deflation of the balloon. Stent placement benefits these cases [10].

Early detection and treatment of PVS or PVT are paramount to avoid portal vein occlusion. Occluded PV has a low success of stent placement. After 1 year of

(a) (b)

#### **Figure 8.**

*Portal vein stenosis treated with balloon angioplasty. (a) Trans-hepatic access and portography; (b) Passage of the guidewire through the site of stenosis; (c) Balloon dilatation; and (d) Final aspect.*

PVT, chances can be as low as 0% [17]. The treatment of a completely occluded PV is directed to the management of portal hypertension, which includes medical treatment, shunt surgery (portosystemic shunt or meso-Rex shunt), and ultimately, retransplantation (**Figure 6**) [18].

## **4. Hepatic artery thrombosis/stenosis**

Hepatic artery complications can be classified into thrombosis and stenosis. Acute complications can be represented by early hepatic artery thrombosis (e-HAT), and chronic complications are related to late hepatic artery thrombosis (l-HAT) and hepatic artery stenosis (HAS). Revascularization strategies for these situations include surgical thrombectomy, endovascular thrombectomy, endovascular thrombolysis, systemic anticoagulation, systemic thrombolysis, and endovascular angioplasty and stent placement. The pathogenesis and best treatment modality of each type of complication will be discussed.

## **4.1 Early hepatic artery thrombosis**

e-HAT presents early in the posttransplant course. There is lack of definition in the literature about the post-LT period in which e-HAT should be classified, some assume 14 days, some 30 days, or even as long as 100 days. It can present asymptomatically and be detected with routine posttransplant DUS, but if left untreated can lead to liver failure and retransplantation. e-HAT has been associated with high mortality rate after LT, around 33% [19].

The incidence varies according to the transplant center, the age of the recipient, the transplant modality, and surgical technique. During the initial experience, rates in children reached 42% and 12% in adult recipients. More recently, the combined reported incidence of e-HAT dropped to 4.4%, and to 1–20% in pediatric recipients. Factors such as the surgical learning curve, development of microsurgical techniques, and the routine use of magnifying lenses during arterial anastomosis are responsible for these improvements. The higher incidence reported in children can be in part explained by the smaller vessels, raising the difficulty of the anastomosis. Centers that have adopted microsurgical technique have in fact reported a low incidence of e-HAT, even with partial grafts, as is the case in LDLT [2, 20]. A study by Li et al., in the setting of adult living donor liver transplantation, reported an incidence of 1.8% of HA complications using magnifying loups instead of the microscope [21].

e-HAT can be associated to surgical technique or intraoperative positioning of the hepatic artery (kinking), and when diagnosed in the first 24h after LT, surgical reintervention to check the position of the hepatic artery, check patency, or even redo the anastomosis is the best approach (**Figure 9**). Other nonsurgical causes of e-HAT include the development of slow arterial flow during an episode of acute rejection, patient hypercoagulability, cytomegalovirus infection, and immunization status, among others. A cytomegalovirus(CMV) recipient/donor mismatch emerged as a concordant risk factor. Patients submitted to a retransplantation are also in an increased risk of e-HAT [19, 20].

Since symptoms are absent during the first hours after e-HAT, routine DUS is paramount to diagnose and immediately treat this complication. Measuring the resistive index is performed as part of the DUS evaluation. A normal resistive index value ranges between 0.60 and 0.80, and values less than 0.50 have been shown to diagnosis HAS or thrombosis with a sensitivity 60% and specificity 77%. Ultrasound can detect up to 90% of all cases of HAT, but false positives can be seen in the setting of hepatic edema, systemic hypotension, or technical aspects limiting

#### *Art and Challenges Involved in the Treatment of Ischaemic Damage*

**Figure 9.**

*Algorithm for the management of early hepatic artery thrombosis (e-HAT).*

the study. CT scan has the advantage of being rapid, not operator-dependent, provides high spatial resolution of small vessels, and gives a superior anatomical overview with the aid of contrast. The combination of absent flow on DUS with confirmation on CT scan is commonly acceptable for the diagnosis of HAT. Other signs such as elevation of liver enzymes, compromise in liver function may be absent, specifically in the setting of LDLT, where the quality of the liver graft masks this alterations [2, 22, 23].

If HAT is unrecognized, the fate of the liver graft will depend on the potential for and the efficiency of developing a collateral arterial circulation and supervening infection within the compromised biliary tree. Untreated, this can progress to liver failure and death [24].

Interventions for e-HAT include urgent revascularization with thrombectomy, vascular anastomosis revision, and thrombolytic drug therapy. Traditionally, the choice was urgent retransplantation or conservative management. Most centers employ a combination of these interventions. There are no randomized controlled data to guide management. Reported studies often lack clear information about graft and patient outcomes and the selection criteria for treatment [24].

Although retransplant has been the first choice of therapy, it is associated with higher morbidity than primary transplant. Surgical options for acute HAT have traditionally included surgical revascularization and open thrombectomy. With major advancements in technology, endovascular management has emerged as a less invasive alternative treatment option.

A revascularization attempt is performed in approximately half of the cases of e-HAT, with a reported success rate of about 50% [20]. Surgical revascularization can be attempted in the first 24h after the diagnosis an e-HAT. Accerman et al performed urgent surgical revascularization in 31 children with diagnosed HAT after LT. Interventions included thrombectomy, with or without fibrinolysis, creation of a new anastomosis and conduit interposition. Success rates were reported in 61% of the cases [25]. Children are more likely than adults to have a successful outcome after early revascularization (61% of adults and 92% of children) [20, 26].

In the study of Pannaro et al., e-HAT required surgical revision in 77% patients and retransplant in 15.4%. Of the patients that required surgical revision, thrombectomy was performed in the majority and few required hepatic artery anastomotic revision. The graft salvage rate for this group was 80% [27].

In case of failed surgical revascularization, thrombolysis can still be pursued, either locally through endovascular therapy or systemically, as recently reported by our group. Systemic alteplase as a rescue therapy salvaged liver grafts in two children with e-HAT [23].

#### **4.2 Late complications—Late HAT and HA stenosis**

Late HAT manifesting months or years after surgery may be asymptomatic or have an insidious course characterized by cholangitis, relapsing fever, and bacteremia. The pathognomonic sign of HAT is the development of nonanastomotic/ complex biliary stricture, most commonly at the hilum. The formation of bile casts and duct ischemia predispose the patient to recurrent cholangitis and obstructions with the development of biliary abscesses and liver infarction [2, 20, 28].

Some patients presenting l-HAT develop a neovascularized liver. Even though these patients are prone to develop biliary complications, they are treated with repeated bile duct drainage procedures (endoscopic and/or radiological), and the graft salvage rate can reach 100% [27]. Factors influencing the likelihood of spontaneous, effective collateral formation are poorly understood but include the site of the arterial thrombosis (closer to the hilum), the graft type (split/reduced grafts), Roux-en-Y hepaticojejunostomy, multiple arteries, and the timing after LT [24].

HAS is an insidious vascular complication occurring after LT. The most common complication seen in patients with HAS is biliary strictures. HAS usually occurs at or near the anastomosis site as a result of operative technique. The reported HAS rate after LT ranges from 5 to 11% [21].

HAS can be suspected when DUS presents a tardus parvus waveform (defined as a waveform with a resistive index < 0.5 and a systolic acceleration time <0.08 seconds), but has a low positive predictive value and a high false-positive rate. CT scan is indicated to confirm the diagnosis, and arteriography can be used both as a diagnostic and a treatment option [24]. Treatment options for HAS shifted from surgical reintervention to IR balloon angioplasty, with or without stent placement (**Figure 10**) [27].

Patients treated with a transluminal radiological intervention can expect a patency rate >90% within 5 years. Repeat interventions may be performed in case of HAS recurrence. Angioplasty is useful in treatment of first-time stenosis, with stenting reserved for resistant stenosis [29].

#### **4.3 Endovascular revascularization**

HAT has been reported to be successfully treated with multiple endovascular techniques, including transcatheter intra-arterial thrombolysis (IAT), percutaneous transluminal angioplasty (PTA), stenting, or a combination of these [29]. Selective thrombolysis via the hepatic artery, IAT, has several advantages such as small thrombolytic dose, high localized concentration, and little influence on systemic coagulation. It is thought to be safe and effective if the infusion catheter is placed inside the thrombus. Despite its local effect, hemorrhage is the most common complication of IAT.

Urokinase (UK) and alteplase (t-PA) are the most common thrombolytic agents used, with no documented advantage of one over the other. Thrombolytic agents (plasminogen activators) convert plasminogen into plasmin, which further cleaves the fibrin strands within the thrombus, leading to clot dissolution. t-PA is a more

**Figure 10.**

*Hepatic artery stenosis treated with balloon angioplasty. (a) Arteriography demonstrating the hepatic artery originating from the superior mesenteric artery and the stenosis (arrow); and (b) Final aspect after balloon dilatation.*

potent activator of plasminogen and has higher affinity for fibrin within the clot. Thrombolytic agents can be infused in spaced doses [19] or continuously [30]. The lowest effective dosage and duration have not yet been determined. Dosages can vary from 1 to 3 mg (t-PA) or from 50,000 to 250,000 IU (UK) [31]. Continuous infusion can be maintained for 2–4 days with different dosing regimens, using up to 9 million units of UK [32]. Intra-arterial thrombolysis should be terminated if there is residual thrombus or persistent HAT after 36–48 h of thrombolytic therapy [33]. The estimated success rate of thrombolysis is of 68% [19].

Careful monitoring of coagulation profile and clinical symptoms is necessary during thrombolysis treatment. Fibrinogen levels should be kept above 100 mg/dl [34]; however, there is no evidence to support that fibrinogen levels are predictive of adverse bleeding; as hemorrhagic complications can also occur with values above 100 mg/dl. If adverse bleeding occurs, thrombolytic agent should be immediately terminated, and any other cause for bleeding should be addressed.

IAT can reveal other reasons for HAT, including kinking, anastomotic stenosis, or stricture, which if left untreated can lead to rethrombosis. The combined use of thrombolysis with PTA and/or stenting has been shown to have better patency and survival rates than thrombolysis alone. Angioplasty is useful in treatment of firsttime stenosis, with stenting reserved for resistant stenosis [35].

#### **4.4 Systemic thrombolysis**

Medical management without surgical or endovascular intervention has yet to be confirmed as an effective treatment option for HAT. Our group recently published the successful outcome with the multimodal treatment for e-HAT after pediatric LT. Two children were successfully rescued with systemic t-PA and heparinization [23].

Posttransplant anticoagulation, even with LMWH as part of the protocol, has been shown to reduce the incidence of HAT, but does not lead to resolution (31, 32). Our posttransplant protocol includes prophylactic heparin when TTPA < 2.5 times control, and aspirin 3mg/kg when the patient resumes oral intake and platelets are >100.000. DUS is performed during the LT, in the first 24h after the transplant, and subsequently according to clinical judgment.

Systemic heparinization can salvage a liver graft after HAT if the patient has a neovascularized liver or if there is HA recanalization, which occurs less frequently. The complete understanding of how systemic heparinization or systemic thrombolysis can actually prevent retransplantation is still under debate [23, 27]. However,

it is a valuable salvage therapy for these patients, and one should not hesitate in administering even if the patients go to a retransplant waiting list.

## **5. Conclusions**

Posttransplant vascular complications jeopardize the liver graft and can impact on graft and patient survival. An impeccable surgical technique, along with close posttransplant surveillance to ensure an early diagnosis and prompt treatment, will enhance the chances to avoid retransplantation. It was not until recently that IR and thrombolysis have replaced retransplantation as the first treatment choice. Complications occurring <24 h after the LT are still best managed with surgical revision, because technical issues are usually responsible and can be addressed. Later occurring complications, however, are best managed nonoperatively, with high success rates for current therapies. Retransplantation is reserved as last resource when previous attempts have failed or when the liver grafts are already beyond salvation.

## **Acknowledgements**

This article was funded by Teaching and Research Institute of Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil.

## **Author details**

Flavia H. Feier\*, Melina U. Melere, Alex Horbe and Antonio N. Kalil Liver Transplantation Unit and Radiology Interventional Unit, Santa Casa de Misericordia de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

\*Address all correspondence to: flavia.feier@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Horvat N, Marcelino ASZ, Horvat JV, Yamanari TR, Batista Araújo-Filho JA, Panizza P, et al. Pediatric liver transplant: Techniques and complications. Radiographics. 2017;**37**(6):1612-1631. DOI: 10.1148/rg.2017170022

[2] Neto JS, Fonseca EA, Vincenzi R, Pugliese R, Benavides MR, Roda K, et al. Technical choices in pediatric living donor liver transplantation: The path to reduce vascular complications and improve survival. Liver Transplantation. 2020;**26**(12):1644-1651. DOI: 10.1002/ lt.25875

[3] Chu HH, Yi NJ, Kim HC, Lee KW, Suh KS, Jae HJ, et al. Longterm outcomes of stent placement for hepatic venous outflow obstruction in adult liver transplantation recipients. Liver Transplantation. 2016;**22**(11):1554-1561. DOI: 10.1002/lt.24598

[4] Jang JY, Jeon UB, Park JH, Kim TU, Lee JW, Chu CW, et al. Efficacy and patency of primary stenting for hepatic venous outflow obstruction after living donor liver transplantation. Acta Radiologica. 2017;**58**(1):34-40. DOI: 10.1177/0284185116637247

[5] Arudchelvam J, Bartlett A, McCall J, Johnston P, Gane E, Munn S. Hepatic venous outflow obstruction in piggyback liver transplantation: Single centre experience. ANZ Journal of Surgery. 2017;**87**(3):182-185. DOI: 10.1111/ans.13344

[6] Hwang HJ, Kim KW, Jeong WK, Song GW, Ko GY, Sung KB, et al. Right hepatic vein stenosis at anastomosis in patients after living donor liver transplantation: Optimal Doppler US venous pulsatility index and CT criteria— Receiver operating characteristic analysis. Radiology. 2009;**253**(2):543-551. DOI: 10.1148/radiol.2532081858

[7] Someda H, Moriyasu F, Fujimoto M, Hamato N, Nabeshima M, Nishikawa K, et al. Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US. Journal of Hepatology. 1995;**22**(6):623-632. DOI: 10.1016/ 0168-8278(95)80218-5

[8] Krishna Kumar G, Sharif K, Mayer D, Mirza D, Foster K, Kelly D, et al. Hepatic venous outflow obstruction in paediatric liver transplantation. Pediatric Surgery International. 2010;**26**(4):423-425. DOI: 10.1007/s00383-010-2564-y

[9] Piardi T, Lhuaire M, Bruno O, Memeo R, Pessaux P, Kianmanesh R, et al. Vascular complications following liver transplantation: A literature review of advances in 2015. World Journal of Hepatology. 2016;**8**(1):36-57. DOI: 10.4254/wjh.v8.i1.36

[10] Tokunaga K, Furuta A, Isoda H, Uemoto S, Togashi K. Feasibility and mid- to long-term results of endovascular treatment for portal vein thrombosis after living-donor liver transplantation. Diagnostic and Interventional Radiology. 2021;**27**(1): 65-71. DOI: 10.5152/dir.2020.19469

[11] Cavalcante ACBS, Zurstrassen CE, Carnevale FC, Pugliese RPS, Fonseca EA, Moreira AM, et al. Longterm outcomes of transmesenteric portal vein recanalization for the treatment of chronic portal vein thrombosis after pediatric liver transplantation. American Journal of Transplantation. 2018;**18**(9):2220-2228. DOI: 10.1111/ajt.15022

[12] Neto JS, Fonseca EA, Feier FH, Pugliese R, Candido HL, Benavides MR, et al. Analysis of factors associated with portal vein thrombosis in pediatric living donor liver transplant recipients. Liver Transplantation. 2014;**20**(10):1157-1167. DOI: 10.1002/lt.23934

[13] Yerdel MA, Gunson B, Mirza D, Karayalçin K, Olliff S, Buckels J, et al. *Revascularization Strategies in Liver Transplantation DOI: http://dx.doi.org/10.5772/intechopen.104708*

Portal vein thrombosis in adults undergoing liver transplantation: Risk factors, screening, management, and outcome. Transplantation. 2000;**69**(9): 1873-1881. DOI: 10.1097/00007890- 200005150-00023

[14] Rizzari MD, Safwan M, Sobolic M, Kitajima T, Collins K, Yoshida A, et al. The impact of portal vein thrombosis on liver transplant outcomes: Does grade or flow rate matter? Transplantation. 2021;**105**(2):363-371. DOI: 10.1097/ TP.0000000000003235

[15] Shibata T, Itoh K, Kubo T, Maetani Y, Shibata T, Togashi K, et al. Percutaneous transhepatic balloon dilation of portal venous stenosis in patients with living donor liver transplantation. Radiology. 2005;**235**(3):1078-1083. DOI: 10.1148/ radiol.2353040489

[16] Sanada Y, Kawano Y, Mizuta K, Egami S, Hayashida M, Wakiya T, et al. Strategy to prevent recurrent portal vein stenosis following interventional radiology in pediatric liver transplantation. Liver Transplantation. 2010;**16**(3):332-339. DOI: 10.1002/lt.21995

[17] Cheng YF, Ou HY, Tsang LL, Yu CY, Huang TL, Chen TY, et al. Vascular stents in the management of portal venous complications in living donor liver transplantation. American Journal of Transplantation. 2010;**10**(5):1276- 1283. DOI: 10.1111/j.1600-6143. 2010.03076.x

[18] Sambommatsu Y, Shimata K, Ibuki S, Narita Y, Isono K, Honda M, et al. Portal vein complications after adult living donor liver transplantation: Time of onset and deformity patterns affect long-term outcomes. Liver Transplantation. 2021;**27**(6):854-865. DOI: 10.1002/lt.25977

[19] Singhal A, Stokes K, Sebastian A, Wright HI, Kohli V. Endovascular treatment of hepatic artery thrombosis following liver transplantation.

Transplant International. 2010;**23**(3): 245-256. DOI: 10.1111/j.1432-2277. 2009.01037.x

[20] Bekker J, Ploem S, de Jong KP. Early hepatic artery thrombosis after liver transplantation: A systematic review of the incidence, outcome and risk factors. American Journal of Transplantation. 2009;**9**(4):746-757. DOI: 10.1111/ j.1600-6143.2008.02541.x

[21] Li PC, Thorat A, Jeng LB, Yang HR, Li ML, Yeh CC, et al. Hepatic artery reconstruction in living donor liver transplantation using surgical loupes: Achieving low rate of hepatic arterial thrombosis in 741 consecutive recipients-tips and tricks to overcome the poor hepatic arterial flow. Liver Transplantation. 2017;**23**(7):887-898. DOI: 10.1002/lt.24775

[22] Banc-Husu AM, Anupindi SA, Lin HC. Resolution of hepatic artery thrombosis in 2 pediatric liver transplant patients. Journal of Pediatric Gastroenterology and Nutrition. 2016;**62**(4):546-549. DOI: 10.1097/ MPG.0000000000001016

[23] Feier FH, Melere MU, Trein CS, da Silva CS, Lucchese A, Horbe A, et al. Early hepatic arterial thrombosis in liver transplantation: Systemic intravenous alteplase as a potential rescue treatment after failed surgical revascularization. Pediatric Transplantation. 2021;**25**(5): e13902. DOI: 10.1111/petr.13902

[24] Heaton ND. Hepatic artery thrombosis: Conservative management or retransplantation? Liver Transplantation. 2013;**19**(Suppl. 2): S14-S16

[25] Ackermann O, Branchereau S, Franchi-Abella S, Pariente D, Chevret L, Debray D, et al. The long-term outcome of hepatic artery thrombosis after liver transplantation in children: Role of urgent revascularization. American Journal of Transplantation.

2012;**12**(6):1496-1503. DOI: 10.1111/ j.1600-6143.2011.03984.x

[26] Warnaar N, Polak WG, de Jong KP, de Boer MT, Verkade HJ, Sieders E, et al. Long-term results of urgent revascularization for hepatic artery thrombosis after pediatric liver transplantation. Liver Transplantation. 2010;**16**(7):847-855. DOI: 10.1002/ lt.22063

[27] Panaro F, Gallix B, Bouyabrine H, Ramos J, Addeo P, Testa G, et al. Liver transplantation and spontaneous neovascularization after arterial thrombosis: "the neovascularized liver". Transplant International. 2011;**24**(9): 949-957. DOI: 10.1111/j.1432-2277. 2011.01293.x

[28] Grimaldi C, di Francesco F, Chiusolo F, Angelico R, Monti L, Muiesan P, et al. Aggressive prevention and preemptive management of vascular complications after pediatric liver transplantation: A major impact on graft survival and long-term outcome. Pediatric Transplantation. 2018;**22**(8): e13288

[29] Pereira K, Salsamendi J, Dalal R, Quintana D, Bhatia S, Fan J. Percutaneous endovascular therapeutic options in treating posttransplant hepatic artery thrombosis with the aim of salvaging liver allografts: Our experience. Experimental and Clinical Transplantation. 2016;**14**(5):542-550. DOI: 10.6002/ect.2015.0189

[30] Figueras J, Busquets J, Dominguez J, Sancho C, Casanovas-Taltavull T, Rafecas A, et al. Intra-arterial thrombolysis in the treatment of acute hepatic artery thrombosis after liver transplantation. Transplantation. 1995;**59**(9):1356-1357

[31] Boyvat F, Aytekin C, Karakayali H, Ozyer U, Sevmis S, Emiroğlu R, et al. Stent placement in pediatric patients with hepatic artery stenosis or

thrombosis after liver transplantation. Transplantation Proceedings. 2006;**38**(10):3656-3660. DOI: 10.1016/j. transproceed.2006.10.169

[32] Zhou J, Fan J, Wang JH, Wu ZQ, Qiu SJ, Shen YH, et al. Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation. Transplantation Proceedings. 2005;**37**(10):4426-4429. DOI: 10.1016/j.transproceed.2005.10.113

[33] Saad S, Tanaka K, Inomata Y, Uemoto S, Ozaki N, Okajima H, et al. Portal vein reconstruction in pediatric liver transplantation from living donors. Annals of Surgery. 1998;**227**(2):275-281. DOI: 10.1097/00000658-199802000- 00018

[34] Semba CP, Bakal CW, Calis KA, Grubbs GE, Hunter DW, Matalon TA, et al. Alteplase as an alternative to urokinase. Advisory Panel on Catheter-Directed Thrombolytic Therapy. Journal of Vascular and Interventional Radiology. 2000;**11**(3):279-287. DOI: 10.1016/s1051-0443(07)61418-3

[35] Laštovičková J, Peregrin J. Percutaneous transluminal angioplasty of hepatic artery stenosis in patients after orthotopic liver transplantation: Mid-term results. Cardiovascular and Interventional Radiology. 2011;**34**(6): 1165-1171. DOI: 10.1007/s00270-010- 0082-x

## **Chapter 6**
