Embolization Therapy: Principles and Clinical Applications, 1 Ed.

Peripheral Vascular Malformations

Jose Luiz Orlando • Francisco Ramos • Bruno C. Odisio

Peripheral vascular malformations arise as a result of a focal vascular differentiation embryologic failure leading to an abnormal development of the vascular system. They are responsible for important functional and aesthetic changes that often impact on the individual’s daily routine. Diagnosis and treatment of this condition is still considered challenging in view of the various presentations and complexity levels of lesions.

CLASSIFICATION AND DESCRIPTION

Mulliken and Glowacki1,2 described in 1982 a useful classification system, which gained acceptance by the scientific community based on the histologic findings, the flow characteristics, and the clinical aspects of the vascular anomalies. According to this classification, vascular anomalies fall into two major categories: hemangiomas and vascular malformations.1,2 Hemangiomas are not included in the scope of the this chapter and therefore will not be discussed.

Vascular malformations arise from dysplastic vascular channels. These channels, generally presented at birth, will grow in proportion to the development of the individual and will never suffer involution.1,3Although congenital, in approximately 10% of patients, the lesions cannot be identified at birth, appearing later triggered by hormonal stimuli during adolescence and gestation or exacerbating their symptoms after infection, thrombosis, or local trauma.4The vascular malformations were initially classified according to the prevalence of the vascular channels in five different forms: venous, lymphatic, capillary, arterial, or combined. In 1993, Jackson et al.,5 based on the classification system by Mulliken and Glowacki,1,2 reclassified vascular malformations considering its hemodynamic characteristics, dividing them into low- and high-flow lesions. The low-flow lesions are classified as venous malformation, lymphatic capillaries, or venolymphatic forms (capillary venous and the lymphatic–venous capillary lesions); the high-flow lesions are divided in arteriovenous malformations (AVMs) and arteriovenous fistulas.6 In 1996, this classification system was adopted and expanded by the International Society for the Study of Vascular Anomalies and is currently widely used.7

PATHOPHYSIOLOGY

The most accepted theory for the origin of vascular malformations is that they are caused by a total or partial agenesis of the capillary bed of a given territory. This agenesis would be associated with primitive persistent arteriovenous communications that constitute the AVM nidus.8 The AVMs are basically characterized by presenting abnormal communications between the arterial and venous system, without the interposition of the capillary network. These shunts are, in most cases, multiple and configured as a conglomerate of vessels known as vascular nidus.9 The advent of digital subtraction selective angiography along with the development of microcatheterization techniques allowed the angioarchitecture of these lesions to be identified with greater precision. The angioarchitecture is divided into three distinct segments: nourishing artery(ies), a nidus, and the draining vein(s).10

The nourishing arteries can be classified as direct or indirect branches and can present as single or multiple branches. The direct branches directly supply the region of the vascular nidus and, in general, have a large diameter. The indirect branches supply the nidus and the surrounding tissues and may have blood flow opposite to its natural direction through anastomoses with neighboring arteries, where other arterial segments participate in the nutrition of the tissue. In this case, the preexisting arterioarterial anastomosis increases their caliber and promotes the passage of blood flow in a reversed direction. This compensatory phenomenon, characterized by the recruitment of collateral vessels to reconstruct the arterial supply distal to the AVM, is usually present in high-flow AVMs.11

The vascular nidus represents the core of the AVM and is interposed between the distal segment of the feeding artery(ies) and the proximal segment of the draining vein(s).12 These arteriovenous communications are called shunts and are responsible for the secondary angiopathy induced by the increased blood flow. The nidus is a complex vascular structure and can be presented in three distinct patterns (Fig. 27.1):

• Plexiform: composed of a tangle of arteriolar and venular structures with a coiled and wrapped aspect. In this pattern, the supplying arteries ends in a cluster of multiple vessels with arteriovenous communications in which one or multiple channels emerge as the venous drainage.

• Fistulas: characterized by the presence of communication between artery and vein called arteriovenous fistulas. In this case, one or multiple arteries of anomalous path starting from a truncal artery empties into the venous system directly or in a venous lake located, for example, in the compartment muscle or subcutaneous tissue.

• Mixed pattern: a combination of both patterns mentioned earlier, with a predominance of one over the other. The nidus may also be constituted by one or more compartments.

The AVM draining veins corresponds mostly to the topography of the lesion and can be classified as deep or shallow. Drainage can occur from multiple compartments to a single main draining vein or smaller caliber accessory veins. Additionally, a single drainage vein from the AVM may branch into other veins, which can be confused with multiple draining veins (Fig. 27.2).

CLINICAL EVALUATION

Vascular malformations can occur anywhere in the body and can have either a localized or extensive distribution pattern. Commonly, its diagnosis is the result of a clinical history and detailed physical examination. The clinical presentation of peripheral AVMs is diverse and can range from asymptomatic to disabling pain cases. The presence of pain may be related to the presence of mass effect, varicose veins, thrombophlebitis, bone erosion, and mixed-origin ulcers caused by venous hypertension due to ischemia caused by preferential blood flow to the vascular malformation in detriment of the normal tissues.1,13

The lesions on the extremities are characterized by the presence of pulsatile tumor of firm consistency and slightly compressible, with thrill or murmur that result from turbulent blood flow.14 Other characteristic findings of these injuries are a wide arterial pulse and the presence of a prominent proximal venous drainage, generally elongated and tortuous. Additionally, changes may occur secondary to the ischemia and the venous hypertension such as edema, skin pigmentation, stasis eczema, ulcers, and gangrene13,15 (Fig. 27.3). The hypertrophy of the involved extremity is a frequent finding and may be evident only in late childhood.16,17 Pelvic AVMs are characterized by an increased soft tissue mass and can cause severe pain, pelvic congestion, sexual dysfunction, and hemorrhage.1820 In the presence of a large number of high-flow fistulae, congestive heart failure can occur in varying degrees as a result of cardiac overload.21

IMAGING EVALUATION

The use of different imaging modalities is an essential tool for differentiating between the different types of vascular malformations and between these and soft tissue tumors, assessing the exact extension of the lesions, and correlating the findings with other anatomical structures involved. The most common imaging modalities used in the diagnosis of vascular abnormalities are the ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT), and angiography.

US is considered the imaging modality of choice for the initial evaluation of patients with soft tissue lesions of possible vascular origin.22,23 The US Doppler allows characterizing the morphologic and hemodynamic aspects of the vascular malformations. The color mapping allows distinguishing the afferent arteries constituted of elongated and tortuous vessels, the nidus that is characterized by a conglomerate of vessels in the core of the lesion, and the draining veins. The hemodynamic changes in high-flow vascular malformations are characterized by the presence of a biphasic pattern with high systolic and diastolic velocities, indicating low resistance due to the presence of shunts. The nidus is recognized by the presence of high-velocity turbulent flow with a mosaic of colors. The venous segment of the malformation presents with a high-flow monophasic pattern that might be associated with some pulsatile pattern (Fig. 27.4). The MRI allows for assessment of the extent of the injury and its relationship to adjacent anatomical structures. It is also useful in differentiating between lesions of high and low flow.3,24 AVMs are characterized as areas of absence of signal (flow-void) on T1 and T2 weighted sequences corresponding to the nurturing arteries and the nidus15,25 (Fig. 27.5). MRI can also help in the differential diagnosis of tumors. Noteworthy are the proliferative hemangiomas that, despite showing hyperintense signal on T2 sequences and intermediate signal on T1 and areas of flow voids, has a well-defined and lobulated contours.3,23,26 Other tumors such as sarcomas, neuroblastomas, hemangiopericytomas, fibrosarcomas, and rhabdomyosarcomas exhibit features of tissue invasion that can be associated with perilesional edema.23,2729 CT provides limited information regarding the extent of the lesion, generally underestimating its size and its flow characteristics when compared to MRI. The use of ionizing radiation is also another disadvantage associated with this method. CT can be useful in the differential diagnosis with soft tissue tumors to evaluate its mass effect and provide more detailed evaluation of changes in the adjacent structures such as bone erosions, periosteal reaction, pathologic fractures, and presence of phleboliths. The phlebolith lesions are characteristic of venous malformations.30 The use of angiography involves the selective catheterization of all pedicles involved for a complete study of the extension of the lesion and its flow characteristics. The angiographic findings of AVMs include feeding artery(ies) with increased caliber and tortuous path, a conglomerate of arteries and veins (nidus), and an early venous filling segment characterized by elongated and large-caliber veins12,31 (Fig. 27.6). An alternative access by direct puncture of the nidus transcutaneously allows for evaluation of extension and flow characteristics31,32 (Fig. 27.7).

TREATMENT

The treatment of AVMs is still a challenge for surgeons and interventional radiologists.33,34 Surgical treatment is usually associated with some technical difficulties due to the absence of a cleavage plane between the lesion and surrounding tissue, bleeding, and inaccessible location. Surgical ligation of the nourishing arteries is ineffective and often results in recurrence of the lesion by the recruitment of numerous arterial and venous branches.17,18,20,3538The introduction of selective catheterization techniques created the possibility of implementing the treatment of vascular malformations through embolization. The evolution and development of new products and the introduction of microcatheters with smaller diameters allows greater selectivity of feeding vessels, making embolization the treatment of choice for vascular AVMs.15,19,39 For a proper treatment planning, it is essential to perform a diagnostic angiography for the study of the vascular anatomy of the lesion and its hemodynamic pattern.21,40 The goal of AVM embolization is the occlusion of the feeding vessels of the vascular nidus, avoiding areas of nontarget embolization (Fig. 27.8). The choice of the embolic material should be based on the lesion’s angioarchitecture, size, length, number of involved vessels, flow characteristics, and pattern of venous drainage.12,41 The limitations to a satisfactory embolization include the presence of elongated and tortuous branches and aneurysms that hinder the progression of the catheter (Figs. 27.9 and 27.10) and the presence of indirect branches or anastomoses nourishing the malformation that prevent the placement of the microcatheter within the nidus (Fig. 27.11). Additionally, these indirect branches may also supply adjacent normal tissues, increasing the risk of nontarget embolization. Most AVMs present both types of nurturing branches, and success of treatment depends on the ability to select the vascular nidus with the microcatheter.12

DEVICE/MATERIAL DESCRIPTION

Guiding Catheters and Introducer Sheaths

Guiding catheters or long introducer sheaths are frequently used to secure access. It also provides stability during catheter exchanges, which is especially useful in situations when the embolic agents occlude the catheter. A guiding catheter or a long introducer sheath is typically tracked over a 0.035-in guidewire and secured close to or at the orifice of the feeding branches, such as a branch of hypogastric artery for a pelvic AVM and a branch of profunda femoral artery for a thigh AVM.

Coaxial Catheter System

Successful embolization of the nidus of an AVM often requires selective catheterization of numerous arterial feeding branches. This is facilitated by using coaxial microcatheter systems. The microcatheter is coaxially introduced through 4-Fr or 5-Fr diagnostic catheter and can be manipulated into the terminal feeding artery. Embolic agents are then delivered via a variety of end-hole microcatheters ranging from 1.5-Fr to 3.0-Fr (most commonly 2-Fr to 2.4-Fr).

Embolic Agents

Glue or tissue adhesive, such as N-butyl cyanoacrylate (NBCA) (Histoacryl; B. Braun Melsungen AG, Melsungen, Germany) and Glubran 2 (GEM Srl, Viareggio, Italy),42 is classified as a liquid, adhesive, nonabsorbable, permanent embolic agent. Tissue adhesives offer great versatility due to the ability to use different dilutions (i.e., proportion of Ethiodol and glue in the solution) in various types of AVM. The tissue adhesive consists of an N-Butil-2 monomer linked with ciano group and connected to carbon radicals that, when in contact with ionic substances such as normal saline or blood, activates the glue polymerization process through the union of molecules of ethylene.43 The liquid nature of this agent allows its passage through microcatheters which, when released very near or within the region of the nidus, initiates a polymerization process that forms a framework around it, occluding blood circulation. Its association with iodized poppy seed oil (Lipiodol UF; Guerbet USA, Bloomington, Indiana) gives radiopacity to the solution and retards the polymerization time, facilitating its handling.44 In the mixture of glue and Lipiodol, the higher the proportion of Lipiodol (for example 3:1 of Lipiodol/glue, respectively), the longer it will take for the glue to get polymerized (solid). The reverse is also true. The higher the concentration of glue (for example 1:3 of Lipiodol/glue, respectively), the faster will be the polymerization time (see Chapter 9).

Onyx (Covidien, Irvine, California) is a liquid, nonadhesive, nonabsorbable, permanent embolic agent.45 Onyx is composed of a certain percentage of ethylene vinyl alcohol (EVOH) copolymer dissolved in dimethyl sulfoxide (DMSO) and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy. It was approved in 2005 for the treatment of AVMs by the U.S. Food and Drug Administration. Its use has been progressively extended to other pathologies.46 It is recommended using specific delivery microcatheters compatible with DMSO: Marathon, Rebar, or UltraFlow HPC (Covidien, Irvine, California).

Its composition consists of 48 mol/L of ethylene and 52 mol/L of vinyl alcohol dissolved in DMSO and associated with the tantalum powder at a concentration of 35% weight per volume to make the product radiopaque.

This product is commercially available in different concentrations The density of Onyx is defined by the concentration of the EVOH varying from 6% to 8%. Onyx is available in three formulations: Onyx 18 (EVOH concentration of 6%), Onyx 34 (8% EVOH), and Onyx HD500 (20% EVOH). Peripheral AVMs are usually treated with Onyx 18. Use of this product requires preparation for a period of 20 minutes in a mixer provided by the manufacturer so that the copol-ymer is mixed homogeneously with the tantalum powder. The active principle of Onyx precipitates upon contact with saline, water, or blood. The solvent DMSO prevents precipitation of Onyx (see Chapter 10).

TECHNIQUE

The access route for embolization is initially established by puncture and catheterization of the artery ipsilateral or contralateral depending on the location of the lesion. The microcatheters are introduced through larger caliber catheters (coaxial system) and kept under continuous infusion in saline. Heparin is used at a dose of 100 units per kilogram of weight with a maintenance bolus dose of 1,000 units per hour. The anticoagulation is used routinely in our practice, but currently, there is no consensus about using it in all AVM embolization cases. The guiding catheter is positioned selectively in the feeding vessel proximal to the lesion, from which are introduced microcatheters ranging from 1.5-Fr to 3.0-Fr depending on the vessel to be treated. Road mapping technique can be used for superselective nidus microcatheterization.

Tissue Adhesive Embolization Technique

The cyanoacrylate is diluted in Lipiodol in proportions ranging from 1:1 to 1:8 depending on the lesion flow characteristics.44,47 The microcatheter is filled with dextrose 5% until immediately before embolization. This maneuver is intended to prevent early polymerization of the glue on the catheter upon contact with blood (dextrose has similar role as the DMSO has in Onyx embolization). The injection of glue through the microcatheter is performed in a slow fashion and under fluoroscopic control until it reaches the end of the microcatheter. The progression of glue inside the nidus is influenced by the dilution and injection pressure applied in the plunger of the syringe. One of the risks associated with cyanoacrylate embolization is the possibility of the catheter adhering to the vessel, preventing its withdrawal. Maneuvers used to minimize this risk include the use of solutions with a lower concentration of cyanoacrylate and heating to reduce its viscosity. Under microcatheter aspiration (negative pressure applied in the syringe connected to the hub of the microcatheter), it also should be quickly pulled out as soon as a satisfactory embolization is achieved.

Onyx Embolization Technique

The first step is to purge the catheter with saline to clear any contrast residue and then prime with solvent solution DMSO. The amount of DMSO required for this will be determined by prior knowledge of the internal lumen of the catheter to be used (microcatheter dead space information is available in the package label). After filling the microcatheter with DMSO, Onyx is aspirated into a syringe provided by the manufacturer and connected to the microcatheter, forming an interface between the DMSO present within the microcatheter and the syringe with Onyx. This is done with the intent of preventing early polymerization and catheter occlusion by the contact of Onyx with blood or saline in the microcatheter. It is recommended that the injection of Onyx is to be performed at a rate of 0.1 to 0.2 mL per minute to promote a slow release and contact of the DMSO with arterial endothelium. The contact of DMSO with the endothelium of the vessel may cause vasospasm, angionecrosis, and/or pain, which is more likely to happen if the injection of the solvent occurs quickly.48 The injection pressure should be sufficient enough to promote progression of the Onyx within the artery and prevent reflux toward the catheter. Reflux is acceptable but should not involve more than 1.0 to 1.5 cm of the distal aspect of the microcatheter. Despite the fact that Onyx is not being considered an adhesive agent, its prolonged injection time followed by reflux around the microcatheter can create difficulties in removing the catheter. The removal of the catheter after the end of the embolization should occur smoothly and progressively. Abrupt maneuvers to remove it increase the risk of rupture of the artery or catheter, increasing the morbidity related to treatment.

Direct Puncture Using Tissue Adhesive Embolization Technique

Catheter embolization can be contraindicated due to lack of an arterial access. It can be related to previous surgical bandages, inadequate embolization proximal to the nidus, presence of marked tortuosity of the vessels supplying the vascular nidus, and the presence of arteriovenous anastomoses that may preclude selective catheterization. For direct puncture of the lesion, various needle lengths can be used according to the depth of the lesion. Superficial lesions can be addressed under direct vision. Deep lesions generally require ultrasound or angiography guidance. The choice of embolic agents relies on the same criteria already established in the intra-arterial embolization and experience of the operator.

CLINICAL APPLICATIONS

The treatment of AVMs is indicated in symptomatic cases or in those with deformities that interfere with daily activities. For a successful embolization, it is necessary to know the angioarchitecture of the lesion, selective catheterization of the supplying vessel(s), and injection of the embolic agent within the nidus. In our experience, the use of systemic heparin and perfusion catheter with saline solution helps to prevent thromboembolic complications. General anesthesia, spinal block, or conscious sedation is mandatory to keep the patient comfortable and steady during the procedure. The angiography is the standard test to characterize the vascular nidus and define treatment. The presence of early opacification of the draining vein(s) during the arterial phase is compatible with arteriovenous fistula. In the presence of a plexiform nidus, a cluster of anomalous and tortuous vessels is generally identified preceding the opacification of the draining veins. In low-flow lesions, it is necessary to perform selective microcatheterization of the branches of small caliber directly related to nutrition of the AVM to define its angioarchitecture.

Embolization may be performed with liquid or solid embolic agents. Liquid agents are the most suitable for the permanent occlusion of AVMs. The embolization success depends on the proper use of the technique and selective occlusion of the malformation without compromising the perfusion of surrounding normal tissues. Onyx has a particularly good applicability in the treatment of AVMs with massive plexiform nidus or nourished by multiple branches. Contrarily, it is not used in the presence of high-flow arteriovenous fistulas, where cyanoacrylate typically is a better embolic agent, with or without flow control techniques assistance.

Cyanoacrylate acts differently from Onyx and promotes vascular occlusion through the process of polymerization, which varies according to the concentration used in dilution with Lipiodol. The technique of injection of cyanoacrylate can vary from slow to fast depending on the dilution chosen and the pattern of intralesional flow. For plexiform AVM lesions, bulky lesions, or low-flow lesions, we recommend using the cyanoacrylate, which can be diluted to low concentrations (15% to 20%). On the other hand, cyanoacrylate can be used in higher concentration solution, ranging from 50% to 70%, in the embolization of high-flow fistulas. In slow-flow lesions nourished by arteries of small caliber in which it is not always possible to position the microcatheter in the nidus, the injection of diluted cyanoacrylate (20% to 30% concentration) is usually effective, allowing satisfactory penetration within the distal aspect of the lesion. Flow reduction techniques may help obtain better control of the injection of the embolic agent. Blood pressure cuffs, tourniquets, or local external compression performed proximal to the lesion can also be used and can contribute to the prevention of nontarget embolization. It favors the agent penetration within the nidus as it delays the progression of the embolic agent into the draining veins. Postembolization angiography is necessary to check the effectiveness of the procedure and at the same time assess the need for reintervention.

There is no consensus in the literature about the ideal way to perform AVM embolization. The treatment may be carried out in a single session to obtain occlusion of the entire lesion or in multiple sessions. Multiple sessions are generally indicated in lesions of great extension to reduce the side effects related to hemodynamic alterations that are responsible for the appearance of edema or hemorrhage.49 The use of particulate agents, such as microparticles, has a temporary effect in promoting vessel occlusion, lasting only a few days, and is not sufficient to promote complete thrombosis, causing recurrence. In addition, high-flow AVMs with large fistulas can promote migration of the particulate agents into the venous system, pulmonary circulation, and potentially to the systemic circulation in case of right-to-left heart shunt, without occluding the fistula. Coils also have limited use because of technical difficulties in obtaining suitable deployment within the fistula, often leading to a proximal occlusion of the artery. In fact, in addition to not occluding the fistula, it also creates a proximal mechanical barrier that potentially precludes proper selective catheterization of the fistula to perform future embolizations of the lesion. For these reasons, the use of particles and coils are not indicated for the treatment of AVMs. The results of embolization may vary from the complete disappearance of symptoms and control of the lesion until partial improvement, meaning a palliative measurement in the treatment of complex lesions, providing comfort and improved quality of life for the patient5052(Fig. 27.12).

POTENTIAL COMPLICATIONS

Although infrequent, complications occurring after AVM embolization are still present in the daily practice. Patients should be informed of the potential risks of treatment. Skin necrosis is one of the potential complications and can be aggravated by infection and bleeding. Other potentially more serious complications include ischemia of organs and tissues as a result of nontarget embolization12,53 (Fig. 27.13). Although less frequent in the treatment of AVMs than in embolization or visceral tumors, the postembolization syndrome can occur after AVM embolization. Symptoms and signs such as pain, fever, leukocytosis, and nausea occur shortly after the procedure and usually resolve within a few days; however, they may persist for more than a week.13

TIPS AND TRICKS

Tips

Angiographic Findings

Characteristics

Arteriovenous fistula

Immediate opacification of artery and vein

Nidus

Conglomerate of arteries and veins

Arterioarterial anastomosis

Large artery that supplies the nidus via a smaller caliber artery

Indirect branches

Arterial branch that supplies normal surrounding tissues and the nidus

Tricks

CONCLUSION

Despite the advances of percutaneous embolization in the treatment of vascular malformations and the low incidence of complications associated with it, only symptomatic patients should be considered for treatment,51 avoiding the treatment of AVM for cosmetic reasons.

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