Continuing Education Activity

Venous stenting is recognized as a possible treatment to help assist patients with symptomatic iliocaval venous obstruction as an alternative to traditional surgery. Iliocaval venous obstruction contributes to the morbidity of chronic venous insufficiency and chronic venous hypertension. This activity reviews the evaluation and treatment of patients with obstructive iliocaval venous obstruction. It highlights the role of the interprofessional team in evaluating and improving care for patients who undergo iliac vein stenting.

Objectives:

• Review the risk factors in identifying patients with iliocaval vein obstruction that benefit from iliiocaval venous stent placement.
• Summarize the current trials relating to iliocaval venous stent placement.
• Explain the common complications associated with iliocaval venous stents.
• Outline the importance of monitoring for post iliocaval venous stenting patients to minimize complications from anticoagulation or early stent failure.

Introduction

Awareness in the treatment of venous disorders through the use of stents has increased over the past decade. Venous stenting is recognized as a possible treatment to help assist patients with symptomatic iliocaval venous obstruction (ICVO) as an alternative to conventional surgery. ICVO contributes to chronic venous insufficiency and chronic venous hypertension.  Symptoms of ICVO include venous claudication, chronic edema and/or venous ulceration, and other manifestations of post-thrombotic syndrome.[1] 

Women and patients with a history of deep venous reflux diagnosed on duplex scans have a higher incidence of ICVO.[2] ICVO may be secondary to iliofemoral deep vein post-thrombotic obstruction (PTO) or non-thrombotic iliac vein lesions (NIVLs, formerly referred to as May-Thurner syndrome).

Hemodynamically significant ICVO may compromise the effectiveness and even causes worsening of symptoms with routine compression therapy and exercise for limb swelling. The use of stenting procedures to treat ICVO, including involvement into the inferior vena cava, has acceptable patency rates and reduction in symptoms in most patients.[3] In a published study with over 1500 patients, iliac vein stenting for ICVO was considered being safe with high patency rates of up to 5 years. Improvement in pain, ulceration, and limb swelling were noted.[4] A follow-up meta-analysis of 37 studies demonstrates good technical success, with minimal periprocedural complications and symptom relief at final follow-up for 5 years. Complication rates are less than 1% for major bleeding, pulmonary embolism, and mortality, with 1.0% to 6.8% for early stent thrombosis.[5]

The initial use of self-expanding stents for the treatment of ICVO employs an endoprosthesis stent consisting of a braided, self-expanding stent composed of cobalt, chromium, and nickel alloy. Early venous stents comprise large diameters, radial force, compression, and fracture resistance. However, its deployment accuracy could be imprecise due to stent foreshortening. The radial force is only present in the body, and thus the stent could collapse at the ends due to the Poisson effect of biomechanical forces.[6] The point of maximal compression in patients with NIVL is between the left common iliac vein (CIV) and the inferior vena cava (IVC). These factors can make it difficult to place the stent with accuracy. 

Most initial venous stents were not designed for use in the venous system.  Initial stent development focused on addressing these challenges by increasing the crush resistance needed in venous stents.[7] Several venous stents have received FDA approval after investigational device exemption trials. These nitinol stents differ in whether they consist of a closed-cell or open-cell configuration. The mechanism of deployment, whether coaxial or triaxial, also varies between the stents. Except for the recent recall of two stents secondary to the improper deployment, these trials demonstrate acceptable efficacy and safety.[8][9][10] 

Based on prior consensus clinical practice guidelines, iliac stenting assists in significantly increased ulcer healing.[11] Primary treatment of iliocaval stenting for obstructive disease without superficial truncal reflux is suggested as first-line treatment in a symptomatic patient with skin or subcutaneous changes, healed or active ulcers.[12]

Indications

In patients with acute deep venous thrombosis (DVT) who have undergone thrombolysis, iliac stenting improves vessel patency and lowers PTO rates.[13] In patients with chronic PTO, the anatomy of the vessel and addressing the symptoms are important. Symptoms may include pain, edema, and nonhealing venous ulcerations without improvement from conservative measures, including infrainguinal intervention.

Symptoms in patients with NIVL can vary and can involve chronic pelvic pain, venous claudication, and edema. However, anatomic considerations do not always correlate with patient symptoms. Some patients with anatomic venous compression found on imaging are asymptomatic.[14] Prophylactic venous stenting of asymptomatic patients with anatomic venous compression is discouraged. There are many causes of lower extremity edema, and further workup to determine the primary etiology of lower extremity edema is prudent to ensure that venous stenting is warranted to obtain the best outcomes for the patient.[12]

Contraindications

Among the potential contraindications for iliocaval stenting, women of the child-bearing age group were evaluated. The results supported the safe stent implantation and the definitive demand for a timely follow-up.[15]

Preparation

Initial diagnostic workup may include a variety of imaging techniques. CT venography, intravascular ultrasound (IVUS), MRI venography, and multiplanar venography have been useful in verifying a diagnosis, including the determination of external compression. Duplex ultrasonography and plethysmography may help evaluate DVT and venous obstruction but are best used in conjunction with other imaging techniques. Contrast-enhanced ultrasound and other provocative maneuvers with duplex ultrasound may delineate hemodynamic significance at rest and improve accuracy.[16] 

Prior published literature demonstrates that using duplex ultrasound, a > 50% venous diameter reduction at the point of compression and peak velocity ratio > 2.5 in the area of compression in the internal iliac vein indicate clinically significant stenosis.[17] A combination of multiplanar venography and IVUS are gold standards for proper stent placement to identify the degree of stenosis and length of the disease. In the case of PTO, venography demonstrates collateral flow and indirect flow. Oblique or lateral views localize the wire anterior to the spine. For patients with symptomatic NIVL, venography demonstrates compression with prestenotic dilatation, contrast stagnation, retrograde flow in the internal iliac vein, and collaterals. For NIVL lesions, IVUS is used to confirm the degree of cross-sectional area reduction in the area of compression. This reduction is compared to a normal segment of the CIV, whether ipsilateral or contralateral.[18] The VIDIO trial demonstrates that compared to multiplanar venography, IVUS is more sensitive in detecting lesions with > 50% cross-sectional area reduction, which may benefit from intervention.[19] 

Patient symptoms have a significant enough impact on quality of life to warrant their consideration due to the permanent nature of these stents. The diameter of veins can vary in size depending on patient position, hydration status, and respiration. Intravenous hydration and intraprocedural instruction to the patient to perform a Valsalva maneuver during IVUS can assist in determining accurate luminal measurements. IVUS is more sensitive to assessing treatable iliofemoral vein stenosis than multiplanar venography and frequently leads to revised treatment plans and the potential for improved clinical outcomes.[19] Additionally, in patients with NIVL, a threshold of >61% diameter stenosis by IVUS may better predict clinical improvement.[20]

Technique or Treatment

The choice of access vessel for stent placement depends on the venous disease's extent, location, and etiology. In patients with an acute DVT, stenting is often performed in conjunction with thrombolysis or mechanical thrombectomy. Venous access sites for acute interventions are commonly the popliteal vein and posterior tibial vein. The mid-femoral access has its advantages of avoiding prone positioning and jugular access if the femoral vein is diseased. In patients with chronic DVT, the extent of disease directs where the end of the venous sheath and stent are positioned. The greater saphenous vein can be accessed to cross a lower extremity occlusion by snaring the wire in the IVC placed via an internal jugular vein (IJV) access and redirecting the IJV wire into the profunda femoris vein or diseased femoral vein. Under venography, directing the stent landing at the lesser trochanter is optimal because of its location of the confluence of the profunda and femoral veins.

After obtaining access with a large sheath, confirmatory imaging is completed, and anticoagulation is given and maintained at an activated clotting time > 250 seconds during treatment. Patients with an acute DVT undergo lytic therapy with completion venography and IVUS to confirm acute thrombus clearance and stent placement for any residual underlying lesions. IVUS imaging is performed, and the percentage stenosis is estimated by comparing the stenotic segment with an area of normal adjacent iliac or common femoral vein (CFV). The vein diameter on IVUS is calculated by the average of the two cross-sectional diameters: transverse larger and perpendicular smaller diameter. For long-segment iliac vein stenosis, when it is difficult to determine the normal vein size, diameter measurements are compared to prior imaging. Known normal diameters of iliac veins for chronically occluded veins: 14 to 16 mm for the CIV, 12 to 14 mm for the external iliac vein (EIV), and 10 to 12 mm for the CFV.[21] 

The diagnosis of ICVO is based on a >50% reduction in the luminal diameter of the vein, with or without the presence of collateral formation. The radiopaque markers on the IVUS catheter will determine a more accurate assessment of the stent length needed to achieve placement in a non-diseased segment. Depending on the length, there may be a size discrepancy between the vessel diameters of the stent landing zones. IVUS can determine accurate assessment. Pre- and post dilatation of venous segments of the diameter is recommended with a high-pressure balloon. Serial dilatation with balloons of increasing diameter may be needed. Predilatation assists in allowing for accurate sizing and stent expansion. With inflation to nominal size, venography can be performed. Vein stent diameter is under measured if contrast is visualized passing around the balloon or if the balloon can be retracted easily. Post dilatation, especially for nitinol stents, provides the maximal resistive force of the stent.

Stents are oversized by 10% to 20% based on diameter measurements from IVUS. The pattern of iliac vein obstruction is classified based on anatomic involvement of the iliocaval venous outflow tract: type I, stenosis of a single venous segment; type II, stenosis of multiple venous segments; type III, occlusion of a single venous segment; and type IV, occlusion of multiple venous segments.[22] When a lesion requires two or more stents, the stents are overlapped by at least 2 cm. Completion multiplanar venography and IVUS are performed to demonstrate good flow and stent opposition to the wall.  Technical success is defined as recanalization of the vein with less than 20% antegrade flow compared with the normal adjacent iliac or femoral vein.[23]

There is a paucity of literature regarding post-procedural follow-up imaging to ensure stent patency and the duration of anticoagulation. After the procedure, patients undergo early ambulation, receiving anticoagulation and antiplatelet therapy according to the physician's discretion; with a history of acute or chronic DVT, patients transition to either a vitamin K antagonist or a direct oral anticoagulant (DOAC) for a variable period of time. For patients with a hypercoagulable state, DOACs are generally administered indefinitely. There are no clear recommendations regarding anticoagulation for patients with NIVL anticoagulation postprocedure. However, post-procedural imaging is usually performed within weeks of the procedure to assess for flow disturbance in the stents and the presence of any mural thrombus. Subsequently, patency is evaluated by duplex sonography at 3 months and 6 months and then at yearly follow-up. With duplex sonography, central and truncal veins are evaluated. Qualitative assessment is made regarding patency, presence of thrombus, phasicity, and augmentation with provocative maneuvers.[23]

Chronic, post-thrombotic iliofemoral, and ICVO is associated with debilitating morbidity. In the presence of a diseased or occluded CFV, failure is common. A hybrid operative procedure of open surgical CFV endovenectomy and endoluminal recanalization or bypass of the obstructed iliofemoral and vena cava segments has been developed and modified.[24] A hybrid approach involving venous stenting and open surgical intervention may be necessary.

Complications

Proper stent size is important to prevent adverse events can from stent migration.  Several venous-dedicated stents have been withdrawn due to issues with stent deployment and migration. If the cross-sectional view of the vein in the area of compression is not accurately measured and the stent is undersized, migration of the stent may occur. Stent migration to the right atrium and intraspinal canal has also been described.[25] However, oversizing a stent can lead to an increase in the incidence of post-procedure back pain.  Although rare, stent explantation has been reported secondary to persistent pain.[26]

The landing zones of stent placement are usually in areas without the involvement of the disease.  Significant inflow disease of the CFV is commonly the primary anatomic cause of stent failure. Thus, adequate inflow is important to obtain before the placement of a venous stent. Avoidance of stent placement at the pelvic curvature or flexion points such as the inguinal ligament can prevent straightening or kinking of the vein leading to possible stent thrombosis. PTO scar extending from the popliteal vein or common femoral vein to the CIV or inferior vena cava requiring multiple stents may be a prognosis for early stent graft failure. Jailing of the contralateral CIV may lead to subsequent contralateral DVT with recurrent ulcers.[27]

Clinical Significance

VIRTUS, a prospective, multicenter trial, demonstrates a twelve-month safety and effectiveness using a dedicated venous stent for ICVO demonstrate improvements in clinical symptoms and quality of life using the Venous Clinical Severity Score (VCSS) through 1-year follow-up.[28] A randomized double-blinded clinical trial demonstrates pain relief via visual analog scale and significant clinical improvement in the VCSS and SF-36 quality of life in patients randomized to iliac vein stenting versus best medical management. Although not statistically significant, the rate of venous leg ulcer healing demonstrates improvement.[29]

Despite successful endovenous thermal ablation vein closure, a 5-year symptom recurrence rate of 20.9% after endovenous thermal ablation (EVTA) could be due to the presence of underlying ICVO.[30] In a retrospective study, symptoms persisting during a mean of four months post EVTA that underwent vein stent placement result in further symptomatic relief in about one-third of patients treated with venous stenting.[31]

Enhancing Healthcare Team Outcomes

The use of venous stenting is increasing to improve symptoms due to venous outflow obstruction. Patient selection involves the assessment of the patient's clinical and anatomic presentation. Work up may involve the use of a multimodality imaging approach. Venous stenting for venous outflow disease can improve the quality of life and improve symptoms of pain, edema, and venous stasis ulcer healing rates.[28] [Level 1]

If criteria are met, prior infrainguinal procedures that fail to address the symptoms should be considered for venous stent placement.[31] [Level 3] Proper training of an interprofessional team is paramount in using venous stents to ensure safety and avoid complications. Nurses, advanced care practitioners, and other clinicians are involved with the workup, intraprocedural patient monitoring, and post-operative care. Post-operative care may involve anticoagulation and further imaging. Further algorithms for managing patients with ICVO are needed to determine the type and duration of anticoagulation and long-term follow-up.[23] [Level 3] Collaborative shared decision-making and communication amongst interprofessional team members are key elements for a good outcome.