Servier – Phlebolymphology

Roshanak Roustazadeh, MD
Department of Vascular Surgery,
European Venous Center,
University Hospital RWTH Aachen,
Aachen, Germany

Mohammed E. Barbati,
MD, FEBVS
Department of Vascular Surgery,
European Venous Center,
University Hospital RWTH Aachen,
Aachen, Germany

Morteza Shahbandari
Ghouchani, MD
Department of Vascular and
Endovascular Surgery, Isfahan
University of Medical Sciences,
Isfahan, Iran

Efthymios D. Avgerinos,
MD, FACS, FEBVS
2nd Department of Vascular
Surgery, Laiko General Hospital,
University of Athens, Greece

Houman Jalaie, MD, PhD
Department of Vascular Surgery,
European Venous Center,
University Hospital RWTH Aachen,
Aachen, Germany

ABSTRACT

Chronic venous obstruction (CVO) is a debilitating condition affecting millions of individuals, leading to significant morbidity and reduced quality of life. This review aims to explore innovative strategies and evidence based approaches to enhance the management and long-term outcomes of patients with CVO. Accurate diagnosis and assessment of CVO severity is crucial for guiding appropriate treatment. Noninvasive techniques like duplex ultrasonography, computed tomography (CT) venography, and magnetic resonance (MR) venography can provide detailed information about the venous system. Invasive venography remains the gold standard for evaluating the extent and severity of venous obstruction. Conventional conservative treatments, such as compression therapy, play a crucial role in CVO management. Compression stockings can improve venous return, reduce edema, and alleviate symptoms. Compression therapy has also been shown to enhance the effectiveness of other interventions, such as endovascular procedures. Emerging treatment modalities, including endovascular venous reconstruction and adjunct surgical endophlebectomy, offer promising alternatives for patients with CVO. Endovascular techniques, such as stenting and angioplasty, can effectively restore venous patency and improve clinical outcomes. Surgical endophlebectomy may be considered in complex cases where endovascular options are limited. Multidisciplinary care, involving vascular specialists, wound care experts, and physical therapists, is essential for optimizing patient outcomes. Ongoing research and clinical trials are further exploring innovative strategies to improve the management and long-term prognosis of individuals with CVO.

Introduction

Chronic venous obstruction (CVO) is a debilitating condition that affects millions of individuals worldwide, often leading to pain, swelling, venous claudication, and ulceration and therefore significant morbidity and reduced quality of life.¹ CVO represents a significant public health concern, affecting a substantial portion of the population. Whereas precise prevalence rates vary depending on the population studied and the diagnostic criteria used, estimates suggest that chronic venous insufficiency, a broader category encompassing CVO, affects approximately 20 to 25 million adults in the United States alone.² The incidence of CVO rises with age, and risk factors include family history, female gender, obesity, pregnancy, prolonged standing, and a history of deep venous thrombosis.³ The impact of CVO extends beyond physical symptoms, significantly affecting patients’ quality of life. The chronic pain, swelling, and limitations in mobility can hinder daily activities, work productivity, and social interactions. Moreover, venous ulcers are challenging to treat and can lead to infections, cellulitis, and a significant decline in functional status. Patients with CVO often experience emotional distress, social isolation, and a reduced overall sense of well-being.⁴

The management of CVO requires a comprehensive approach that addresses both the underlying venous obstruction and the associated symptoms. Treatment options can be broadly categorized into conservative measures, such as compression therapy, wound care, and lifestyle modification, such as exercise and weight loss, and more invasive interventions, including endovascular venous reconstruction and in rare cases, adjunct surgical endophlebectomy.⁵

Despite the availability of various treatment modalities, improving clinical outcomes in these patients remains a challenging task for health care professionals. This review aims to explore innovative strategies and evidence-based approaches to enhance the management and long-term outcomes of patients with chronic venous obstruction.

Thorough diagnosis and severity assessment

Accurate diagnosis and assessment of CVO severity are crucial for guiding appropriate treatment strategies and improving the clinical outcomes. Various diagnostic tools are available, each with unique strengths and limitations. Duplex ultrasonography is a widely used noninvasive technique that can assess venous patency, reflux, and obstruction, with a reported sensitivity and specificity of 90% to 95%. According to European guidelines, duplex ultrasound should be the first line diagnostic modality for evaluating CVO due to its high accuracy, availability, and noninvasive nature.⁶ Computed tomography (CT) venography and magnetic resonance (MR) venography are advanced imaging techniques that can provide detailed anatomical information about the venous system, with sensitivities and specificities ranging from 80% to 95%. The 2022 European guidelines by De Maeseneer et al recommend considering CT venography and MR venography when additional anatomical information is needed, such as in complex cases or for treatment planning (Figure 1).^6,7

Invasive techniques, such as venography, remain the gold standard for evaluating the extent and severity of venous obstruction, with a sensitivity and specificity approaching 100%. The choice of diagnostic modality should be based on clinical presentation, resource availability, and health care provider expertise.

Figure 1. Multimodal imaging of chronic venous obstruction (CVO). A) Magnetic resonance venography (MRV) highlighting bilateral CVO. Yellow arrows indicate the presence of postthrombotic synechiae in the common femoral veins. Red brackets show the extensive collaterals developed due to the bilateral CVO. B) Duplex ultrasound displaying postthrombotic synechiae within the deep femoral vein in a patient with CVO extending below the inguinal ligament. C) Intravascular ultrasound (IVUS) of common femoral vein following the recanalization. The yellow dot marks the position of the IVUS catheter, and the red arrow points to the postthrombotic synechiae inside the vein.

Thorough diagnosis and severity assessment

Clinical venous and Villalta scores are key tools for assessing CVO severity. The venous clinical severity score (VCSS) focuses on obstruction and reflux, whereas the Villalta score evaluates postthrombotic syndrome (PTS) symptoms. A Villalta score of 10 to 14 signifies moderate PTS, and 15 or higher indicates severe PTS. These scores, correlating with obstruction extent, guide decisions regarding endovascular venous recanalization and are useful for evaluating symptoms improvement after venous recanalization.⁸

The CEAP classification, ranging from C0 (no visible signs) to C6 (active ulceration), assesses chronic venous disease severity. Higher classes indicate more advanced disease. This system comprehensively evaluates clinical, etiological, anatomical, and pathophysiological aspects, guiding treatment and monitoring progression.⁹

Conservative management

Compression therapy

Compression therapy is a well-established and crucial component in the management of CVO. Compression stockings apply external pressure on the lower extremities, which helps improve venous return, reduce edema, and alleviate symptoms like pain and heaviness. Studies have demonstrated that the use of compression stockings can significantly enhance the clinical outcomes of patients with CVO, including decreasing the risk of ulcer formation and recurrence. Furthermore, compression therapy has been shown to enhance the effectiveness of other interventions, such as endovascular venous stenting, by facilitating improved venous outflow and reducing the risk of postprocedural complications.¹⁰ Adhering to long-term compression therapy is essential, as it can help prevent the progression of the disease and improve the overall quality of life for patients with CVO.

Wound care and local therapies

Proper wound care is essential for the management of venous leg ulcers, which often develop as a result of CVO. The primary goals of wound care are to promote healing, prevent infection, and address any underlying factors contributing to the ulcer formation. Strategies for effective wound management include regular debridement, moisture-retentive dressings, and the use of advanced therapies like negative pressure wound therapy and bioengineered skin substitutes.^11,12 Additionally, local therapies such as intermittent pneumatic compression and topical medications like pentoxifylline or aspirin can be used to enhance the healing process and reduce the risk of recurrence.¹³

Anticoagulation and antithrombotic agents

Besides compression therapy, the use of anticoagulation and antithrombotic medications is a crucial component of the conservative management of CVO. Anticoagulation, particularly with vitamin K antagonists or direct oral anticoagulants (DOACs), has been shown to reduce the risk of recurrent thrombosis and the development of PTS.¹⁴

According to the 2022 European guidelines by De Maeseneer et al, DOACs are recommended as the preferred anticoagulant option for patients with CVO.⁶ DOACs have been found to be effective in reducing the risk of PTS and are associated with a lower risk of bleeding than are vitamin K antagonists. The guidelines suggest using DOACs for at least 6 months to 1 year, with the potential for longer-term anticoagulation depending on the individual patient’s risk factors and response to treatment.

In contrast, the evidence supporting the use of antiplatelet agents in the management of CVO is limited. Whereas antiplatelet drugs such as aspirin or clopidogrel may have a role in the prevention of arterial thrombosis, their efficacy in reducing the risk of PTS or improving clinical outcomes in patients with CVO has not been conclusively demonstrated.¹⁵ The 2022 European guidelines do not recommend the routine use of antiplatelet agents for the management of CVO as the potential benefits are outweighed by the risk of bleeding and other adverse events.⁶

Exercise and lifestyle modifications

Regular physical activity and healthy lifestyle choices can provide significant benefits for individuals with CVO.16 Exercise, such as walking, swimming, or other low-impact activities, has been shown to alleviate symptoms, reduce edema, and enhance overall quality of life in this patient population.^6,17 Similarly, maintaining a healthy body weight and adopting an active lifestyle can play a crucial role in managing the long-term consequences of CVO.^15,18 Jayaraj et al investigated the impact of body mass index (BMI) on initial presentation and outcomes of endovascular venous recanalization and stenting in 464 patients with CVO.19 Their findings suggest that whereas a higher BMI is associated with more severe venous hypertension symptoms, there were no significant differences in postprocedural clinical, stent patency, or quality-of-life–related outcomes between patients with normal, overweight, and obese BMI.¹⁹

Endovascular interventions for chronic venous
obstruction

Endovascular interventions have emerged as a crucial component in the management of CVO, offering a minimally invasive approach to address the underlying anatomical abnormalities and improve clinical outcomes. Endovascular venous recanalization, such as angioplasty and stenting, is recommended for symptomatic patients with iliofemoral venous outflow obstruction.^20,21 The procedure is considered when conservative treatment options, such as compression therapy and medication, have proven insufficient in managing the symptoms of CVO.^16,22-24 This minimally invasive approach aims to restore venous patency, improve venous outflow, and alleviate symptoms associated with CVO (Figure 2).^23-26 Several studies have demonstrated the effectiveness of endovascular interventions in improving clinical outcomes, reducing the risk of ulceration, and enhancing the quality of life for patients with CVO.^27-29

Implications of inflow disease on treatment outcomes

A range of underlying and technical factors influence the long-term success of endovascular interventions for CVO. Whereas technical aspects like stent design, material, and reconstruction technique can be optimized to improve long-term patency, it is crucial to recognize the impact of concurrent inflow disease on treatment outcomes.^20,22,30 The femoral vein and deep femoral vein play a vital role in inflow, providing the major return of blood from the lower extremities to the stented tract.²² The quality of inflow in these veins can be affected by factors such as vessel diameter, the degree of obstruction, and the extent of the pathology. Clinical evidence underscores the significance of inflow quality in determining stent outcomes. Several studies have investigated the impact of inflow on treatment success, revealing that patients with better inflow quality tend to experience more favorable long-term outcomes after stent implantation.^22,31

The International CVO Classification Study Group developed an inflow grading system (Jalaie classification) to assess the quality of venous inflow and inform appropriate treatment strategies.³⁰ This inflow classification is based on preoperative Doppler ultrasound findings of the abdominal, pelvic, and lower-extremity veins, which must be confirmed by at least 1 complementary imaging modality such as CT venography or MR venography to determine the extent of pathology. Patients are then categorized into one of 5 classification types according to the anatomical distribution of venous involvement (Figure 3).³⁰ This classification delineates 5 distinct categories based on the anatomical location and extent of the obstruction.

Figure 2. Phlebographic evaluation before and after stent deployment in left femoroiliac vein occlusion. A) Initial intraoperative phlebography illustrating the occlusion of the left femoroiliac veins, indicated by a red bracket. A spontaneous palmar collateral to the right side is highlighted with a yellow arrow. B) Final phlebography after stent deployment demonstrating an unobstructed washout of contrast through stents (green bracket). Notably, the previously visible collaterals have vanished, indicating successful alleviation of the venous obstruction and restoration of normal venous flow.

Figure 3. Classification system for chronic venous obstruction (CVO) of femoroiliac tract. This classification delineates 5 distinct categories based on the anatomical location and extent of the obstruction. After reference 30: Jalaie et al. Eur J Vasc Endovasc Surg. 2024:S1078-5884(24)00873-6. © 2024, The Author(s). Published by Elsevier B.V. on behalf of European Society for Vascular Surgery.

Figure 4. Intravascular ultrasound (IVUS) imaging of May-Thurner syndrome before and after stent placement. A) IVUS before stent implantation illustrates the left common iliac vein (v) being compressed by the overlying right common iliac artery (a), leading to a narrowed passage. B) IVUS after stent implantation: a stent (white dots) has been placed in the left common iliac vein (v) to relieve the compression by the right common iliac artery (a).

Intravascular ultrasound (IVUS) has become an indispensable tool in the management of CVO, playing a crucial role in both the diagnostic and therapeutic phases of endovascular venous recanalization and stenting.³⁷ Unlike conventional venography, which provides a two-dimensional luminal view, IVUS offers a real-time, cross-sectional visualization of the venous anatomy.³⁷ This detailed imaging modality allows for a comprehensive assessment of the location, extent, and severity of venous stenosis or occlusion, venous wall characteristics, and precise identification of external compression points, such as May-Thurner syndrome, which may contribute to venous obstruction (Figure 4A).^10,38

The use of IVUS during endovascular interventions significantly enhances procedural accuracy and effectiveness.³⁹ IVUS guidance is particularly valuable for deciding on the optimal landing zones and stent sizing, eg, precise stent length selection based on accurate measurements of the venous lumen.10 Furthermore, IVUS allows for accurate stent placement by ensuring optimal stent positioning (Figure 4B), spanning the entire length of the obstruction and minimizing the risk of stent malapposition or migration.

Moreover, IVUS enables the evaluation of the postintervention result, confirming the adequacy of the venous recanalization and the absence of residual stenosis, stent deformation, or procedural complications. Studies have demonstrated that the use of IVUS during endovascular venous recanalization and stenting is associated with improved clinical outcomes. IVUS-guided procedures have shown higher primary and secondary patency rates than venography-guided interventions.³⁹ The precise stent sizing and placement facilitated by IVUS minimize the need for reintervention. Last but not least, patients undergoing IVUS-guided interventions often experience greater improvement in symptoms, such as pain, swelling, and ulcer healing.^10,22

Emergence of dedicated stents

Dedicated venous stents offer several advantages over other stents commonly used for endovascular venous stenting.^40,41 These specialized stents are engineered specifically for the venous system, accounting for the unique anatomical and physiological characteristics of veins. Unlike stents primarily designed for the arterial system, dedicated venous stents exhibit enhanced flexibility and higher radial force, which aids in accommodating the natural compression and pulsatility inherent to the venous vasculature. Additionally, venous stents typically feature a longer length to address the extensive nature of venous obstructions.⁴² These design features contribute to improved conformability, decreased risk of venous wall injury, and enhanced long-term patency compared with the off-label use of arterial stents in the venous system.^41-43

Endophlebectomy for chronic venous obstruction

For patients with extensive type 4 and 5 CVO characterized by postthrombotic trabeculation involving the CFV and extending into the main inflow veins, the management remains challenging due to the impaired venous inflow.⁴⁴ In a highly selected subgroup of individuals with type 4b CVO, endophlebectomy, a specialized surgical intervention, may be considered. This procedure aims to remove the obstructive trabeculation from the CFV and the orifice of its tributaries, particularly the deep femoral vein (Figure 5).^45,46 When implemented in conjunction with iliac vein stenting, endophlebectomy can help provide adequate venous inflow by securing supply from the major side branches of the CFV, thereby mitigating the risk of early stent thrombosis.⁶

However, endophlebectomy is associated with a high rate of complications, such as bleeding and infection, which puts limits on its use in clinical settings.⁶

Figure 5. Intraoperative visualization of dissection of synechiae and postendophlebectomy clearance. A) Dissected intraluminal synechiae (yellow arrow) and B) the cleared vein after endophlebectomy. The presence of the guidewire in situ indicates successful recanalization. After reference 46: de Wolf et al. Br J Surg. 2017;104(6):718-725. Images provided courtesy of H. Jalaie.

Postprocedural care and surveillance

Postprocedural care and surveillance Postoperative care focuses on preventing in-stent thrombosis and ensuring long-term procedural success. Regular follow ups are essential to promptly detect and address any in-stent thrombosis or stenosis.⁶

Anticoagulation regimens after endovascular intervention

Adequate anticoagulation is essential after endovascular treatment for CVO. The procedure can induce a hypercoagulable state postoperatively, increasing the risk of early in-stent thrombosis, which is the most common early complication.⁴⁷ This underscores the critical importance of providing sufficient therapeutic anticoagulation both during and immediately after the procedure.⁴⁸ Maintaining appropriate anticoagulation in the initial 6 to 12 months is crucial to prevent thrombotic complications in the newly recanalized venous segments. Low-molecular-weight heparins are recommended for the first 2 weeks due to their anti-inflammatory and anticoagulant properties.49 Subsequently, low-molecular-weight heparins are often replaced by DOACs. In cases of ineffective anticoagulation or recurrent thrombosis with DOACs, a switch to vitamin K antagonists with a target international normalized ratio between 2.5 and 3.5 is recommended.^6,50 There is no consensus regarding the use of antiplatelet therapy yet.⁵¹

Compression therapy

Postoperative adjunctive compression therapy, along with early mobilization, plays a crucial role in maintaining early and long-term patency. Patients are advised to use class 2 open-toe compression stockings for at least 1 year postoperatively. Additionally, intermittent pneumatic compression devices may be utilized to support venous return. Compression therapy helps improve venous return, reduce edema, and prevent the development of PTS. It is an essential component of the comprehensive management approach for patients with CVO, complementing other interventions such as anticoagulation and endovascular procedures.^6,52,53

Follow-up and surveillance

Close postoperative surveillance with clinical examination and duplex ultrasound is essential to monitor stent patency and detect any complications in a timely manner, as recommended by the 2022 European guidelines on CVO.6 Thrombotic complications tend to occur early in the postoperative period, making it crucial to act quickly. The golden period to rescue a thrombosed stent using mechanical aspiration thrombectomy and thrombolysis is the first 2 weeks. Therefore, according to the guidelines, it is of utmost importance to perform the first duplex ultrasound control prior to discharge and within 2 weeks of the recanalization procedure. Subsequent follow-ups should be scheduled at 6 weeks, 3 months, 6 months, and then annually to ensure ongoing monitoring and timely intervention if needed, as guided by the recommendations.⁵⁴

Conclusion

The management of CVO requires a multifaceted approach, combining conservative treatments like compression therapy, anticoagulation, and lifestyle modifications with targeted endovascular interventions. Endovascular techniques, including stent placement, play a pivotal role in improving clinical outcomes by restoring venous patency and enhancing venous return. Ensuring adequate venous inflow is also essential for successful endovascular interventions. Furthermore, the use of IVUS is crucial in defining the appropriate landing zones for stent placement, optimizing procedural outcomes. However, these procedures present challenges, and careful patient selection based on the proposed inflow classification, tailored anticoagulation regimens, and close postoperative surveillance are crucial to optimize long-term results. A comprehensive strategy integrating both conservative and interventional approaches is essential for achieving optimal outcomes in patients with CVO.



CORRESPONDING AUTHOR
Houman Jalaie, MD, PhD
Department of Vascular Surgery,
European Vascular Center AachenMaastricht, Univeristy Hospital RWTH
Aachen, Pauwelsstraße 30, 52074
Aachen, Germany
EMAIL: hjalaie@ukaachen.de


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