III Guidelines and Consensus Statements: An Overview
To date, no document has comprehensively focused on all aspects of rehabilitation for patients with venous diseases of the lower limbs. Rehabilitation of these patients consists of all nonpharmacological and nonsurgical interventions aimed at prevening venous disease progression and complications, reducing symptoms, and improving quality of life. With the exception of medical elastic compression stockings, physical therapy and rehabilitative protocols are not mentioned or only partially mentioned in the recent guidelines on chronic venous disease. However, the rehabilitation approach should be tailored to the specific needs of each patient, depending on the severity of chronic venous disease, the location and pattern of venous lesions, age, motor deficits, comorbidities, and psychosocial conditions. Venous rehabilitation is based on four main strategies: (i) lifestyle adaptations and occupational therapies; (ii) physical therapies; (iii) adapted physical activities; and (iv) psychological and social support. Caggiati presented a “Decalogue” of venous rehabilitation, which includes the main diagnostic and therapeutic steps of venous rehabilitation (Phlebology. 2018). Finally, he highlighted that the currently available studies are not corroborated by evidence-based analysis of results concerning the long-term evolution of venous disease, the adherence of patients to rehabilitative protocols, and comorbidities. Furthermore, they almost all focus on patients with severe venous insufficiency (C5, C6). Thus, well-designed clinical trials are required to evaluate the efficacy of the described rehabilitative protocols in influencing the evolution of venous disorders. On the other hand, it seems appropriate that studies evaluating the efficacy of any pharmacologic or surgical treatment consider the prescription and the adherence to rehabilitative protocols.
Pelvic congestion syndrome (PCS) is one of the most important causes of chronic pelvic pain in women, because of pathological venous flow in ovarian and pelvic veins. Ovarian vein dilatation is seen in 10% of women, with a probability of developing PCS in up to 60% of this population. Lazarashvili explained the importance of a consensus document on this matter, as strong evidence about prevalence and quality of life or common protocols aimed at evaluating the effectiveness of different diagnostic or treatment options exists. The registration of the document was made at the 2015 International Union of Phlebology Chapter Meeting in Seoul and, as a first step, a review aimed at identifying and analyzing the main issues in the diagnosis and treatment of PCS was published (Acta Phlebologica. 2016;17(1):23- 26). Furthermore, in 2016, a special issue of Phlebolymphology was published, which included seven review-type articles on the diagnosis and management of PCS. Lastly, the first international meeting dedicated to PCS was organized in Krakow in December 2017. Currently, the final document, written by 26 members of the editorial group, is undergoing a final revision process and preparing for press.
Foam sclerotherapy is an extremely common procedure performed in the world to treat veins as a sole treatment as well as an adjunct for other treatments. However, some adverse effects of this treatment have been reported. In particular, the incidence in triggering a migraine aura, usually in the form of visual disturbances, is increased with a foam vs liquid sclerosant. Moreover, after sclerotherapy, duplex ultrasound has enabled the visualization of asymptomatic deep vein thrombosis (reported incidence, 1% to 3%). Finally, albeit rare, some reports of transient ischemic stroke or stroke after sclerotherapy have been described. Wong explained the main objectives of the Document on Contraindications of Sclerotherapy. The first goal is to conduct a critical reevaluation of the contraindications to modern sclerotherapy in light of the adverse reactions described above using an evidence-based approach as much as possible. The second can be identified as a population at risk for an increased occurrence of adverse effects and, where possible, recommend treatment modifications or precautionary methods in these specific populations. Finally, the recommendations of the document are to be graded based on quality of evidence. A panel of experts is still working on the documents, but a number of key points have already been defined. Regarding the absolute contraindication to sclerotherapy, they can be summarized as the following: (i) known anaphylactic reaction to the selected sclerosant; (ii) acute deep venous thrombosis and/or pulmonary embolism or acute extensive superficial venous thrombosis; (iii) transient ischemic stroke, stroke, seizure or myocardial ischemic event complicating previous sclerotherapy; (iv) severe local or widespread infection or systemic illness; and (v) chronic limb threatening ischemia. Instead, the following conditions should be considered relative contraindications: (i) pregnancy, breast-feeding, or the first 3 months postpartum; (ii) known patent foramen ovale and/or reversible neurologic symptoms associated with migraine aura after previous sclerotherapy; (iii) hypercoagulable state (including past history of deep vein thrombosis or pulmonary embolism, past history of extensive superficial vein thrombosis, thrombophilia, immobility, active cancer); (iv) long-haul travel preand postsclerotherapy; (v) chronic kidney or liver disease; and (vi) special patient groups, such as morbid obesity, patients on specific medications (like minocycline, tamoxifen, and disulfiram), or patients with psychosocial factors.
Gloviczki presented the fourth revised edition of the Handbook of Venous Disorders, published in 2017. This volume provides the most up-to-date information on evaluating and treating venous and lymphatic diseases and malformations. It is a comprehensive book packed with useful information on evaluation, diagnostic imaging, and medical, endovascular, and surgical management of acute and chronic venous diseases. It includes new chapters on foam sclerotherapy, radiofrequency ablation, and laser treatment for varicosities and chronic venous insufficiency and on catheterdirected thrombolysis and venous stenting. There are useful diagnostic and treatment algorithms and evidence-based guidelines. The Handbook of Venous Disorders is written and edited by leaders and founding members of the American Venous Forum. Several chapters were written by international experts in venous disease.
Based on currently available evidence, thermal ablation, foam sclerotherapy, and surgery to treat varicose veins and more advanced chronic venous insufficiency are safe, with a low complication rate, and low morbidity. Endovenous interventions, however, have fewer early complications and less periprocedural pain and disability. All interventions resulted in significant and clinically important improvements in symptoms, signs, and quality of life (QOL). Members of the SVS/AVF coalition on chronic venous disease (CVD) are confident at a high / intermediate level of interventions for symptomatic varicose veins and the advanced forms of CVD improve immediate / near-term health outcomes. The SVS/AVF has a very low level of confidence that interventions improve early and mid-term health outcomes in asymptomatic patients with varicose veins or other signs of chronic venous insufficiency.
Although current data show that stenting of iliofemoral and inferior vena cava obstructions is emerging as a safe and effective treatment, level 1 data from randomized controlled clinical trials are needed for a more precise assessment of this treatment modality, especially with regard to patient-reported outcomes, QOL, standardization of intravascular ultrasound imaging diagnostic criteria, hemodynamic assessment for reporting treatment outcomes, and assessment of the risk for late stent-related complications. Many of these questions could be addressed using the numerous outpatient venous care centers that have proliferated across America. In terms of interventions for chronic venous insufficiency, a randomized controlled trial comparing endoluminal therapy with best medical therapy and compression should be undertaken and hopefully completed within a decade. Furthermore, the ATTRACT trial (Acute venous Thrombosis: Thrombus Removal with Adjunctive Catheter directed thrombolysis) will answer whether postthrombotic syndrome is reduced by active thrombus clearance compared with anticoagulation and compression, and the C-Tract trial (Chronic venous Thrombosis: relief with adjunctive catheter-directed therapy), if funded, will provide further evidence to support venous stenting for the treatment of chronic venous insufficiency.
Patients with iliofemoral deep vein thrombosis represent an opportune subset of patients for acute interventional management with currently available techniques. This subset of patients with proximal deep vein thrombosis has a worse prognosis, is less well studied, and benefits more from acute intervention compared with all patients with proximal deep vein thrombosis or calf vein deep vein thrombosis. The increased morbidity and worse prognosis in this cohort of patients are partially because of the anatomy of lower extremity venous outflow. Invasive catheter-based therapies that remove a thrombus and correct venous outflow obstructions improve outcomes and morbidity in patients with iliofemoral deep vein thrombosis. Future trials that address iliofemoral deep vein thrombosis specifically will improve our understanding and management of this higher-risk subset of patients with deep vein thrombosis.
Cyanoacrylate embolization using the Venaseal catheter technique has been used to treat more than 200 refluxing saphenous veins over a 3-year period. N-butyl cyanoacrylate is delivered at 3 cm intervals along the vein starting 5 cm distal to the saphenous junction under ultrasound guidance. Cyanoacrylate embolization is the preferred treatment for all patients requiring an intervention for saphenous reflux with a vein diameter ≥4 mm. Reasons to prefer endovenous thermal ablation include no need for tumescent anesthesia and a quicker recovery time; endovenous thermal ablation produces more reliable outcomes vs ultrasound-guided sclerotherapy. Reasons for refusal were concerns about embolisms, dislike of having a permanent foreign substance implanted, and the cost. As a result, more than 700 veins were treated by endovenous thermal ablation in the same period. Cumulative occlusion rates were similar in the two unmatched groups, with a 95% occlusion for cyanoacrylate embolization at 12 months. Quality of life scores significantly improved after cyanoacrylate embolization. Recurrences occurred in veins >6 mm in diameter since a double dose of cyanoacrylate is delivered for larger veins or at segments of dilatation. Measurements of the upper end of occlusion shortly after treatment showed that 90% were within 5 cm from the junction with just one protruding into the deep vein. Most patients had little postoperative pain or inflammation, but 15% developed a significant inflammatory reaction along the vein, often just on one side after bilateral treatment.
Bradbury emphasized that the “endovenous revolution” changed everything, including industry involvement, physician interest, patient demand, and purchaser attention. This “revolution” led to an update of the UK NICE clinical guidelines. Now, there is a NICE treatment hierarchy. For people with confirmed varicose veins and truncal reflux, the guidelines recommend using endothermal ablation and endovenous laser treatment of the long saphenous vein. If endothermal ablation is unsuitable, ultrasound-guided foam sclerotherapy should be used. If ultrasound-guided foam sclerotherapy is unsuitable, surgery should be used. If incompetent tributaries are to be treated, treating them at the same time should be considered. Compression hosiery should not be used to treat varicose veins unless interventional treatment is unsuitable. An analysis of a prospective electronic general practitioner database in the UK was conducted 18 months before and after the NICE clinical guidelines. The results show that there was an increase in referrals and interventions for varicose veins, as well as a reduction in compression hosiery prescriptions. Bradbury concluded that having the NICE clinical guidelines is better than not having them, but 4 to 5 years later, the national impact is difficult to assess.
The guidelines for the management of chronic venous disease (CVD) of the lower limbs were developed under the auspices of leading phlebological societies and were published in International Angiology in April 2014. In these guidelines, the levels of evidence range from level A to level C and the strength of the recommendations is either 1 or 2. The faculty is now involved in updating and producing the guidelines for 2018. First, Nicolaides discussed the classification and severity of CVD issues. He emphasized that a practical method of grading the severity of symptoms is needed. Secondly, he reported that the guidelines concerning the pathophysiology of CVD and the clinical aspects in chapter 2 remained mainly unchanged, but many issues need to be updated, such as the pathophysiology of symptoms, the pathophysiology of C0s patients. In addition, the section on microcirculation needs to be updated, a section on hemodynamic changes needs to be added, and the evidence for progression and the contribution of pelvic vein obstruction or reflux needs to be updated. Nicolaides focused on the anatomic and hemodynamic factors associated with increased severity of CVD. He reported that chapter 3 on the magnitude of the problem must be combined with chapter 4 on the socioeconomic aspects of CVD.
Regarding the classification of CVD in chapter 5, the pros and cons of the clinical, etiological, anatomical, pathophysiological (CEAP) are debated. As CEAP is unsuitable for continuous monitoring, the revised Venous Clinical Severity Score (rVCSS), disease specific QOL measures, visual analog scale (VAS) tools, and the recurrent varicosities after surgery (REVAS) classification will be recommended. In chapter 6 concerning investigations, it will be stressed that there is no single test that can provide all information needed to make a clinical decision and plan a management strategy. The speaker presented the noninvasive methods for studying the microcirculation in CVD, which include skin blood flow and venoarterial response to standing measured by laser Doppler, capillary filtration, skin Po2 and Pco2, capillaroscopy, and orthogonal polarization spectral (OPS) imaging. Nicolaides pointed out that many values determined by OPS are progressively altered from C1 to C6 patients and are significantly different from those of healthy subjects.
In the compression chapter, it will be highlighted that compression relieves symptoms and reduces edema in patients with CEAP classes 1-5 (1A). Compression will be recommended immediately after sclerotherapy, thermal ablation, or stripping of varicose veins (2C). Compression will also be recommended for the healing of ulcers (1A) and after deep vein thrombosis to prevent postthrombotic syndrome (1B). Meta-analyses have been performed to determine the magnitude of the effect of venoactive drugs on each symptom and the level of available evidence, which showed that micronized purified flavonoid fraction (MPFF) and ruscus extracts are highly effective in reducing symptoms and edema in patients with CVD. In chapter 10 on superficial vein incompetence, the following 2017 recommendations were made: thermal ablation (1A), old type surgery (2A), open modern surgery (1A), ultrasound guided foam sclerotherapy (1A), steam, VenaSeal, mechanochemical endovenous ablation (MOCA) (1B), CHIVA (2B).
earon explained the grading of recommendations, whereby strength can be grade 1 (strong) or grade 2 (weak) and quality of evidence can be grade A (high), grade B (moderate), or grade C (low). He started with the choice of anticoagulant. If a patient has no cancer, then direct oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) (grade 2B) and VKAs are recommended over low-molecular-weight heparin (LMWH) (grade 2C). If a patient has cancer, LMWH is recommended over VKAs (grade 2B) and over DOACs (grade 2B). Regarding inferior vena cava filters in addition to anticoagulation, filters are not recommended if the patient is receiving anticoagulation (grade 1B), but filters are recommended if the patient is not receiving anticoagulation (grade 1B). The next topic was stockings to prevent postthrombotic syndrome. For patients with acute deep vein thrombosis, graduated compression stockings (GCSs) were not recommended (grade 2B). In patients with subsegmental pulmonary embolism and a lower risk of recurrence, clinical surveillance is recommended over anticoagulation (grade 2C). In patients with a higher risk of recurrence, anticoagulation is recommended over clinical surveillance (grade 2C). In patients with a pulmonary embolism and no hypotension, thrombolysis is not recommended (grade 1B), in patients with a pulmonary embolism and hypotension, with a low risk of bleeding, thrombolysis is recommended (grade 2B), and in selected patients who have deteriorated, but are not yet hypotensive, with a low risk of bleeding, thrombolysis is not recommended (grade 2C). In patients with recurrent venous thromboembolism on anticoagulants, the diagnosis should be reevaluated and a remediable cause (treatment factors or patient factors) should be found. If confirmed and no remediable cause is present, patients on DOACs or VKAs should be switched to LMWH (grade 2C). For patients already on LMWH, the dose should be increased (grade 2C).
The speaker emphasized that the basis for carrying out mapping is the International Union of Phlebology consensus document of duplex ultrasound investigation of the veins of the lower limbs. The following veins must be recorded on the maps: great saphenous vein, anterior accessory saphenous vein, posterior accessory saphenous vein, anterolateral vein of the thigh, posteromedial vein of the thigh / vein of Giacomini, superficial and tibial veins, posterior arcuate vein, intersaphenous vein, small saphenous vein, and lateral thigh and calf veins. Other structures and assessments should include duplication, absence or agenesis, large perforators, small saphenous artery, popliteal compression, baker’s cyst. The following graphic notations have been decided:
• Competent: blue, arrow up;
• Incompetent: red, arrow down;
• Stripped: dotted line;
• Ablated/sclerosed: grey line;
• Acute thrombosis: interrupted dots; and
• Chronic fibrosis: grey line.
de Maeseneer concluded that consistent graphic and content standards are required. The International Union of Phlebology Venous Mapping Consensus Committee will lead the way.
The speaker stated that many different venous maps made by different professionals could provide a possible source of confusion. Venous mapping can be prepared before, during, and after a procedure. Venous mapping before treatment should be done according to the guidelines and the anatomy should be described according to consensus and literature. Possible variants should be evaluated and pathologies excluded. Concerning mapping during treatment, the speaker emphasized that it is very important to have a descriptive framework always available for the best execution of the procedure or for possible strategic changes. He believes that the best way is to draw the map directly on the skin with different colors for different cases. Regarding mapping after treatment, he highlighted that it is very important to verify the results and this may be very useful in the relationship with the patient. Aluigi concluded that ultrasound is the method of choice for performing venous mapping. Accurate nomenclature of the veins of the lower limbs is still a problem. Incorrect identification of the lower limb veins and variants can become an important source of confusion. The speaker remarked that it is essential that all professionals involved use common terminology, a common methodology, and a common record keep method.
Gloviczki introduced the levels of evidence and grades of recommendation. In 2017, 300 guidelines described in 68 chapters by 118 authors were published in the Handbook of Venous and Lymphatic Disorders. In the clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum, early thrombus removal strategies have a 2C recommendation for a first episode of deep vein thrombosis, with symptoms for less than 14 days, a low risk of bleeding, good functional capacity, and a long life expectancy. If phlegmasia cerulea dolens is presented, there is a 1A recommendation for the same treatment. Regarding technique, pharmacomechanical thrombolysis is recommended over catheter-directed pharmacologic thrombolysis alone if the expertise and resources are available (2C). Self-expanding metallic stents are recommended for the treatment of chronic iliocaval compressive or obstructive lesions that are uncovered (2C). The speaker discussed the problems of the ATTRACT trial (Acute venous Thrombosis: Thrombus Removal with Adjunctive Catheter-directed Thrombolysis). In his opinion, the Vilalta scale is imperfect and subjective, the primary end point of the study did not focus on symptom improvement, enrolled femoropopliteal deep vein thrombosis patients were 43%, and there were few patients receiving iliac vein stents.
Gloviczki presented the guidelines of the American Venous Forum on endovascular reconstruction for iliac vein obstruction. Endovenous stenting is the current “method of- choice” for the treatment of symptomatic primary and postthrombotic iliac veinobstruction (1B). The clinical, etiological, anatomical, pathophysiological (CEAP) classification is recommended to describe chronic venous disease (1B). There is a recommendation against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (1B). In the REACTIV trial (Assessment of Conservative and Therapeutic Interventions for Varicose veins) at 2 years, high ligation and stripping as well as phlebectomy provided better symptom relief, cosmetic results, and significantly greater improvement in quality of life than conservative management. Compression is recommended as the primary treatment for healing venous ulcers (1A).