V – Treatment

Acute venous disease

Deep venous thrombosis – how to treat in daily practice?

A. Comerota

In the first part of his presentation, A. Comerota dealt with the high prevalence of postthrombotic syndrome (PTS) in patients with iliofemoral DVT and defended the American College of Chest Physicians (ACCP) guidelines recommending thrombus removal, including venous thrombectomy and catheter-based procedures designed to eliminate clots, in patients with iliofemoral DVT. Following venous thrombectomy, patients should receive the same intensity and duration of anticoagulation as those patients who are treated with anticoagulation alone (ACCP recommendation Grade 1 C). In the author’s opinion, catheter-directed thrombolysis is the preferred method of managing patients with iliofemoral DVT, but anticoagulation alone without thrombus removal is indicated in the majority of patients.
In the second part, the author presented the principles that should be adopted for successful anticoagulation of patients with acute DVT. The principal therapeutic objectives in DVT must be to reduce thrombus extension and recurrence, avoid PE and reduce PTS incidence. For this reason, sustained adequate therapeutic anticoagulation is necessary from the onset of therapy. Early subtherapeutic anticoagulation is associated with a 15-fold increase in the risk of recurrence. Initial anticoagulation with a heparin compound or fondaparinux should continue for at least a five-day overlap with vitamin K antagonist (VKA) and the international normalized ratio (INR) should be >2 for 24 hours before heparin is discontinued. Subtherapeutic VKA doses increase DVT recurrence and does not protect against bleeding complications. Supratherapeutic VKA doses do not reduce DVT recurrence and increase bleeding risk. Patients must be stimulated to ambulate early wearing a 30-40 mm Hg ankle-gradient compression stocking during their waking hours to speed recovery and reduce postthrombotic morbidity (ACCP recommendation Grade 1 A). Duration of anticoagulation and risk of recurrence were other aspects discussed. Patients with a transient risk for DVT must be anticoagulated with VKA for a minimum of three months. In the author’s opinion, in case of unprovoked DVT, patients should receive VKA for at least three months and then reevaluated for long-term (indefinite) therapy. Reevaluation must analyze patient status, ultrasound study, and D-dimer activity. Thrombus presence and D-dimer higher than 250 ng/mL increase the risk of recurrence of DVT. In these cases, patients are anticoagulated indefinitely and reviewed every six months. Patients with isolated calf DVT should be treated with three months of anticoagulation (ACCP recommendation Grade 1 A). For unprovoked recurrent DVT, indefinite anticoagulation is superior to six months of anticoagulation, but carries a higher bleeding risk. Patients with malignancy are best treated with low-molecularweight heparin (LMWH) rather than a VKA. LMWH should initially be given for the 3-6 months, after which the patient should be reevaluated. Subsequent therapy with VKA or LMWH should continue indefinitely or until the cancer is resolved.

Thromboembolic Disease

Chairperson: W. Blättler
Moderator: M. Meissner

Current status of thrombolysis and thrombectomy in iliofemoral deep vein thrombosis
A. Comerota

Iliofemoral DVT, if treated with anticoagulation alone, carries a very high risk of postthrombotic syndrome (PTS), as well as a significant risk of recurrence. The strategy of thrombus removal – venous thrombectomy or a catheter-directed procedure – results in better outcome (better venous patency, preserved valve function, less PTS) with acceptable safety. Nevertheless, the lack of randomized controlled trials comparing this strategy with anticoagulation alone has not allowed a strong recommendation so far. In the last ACCP guidelines on antithrombotic therapy (2008), the recommendation for venous thrombectomy and catheterdirected thrombolysis in the case of extensive proximal DVT is graded 2B; the recommendation for pharmacomechanical thrombolysis is 2C. There is a strong recommendation for the same intensity and duration of anticoagulation as for the patients treated with anticoagulation alone (grade 1C). Two large randomized trials of thrombus removal strategy are underway (CAVENT, ATTRACT).

Catheter-directed thrombolysis in deep vein thrombosis
N. Bækgaard, R. Broholm, LP. Jensen

Review of the recent literature demonstrates the good outcome and acceptable safety of catheter-directed thrombolysis of proximal DVT in selected patients, but this method is still underutilized. The possible indications are sudden onset of symptoms, no contraindication, good clinical reserve, anatomical cause of DVT, iliofemoral location, acute leg compromise, failure of standard anticoagulation therapy, and high risk of PE. So far, few publications have documented the longterm results of catheter-directed thrombolysis. The results, however, are not fully comparable due to different inclusion criteria and methodological differences (doses of thrombolytic drug, doses of heparin, techniques – catheter-directed thrombolysis alone, pharmacomechanical thrombolysis, angioplasty, and venous stenting). In the study of the Oslo group, there was a significantly better patency rate compared with anticoagulation alone, but disappointingly no difference in the presence of reflux in the common femoral vein. In the study from Copenhagen, 89% patients were without reflux. The study of the authors´ institution was finally presented (highly selected population, 103 legs treated for DVT, median follow-up 50 months). The results were very satisfactory – no mortality, low morbidity, no venous claudications or skin changes, 87% preserved venous patency 6 years after DVT.

Endovascular deep vein thrombosis interventions
S. Vedantham

Because of the endovascular “evidence gap” (lack of randomized controlled trials comparing endovascular procedures with anticoagulation alone in DVT), these methods are currently underutilized in clinical practice. The objections to their use could be the invasiveness and potentially higher risk, possible medicolegal issues, and higher costs. There is also a lack of skilled interdisciplinary networks of physicians and of a standardized DVT lysis protocol.
ATTRACT is a phase III, open label, randomized, controlled, multicenter trial in the USA, comparing anticoagulation alone with pharmacomechanical catheterdirected thrombolysis. It is planned to enroll 692 patients with acute symptomatic proximal DVT (inferior vena cava, common femoral vein, femoral vein). The primary objective is to prove the efficacy of interventional methods in preventing PTS (evaluated 24 months after DVT with the Villalta score, design planned to prove 33% risk reduction). Secondary questions in ATTRACT will be the effect of invasive treatment on PTS severity, quality of life, early symptom relief, safety, costeffectiveness, valvular reflux.
ATTRACT is interdisciplinary and includes representatives of diverse medical specialties participating in the investigators network as well as in the steering committee.

New anticoagulants in the treatment of venous thromboembolism
H. Decousus

The reference therapy for acute VTE includes initial therapy with heparin or LMWH or fondaparinux followed by long-term warfarin administration. The disadvantages of this therapy should be overcome by new anticoagulants.
Idraparinux is an indirect factor Xa inhibitor with a very long half-life allowing once weekly dosing without the need for laboratory monitoring. The initial results have revealed an increased risk of bleeding. In the Van Gogh DVT and Van Gogh PE trials, idraparinux (for initial as well as for long-term treatment) was compared with standard anticoagulation therapy, with similar efficacy for DVT but worse outcome for PE (higher rate of early PE recurrence).
Idraparinux has been replaced by idrabiotaparinux, a biotinylated substance with available antidote. It has been compared with standard therapy in the EQUINOX study for DVT (results not yet published, but the efficacy of the two treatments was similar) and the CASSIOPEA study for PE (nearly finished; unlike Van Gogh PE, the initial therapy was enoxaparine in both groups).
Rivaroxaban is an orally available direct Xa inhibitor, administered once daily, without the need for laboratory monitoring. It has been evaluated in the EINSTEIN phase II study for proximal DVT and is currently being evaluated in the EINSTEIN phase III study for DVT and PE.
Apixaban is another direct Xa inhibitor. The main difference from rivaroxaban is predominant biliary/fecal metabolism and potential use in renal insufficiency. BOTTICELLI is a phase II study for proximal DVT and AMPLIFY is a phase III study for proximal DVT and PE.
Dabigatran is an oral, direct IIa inhibitor with prevalent renal metabolism, evaluated in RE-COVER 1 and 2 studies.
Rivaroxaban and dabigatran have already been approved in Europe for VTE prophylaxis in major orthopedic surgery.

Calf vein thrombosis – how to treat?
J. Lohr

According to the author there are several reasons for routinely scanning calf veins in patients with suspected DVT: to detect superficial venous thrombosis, to detect DVT, to evaluate the propagation of thrombosis, to assess potential for embolism, to “look where it hurts”, and to exclude other pathologies, like Baker cysts, neoplasm, hematoma, etc. There are also several arguments for not scanning the calf veins: low incidence (not justified), rare for propagation or embolization, complicates and lengthens the examination. But the speaker emphasized that the ICAVL 2008 recommends compression imaging for both posterior tibial and peroneal veins and also for the gastrocnemius and soleus veins in the evaluation of possible thrombosis in symptomatic patients. There are several obstacles to distal ultrasonography, like obesity, epifascial edema, interstitial edema, inability of the patient to sit upright, but these are not so frequent in daily practice. A meta-analysis of studies comparing ultrasound in symptomatic patients with venography shows a sensitivity for distal veins of 73% and a specificity of 93%. The prevalence of isolated calf vein thrombosis (v. poplitea and below) is 5-12% in symptomatic DVT patients, but is much higher in asymptomatic DVT patients (15% after hip-knee surgery and 45% after CABG). Isolated calf DVT rarely causes symptoms, but in 20-30% of cases untreated symptomatic calf DVT extends to the proximal veins mostly within one or two weeks of presentation. Both symptomatic and asymptomatic calf DVT propagates with equal frequency. Isolated calf DVT is associated with about half the risk of recurrence of proximal DVT or PE. In more than 90% of cases of proximal DVT, there is associated calf vein involvement. Calf vein thrombi can embolize and cause symptomatic PE in 0.5-13% of cases, according to different studies. Taking these data into account, the American Society of Chest Surgeons recommendation in symptomatic calf DVT patients is at least 6-12 weeks of anticoagulation. The anticoagulation prevents further thrombus deposition, reduces the risk of interval recurrent thrombosis, the established thrombus undergoes stabilization or endogenous lysis, and after 3 months of therapeutic anticoagulation the frequency of extension of symptomatic isolated calf vein thrombosis is reduced from 29% to 0%. The natural history of untreated calf vein DVT involves a 20-29% recurrence rate within 3 months, 4-46% postthrombotic manifestations, 20% valvular incompetence, up to 32% propagation, and 33% silent PE on lung scan. In treated patients the recanalization is rapid, with 50% clot reduction in 1 month and with total clearing by 1 year. Reflux is present in 24% of cases at one year. Many trials (PREVENT, ELATE, THRIVE III) demonstrate that long-term anticoagulation in patients with idiopathic VTE, including those with isolated calf DVT, is a safe and effective strategy.

TULIPA registry – recent practice in diagnosis and treatment of deep vein thrombosis
R. Bauersachs

In this presentation P. Bauersachs from Germany shared with us the results of the TULIPA registry demonstrating that the management of patients with suspected DVT has changed substantially over the past 15 years. The aim of this registry was to assess current real-world practice and performance of the diagnostic workup of patients with suspected DVT in ambulatory care in Germany. A total of 4976 consecutive patients with suspected DVT were included by 326 ambulatory care vascular specialists in a nationwide, prospective DVT registry. Signs, symptoms, and preceding management were recorded and the patients were assigned to group A (DVT confirmed), group B (DVT excluded) or group C (diagnosis pending). Follow-up was performed at day 90 and VTE events and deaths were adjudicated centrally. The TULIPA registry results show us that the diagnosis work-up was done on the same day in 58% of patients, 15% had received treatment from their GP to bridge the time to diagnosis, while 14% received treatment for a different suspected disease. Diagnostic workup included mainly ultrasound (96%), D-dimer test (36%), venography (6%), and CT and MRI (0.5%). After the workup, 28% of the patients were in group A, 68% in group B, and 4% in group C. Men had a higher prevalence than women. Objective clinical findings were more common in men, and in more than half of the women an alternative diagnosis was more likely than DVT. DVT was distal in 61.7% of cases. The discriminative value of the Wells score was very high. 9% of DVT patients had combined DVT and superficial thrombophlebitis, 5% underwent testing for concomitant PE, and 85.3% received outpatient treatment. Secondary hospitalization was necessary in 2.2% of patients. In group B, 4 patients (0.31%) had confirmed symptomatic VTE (diagnostic falsenegative rate <1%), compared with 18 in group C (9.1%). The author concluded that within the two-level ambulatory patient care system covered by the TULIPA registry, which is the largest German research project, diagnostic workup of patients with suspicion of DVT was performed in due time. GPs refer patients according to their risk factor profile. Pretreatment anticoagulation was applied appropriately. Almost all patients underwent imaging procedures, mostly complete compression ultrasound. Even though the guidelines-recommended pathway regarding D-dimer testing was followed in only 32% of cases, the diagnostic safety of excluding DVT in this real-world setting was excellent and as good as in prospective management studies. Long-term follow-up data of the TULIPA patients will be available next year.

Anything new in travel-related venous thromboembolism?
B. Eklöf

The speaker started his presentation by enumerating the proven or supposed risk factors for air travel–related venous thromboembolism (ATVT), which include patient-related internal factors (age more than 60 years, overweight, previous VTE, recent surgery/injury, pregnancy/postpartum, malignancy, cardiorespiratory diseases, thrombophilia, varicose veins, other chronic diseases, etc) and cabinrelated external risk factors (immobilization, coach position, low air pressure, relative hypoxia, dehydration). Based on alarming previous reports of ATVT, the WHO organized a consultation in Geneva in 2001 where the experts agreed that there is probably an association between air travel and VTE, but such an association is likely to be small and mainly affects passengers with additional risks for VTE. Similar risks may exist for other forms of travel, but the available evidence does not permit an estimation of the actual risk and therefore public recommendation cannot be made at present. It was the unanimous view of the participants that further multicenter, epidemiological, international, pathophysiological and preventive studies regarding ATVT should be undertaken as soon as possible. For this purpose the WRIGHT project (WHO Research Initiative on Global Hazards of Travel) was created. The project has received partial funding, so in Sydney in September 2005 four preliminary results were reported. The conclusions were as follows: air travel is associated with an increased risk of VTE and the risk is slightly higher after exposure to a succession of flights; thrombin generation occurs in some individuals after an 8-hour flight, suggesting that more than just immobilization causes ATVT; the risk of developing VTE seems to be lower in Dutch airline pilots than in the Dutch population; hypobaric hypoxia is not associated with prothrombotic alterations and is unlikely to contribute to the risk of ATVT; traveling for more than 4 hours by any transportation mode increased the risk of VTE twofold; this was more apparent with air travel, suggesting flight-related factors that are absent during travel by other modes. In summary, the WRIGHT project tells us that air travel is associated with an increased risk of VTE. This increased risk applies to other forms of travel where travelers spend long periods seated. Obesity, height, use of contraceptives, and the presence of prothrombotic abnormalities increase the risk. The results of the WRIGHT project suggest that over 150 000 of two billion air passengers per year will develop ATVT, of whom 7500 will suffer fatal PE. For this reason it is essential that the prevention study proposed for phase II of the WRIGHT project is carried out and that future passengers are adequately informed about their risk and the optimal mode of prevention. It is hoped that the suggested research projects will answer these questions within the next few years. While waiting for the outcome of the research, at this moment we can also report the conclusions of a Conference on Traveler’s Thrombosis organized in Hall, Austria, 2006, the updated version of which was published in VASA 2008, resulting the following consensus: cabin-related risk factors can be remedied by drinking plenty of nonalcoholic fluids, moving feet and legs and taking deep breaths several times every hour; passenger-related risk factors that can trigger any of the factors in Virchow’s triad may be potentiated by the cabinrelated risk factors; awareness of this problem has to be increased among the public as well as among doctors. Each person should be advised before flying by a physician, based on the individual level of risk (low, medium, high). In highrisk patients, prevention consists of general measures, compression stockings, and pharmacological methods (LMWH or pentasaccharides).

How to treat superficial thrombophlebitis?
M. de Maeseneer

In the introduction of her presentation, the speaker stressed that the clinical diagnosis of superficial thrombophlebitis (ST) seems to be easy, but often underestimates the real extent of the disease and also often overlooks the presence of associated DVT or PE. That’s why ST is a serious illness as it may lead to DVT and even PE in certain cases. The thrombus could directly extend through the saphenofemoral (SF) junction or saphenopopliteal (SP) junction often with a “free floating tail” or appear as non-contiguous ipsi-or contralateral DVT. The incidence of VTE in ST ranges from 5% to 32%, depending on the study. Therefore, duplex scanning is mandatory to evaluate the extent of the thrombus and to detect any associated DVT. A wide variety of therapeutic measures have been described: local applications (cold pack, gel, cream, spray, etc.), local incision with expression of clot, immediate mobilization with compression bandages or stockings, NSAIDs (no antibiotics), and anticoagulation with heparin (LMWH or unfractionated heparin) or oral anticoagulants. The main practical problem is to find out which particular treatment will be appropriate for each single patient. Some cases of ST are clear-cut and there is no doubt regarding the appropriate therapeutic option. For instance, a limited ST in a varicose tributary can be treated with simple local measures, mobilization with compression bandages or stockings, and specific treatment of underlying disease in a later phase, whereas an ST associated with DVT will be treated as DVT. However, there is less consensus in the literature regarding non-clear-cut cases, such as extensive ST of the main trunk of the great or small saphenous vein. Several recent papers (The Stenox Study Group, Marchiori et al., The Vesalio Investigators Group, Cochrane Database Systematic Review by Di Nisio et al. And the ACCP guidelines 2008) suggest the use of intermediate or high doses of unfractionated heparin or LMWH for at least 4 weeks. In cases where ST is close to the SF or SP junction, anticoagulation with VKA for 1-3 months might be indicated. Surgery is recommended long after the acute ST episode. Future studies are needed to optimize our strategy in patients with extensive ST.

Interaction of detergent sclerosants with the coagulation system: an update

K. Parsi

Two sclerosing agents – polidocanol, a nonanionic detergent, and sodium tetradecyl sulfate (STS), an anionic detergent, have been tested for their interactions with the hemostatic system. Several in vitro assays have evaluated the effects of these substances on various components of the coagulation system.
The tests assessing coagulation reactions – thrombin time (TT ), prothrombin time (PT) and activated partial thromboplastin time (APTT) – revealed a different effect of these agents: the coagulation times were minimally affected by polidocanol, but significantly prolonged after STS at higher concentration (>0.6%). The two further tests (factor Xa clotting time and surface-activated clotting time) are phospholipiddependent, ie, influenced by platelet count and function (while platelets provide their surface with phospholipids for coagulation reactions). These two tests again revealed little effect of polidocanol, but surprisingly the effect of STS differed between low concentrations (0.1-0.3%)—shortening of coagulation time—and high concentrations—prolonging of coagulation time. This would suggest activation of platelets at lower concentrations and destruction of platelets at higher concentrations.
The activity of respective coagulation factors was then measured after incubation of plasma with both sclerosants. The results demonstrated little effect of polidocanol, but a significant decrease of the activity of some coagulation factors was seen after STS (especially of the factors V and VII), which could be explained by proteolysis of these factors.
Further tests showed that at high concentrations both agents caused platelet lysis. The release of prothrombotic, platelet-derived microparticles was proven with both agents at low concentration.
The effect of sclerosants on the natural anticoagulant system was then assessed by the measurement of protein C, protein S, and antithrombin levels and by performing a functional test of activated protein C (APC) resistance. STS at high concentration significantly decreased levels of protein C, protein S and antithrombin, while polidocanol at high concentration had some effect on protein S only (moderate decrease). However, polidocanol induced APC resistance to some degree.
In a comparison with heparin (the effect on APTT), STS acted as an anticoagulant (similar but much weaker than heparin). Moreover, when added to heparin, STS potentiated the anticoagulant effect of heparin (such an effect was not observed after polidocanol).
To summarize the result of all these heterogeneous tests, STS at high concentration had some antithrombotic as well as prothrombotic properties, but the net effect can be characterized as antithrombotic. The effect of polidocanol at high concentration is probably neutral. Conversely, both STS and polidocanol at low concentrations have a net prothrombotic effect.
Finally, the effect of sclerosants on red blood cells and endothelial cells was tested, as well as the interaction with plasma components, including albumin. Both sclerosants caused the lysis of erythrocytes and endothelial cells. However, the neutralizing effect of albumin on the sclerosants was protective.
The practical implication is the suggestion to increase the concentration and reduce the volume of sclerosants and to inject rather than infuse them.

Chronic venous disease

A – GENERALITIES

Servier Symposium: Management of chronic venous disease: therapeutic
recommendations

Chairpersons: A-N. Nicolaides, E. Rabe
What’s new in guidelines?
A. Comerota

Guidelines for patient care offer recommendations to physicians for diagnosis and management of common diseases that generally apply to the typical patient. The presentation addressed some of the newer guidelines to help clinicians manage patients with chronic venous disease of the lower extremities.
The method of determining the strength and quality of the recommendations deserves mention. Recommendations are generally accompanied by a number, which refers to the strength of the recommendation, and a letter, which refers to the quality of the evidence supporting the recommendation. The guidelines for chronic venous disorders use three levels of strength: Grade I is a strong recommendation, Grade II a moderate, and Grade III a weak recommendation. The recent ACCP guidelines use only two levels for the strength of their recommendations: Grade 1 for strong and Grade 2 for weak.1 They further indicate that statements accompanied by a Grade 1 level are “recommendations” and statements accompanied by a Grade 2 level are “suggestions.”
The quality of evidence upon which the strength of the recommendation is based ranges from “A” for high quality, which is consistent evidence from randomized trials, to “B” for moderate quality, which is evidence from nonrandomized trials or inconsistent evidence from randomized trials. Level “C” is low quality, which is suggestive evidence from nonrandomized trials, observational reports, or expert opinion.

Classification and severity scoring of chronic venous disease are important to consider when building guidelines. A widely accepted, objective, and standardized classification system is crucial for accurate and reproducible description of patients. Lack of precision in diagnosis and description leads to conflicting reports of disease distribution and a poor understanding of the management of specific venous pathology. A standardized classification facilitates improved precision of communication and serves as a foundation for accurate reporting of the severity of disease and response to treatment. The CEAP classification (Clinical, Etiology, Anatomy, Pathology) was proposed and subsequently adopted worldwide as a basis for improved patient description.

Understanding the pathophysiology of a disease state is a prerequisite to effective treatment. Results from studies that demonstrate treatment efficacy lead to guideline recommendations. The apparently simple concept of venous hypertension being responsible for chronic venous disease belies the complex cellular and molecular processes set in motion by the abnormal venous hemodynamics. Ambulatory venous hypertension is the hemodynamic pathology, with its underlying components being venous valvular incompetence, luminal obstruction, and failure of the calf muscle pump. The seminal role of leukocyte activation as a result of venous hypertension was recognized following basic animal experiments and human research. Animal models of venous hypertension demonstrated increased numbers of leukocytes in the skin of extremities with venous hypertension.

What’s new in guidelines?
The recent ACCP guidelines1 have added important new recommendations and suggestions for the treatment of iliofemoral venous thrombosis, venous thrombectomy, catheter-directed thrombolysis, early ambulation and compression, Intermittent pneumatic compression, pentoxifylline, and micronized purified flavonoid fraction (MPFF; Daflon 500 mg). This last compound is the only mentioned phlebotropic drug in the ACCP guidelines

Reference:

1. Kearon C, Kahn SR, Agnelli G, Goldhaber SZ, Raskob G, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: ACCP evidence-based clinical practice guidelines (8th ed). Chest 2008;133(6):454S-545S.

Management of chronic venous disease: the example of Daflon 500 mg
A-A. Ramelet

Among the pathological processes involved in the development of chronic venous disease, the sequence of leukocyte adhesion, endothelial interaction, activation, and migration, and its association with valvular damage have focused attention on available molecules with known activity on this chain of events. MPFF (Daflon 500 mg), consisting of 90% diosmin and 10% other flavonoids, reduces leukocyte interaction with the endothelium in acute venous hypertension and inflammation, reinforces venous tone, reduces abnormal capillary permeability, and increases lymphatic drainage.
Chronic venous disease may be associated with a wide range of lower limb symptoms, which may be present in any class of the CEAP classification: leg heaviness, discomfort, itching, cramps, pain, paresthesia, sensation of swelling, and edema.
Venoactive drugs may be indicated as a first-line treatment for chronic venous disease–related symptoms in C0s to C6s patients. In the most recent guidelines for the management of chronic venous disease, three agents, including Daflon 500 mg, received a Grade A level of evidence for their effects on venous symptoms. Daflon 500 mg is effective from the earliest stages of chronic venous disease. Symptom relief is achieved rapidly, as demonstrated in three randomized controlled studies. Three further studies have also demonstrated beneficial effects of Daflon 500 mg on edema, and a significant correlation between the improvements in the symptom score of sensation of swelling and a decrease in ankle circumference.
Postoperative recovery after venous surgery is enhanced by Daflon 500 mg, as established in 2 recent studies. Mean pain scores in women with pelvic congestion syndrome are significantly lower in Daflon 500 mg-treated patients than in patients receiving placebo.
The efficacy of Daflon 500 mg in promoting venous ulcer healing has been demonstrated in a meta-analysis of 723 patients. As a result, Daflon 500 mg was assigned a Grade 1B as adjunctive treatment in ulcer healing in the recent guidelines of the American Venous Forum.

Unmet needs in assessment of symptoms and signs
A. Jawien

Chronic venous disease, which is highly prevalent among populations of Western countries, induces pain and discomfort and significantly reduces quality of life, but lacks specific and consensual instruments for adequate assessment of its signs and symptoms.
For vascular specialists who strive to find something better for their patients and are willing to change based on what they find, outcomes must be analyzed and presented in such a way as to be shared and compared. Needs are still unmet regarding the tools currently available for the assessment of the therapeutic efficacy of drugs, in particular Daflon 500 mg, in reducing symptoms and signs. Tools available to physicians to assess the efficacy of treatments in reducing symptoms and signs: The CEAP classification, a universally adopted classification of chronic venous disease signs, has facilitated meaningful communication about the disease. The adjuncts to the CEAP that are likely to show the greatest score change in response to therapy are a useful complement to the CEAP classification, and should be used for research. Besides these physician-generated tools, previous methods remain valid for objective measurement of symptoms and signs of chronic venous disease. For symptoms, practitioners may use visual analogue scales such as the 10-cm VAS. For assessment of venous edema, leg volume can be assessed simply by ankle and calf circumferences. Other methods reported are water displacement volumetry, optoelectronic methods, CT scanning, MRI, and dual X-ray absorptiometry. For leg ulcers, the parameters most frequently used to measure a wound are the lengths of the principal axes, the projected surface area, and the perimeter. Most methods have been used for the study of Daflon 500 mg’s efficacy. Tools adapted to patient-reported outcome: Patient-reported quality-of-life assessments are valuable adjuncts to both clinical observations and physician-generated assessments. At least seven specific scales adapted to chronic venous disease (Aberdeen Varicose Veins Questionnaire, Charing Cross Venous Ulceration Questionnaire, Tübingen, Franks, Freiburger, VEINES-QoL, and CIVIQ) have been developed until now, pointing to the need for a single scale applicable to a wide spectrum of diseases and validated in many languages. Most of these tools are validated in a single language, while thirteen linguistic versions of the CIVIQ were validated according to the forward/backward methodology. CIVIQ has been extensively used as a means of assessment in the treatment of chronic venous disease patients at all stages of the disease.

Recent guidelines in chronic venous disease: the place of Daflon 500 mg
A-N. Nicolaides

Because chronic venous disease is common in Western populations and because both specialists and general practitioners have to deal with it, there is a need for practical support in its daily management and more particularly for evidencebased guidelines.
Regarding chronic venous disease management, recent guidelines have reviewed the place of venoactive drugs in the treatment of symptoms, edema, and venous leg ulcer.
Guidelines on chronic venous disease–related symptoms: A group of 14 experts, chosen to be representative in the fields of angiology, dermatology, and vascular surgery, from countries in which venoactive drugs were available and who had experience of their clinical use, published in 2005 the Siena consensus paper on the efficacy of venoactive drugs in relieving symptoms. Data from randomized, controlled trials were selected according to the predefined criteria of evidence-based medicine and were classified as Grade A (randomized controlled trials with large sample sizes, meta-analyses with homogeneous results), Grade B (randomized controlled trials with small sample size), or Grade C (other controlled trials, non-randomized controlled trials). Outcomes included only symptoms at any stage of the disease. The experts agreed that venoactive drugs were indicated to relieve venous symptoms CEAP clinical class C0S through to painful venous ulcers (C6S). MPFF (Daflon 500 mg) was assigned a Grade A in this indication.
Guidelines on venous edema: International guidelines on the management of chronic venous disease used the same grading system as that of the Siena experts. Outcomes included not only symptoms but also edema and venous ulcer healing. When considering venoactive drugs, the guidelines largely summarized and endorsed the positive findings of the recent Cochrane reviews and highlighted the evidence of efficacy of several venoactive drugs in chronic venous disease–related edema. Daflon 500 mg was assigned a Grade A recommendation in venous symptoms and edema, and as an adjunct to standard compression treatment in the healing of venous ulcers.
Guidelines on venous leg ulcer: Based on the GRADE system described by Guyatt et al, the recent guidelines (2008) of the American College of Chest Physicians recommended Daflon 500 mg to be added to compression (Grade 2B) in the treatment of venous leg ulcers in patients with venous thromboembolic disease. In the last edition of the Handbook of Venous Disorders (2009), the use of Daflon 500 mg in combination with compression in longstanding or large venous ulcers was recommended (Grade 1B).

Conclusion
A-N. Nicolaides

This symposium provided a clear and comprehensive review of the latest advances in the field of chronic venous disease. Major advances in the management and prevention of chronic venous disease have occurred in the last few years. The stimulus has been the realization of the magnitude of the problem and the better understanding of the pathophysiology of the condition in terms of the macrocirculation and microcirculation and at the molecular level. It should be remembered that DVT might be responsible for some of the most severe forms of chronic venous disease and prevention of acute venous disease is part of the management of the chronic venous disease.
The most important advance in understanding the pathophysiology has been the realization that changes in blood shear stress, with activation of leukocytes and endothelial adhesion followed by subendothelial migration, stimulation of proteolytic enzymes such as MMPs, and accumulation of extracellular material have a key role in the development of chronic venous disease. With this as background knowledge, drugs like Daflon 500 mg can ameliorate the above mechanisms. The development and availability of appropriate tools to assess the severity of symptoms and the objective determination of treatment efficacy in improving signs such as edema, venous ulceration, and quality of life have enabled us to embark on appropriate randomized clinical trials. The results have provided level I evidence and grade A recommendations for therapies: compression, medication, and surgery. Medications such as Daflon 500 mg have now a proven place with grade A recommendations for the whole spectrum of chronic venous disease, ie, early disease, as an adjunct to surgery in moderate and advanced disease, and in the treatment of leg ulcers. Recommendations are now available in guidelines for the management and prevention of chronic venous disease developed both in North America and Europe.

B – CONSERVATIVE TREATMENT

Special issue in Phlebology

Chaiperson: J. Cabrera
Moderator: A-A. Ramelet

Recovery of vein dilatation by photochemical-induced collagen cross-linking
A. Frullini
The author proposed a new treatment to recover valve function and original vein diameter. Riboflavin combined with UV-A light generates a photo-polymerizing effect with formation of new links in the collagen structure. The same treatment is used in an ectatic disease of the cornea (keratoconus). This method is not operator-dependent, does not cause endothelial or nonvalvular lesions or damage to surrounding structure, and does not generate inflammation. He reported his experience with human fresh GSV samples exposed to a light-emitting diodeblue led (L:450 nm-480 nm) for 15 min and supplied with vitamin B2 (riboflavin) or saline solution (control). Histological findings showed that the vein wall thickness almost tripled and the endothelium was unaffected. In conclusion, the author suggested that this treatment could be indicated in initial disease, deep vein insufficiency, telangiectasia and perhaps to recover ectatic veins for arterial bypass or for enlarged arteriovenous fistulas in dialysis patients. Clinical trials will be necessary to assess the method.

A new pharmacomechanical method of endovenous ablation: Clarivein®
S. Elias

The author presented a new endovenous device—Clarivein—consisting of a catheter for endovenous mechanical vein wall destruction and a device for the simultaneous infusion of liquid sclerosant to enhance venous ablation without tumescent anesthesia. His experience includes 30 limbs with varicose veins (GSV only) at C2 24 p, C3 2 p, C4 4 p. GSV medium size 8.1 mm. GSV length treated 36 cm. GSV treatment time 14 min. 30/30 closed at 1 month, 19/20 at 3 month, 7/8 at 6 month. He reported 3 subcutaneous ecchymoses, minimal pain, no DVT, no nerve injury, no skin injury. This method represents a simplification and advance in the treatment of varicose veins.

Age-related macular degeneration and venous insufficiency
F. Chleir

Age-related macular degeneration (AMD) includes two forms: wet AMD occurs when abnormal new blood vessels start to grow from the choroid, dry AMD occurs when the light-sensitive cells in the macula break down, gradually blurring central vision.
Duplex scanning was used to study ocular blood flow and so assess the relationship between varicose veins and AMD in 40 patients . Arteries showed the slowest speed and low resistance particularly in wet AMD. Wet AMD indicated vasodilation with neovascularization and opening of arteriovenous shunts. Dry AMD showed dilation and blood stasis like varicose veins, but it was not clear whether the vessel abnormalities were the cause or consequence of venous disease.

My technique in compression treatment – bandages or stockings?

H. Partsch

Compression must be tailored to individual needs, according different clinical conditions. Several patient-oriented factors should be considered, eg, the underlying disease (venous, lymphatic, arterial involvement), size and configuration of the extremity, age, walking ability, pain, and discomfort. The compression tools differ mainly in terms of the applied pressure, the elastic properties of the material, and the duration of wear.
There are several indications for compression therapy with bandages or stockings in therapy and maintenance phases. In the therapy phase, for severe stages of CVI (CEAP C4 – C6), after varicose vein ablation by different methods, and for the initial treatment of lymphedema, superficial and DVT compression devices providing a high massaging effect during walking (“high working pressure”) are preferred (inelastic bandages like Unna-boots, cohesive and adhesive bandages, multicomponent bandages with high stiffness). Such bandages applied with an initial pressure of more than 50 mm Hg need to be applied by trained personnel. The speaker emphasized that randomized and observational studies showed faster resolution of pain and swelling with early ambulation and leg compression compared with immobilization, and a similar incidence of new PE on routine repeat lung scanning after 10 days of treatment. These observations suggest that mobile patients with DVT should remain ambulant. In addition, intermittent pneumatic compression pumps may be beneficial, but this must be investigated. In the maintenance phase, medical compression stockings must be considered as the basic management in all patients with CVI in order to reduce pain and prevent massive swelling and ulcer recurrence. Except in cases of severe swelling of the thigh, knee-high compression stockings are usually sufficient. Compliance, which is the most important practical problem, can be improved by special aids to alleviate donning of stockings, by information and education of the patients, but also by special tricks like putting on two stockings, one over the other. With the use of compression stockings in venous ulcers one can expect a healing rate of 84% in 12 weeks, if ulcers are not too large (< 5 cm), not too longstanding (< 6 months) and frequently with the concomitant use of appropriate pressure pads.

C – NON-CONSERVATIVE TREATMENT

Guest lecture

Chairperson: J. Bergan

Phlebology in the last 50 years: varicose veins and venous ulcers.
K. Burnand, C. Jeanneret

Varicose veins are known from extreme antiquity, but only 50 years ago the early definitions emphasized the description of the tortuous dilated vein. The modern definition of varicose veins is “…subcutaneous, permanently dilated veins equal to more than 3 mm in diameter in the upright position…”. Van Bemmelen et al introduced duplex measurements of venous reflux for estimation of CVI (1989). In 1995 Porter et al introduced the CEAP classification, which is routinely used in many countries now. Crossectomy and different types of stripping in addition to compression therapy have been the gold standard for more than 100 years. The high postoperative recurrence rate studied over a very long follow-up gave way to the development of new endovascular techniques. VNUS closure and endovenous laser therapy are new methods that eliminate reflux and large varicose veins without crossectomy. VNUS closure abolished reflux and varicose veins in 95.7% cases during 2-3 years of follow-up, and endovenous laser therapy has given similar results. Foam sclerotherapy is the method of a choice in the treatment of large varicose veins. In comparative studies, foam sclerotherapy was more effective than liquid. However, not all endovascular techniques have been studied in large randomized controlled trials with long-term follow-up. Venous ulcers are a more serious complication of CVI. It is generally estimated that 1% of the population will present with one or more episodes of venous ulcers during their lifetime. In the last 50 years there have been a number of new theories on the etiology of venous ulcers, but the mechanism of ulceration is still unknown. Venous ulcers are still managed by compression bandaging. Multilayer bandaging systems have been shown to be effective in healing 80% of venous ulcers within a year. Unfortunately, 20% of patients with C6 have recalcitrant ulcers requiring more investigation. Establishing which ulcers do not heal with compression would be very helpful so that more radical techniques such as tangential excision and mesh split skin grafting or the use of skin substitutes could be applied at an earlier stage. There is no evidence that abolishing superficial venous reflux by surgery enhances ulcer healing (the ESCHAR Trial), but it is clear that abolishing superficial reflux and regularly wearing compression stockings does reduce ulcer recurrence. In the last 50 years the management of venous ulceration has come a long way, with level one evidence now available for a number of investigations and treatments. It is, however, clear that a number of areas still require much more investigation. There are several important unsolved problems:
The cause of venous ulceration remains unknown
There is no diagnostic test for venous ulcers
The value of eradicating incompetent perforating veins has not been established
Deep vein obstruction is not quantifiable
Postthrombotic ulcers continue to recur despite adequate compression
Postthrombotic veins cannot at present be returned to normal function

Sclerotherapy treatment of reticular and telangiectatic veins.

J-J. Guex

Reticular varices and telangiectatic veins are serious cosmetic problems for large populations. These vascular abnormalities can be responsible for different symptoms such as heaviness, itching, tingling, burning, feeling of swelling, and pain. Therefore their treatment is not only for cosmetic but clinical reasons too. Sclerotherapy is most commonly used for the treatment of reticular varices and telangiectatic veins. Its technique is demanding and requires care, practice and knowledge. Clinical investigation (Level 1) and bilateral duplex scanning (Level 2) are necessary prior to treatment. Varicose veins must be treated before reticular varices and telangiectatic veins. Several devices such as Veinlite®, Syris®, and video projection can improve visualization of the pathological veins. Low-concentration sclerosing agent should be injected very slowly. Local compression with cotton balls and adhesive tape are sufficient in most cases. Light massage and anti-inflammatory cream may be recommended for prevention of bruising. Poor sclerotherapy can be divided into objective and subjective groups. Objective bad results usually include matting, discoloration, necrosis, scaring, and inefficiency of the procedure. Employment of sound techniques should avoid these problems. Subjective bad results are a usually problem of miscommunication between the phlebologist and the patient. Sclerotherapy of reticular veins and telangiectasias is not recommended in the case of deep venous incompetence with CVI.

Foam Sclerotherapy in 2009 (STD Pharmaceutical Symposium)

Chairman: L. Tessari
Foam sclerotherapy- the state of the art
P. Coleridge-Smith

P. Coleridge-Smith dealt with controversial issues of foam sclerotherapy and posed three questions: How well does foam sclerotherapy work? How safe is it? What do we do to optimize it?
The author reported his personal experience of an early occlusion rate of 100% in both GSV and SSV, GSV 88% SSV 83% at 1 year, GSV 88% SSV 91% at 5 years with a recurrence rate of 13%. As for adverse events, Henriet (1999) reported 9 visual disturbances/10 000 treatments, Guex (2005) 0.4% visual disturbance/12 173 treatments, and Morrison (2008) 8% with air foam (49 treatments), and 3% with CO2 foam (of 128).
Hansen (2007) in 20 patients showed bubbles in the R atrium after 9-59 s in all patients, 13 of 20 showed bubbles in the L atrium: migraine + visual disturbance in 7 cases, 7 of 20 showed no bubbles in the L atrium: migraine + visual disturbance in 3. Regan (2008) studied 50 patients, treated by foam sclerotherapy – Varisolve, with transcranial Doppler and MRI. Transcranial Doppler showed a bubble rate of 90% in the middle cerebral artery and in all patients MRI was normal 1, 7, and 28 days after treatment.
In conclusion, foam sclerotherapy is effective in obliterating veins with a recurrence rate of 10-20% at 5 years, which is no worse than surgical treatment. Larger volumes (> 10 ml) are more effective than small volumes (< 5 ml). Adverse events are more frequently reported with larger volumes of foam. Carbon dioxide foam is associated with fewer events. Varisolve – foam results in no MRI detectable cerebral lesions.

Foam sclerotherapy in Italy with postsclerotherapy compression
A. Cavezzi

A. Cavezzi discussed some key points of foam sclerotherapy. The Tessari method has become the reference when forming the sclerosant foam. Bubble size depends on the type of drug and gas used. The CO2-O2 mixture used to form the foam is less durable and has smaller bubbles. Low silicone syringes and large (21-25 G) needles are used to avoid foam degradation. As adjuvant measures: elevation of the limb during the procedure and post-injection immobilization without Valsalva delaying local compression + stockings. In the majority of cases foam sclerotherapy does not obliterate veins completely but transforms a high volume refluxing system in a low volume refluxing or antegrade flow system.

Recurrent varicose veins – foam sclerotherapy
M. Perrin

M. Perrin reviewed the treatment of recurrent varicose veins, which after operative treatment are a common, complex, and costly problem. A new term PREVAIT (presence of varices residual or recurrent). The presence of PREVAIT is stated between 20 to 80%. Clinical diagnosis remains essential but does not allow a precise assessment of PREVAIT. Duplex scan is mandatory.
Interventional treatments for recurrent varicose veins include:
• non invasive treatment (drugs, compression) that may improve only symptoms.
• invasive treatment namely open redo surgery
• minimally invasive treatment including thermal ablation (endovenous laser, radiofrequency) and chemical ablation (liquid and foam sclerotherapy.
There is no data comparing sclerotherapy outcome after operative versus nonoperative treatment. Some data are available to estimate recurrent varicose vein operative treatment outcome. Open redo surgery provides variable results. Sclerotherapy is minimally invasive and repeatable and has provided good results. In asymptomatic patients without severe signs of venous insufficiency the decision to treat depends on the severity of the non invasive findings.
In symptomatic patients with recurrent varicose veins and hemodynamic anomalies or with varices at C4-C6 of CEAP interventional treatment must be considered.
Although randomized controlled trials comparing outcomes of invasive and minimally invasive treatments are not available there is a large consensus for recommending ultrasound guided foam sclerotherapy as first line treatment in all patents except when the DS identifies a major reflux at saphenous femoral junction.

Foam sclerotherapy treatment in varicose veins-results from 1200 cases
A. Bradbury

A. Bradbury reported his personal experience with over 1000 patients treated with ultrasound-guided foam sclerotherapy. Clinical and duplex follow-up was at 1, 6, 12, and 24 months. He reported a complete truncal occlusion rate of 83% and complete absence of visible varicose veins at a rate of 85% at 12 months. Rapid ulcer healing and low recurrence. Quicker return to normal activities and less pain, bruising and analgesia than after surgery. Statistically significant improvements in both physical (disease-specific) and nonphysical (relationships, appearance etc,) symptoms. A low level of side effects and complications: 2 DVTs (0.2%), 5 visual disturbances (0.5%), 2 migraine (0.2%), 1 allergy. In conclusion, ultrasound-guided foam sclerotherapy for varicose veins is extremely safe clinically and cost-effective.

Closure Fast®, indication and procedure

T. Proebstle

The energy dosing problem that hampered radiofrequency ablation has been overcome with radiofrequency segmental thermal ablation Closure Fast. 100% immediate occlusion with an annual recanalization rate not exceeding 1-2% should be the benchmark. Sufficient energy dosing must be questioned in treatment of large veins with bipolar radiofrequency. Despite higher energy dosing, radiofrequency segmental thermal ablation has a good side effect profile.

Varicose Veins

Chaiperson: M. Perrin
Moderator: J. Barrett
Tributary treatment in saphenous insufficiency – outcome after 4 years
P. Pittaluga

The author presented the midterm results of a retrospective study of varicose vein phlebectomy with conservation of a refluxing saphenous vein.1 Clinical examination and duplex ultrasound were performed prior to the surgical procedures, 6 months and 1 year after, and then once a year. The study included 811 lower limbs operated on for first-time varicose veins with a preoperative a saphenous vein reflux >0.5 seconds. Surgery was of the GSV in most cases, and of the small saphenous vein in 2.3%. Saphenous vein reflux was reduced to < 0.5 seconds in approximately 70% of cases during the follow-up and at 4 years after surgery. Symptoms improved or disappeared in 80% during follow-up. Four years after surgery, the recurrence rate was below 88%. When ostiotruncal saphenous vein reflux extended to the malleolus preoperatively, the elimination of the saphenous vein reflux was less frequent. It was concluded that varicose vein phlebectomy with conservation of a refluxing saphenous vein can be an effective treatment in the midterm for the signs and symptoms of saphenous vein insufficiency and leads to nonsignificant saphenous vein reflux in more than two of three cases.

Reference:

1. Pittaluga P, Chastanet S, Rea B and Barbe R. Midterm results of the surgical treatment of varices by phlebectomy with conservation of a refluxing saphenous vein. J Vasc Surg. 2009;50:107-118.

Do we need saphenofemoral junction ligation in endovenous procedures?
B. Disselhoff

The author presented a randomized clinical trial to evaluate endovenous ablation (EVA) of the GSV with and without saphenofemoral junction (SFJ) ligation. 43 patients with bilateral varices were enrolled and treated in one limb with EVA alone and in the other limb with EVA +SFJ ligation. Follow-up with duplex scanning was performed at 6, 12, 24 months. After 2 years the recurrence rate was 17% in the EVA group and 13% in the EVA + SFJ ligation group. The occlusion rate was 88% in the EVA group and 98% in the EVA+SFJ group. Recurrences were caused by an incompetent SFJ (9%) and incompetent tributaries (8%) in the EVA group, while in the EVA + SFJ ligation group recurrences were due to neovascularization. There was no significant between-group difference in bruising, pain score, or tightness . In conclusion, the addition of SFJ ligation made no difference to the short-term outcome.

Foam sclerotherapy – the challenge of neurological symptoms.
N. Morrison

The author focused his presentation on the neurological symptoms during foam sclerotherapy. 59 patients underwent ultrasound-guided foam (CO2/O2) sclerotherapy for saphenous and nonsaphenous leg veins were studied with transcranial Doppler monitoring of the middle cerebral artery. The incidence of high-intensity transient signals was of 32% in all patients. 63% of asymptomatic patients had high-intensity transient signals compared with only 37% of symptomatic patients. The incidence of high-intensity transient signals was not significantly different between patients receiving <10 ml of foam and those receiving >10 ml. The incidence of symptoms in the low volume group was double that in the high volume group.
In conclusion the injection of CO2/O2 sclerosant foam in superficial veins resulted in detection of emboli in the middle cerebral artery in 1/3 of patients treated. Silent emboli were frequent. Incidence of symptoms or high-intensity transient signals was not avoided by injecting less than 10 ml.

Pathophysiology of visual disturbance occurring after foam sclerotherapy
J-L. Gillet

A prospective multicenter study was carried out to validate the hypothesis that visual disturbances after foam sclerotherapy correspond to aura and are not transient ischemic cerebrovascular events.
20 patients (C2 in 16, C3 in 4) treated with foam sclerotherapy (volume of injected air 5 to 10 ml) were studied with MRI (T1, T2, T3, diffusion) within 14 days after treatment. Visual disturbances occurred in 8 patients, dysphasic speech disturbance in 1, headache in 11. All MRIs were normal.
This study showed that visual disturbances occurring after foam sclerotherapy correspond to aura and suggested a pathophysiological hypothesis resting on the release of endothelin that would reach the cerebral cortex through a patent foramen ovale. Endothelin has been shown to trigger aura.

Iliofemoral obstruction – how to treat the disease?

S. Raju, P. Neglen

This presentation was divided into two parts: S. Raju discussed the pathophysiology of iliac venous obstruction and P. Neglen gave the technical details of treating this underdiagnosed disease.
CVI has two main causes: postthrombotic syndrome, which produces obstruction and venous reflux, and primary venous insufficiency without previous DVT. Venous reflux may occur in both cases, but in the majority of patients there is an associated underdiagnosed iliac vein stenosis. Nonthrombotic iliac vein lesions, such as the webs and spurs described by May and Thurner, are commonly found in the asymptomatic general population. However, the clinical syndrome, variously known as May-Thurner syndrome, Cockett syndrome, or iliac vein compression syndrome, is thought to be a relatively rare contributor to CVI, predominantly affecting the left side of young women. In the author’s opinion, intravenous ultrasound can detect iliac vein stenosis unseen in phlebographic studies. Ascending phlebography continues to be the gold standard for venous iliac stenosis, but must be done in different projections to detect iliac venous stenosis, which often does not appear in anteroposterior projection. Correction of iliac venous stenosis, without correction of associated reflux, offers a high rate of venous ulcer healing and improvement in pain/edema, with a low recurrence rate during long periods of follow-up.1 S. Raju recommends treatment of iliac vein stenosis based on clinical considerations in patients with pain, swelling, skin changes, or ulcers with an iliac vein stenosis where previous conservative measures have failed.
In the second part of the session, P. Neglen presented the technical details of performing an iliac vein angioplasty. Arterial techniques are not necessarily transferable to veins. This technique must be done in a fully equipped endovascular/angiographic suite and intravenous ultrasound is mandatory to achieve optimal outcome. Stenting is mandatory in the treatment of venous obstruction because, if not stented, the venous stenosis will recur early. The authors recommend access to the femoral vein below the suspected obstruction under ultrasound-guided vein puncture. In cases of treating stenosis close to the confluence of the common iliac veins, especially when using Wallstents, the stent has to be placed well into the IVC to reduce proximal restenosis. The “double-barrel” stenting technique is recommended in cases of bilateral occlusion. Usually, large stents are employed (14-18 mm diameter). Incidence of vein rupture is low in spite of use high balloon pressures (more than 18 atm). The stent is redilated after insertion to achieve a good wall apposition as evaluated by intravenous ultrasound. The entire obstruction is covered as outlined by the intravenous ultrasound to ensure adequate in- and outflow, which is crucial for long-term patency. Overlap of stents more than 2 cm is essential and should be extended caudally to the inguinal ligament when necessary. The patency rate is related to incomplete treatment or other factors, not to metal load. Patients are anticoagulated preoperatively with LMWH. After the surgical procedure, low-dose aspirin is used and, in patients previously treated with anticoagulant, oral anticoagulation is reintroduced. Sequential compression therapy is used postoperatively.

Reference

1. Raju S, Neglen P. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in pathogenicity. J Vasc Surg. 2006;44:136-143; discussion 144.

Lasers And Veins

R. Weiss

Use of the laser (light amplification by stimulated emission of radiation) was presented with a view to treating telangiectasias. The arguments in favor of the laser for leg veins were cited as easier technically, less bruising, easier for smaller vessels, and reduction of telangiectatic matting.
It was stated that one must always keep in mind a logical progression in the treatment of leg telangiectasias: 1- Begin with cut-off of reflux from SFJ/SPJ (surgery, endoluminal laser closure or radiofrequency); 2 – Ambulatory phlebectomy of tributary veins (usually > 4 mm); 3 – Sclerotherapy of remaining veins; 4 – Laser or intense pulsed light for remaining telangiectasias.
It was necessary to define optimal parameters for each procedure, as wavelength, pulse duration, fluence, spot size, and adequate cooling to avoid epidermal damage. Suggested types of cooling included gel (cold, refrigerated), contact cooling, dynamic cooling by spray, and air cooling. It was also explained why cooling is necessary: 1 – normal skin temp is around 33ºC; 2 – a 15 msec pulse of 70 J/cm2 heats the skin to 43-45ºC; 3 – with contact cooling the skin cools to 15ºC and after a laser pulse the skin heats to 25-30ºC; 4 – with dynamic cooling the skin cools to 12ºC and after a laser pulse the skin heats to 30ºC.
The indications for use of the laser on leg telangiectasias were as follows: 1 – contraindications to sclerotherapy; 2 – inexperience with sclerotherapy; 3 – resistant matted telangiectasias; 4 – fine caliber, pink telangiectasias, which may be difficult to treat with any technique.
It was concluded that sclerotherapy for telangiectasias still remains the gold standard, in more than 95% of cases. However, in less than 5% of cases lasers can be used, in particular, long-pulse Nd: YAG 1064 lasers.

Session of the American College of Phlebology

Preliminary results of low-energy density laser ablation treatment of incompetent truncal veins.
J. Mauriello, E-J. Sanchez, J. White, W. Schroedter, B. White

J. Mauriello presented preliminary data on laser treatment using a low wavelength of 1470 nm and low linear endovenous energy density. 49 vessels (21 GSV, 27 SSV, 1 anterior accessory) in 24 patients were treated (6 C2, 12 C3, 5 C4, 1 C5 CEAP). Mean diameter of GSV at SFJ was 8.1 mm and of proximal SSV 4.9 mm. The veins were ablated using radial emitting fibers at 3 watts, delivering a mean low linear endovenous energy density of 25.6 joules/cm. Postprocedure followup with duplex was at 6 months. After the procedure only two GSVs remained patent but sclerotic with flow for 3.6 cm from the superficial epigastric vein, but were distally occluded. Minimal perioperative pain and bruising, no paresthesia or heat. At 6 months one SSV was recanalized. The same two GSV remained patent for 4-6 cm past the superficial vein and closed distally. Low-energy density laser ablation was effective in chronic venous disease treatment with minimal patient discomfort.

Compression therapy after phlebologic interventions: How Much? How Long? How High? A United States Perspective
T. Morrison

T. Morrison reviewed the compression protocols used for cosmetic and medical vein procedures in the USA. There are five different classifications for compression: British, German, French, European, USA standard. The British standard Class one is 18-24 mm Hg, while USA Class one standard is 20-30 mm Hg. There is a need to refer to mm Hg instead of Class I or II. Compression stockings are classified on the basis of the pressure applied at the ankle. The survey supported the use in the United States of compression stockings after cosmetic and medical vein procedures. The majority (44%) used compression for 3 weeks after cosmetic sclerotherapy, and for 2 weeks (68%) after endovenous thermal and chemical ablation and phlebectomy. The majority (42%) used 20-30 mm Hg after cosmetic procedures. 15% used 20-30 mm Hg after medical procedures. The majority used thigh-high compression after cosmetic and medical vein treatments.

Effectiveness of single injection of sodium tetradecyl sulfate in predicting outcomes following ultrasound foam sclerotherapy using an ultrasound scoring system
P. Raymond-Martimbeau

P. Raymond- Martimbeau showed the effect of different sodium tetradecyl sulfate (STS) concentrations on an ultrasound scoring system to predict outcomes following ultrasound foam sclerotherapy of the great saphenous vein (GSV). 64 sclerosed proximal GSVs in 42 patients with saphenofemoral junction incompetence were classified into four groups (A, B, C, D). The vein score was composed of vein wall thickness, lumen filling percentage, and vein diameter reduction.
Each group received a single injection of STS . Group A with 1% STS 4 ml, Group B with 1% STS 8 ml, Group C with 3% STS 4 ml and Group D with 3% STS 8 ml. The GSVs were analyzed at 1 month and 1 year post-injection.
The overall ultrasonic score was significantly affected by the STS concentration. Using the Tukey post hoc test showed that group A had a significantly lower overall score than group B . There was no significant difference in the ultrasonic score between any other groups . Time of scoring also had significant effect on the overall ultrasonic score, with the score being significantly higher at one year than at one month (except for group D). There was also significant interaction between concentration and time of scoring . In conclusion, the ultrasonic score was significantly affected by STS concentration, time of scoring, and interaction between the two factors. Ultrasonic great saphenous vein sclerosis images can be differentiated by their characteristic features of wall thickness, endoluminal filling, and vein diameter reduction.

The complementary roles of surgery, endovenous thermal ablation, and foam sclerotherapy in the treatment of chronic venous insufficiency – the U.S. perspective.
N. Morrison

N. Morrison gave a personal overview on the complementary role of surgery, endovenous thermal ablation in the treatment of chronic venous disease. The objectives of the various treatments proposed are the ablation of axial and perforator vein reflux, improvement of leg function and cosmetic appearance, and minimization of recurrence and complications.
In the U.S., minimally invasive, percutaneous, endovenous treatment methods have largely replaced the traditional surgical procedure. Adjunctive treatment is considered to avoid recurrences in saphenous vein and include ablation of incompetent accessory saphenous tributaries, persistently incompetent perforator veins, and incompletely ablated truncal veins. Incompetent distal saphenous vein, incompetent tributaries and persistently incompetent perforators must be eliminated.
Mid-term results of endovenous thermal ablation seem to be similar to those of surgical treatment, with fewer complications. Endovenous foam chemical ablation also appears to be effective, with infrequent complications, but with rare serious neurologic adverse events.

VNUS workshop

Chairpersons: T. Proebstle, M. Vasquez
This workshop on the use of radiofrequency for ablation of varicose veins was organized by VNUS Laboratories.

Small Saphenous Veins with ClosureFAST
J. Alm

The first speaker, J. Alm reported on the use of ClosureFAST in small saphenous vein disease. In this study, 603 limbs in 468 patients were treated. The mean length of the small saphenous vein treated was 24.9 centimeters, and the mean procedure duration was 12 minutes. After one year of follow-up, 97.9% of treated veins were occluded. A low proportion of patients had paresthesia in the weeks following the procedure (2.1%), and this proportion further decreased after six weeks. J. Alm was asked by the audience how to minimize this complication, and in particular whether trying to localize nervous structure before the procedure would help. However, the use of tumescent anesthesia separates the catheter from adjacent structures, which minimizes such complications.

ClosureFAST, 3-year follow-up
T. Proebstle

T. Proebstle gave the 2-year follow-up results of a multicenter multinational study using ClosureFAST for the great saphenous vein in varicose disease. The 225 patients included (female 74%, 295 limbs) were managed in an outpatient setting, under tumescent local anesthesia. Combined procedures were allowed, and 13% and 56% of patients underwent concomitant sclerotherapy or miniphlebectomy, respectively. Three days after the procedure, 99.7% of treated veins were occluded. After two years, the occlusion rate was still very high: 95.2%. Only 3 patients had clinically relevant recanalizations. Regarding the side effects, the rate of paresthesia was 3.4%, 2.0%, and 0.0% at 3 days, 3 months, and one year, respectively. No DVT was observed. Many questions were raised by the audience. As regards to how distally the vein can be treated, the answer was that typical treatment would go down to the upper calf, but could be limited to mid-thigh or conversely to lower calf according to the lowest level of vein incompetence. There are no recommendations about thromboprophylaxis, but such treatment should be considered in high-risk patients. When asked where to start the treatment, T. Proebstle reminded the audience never to start the treatment less than 2 cm from the saphenofemoral treatment, regardless of the epigastric vein insertion. Also, he stressed the importance of not immediately treating subcutaneous or extrafascial veins when they are not at least 1 to 1.5 cm deep under the skin.

Perforators with the VNUS RFS catheters
M. Vasquez

M. Vasquez reported his experience in the treatment of perforators with radiofrequency catheters. He first discussed whether or not adjunct procedures to perforators are required when treating saphenous veins. In a longitudinal study of patients initially treated with radiofrequency, in which the one-year occlusion rate was 87%, there was no need for a new procedure during follow-up in 70% of patients. Among the 30% of patients who underwent complementary treatment, only 3% had perforator treatment. Thus, it is not recommended to systematically treat the perforators as an adjunct to the treatment of saphenous veins. If indicated during follow-up, treatment of perforators could be made using radiofrequency. The treatment should never be performed closer than 0.5 cm from the deep vein, and when an artery is seen adjacent to the perforator vein. The treatment should be performed under ultrasonographic control, and the lack of DVT should be checked by ultrasound 72 hours after the procedure. However, M. Vasquez told the audience that he was not very happy with the results, with a success rate of only 50%. Concomitant foam sclerotherapy of the remote tributary behind the treated segment could be of interest. On the other hand, he had doubts that foam sclerotherapy could be used alone given the size and the very rapid washout of some of these vessels.

Closure vs Laser (Recovery Study)
O. Goeckeritz

Finally, O. Goeckeritz presented the results of the RECOVERY study, a multicenter, multinational, single-blind, randomized trial that compared Closure versus laser for the treatment of saphenous veins. End points were the occlusion of the vein and the complications of the procedure. Of the 87 patients included, 46 were treated with radiofrequency and 41 with laser. At one month, all patients in both groups had satisfactory venous occlusion, and no between-group differences were observed at one month in terms of VCSS and quality of life score. However, statistically significantly fewer adverse effects were observed in patients treated with radiofrequency. Pain and tenderness scores at one week, as well as use of analgesic drugs, were less important in this group. On the other hand, more patients in the radiofrequency group developed an ecchymosis. No serious adverse events were seen in any group. Paresthesia was observed in 1 patient in the Closure group, and in 2 patients in the laser group. No DVT was observed in any group. The conclusion was that both methods are effective and safe for the treatment of varicose veins, but that post-procedure pain and tenderness could be less when radiofrequency is used.

Postthrombotic syndrome

The Neovalve in Postthrombotic syndrome – Tips and Tricks
O. Maleti

Postthrombotic syndrome after an episode of DVT is produced by the presence of an axial reflux uninterrupted from the groin to the calf. Until now, several valve repair techniques (valvuloplasty, valve transposition, or use of cryopreserved and bioprosthetic venous implantation) have been used, but all have several limitations: postoperative thrombosis, inadequate segments for transplant, incompetence of transplanted venous segments, etc.
Some noninvasive studies must be done before to indicate a neovalve construction. Duplex ultrasound and air plethysmography studies should be performed to determine the residual volume after calf contraction. In addition, ascending and descending venography are considered mandatory before valve venous reconstruction. The hemodynamic, morphological, and clinical parameters are of vital importance in deciding whether to perform such procedures. Cava and iliac vein patency, state of femoropopliteal venous segment, amount of deep venous reflux from cava to calf, presence of good calf contraction, and the presence of efficient deambulation are other aspects that must be considered before neovalve reconstruction. Clinically, deep venous surgery is indicated in cases of severe CVI (grades C6 of CEAP). The speaker then discussed the details involved in neovalve reconstruction. The recommendation involved valve reconstruction in the midthigh segment thereby avoiding the proximal and distal thigh segments, as this is an easier location to tackle. Removal of all adventitial layers is recommended. Different kinds of venotomy can be used, but the author recommended longitudinal venotomy as a better option for reconstruction. After this, it is necessary to do an endophlebectomy to remove all the fibrotic intraluminal material that appears after a DVT. There are two different technical options to create a neovalve, depending on the parietal conditions (monocusp or bicusp neovalve). The author recommended flap fixation in the semi-open position to avoid flap collapse with venous reflux.
Postoperative therapy is based on anticoagulation, early physiotherapy, and elastic compression. Patients are anticoagulated with unfractionated heparin during the surgery and the day after. This is followed by LMWH for 2 days and oral anticoagulation for 6 months. Leg elevation (22º), pneumatic intermittent compression and physiotherapy, and short-stretch bandage are mandatory after the surgical procedure. Patient deambulation is restored the second postoperative day. Ulcers must be cleaned every day and bandaging maintained until the ulcer heals. The most common postoperative complications are hematoma and seroma, which can be avoided by careful peroperative surgical dissection and hemostasia. The indications of this technique are patients with severe chronic insufficiency (class C6 of CEAP) and some cases of C5 and C4b with severe reflux (Kistner class IV) in patients with good ankle movement and normal deambulation without peripheral arterial disease. Superficial venous reflux and calf perforator insufficiency must be corrected before any intervention. Before surgery it is necessary to reduce leg edema, improve the inflammatory process, and clean the ulcer. Severe thrombophilic diseases, heparin contraindication, previous PE with low residual breath capacity are contraindications to this procedure. Femoral, iliac, or cava stenosis is a relative contraindication that can be corrected.
Finally, the author presented a series of 51 procedures in 46 patients treated during the last 8 years with a follow-up of 42 months (1-96). The neovalve competence obtained with this technique was 86% with an ulcer healing rate of 91% and ulcer recurrence in only two cases. DVT appeared in 7.8% of the cases during follow-up.
In conclusion, neovalve constructions can be a good way to correct venous reflux after DVT in selected patients with severe postthrombotic syndrome.

Deep Venous Insufficiency

Chaiperson: O. Maleti
Moderator: N. Labropoulos

Three-year follow-up of patients with deep vein thrombosis monitored in the TULIPA registry
H. Gerlach
TULIPA is a registry of DVT patients in Germany, established to monitor DVT management. A representative cohort of 310 patients (50.7% men, mean age 57.3 years) was followed up. Thrombosis was located in proximal veins in 49.4%, in calf veins in 36.1%, and in muscle veins in only 14.5%. The patients underwent follow-up examination 3 years later. The prevalence and severity of PTS were assessed clinically (Prandoni score). PTS was present in 34.7% in the total group, and was more frequent after proximal DVT. However, after isolated muscle vein thrombosis, mild PTS was relatively frequent and even the prevalence of severe PTS was not negligible. The modality of DVT treatment was also evaluated. Anticoagulation had lasted more than one year in only 25% of patients. Compression stockings had been used immediately after DVT diagnosis in 92.8%. One year later, 81.8% of patients still continued wearing compression stockings (80% of them persistently, mostly compression class II). In summary, the recent guidelines for DVT treatment have been followed quite adequately. One surprising result is the relatively high prevalence of PTS after isolated muscle vein thrombosis.

The time sequence of the development of axial deep reflux following lower limb deep vein thrombosis – A prospective study over 5 years.
A. Van Rij

114 patients (122 limbs) with DVT underwent follow-up examination (clinical assessment, duplex ultrasound, and air plethysmography). The patients were divided into three groups – extensive (iliofemoral) thrombosis, thrombosis of the thigh, and thrombosis of the calf. Venous recanalization was similar and quite satisfactory in all groups and occurred mostly in the first year after DVT. There was an inverse relationship between reflux and clot load. 5 years after an iliofemoral thrombosis, 45% of patients had axial reflux as a consequence of segmental reflux progression, with continuing deterioration. Axial reflux was predicted by pathological venous filling index and impaired outflow at two years. If DVT was isolated at the calf, popliteal, or femoral region, only segmental reflux was present.

Iliac vein stenting – Indications and long-term results
S. Raju

Iliac venous stenting is a low-risk procedure, with negligible mortality and minor morbidity. Moreover, venous stents have better patency and less in-stent restenosis than arterial stents. Following stenting, only aspirin therapy is needed (if no thrombophilia is present). Intravascular ultrasound is often needed to diagnose iliac vein obstruction.
The long-term results of iliac vein stenting were presented. 528 limbs with combined obstruction and reflux underwent this procedure. In follow-up, good stent patency was documented, as well as a substantial improvement of symptoms (pain, swelling), ulcer healing, and better quality of life. Reflux remained unchanged or improved.
In summary, correction of iliac vein obstruction by stenting can lead to substantial and lasting symptom remission and this procedure might be suggested even from stage C3 of the clinical CEAP classification.

Long-term results of stenting for iliofemoral vein obstructive lesions
O. Hartung

98 patients (104 limbs) with obstruction of iliofemoral veins underwent venous stenting. All patients were symptomatic (venous claudication, pelvic congestion, venous insufficiency). The etiology of the obstruction was: May-Thurner syndrome, previous DVT, retroperitoneal fibrosis, congenital vein hypoplasia. The patients were examined with duplex ultrasound and CT or MR angiography prior to stenting. The procedure was performed via percutaneous access and self-expanding stents were used. There were no major complications; early complications were rare (early rethrombosis in 2 cases). During follow-up, 7 patients had restenosis and 4 cases of rethrombosis occurred. Long-term patency rates were satisfactory. Stenting as a treatment of choice for iliofemoral venous obstruction was further discussed and the following indications were suggested: patients symptomatic or disabled despite medical therapy; with no malignancy; with or without reflux. Thrombophilia, pregnancy, and the presence of an inferior vena cava filter or clip are not contraindications. After DVT, the procedure should be delayed for 6 months, but could be successful even many years after the event.

Prevention of postthrombotic syndrome by compression therapy – evidence from comparative studies.
H. Partsch

Elastic compression stockings (ECS) and early ambulation are recommended in mobile DVT patients. Reducing the incidence of PTS with ECS is very well documented. Therefore, their use after DVT is recommended in the last ACCP evidence-based guidelines with 1A grade. ECS should be started as soon as possible and continued for at least 2 years. However, one survey documented limited adherence to these guidelines and great differences between respective countries in ECS use.
169 patients with proximal DVT were randomized to ECS versus no ECS use. During follow-up, skin changes occurred significantly more often in the non-ECS group. Symptom relief was significantly better in the ECS group during the first year, but not thereafter.
In conclusion, in DVT treatment, not only adequate anticoagulation (preventing recurrence) but also antistasis measures (preventing PTS) are necessary.

Impact of iliofemoral thrombosis on the development of postthrombotic syndrome
N. Labropoulos

A prospective study of patients with acute first iliofemoral DVT was performed. The patients were divided into three groups (DVT above and below the inguinal ligament or both above and below the ligament). Patients with previous DVT, chronic venous disease, thrombolysis, short life expectancy, or interruption of oral anticoagulation were excluded. Finally, 301 limbs were included with a mean follow-up of 3.8 years.
In the long term, the thrombotic burden had a marked impact on the development of PTS. Isolated iliac DVT had a good outcome, but the number of patients was too small for drawing firm conclusions. Iliofemoral DVT had the worst outcome (the most frequent progression to skin damage). These results suggest that more aggressive treatment (eg, pharmacomechanical thrombolysis) is probably appropriate for iliofemoral DVT. Two large randomized trials are expected to demonstrate the efficacy and safety of the interventional therapy (CAVENT, ATTRACT).

Neovalves in postthrombotic syndrome: long-term results.
O. Maleti

Conservative therapy is often insufficient to control the symptoms of PTS. The valvular incompetence may occur due to partial or complete destruction of the valve. Neovalve construction is one possible technique for correction of valve insufficiency. The long-term results of 51 neovalve construction operations were presented. 51 consecutive patients with severe CVI underwent surgery, with a mean follow-up of 42 months. The technique was modified during the study leading to better neovalve competence. The clinical improvement following neovalve construction was substantial (cumulative ulcer healing 91%, significant improvement in patients of class C5), and safety was satisfactory (mortality 0, minor complications in 17.5%).
The results suggest good efficacy of this technique in patients with PTS. However, symptoms may recur due to the natural evolution of venous disease.

The future of artificial venous valves
M. Dalsing

Artificial venous valves can be defined as any venous valve substitute. Two groups are distinguished – non-autologous and autologous valves. Many experimental and clinical studies have been done so far. Clinically, only autologous valves demonstrated any longevity. With non-autologous valves, the choice of material is the difficult task.
A percutaneous approach will likely be the most appropriate, using self-expanding metal designs (but with minimal metal exposed to the blood flow). Other possibilities are still being studied: bioabsorbable organic biopolymers, corroded metals, decellularized allograft valves. Tissue engineering is promising in this field, with the possibility of creating a tube from various natural or synthetic materials seeded with fibroblasts.
Research on artificial valves is still in its early stages and many problems remain to be solved: mechanical and biological challenges to the valve, the risk of rejection, the risk of early thrombosis or delayed fibrosis.

Venous malformation

Venous Malformations and Lymphedema

Chairperson: B-B. Lee
Moderator: N. Piller

Comparative prospective study between volume and low and high interface pressure under short-stretch compression bandages in the treatment of breast cancer lymphedema
R. Damstra, H. Partsch

R. Damstra presented a prospective study in which the authors compared the efficacy of low-pressure versus high-pressure short-stretch compression bandages in patients with postmastectomy arm lymphedema, stage 2,3 (with pitting edema). 36 breast cancer patients with one-sided lymphedema of the arm were randomized into two groups: Group A (n=18) received short-stretch bandages applied with low pressure, between 20-30 mm Hg, and group B (n=18) the same type of bandages applied at a pressure of 44-58 mm Hg. The pressures under the bandages were measured at distal and proximal levels (wrist and elbow) using air-filled transducers (Kikuhime device). The bandages were renewed after 2 and 24 hours. Arm volume was measured by water displacement volumetry before bandage application, after removal of the bandages at 2 and 24 hours. The results show that the arm volume reduction was significantly greater in group A (low pressure) at 2 hours and there were no significant differences between the two groups at 24 hours. Assessed using a visual analogue scale, bandages in group A were better tolerated.
In conclusion, the speaker pointed out that in contrast to the leg, where a doseresponse relationship between compression pressure and volume reduction could be demonstrated, in arm lymphedema light short-stretch bandages provoke fewer complaints and are as effective as tightly applied short-stretch bandages after 24 hours. Whether these different results are caused by the various pathophysiological conditions (eg, muscle pump differences, pathological lymphatic drainage characteristics of the arm, etc…) remains a question of debate.

Miscellaneous

Esthetic treatments and phlebology practice

M. Goldman

Venous abnormalities are often associated with other cosmetic problems and skin diseases such as pigmentation, solar lentigos, angiomas seborrheic keratosis, scars, etc. Elimination of the scar telangiectasia may reduce the swelling and bulkiness of the scar and normalize the surface texture. Phlebectomy, sclerotherapy, and different types of lasers are commonly used in these cases. Ambulatory phlebectomy or foam sclerotherapy is used to treat veins > 4 mm. Only then would one consider the laser or intense pulsed light for any remaining veins. Prominent veins on the breast, forehead, and eyelid are not uncommon and patients often seek their removal. Sclerotherapy is a procedure that has been successfully used to permanently remove them.