Servier – Phlebolymphology

VII. News in the research on
the chronic venous disease –
pathophysiology, anatomy and
symptoms

How vein disease begins – insufficiency in children and adolescents
Johann Chrisof Ragg (Germany)
Recent studies on the onset of intra and epifascial venous disease show four major components: (i) congenital valve lesions; (ii) stress-induced valve decompensation, as seen in heavy workers or athletes; (iii) stasis-induced inflammatory valve degeneration; and (iv) usually secondary phlebitis. As congenital venous valve damage is the first to occur in life, it should prepare a primary pattern of an individual course of venous disease. Therefore, using high-frequency ultrasound systems (Siemens Juniper, Zonare One Pro, Mindray M9, 16-23 MHz; Vevo MD, 16-32 MHz), Johann C. Ragg examined 102 children and adolescents aged 6 to 18 years (mean, 12.5 years; 59 females, 43 males) who were all asymptomatic. Investigation time was limited to 15 minutes. In case of visible vein changes (protruding, more intense color, increased diameter), ultrasound imaging was started at that site. Otherwise, systematic screening of saphenous veins and typical perforator locations was performed. Overall, 71/102 children (58.8%) and 60/204 legs (34.8%) showed relevant venous pathologies. Lesions were mainly located in the great saphenous vein (60/204 [29.4%]) vs primary saphenous side-branch varices (3.9%), small saphenous vein (3.4%), and perforator veins (1.0%). Lesions in the great saphenous vein in the lower leg occurred in 61.0% of the patients with lesions. In the subgroup of children aged 6 to 8 years, 11/23 (47.8%) already showed a relevant pathology; 42.3% of all cases were related to a single valve failure. Among these, unilateral commissural mismatch was the most frequent pattern (70.0%). In conclusion, the unexpected high incidence of detected valve lesions in children, particularly in the younger ones, could be best explained by congenital disease. The challenge is to understand which patients and at which age might have preventive benefit from early detection and eventually a cost-effective therapy.

Anatomy and 3D modeling of the popliteal fossa perforating veins
Jean Francois Uhl (France)
The aim of this study was to make an anatomical description of the bony venous perforator veins at the knee level, which are frequently missed during investigation of patients with chronic venous disease. Therefore, venous mapping of 25 000 patients and 1200 computed-tomography venographies before surgery for varicose veins were examined. Anatomically, these perforator veins were defined as “perforating veins feeding a varicosenetwork of the popliteal area not connected to a tributary of small saphenous vein,” with a prevalence of about 4%. Anatomically, they have four main characteristics: (i) always located laterally from the midline; (ii) end in the lateral aspect of the popliteal vein; (iii) located, on average, 2 cm above the saphenofemoral junction; and (iv) no connection to the small saphenous vein. They are very frequently observed in REVAS (recurrent varices after surgery) after ligation of the small saphenous vein, commonly associated with other refluxing perforator veins and to more severe chronic venous disease (the C of CEAP). In all cases, one must look for a systolic reflux of the perforator veins and eliminate a vicarious shunt due to a venous obstruction, in particular a Hunter’s canal stenosis.

Anatomy of the bony perforators veins of the knee
Jean Francois Uhl (France)
The aim of this study was to make an anatomical description of the bony vein perforator veins at the knee level, which are frequently missed during investigation of patients with chronic venous disease. Multiple series of anatomical slices of fresh cadavers injected with green latex and a series of CT venographies as well as Duplex color investigations were used to study their precise location and the connections with the venous network of the knee. Anatomically, these perforator veins are commonly located anteriorly around the patella, and posteriorly in the inter-condylar grove, medially and laterally. Their connections with the popliteal vein are multiple. During Duplex ultrasound assessment, as well as CT venography, they are often ignored due to their small caliber.

The physiological hypothesis is that, at the knee level, the spongy bone of both tibia and femur epiphysis is important for the production of red blood cells. They connect the venous system in the popliteal vein by several tiny perforators. In practice, these tiny perforators are not investigated and are ignored by sonographers. They should be distinguished from the large perforator veins of the tibial diaphysis responsible for varicose veins of the leg.¹ These perforator veins could also be linked to the so-called “phleboarthrosis” that was described recently.^2-4 The bony perforator veins of the knee are commonly responsible for reticular veins or telangiectasias around the knee, but they are underdiagnosed by sonographers. This explains why the injection of these cosmetic lesions around the knee frequently leads to recurrence.

References
1. Ramelet AA, Crebassa V, D’Alotto C, et al. Anomalous intraosseous venous drainage: bone perforators? Phlebology . 2016;32:241-248. 2.
2. Giovanni B, Agus M, Agus A. Phleboarthrosis. Acta Phlebologica . 2017;18:63- 64.
3. Lejoyeux R. Study of a case of phleboarthrosis. Treatment with strapping and sclerosing injections. Phlébologie . 1972;25:35-37.
4. Hach W. Das arthrogene Stauungssyndrom. Das aktuellephlebologische . 2003;3.

A systematic review of the relationships between venous diameters, clinical severity and quality of life
Matthew Tan (UK)
Chronic venous disease (CVD) represents a significant impact on patients’ health-related quality of life (HRQOL). To help guide further management, truncal vein diametersare recorded during duplex ultrasound assessment; these diameters can be used to determine treatment eligibility, for example, by insurance companies. While some studies have shown an association between truncal diameters and both clinical severity and HRQOL scores, this relationship is still poorly characterized. This systematic review aims to synthesize the evidence in the literature pertaining to such relationships to better inform CVD management. Full text studies in English reporting on the relationship between great and/or small saphenous vein diameters and clinical severity and/or HRQOL scores were included. Papers reporting only on truncal vein diameters, clinical severity, or HRQOL scores without describing their relationship and papers focusing on nontruncal veins were excluded. Eleven studies were included in this review, involving a total of 2732 limbs with symptomatic C₀-C₁ disease and C₂-C₆ disease. Relationships between truncal vein diameters and both clinical severity and HRQOL scores were reported in four studies, with the other seven studies reporting on relationships with clinical severity only. Validated classification tools were used to measure both HRQOL (AVVQ, ClVIQ, VElNES-QoL/Sym, VVSymQ) and clinical severity (CEAP, VCSS).

Truncal vein diameters were related to CEAP stages in seven studies; the majority of studies observed increasing diameters with increasing clinical severity. Four studies reported weak positive correlations between the venous clinical severity score (VCSS) and increasing vein diameters. One study also reported diameters to be correlated with individual VCSS components. However, all studies included in this review failed to show any significant relationship between truncal vein diameters and any HRQOL score. Therefore, current studies suggest that, in CVD, truncal vein diameters exhibit a weak association with clinical severity, but not HRQOL scores, and therefore the patients’ perceived impact of CVD. This suggests that truncal vein diameters should not be utilized as a criterion for treatment eligibility.

The Villalta score is a better predictor for pre-existing chronic venous disease than for the development of post thrombotic syndrome
John Fish (US)
Patients with chronic venous disease (CVD) without a history of thrombosis may show some of the same signs and symptoms as those with postthrombotic syndrome. A previous study showed that the contralateral leg of those with a first unprovoked deep venous thrombosis (DVT) also displayed elevated Villalta scores in 40% of patients. The effect of a DVT on the Villalta scores appears to be unpredictable. Although the Villalta scores is a validated tool for classifying postthrombotic syndrome (score >4), misclassification bias may exist. The authors set out to prospectively compare the Villalta scores and venous clinical severity score (VCSS) in patients with and without a history of DVT to determine the degree of misclassification bias as well as any changes in Villalta scores that occurred after the first development of DVT. Patients with chronic venous disease were prospectively enrolled from a single vein center over a period of 12 months. Villalta scores and VCSS were completed for all patients, as well as a bilateral duplex ultrasound. Positive misclassification bias was defined as the percentage of patients identified with postthrombotic syndrome (Villalta scores >4 and a history of DVT), but without reflux or obstruction in the deep veins on venous duplex. Negative bias was defined as the percentage of patients identified as not having postthrombotic syndrome (Villalta scores ≤4 or no history of DVT), but were found with postthrombotic changes in the deep veins.

The studied prospectively enrolled 288 patients with C₂ to C₆ disease, of whom 258 had no history of DVT and a mean Villalta score of 8.12±4.91; 70% of the patients had a score consistent with having postthrombotic syndrome. Villalta scores correlated well with VCSS in this study population. Twelve of these patients subsequently developed DVT during the course of the study, and there were no significant changes in the Villalta scores. The patients with a history of DVT (n=30) had a mean Villalta score of 9.57±5.78. Of these patients, 26 had a Villalta scores ≥4 and would be given the diagnosis of postthrombotic syndrome. Of the 26 patients, 11 (42%) had normal deep veins on ultrasound (including pelvic veins), representing a positive bias. Although the use of the Villalta score is used as a basis for defining postthrombotic syndrome, the score appears to correlate well with VCSS in patients with CVD and does not significantly increase in patients before or after the first episode of DVT. This positive misclassification bias of 42% suggests that the use of the Villalta score may heavily misclassify those with primary CVD as postthrombotic syndrome. The value of the score was also not significantly higher in patients with a history of DVT compared with those with CVD without a history of DVT.

Is the differential diagnosis of lipoedema by means of high-resolution ultrasonography possible?
Tobias Hirsch (Germany)
The current German guidelines on treating lipedema recommend the use of flatknitted compression material and manual lymphatic drainage as well as liposuction. Differentiating lipedema from obesity and asymptomatic lipohypertrophy frequently proves difficult. However, a reproducible and objective differential diagnosis is the foundation of an expedient and cost-effective treatment. Therefore, as part of a multicenter registry study (five centers), ultrasound scans were performed on the legs (n=294) from 147 patients with lipedema (n=136), lymphedema (n=20), lipedema with secondary lymphedema (n=30), lipohypertrophy (n=42), and obesity (n=30), as well as healthy individuals (n=36). Measurements were performed on the thickness of the cutis and subcutis of the lower and upper leg and on their compressibility. An analysis of the sonomorphology was also conducted.

Special sonomorphological properties that allow lipedema to be differentiated from other disease entities and from healthy individuals have yet to be identified consistently and conclusively. The compressibility of the cutis-subcutis complex is completely unspecific and does not allow any conclusions to be drawn concerning lipedema. It has not been possible to detect fluid retention in patients with lipedema. Therefore, to date, the qualitative differentiation of the anatomical and pathomorphological features of lipedema from those of painless lipohypertrophy, obesity, and the skin/subcutaneous tissue from healthy people using sonographic imaging has not been possible to a satisfactory degree. Due to the large individual variation in findings and the likewise considerable differences in ultrasound scanners and their configuration, it is also currently impossible to obtain reproducible results that would enable the individual disease entities to be distinguished clearly. Contrary to expectations, the compressibility of the cutis-subcutis complex is entirely nonspecific. No sonographic correlate for clinical phenomena, such as the mattress phenomenon, could be established. Although ultrasound enables accumulations of interstitial fluid to be demonstrated, it does not provide any indications of edema etiology. As it was not possible to demonstrate fluid accumulations in patients with “painful lipohypertrophy,” the description of this disease as “lipedema” is misleading and shouldbe reconsidered. Currently, it must be assumed that, in routine care, essentially only the medical history and clinical findings are available for confirmation of the diagnosis of lipedema and its differential diagnosis.

The athlete’s vein: venous adaptations of the lower limb in endurance athletes
Kate Thomas (New Zealand)
It is established that arteries in athletes are larger, have thinner wall and have a demonstrated increase in vasodilatation during exercise. The objective of the study was to determine the impact of endurance exercise (20 minutes) on lower-limb venous morphology and function in athletes (n=20) compared with untrained controls (n=20). Prior to exercise, athletes had veins (profunda femoris, medial gastrocnemius, peroneal) with larger diameters and more perforators than normal controls. The venous volume was higher in athletes (160±41 vs 131±40 mL; P=0.03). The venous refilling time was also higher (169±42 vs 112±38 seconds; P<0.01). The venous filling index, which, in the absence of reflux, indicates arterial inflow, was not significantly different (0.9 vs 1.1 mL/s; P=0.15). After 30 minutes of exercise, there was an increased flow in the superficial veins, deep veins, and perforators. The increase was higher in athletes. For example, at 2.5 minutes after exercise, the mean flow in the common femoral vein was approximately 1100 mL/min in the athletes and only 750 mL/min with full recovery to normal resting flows in both groups at 20 minutes. The great saphenous vein was dilated in both groups. After exercise, venous volume decreased in the athletes, but was unchanged in normal controls. The venous filling index increased in both groups 2 to 5 times, indicating increased arterial inflow with a corresponding decrease in refilling time. The unchanged ejection fraction in the presence of an increased venous volume in the athletes suggests an increased ejected volume in this group.