Comparison of Four Haemodynamic Tests that Quantify Superficial Venous Insufficiency.

OBJECTIVES: Reflux assessment with ultrasound (U/S) is usually qualitative. Quantitative measurements of superficial venous insufficiency (SVI) include the venous arterial flow index (VAFI), recirculation index (RCI), venous filling index (VFI), and the postural diameter change (PDC) of the saphenous trunk. The aim was to investigate their relationship. MATERIALS AND METHODS: This was an observational study performed on patients with varicose veins and hospital employees. Four haemodynamic parameters were measured in 21 legs from 16 subjects. Legs were divided into no reflux (n = 7) and reflux (n = 14). The VAFI is the U/S ratio of common femoral vein volume flow divided by the common femoral artery volume flow, performed supine. The RCI is the U/S ratio of reflux volume over antegrade volume within the saphenous trunk after calf compression, standing. The VFI is the rate of calf volume increase on dependency measured in mL/s, using air plethysmography. The PDC is the percentage reduction of the saphenous trunk diameter from standing to lying, using U/S. RESULTS: The clinical part of the CEAP classification was: C0 = 3, C1 = 4, C2 = 5, C3 = 1, C4a = 1, C4b = 6, C5 = 1. All four tests demonstrated significant differences between the two groups with minimal overlap (Mann Whitney U test): VAFI (p = .028), RCI (p < .0005), VFI (p = .001), and PDC (p = .014). Furthermore, significant correlations were observed with the tests: VAFI vs. RCI (r = .532, p = .015), VFI (r = .489, p = .025) and PDC (r = -.474, p = .030); RCI vs. VFI (r = .446, p = .043) and PDC (r = -.527, p = .014). CONCLUSIONS: Superficial venous drainage insufficiency should not be confined to an U/S assessment of the presence of reflux, which is qualitative. Quantitative data may be provided using the VAFI, RCI, VFI, and PDC. Understanding why there are significant correlations among these parameters and the preferred objective reference test requires further work.

The Discord Outcome Analysis (DOA) as a Reporting Standard at Three Months and Five Years in Randomised Varicose Vein Treatment Trials.

OBJECTIVES: Treatment success for chronic superficial venous insufficiency could be defined as an improvement in three domains: (i) disease specific quality of life, (ii) clinical severity, (iii) reflux. The aim was to report these at five years using a Venn diagram to profile the outcomes: a discord outcome analysis (DOA). METHODS: Patients (n = 50 patients/legs in each treated group) were randomised to endovenous laser ablation (EVLA) with concurrent phlebectomies vs. ultrasound guided foam sclerotherapy (UGFS). Outcomes were assessed using three domains: (i) Aberdeen varicose vein questionnaire (AVVQ), (ii) venous clinical severity score (VCSS), (iii) venous filling index (VFI) of air plethysmography. Change scores were calculated by subtracting the final score after treatment from the baseline score before treatment to quantify the improvement. This was followed by a DOA profile for each patient where a discord was defined as the percentage of patients with a numerical deterioration in one or two domains. RESULTS: The median [interquartile range] follow up was 68 [64-72] months. Follow up in all three domains was EVLA: 45/50, UGFS: 42/50. On ultrasound examination, GSV occlusion at some point above the knee was 93% for EVLA and 64% for UGFS (p = .001). There was no significant difference in improvement between the two treatment groups in the VCSS and the VFI. However, the EVLA group had a statistically significant AVVQ improvement (p = .004). Using a DOA, only 76% EVLA versus 60% UGFS had success in all three domains. Using improvement thresholds, this reduced to 54% and 39%, respectively. The commonest discord pattern was an improvement in the VCSS and VFI but deterioration in the AVVQ. CONCLUSIONS: A DOA demonstrated that the definition of success is reduced if deterioration in one or two domains is taken into account. A DOA should be considered as a reporting standard for comparative analyses.

Impact of preclinical carotid atherosclerosis on global cardiovascular risk stratification and events in a 10-year follow-up: comparison between the algorithms of the Framingham Heart Study, the European SCORE and the Italian 'Progetto Cuore'.

BACKGROUND: The aim of the study was to compare three widely used algorithms for stratification of the global cardiovascular risk (GCVR): the Framingham Heart Study (FHS) score, the European systemic coronary risk estimation (SCORE) and the Italian 'Progetto Cuore' (heart project) score. It was also investigated how preclinical carotid atherosclerosis (pre-ATS) might influence the incidence and improve the risk prediction of cerebrovascular and cardiovascular events. METHODS: Subjects (n = 358) without previous history of cardiovascular disease (CVD) were recruited and the GCVR was calculated for each patient. An ultrasound evaluation of the carotid arteries was also performed. RESULTS: According to SCORE, the recruited population had globally a low risk of cardiovascular mortality and the risk equation estimated a GCVR of 2% in spite of the in spite of the observed rate of 0.8% (95% CI -0.001 to 0.02) of fatal events. The FHS and the 'Progetto Cuore' risk equations, regarding a 10-year risk of fatal and nonfatal events, predicted a low GCVR of 31 and 30%, an intermediate risk of 64 and 66%, and a high risk of 5 and 4% of the population respectively. They also estimated a general GCVR of 6.9 and 6.4% respectively versus an observed event rate 27.7 (95% CI 23.0 to 32.0). The discriminative power, calculated with the area under the receiving operator curve (AUROC), was 0.53 for SCORE, 0.54 for FHS and 0.55 for Progetto Cuore. Based on the ultrasound evaluation of carotid arteries, a first clinical event at 10-year follow-up was reported in 3% of subjects with normal ultrasound examination, 32% with intima-media thickening (IMT) and 62% with asymptomatic carotid plaque (ACP). CONCLUSION: The present study has evaluated for the first time the prediction of GCVR in an asymptomatic population, comparing three different risk scores. Carotid pre-ATS was related to the major cardiovascular risk factors (RFs) and was independently associated with a major incidence of cerebro- and cardiovascular events, therefore enhancing the predictive value of the three different risk scores.

Compression therapy after invasive treatment of superficial veins of the lower extremities: Clinical practice guidelines of the American Venous Forum, Society for Vascular Surgery, American College of Phlebology, Society for Vascular Medicine, and International Union of Phlebology.

Guideline 1.1: Compression after thermal ablation or stripping of the saphenous veins. When possible, we suggest compression (elastic stockings or wraps) should be used after surgical or thermal procedures to eliminate varicose veins. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 1.2: Dose of compression after thermal ablation or stripping of the varicose veins. If compression dressings are to be used postprocedurally in patients undergoing ablation or surgical procedures on the saphenous veins, those providing pressures >20 mm Hg together with eccentric pads placed directly over the vein ablated or operated on provide the greatest reduction in postoperative pain.[GRADE - 2; LEVEL OF EVIDENCE - B] Guideline 2.1: Duration of compression therapy after thermal ablation or stripping of the saphenous veins. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after treatment. [BEST PRACTICE] Guideline 3.1: Compression therapy after sclerotherapy. We suggest compression therapy immediately after treatment of superficial veins with sclerotherapy to improve outcomes of sclerotherapy. [GRADE - 2; LEVEL OF EVIDENCE - C] Guideline 3.2: Duration of compression therapy after sclerotherapy. In the absence of convincing evidence, we recommend best clinical judgment to determine the duration of compression therapy after sclerotherapy. [BEST PRACTICE] Guideline 4.1: Compression after superficial vein treatment in patients with a venous leg ulcer. In a patient with a venous leg ulcer, we recommend compression therapy over no compression therapy to increase venous leg ulcer healing rate and to decrease the risk of ulcer recurrence. [GRADE - 1; LEVEL OF EVIDENCE - B] Guideline 4.2: Compression after superficial vein treatment in patients with a mixed arterial and venous leg ulcer. In a patient with a venous leg ulcer and underlying arterial disease, we suggest limiting the use of compression to patients with ankle-brachial index exceeding 0.5 or if absolute ankle pressure is >60 mm Hg. [GRADE - 2; LEVEL OF EVIDENCE - C].

Underwater Sonography of Leg Veins.

OBJECTIVES: Hydrostatic compression (HC) occurring during body immersion is considered beneficial for venous return from the lower limbs. No study has evaluated the effects of HC on the veins of the lower limbs using duplex ultrasound (DU). The purpose of this study was to use DU to evaluate the morphology and flow of the leg veins during immersion. DESIGN: The femoral and great saphenous veins were evaluated before and during immersion in a specifically built pool, in normal and varicose limbs. RESULTS: HC reduces vein size in both normal and varicose limbs. During immersion spontaneous flow increases whereas when present, blood reflux decreases. DISCUSSION: This pilot, proof of concept study has demonstrated the feasibility of DU investigation of leg veins during immersion. Larger series of underwater DU evaluations of normal and varicose legs are necessary to quantify and better explain the effects of HC on the veins of the lower limb.

Validation of a Gravitational Model to Study Local Endogenous Biomarkers in Chronic Venous Insufficiency.

OBJECTIVE/BACKGROUND: Unlike most systemic chronic diseases, chronic venous insufficiency (CVI) is ideal to study using endogenous biomarkers. The stimulus causing damage can be turned on and off with gravitational positioning and venous blood samples can be taken locally. Annexin V (apoptosis) and microparticles (cell membrane debris) were used as markers of cell destruction, with matrix metalloproteinases (MMPs) as markers of tissue remodelling. The aim of this proof of concept study was to validate a gravitational model by investigating whether standing induced biochemical stress and whether recovery occurs on lying and after compression. METHODS: Fourteen patients (C4a-b) and 14 volunteers (C0-1) were tested under three supervised laboratory conditions for 1 h on separate days: (i) stationary standing on a small paper square; (ii) lying with both legs elevated 20°; (iii) compression standing using a 23-32 mmHg below knee stocking. Immediately after each condition, venous blood was withdrawn from the ankle. Commercial enzyme linked immunosorbent assay kits were used for batch analysis of the plasma samples. RESULTS: Median (interquartile range [IQR]) values of annexin V (AU/mL) and microparticles (nM) standing were as follows: volunteers 2.9 (2 - 3.4) and 10.2 (8.8 - 13.8), and patients 2.2 (1.3 - 6) and 11.3 (7.7 - 20), respectively. Significant reductions were observed lying: volunteers 2.1 (1.5 - 2.7; p = .019) and 8.5 (7.4 - 9.4; p = .041), patients 1.7 (1.2 - 2.7; p = .004) and 8.5 (7.0 - 11.4; p = .041), respectively. Globally, all median MMP values in the patients reduced with lying and with compression versus standing (p = .004). Individually, significant reductions occurred in MMPs 2 and 13 with compression and MMPs 3, 7, 8, 9, 10, and 12 on lying. Lying was more effective at reducing MMP levels than compression. CONCLUSION: Annexin V and microparticle concentrations are responsive to elevation and compression after 1 h. In the patients, all the tested MMPs decreased after lying and with compression versus standing. This model provides evidence supporting gravitational protection in the treatment of CVI.

Neuromuscular electrical stimulation reduces sludge in the popliteal vein.

BACKGROUND: The common peroneal nerve stimulator (CPNS) is a UK-approved device for reducing venous thromboembolism (VTE) risk. It resembles a wrist watch and is placed over the common peroneal nerve, discharging electricity at a rate of 1 impulse/s. It has been presumed that as blood flow slows, erythrocytes aggregate into ultrasound-detectable echogenic particles, described as venous sludge. The aim of the study was to determine whether the CPNS reduces venous sludge by using an ultrasound-derived gray-scale (0-255) venous sludge index (VSI). METHODS: Twenty-five healthy volunteers had their right popliteal vein video recorded using B-mode ultrasound at 22 frames/s in longitudinal and transverse views, standing and lying. This was performed first with the CPNS off and then with the CPNS on. The CPNS impulse intensity used was set from 1 to 7 for each individual, and the level was sufficient to cause an outward jerking movement of the foot. A single frame of the possible 154 frames, lasting 7 seconds, was selected using a random number generator for the image analysis. The "brightness" of the erythrocyte aggregates (pixels) within a circular sampling area was quantified using the VSI. The brighter the sample, the greater the sludge. RESULTS: Values are expressed as median (interquartile range). On standing with the device off, there was a significantly higher VSI (P < .0005) compared with lying (longitudinal view, 27.7 [18.8-41.4] vs 11.7 [5.5-17.5]; transverse view, 20.7 [13.6-32.2] vs 11.4 [6.3-15.9]). Activation of the CPNS significantly reduced all the VSI values (P < .0005) shown (longitudinal view, 2 [1.1-3.2] and 1.5 [0.5-3.1]; transverse view, 1.1 [0.6-2.7] and 0.8 [0.5-2.1]). CONCLUSIONS: The CPNS device significantly reduces venous sludge within the popliteal vein irrespective of whether the subject is standing or lying down or of the longitudinal or transverse position of the ultrasound transducer. The principal mode of action of the device in the claim that it may reduce venous thromboembolism risk may be through a reduction of venous sludge. However, the relationship between erythrocyte aggregation, venous stasis, and venous thromboembolism risk requires more investigation.

Optimizing calf muscle pump function.

Background The tip toe manoeuvre has been promoted as the gold standard plethysmography test for measuring calf muscle pump function. The aim was to compare the tip toe manoeuvre, dorsiflexion manoeuvre and a body weight transfer manoeuvre using the ejection fraction of air-plethysmography and evaluate which has the best pumping effect. Methods Sixty-six archived tracings on 22 legs were retrieved from an air-plethysmography workshop and analysed. Pumping performance was measured using the calf volume reduction after each manoeuvre. Results Expressed as median [inter-quartile range], body weight transfer manoeuvres resulted in a significantly greater ejection fraction (%) than tip toe manoeuvres at 59.7 [53.5-63.9] versus 42.6 [30.5-52.6], P < 0.0005 (Wilcoxon). There was no significant difference in the ejection fraction between the tip toe manoeuvre versus dorsiflexion manoeuvre, P = 0.615. The repeatability (confidence interval: 95%) of 66 ejection fraction tests was excellent: tip toe manoeuvre (±1.2), dorsiflexion manoeuvre (±1.3) and body weight transfer manoeuvre (±1.6). Conclusion The body weight transfer manoeuvre appears to be a better method of measuring the full potential of the calf muscle pump with a 40.1% relative increase in the ejection fraction compared to a tip toe manoeuvre. Exercises which involve body weight transfers from one leg to the other may be more important in optimizing calf muscle pump function than ankle movement exercises.

Venous Thromboprophylaxis With Neuromuscular Stimulation: Is It Calf Muscle Pumping or Just Twitches and Jerks?

The common peroneal nerve stimulator (CPNS) is a UK-approved device for reducing venous thromboembolism risk. It resembles a wrist watch and is placed over the common peroneal nerve to fire at 1 electrical impulse/sec. The aim was to quantify the claim that it drives the venous muscle pump and imitates walking. Twelve healthy volunteers performed 10 tip-toe maneuvers and 10 ankle dorsiflexions to imitate walking movements. The reductions in calf volume were recorded using air plethysmography (APG). The common peroneal nerve was stimulated for over 10 seconds at each of the 7 increasing electrical impulse settings, and the volume reductions were measured for comparison. The results are expressed as median (interquartile range) absolute (mL), and percentage reduction in calf volume. Tip-toe and dorsiflexion pumping maneuvers were not significantly different: 59 (33.6-96.1), 81.9% vs 51.4 (34-68.5), 59.7%, respectively ( P = .53). However, they both outperformed the CPNS: 10.8 (7.3-18), 13.2% at P = .002 and P = .002, respectively. Qualitatively, the CPNS registered on the tracings as a small spike (muscle twitch) at low settings, with larger amplitudes (ankle jerk) at higher settings. The CPNS activity spikes were discrete, lasting a median (range) of 0.24 (0.16- .3) seconds. The claim that the CPNS empties veins by pumping is supported statistically. However, the amount is small versus the tip-toe and dorsiflexion maneuvers. Furthermore, the CPNS has a short activity profile on the APG trace. Innovations that produce sustained contraction and involve the posterior calf compartments may improve pumping.

Validation of the novel venous drainage index with stepwise increases in thigh compression pressure in the quantification of venous obstruction.

BACKGROUND: Venous drainage from the leg is poorly understood, and it is difficult to quantify it hemodynamically. Attempts have been made using duplex ultrasound scanning and venous occlusion air plethysmography (APG). However, they have limited value in day-to-day clinical practice. This is because venous drainage measurements have never been validated successfully against increasing obstruction pressures. The hypothesis is that the novel gravitational venous drainage index (VDI) in milliliters/second is reduced in response to increasing venous obstruction, and the aim was to quantify this, using stepwise inflations of a thigh cuff. METHODS: Venous drainage tracings were obtained with APG using a dependency to elevation maneuver on the right legs of 21 volunteers (9 female) without venous disease. The test was performed once without a thigh cuff and then with a contoured thigh cuff (18 cm wide) inflated in steps at 10, 20, 30, 40, and 50 mm Hg just before elevation. The function of the thigh cuff was to mimic venous obstruction. The drainage volumes were obtained once the tracing from the elevated cuffed leg decreased to a steady line, when arterial inflow equals venous outflow. The VDI was calculated in the same way as the opposite maneuver, the venous filling index, is obtained from the venous filling tracing (elevation to dependency maneuver), namely, VDI = 90% venous drainage volume/venous drainage time to 90%. The drainage reserve volume (DRV) was defined as the undrained volume caused by the venous obstruction from the thigh cuff. RESULTS: With stepwise inflations of the thigh cuff at 0, 20, 30, 40, and 50 mm Hg, the median VDI is reduced (26.1, 24.1, 12.1, 7.8, 5.4) and the DRV is increased (0, 5.3, 15.4, 45.5, 62.6). Furthermore, the VDI reductions and the DRV increases correlated significantly (P < .0005) with increasing obstruction pressure at r = -0.69 and r = 0.793, respectively (Spearman). CONCLUSIONS: The VDI is a novel APG parameter derived from a dependency to elevation maneuver that represents the gravitational venous drainage rate of the leg. The DRV is the undrained venous volume caused by the obstruction from an inflated thigh cuff. Both parameters have been demonstrated to respond to and to correlate with increasing venous obstruction pressures. Their potential clinical value in assessing the hemodynamic significance of an iliac or femoral stenosis and in the screening and selection of patients requiring iliac stenting and follow-up requires further investigation.

Are Inflammatory Biomarkers Increased in Varicose Vein Blood?

OBJECTIVES: To test for the presence of inflammatory biomarkers in blood taken from varicose veins versus antecubital blood of the same patient and compare this to levels in healthy controls. METHODS: Using a multiplex biochip array method (Randox, United Kingdom), the interleukins (ILs) IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10; vascular endothelial growth factor; interferon γ, tumor necrosis factor α ; monocyte chemotactic protein 1 (MCP-1); and epidermal growth factor were measured in citrated plasma samples drawn from the arms and legs of 24 patients with varicose veins and 24 controls. RESULTS: Expressed as median (interquartile range) in pg/mL, leg samples from patients with varicose veins had significantly higher levels of IL-8 and MCP-1 compared to their own arm samples (IL-8: local 2.3 [1.71-3.3] vs systemic 2.3 [1.62-2.98], P = .023; MCP-1: local 114.42 [84.29-139.05] vs systemic 103.56 [79.75-126.42], P < .0005). This was not observed in the control group. Leg samples from both patients with varicose vein and controls had higher levels of IL-6 compared to their own arm samples (patients: local 1.67 [0.82-4.48] vs systemic 1.24 [0.58-3.26], P = .002; controls: local 1.23 [0.83-1.7] vs systemic 1.03 [1.7-1.52], P = .005). No significant differences were detected with the other biomarkers. CONCLUSIONS: Blood drawn from the site of varicose veins appears to have significantly increased concentrations of IL-6, IL-8, and MCP-1 when compared to the same patient's arm blood. This supports the hypothesis that inflammation is activated from the tissues drained by the varicose veins.

Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence.

There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

Quantifying saphenous recirculation in patients with primary lower extremity venous reflux.

BACKGROUND: The great saphenous vein (GSV) in patients with superficial venous insufficiency might act as a beneficial conduit for antegrade venous drainage and also as a harmful conduit for promotion of reflux and/or recirculation and subsequent skin changes. The aim of this study was to measure the antegrade and retrograde GSV volume displacements during calf compression and release maneuvers. This was used to quantify harm over benefit with a recirculation index (RCI). METHODS: Sixteen legs (nine right) from 16 patients (nine male) with primary superficial venous insufficiency were scanned standing with duplex ultrasound, at the upper thigh GSV, 10 cm below the sapheno-femoral junction. The clinical, etiological, anatomical, pathophysiological class was C2 = 3, C3 = 2, C4a = 6, C4b = 4, C5 = 1. The median age (range), venous clinical severity score, and refluxing GSV diameter were 63 (21-79) years, 8 (4-16), and 7 (5-10) mm, respectively. A manual calf compression and release (MCCR) maneuver was performed once, and a cyclical calf compression and release (CCCR) three times for repeatability. With the CCCR maneuver, the calf-cuff and inflation-deflation pump provided a cyclical compression pressure of 120 mm Hg (3 seconds) with a release time of 16.4 seconds to standardize venous refilling time. RESULTS: The results are expressed as median [interquartile range]. The CCCR compared with the MCCR resulted in longer reflux duration (16.4 [8.2-16.4] seconds vs 5.7 [3.7-6.8] seconds; P < .0005), higher time-averaged mean velocities in reflux (23.5 [14.9-27.9] cm/s vs 14.1 [9-17.6] cm/s; P < .0005) and greater reflux volume displacements (81.7 [38.8-152.8] mL vs 27.3 [16.4-53.4] mL; P < .0005). There were significant correlations between increasing antegrade volume measurements and increasing reflux volume measurements irrespective of whether CCCR, (r = 0.841; P < .0005) or MCCR (r = 0.762; P = .001) was used. This implies that the displaced antegrade volume might have a causal effect on the resulting reflux volume. The ratio of reflux volume/antegrade volume (RCI) was 2.14 [1.58-2.74] with the CCCR. This supports the recirculation phenomenon. Adjusted to a standard median for each leg, the repeatability limits (three times) of the RCI was excellent at 2.14 (95% confidence interval, 2.09-2.21). CONCLUSIONS: In this study we measured the behavior of the GSV in terms of harmful reflux over beneficial drainage using the RCI. We recognize that reflux values depend on the type of provocation test and the amount of displaced antegrade volume. This limitation might be overcome by factoring reflux as an expression of antegrade flow using the RCI. When standardized, a test for quantifying saphenous recirculation might have many clinical applications. The next step should be a prospective study to validate the RCI with clinical and quality of life parameters.

Endogenous pro-thrombotic biomarkers from the arm and leg may not have the same value.

OBJECTIVE: Assessments of endogenous pro-thrombotic biomarkers are performed invariably on arm blood. However, the commonest site for thrombosis is in the leg. A leg blood sample may reflect local pro-thrombotic processes more accurately than systemic arm blood. The aim was to determine whether pro-thrombotic biomarkers from standard venous arm samples differed significantly from leg samples. METHOD: Concurrent blood samples were taken from an ankle/lower calf varicose vein and an ante-cubital vein in 24 patients awaiting laser treatment as well as age approximated and sex matched healthy controls without venous disease. The following assays were performed: thrombin-antithrombin (ng/ml), antithrombin (%) activity, microparticles (nM), fibrinogen (mg/dl), prothrombin fragment 1.2 (F1.2) (pM) and P-selectin (ng/ml). RESULTS: Expressed as median (inter-quartile range). Significant arm/leg differences were observed in thrombin-antithrombin, antithrombin, prothrombin fragment 1.2 and P-selectin. The legs of patients had significantly reduced antithrombin activity and P-selectin concentrations compared to their arms (leg: 101 (90-108) versus arm: 112 (99-126), P = 0.001 and leg: 42 (26-52) versus 45 (27-52), P = 0.044, respectively). Control leg samples had significantly increased thrombin-antithrombin and P-selectin compared to control arm samples (leg: 2.1 (0.9-3.2) versus arm: 0.8 (0.5-1.7), P = 0.015 and leg: 36 (24-50) versus arm: 30 (23-41), P = 0.007, respectively). However, the control legs had significantly reduced F1.2 (leg: 265 (230-333) versus arm: 299 (236-361), P = 0.028). No significant arm/leg differences were detected in the microparticle or fibrinogen levels. CONCLUSIONS: These findings indicate that venous arm blood is significantly different from venous leg blood in four out of six biomarkers studied. Recognition of local venous leg sampling as a site for investigation may unravel why the leg has a greater predisposition to thrombosis and lead the way towards an arm/leg differential test.

Gravitational venous drainage is significantly faster in patients with varicose veins.

OBJECTIVES: It has been proposed that varicose veins may be caused by a degree of impeded proximal venous drainage (pelvic venous obstruction) in the same way that biological tubes dilate in response to an obstruction. The venous drainage index (VDI) of air-plethysmography (APG) was used to test this hypothesis. A dependency to elevation manoeuvre was used to provoke gravitational venous drainage. A rapid reduction in calf volume implied good drainage. METHODS: This was a single centre, proof-of-concept study comparing gravitational venous drainage in varicose vein patients and controls. Leg filling and drainage manoeuvres (elevation to dependency and dependency to elevation) were performed three times per leg in 15 patients (7 male, 8 right) and 16 controls (3 male, 8 right). The VDI was measured in the same way the established venous filling index (VFI) is calculated to quantify filling: VDI = 90% of venous drainage volume (90VDV)/90% venous drainage time (VDT90). RESULTS: The patients were significantly older at 58 (41-75) years versus the controls 47 (18-58), p = 0.001. There was no significant difference between the groups in weight, height, BMI or common femoral vein diameter. The patients were (C2 = 8; C3 = 1, C4 = 6), VCSS 4 (1-11) with a median refluxing proximal thigh saphenous diameter of 6 (5-11) mm. The median (inter-quartile range) VFI and VDI (both in mL/s) in the control tests (n = 48) were 1.3 (0.9-1.9) and 33.8 (21.5-55), respectively. The VFI and VDI in the patient tests (n = 41) were significantly faster at 6.2 (3.5-9.4), p < 0.0005, and 47.1 (36.1-66.3), p = 0.002, respectively. Adjusted to a standard mean for each leg, the reproducibility limits (×3) of the VDI was very good at 39.7 (95% CI: 36.5-42.9) in controls and 52.9 (95% CI: 49.7-56.1) in patients. CONCLUSION: The VDI was significantly greater in patients with varicose veins compared to controls. It is unlikely that impeded gravitational drainage is a significant factor in the pathophysiology of varicose veins.

d-Dimer Levels are Significantly Increased in Blood Taken From Varicose Veins Compared With Antecubital Blood From the Same Patient.

d-Dimer is a prothrombotic biomarker and a very sensitive measure of endogenous fibrinolysis. It is used as a screening test for suspected deep vein thrombosis. This study investigated whether d-dimer levels were increased in the varicose veins of patients in comparison to their own arm samples. Patients, n = 24, 17 male, age 45 (25-91), C2-6, awaiting saphenous laser ablation were compared to matched controls, n = 24, 17 male, age 42 (24-89). Concurrent venous blood samples were taken from the arm and a lower calf/ankle (varicose) vein. The median (interquartile range) d-dimer (ng/mL) level was significantly greater in the ankle than in the arm blood of the same patient at 319 (164-631) versus 281 (167-562), P = .003, Wilcoxon. This did not occur in the controls at 269 (80-564) versus 262 (106-526), P = .361, Wilcoxon. The results indicate increased endogenous fibrinolysis in varicose veins compared with arm blood. This suggests there is more thrombotic activity or dissolution of formed subclinical fibrin thrombus which may explain the association of varicose veins with superficial vein thrombosis. This contrasts with earlier studies reporting a local reduction in fibrinolysis in venous disease.

Pneumatic thigh compression reduces calf volume and augments the venous return.

OBJECTIVES: Reactive hyperaemia following thigh compression increases arterial inflow and venous outflow. The net effect can be measured by changes in calf volume quantified using air-plethysmography. The objective was to investigate the effect of thigh compression on venous return. METHOD: The right legs of 19 consecutive volunteers (14 male), median age 31 (25-56) years, were studied in the supine position using air-plethysmography. The clinical, etiological, anatomical, pathophysiological (CEAP) class was C0. A thigh-cuff, 12 cm wide, was inflated in increments of 10 mmHg, from 0 to 80 mmHg. After each inflation step, the calf volume increased to a plateau and was recorded. At 80 mmHg, the thigh-cuff was deflated suddenly with the calf volume decreasing until baseline. Calf volume changes were recorded and stored for analysis. RESULTS: There was a stepwise increase in the venous volume of the calf with each incremental rise in thigh-cuff pressure up to 80 mmHg (p < .0005, Friedman). The median (interquartile range) increase in venous volume from 0 to 80 mmHg was 87 (65-113) mL (p < .0005, Wilcoxon). The volume change below the original baseline following thigh-cuff release was -16 (-12 to -25) mL (p < .0005, Wilcoxon). CONCLUSIONS: Once optimised, intermittent pneumatic compression of the thigh may have a therapeutic role in augmenting the venous return and reducing leg swelling in patients.