VIEW-VLU observational study of the effect of Varithena on wound healing in the treatment of venous leg ulcers.

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates. METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included wound healing rate (change in wound perimeter), wound closure at 12 weeks after treatment, and time to wound closure. Secondary outcomes included VLU recurrence, numeric pain score at the ulcer location, EuroQol five-dimension five-level questionnaire quality-of-life index, and the Venous Clinical Severity Score. Patients were followed for 12 months. RESULTS: We enrolled 76 patients (80 ulcers) from 14 sites across the United States and Canada (mean age 63.6 ± 13.7 years, 39.5% female, mean body mass index 36.3). Of the enrollees, 96.3% presented with great saphenous vein incompetence. The mean baseline wound perimeter was 117.2 ± 107.4 mm and 26.3% of wounds (21/80) were circumferential. The mean ulcer age was 34.8 ± 51.8 weeks at first presentation and the mean compression therapy duration was 26.4 ± 35.9 weeks. The median wound perimeter decreased by 16.3% from baseline in the first 2 weeks after the procedure and by 27.0% at 12 weeks. By 12 weeks, 53.8% of wounds (43/80) were healed. The median time to ulcer closure by Kaplan-Meier analysis was 89 days (95% confidence interval, 62.0-117.0). In a Kaplan-Meier analysis of initially healed wounds, 88.9% (95% confidence interval, 76.9-94.8) remained closed at 12 weeks after closure. The mean numeric pain scores (ulcer site) improved by 41.0% and 64.1% at 12 weeks and 12 months after the procedure, respectively. The health-related quality-of-life index (scale of 0-1) improved from 0.65 ± 0.27 at baseline to 0.72 ± 0.28 at 12 weeks and 0.73 ± 0.30 at 12 months. By 12 weeks after treatment, the mean target leg Venous Clinical Severity Score had significantly decreased by 5.8 points, and by 12 months it had decreased by 10.0 points. CONCLUSIONS: Treatment with 1% polidocanol microfoam was associated with promising wound healing rates and low recurrence rates for VLUs, despite a challenging patient population with recalcitrant ulcers, a large percentage of which were circumferential, in patients with high body mass indexes.

Pathogenesis of varicose veins.

Despite the high prevalence of varicose veins and the recent surge in research on the condition, the precise mechanisms underlying their development remain uncertain. In the past decade, there has been a shift from initial theories based on purely mechanical factors to hypotheses pointing to complex molecular changes causing histologic alterations in the vessel wall and extracellular matrix. Despite progress in understanding the molecular aspects of venous insufficiency, therapies for symptomatic varicose veins are directed toward anatomic and physical interventions. The present report reviews current evidence identifying the underlying biochemical alterations in the pathogenesis of varicose veins.

Popliteal vein reflux is associated with increased rates of thrombotic complications after small saphenous vein closure procedures.

BACKGROUND: Venous insufficiency in the small saphenous vein (SSV) is significantly less common than venous insufficiency in the great saphenous vein; the impact of popliteal vein reflux on SSV closure procedural outcomes has yet to be studied. METHODS: A retrospective analysis was performed on 150 SSV closure procedures from 2015 to 2019. Preoperative demographic analysis was performed, after which univariate analyses were performed for postoperative occlusion rates and combined rates of endothermal heat-induced thrombus (EHIT) and endovenous foam-induced thrombus (EFIT). RESULTS: The cohort had a mean age of 58 years, and 116 (77%) were female. Fifty-four patients had C2 disease, 76 had C3 disease, 15 had C4 disease, 1 had C5 disease, and 4 had C6 disease. Twenty-three patients (15.3%) were noted to have popliteal vein reflux on their initial venous insufficiency ultrasound study, compared with 127 (84.6%) who did not. Treatment modalities included 84 radiofrequency ablations (56.0%), 37 polidocanol endovenous microfoam (24.6%), and 29 laser ablations (19.3%). When comparing patients with popliteal vein reflux with those without, there was no significant difference in the occlusion rates at their immediate postoperative visit (99.2% vs 95.6%) or at their 6-month postoperative visit (92.1% vs 91.3%). EHIT/EFIT was noted in 4 of the 23 patients with popliteal vein reflux compared with 4 of the 127 patients without popliteal vein reflux (17.3% vs 3.1%; P = .01). All eight instances of EHIT/EFIT were classified as either arteriovenous fistula class I or II EHIT or EFIT, and all were successfully treated without progression to deep vein thrombosis. CONCLUSIONS: The presence of popliteal vein reflux has no impact on postoperative occlusion rates at 6 months; however, it is associated with a significantly increased rate in EHIT and EFIT. Patients should be counseled on this increased risk should they undergo SSV treatment with known popliteal vein reflux.

Clinical presentation of women with pelvic source varicose veins in the perineum as a first step in the development of a disease-specific patient assessment tool.

OBJECTIVE: Pelvic venous incompetence can cause symptomatic varicose veins in the perineum, buttock, and thigh. Presentation, symptom severity, and response to treatment of pelvic source varicose veins are not well defined. Currently available tools to measure the severity of lower extremity venous disease and its effects on quality of life may be inadequate to assess disease severity in these patients. The purpose of this study was to evaluate the histories, demographics, and clinical presentations of women with pelvic source varicose veins and to compare these data to a population of women with nonpelvic source varicose veins. METHODS: A total of 72 female patients with symptomatic pelvic source varicose veins were prospectively followed up. Age, weight, height, parity, and birth weights of offspring were recorded. Both pelvic source varicose veins and saphenous incompetence were identified by duplex ultrasound. Patients were queried as to their primary symptoms, activities that made their symptoms worse, and time when their symptoms were most prominent. Severity of disease was objectively evaluated using the revised Venous Clinical Severity Score (rVCSS) and 10-point numeric pain rating scale (NPRS). RESULTS: Compared with women without a pelvic source of varicose veins (N = 1163), patients with pelvic source varicose veins were younger (mean, 44.6 ± 8.6 vs 52.6 ± 12.9 years; P < .001), had lower body mass index (mean, 21.9 ± 2.8 vs 25.8 ± 6.2; P < .001), and had larger babies than the U.S. population mean (mean, 3656 ± 450 g vs 3389 ± 466 g; P < .001). The most common symptoms were aching (68%), throbbing (47%), and heaviness (35%). In premenopausal patients, 70% noted that symptoms were worst during menses. NPRS score varied from 0 to 8 (mean, 4.9). The correlation between rVCSS (mean 5.6 ± 1.9) and NPRS was small (r = 0.26; P = .03). There was a modest correlation between older age and lower NPRS scores (r = -0.39; P < .001). CONCLUSIONS: Women with pelvic source varicose veins are a unique subset of patients. They are younger and thinner than those with nonpelvic source varicose veins, have larger infants than the general U.S. population, and have an inverse correlation between age and pain. As the majority of premenopausal patients have increased symptoms during menses, this may be due to hormonal influence. As it is poorly associated with patient-reported discomfort, the rVCSS is a poor tool for evaluating pelvic source varicose veins. A disease-specific tool for the evaluation of pelvic source varicose veins is critically needed, and this study is a first step in that endeavor.

Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.

AIMS: Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. METHODS AND RESULTS: To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase ß1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase ß1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. CONCLUSION: The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.

Factors influencing the incidence of endovenous heat-induced thrombosis (EHIT).

INTRODUCTION: Extension of thrombus from the great saphenous vein into the common femoral vein can be an early postprocedural complication of endothermal ablation (ETA). METHODS: A retrospective review was performed over a 3-year period. Intraprocedural ultrasound images demonstrating the distance of the catheter tip to the saphenofemoral junction (SFJ) were available for 519 procedures, and this distance was measured. RESULTS: Twenty-one (4.0%) cases of endovenous heat-induced thrombus (EHIT) were diagnosed. In all, 15 (6.4%) EHITs occurred following endovenous laser ablation and 6 (2.1%) after radiofrequency (P = .02). Distance from catheter tip to SFJ, vein diameter, concomitant treatments, and perioperative anticoagulation were not significant risk factors for EHIT. Of the clinical factors assessed, gender (P = .002), Clinical, Etiologic, Anatomic and Pathophysiologic classification 3 to 6 (P = .003), history of prior thrombosis (P = .04), and Caprini thrombosis risk factor assessment score (P = .004) were significant. On multivariate analysis, Caprini score (P = .0002) and male gender (P = .0003) remained significant. CONCLUSIONS: Male gender and increased Caprini score are predictive factors for EHIT following ETA.

Venous ablation therapy: indications and outcomes.

Venous disease has long been recognized as a progressive, debilitating, and recurrent problem. Until recently, venous insufficiency was often undertreated due to a lack of therapeutic modalities. During the past decade, an explosion in the treatment options has occurred. Endovenous ablation therapy has nearly replaced the conventional surgical treatments for patients with superficial venous insufficiency. Dramatic changes in therapy are also available for deep venous thrombosis but are not the subject of this review. These newer techniques are much less invasive and consequently have reduced risks of wound complications or bleeding. In addition, they can be performed easily in the office setting with local anesthesia. Higher-risk patients can now be considered for these less invasive treatments to reduce their ambulatory venous hypertension. With the lower procedural risks and the dramatically shortened recovery times, earlier intervention can be entertained. This helps prevent the development of venous stasis ulceration and other sequelae of progressive venous insufficiency.