Effects of 1064-nm Nd:YAG long-pulse laser on polidocanol microfoam injected for varicose vein treatment: a controlled observational study of 404 legs, after 5-year-long treatment.

Sclerotherapy continues to be the treatment of choice for varicose veins in the legs. However, isolated treatment using microfoam or lasers requires a high number of sessions to eliminate them. In 2013, we published results about the efficacy and safety 3 years after the combined treatment with microfoam injections and subsequent application of Nd:YAG laser. The aim of this paper is to clinically evaluate the treatment of varices in a control visit after 5 years, when polidocanol microfoam is used and is immediately irradiated in the tissue with 1064-nm Nd:YAG laser beam. The outcome persistence after 5 years was studied in the legs that had received combined treatment and had been studied 3 years after treatment. Patients were contacted by phone, interviewed, and examined with echo-Doppler. Out of the 259 patients who were contacted, 221 agreed to make the appointment, although in the end, only 202 came, which meant analysing 404 legs. At 5 years, the clearance rates were very high: patients were included in class CEAP C1 showing vessels of from 0.5 to 3 mm diameter. The patients showed a high level of satisfaction. Regarding adverse effects, only 4 cases of hypopigmentation described in the previous publication persisted. Although the action mechanisms between the microfoam and the Nd:YAG laser must still be elucidated, it is notable that combining microfoam with laser exposure obtained a complete, effective treatment of legs in only 2 sessions, with high clearance rates and high level of satisfaction among patients.

Treatment of Truncal Incompetence and Varicose Veins with a Single Administration of a New Polidocanol Endovenous Microfoam Preparation Improves Symptoms and Appearance.

OBJECTIVE: This multicenter, parallel group study was designed to determine if a single administration of ≤15 mL of pharmaceutical-grade polidocanol endovenous microfoam (PEM, now approved in the United States as Varithena [polidocanol injectable foam], BTG International Ltd.) could alleviate symptoms and improve appearance of varicose veins in a typical population of patients with moderate to very severe symptoms of superficial venous incompetence and visible varicosities of the great saphenous vein (GSV) system. METHODS: The primary endpoint was patient-reported venous symptom improvement measured by change from baseline to Week 8 in 7-day average VVSymQ score. Co-secondary endpoints measured improvement in appearance of visible varicose veins from baseline to Week 8, as measured by the Independent Photography Review-Visible Varicose Veins (IPR-V(3)) and Patient Self-assessment of Visible Varicose Veins (PA-V(3)) scores. Patients were randomized to five groups: PEM 0.125% (control), 0.5%, 1%, 2%, or placebo. Adverse events (AEs) were recorded at each study visit. Tertiary endpoints measured duplex ultrasound response, changes in venous clinical severity score, and the modified Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms. RESULTS: At Week 8, VVSymQ scores for the pooled PEM group (0.5% + 1% + 2%; p < .0001) and individual dose concentrations (p < .001) were significantly superior to placebo. Mean changes from baseline to Week 8 in IPR-V3 and PA-V(3) scores were significantly greater for pooled PEM than for placebo (p < .0001). Most AEs were mild and resolved without sequelae. No pulmonary emboli were reported. CONCLUSIONS: This study demonstrated that a single administration of up to 15 mL of PEM is a safe, effective, and convenient treatment for the symptoms of superficial venous incompetence and the appearance of visible varicosities of the GSV system. Doses of 0.5%, 1%, and 2% PEM appear to have an acceptable risk-benefit ratio.

Factors associated with recanalization and reintervention following below knee polidocanol endovenous microfoam ablation for great saphenous and small saphenous veins.

BACKGROUND: Polidocanol endovenous microfoam (PEM) has been used to treat lower extremity venous reflux for almost one decade with specific advantages for below knee (BK) truncal veins where thermal ablation poses a risk of injury to adjacent nerves. The current literature of the BK segment often examines short-term outcomes with modest sample sizes. We aim to identify factors associated with recanalization and reintervention in this subset of patients. METHODS: We performed a retrospective study of a prospectively maintained database of patients from a single institution who underwent 1% PEM ablation for BK great saphenous vein (GSV) and small saphenous vein (SSV) reflux. Patients underwent duplex ultrasound (DU) within 7 days after injection, every 3 to 6 months for 1 year, and every 6 to 12 months thereafter. Patients with symptomatic recanalization underwent reintervention. The 26 patients lost to follow-up without DU after ablation were excluded. The factors associated with recanalization and reintervention were examined by multivariate and nonparametric analyses. RESULTS: Between March 2018 and July 2023, 411 patients (166 male, 245 female) with 573 treated limbs (284 right, 289 left) met the study criteria. Of the 573 included limbs, 457 (79.8%) had undergone prior above knee saphenous ablations. A total of 554 BK GSV and 42 SSV ablations were performed. The most recent DU was performed at a mean of 231 ± 329 days. The overall recanalization rate was 10.6% (55 GSVs and 8 SSVs) at a mean follow-up of 104 ± 180 days. Comparing the closed and recanalized veins, we found no significant difference in age (P = .90), treated laterality (P = .14), patient body mass index (P = .59), preprocedural CEAP (clinical-etiology-anatomy-pathophysiology) score (P = .79), recanalization rate in GSVs vs SSVs (P = .06), or administered PEM volume (P = .24). The recanalized veins had significantly larger preprocedural diameters than the veins that remained closed (recanalized, 4.9 mm; closed, 4.3 mm; P = .001). Men had higher incidence of recanalization than women (men, 14.2%; women, 8%; P = .015). Anticoagulation use was associated with recanalization (odds ratio, 1.96; 95% confidence interval, 1.1-3.6; P = .03). Early recanalization at the first DU accounted for 31 failures (49.2%) and had a significantly lower administered PEM volume compared with later recanalization (early, 4 mL; late, 5 mL; P = .025). There were no significant differences between the 33 recanalized patients requiring reintervention (52.4%) and the 30 who did not. Twenty-four reinterventions were performed with PEM, 100% of which remained closed at a median of 160 days (interquartile range, 257 days). CONCLUSIONS: PEM is successful for the treatment of BK GSV and SSV reflux with a closure rate of 89% at a mean of 231 days and shows promise as salvage therapy. Most cases of recanalization were noted in the early postprocedure period and were associated with a lower PEM volume. A larger vein diameter, male sex, and anticoagulation use are associated with higher rates of recanalization.

Increased body mass index and vein diameter are associated with incomplete target vein closure following microfoam ablation of incompetent saphenous veins.

OBJECTIVE: Patient characteristics and risk factors for incomplete or non-closure following thermal saphenous vein ablation have been reported. However, similar findings have not been clearly described following commercially manufactured polidocanol microfoam ablation (MFA). The objective of our study is to identify predictive factors and outcomes associated with non-closure following MFA of symptomatic, refluxing saphenous veins. METHODS: A retrospective review of a prospectively maintained patient database was performed from procedures in our Ambulatory Procedure Unit. All consecutive patients who underwent MFA with commercially manufactured 1% polidocanol microfoam for symptomatic superficial vein reflux between June 2018 and September 2022 were identified. Patients treated for tributary veins only, without truncal vein ablation, were excluded. Patients were then stratified into groups: complete closure (Group I) and non-closure (Group II). Preoperative demographics, procedural details, and postoperative outcomes were analyzed. Preoperative variables that were significant on univariate analysis (prior deep venous thrombosis [DVT], body mass index [BMI] ≥30 kg/m2, and vein diameter) were entered into a multivariate logistic regression model with the primary outcome being vein non-closure. RESULTS: Between June 2018 and September 2022, a total of 224 limbs underwent MFA in our ambulatory venous center. Of these, 127 limbs in 103 patients met study inclusion criteria. Truncal veins treated included the above-knee great saphenous vein (Group I: n = 89, 77% vs Group II: n = 7, 58%; P = .14), below-knee great saphenous vein (Group I: n = 7, 6% vs Group II: n = 0; P = .38), anterior accessory saphenous vein (Group I: n = 17, 15% vs Group II: n = 4, 33%; P = .12, and small saphenous vein (Group I: n = 4, 4% vs Group II: n = 1, 8%; P = .41). Complete closure (Group I) occurred in 115 limbs, and 12 limbs did not close (Group II) based on postoperative duplex ultrasound screening. The mean BMI in Group II (36.1 ± 6.4 kg/m2) was significantly greater than Group I (28.6 ± 6.1 kg/m2) (P < .001). Vein diameter of ≥10.2 mm was independently associated with truncal vein non-closure with an odds ratio of 4.8. The overall mean foam volume was 6.2 ± 2.7 ml and not different between the two cohorts (Group I: 6.2 ± 2.6 ml vs Group II: 6.3 + 3.5 ml; P = .89). Post MFA improvement in symptoms was higher in Group I (96.9%) compared with Group II (66.7%) (P = .001). The mean postoperative Venous Clinical Severity Score was also lower in Group I (8.0 ± 3.0) compared with Group II (9.9 ± 4.2) (P = .048). The overall incidences of ablation-related thrombus extension and DVT were 4.7% (n = 6) and 1.6% (n = 2), and all occurred in Group I. All were asymptomatic and resolved with anticoagulation. CONCLUSIONS: Microfoam ablation of symptomatic, refluxing truncal veins results in excellent overall closure rates and symptomatic relief. BMI ≥30 kg/m2 and increased vein diameter are associated with an increased risk of saphenous vein non-closure following MFA. Non-closure is associated with less symptomatic improvement and a lower post-procedure reduction in Venous Clinical Severity Score. Despite the incidence of ablation-related thrombus extension and DVT in this study being higher than reported rates following thermal ablation, MFA is safe for patients with early postoperative duplex ultrasound surveillance and selective short-term anticoagulation.

Factors associated with ablation-related thrombus extension following microfoam versus radiofrequency saphenous vein closure.

OBJECTIVE: Polidocanol endovenous microfoam ablation (MFA) is approved by the US Food and Drug Administration for great saphenous vein (GSV) closure, yet there are few published data on the subsequent risk of ablation-related thrombus extension (ARTE). Recent societal practice guidelines recommend against routine postprocedure duplex ultrasound (DU) examination after thermal ablation of the GSV in asymptomatic patients. At present, limited data do not allow this recommendation to extend to MFA. Our aim is to identify characteristics and outcomes associated with ARTE following MFA vs radiofrequency ablation (RFA). METHODS: A retrospective review of a prospectively maintained database was conducted of patients who underwent MFA and RFA closure of incompetent above-knee GSVs. Patients treated for isolated tributary vein treatment or did not have a postprocedure DU examination within 48 to 72 hours were not included. Patients were classified into two groups: ARTE and no ARTE. Demographic data, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, operative details, postprocedure (48-72 hours) DU findings, and adverse events were analyzed. Variables that were significant on univariate analysis were evaluated using multivariate logistic regression with the primary outcome being development of ARTE. RESULTS: Between June 2018 and February 2023, 800 limbs were treated with either MFA (n = 224) or RFA (n = 576). Ninety-six GSVs treated with MFA met the study criteria. One hundred fifty successive GSVs treated with RFA during the same period were included as a comparison group. There was no statistically significant difference in baseline demographics between the two groups. Six patients (2.4%) demonstrated ARTE on postoperative DU examination at 48 to 72 hours (MFA, n = 5 [5.2%]; RFA, n = 1 [0.7%]; P = .02). Saphenous vein ablation with MFA (P = .045) and a vein diameter of >10 mm (P = .017) were associated with ARTE on both univariable and multivariable analysis. All patients who developed ARTE were treated with oral anticoagulants (mean, 15.6 days). Body mass index, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, microfoam volume, operative time, and prior deep venous thrombosis were not predictive of ARTE. CONCLUSIONS: ARTE after above-knee GSV closure occurred more frequently after MFA. Our results suggest that a saphenous vein diameter of >10 mm may be associated with ARTE. Despite this finding, all patients with ARTE were treated with short-term anticoagulation with no related complications. Until larger studies with high-risk subgroups have been studied after MFA, DU examination should be performed routinely after this procedure and patients with ARTE anticoagulated until the thrombus retracts caudal to the saphenofemoral junction or is no longer present on DU examination. Current societal guidelines recommending against routine post-thermal ablation DU examination should not be applied to similar patients after saphenous nonthermal MFA ablation.

Comparative effectiveness of non-compounded polidocanol 1% endovenous microfoam (Varithena) ablation versus endovenous thermal ablation utilizing a systematic review and network meta-analysis.

OBJECTIVE: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence. METHODS: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the closure rate ≥3 months after procedure and the average change in the Venous Clinical Severity Score. For the subgroup of venous ulcer patients, the ulcer healing rate was the primary effectiveness outcome. The secondary outcomes included safety and patient-reported outcomes. Network meta-analyses were conducted on outcomes having sufficient data. Categorical outcomes were summarized using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity tests and estimates of network inconsistency were used to investigate the robustness of our meta-analysis. RESULTS: We found that polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure (OR, 0.65; 95% CI, 0.36-1.18; P = .16). Although not the primary aim of the study, the network meta-analysis also provided evidence to confirm our supposition that polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds for vein closure (OR, 2.91; 95% CI, 1.58-5.37; P < .01). A sensitivity analysis using the longest available time point for closure in each study, with a minimum of 12 months of follow-up (median, 48 months; range, 12-72 months), showed results similar to those of the main analysis. No association was found between the risk of deep vein thrombosis and the treatment received. The available data were insufficient for a network meta-analysis of Venous Clinical Severity Score improvement and ulcer healing rates. CONCLUSIONS: Polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure and deep vein thrombosis risk for chronic venous insufficiency treatment, based on a network meta-analysis of published evidence. Polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds of vein closure. A sensitivity analysis found venous closure findings were robust at follow-up intervals of 12 months or greater and for up to 6 years. New evidence meeting the inclusion criteria for this review will be incorporated at regular intervals into a living network meta-analysis.

A systematic review on ablation techniques for larger saphenous veins in patients with symptomatic superficial venous disease.

OBJECTIVE: The aim of this study was to summarize the existing evidence for the treatment of saphenous veins >10 mm in diameter, to determine whether there were vein size limits for treatment modalities, and to determine if there are specific technical considerations for treatment of large veins. METHODS: We searched the literature for reports of treatment methods and outcomes for patients with large-diameter saphenous veins treated with various ablation methods between 1993 and 2023. These studies were evaluated for the size of the vein determined as "large diameter," type of ablation method, study type, outcomes, adverse events, and any technical considerations noted. A systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The COVIDENCE software was used for full-text screening and data extraction. Three reviewers reviewed the data, and the content expert served as the tiebreaker. RESULTS: Seventy-one records were identified, of which 24 studies were deemed appropriate for extraction. Most of the studies identified reported outcomes of endovenous thermal ablation modalities. There were fewer studies on non-thermal, non-tumescent techniques, and these studies reported an overall lower occlusion rate compared with endovenous thermal ablation techniques. CONCLUSIONS: Large head-to-head trials or randomized controlled that compare all the modalities over a long follow-up duration are yet to be performed. In the existing literature, there is considerable heterogeneity in terms of the study size, design, definition of large veins, site of vein measurement, and follow-up periods, making it challenging to make fair comparisons and draw firm conclusions. Currently available evidence supports the use of endothermal ablation techniques for the treatment of veins >10 mm in diameter as they have a more favorable efficacy and safety profile and have a larger body of evidence available compared with non-thermal, non-tumescent techniques or surgery.

Early results following comparison of radiofrequency and microfoam ablation of large diameter truncal veins demonstrate high closure rates and symptomatic relief.

OBJECTIVE: Endovenous closure of truncal veins with a large diameter (LD) (≥8 mm) has been associated with higher risk of post ablation thrombus propagation into the deep venous system. Similar findings after Varithena microfoam ablation (MFA) have not been characterized. The study objective was to analyze outcomes after both radiofrequency ablation (RFA) and MFA and of LD truncal veins. METHODS: A retrospective review of a prospectively maintained database was performed. All patients who underwent MFA and RFA for LD symptomatic truncal vein reflux (≥8 mm) were identified. All patients had postoperative duplex (48-72 hours) scanning. Patients underwent subsequent clinical follow-up at 3 to 6 weeks. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, adverse thrombotic events, and follow-up data were abstracted. RESULTS: Between June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent truncal vein (great, accessory, and small saphenous) closure for symptomatic reflux. Sixty-six limbs in the MFA group met inclusion criteria. Sixty-six consecutive limbs treated with RFA during the same time period were included as a comparison group. The mean truncal vein diameter treated was 10.5 mm (RFA, 10.0 mm; MFA, 10.9 mm). Twenty-nine limbs (44%) in the RFA group underwent concomitant phlebectomy. Tributary veins were concomitantly sclerosed in 34 MFA limbs (52%). Total procedural times were shorter in the MFA group (MFA, 31.6 minutes vs RFA, 55.7 minutes) (P < .001). Immediate closure rates were 100% and 95% in the RFA and MFA groups, respectively. Venous Clinical Severity Scores improved after treatment in both groups (RFA, from 9.5 to 7.8; P ≤ .001) (MFA, from 11.3 to 9.0; P ≤ .001). In the RFA and MFA groups, 83% and 79% of venous ulcers healed during the study period, respectively. Symptomatic superficial phlebitis occurred after RFA in 11% and 17% MFA. The incidence of postablation proximal deep venous thrombus extension was 3.0% in the RFA group and 6.1% in the MFA group, which was not statistically significant. All resolved with short-term oral anticoagulant therapy. No remote deep venous thromboses or pulmonary emboli occurred in either group. CONCLUSIONS: High early closure rates, symptom relief and ulcer healing rates can be achieved after RFA and MFA of LD saphenous veins. Both techniques can be used safely across a wide array of CEAP classes. Longer term studies are required to characterize the durability of MFA closure and sustained symptom relief in LD truncal veins.

Eradication of the nidus in arteriovenous malformations with a dominant outflow vein in the lower extremities using coils and absolute ethanol.

OBJECTIVE: In the present study, we summarize our experience in locating the nidus of arteriovenous malformations (AVMs) with a dominant outflow vein (DOV) in the lower extremities and eradicating the nidus with ethanol and coils. METHODS: Twelve patients with lower extremity AVMs who underwent ethanol embolization combined with DOV occlusion from January 2017 to May 2018 were enrolled in the present study. Selective angiography was used to locate the nidus of the AVMs, which was eradicated using ethanol and coils via the direct puncture pathway. All treated patients underwent postoperative follow-up (mean, 25.5 months; range, 14-37 months). RESULTS: The 12 patients underwent a total of 29 procedures (mean, 2.4; range, 1-4) with 27 detachable coils and 169 Nester coils (Cook Medical Inc, Bloomington, IN). Of the 12 patients, 7 (58.3%) had a complete response and 5 (41.7%) a partial response. Three patients (25%) had minor complications such as blister and superficial skin ulcers during follow-up. However, they recovered spontaneously and completely. No major complications were recorded. CONCLUSIONS: Ethanol embolization combined with coil-assisted DOV occlusion has the potential to eradicate the nidus of lower extremity AVMs with acceptable complication rates.

Comparison of outcomes following polidocanol microfoam and radiofrequency ablation of incompetent thigh great and accessory saphenous veins.

BACKGROUND: Microfoam ablation (MFA) and radiofrequency ablation (RFA) are both approved by the Food and Drug Administration for treatment of proximal saphenous truncal veins. The objective of our study was to compare early postoperative outcomes between MFA and RFA following treatment of incompetent thigh saphenous veins. METHODS: A retrospective review of a prospectively maintained database was conducted of patients who underwent treatment of incompetent great saphenous veins (GSVs) or anterior accessory saphenous veins (AASVs) in the thigh. All the patients underwent duplex ultrasound of the treated leg at 48 to 72 hours postoperatively. Patients were excluded from analysis if concomitant stab phlebectomy was performed. Demographic data, CEAP (clinical, etiologic, anatomic, pathophysiologic) class, venous clinical severity score (VCSS), and adverse events were recorded. RESULTS: Between June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent venous closure for symptomatic reflux. A total of 200 consecutive thigh GSVs and ASVs treated within the study period using either MFA (n = 100) or RFA (n = 100) were identified. The patients were predominantly women (69%) with a mean age of 64 years. The preoperative CEAP classification was similar between the MFA and RFA groups. The mean preoperative VCSS was 9.4 ± 2.6 for the RFA patients and 9.9 ± 3.3 for the MFA patients. Among the RFA patients, the GSV was treated in 98% and the AASV in 2% compared with the GSV in 83% and the AASV in 17% in the MFA group (P < .001). The mean operative time was 42.4 ± 15.4 minutes in the RFA group and 33.8 ±16.9 minutes in the MFA group (P < .001). The median follow-up was 64 days for the study cohort. The mean postoperative VCSS declined to 7.3 ± 2.1 in the RFA group and 7.8 ± 2.9 in the MFA group. Complete closure occurred in 100% of the limbs after RFA and 90% after MFA (P = .005). Eight veins were partially closed and two remained patent following MFA. The incidence of superficial phlebitis was 6% and 15% (P = .06) after RFA and MFA, respectively. Overall, symptomatic relief was 90% following RFA and 89.5% following MFA. The complete ulcer healing rate for the entire cohort was 77.8%. Deep venous proximal thrombus extension (RFA, 1%; vs MFA, 4%; P = .37) and remote deep vein thrombosis (RFA, 0%; vs MFA, 2%; P = .5) showed a trend toward being higher following MFA but the difference did not reach statistical significance. All were asymptomatic and resolved with short-term anticoagulation therapy. CONCLUSIONS: MFA and RFA are both safe and effective for treating incompetent thigh saphenous veins, with excellent symptomatic relief and a low incidence of postprocedure adverse thrombotic events. RFA resulted in improved complete closure rates following initial treatment compared with MFA. The operative times were shorter with MFA. Both modalities can be used for patients with active venous ulcers with good healing rates. Longer term studies are required to characterize the durability of MFA closure for above knee truncal veins.

The 2022 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the management of varicose veins of the lower extremities. Part I. Duplex Scanning and Treatment of Superficial Truncal Reflux: Endorsed by the Society for Vascular Medicine and the International Union of Phlebology.

The Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society collaborated to update the 2011 Society for Vascular Surgery/American Venous Forum clinical practice guidelines and provide new evidence-based recommendations on critical issues affecting the care of patients with varicose veins. Each recommendation is based on a recent, independent systematic review and meta-analysis of the diagnostic tests and treatments options for patients with lower extremity varicose veins. Part I of the guidelines includes evidence-based recommendations for the evaluation of patients with CEAP (Clinical Class, Etiology, Anatomy, Pathology) class 2 varicose vein using duplex ultrasound scanning and other diagnostic tests, open surgical treatment (ligation and stripping) vs endovenous ablation techniques, thermal vs nonthermal ablation of the superficial truncal veins, and management of incompetent perforating veins in CEAP class 2 disease. We have also made recommendations on the concomitant vs staged treatment of varicose tributaries using phlebectomy or liquid or foam sclerotherapy (with physician-compounded foam or commercially prepared polidocanol endovenous microfoam) for patients undergoing ablation of incompetent superficial truncal veins.

Prospective randomized trial of antithrombotic strategies following great saphenous vein ablation using injectable polidocanol endovenous microfoam (Varithena).

OBJECTIVE: Postablation deep vein thrombosis (DVT) represents a potentially serious complication after Varithena polidocanol endovenous microfoam (PEM) ablation. The following primary outcomes were assessed: whether (1) adjunctive apixaban anticoagulation or (2) mechanical deep venous system (DVS) saline flushing could decrease saphenofemoral junction (SFJ) thrombus extension (postablation superficial thrombus extension [PASTE]) and/or DVT compared with compression alone, after great saphenous vein (GSV) PEM ablation. METHODS: Varithena 1% PEM ablation patients were randomized to (1) SFJ compression, (2) compression and DVS saline flushing, or (3) compression, DVS saline flushing, and 5 days of postprocedural 5 mg oral apixaban anticoagulation twice daily. Duplex imaging was obtained 7 to 10 days after PEM ablation and PASTE/DVT incidence (primary end point) was compared between groups at this time point. RESULTS: We treated 304 limbs in 257 patients with PEM. Overall, 103 limbs received SFJ compression (group C, 33.8%), 101 received compression and deep venous flushing (group D, 32.9%), and 100 received compression, deep flush, and anticoagulation (group A, 33.2%). Mean ultrasound follow-up time was 9.7 days (all patients) with a primary GSV closure rate of 92.4%. SFJ PASTE (II-IV) occurred in 0.9%, 1.0%, and 0% (groups C, D, and A, respectively). DVT occurred in 16.7%, 14.7%, and 1.98% (groups C, D, and A; χ2, P = .002). Patients in group A receiving apixaban anticoagulation had a significant reduction in DVT compared with patients in group C (1.98% vs 16.7%, χ2; P < .001); likewise, patients in group A had a significantly decreased DVT occurrence compared with group D (14.7% vs 1.98%; χ2, P = .00162), whereas patients in groups C and D were not statistically different (16.7% vs 14.7%; χ2, P = .60). CONCLUSIONS: (1) Neither adjunctive DVS flushing nor anticoagulation decreased clinically relevant SFJ PASTE (II-IV) incidence, which remained similarly low across all groups and ranged between 0% and 1%, regardless of adjunctive DVS flushing or anticoagulation. This rate was significantly lower than prior reports (2.3%-4.1%). (2) DVS flushing had no influence on the rate of DVT. Observed PEM-induced DVT incidence using SFJ compression alone or compression with DVS flushing (16.7% and 14.7%, respectively) was significantly higher than prior reports (2.5%-9.6%). This finding may relate to the greater extent of AK/BK GSV territory treated in the present study. (3) Five days of postprocedural oral apixaban anticoagulation, 5 mg given twice daily, significantly decreased DVT occurrence to 1.98%, compared with nonanticoagulated patients (16.7%). This finding is comparable with the DVT rates reported after endovenous thermal ablation (0.7-1.7%). (4) Postprocedural apixaban anticoagulation may have a significant preventive role in decreasing DVT occurrence after PEM ablation.

Results of polidocanol endovenous microfoam in clinical practice.

BACKGROUND: Initial phase III clinical studies with polidocanol endovenous microfoam (PEM) demonstrated its safety and efficacy in the treatment of superficial venous reflux. In those studies, the primary outcome requirement was to assess the improvement in symptoms related to superficial venous disease. The goal of the present study was to evaluate the efficacy of PEM technology in routine clinical practice-specifically, the closure rates after treatment. METHODS: We performed an observational study during which data were prospectively collected from 2 vein centers using an electronic database. Patients with CEAP (clinical, etiologic, anatomic, pathophysiologic) class ≥2 and symptomatic superficial axial reflux (great saphenous vein, anterior accessory saphenous vein, and small saphenous vein) were included and followed up prospectively. PEM was used to treat the saphenous vein and varicosities. The CEAP classification was used to classify chronic venous disease, and the venous clinical severity score (VCSS) was applied to measure the disease severity. Pain and discomfort were assessed using a visual analog scale, and the residual veins were assessed by physical examination. RESULTS: PEM was used to treat superficial reflux in 60 patients. The CEAP classification was C2 for 32 patients, C3 for 14, C4 for 10, and C5 for 4 patients. The average pretreatment VCSS was 7.3. The saphenous vein diameter was 6.5 mm, and the average length was 31 cm. The average volume of PEM used to treat the saphenous veins was 9.3 mL. The closure rate at 3 and 6 months was 93% (54 of 58) and 93% (51 of 55), respectively. The VCSS had improved from 7.3 to 1.4. Complications included 1 case of deep vein thrombosis (1.7%), 5 patients (8.3%) with thrombophlebitis, and 4 patients (6.6%) with skin pigmentation. CONCLUSIONS: PEM is safe and effective for the treatment of saphenous reflux and varicosities. The early closure rates using PEM were maintained at 6 months and are comparable to the results reported with nonthermal, nontumescent technologies and thermal tumescent technologies.

A new automated system for the preparation of sclerosant foam: A study of the physical characteristics produced and the device settings required.

OBJECTIVES: To determine the quality of sclerosant foam produced with an automated preparation system with multiple combinations of sclerosing agents, gases, and device settings. METHODS: Single-use mixing capsules filled with air or O2/CO2 and polidocanol (0.25, 1, or 3%) or sodium tetradecyl sulfate (0.2 or 1%) were coupled to a customized magnetic stirrer. Stirring speed and time were adjusted between 1500 and 4000 r/min and 30 and 60 s, respectively, and characteristics of the foam produced were measured: half-life, bubble diameter, and gas-to-liquid ratio. RESULTS: With optimized device settings, the following foam characteristics were obtained: half-life range, 1.4 ± 0.9 to 5.2 ± 0.6 min; bubble diameter, 84 ± 14 to 119 ± 6 µm; and gas-to-liquid ratio, 5:1-7:1. Sodium tetradecyl sulfate foam was quicker to form than polidocanol but faster to degrade. Foams with low sclerosant concentrations and O2/CO2 required higher speed and longer time. CONCLUSIONS: Suitable foam characteristics could be obtained with all combinations of sclerosing agent, concentration, and gas.

High-Throughput and Self-Powered Electroporation System for Drug Delivery Assisted by Microfoam Electrode.

Electroporation is an effective approach for drug and gene delivery, but it is still limited by its low-throughput and severe cell damage. Herein, with a self-powered triboelectric nanogenerator as the power source, we demonstrated a high-throughput electroporation system based on the design of biocompatible and flexible polypyrrole microfoam as the electrode within the flow channel. In particular, to lower the imposed voltage, one-dimensional (1D) Ag nanowires were modified on the microfoam electrode to build up a locally enhanced electric field and reduce cell damage. The self-powered electroporation system realized a successful delivery of small and large biomolecules into different cell lines with efficiency up to 86% and cell viability over 88%. The handle throughput achieved as high as 105 cells min-1 on continuously flowed cells. The high-throughput and self-powered electroporation system is expected to have potential applications in the fields of high-throughput drug and gene delivery for in vitro isolated cells.

A multicenter, randomized, placebo-controlled trial of endovenous thermal ablation with or without polidocanol endovenous microfoam treatment in patients with great saphenous vein incompetence and visible varicosities.

Objectives * Varithena 017 Investigator Group: Michael Vasquez, MD, Venous Institute of Buffalo, Amherst, NY; Antonios Gasparis, MD, Stony Brook University Medical Center, Stony Brook, NY; Kathleen Gibson, MD, Lake Washington Vascular, Bellevue, WA; James Theodore King, MD, Vein Clinics of America, Oakbrook Terrace, IL; Nick Morrison, MD, Morrison Vein Institute, Scottsdale, AZ; Girish Munavalli, MD, Dermatology, Laser & Vein Specialists of the Carolinas, Charlotte, NC; Eulogio J. Sanchez, MD, Batey Cardiovascular Center, Bradenton, FL. Varithena® is a trademark of Provensis Ltd, a BTG International group company. To determine the efficacy and safety of polidocanol endovenous microfoam (PEM 0.5%, 1.0%) and placebo each administered with endovenous thermal ablation. Methods A multicenter, randomized, placebo-controlled, blinded study was conducted in patients with great saphenous vein incompetence and symptomatic and visible superficial venous disease. Co-primary endpoints were physician-assessed and patient-assessed appearance change from Baseline to Week 8. Results A total of 117 patients received treatment (38 placebo, 39 PEM 0.5%, 40 PEM 1%). Physician-rated vein appearance at Week 8 was significantly better with PEM ( p = 0.001 vs. placebo); patient-assessed appearance trended similarly. Polidocanol endovenous microfoam provided improvements in clinically meaningful change in patient-assessed and physician-assessed appearance ( p < 0.05), need for additional treatment ( p < 0.05), saphenofemoral junction reflux elimination, symptoms, and QOL. In PEM recipients, the most frequent adverse event was superficial thrombophlebitis (35.4%) Conclusions Endovenous thermal ablation + PEM significantly improved physician-assessed appearance at Week 8, increased the proportion of patients with a clinically meaningful change in appearance, and reduced need for additional treatment. www.clinicaltrials.gov (NCT01197833).

Benefits of polidocanol endovenous microfoam (Varithena®) compared with physician-compounded foams.

OBJECTIVE: To compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests. METHODS: Foam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods. RESULTS: Polidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p < 0.035). The same result was obtained at different liquid to gas ratios (1:4 and 1:7) for physician-compounded foams. In all tests performed, CO2 foams were the least stable and different O2:CO2 mixtures had intermediate performance. In the biomimetic vein model, polidocanol endovenous microfoam had the slowest degradation rate and longest calculated dwell time, which represents the length of time the foam is in contact with the vein, almost twice that of physician-compounded foams using room air and eight times better than physician-compounded foams prepared using equivalent gas mixes. CONCLUSION: Bubble size, bubble size distribution and stability of various sclerosing foam formulations show that polidocanol endovenous microfoam results in better overall performance compared with physician-compounded foams. Polidocanol endovenous microfoam offers better stability and cohesive properties in a biomimetic vein model compared to physician-compounded foams. Polidocanol endovenous microfoam, which is indicated in the United States for treatment of great saphenous vein system incompetence, provides clinicians with a consistent product with enhanced handling properties.

Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery.

Microfoam Sclerotherapy for Varicose Veins: a Retrospective Analysis of a Modified Technique.

Varicose veins (VVs) are generally characterized by their elongated, twisted, bulging, superficial appearance on the lower extremities and usually present with acute or chronic venous diseases. Despite diagnostic and surgical advances in the management of VV, patients suffer from post-therapeutic complications and recurrence. We present findings from a retrospective study of a modified treatment modality in patients with varicose veins who attended St. Thomas Institute of Research on Venous Diseases, Changanassery, Kerala. The hospital caters to patients from India and outside. Out of 14,707 patients treated from 1997 till May 2013, 6,350 patients from January to March 2011 were selected for the study from the routine clinical practice (mid-segment) to facilitate follow-up. They were categorized according to Clinical Etiologic Anatomic Pathophysiologic (CEAP) clinical classification system. Baseline data were accrued using a questionnaire. Patients were treated by microfoam sclerotherapy giving a maximum importance to smaller veins, depicting a modified technique of microfoam sclerotherapy (MMFST). This is based on the significance of microscopic venous valves (MVVs) in the development of chronic venous disease (CVD). Follow-up was according to a predefined schedule, and improvements and complications were recorded. A positive family history of VVs was reported in 85.23 % of patients. Half the study population belonged to CEAP clinical class IV. There were no significant complications in patients throughout the 2 to 6 years of follow-up. Recurrence was rarely reported during follow-up and was corrected by repeating the procedure as required during follow-up. MMFST is an innovation in the treatment of VVs based on new principles, with the potential to control and revert the symptoms of CVD, with minimal complications.

Microcellular foams made from gliadin.

We have generated closed-cell microcellular foams from gliadin, an abundantly available wheat storage protein. The extraction procedure of gliadin from wheat gluten, which involves only the natural solvents water and ethanol, respectively, is described with emphasis on the precipitation step of gliadin which results in a fine dispersion of mostly spherical, submicron gliadin particles composed of myriad of protein molecules. A dense packing of these particles was hydrated and subjected to an atmosphere of carbon dioxide or nitrogen in a high-pressure cell at 250 bar. Subsequent heating to temperatures close to but still below 100 °C followed by sudden expansion and simultaneous cooling resulted in closed-cell microcellular foam. The spherical gliadin templates along with the resulting foam have been analyzed by scanning electron microscope (SEM) pictures. The size distribution of the primary particles shows diameters peaked around 0.54 µm, and the final foam cell size peaks around 1.2 µm, at a porosity of about 80 %. These are the smallest foam cell sizes ever reported for gliadin. Interestingly, the cell walls of these microcellular foams are remarkably thin with thicknesses in the lower nanometer range, thus nourishing the hope to be able to reach gliadin nanofoam.