Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. Methods: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. Results: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan–Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73–82) for vonapanitase and 76% (95% CI, 70–82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan–Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44–55) for vonapanitase and 43% (95% CI, 35–50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. Conclusions: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841)

Objective Hypersensitivity reaction presenting as a distinctive erythematous rash has been reported following VenaSeal™ cyanoacrylate adhesive closure. We report the frequency of hypersensitivity reactions, time to onset, duration, and severity of symptoms in patients treated with cyanoacrylate adhesive closure at a single institution. Patient and procedural factors associated with hypersensitivity reactions were evaluated. Methods A combined retrospective/prospective review of cyanoacrylate adhesive closure-treated patients was conducted over five years. Data collected from electronic medical records were reviewed for the presence of hypersensitivity reactions along with the time of onset, duration of symptoms, and severity of reaction. Severity was classified as mild if no treatment or over the counter medication was provided, moderate if steroids were required, and severe if the reaction lasted >30 days or required vein excision. Results Three hundred and seventy-nine limbs were treated in 286 patients (313 treatment days). Hypersensitivity reactions occurred in 18 patients (5.8% treatments, 6.3% patients). Thirteen were mild (4.2%), four were moderate (1.3%), and one was severe (0.3%). No patient or procedural predictive factors for hypersensitivity reaction were identified other than a trend towards decreased hypersensitivity reactions in patients with Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) clinical class C4–C6 (p = .06). Second limb treatment on a subsequent day was performed in 27 patients, and no hypersensitivity reactions occurred. Symptom onset time ranged from 1 to 23 days, with a mean of 13 days (confidence interval (CI) ±3.5 days). Duration of symptoms ranged from 3 to 28 days (mean 10.8 CI ±4.9 days). Conclusions Hypersensitivity reactions occurred in 6.0% of patients treated with cyanoacrylate adhesive closure, but most were mild and self-limited. Severe reactions were uncommon. No predictive patient or procedural factors were found to be associated with hypersensitivity reactions other than a trend towards decreased risk in patients with advanced CEAP clinical class. Previous cyanoacrylate adhesive closure treatment was not a predictive factor for hypersensitivity reaction in patients undergoing treatment at a later date.

ObjectiveArteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis.MethodsPATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates.ResultsThe Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use.ConclusionsVonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

PURPOSE:Studies examining cyanoacrylate closure of saphenous veins with the VenaSeal™ System have not allowed concomitant procedures for tributaries at the time of the index procedure. Outside of clinical trials, however, concomitant procedures are frequently performed in conjunction with endovenous ablation. We report on the frequency of need for saphenous tributary treatment three months after cyanoacrylate closure of the treatment of great saphenous vein, small saphenous vein, and/or accessory saphenous vein.METHODS:Fifty subjects with symptomatic great saphenous vein, small saphenous vein, and/or accessory saphenous vein incompetence were treated with no postprocedure compression stockings. Concomitant procedures were not allowed. Treating physicians predicted the type and nature of any concomitant procedures that they would usually perform at the time of ablation, if not limited by the constraints of the study. Evaluations were performed at one week, one and three months and included duplex ultrasound, numeric pain rating scale, revised venous clinical severity score, the Aberdeen Varicose Vein Questionnaire, and time to return to work and normal activities. At the three-month visit, the need for and type of adjunctive procedures were recorded.RESULTS:Complete closure at three months was achieved in 70 (99%) of the treated veins (48 great saphenous veins, 14 accessory saphenous veins, eight small saphenous veins). Revised venous clinical severity score improved from 6.4 ± 2.2 to 1.8 ± 1.5 (P < .001) and Aberdeen Varicose Vein Questionnaire from 17.3 ± 7.9 to 6.5 ± 7.2 (P < .0001). Sixty-six percent of patients underwent tributary treatment at three months. The percentage of patients who required adjunctive treatments at three months was lower than had been predicted by the treating physicians (65% versus 96%, p=.0002).CONCLUSIONS:Closure rates were high in the absence of the use of compression stockings or side branch treatment. Improvement in quality of life was significant, and the need for and extent of concomitant procedures was significantly less than had been predicted by the treating physicians.

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.

Purpose Cyanoacrylate closure of the great saphenous vein with the VenaSeal™ Closure System is a relatively new modality. Studies have been limited to moderate-sized great saphenous veins and some have mandated postoperative compression stockings. We report the results of a prospective study of cyanoacrylate closure for the treatment of great saphenous vein, small saphenous veins, and/or accessory saphenous veins up to 20 mm in diameter. Methods Fifty subjects with symptomatic great saphenous vein, small saphenous veins, and/or accessory saphenous veins incompetence were each treated at a single session. Compression stockings were not used post-procedure. Subjects returned to clinic at week 1 and again at one month. Post-procedure evaluations were performed at seven days and one month and included numerical pain rating score, revised venous clinical severity score, the Aberdeen Varicose Vein Questionnaire score, and time to return to work and normal activities. Duplex ultrasound was performed at each visit. Findings Procedural pain was mild (numerical pain rating scale 2.2 ± 1.8). All treated veins (48 great saphenous vein, 14 accessory saphenous veins, and 8 small saphenous veins) had complete closure by duplex ultrasound at seven days and one month. Mean time to return to work and normal activities was 0.2 ± 1.1 and 2.4 ± 4.1 days, respectively. The revised venous clinical severity score was improved to 1.8 ± 1.4 (p < .001) and Aberdeen Varicose Vein Questionnaire score to 8.9 ± 6.6 (p < .001) at one month. Phlebitis in the treatment area or side branches occurred in 10 subjects (20%) and completely resolved in all but one subject (2%) by one month; 98% of subjects were “completely” or “somewhat” satisfied, and 2% “unsatisfied” with the procedure at one month, despite the protocol disallowance of concomitant side branch treatment. Conclusions Cyanoacrylate closure is safe and effective for the treatment of one or more incompetent saphenous or accessory saphenous veins. Closure rates were high even in the absence of the use of compression stockings or side branch treatment. Time back to work or normal activities was short and improvements in venous severity scores and QOL were significant, comparing favorably with alternative treatment methods.

In patients treated with IV sclerosant foams, circulating gas bubbles reach the right heart and are usually filtered out by the lung. In patients with right-to-left (RL) shunts, bubbles may enter the arterial circulation. It is unknown whether these bubbles can cause microvascular infarctions. This study investigates whether patients with MCA bubbles detected during treatment with a proprietary polidocanol microfoam (MF) experience subclinical events. Patients with SFJ incompetence and great saphenous vein (GSV) reflux (CEAP 3-5) who are ≤ 60 years and free of arteriovascular disease can be enrolled in this IND study. Transcranial Doppler (TCD) with agitated saline contrast assesses presence of RL shunt prior to treatment. GSV incompetence is treated by injection of a proprietary polidocanol MF formulated with a gas mixture designed to maintain physical MF characteristics while accelerating bubble absorption, and dispensed via a canister system controlling density and bubble size (the Varisolve procedure). During and after the procedure patients undergo TCD monitoring of the MCA for 1 hr. Patients with detectable MCA bubbles receive intensive surveillance for microinfarction including MR with diffusion-weighted imaging at 1, 7 and 28 days, neurological exam, perimetry, and cardiac markers. TCD and MRI are assessed by blinded central reviewers. Recruitment will continue until 50 patients with MCA bubbles during the procedure are evaluated (projected Spring 2008). In patients with GSV incompetence screened for enrollment, RL shunts are diagnosed in 1/3 of patients. In shunt-positive patients treated with polidocanol MF, 90% have detectable MCA bubble emboli during the procedure, but the number of bubbles is low (maximum 13 bubbles in patient with Grade V shunt). After evaluation of 11 patients with MCA bubbles, none have developed new MRI lesions, neurological or visual field abnormalities, or elevated cardiac markers. Patients undergoing foam sclerotherapy are commonly exposed to gas bubbles in the cerebral (arterial) circulation. A proprietary polidocanol MF with controlled density, bubble size and gas mix has not been associated with evidence of microinfarction.

Endovenous laser treatment (EVLT) has become a standard therapy for the treatment of superficial venous insufficiency. It offers a rapid, office-based therapy with minimal patient downtime and an easier recovery than traditional surgical treatment. EVLT is effective and durable and can successfully treat saphenous truncal insufficiency and accessory branches with low complication rates. EVLT can increase patient satisfaction and enable the treatment of a wider variety of patients with a more efficient procedure compared with traditional techniques.

Foam sclerotherapy has been refined over the past decade to become a safe and effective treatment for varicose veins and venous insufficiency. Using duplex ultrasound guidance, it can be used to treat large and small varicosities, saphenous trunks, incompetent perforating veins, and venous stasis ulcerations. Serious complications are rare, and in experienced hands, efficacy rivals that of traditional surgical ligation and stripping. Disadvantages of the technique are the need in many cases for more than one treatment session, and lack of US Food and Drug Administration approval of all currently available sclerosants. Foam sclerotherapy offers advantages of low cost, quick patient recovery, and ease of use; as such, it is an important tool for modern vein treatment.

PURPOSE:The typical leg bypass surveillance program begins with a duplex scan evaluation of the vein graft 3 months after surgery; studies are repeated every 3 months during the first year of follow-up and are fully reimbursed by our Medicare carrier. Some authors have recommended early (before discharge or first postoperative visit) duplex scanning to identify high-risk grafts. However, the natural history of velocity disturbances detected with early scans is unclear, and furthermore, such studies are not reimbursed by Medicare. METHODS:We reviewed all infrainguinal vein bypass grafts prospectively entered into a surveillance protocol that included an early (<6 weeks) duplex scan study. Routine completion angiography was performed at the initial operation in all patients. Early duplex scan results, the need for graft revision, and detailed follow-up of these bypass grafts were analyzed. RESULTS:Early duplex scans were performed in 224 bypass grafts placed in 204 patients. Early scans were abnormal (peak systolic velocity [PSV], >200 cm/s) in 58 grafts (26%). Six grafts of the 58 (10.3%; 2.7%) with an early abnormal duplex scan and unrepaired defects occluded during the follow-up period. Thirty grafts were revised on the basis of the initial early scan; 23 of these revisions were performed for critical or rapidly progressive lesions in the first 3 postoperative months. Seven lesions progressed more slowly and were repaired at a mean of 8 months after surgery. Interestingly, 22 flow abnormalities (37%) resolved or stabilized despite a PSV of more than 300 cm/s in six cases (27%). Clear duplex scan evidence of regression or progression of these early flow abnormalities occurred within 3 months in 51/58 cases (88%). A total of 68 grafts (30%) were revised during the entire study period; 30 of these (44%) were on the basis of the early abnormal scan. CONCLUSION:Despite normal completion arteriography, early graft velocity abnormalities are strikingly common and were detected in 26% of the 224 infrainguinal vein grafts in this series. These lesions were clinically important because 52% necessitated revision. Surprisingly, however, 38% of these early flow disturbances resolved, despite a PSV of more than 300 cm/s in 27% of cases. Early duplex scan surveillance singularly detects a clinically significant subgroup of grafts that need revision. The possible origin of these early lesions deserves further inquiry, but on the basis of its clinical yield, we recommend that early duplex scan surveillance of infrainguinal bypass grafts should be routine and should be considered for Medicare reimbursement.