Summaries of recent phlebological abstracts

Eur J Appl Physiol 2018; 118: 321–329.

The authors studied 38 adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm²). The participants were randomly allocated to exercise or control groups. Exercise participants (n = 18) were invited to attend three weekly supervised sessions for 12 weeks of lower-limb aerobic and resistance exercise. Using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and three months. Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg).

Thirty-seven participants completed follow-up assessments. Median session attendance was 36 (range: 2–36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at three months in both the ulcerated and non-ulcerated legs. Peak CVC responses to SNP were also greater in the exercise group at three months in the ulcerated leg, but not the non-ulcerated leg.

The authors concluded that supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.

Eur J Vasc Endovasc Surg 2018, Epub, doi: 10.1016/j.ejvs.2018.05.028.

The authors compared, in a randomized clinical trial, early and two-year results for N-butyl cyanoacrylate (NBCA), radiofrequency ablation (RFA), and endovenous laser ablation (EVLA) without phlebectomy in the treatment of varicose veins.

A total of 525 patients were blindly randomized into NBCA, RFA, and EVLT cohorts (175 patients to each group), and 460 patients were monitored for two years (ultrasound at 2 days and 6, 12, and 24 months). The primary endpoint was the saphenous vein occlusion rates; the secondary endpoints were peri- and post-procedural pain, complications, and time to return to work.

The numbers of patients lost to follow-up were NBCA 7, RFA 26, and EVLA 36. Occlusion rates were similar at 6, 12, and 24 months (six months (NBCA 98.1%, RFA 94.1%, and EVLA 95.1%, p = .14), one year (NBCA 94.7%, RFA 92.5%, and EVLA 94.2%, p = .72), two years (NBCA 92.6%, RFA 90.9%, and EVLA 91.5%, p = .89)). Peri-procedural pain was significantly lower after NBCA (p < .001). Complication rates (DVT, bleeding, and phlebitis) were similar. Time to return to work was shortest after NBCA (NBCA 1.04 days, RFA 1.56 days, and EVLA 1.31 days) (p < .001) with 95% (NBCA), 50% (RFA), and 75% (EVLA) of patients returning to work on Day 1. Pre-procedural venous clinical severity scores (VCSSs) were the same in all groups. A decrease was observed in VCSS values in all groups at six months, and this persisted to the final measure at two years. However, VCSS scores at six months and two years were significantly lower in the NBCA group (p < .001). Foam sclerotherapy was subsequently applied to varicose tributaries in 18 patients from all groups.

The authors concluded that no differences were observed in occlusion rates; however, NBCA appeared superior with respect to peri-procedural pain, return to work, and decreased VCSS.

Cochrane Database Syst Rev 2018; 6: CD012583.

The authors, using network meta-analysis (NMA), assess the probability of complete ulcer healing associated with alternative dressings and topical agents. In addition, the authors ranked treatments in order of effectiveness, with assessment of uncertainty and quality evidence. In March 2017, the authors searched the Cochrane Wounds Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. They also scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. The authors updated this search in March 2018. The authors included published or unpublished randomized controlled trials (RCTs) that enrolled adults with venous leg ulcers (VLUs) and compared the effects of at least one of the following interventions with any other intervention in the treatment of VLUs: any dressing or any topical agent applied directly to an open VLU and left in situ. They excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factors and other biological agents, larval therapy and treatments such as laser, heat or ultrasound. Studies were required to report complete wound healing to be eligible.

A total of 78 RCTs (7014 participants) were included in this review. Of these, 59 studies (5156 participants, 25 different interventions) were included in the NMA, resulting in 40 direct contrasts which informed 300 mixed-treatment contrasts. The evidence for the network was of low certainty. This judgement was based on the sparsity of the network leading to imprecision and the general high risk of bias in the included studies. Sensitivity analyses also demonstrated instability in key aspects of the network and results are reported for the extended sensitivity analysis. Evidence for individual contrasts was mainly judged to be of low or very low certainty. The uncertainty was perpetuated when the results were considered by ranking the treatments in terms of the probability that they were the most effective for ulcer healing, with many treatments having similar low probabilities of being the best treatment. The two most highly ranked treatments both had more than 50% probability of being the best (sucralfate and silver dressings). However, the data for sucralfate were from one small study, which means that this finding should be interpreted with caution. When exploring the data for silver and sucralfate compared with widely used dressing classes, there was some evidence that silver dressings may increase the probability of VLU healing, compared with non-adherent dressings: RR 2.43, 95% CI 1.58 to 3.74 (moderate-certainty evidence in the context of a low-certainty network). For all other combinations of these five interventions, it was unclear whether the intervention increased the probability of healing; in each case, this was low- or very low-certainty evidence as a consequence of one or more of imprecision, risk of bias and inconsistency.

The authors essentially could only conclude that more research is needed to determine whether particular dressings or topical agents improve the probability of healing of VLUs.

Int Angiol 2017; 36: 565–568.

The authors investigated the relationship between nocturnal symptoms and anatomic locations of superficial venous insufficiency. A retrospective one-year review of 371 consecutive patients presenting to a venous disease practice was conducted. Patients underwent a comprehensive exam including duplex scans. Female patients made up the majority (315/371, 85%) with an average age of approximately 56 years. The 56 men had a mean age of 63.2. Ninety-two percent of patients had findings of superficial venous reflux with the anatomic site of involvement as follows: GSV (51%), SSV (16%), and tributaries (33%). Thirty-two percent of patients experienced leg cramps (LC) and 16% experienced restless leg syndrome (RLS). The patterns of reflux did not differ between patients with nocturnal symptoms compared to those without nocturnal symptoms. Nine percent of patients with nocturnal symptoms had no evidence of venous disease. Of those patients with LC, 76% had reflux in the GSV, 48% had reflux in the SSV, and 92% had reflux in at least one segment of the superficial venous system. Of those patients with RLS, 78% had reflux in the GSV, 35% had reflux in the SSV, and 87% had reflux in at least one segment of the superficial venous system.

The authors concluded that there is no significant difference between patterns of superficial venous reflux in patients with nocturnal symptoms compared to those without nocturnal symptoms. In addition, the presence of nocturnal symptoms does not predict a specific pattern of disease. The authors suggested another study to determine whether correction of the main truncal disease is sufficient or if treatment of both the truncal and tributary veins is necessary for alleviation of nocturnal symptoms.

J Vasc Surg: Venous and Lym Dis 2018; 6: 575–584.

This is a retrospective single-center study of patients diagnosed with deep vein thrombosis (DVT) on duplex ultrasonography (DUS) from 1 January 2011 to 31 December 2013 that received a follow-up DUS. Patient demographics, risk factors, medications, and DUS findings were recorded. Ten segments from the common femoral to distal calf veins were checked for the presence of residual venous obstruction (RVO), DVT propagation, and recurrence. RVO was defined as any non-acute venous obstruction with more than 40% of luminal diameter remaining during compression or the presence of chronic post-thrombotic occlusive disease. DVT recurrence or propagation (rDVT) was measured as either a new acute DVT in the previously involved segment or involvement of a new segment in the same extremity. A total of 185 lower extremities representing 156 patients met the inclusion criteria. RVO was noted in 61.1% of limbs. The three-year rDVT rate was 10.3%. Patients with recurrent venous thromboembolism or thrombophilia had a higher risk of developing RVO (odds ratio (OR), 2.89, P < .01; OR, 4.39, P ¼ = .04, respectively). Extremities with larger clot burden had an increased risk of RVO on follow-up DUS (OR, 1.25 per segment; P < .01). The presence and degree of RVO on follow-up DUS had an increased risk of rDVT on subsequent DUS (OR, 3.90, P = .04; OR, 1.21 per segment, P ¼ = .04, respectively). Limbs with complete resolution of DVT by DUS had a significantly decreased risk of rDVT (OR, 0.26; P = .04). In 185 lower extremities of 156 patients with acute DVT, follow-up duplex ultrasound demonstrated RVO in 61.1%; larger initial clot burden was associated with an increased risk of RVO. Recurrent DVT was associated with the presence and degree of RVO, and limbs with no RVO had a decreased risk of recurrence or progression. The authors suggest using follow-up duplex ultrasound in patients with DVT to identify those at an increased risk for recurrence or progression and help guide the duration of anticoagulation therapy.

Eur J Vasc Endovasc Surg 2018; 56: 247–254.

In this prospective observational study, 12 participants with unilateral post-thrombotic obstruction of the iliac and/or common femoral veins (CFVs) underwent a treadmill stress test with invasive pressure measurements in the CFVs and dorsal foot veins of both affected and non-affected limbs. This was performed the day before and three months after stenting the obstructed tract. Paired sample t-tests were used to compare the treatment effect and univariable linear regression analysis to determine the association with improvement in quality of life. Before treatment, CFV pressure increased 34.8 ± 23.1 mmHg during walking in affected limbs compared with 3.9 ± 5.8 mmHg in non-affected limbs. This pressure rise decreased to 22.3 ± 24.8 mmHg after three months’ follow-up compared with a 4.0 ± 6.0 mmHg increase in non-affected limbs (26.2 mmHg difference; 95% CI: 41.2 to 11.3). No such effect was found in the dorsal foot veins. The VEINES-QOL increased 25.3 ± 11.3 points after stenting and was significantly associated with a decrease in CFV pressure rise during walking (regression coefficient 0.4; 95% CI: 0.1–0.6). This prospective observational study using invasive pressure measurements during a treadmill stress test demonstrates that ambulatory venous hypertension, caused by post-thrombotic iliofemoral venous obstruction, can be significantly reduced by stenting. It also shows that this is associated with a reduction in venous claudication and a significant improvement in quality of life. These results substantiate the use of stenting in patients suffering from post-thrombotic iliofemoral venous obstruction that is resistant to conservative treatment.

Ann Vasc Surg 2018. Epub ahead of print, pii: S0890-5096(18)30589 doi:10.1016/j.avsg.2018.06.009.

Cyanoacrylate embolization (CAE) technique threatens to shake the glory of the currently well-established endovenous methods. We have analyzed all previous studies by searching MEDLINE base using PubMed. Although the idea of using n-butyl cyanoacrylate (NBCA) glue in medical purposes was not new, the very first in vivo and animal experiments using NBCA for vein closure were conducted just at the beginning of this millennium. The results of these studies gave warranty to begin with the first interventions in humans. Early studies reported very high success rates of more than 90%, with the longest follow-up period of 36 months. There were no major adverse events reported, while the minor ones – mostly phlebitic reactions – were defined as mild-to-moderate. The newest head-to-head studies showed that CAE is a non-inferior technique to other endovenous methods, with higher occlusion rates and fewer adverse events. The short procedure time and not using tumescent anesthesia or compressive stockings reduce patient discomfort to the minimum. This is definitely a step forward in answering the demands of modern “walk in – walk out surgery.” As an easy-to–handle technique, CAE undoubtedly pierces its path to the top of varicose veins surgery but more head-to-head clinical trials with longer follow-up periods are necessary to obtain a plain picture.