Landmark EVRA trial provides first Level 1 evidence for early endovenous ablation
Rick de Graaf:
What comes next in deep venous stenting
Ultrasound-guided foam sclerotherapy of small saphenous vein as effective as endovenous laser ablation for venous clinical severity score and quality of life at one year The first full results of the Early Venous Reflux Ablation (EVRA) ulcer study were presented at the Charing Cross Symposium (CX; 24–27 April, London, UK). The presentation was accompanied by simultaneous publication in the New England Journal of Medicine.
he randomised trial revealed that early endovenous ablation outperforms deferred treatment in healing leg ulcers. It shows early ablation of superficial venous reflux results in faster healing of venous leg ulcers and freedom from ulcers for much longer time than with deferred ablation. Early treatment is also cost-effective, which means that the findings of this trial, which provide the first high-quality data backing early ablation, will have global implications for clinical practice and patient care pathways. Nearly 90% of the CX voters agreed with the motion that the EVRA trial will change clinical practice. “This presentation continues the great tradition of trials to come out from Imperial College at the Charing Cross Symposium,” said chief investigator of the trial,
Alun Davies, Imperial College London, UK, who presented the clinical results along with the team at a late-breaking trials session. The EVRA ulcer study was funded by the National Institute for Health Research Health Technology Assessment Programme and Davies estimated that these findings, if implemented in clinical practice, could save the UK’s National Health Service (NHS) a signifiant amount every year. The ESCHAR trial previously showed that surgical correction of superficial venous reflux in addition to compression bandaging does not improve ulcer healing but reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer-free time. While compression bandaging is the mainstay Continued on page 2
Preliminary results presented at the Charing Cross Symposium (24–27 April, London, UK) by Claudine Hamel-Desnos (Caen, France) show that at one-year follow-up, the rate of occlusion of the small saphenous vein is lower after ultrasound-guided foam sclerotherapy than after endovenous laser ablation, but the clinical improvement is similar in both groups and remains stable.
his is the first result of the Fovelass study: a multicentre, randomised, controlled study comparing endovenous laser ablation and ultrasound-guided foam sclerotherapy regarding the rate of occlusion in the small saphenous vein, eventually with a three-year follow-up. The study is ongoing. Data from 158 patients, at 12 centres, were included in the study of which 78 underwent ablation, and 80 had sclerotherapy. Both groups were homogenous: 75% female, mean age 58 years. There were no significant anatomical differences of the small saphenous vein between ablation and sclerotherapy patients (the mean diameter at mid-calf was 6mm and 5.8mm Continued on page 4
Landmark EVRA trial provides first Level 1 evidence for early endovenous ablation Continued from page 1
of leg ulcer treatment, early intervention has long been taboo in certain circles. At present, in the UK, the management of venous ulcers is based on the ESCHAR trial and involves using compression bandages to heal the ulcer and subsequent surgery to treat the underlying reflux to reduce the risk of recurrence. However, the American Venous Forum has made a Grade 2, Level C recommendation in favour of early intervention in active ulceration based on the results of some cohort studies—despite randomised controlled trial evidence that there was no benefit. The aim of the EVRA ulcer trial is to clarify this contentious issue. The study set out to evaluate whether early endovenous ablation can improve venous ulcer healing in addition to compression therapy. The triallists including Manj Gohel (Cambridge, UK), reported the rationale and study methods; Francine Heatley (London, UK) provided data on the recruitment and demographics; and David Epstein (Granada, Spain) reported on the health ecomics analysis of the trial. The investigators reported in the NEJM that venous disease is the most common cause of leg ulceration. “Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on healing remains unclear,” they write. “The usual journey for a patient who presents with a leg ulcer is that they may be seen in primary care, or a wound health care centre. Often, they do not get referred on to a vascular specialist for evaluation to see if their veins can be treated. One of the mainstays of treatment is just use of compression therapy,” Davies noted. Investigators working in 20 centres in the UK randomly assigned 450 patients with venous leg ulcers and superficial venous reflux to either an ‘early’ group of 224 patients that received compression therapy (with stockings or bandages) followed by endovenous ablation within two weeks, or a
‘deferred’ group that received compression therapy followed by deferred ablation, i.e. after the leg ulcer had healed, “which often in the UK is regarded as standard practice,” said Davies. The latter group consisted of 226 patients. Of these, 31 patients were lost to follow-up or withdrew and 12 died, leaving 387 patients in the per protocol analysis. The primary outcome measure was the time to ulcer healing from the date of randomisation. The secondary outcome measures were the rate of ulcer healing at 24 weeks; the length of time free from ulcers (ulcer-free time) during the first year after randomisation; and patient-reported healthrelated quality of life as measured by Venous Clinical Severity Score (VCSS), Quality of life (AVVQ, EQ-5D-5L, SF36) and costeffectiveness. In the trial, treatment modality and strategy was determined by the treating clinical team. Endovenous ablation included the use of foam, endothermal ablation and non-thermal techniques. “The outcomes of all modalities are good, and we are not going to break down the data by technique,” Davies commented. With a sample size of 450 patients (or 254 leg ulcer healing events), the study was powered to detect 15% difference in a 24week healing rate (60% vs. 75%) with 90% power and 5% significance.
Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early intervention group than in the deferred intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval, 1.13 to 1.168; p=0.001). The median time to ulcer healing was 56 days (95% CI, 49 to 66) in the early intervention group and 82 days (95% CI, 69 to 92) in the deferred-intervention group. The hazard ratio for ulcer-free time in the early group was 1.54 (95% CI, 1.07–2.21) p=0.02. At both six weeks and six months, the group that received early intervention had significantly
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better quality of life scores. With regard to procedure complications, there were more instances of deep vein thrombosis in the group receiving early intervention, than in the group receiving delayed intervention. “EVRA is the first large randomised trial to confirm that early endovenous ablation accelerates ulcer heaIing. In the UK, and worldwide, it is important to look at whether a treatment is costeffective. We found the pathway of early intervention was undoubtedly costeffective. The results revealed an 86–99% probability that early intervention is cost-effective at the UK National Institute for Health and Care Excellence (NICE) threshold,” explained Davies.
“These data highlight the need for a major review of leg ulcer care pathways worldwide so that we can implement a strategy for rapid assessment and ablation of superficial venous reflux for patients with venous leg ulcers. Education of patients, nursing teams, healthcare professionals and commissioners is essential,” Davies stated at a CX Press Conference. At the Charing Cross Symposium, Raghu Kolluri, Columbus, USA, commented on the ramifications of the trial to say: “EVRA showed faster ulcer healing, more ulcer-free days and cost savings. Several recommendations such as the current Society for Vascular Surgery (SVS)/American Venous Forum (AVF)
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guidelines are based on evidence at the level of 2C, and we hope that this will change to incorporate EVRA into the treatment algorithm. It is also important to educate all involved in venous leg ulcer care.” Davies reiterated the point, “We will undoubtedly need to see a rewrite of many of the international the global guidelines but one of the key things is to empower the nurses and people with leg ulcers to actually seek referral to a vascular specialist and to persuade the insurers globally, and commissioners in the UK, i.e., those who monitor and dispense healthcare budget that endovenous ablation is a very cost-effective way to treat patients. In the UK, we hope to see patients, rather than languishing in the community, being referred for very early evaluation and early intervention. As you can see from the data, we were unable to randomise over a third of patients because they had their leg ulcer present for more than six months, and there is a large group of people who have chronic leg ulcers who never really get assessed for intervention. Education of patients and those with first contact with patients for referral to a specialist who can carry out the appropriate evaluation and treatment is vital.” As for future research, Davies told Venous News, “We have been lucky enough to receive funding from the NIHR to follow up the EVRA cohort of patients, so we hope to present three-year recurrence rates in 18–24 months’ time.”
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Ultrasound-guided foam sclerotherapy of small saphenous vein as effective as endovenous laser ablation for venous clinical severity score and quality of life at one year Continued from page 1
respectively). Duplex ultrasound data eight days postoperatively show that both the ablation and the sclerotherapy groups have complete occlusion of the small saphenous vein. However, at the one-year follow-up, there was
a significant difference between the level of occlusion of the small saphenous vein in the two patient groups. The ablation group had a relatively high degree of occlusion, at 95.2%, whereas the average small saphenous vein occlusion for the sclerotherapy group after one year is 60%. Hamel-Desnos and colleagues also conducted a literature review and meta-analysis. The duplex ultrasound data showed that the ultrasoundguided sclerotherapy group for segmental occlusion at day eight had had a main occlusion length of 15cm. At six months, the main occlusion length was 16cm and at one year the occlusion length was 14.8cm. At one year, the mean diameter of the ultrasound-guided sclerotherapy recanalisation group was 1.9mm. “On day eight, the rate of occlusion
was very high,” said Hamel-Desnos. She continued, “It was more than 90% for both groups. However, at one year, the rate of occlusion was 96% for laser, but only 60% for foam.” The length of vein occlusion for complete occlusion was about 20cm for both groups, though a little greater for ultrasound-guided foam sclerotherapy. “For foam, in the case of a segmental occlusion, the mean length of occlusion was about 15cm which is not so bad. Also we have noticed that in the case of recanalisation, the mean diameter was only 1.9mm at one year,” Hamel-Desnos said. The diameter of the vein diminished quicker in the laser group than in the foam group and almost all patients were symptomatic at day zero. Conversely, 80% of these patients were asymptomatic at one
year. The validation of Venous Clinical Severity Score (VCSS) score was highly improved in both groups, with no difference even at one year. The quality of life scores were improved at six months and remained stable at one year for both groups with no difference between them. “A complementary sclerotherapy was carried out in just a few cases, while no phlebectomy was performed and at one year, varicose veins in the small saphenous vein region were much less frequent than on day zero,” added Hamel-Desnos. Hamel-Desnos concluded: “Our preliminary results show that at oneyear follow-up, the rate of occlusion of the small saphenous vein is lower after foam than after laser but the clinical improvement is similar in both groups and remains stable.”
CX audience rejects idea that ATTRACT has the final say on thrombolysis in deep vein thrombosis According to a debate at the Charing Cross Symposium (CX; 24–27 April, London, UK), the vast majority of CX delegates disagreed with the view that the ATTRACT trial has provided the definitive answer on the use of pharmacomechanical catheter-directed thrombolysis for deep vein thrombosis—more than 80% voted against the motion “ATTRACT is the final word on lysis of proximal deep vein thrombosis”.
he ATTRACT trial, which was presented at CX 2017, found that the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not reduce the risk of post-thrombotic syndrome in patients with proximal deep vein thrombosis. However, it did find that—compared with anticoagulation alone—the combination did result in a higher risk of bleeding or ischaemia due to femoropopliteal or infrapopliteal disease, suggesting that vein bypass should be offered to all appropriate patients. The aim of the CX Debate was to discuss whether or not the trial meant the end for exploring the use of pharmacomechanical catheter-directed thrombolysis in this subgroup. Speaking against the motion that ATTRACT has final say, Mitchell Silver (Columbus, USA) said that there were several “facts” about the ATTRACT trial that undermined its findings. These included that the results did not apply to the patients “we treat every day”, with Silver claiming “only one in 50 patients screened were randomised” and that “these results are not generalisable”; that the primary endpoint was “flawed” because the Villalta score (used to assess post-thrombotic syndrome) was applied in a binary fashion, which was a too stringent approach to use for the primary endpoint; and that “ATTRACT was too underpowered to look at the group that has the highest risk of post-thrombotic syndrome and benefits the most from intervention”. Regarding the higher bleeding rate seen in ATTRACT, he noted that the median duration of tissue plasminogen activator (tPA) treatment was “21 hours” and that a shorter treatment time would result in less bleeding. Brian DeRubertis (Los Angeles, USA), who was speaking for the motion, said for the sake of
debate he would argue that ATTRACT was the final word on lysis due to the rigorous and welldesigned nature of the trial, but acknowledged that the study had its limitations. However, he said that the problems with ATTRACT were “common to all randomised trials”, as issues of patient accrual oftentimes require compromise in inclusion criteria and because of the fact that lessons are learned during the conduct of the trial. “Randomised controlled trials strike a balance between broad applicability to different patient populations, obtaining answers to specific questions of interest and timely completion of the trial,” DeRubertis commented. He added: “Our goal with welldesigned clinical trials should be to look deeper into the trial results, beyond the abstract or publication headlines, and see if there are valid lessons to be learned.” Summing up his view on the study, he stated: “I think we can learn a lot from ATTRACT and any similar trial going forward. Among the specific lessons we have learned from ATTRACT is that while not all patients would be expected to benefit from lysis, there is a subset of younger patients with proximal iliofemoral disease that can be expected to derive significant benefit.” After DeRubertis and Silver had stated their arguments, the discussion moved onto what further trials were needed and, in particular, the endpoints that should be used. According to Silver, a “modern era” deep vein thrombosis trial was in the planning stages. He explained, unlike the ATTRACT trial, this would use current approaches—such as intravascular ultrasound (IVUS), shortened tPA procedure time, and “mandated post-procedural imaging”. “The question will be answered,” he claimed. However, speaking from the audience, Mark
Michael Silver and Brian DeRubertis
Meissner (Seattle, USA) declared it to be “absolute nonsense” to continue funding research in this area “until you spend five years finding another outcome measure”. He added you cannot do it as part of a randomised trial, commenting “we are throwing very good money away if we keep asking the wrong question. Although very well done, we get a right answer but not one that is useful. It is not helpful to ask if pharmacomechanical catheter-directed thrombolysis is a first-line therapy for all-comers— we all know that it is not—and then look at an absolutely nonsensical clinical outcome measure to support it. So, I do not think we should throw another dime at this.”
Changes to lumen shape may be more important than area in venous stenting patient outcomes Data presented at the Charing Cross Symposium (24–27 April, London, UK) indicate that a rounder post-stent lumen shape has a positive correlation to 12-month patient improvement, placing emphasis on the change of lumen shape from pre- to post-stent and its effect on outcome. The data were presented by Lowell Kabnick (New York, USA).
ith the emergence of dedicated venous stents understanding the role of individual design elements (cell architecture, radial strength, flexibility) in the performance of the stent and, more importantly, how this therapy improves patient outcomes is critical in continuing the treatment pathway and continued improvement of stents. Kabnick maintained that stent design matters because while area is important, for a given perimeter, lumen shape impacts area, flow and pressure, and aspect ratio is a better predictor of stent performance and patient outcomes. He solidified his point by referring to a study published in the Korean Journal of Radiology in 2015 (Stent compression in iliac vein compression syndrome associated with acute ilio-femoral deep vein thrombosis) which demonstrated that better patency is associated with rounder lumen. The study included 48 patients with iliac compression and acute deep vein thrombosis followed for an average of 20 months. Follow-up was performed with
CT (computed tomography) venography and stent compression was considered significant if lumen compression was greater than 50% (aspect ratio 1:2). The study found that significant stent compression was inversely correlated with stent patency (p<0.001). “What we are trying to determine is whether shape influences better patient outcomes. We have found that healthy veins are highly compliant and change shape dynamically when pressure and flow change. The VIRTUS study provides a rich database of patient imaging studies and outcomes. We went through it and came up with the following question: Is change in post-stenting vessel shape a predictor of patient outcomes?” he said. Kabnick reported what he found from taking a “deeper dive” into the VIRTUS feasibility cohort with an early look at lumen shape and 12-month patient outcomes. Intravascular ultrasound (IVUS) measurements were used pre- and post-stenting to get maximum and minimum diameters and calculate aspect ratio (maximum diameter
[major axis]/minimum diameter [minor axis]). He found that the median pre-stent area was 43mm2 vs. a median post-stent area of 130mm2, a 74% increase. But the aspect ratio went from a median of 2.8 pre-stent (an ellipsoid) to a median of 1.3 post-stent (a circle), a -45% change. Increased area meant a significantly rounder shape. “Is the area important? Sure it is, however, the question is whether the aspect ratio is a better predictor of patient outcomes. We used the VCSS [Venous Clinical Severity Score] to look at the impact and found that the mean VCSS change (pre-stent to 12 months) was 5 (p<0.001). When we looked at the relationship between post-stent vessel change and 12-month patient outcome, there was no clear pattern for area change, while change in aspect ratio is clearer,” Kabnick said. He further noted that aspect ratio showed a linear pattern with a moderately positive relationship between decreased ellipticity and clinical improvement. “Patients with the greatest lumen change oval to round most likely exhibit clinical improvement,” Kabnick explained. He concluded that changes to pre-stenting lumen shape may be more important than area as rounder poststent lumen shape has a positive correlation to 12-month patient improvement as measured by VCSS.
Reviewing five years of deep venous stenting: What comes next? RICK DE GRAAF COMMENT & ANALYSIS For many venous specialists, dedicated venous stents represent the future—and the promise of an ideal venous stent on the horizon is a central topic of discussion. In this article, Rick de Graaf reviews the recent history of venous stenting and outlines the questions that need to come next.
bviously, treatment of deep venous obstructions with stents goes much further back than just five years. The first reports of successful deep venous stenting originate from Germany, Sweden and the USA in the early 1990s. Mainstream attention increased rapidly in the early 2000s, after publications by the Stanford group (O’Sullivan and Dake) and of the bestknown series by Neglen and Raju. Nevertheless, the last five years may truly qualify as a new era. Deep venous interventions blossomed intensely during this time, with multiple centres in Europe and the USA exploring interest in the endovascular approach. Both physicians and industry sought new innovative techniques and devices and thus, dedicated venous stents were developed. Deep venous treatment became a returning popular theme at major conferences around the world. Thereby, discussions over approach, strategy and devices intensified with a host of questions: Which imaging modality should be used? Is any stent superior over others? Do we need recanalisation devices? Which patient does well after recanalisation and which patient does not? How do we identify
the optimal patient for intervention? Why do stents reocclude and how do we prevent it? What is the best antithrombotic strategy— anticoagulation, antiplatelets or both; and how much is needed, how long for, etc. The list goes on and on. A few major points should be discussed, in order to shed light on the current state of venous stenting procedures. The first dedicated stents came to the market around 2012. At the time, the Wallstent was not considered good enough. Admittedly, the Wallstent caused some problems—in my own experience as well—and some were difficult to solve. Nevertheless, since 2012, I have not seen a perfect stent appear. Every stent has specific pros and cons. Some downsides are so destructive however, that the problems caused by the stent cannot be solved anymore, at least not through endovascular means. Sometimes, it even feels like a step backwards. Although newer stents may be easier to deploy and can be positioned more accurately, it is important to note that there is no scientific evidence that any of the new stents perform better than the Wallstent. Certainly, new stents will continue to enter the market in the coming years, some
with well thoughtout designs that may help to boost clinical success, others with anti-proliferating drug coatings or another unsubstantiated smart marketing gimmick. Still, these stents should not be expected to magically shift the patency to 100%. Naturally, this does not mean we should not continue to look for innovations to support our daily practice and optimise patient outcome. However, if stent design does not fully account for stent patency, what does? As can be extracted from Virchow’s triad, unfavourable haemodynamics or increased coagulability may be additional reasons for stent occlusion. Low flow may cause thrombosis, but we do not know how much flow is enough. I have seen some patients with dreadful flow with patent stents after many years, while others have excellent flow yet still occlude. Although the need of antithrombotic therapy after deep venous stenting is beyond discussion, the exact concentration, duration and type remain debatable. Direct anticoagulants (DOACs) seem to slowly but surely be surpassing vitamin K-antagonists as primary oral anticoagulants (OACs); however, some interventionalists challenge the superiority of OAC in favour of antiplatelets. Due to the multifactorial nature of stent reocclusions, it will be extremely hard if not undoable to find superiority of one medical treatment over the other. It is important however to scrutinise the optimal antithrombotic strategy for the individual patient. Attention for resistance to certain medications should also be advocated for deep venous interventions; close collaboration with haematologists therefore is recommended. Stent reocclusion is cumbersome to treat and increases the risk of (fatal) pulmonary emboli. The deal may not be sealed with an open stent however. Why do some patients benefit
from an open stent while others seem not to improve? For one, the complaints may not have been venous-related in the first place. So, do we need better or different scoring systems? Although the Villalta scale is most widely used, it has not been published in a peer-reviewed journal and is open for critique. Another reason may be inadequate venous outflow from the leg, either by continued venous insufficiency due to valve destruction or absence of inline flow towards the stents. Previously created collateral pathways may inadequately distribute a significant blood volume away from the stented venous segments. Thus, patent iliac stents do not necessarily prevent venous hypertension in the leg. Maximising complete and fast outflow of the leg into the stents is the prerequisite. Finally, some patients may not qualify for treatment in the first place. Patient selection should be one of the key points of interest. Extensive post-thrombotic scarring of all major inflow veins may preclude autonomous long-term stent patency. Surely, an arteriovenous fistula can be placed in all of these patients. The stents are likely to stay open—that is, until restenosis by intimal hyperplasia. However, when spontaneous venous blood flow from the leg is compromised it is unlikely that the patient will do better. In conclusion, the last five years established the bottlenecks of a procedure that nevertheless has proved very successful and safe. Optimisation of antithrombotic therapy and flow enhancement may result in the unchallenged status of deep venous stenting. Rick de Graaf is director of Radiology, Interventional Radiology and Nuclear Medicine at the Clinical Centre of Friedrichshafen, Germany
Pelvic venous disorders
Moving towards a paradigm shift for pelvic venous disorders with launch of International Pelvic Venous Work Group Treatment of patients with pelvic venous disorders is a “controversial topic,” Kathleen Gibson (Lake Washington Vascular Surgeons, Bellevue, USA) said at the Charing Cross Symposium (CX; 24–27 April, London, UK), as there is “no consensus on the best mode of treatment and no long-term outcome data” on the subject. To meet this global lack of guidelines and evidence-based clinical data, the International Pelvic Venous Work Group (IPVWG) launched last year with the aim of developing standardised classification systems and tools for clinical research and treatment of pelvic venous disorders. The group is supported by the American College of Phlebology (ACP) Foundation and the Society of Interventional Radiology Foundation (SIRF), and involves a multidisciplinary range of representatives from venous, phlebological, radiological, surgical and gynaecological societies and institutions.
mbolisation as a treatment for chronic pelvic pain is widely in use in the venous community, with two systematic reviews of case series and trials showing a link between embolisation and improved outcomes in affected women. However, as Neil Khilnani (Weill Cornell Medical College of Cornell University, New York, USA) maintained in a pelvic vein session at CX, “There is evidence that supports that patients do get better, but the evidence is weak.” Khilnani, who initiated the IPVWG, stated the group is “taking on the responsibility of accumulating evidence relatively rapidly”. He told Venous News, “There are clear evidence gaps in taking care of patients with pelvic venous disorders, and as a group, we have embarked on a process to address those evidence gaps that exist within that area.” Undermining the findings of the systematic reviews and, in general, trials or case series of pelvic venous disorders, is the heterogeneity of outcome measures, treatments techniques and diagnostic criteria. Mark Meissner (University of Washington, Seattle, USA) commented during the same session at CX, “The current state we are in is this alphabet soup of pelvic venous disease. We have this group of syndromes—Nutcracker, pelvic congestion, May-Thurner—none of which make a lot of sense.” The poorly defined and overlapping nature of the syndromes, along with gaps in knowledge about the pathophysiology underlying the syndromes, leads to “a number of errors” in diagnosis and subsequently causes poor treatment outcomes, Meissner argued. In the
following presentation, Melvin Rosenblatt (St Vincent’s Medical Center, Bridgeport, USA) echoed this sentiment, saying, “There is enough overlap between these syndromes to cause confusion,” and as “we do not have a good definition … the reality is we have to get rid of this concept of syndrome.” Meissner similarly suggested disposing of the syndromes, in order to introduce “a new paradigm” in the area. Not enough is known, however, about the pathophysiology or aetiology of the syndromes, and previous literature has been mainly focused on finding and treating venous reflux as the cause of pelvic venous disorder symptoms. Gibson and Khilnani both point out that venous obstruction has emerged as a component involved in the disorders. “We are talking about both reflux and obstruction,” Gibson said to Venous News, “and although there are groups that have been working in these areas that think what they are doing is the right thing in terms of treatment and diagnosis, when they present their data, their outcome measures are all vastly different because there is no standardisation. So, you cannot perform a meta-analysis in a really good way to know whether we are helping people or not.”
graded data results. “It was clear that we need to have the proper tools before we embark on outcomes research in this area,” Khilnani said. “There is no point in doing research if we are not going to be able to define our patients very clearly,” Khilnani explained, pointing to the lack of disease criteria and discriminative tools for pelvic venous disorders. He added that validated endpoints were also a central discussion point during the consensus panel, with a lot of priority placed on a quality of life assessment tool to track patient improvement or deterioration in response to treatment. “We wanted to include the patient’s voice, and also make the tool FDA acceptable”, to allow tool use in device and drug labelling studies. Following a vote, the consensus panel selected five “top issues” to prioritise. These included a series of consensus multidisciplinary meetings to develop diagnostic criteria for pelvic venous disease, as well as a discriminative tool, a quality of life tool, a clinical scoring tool and finally a meeting to develop guidelines for evaluating and treating patients with symptoms related to the disease. There currently are “very few guidelines in the gynaecologic community that affirms the disease even exists”, Khilnani said, “let alone gives us guidance in terms of what to do.” Nor is there much guidance given in the Venous Disease Guidelines, Khilnani pointed out, offering only a 2B recommendation for treatment of reflux for pelvic pain. No recommendations are given for obstruction or pelvicorigin varicose veins. Currently in progress, however, is
the work to develop discriminative tools. Two classification systems have been submitted by Rosenblatt and Meissner, who presented their respective tool proposals at CX. Meissner suggests a tool operating on distinctions in six categories of clinical presentations: 0. No clinical manifestations of venous disease 1. Non-cyclic chronic pelvic pain of venous origin 2. Pelvic origin lower extremity varices 3. Lower extremity oedema of pelvic venous origin 4. Venous claudication 5. Chronic left flank pain of venous origin with or without haematuria a. Left flank pain b. Haematuria “This is the tool I personally favour, in that it is very cohesive with CEAP,” Meissner explained, adding that further designation of aetiology, anatomy and pathophysiology would be included in the classification. In Meissner’s examples of what the proposed classification would look like, a case of post-thrombotic venous claudication could be described as C4ESA LCIV,LEIVP O. Aligning with CEAP, C here indicates clinical category (as described above), E indicates primary or secondary aetiology, A refers to anatomy—in this example, involvement of both the left common and external iliac veins, and the P distinguishes between reflux or obstruction in pathophysiology. A strength of this system, Meissner maintained, is the wide-spread familiarity with CEAP among vascular surgeons, which could mean uptake of Continued on next page
Developing standardised tools and measures
In 2017, the SIRF funded a multidisciplinary Research Consensus Panel that convened in October of last year in Washington DC, USA, to identify research questions and prioritise tools needed to perform clinical trials with high evidence-
Pelvic venous disorders
Continued from previous page
a pelvic-specific version should prove easier than the introduction of a novel system. Rosenblatt in contrast proposed a discriminative instrument that departs from the CEAP structure, relying on a three parameter classification: Pathology (P), symptom location (S) and varicosity location (V). Similar to CEAP, use of subscript defines variables within these categories, but the classification system is “very different” to Meissner’s, Rosenblatt said. With five variables of pathology and symptoms respectively, and four variables of varicosities, the tool emphasises location of problem areas for the patient. Rosenblatt explained, “the reality is, these are the parameters that will govern what I will do for the patient.” In addition to the numeric values of the three parameters, subscripts can provide information on the character of the symptoms as well as localisations such as right, left, or bilateral. Showing a few examples, Rosenblatt argued the tool produces classifications that are “simpler in terms of their configuration” compared to Meissner’s pelvic-specific CEAP examples. A patient with left gonadal vein reflux, pelvic pain and pelvic varicosities would in Rosenblatt’s proposed instrument be defined as P1,LS1V1. “The more letters you add, the more subscript you add, the more complicated it becomes,” he told his audience at CX, “and we want this tool to be accepted not only by vascular communities, but by the community at large— particularly the gynaecologic community that sees these patients primarily.” A face-to-face meeting of the IPVWG scheduled for July 2018 is set to host a discussion to develop a consensus on a final discriminative tool to move forward with, and begin to introduce it internationally. Meanwhile, Khilnani reported that a seed grant has been awarded by the SIR to work on developing a quality of life or patient-reported outcome tool, a
Mark Meissner and Melvin Rosenblatt
project led by Khilnani along with Gibson, Meissner and gynaecologist Lee Learman (Florida Atlantic University, Boca Raton, USA). Khilnani maintained that establishing diagnostic criteria (disease definition) as well as treatment and reporting standards remain “on the horizon”. “We started out with the idea that we needed to improve guidelines”, and to do so the group set out to initiate randomised clinical trials. However, “as we started out we realised that a lot of preliminary work was needed; we saw other venous trials, like ATTRACT, come out that were criticised because the outcome measures had flaws. So we decided to make sure we got
the horse in front of the cart, not to proceed in doing randomised studies but rather to initiate our analysis instead on what tools we needed to be able to do those studies.” Khilnani emphasised the project’s aim to “fast-track” development of its proposed instruments, with hopes that publications and implementation of the new tools will quickly follow the decision-making meetings like the one taking place in July. The original goal of the initiative, to provide robust clinical evidence for comprehensive guidelines in the field, thus remains visible at the end of the conscientious and methodical path to standardisation that the IPVWG has taken on.
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Predictable Deployment The VICI VERTO VENOUS STENT delivery system is designed to deploy peripheral to central for predictable placement at a distal confluence
A unique closed-cell geometry with 24 strut rings and alternating curved bridges work together forming uniform coverage with strength and flexibility specifically for the venous system
Advancing the Treatment of Venous Disease The VICI VENOUS STENT is CE Marked under the European Medical Devices Directive (93/42/EEC) and approved by the Australian Therapeutic Goods Administration and commercially available in Europe and Australia. CAUTION: Investigational device. Limited by United States law to investigational use. The VICI VERTO VENOUS STENT® is CE Marked under the European Medical Devices Directive (93/42/EEC) and commercially available in Europe. The VICI VERTO VENOUS STENT is not available for sale in the United States. VENITI, VICI VENOUS STENT, and VICI VERTO VENOUS STENT are registered trademarks of VENITI, Inc. ©2017 VENITI, Inc. All Rights Reserved. Produced in the U.S. VENITI, Inc | 4025 Clipper Court | Fremont, CA 94538 | www.veniti.com
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Alun H Davies Alun Davies is a Welsh-born leading expert in the venous field, one of the Editors-inChief of Venous News, and currently in the spotlight as chief investigator of the EVRA ulcer trial. In this profile, Davies talks about the implications of the trial, the greatest developments and disappointments during the course of his career, and the story of a patient whose wife had to leave to water the plants for the Royal Family. Why did you decide you wanted a career in medicine, and what led you to the vascular and venous fields?
When I was at school, I wanted to be either a priest, lawyer or doctor. My family doctor was great and used to give children miniature Cadbury chocolates— this may have been the turning point—but more likely it comes down to the fact that sciences were my stronger suit. Once I started in Cambridge, I found that anatomy was a great subject and decided that surgery was the option for me. When I moved over to Oxford to do my clinical training, I met an exceptional group of clinicians who were surgeons and great teachers. Having become the Professorial Surgical Houseman in Oxford working for Professor Peter Morris, I confirmed my intent to do general and vascular surgery. My subsequent career developed, with stints in Oxford, Cambridge, Plymouth (all UK) and Boston, USA, before moving to London back in the UK. I chose to specialise in the vascular and venous field because my thesis work was on femoro-distal bypass and vein quality, for which I subsequently was awarded a Hunterian Professorship. I have had both arterial and venous research interests, and one great achievement has been to support a number of trainees with their clinical and research training.
Who were your most important career mentors and what wisdom did they impart to you?
I have had many people who have supported my vascular endeavours. One surgeon whose wisdom does stand out, particularly as I age, was a consultant who was the lead on my first surgical firm, examined me in finals and whom I had the pleasure of working for at the urology registrar. “Alun,” he told me, “the best bit of surgery is your relationship with the patient, as everyone is able to offer surgery.”
What has been the biggest development in venous medicine during the course of your career? The major change has been the development of duplex imaging in the management of patients with venous disease. From a treatment perspective, the new endovenous techniques—initially in the form of endothermal ablation—are a big development in the field.
What has been the biggest disappointment?
Unfortunately, I would say it is the lack of progress on the development of a valve to treat deep vein incompetence. The other disappointment is that despite all the new endovenous treatments, the recurrence rates after interventions seem to be the same.
You are the chief investigator of the EVRA trial, which showed that early ablation of superficial venous reflux
results in faster healing of venous leg ulcers. How you see these results affecting current practice? The results will hopefully empower providers and patients via guidelines and education and ensure that patients who present with a leg ulcer will be referred for early assessment including duplex, as well as for endovenous ablation to be offered within two weeks if suitable.
Given that this is a UK study, do you think the results will have an impact in practice outside of the UK? The results will have a global impact, as there has been an ongoing debate on the timing of venous intervention in patients with leg ulcers, specifically whether intervention should occur when the ulcer is open or healed. This discussion was fuelled by the ESCHAR trial, which showed benefit of intervention only in terms of leg ulcer recurrence. One would hope that the results of the EVRA study will cause much stronger recommendations in the Society for Vascular Surgery (SVS) and American Venous Forum (AVF) guidelines.
How does it feel to have had your research published in the New England Journal of Medicine?
Obviously, it is great and I feel very privileged. This has been a mass undertaking by a large number of individuals, many of whom I do not know personally. So I would like to say a big thank you to all involved as well as to the patients.
What is next for you in your research? We have been fortunate to have funding from
Interview the National Institute of Health Research (NIHR) to follow up the EVRA cohort of patients, so we hope to present threeyear recurrence rates in 18–24 months’ time. There are numerous other ongoing studies, one for example is evaluating the benefit of neuromuscular electrical stimulation in claudicants, while another study is evaluating
whether there is any adjuvant benefit in wearing compression stockings for patients receiving low molecular weight heparin for deep vein thrombosis prophylaxis.
What is the most interesting paper or presentation that you have seen recently? The ATTRACT trial, as this study has raised many questions regarding how we should proceed with patients who need venous thrombolysis.
The Royal Society of Medicine Venous Forum released a guidance document earlier this year on the management of leg ulcers. What is the importance of this type of guidance and why is it needed?
The need for the document was to reinforce the recommendations of the UK National Institute for Health and Care Excellence (NICE) on leg ulcer management. The need for early referral to a vascular specialist is key, and the document was aimed at educating other healthcare professionals, commissioners and the public to ensure this cohort of patients care is improved, as it is a significant healthcare burden.
What was the proudest moment in your career to date?
My proudest moment thus far was probably when I was a trainee, being awarded a Hunterian Professorship of the Royal College of Surgeons, and delivering the subsequent lecture to my colleagues and family at the London Vascular Debating Society.
What three questions in venous medicine still need to be answered?
1. What is the role of deep venous stents? 2. Is there a need for a deep venous valve? 3. How can we stop the progression of venous disease?
Could you tell us about one of your most memorable cases?
I once had a patient with a ruptured abdominal aortic aneurysm who needed traditional repair. The patient’s wife was the royal florist, and she had to leave her husband in the hospital to go and do the royal flowers. The patient made a great recovery, and a year later I was invited to be the guest of honour as they hosted a “great to be alive” black tie dinner at the European Academy of Arts, near Buckingham Palace.
What advice do you hope your mentees and students will always follow?
If you do not enjoy your job, do not do it. Medicine is a great privilege.
What are your interests outside of medicine?
I greatly enjoy good food—both cooking and eating—and wine tasting is also something I appreciate. I like to travel when I can, often enjoying the architecture of churches and other buildings, and especially to go skiing or to relax on a cruise. As a Welshman living in England, I also of course love all things Welsh—including the Wales RUFC rugby team.
Professor of Vascular Surgery and head of Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College School of Medicine, Charing Cross & St Mary’s Hospital, London, UK Honorary Consultant Surgeon, Imperial College NHS Trust and Chelsea & Westminster NHS Trust, London, UK Clinical Director of Imperial Private Halth Care (NHSPPU), London, UK
2014 DSc, University of Oxford, Oxford, UK 1994 Certificate of Specialist Training (European Community) 1993 DM, University of Oxford, Oxford, UK 1992 MA, University of Oxford, Oxford, UK 1985 MA, University of Cambridge, Cambridge, UK 1981-84 BM BCh. Clinical Studies, University of Oxford Medical School, Oxford, UK 1978-81 BA, University of Cambridge, Cambridge, UK
2018 Medal of Distinction for Education UIP 2015 Lifetime award Australasian College of Phlebology 2011 Order of Phlebology Medal for excellence in clinical research 2003 European Venous Forum Prize 2002 Fellow of the Society of Vascular Medicine and Biology 1993 Hunterian Professor, Royal College of Surgeons England
Fellow of the Royal Society of Medicine British Medical Association European Society of Vascular Surgery European Venous Forum Surgical Research Society Fellow Association of Surgeons of Great Britain & Ireland Society of Academic Surgeons American Institute of Ultrasound in Medicine International Society of Cardiovascular Surgery Vascular Surgical Society of Great Britain & Ireland American Venous Forum British Association of Atherosclerosis Society of Vascular Medicine & Biology European College of Phlebology
Pilot randomised controlled trial will evaluate embolisation for chronic pelvic pain A pilot study in the UK seeks to analyse the effectiveness of embolisation of incompetent veins in the treatment of chronic pelvic pain in women, as well as conducting a cost analysis of the treatment. David Thompson, (Wythenshawe Hospital, Manchester, UK) presented the study at the 2018 Charing Cross Symposium (CX; 24–27 April) in London, UK.
hronic pelvic pain, Thompson explained, is a large-scale problem all over the world, with a worldwide prevalence of 24% and a leading cause of impaired quality of life in younger women, it accounts for 20–40% of gynaecology referrals in the UK. “Unfortunately,” Thompson added, “over 40% of women fail to achieve a satisfactory diagnosis.” An ongoing trial based in Manchester, UK, will evaluate trans-venous occlusion of incompetent pelvic veins as a treatment for chronic pelvic pain in women. It is a pilot randomised controlled trial, funded by the UK’s National Institute for Health Research. The aim of the trial is to answer a series of research questions, the primary being: Does treatment of pelvic vein incompetence by transvenous occlusion improve symptoms of chronic pelvic pain (as assessed using the validated Short Form McGill Pain Score) .Secondary questions
include measuring improvement of health status in patients and the cost-effectiveness of the treatment. Currently 55 women aged 18–54 with chronic pelvic pain and pelvic vein incompetence as demonstrated by transvaginal ultrasound have been enrolled. 47 subjects have undergone venography and been randomised to either venography only or to also receive treatment with embolisation, occluding the refluxing vein or veins with metallic coils and/or STS foam, according to the preference of the radiologist. Repeat venography was performed in treated veins, to confirm occlusion. “We are encouraged not to pursue embolisation into the thigh or buttocks, as this is primarily a trial for chronic pelvic pain rather than varicose vein treatment,” Thompson said. Follow-up is performed with completion of questionnaires at one week, three months, six months and 12 months. Of the 55 patients enrolled, 22 have fully completed the study
with 12-month follow-up. Although the aim of the trial is to get 100 patients enrolled, Thompson said that “we may have been optimistic about the rate that we can recruit.” “As we have just heard, although embolisation for chronic pelvic pain has taken off, there is little good evidence for it,” Thompson said, referring to the previous talk by Neil Khilnani (Cornell University, New York, USA) which highlighted the lack of good evidence available for treatment of chronic pelvic pain. “The only randomised controlled trial compared hysterectomy with embolisation, of which embolisation came out better.” ““Hopefully this trial and its associated economic analysis will guide future research in the form of a definitive multi centre randomised controlled trial,” Thompson concluded. “It will certainly answer two— hopefully three—recommended areas of research by the recent Health Technology Assessment. Ultimately, it will help the Royal College of Obstetricians and Gynaecologists and the UK National Institute for Health and Care Excellence (NICE) in the development of evidence based guidance in management of pelvic vein incompetence in women with chronic pelvic pain.”
Deep venous obstruction interventions: What is needed in 2018 CEES WITTENS COMMENT & ANALYSIS Cees Wittens writes for Venous News about the current state of deep venous obstruction interventions, what we might expect in the near future, and what is needed in terms of new technology, strategy and policy in 2018.
n general, everybody is focusing on better equipment to improve care, but if we look back and evaluate what has been published on deep venous obstruction (DVO) intervention and what is mentioned during recent meetings, I suggest we focus on improved patient selection and quality driven care first. Unfortunately, to identify patients for a DVO intervention we need proper selection criteria, as we have in arterial disease: A 5.5cm diameter for infrarenal aneurysms, an ankle-to-brachial pressure index threshold in obstructive disease, or an internal carotid artery diameter reduction in symptomatic transient ischaemic attack patients. As a result, we see patients being treated for DVO with hardly any improvement in quality of life (QoL) or clinical scores. Therefore, it is key that we develop the selection criteria to better predict which patient will improve after a successful intervention. This starts with the evaluation of the complaints of the patient and the possibility to improve the QoL. If this is not expected, an intervention should not be performed. There have been publications showing that stenosis of more than 50% can
be detected with magnetic resonance venography (MRV), duplex or intravascular ultrasound (IVUS), and should be treated. There are even studies comparing these diagnostic tools in order to select the best tool to identify those stenoses. But because all measurements are performed in a supine position at rest, maybe with Valsalva maneuvers or calf activities, they are not conclusive. At this point, there is no proof that a 50% stenosis rate relates to clinical symptoms, and therefore it is not an appropriate measure to select patients for an intervention. The presence of collaterals combined with 50% stenosis increases the chance that an intervention might improve the clinical scores and QoL. In general, we also need a better uniform registration (volume flow, flow direction, vessel diameter, with or without flow augmentation) of the MRV, Duplex and IVUS outcomes in order to compare the results and learn which detected pathology influences outcome. In acute deep vein thrombosis (DVT) these diagnostic tools are used to identify a DVT, but in all publications the identified DVT are called iliofemoral, femoral, proximal, central, peripheral and so on. However,
these “locations” can refer to proximal of the knee or groin or even higher. We need a better classification, such as the Lower Extremity Thrombosis (LET) classification, to categorise these DVTs and evaluate different treatment strategies. We tried to do pressure measurements in the chronic cases, but because these are also performed in a supine position at rest they hardly show any usable data. This is why we are developing a 24-hour pressure measurement in the common femoral vein to get more information and potential selection criteria. A technical solution to do this might be what we need in 2018. The fact that we do not register the potential improvement is also related to the fact that the used scoring systems like the VCSS or Villalta are not adequate enough. For example, both scores lack a question related to venous claudication and score not specifically related to venous disease, e.g. oedema or symptoms, which also blur the outcome. We need a better general applicable scoring system to quantify venous disease from varicose veins to venous ulcers with or without a previous DVT. The same applies to the generic and disease specific QoL questionnaires. The generic questionnaires are, as expected, also influenced by other concomitant diseases and not all can be used to perform cost-effective analysis. The Eq5D5L questionnaire is the most appropriate, but not used consistently, making comparisons impossible. Disease specific questionnaires also have their own restrictions. Some are only applicable for varicose veins while others can only be used in ulcer patients. A new generally applicable questionnaire should be developed combining the Eq5D5L with a new disease specific questionnaire in which questions related to venous claudication are also included.
All those clinical scores only address leg problems and we do not have any specific questionnaire for venous disease located in the upper extremity, nor for pelvic congestive syndrome (PCS). In PCS, more awareness is needed to identify obstructive disease, especially a May-Thurner Syndrome or a nutcracker syndrome. Improvements in interventional equipment like thrombectomy devices, stents with optimal flexibility, porosity and radial forces etc., and postoperative care measurements like non-invasive flow augmentation devices, as well as of course the new direct oral anticoagulants are crucial for improved outcomes, but the above mentioned issues should in my opinion be addressed first. Therefore, in 2018 our goals should be: To improve the diagnostic criteria and register all results in a standardised fashion, in order to identify clinically relevant criteria to improve care and patient selection. This will improve the quality of venous care and reduce inappropriate care, which unfortunately is still a realty and should be abandoned. An obligatory registry will potentially influence this. A follow-up with standardised clinical and QoL scores will also measure the quality of care and can identify the physicians, departments or even hospitals that do better or worse. By using these benchmark data in a region or country, care can be improved where necessary. As a result, the driving force for everybody involved in deep venous obstruction interventions should be proper patient selection and quality driven care.
Cees Wittens is head of Venous Surgery at the Maastricht University Medical Center in Maastricht, the Netherlands
One-year results of ACCESS PTS study brings “hope” for post-thrombotic syndrome patients The one-year results of the ACCESS PTS trial have shown that EKOS therapy (BTG) statistically improves post-thrombotic syndrome scores and sequelae as well as quality of life outcomes. Presenting the data at the Charing Cross Symposium (24–27 April, London, UK) Mark Garcia (Wilmington, USA) said that these results mean that “hope is here for post-thrombotic syndrome patients who have failed standard of care therapy”.
arcia maintained that the current standard of care for those suffering from chronic veno-occlusive disease and post-thrombotic syndrome, which includes anticoagulation, compression, elevation and when necessary, wound care, is simply not sufficient. Therefore, the ACCESS PTS (Accelerated thrombolysis for postthrombotic syndrome using EKOS) study was initiated. It is a prospective, multicentre study at 29 sites looking at symptomatic lower extremity deep vein thrombosis that was present for greater than six months. Patients had to have at minimum femoral deep vein thrombosis to be included in the study, while those with isolated iliofemoral deep vein thrombosis were excluded. The deep vein thrombosis had to be ultrasound documented for at least six months and patients were required to have failed a minimum of three months of conservative therapy— including therapeutic anticoagulation and compression—as well as a baseline Villalta score of ≥8. The primary endpoints were a reduction of 4 on the Villalta scale at 30 days compared to baseline in at least 50% of patients and an increase in blood flow calculated by time to washout in the affected segments. Seventy-eight patients (82 limbs) with mean deep vein thrombosis time of 13.2 months were included in the study. Garcia reported that a 4 point reduction in the Villalta scale at 30 days was seen in 67% of the patients treated (p=0.003, confidence interval [CI] 95%). The overall Villalta results saw a mean improvement of 49% from baseline out to 365 days, and went from a mean baseline score of 15.5 (severe PTS) to 7.8 (mild PTS) at one-year (p< 0.0001). Similarly, the VCSS results showed a mean improvement of 42.7% from baseline
at 365 days, from a score of 12 down to 6.9 (p< 0.0001). As for quality of life results, the VEINES-QOL found a mean improvement of 36.4% at 365 days with a baseline score of 61.1 that improved to 79.9 at 365 days. Garcia reported that the safety endpoint was met, with only one major bleed related to anticoagulation, recurrent deep vein thrombosis in three patients, and pulmonary embolism in one patient within 30 days but after initial discharge home. In conclusion, the ACCESS PTS study found that for patients suffering from chronic veno-occlusive disease and post-thrombotic syndrome, endovascular intervention using EKOS therapy is a safe and effective treatment for not only recanalizing chronic venous occlusions, but also in reducing the post-thrombotic sequelae based on Villalta and VCSS scores as well as improving the patients quality of life.
A four-point reduction in the Villalta scale at 30 days was seen in 67% of the patients treated ... The overall Villalta results saw a mean improvement of 49% from baseline out to 365 days
Questions raised on the need for a venous valve At the moment, there are not enough data to make a conclusive decision on the need for a venous valve. That is according to Mark Meissner (Seattle, USA) who presented his findings at the Charing Cross Symposium (24–27 April, London, UK).
eissner maintained that to determine whether a venous valve is necessary, four questions must be answered; 1) Is deep venous reflux after correction of superficial reflux and proximal obstruction associated with ulcer recurrence? 2) If so, does correction of isolated deep venous reflux reduce recurrence? 3) If so, how many patients would benefit from a prosthetic valve (is there a market)? 4) Is long-term competency technically and biologically feasible? Referring to highly cited articles, Meissner pointed out that while he truly believes that relieving proximal obstruction is important, he thinks “it is a leap of faith to suggest that that is
actually supported by the data”. Answering each question in turn, he consulted the existing data to find a conclusion. As for whether deep venous reflux is associated with ulcer recurrence, he looked at the ESCHAR trial. “If we look at the follow-up from the ESCHAR trial, we can see that 144 limbs had one-year ultrasound follow-up and in these limbs 17.4% had recurrence at three years. Surprisingly, there was no statistically significant relationship between persistent deep reflux and ulceration, with no difference between those in deep venous reflux, those who had a recurrence and those who did not have a recurrence. In contrast, there did seem to be a benefit in that those patients who did have an increase in venous refilling time after surgery were more likely to not have an occurrence than those who had no improvement,” Meissner said. The conclusion of the study was that venous refilling time is predictive of recurrence, but ultrasound-detected deep venous reflux is not. In relation to whether deep venous reflux correction reduces recurrence, Meissner explored the results of eight valvuloplasty series, noting that there are no randomised trials that evaluate healing and recurrence. He found that in a total of 677 patients, only 59% had competent valves and ulcers were either not healed or recurrent in one-third of patients. In a series of trials of the use of neovalve in only 98 post-thrombotic patients, valve competence was 87% and ulcer non-healing or recurrence was found in 13% of patients. “For the second question I think we have to conclude that there may be a suggestion of a benefit, but this is very low-quality evidence and if I
was considering investing in this, I probably would not do it based on this information,” he stated. As for what the estimate of patients who might possibly benefit from a venous valve could be, Meissner argued that the data are also conflicting, and that one can come up with largely varying figures depending on how the math is done, thus leaving this question up for debate. Finally, addressing whether the technical hurdles of a venous valve are insurmountable, he reported that there are a lot more data available from animals studies, and that the initial human experience with a venous valve is very limited and is not very encouraging. In conclusion, Meissner surmised that in response to the question of a need for a venous valve, the answer is “a solid maybe” and that there are not enough strong data to decide at this time. Giving his thoughts on the need for a venous valve, Meissner’s fellow panellist, Rick de Graaf (Friedrichshafen, Germany) commented, “there needs to be more attention given to deep venous pathology before it leads to post-thrombotic syndrome and more focus on those compression syndromes because when compression syndrome and venous hypertension is there for a long time, then valve incompetence might occur and then we get into a new set of patients. As for how many patients there are who might benefit from a valve, I do not know, and I do not know how many patients will actually keep open veins because of those valves and how many patients afterwards would do better, but I do know that there is still a very large community that we need to find to help.”
“Dramatic results” of cyanoacrylate glue ablation in younger patients with pure venous erectile dysfunction A small, single-centre study is assessing the use of cyanoacrylate adhesive embolisation in the treatment of erectile dysfunction due to venous leakage. The study highlights a growing interest in minimally invasive procedures to treat venogenic dysfunction, as well as a rising trend of idiopathic erectile dysfunction in younger men and the possibility of restoring erectile functionality in patients with erectile dysfunction caused purely by venous leakage.
arly results of the study found that although cyanoacrylate glue ablation of the deep dorsal vein and its bifurcation is safe and effective in the short term, the key to patient selection and good outcomes is to identify cases of pure venous erectile dysfunction, using duplex ultrasound, cavernosography or haemodynamic testing. “Erectile dysfunction is common,” Sriram Narayanan (National University of Singapore, Singapore) told the audience at the Charing Cross Symposium (CX; 24¬–27 April, London, UK). “The truth is, about 40% of men in their 40s, 50% in their 50s and 70% in their 70s have some degree of erectile dysfunction.” Half of erectile dysfunction cases are vascular, of which two thirds are arterial or mixed and one third is venous, Narayanan said. Whether or not adequate inflow exists, a persistent venous leak or venous drainage can be the cause of erectile dysfunction as the functionality importantly depends not only on inflow, but also on the passive compression of the venous outflow. Narayanan described the condition, named in the ICD-10 definition as Corporo veno-occlusive erectile dysfunction, as “failure of venous occlusion to take place.” Although this venous drainage-caused erectile dysfunction can stem from trauma such as pelvic fracture or radical pelvic surgery, Narayanan said that “sadly, there is a rising idiopathic cause—we do not know why—in younger men, in their 30s and 40s.” While Narayanan highlighted previous treatment strategies such the ligation and stripping of the deep dorsal vein and its branches, as performed extensively by Peter Lim (Institute for Men’s Health, Singapore), minimally invasive procedures are now being investigated. In Narayanan’s early findings of ablation with cyanoacrylate
adhesive in 10 patients, four patients were aged 50 or older, and six were younger, with an overall age range of 29–83 years. Pure venous dysfunction was found in 100% of the younger cohort, while the older group included three cases of mixed arteriovenous and one of pure venous dysfunction. At 29, the youngest patient’s dysfunction had been caused by the trauma (pelvic fracture and bladder rupture) of a motorcycle accident five years prior to treatment. In patient selection and follow-up, Narayanan explained he performs a full assessment, using International Index of Erectile Function and the Sexual Health Inventory for Men (SHIM) questionnaires, the latter of which is commonly used to establish diagnosis of erectile dysfunction. Comparing patients’ pre-operative SHIM scores to six-week follow-up, “there were three patients in the older age group who did not quite reach the scores they would like, while one patient—the 29-year old with massive trauma—whose leak was ablated but there was no response at all”, Narayanan said. “What is important to note is that you need to ablate the bifurcation of the deep dorsal vein, and try to avoid the spongiosal vein,” as ablation of both may result in problems with priapism, Narayanan explained. He concluded, “at least for the younger patients, glue ablation has very good results, but the key is to identify pure venous erectile dysfunction.” For carefully selected cases, Narayanan suggested the treatment can have “dramatic results” in terms of erectile functionality and quality of life. Erectile dysfunction caused by trauma, however, may have mixed results, and for arteriovenous causes, Narayanan explained that the arterial inflow insufficiency must first be dealt with before it is Sriram Narayanan possible to evaluate potential venous leakage.
AESTHETIC PHLEBOLOGY By Kasuo Miyake
Photo-documentation in aesthetic phlebology
At the early stage of venous insufficiency, dermatological alterations may be the only manifestation of the disease, and photography is the tool the vascular surgeon has to document and quantify the course of treatment, writes Kasuo Miyake.
enous pathologies in the lower limbs are closely related to the skin and subcutaneous tissue. Ectoscopy is a fundamental part of the physical examination and is the basis of the CEAP clinical classification. Photography is the tool the vascular surgeon has to document and quantify the course of treatment. Proof of this lies in the work involving the treatment of this subgroup. Whether with sclerotherapy, laser, or the combination of both, all treatments use pre- and post-photos as the main parameter of determining the success of the therapy employed. Photography is taught with the purpose of monitoring venous lesions in lower limbs for academic purposes, but in clinical practice, clinics rarely photograph patients. The low rates of photography in clinics, we believe, can be attributed to the cost of the equipment, the time required for the photography and the matching of the photos before and after, the lack of technical knowledge in photography and the difficulty of organising the image files. We use photography as one of our working tools. Our goal is to produce similar images at various stages of treatment without using any trick to infer improvement. We are adept at working with DSLR machines in automatic mode with use of external flash in TTL mode reflected to the white ceiling (Figure 1). Increasing the light source helps standardise and isolate the treatment as the contributing component to a patient’s improvement. A practical example of increasing the light source using the flash is to reflect it to the ceiling. Thus, the flash illuminates the entire area above the scene and makes it a soft source of light for the object. This technique is only possible with external flash cameras and it should be remembered that the ceiling and walls of the room must be white (Figure 1). Our objective is that only clinical changes are noticeable from photo to photo. We must establish a routine, always photographing in the same environment, with the same camera and with equivalent photographic parameters. We have photographed 100% of patients undergoing procedures for more than a decade. Usually two or more photos are taken of each incidence. Combined telangiectasias are documented with and without augmented reality to highlight the presence of the feeding vein. The strategy is interesting for the control of the short-term evolution (one to three weeks) where the inflammation triggered by the procedure can mask the final result, but the occlusion of the feeding vein shows good prognosis of the treatment. As a general rule, the decubitus position works very well for the recording of ulcers, telangiectasias and, in particular, reticular veins with use of augmented reality. Tributary veins are better recorded with patients in the standing position. Photography is key to monitoring a patient’s progress. The Lightroom software also allows for side-by-side photo comparison, a feature we use at the time of postprocedure photography—our parameter of success (Figure 2). Our “phlebosuite”, a complete aesthetic phlebology procedure room, is mounted with two full HD screens side by side and we keep the pre-reference photo on the left screen and the newly captured image is automatically directed to the right screen. As a rule, the result of the treatment of microvarices tends to be underestimated before access to pre- and post-photography. With this real-time visualisation routine, both the medical staff and patients have a more real idea of the evolution of the pathology, facilitating decision making and adherence to treatment. In conclusion, at the early stage of venous insufficiency, dermatological alterations may be the only manifestation of the disease, and photography is the tool the vascular surgeon has to document and quantify the course of treatment. At our centre, we have developed a simple and effective protocol for the vascular surgeon to obtain high resolution and reproducibility in their photos. The objective is to produce similar images at various stages of treatment (Figure 3). Our advice is that a routine must be established, with the photographs always being done in the same environment, with the same camera and with equivalent photographic parameters. The decubitus position works well for the recording of ulcers, telangiectasias and reticular veins with the use of augmented reality. Tributary veins are better recorded with patients in the standing position. We recommend the use of DSLR cameras because of their cost and professional appearance, and the possibility of using external flash. We suggest the implementation of a process for storage and organisation of the files, with two different strategies to organise the photos on a daily basis: Identification at the end of the routine, or pre-identification with the tethering technique. Kasuo Miyake is at Clinica Miyake, São Paulo, Brazil
Figure 1. Photo-documentation with the external flash pointed to a white ceiling and the camera is connected by a tethering cable (orange) to a two-screen computer.
Figure 2. Example of post-treatment control with transdermal laser associated with Dextrose 75% (CLaCS). The use of augmented reality image facilitates diagnosis, treatment guidance and visualisation of the result.
Figure 3. Evolution of the surgical treatment: Endovenous laser ablation of the right great saphenous vein, ligation of perforant veins and removal of tributaries in orthostatic position. Left to right: Before, three days and two months after procedure.
Clinical News Prospective clinical data on the FlowTriever system confirms excellent results in the treatment of pulmonary embolism
Inari Medical has announced the presentation of results from its FlowTriever Pulmonary Embolectomy (FLARE) clinical study that evaluated the safety and effectiveness of the FlowTriever Retrieval/Aspiration System for the treatment of pulmonary embolism. The results were presented by Thomas Tu, an interventional cardiologist at Baptist Health, Louisville, Kentucky, during the Scientific Sessions of the Society for Cardiovascular Angiography and Interventions (SCAI; 25–28 April) held in San Diego, USA. The FLARE study is a prospective, multicentre, single-arm study evaluating the FlowTriever System in 106 patients with acute PE at 18 sites in the USA. Patients with proximal pulmonary embolism and right heart strain (RV/LV ratio ≥0.9) were eligible to participate. Treatment with the FlowTriever System was used to mechanically remove blood clots in the pulmonary arteries. The mean RV/LV ratio in the study decreased from a baseline 1.53 to 1.15 at 48 hours post-procedure, a difference of 0.39 (p<0.0001). The study also demonstrated excellent safety at 30 days, with a low 3.8% rate of major adverse events and no device related complications. Median intensive care unit stay was one day and overall median length of hospital stay was three days. “The significant improvement in right heart function shown with the FlowTriever System compares very favorably with outcomes of other techniques used to treat pulmonary embolism,” said Tu. “At the same time, the impressive safety profile reflects the advantages of FlowTriever’s purely mechanical approach which avoids the use of thrombolytic drugs and resulting risk of bleeding complications.” “The results of the FLARE study mark an exciting advancement in the treatment FlowTriever of acute pulmonary embolism patients,” stated Victor Tapson, associate director of the Pulmonary and Critical Care Division at Cedars-Sinai Medical Center in Los Angeles, USA, and co-principal investigator of the study. “Until now, there has not been an approach to rapidly restore flow to reverse right heart strain without the use of thrombolytic drugs and their inherent risk of bleeding complications.” The FlowTriever System represents a breakthrough in treatment options for this large patient population,” added Ken Rosenfield, section head for Vascular Medicine and Intervention at Massachusetts General Hospital and co-principal investigator of the study. “These results indicate that mechanical thrombectomy with the FlowTriever System will play an increasing role in the management of pulmonary embolism.”
the risk of fracture should be quite low, and in fatigue tests we did not see any fractures with the device,” he states. Kucher also says that although the main advantage of blueflow is its high flexibility, the device can also provide resistance in areas where more radial force is needed. “The stent is so flexible that you can wrap it around your finger without compromising the lumen. In PTS, you do not need much resistance in the groin, but in cases where there is a need for resistance, you can compress the stent and get more radial force.” “Having seen the limitations of other dedicated venous stents on the market, we wanted to come up with a solution that offers more options to physicians when stenting below the inguinal ligament,” says Georg Landsberg, plus medica founder and CEO. “We are now looking forward to collecting more data with blueflow and seeing how this stent performs in the long term, especially in this important area below the ligament.”
FDA approves venous indication for VASCADE closure system
Cardiva Medical, a vascular closure device company, has announced it has received approval from the US Food and Drug Administration (FDA) for an expanded indication of the VASCADE Vascular Closure System. Already approved for use in arterial closure, the closure system is now FDA approved for use in 5-7F femoral venous closures as well. This expansion creates an opportunity to better treat patients undergoing interventional cardiac catheterisation procedures, while also greatly increasing the available market for the device. The system consists of a thrombogenic bioabsorbable collagen patch and proprietary collapsible disc technology that is clinically proven to safely and effectively achieve haemostasis while minimising complications. Unlike manual compression, which is the current standard for femoral access site closure, the device does not require prolonged, heavy pressure and extended bed rest to ensure haemostasis. “VASCADE has performed exceptionally well for our current patients, and this new indication will empower many physicians to use VASCADE for vein closure,” says Joseph De Gregorio, chief of invasive cardiology at Englewood Hospital and Medical Center in Englewood, USA. “Successful vessel closure, and enabling a patient to walk as soon as possible after their procedure, are critical factors for recovery from interventional procedures. The ease of use of the VASCADE system and its compelling clinical data will make it an attractive new option for closure following vein procedures.” Results of a study evaluating the system for venous closures were published in Vascular Disease Management. The authors noted that the “device achieved complete haemostasis without any recorded vascular complications and was effective in providing earlier ambulation and discharge compared with our standard protocol for manual compression.” In the same article, the authors emphasise that access site complications remain the most common complication from cardiac catheterisation procedures that require venous access. Vascade
Ten patients successfully treated with recently CE-marked venous stent
Medical device company Plus medica has announced that 10 patients have been treated with the company’s blueflow Venous Stent. The first cases were performed by Michael Lichtenberg, Klinikum Arnsberg, Arnsberg, Germany, and Nils Kucher, University Hospital Zurich, Zurich, Switzerland. The blueflow Venous Stent, developed and manufactured in Germany, is a highly flexible nitinol, hand-woven, two-wire braided stent designed to treat venous outflow obstructions of the lower extremities. The device is being primarily used as an extension stent in patients with post-thrombotic syndrome (PTS) and lesions that extend below the inguinal ligament. Lichtenberg, who performed the first-in-man case with blueflow and an additional five cases in March, says that the venous stent showed very good results in all patients. He adds, “We were pleasantly surprised with the performance of the device. We could implant the stent perfectly in the common femoral vein and the external iliac vein. Proximally, we implanted other dedicated venous stents and then used blueflow as an extension, and with this combination we have achieved very strong clinical outcomes so far.” In Zurich, Kucher implanted blueflow in four PTS cases of various causes, and all patients experienced relief from symptoms such as pain and swelling following stent implantation. He comments that the characteristics of blueflow make the stent an ideal solution for the inguinal ligament area. “Until now, we did not have a stent for this indication. Laser-cut stents often present problems in the ligament area as they are a bit too stiff and tend not to move with the vessel. As blueflow is a woven stent, it does move with the vein. At least theoretically,
Calendar of events 20–23 June
SVS: Society for Vascular Surgery Vascular Annual Meeting Boston, USA W vascular.org 25–26 June
Royal Society of Medicine Venous Forum Annual Meeting London, UK W rsm.ac.uk 28–30 June
European Venous Forum Athens, Greece W europeanvenousforum.ac.uk
8th Venous Imaging Masterclass Paris, France W anatomy-masterclass.com 22–25 September
CIRSE: Cardiovascular and Interventional Radiological Society of Europe Annual Congress Lisbon, Portugal W cirse-2018.org 25–28 September
ESVS: European Society for Vascular Surgery Annual Meeting Valencia, Spain W esvs.org
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