Venous News 12 – November 2019 (US Edition)

November 2019 | Issue 12 Manj Gohel: Preliminary guidelines for SVT

Anelise Rodrigues: Augemented reality in phlebology

Page 7

Page 15

Future trials on the management of DVT “have to focus on technical success” following ATTRACT

Profile

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Foam “has not been established as superior” to liquid sclerotherapy for the treatment of C1 disease

“ATTRACT and CAVA are not the end of our treatment; they are the beginning of a road to prove which patients will benefit most from treatment,” argued Stephen Black (Guys and St Thomas’ Hospital, London, UK), speaking at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain). He added that more data are needed following the ATTRACT trial, which concluded that catheter-directed thrombolysis does not reduce the risk of postthrombotic syndrome (PTS) in lower extremity deep vein thrombosis (DVT) patients.

T

he hot topic symposium session—which asked the question “Does ATTRACT change our DVT management practice?”—addressed criticism of the ATTRACT trial and considered what the future might hold for DVT interventions. As part of the session, Wael Saad (Washington University, St Louis, USA), Gerard O’Sullivan (Galway University Hospital, Galway, Ireland) and Rick de Graaf (Clinic of Friedrichshafen, Friedrichshafen, Germany) gave an overview of the study, explaining why its findings alone will not have a significant impact on practice.

ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-directed Thrombolysis), as described by investigator Saad, was “a multi-centre, randomised, open-label and assessor-blinded phase three trial with two limbs; the control standard of care, which was anticoagulation and compression stockings (30–40mmHg), and the pharmaco-mechanical group—anticoagulation and compression stockings in addition to catheter-directed therapy”. Furthermore, the development of PTS [defined as a Villalta score ≥5] or an ulcer on the ipsilateral leg anytime between six and 24 months was established as the primary outcome.

Results of the trial showed that there was no significant difference between the two treatment groups

John Kaufman:

Speaking at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland), Neil Khilnani (New York, USA) underlined that the current literature on sclerotherapy, in addition to guidelines from the European Consensus and American Society for Dermatologic Surgery (ASDS), does not find a “tremendous advantage for foam” over liquid. Although sclerotherapy is recommended for treating C1 veins, foam sclerotherapy is only considered appropriate when it is in a weaker form.

BEFORE ADDRESSING THE potential advantages and disadvantages of using foam, Khilnani commented: “I think it is fairly well established that the treatment for C1 disease, regardless of whether you use liquid or foam, begins with the larger C1 veins and progresses to the smaller C1 veins. Most practitioners using detergent sclerosants are going to be using foam: either polidocanol or sotradecol.

“To get successful sclerosis, as opposed to thrombosis, you need to have an adequate concentration and you need to deliver that concentration to the endothelium for an appropriate length of time to get the injury that we are looking for.”

With regard to the benefits of foam over liquid, Khilnani highlighted the difference in kinetics between the two and how important this may be.

While liquids layer when injected into the vein, diluting the concentration of the sclerosant, foam

Stephen Black

Continued on page 2 Continued on page 4

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November 2019 | Issue 12

Conference coverage

Foam “has not been established as superior” to liquid sclerotherapy for the treatment of C1 disease Continued from page 1

displaces blood and “allows a more circumferential contact,” stopping flow at least transiently to increase contact time, and slowing the rate at which the sclerosant dilutes in the body. “Effectively, foam is a stronger sclerosant for a similar drug concentration and volume with regard to sclerotherapy,” added Khilnani.

Despite these advantages, especially in larger and medium-size veins, it was also emphasised that some of the benefits of foam are lost in the smaller veins, “primarily because liquid can displace blood fairly effectively in the telangiectasia and smaller reticular veins”.

Furthermore, the use of foam in sclerotherapy procedures can also lead to irritating complications which, as Khilnani revealed, “take up time in the doctor-patient relationship”. Citing a systematic review completed by Alun Davies (London, UK) et al, which reported that up to 2% of patients treated with foam sclerotherapy are affected by visual disturbances, Khilnani added that while these side-effects can occur with liquid sclerotherapy too, it is almost entirely the result of foam being used.

As well as the potential drawbacks of using foam, its production is also said to “involve some thought and some work,” with different techniques of producing and maintaining that foam varying in terms of the drug used, the initial concentration of the drug, and the syringe that is used. Other factors include the time, from production to its use, and the gas that is used.

“Foam stability is an issue too,” argued Khilnani, “as there is definitely more work required when you are doing foam sclerotherapy than when you are doing liquid sclerotherapy, concerning the management of your sclerosant”.

Khilnani also drew attention to literature published on the effectiveness of foam compared to liquid; in a trial conducted by Jean-Patrick Benigni (Paris, France), ten patients were treated with either polidocanol (foam) or liquid sclerotherapy, with each patient undergoing five sessions. Commenting on the results, Khilnani explained: “When we look at the data from that paper, less injections for foam were needed to complete the

Neil Khilnani

Patients with SVT are at a substantial risk of thromboembolic complications, and we should not forget that one third of these patients have unapparent DVT or even PE.”

Pictured left to right: spider veins before and after treatment

Editors-in-chief: Stephen Black, Alun Davies, Manj Gohel

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study than for liquid, and patient satisfaction was a bit higher, but there was more staining and matting in the patients who were treated with foam.”

The findings of this study support those of another investigation conducted by Philippe Kern (Vevey, Switzerland), in which patients were randomised to either 0.25% polidocanol foam during one treatment session—in addition to the use of graduated compression stockings—or liquid sclerotherapy with a 0.25% pure chromated glycerin, 0.25% polidocanol solution. Focusing on the outcome of the trial, Khilnani asserted that there was no difference found at all in terms of patient satisfaction, as well as no difference in the blinded photographic analysis.

Moreover, side effects were more prevalent in patients treated with foam.

Considering this evidence and the recommendations of sclerotherapy guidelines, Khilnani concluded: “Foam is certainly an appropriate tool to be used but at this point it has not been established as superior to liquid, and so in my own personal opinion, I use liquid sclerotherapy for all C1 disease, reticular veins and spider veins.

“Before the tomatoes get launched and fired at me from a distance, I think that vein elimination is equivalent and that foam requires more time, both up front in terms of discussing the side effects and complications with the patient, and then finally in making the foam. Even then, there are possible complications in terms of pigmentation and matting.”

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November 2019 | Issue 12

Deep vein thrombosis

Future trials on the management of DVT “have to focus on technical success” following ATTRACT Continued from page 1

in terms of primary outcomes, with 47% of patients in the CDT plus anticoagulation cohort developing PTS between six and 24 months, compared to 48% in the control group. Moreover, there was no difference in safety outcomes between the two groups. Of the trial’s conclusion, Saad said: “The addition of pharmaco-

being found.

Another problem with the study was the use of the Villalta scale which, as O’Sullivan asserted, “has never been published or subjected to the level of statistical analysis one would expect for a scale that is so widely used”. Although it is considered a useful tool for longterm patient follow-up, Villalta is heavily weighted towards swelling, skin changes and ulceration, failing to account for venous claudication and other aspects, such as weight gain. “Venous claudication and weight gain are the two most common problems my patients have after one year, but there is no mention of them in Villalta” added O’Sullivan.

Beyond issues with recruitment and classification, the lack of dedicated imaging was also a drawback to the trial, as there was no magnetic resonance venography (MRV) scan before operation, no intravascular ultrasound (IVUS) during operation, and no ultrasound

the patient to develop PTS,” as well as findings from the European Journal of Vascular and Endovascular Surgery (EJVES) that show removing as much thrombus as possible reduces the chances of recurrent DVT. Although the ATTRACT trial offered a different conclusion, suggesting that DVT should not be managed with endovascular treatment at all, de Graaf described this option as unrealistic, affirming that iliofemoral DVT with less than 14 days of symptoms should be treated. Like Saad and O’Sullivan, he also highlighted key areas of criticism such as “insufficient stenting”— which can lead to many obstructions being missed—and “inadequate evaluation of thrombus removal”; according to de Graaf, “angiography is not good enough,” with IVUS representing a better imaging option.

The future of the practice

With a level of consensus established amongst the presenters regarding the potential impact, or lack thereof, of the ATTRACT trial, focus also turned to the lessons that can be learned from the failure to achieve successful results. “We have to focus on technical success,” argued Black, who added: “When you look into the supplementary tables, ATTRACT was only successful in 60% of patients who were treated. If you have only 60% of technical success, it is not surprising that there is no difference in outcome.”

In order for future trials in the space to achieve higher levels of technical success, Black underlined a number

Venous claudication and weight gain are the two most common problems my patients have after one year.”

Pictured left to right: Stephen Black, Rick de Graaf, Gerard O’Sullivan and Wael Saad at CIRSE 2019

mechanical catheter directed fibrinolysis in symptomatic patients with proximal lower extremity DVT did not reduce the risk of PTS.”

Problems with the ATTRACT trial

In his review of the study, Saad underlined that there was a “considerable” amount of missing assessment, with 80 patients (two thirds of which were in the control group) not providing any data. In addition to this, a large number of patients were excluded by the criteria of the trial, including those suspected of non-compliance with protocol. Saad also revealed that investigators “encountered a lot of patients who initially enrolled but, when they found out they would receive anticoagulation alone, withdrew from the study”.

Following Saab’s presentation, O’Sullivan also drew attention to “flawed recruitment” as a shortcoming of the study, highlighting that only one in 50 patients (692 in total out of 27,000) made the cut for ATTRACT. “It is not generalisable to real-life, day-to-day practice,” he said, agreeing with Saab that while it is normal for trials to reject a proportion of patients, 98% is far more than usual. On the other hand, a decision to include femoropopliteal DVT patients to try and increase recruitment resulted in the de-powering of the iliofemoral arm, preventing any “statistically significant” results from

When you look into the supplementary tables, ATTRACT was only successful in 60% of patients who were treated.” mandated following operation, despite this being a routine procedure in any European centre. The lack of dedicated venous kit, including venous dedicated stents, was noted too by O’Sullivan as a problem with the trial.

Has ATTRACT impacted practice?

Presenting on whether or not the findings of the ATTRACT trial have had any significant effect on his practice, de Graaf stated that before the study, he treated patients with iliofemoral DVT, using an MRV to select the uncomplicated fresh clot, stenting the underlying cause as opposed to residual thrombosis, and removing as much of the thrombus as reasonably possible. He also drew attention to other literature, emphasising that “the more thrombus you take out, the less likely it is for

of key areas for investigators to take note of, explaining that attention to detail is absolutely crucial for a better standard of results. “This means really rigorous anticoagulation strategies,” he said, “making sure the patient is fully anticoagulated when they have finished the procedure”.

Other adjuncts to standard of care, such as intermittent pneumatic compression (IPC) and the use of stockings, need to be monitored carefully, as well as strictly conducted follow-up and surveillance. In addition to this, Black commented that “in all of these studies, if the vein was open long-term the patient did better, so the whole point is that open vein equals good results of patients”.

The future of trials in this space, according to Black, will also be affected by the introduction of new, mechanical devices, prompting a movement away from catheter-directed therapy to safer treatment, lowering the bleeding risk of patients by “reducing dependence on lytic”. Patient-centre outcome measures are also important argued Black, with a replacement for Villalta needed that takes the needs of the individual patient into account.

Black also provided a cost-effectiveness analysis, and stated: “With this data, and based on UK results, treating patients is still cost-beneficial and may even be dominant over not treating them despite the bad outcomes we saw in ATTRACT. This means that if we get better at outcomes and make the procedures safer, we are going to get a very cost-effective treatment for our patients and this is principally because you reduce the rate of moderate and severe PTS.” Furthermore, Black concluded: “Better selection and outcome measures are needed, we need to commit to registries first and then run further trials—which is absolutely needed if we are going to influence the payers and other bodies which allow us to continue to perform interventions—and there will be new devices in the future that will change our patient treatment.”

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November 2019 | Issue 12

Classification tools

Improved instruments required for classification of chronic venous disease Current classification tools for the diagnosis of chronic venous disease, including acute deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS), include “redundant” elements that are unimportant to patients, according to an address delivered by Mark Meissner (Seattle, USA) at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland). It was also emphasised that existing instruments do not account for some elements that are important to patients, such as venous claudication.

S

peaking to delegates at UIP, Meissner began: “If we look at current interventions for acute deep vein thrombosis (DVT), we have a number of high-profile recent successes such as the direct oral anticoagulant (DOAC) extended therapy for unprovoked or recurrent DVT, but we have also had some highprofile failures, such as the use of stockings for the prevention of post-thrombotic syndrome in the SOX trial and in the ATTRACT trial.”

Questioning the audience on why PTS prevention trials are failing while DVT prevention trials are proving successful, Meissner drew attention to the findings of the SOX and ATTRACT studies; in the SOX trial, 806 patients were randomised either to 30mm or 40mm knee-high stockings, or a placebo. Ultimately, there was no significant difference in the primary outcome of PTS—as defined by the Ginsberg score—between both groups (13% and 14%, respectively). Results of the ATTRACT trial, which randomised patients to either catheter-directed thrombolysis or standard anticoagulation treatment, demonstrated a similar lack of difference.

While it is possible, Meissner argues, that these were not beneficial interventions—resulting in unsuccessful results across both trials—the instrument used for measuring a primary outcome of PTS may also present a “significant problem” for clinicians.

“There are essentially three instruments that have been used,” said Meissner, asserting the limitations of existing classification methods. The Ginsberg score, described by Meissner as a qualitative rather than quantitative tool, defines whether or not a patient has PTS based on yes or no answers to questions regarding pain and swelling, while the venous clinical severity score (VCSS), a questionnaire prone to “some error in observability,” is also considered to have problems.

The third and most commonly used instrument is the Villalta scale, which has been accepted as the gold standard in diagnosing PTS, even though it has “never been published”. Nevertheless, Meissner agrees that “it does include some of the elements we look for,” including pain, heaviness, oedema, skin induration, hyperpigmentation, and redness. However, Meissner also highlighted the limitations of this classification tool, referring to the findings of a qualitative structure interview with 16 post-thrombotic patients on what is truly important for them.

He said: “It was revealed that four domains are of primary importance; first and foremost is agonising discomfort. This was rarely described by patients as pain and did not fit very well into the Villalta instrument, and was usually described as heaviness, restlessness, pressure or venous claudication, but not typically as pain.”

Results of UK study find that Villalta scale is not disease-specific Evidence from a recent study conducted by Imperial College London, UK has further demonstrated that the Villalta scoring system is not disease-specific and correlates with other tools for measuring venous outcomes. The results have implications for the ATTRACT trial, affirming that the Villalta scale is an imperfect method of identifying and measuring post-thrombotic syndrome.

PRESENTED BY KEMAL Kemal (London, UK) at the International Union of Phlebology chapter meeting (UIP; 25– 27 August, Krakow, Poland), the findings of the study contributed to extensive discussions in Krakow on whether the Villalta scale remains fit for purpose.

While the use of Villalta scores is still the gold standard for diagnosing and classifying post-thrombotic syndrome, “providing it is used with a venousspecific quality of life (QoL) score”, there are limitations to this classification.

Kemal said: “One of the main issues seems to be that the signs and symptoms looked at by the Villalta score questionnaire are not specific to postthrombotic syndrome and in fact exist in chronic venous disease also. The other issue we are finding is that patients who have deep venous disease but no duplex evidence of obstruction are getting a false positive diagnosis of post-thrombotic

syndrome.” In addition to this, patients without deep vein thrombosis (DVT) have also scored highly with the Villalta system.

Given the criticism faced by the classification scale, which was originally designed to be disease-specific, the Imperial College study aimed to compare Villalta to other clinical severity and QoL tools in a group of patients with no history of post-thrombotic syndrome.

Of the 110 patients enrolled in the prospective, single-centre study (43 male, 67 female), all had duplex evidence of superficial venous disease or deep venous disease.

As part of the study, a clinician filled out a series of classifications, including the Villalta scale, CEAP classification and venous clinical severity scores (VCSS), while the patient themselves filled out the Aberdeen Varicose Vein Questionnaire (AVVQ) and VEINES-

Meissner also explained that while skin changes are important to patients suffering with a painful ulcer, all other forms of skin change—which represents four components of the Villalta scale—were “not important to patients at all”. Other areas that were considered important ranged from fluctuating heaviness and swelling to the fear of recurrence and loss of social interaction because of physical problems encountered as a result of chronic venous disease.

It was concluded that the Villalta scale does not represent the full scope of typical post-thrombotic

If we look at current interventions for acute deep vein thrombosis, we have a number of high-profile recent successes [...] but we have also had some high-profile failures.” complaints or their importance to patients. In addition, studies presented at UIP 2019, including an investigation conducted by Imperial College London, UK, underlined that the Villalta scale is not disease-specific and overidentifies mild PTS, which has no significant impact on a patient’s quality of life. This suggests that a more optimal instrument is required.

Meissner himself concluded: “Recent large randomised trials investigating the prevention of PTS have largely been negative; it is certainly possible that these interventions are truly ineffective, but it is equally likely that these clinical trials are flawed and one of the big reasons is the inappropriate outcome measures.”

QoL/SYM questionnaire. Regarding the latter assessment tools, Kemal commented: “VEINES-QoL has been used extensively and has been validated in chronic venous disease, as well as in patients who have DVT, and so has AVVQ.” Turning his attention to the results of the study, Kemal highlighted that the mean Villalta score of the cohort was eight, indicating mild post-thrombotic syndrome despite the fact that none of the patients have ever had DVT. In terms of the relationship between different scoring systems, results also showed a moderate correlation between Villalta scores and the CEAP classification, as well as between Villalta and the VEINES-SYM questionnaire. In addition, a moderate

Our results demonstrate and provide further evidence that Villalta correlates well with chronic venous disease assessment tools, which implies it is not diseasespecific.”

correlation was noted between Villalta and VCSS, and Villalta and AVVQ. The only clinical severity and QoL tool which the Villalta scale did not have a moderate correlation with was the VEINES-QoL questionnaire, which correlated strongly with the VEINESSYM questionnaire but “rather weakly” with other classification systems.

Kemal concluded: “Our results demonstrate and provide further evidence that Villalta correlates well with chronic venous disease assessment tools, which implies it is not disease-specific. We know that pre-existing chronic venous disease plays a big role in patients who have DVT, and 50% of patients who have a DVT will also have pre-existing chronic venous disease, and this may indicate the outcome with Villalta.

“This does have implications for studies such as ATTRACT, which use Villalta to assess outcomes, and we believe that it may be more beneficial to be used as a dynamic marker rather than something static, so to look at something different over a period of time.”

In response to a question about the continued use of the Villalta scale and whether it remains the gold standard, Kemal added: “I think the problem we have is that we don’t have an alternative currently, so we will continue to use Villalta until something else is established. Some small studies have validated it, so although not diseasespecific as it was designed to be, it has some use.”

Issue 12 | November 2019

A look at preliminary guidelines for superficial vein thrombosis Manj Gohel Comment & Analysis At the European Society of Vascular Surgery annual meeting (ESVS 2019; 24–27 September, Hamburg, Germany), preliminary venous thrombosis guidelines were presented for the first time. Chaired

by Stavros Kakkos (Athens, Greece) and Manj Gohel (Cambridge University Hospitals, Cambridge, UK), and supported by an international writing group comprised of recognised thrombosis experts, the finalised guidelines will be published in 2020 and add to the list of ESVS treatment guidelines for a range of arterial and venous disorders.

I

n recent years, the venous field has witnessed a considerable number of advances, and a range of new evidence, on thrombosis. The guideline writing committee, which was comprised of a wide variety of medical professionals, represented the diverse range of specialities involved in the management of venous thrombosis internationally. Previous thrombosis guidelines, such as those published by the American College of Chest Physicians (ACCP) or the American Society of Haematology (ASH), have provided important support for clinical teams. However, several common and challenging areas are not extensively covered in these publications.

One important area extensively covered in the ESVS guidelines is the management of superficial vein thrombosis (SVT), also known as thrombophlebitis. Patients with SVT are frequently referred to acute thrombosis services, primarily to exclude the more serious differential of deep vein thrombosis (DVT). However, the true importance and potentially serious complications of SVT have not been well-appreciated. Several studies have demonstrated that SVT is associated with a high risk of recurrence, progression to DVT or pulmonary embolism (PE), particularly in the first three months.

Overall, there is a greater appreciation that SVT is not the benign entity that many clinicians have traditionally perceived it to be.

Important randomised clinical trials have highlighted the importance of whole leg ultrasound assessment to provide detailed information of the site and extent of the venous thrombosis. On the basis of ultrasound assessment, risk stratification

can be performed, guiding targeted anticoagulation therapy to reduce the risk of progression to DVT or PE. The vast majority of patients with SVT have superficial venous reflux and associated venous stasis. Moreover, an area of great controversy is the role and timing of superficial venous ablation in patients with SVT. Traditionally, some patients have been managed with expedited surgical ligation of saphenofemoral or saphenopopliteal junctions, to eliminate the risk of thrombus progression into the deep system. However, the more widespread evidence for the use of anticoagulation has largely eliminated the need for any acute venous intervention. Repeat duplex ultrasound imaging and deferred intervention is probably justified for the majority of patients. Any superficial venous intervention during the period

Superficial vein thrombosis venous thrombosis. Less common than lower extremity DVT, upper extremity thrombosis is most commonly associated with intravenous catheters. However, the management of ‘effort thrombosis’, also known as Paget Schröetter syndrome, is particularly controversial. Enormous variations exist in clinical care, ranging from conservative management with anticoagulation alone, to a much more aggressive approach involving early thrombus removal, with prompt first rib resection to decompress the thoracic outlet.

In the absence of randomised trials, the committee relied on non-randomised evidence from observational studies and many of the recommendations are likely to have been extrapolated from studies of lower extremity DVT. While aggressive thrombus removal may be justified in some individuals, anticoagulation alone is likely to be adequate for the majority of patients with upper extremity DVT. When considering the use of early thrombus removal for patients with acute iliofemoral and femoropopliteal DVT, the ATTRACT trial has resulted in considerable controversy and debate.

The primary outcome results failed to demonstrate a significant benefit for early thrombus removal strategies over anticoagulation alone. A subsequent analysis, including only patients with iliofemoral DVT, did suggest that moderate-to-severe post-thrombotic syndrome (PTS) may be prevented in a subset of patients treated with aggressive thrombus removal. The real challenge remains patient selection, as most patients with acute iliofemoral DVT do not develop significant PTS when managed with anticoagulation alone.

Additional areas of uncertainty are the indications and role of stenting after early thrombus removal, the optimal modality for thrombus removal and the ideal post-intervention anticoagulation policy.

While there may be some evidence to suggest that more technically successful thrombus removal may yield greater clinical benefits, the best approach to reach this goal is unclear.

One novel area that was covered in detail, as part of the 2020 venous thrombosis guidelines presented at ESVS 2019, will be the use of compression

Despite the enormous volume of published venous research, there remain several areas with just a few high quality (and no randomised) clinical trials.” of acute inflammation is likely to be associated with a higher risk of periprocedural venous thromboembolism.

Despite the enormous volume of published venous research, there remain several areas with just a few high quality (and no randomised) clinical trials. Such conditions present a huge challenge to guideline writing committees, particularly when the condition is common. One such area is the management of upper extremity

therapy in the acute and later phase after lower extremity DVT. There remains a general reluctance to initiate compression therapy for patients immediately after diagnosis of acute DVT, possibly due to concerns about pain, patient compliance or fears over pulmonary emboli.

However, several randomised trials have demonstrated the clear benefits of compression therapy in the acute phase to alleviate symptoms of pain and oedema, and reducing residual vein obstruction.

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Extended use of compression has been the subject of several randomised trials, with most demonstrating a beneficial effect in reducing the risk of postthrombotic syndrome at 24 months with the use of compression stockings.

The recent IDEAL DVT study further advanced our understanding by demonstrating that patients wearing stockings after acute DVT and with few symptoms (evaluated by Villalta score) can discontinue stockings after six or 12 months, and without any increase in PTS risk at 24 months. This evidence empowers clinical teams to

More widespread [...] compression, including in the acute phase after diagnosis of DVT, is likely to be a relatively easy and cheap intervention.” better customise treatment duration to individual patients, avoiding the cost and inconvenience of prolonged use of compression where it is unnecessary.

More widespread use of compression, including in the acute phase after diagnosis of DVT, is likely to be a relatively easy and cheap intervention to improve patient symptoms and quality of life.

The guidelines will also cover a range of other key areas: the treatment of calf vein thrombosis, type and duration of anticoagulation therapy after provoked and unprovoked DVT, surveillance after DVT, indications and use of inferior vena cava (IVC) filters, catheter-related thrombosis and a range of special patient populations, including pregnant patients and those with inherited or acquired thrombophilia. It should be recognised that there remain many areas within venous thrombosis where the quantity and quality of available evidence is poor.

While there have been advances in the evidence base, many questions remain, most notably how to best select the patients most likely to benefit from the plethora of effective interventions that are now available. Despite these uncertainties, it is clear that health professionals from a wide array of medical and surgical specialities have an important role to play. Haematologists, vascular surgeons, angiologists, internal medicine specialists and others have to work in close collaboration to share experience and skills. Only then do we stand a chance of addressing the outstanding areas of uncertainty in the management of venous thrombosis.

Manj Gohel is a consultant vascular and endovascular surgeon at Cambridge University Hospitals, Cambridge, UK.

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November 2019 | Issue 12

Endovenous laser ablation

EVLA-based study confirms laser crossectomy as superior method of preventing AAGSV reflux Laser crossectomy of the GSV has been established as a more effective method of preventing secondary anterior accessory great saphenous vein (AAGSV) reflux than treatment modalities that leave stumps. As part of a randomised controlled study comparing the technique with infra-epigastric closure, it was also affirmed that consideration of AAGSV anatomy is pivotal when making the right choice of strategy.

RESULTS OF THE investigation were presented at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland) by Johann Chris Ragg (Berlin, Germany), who explained how his interest in this comparison of modalities developed.

“Some years ago, I was shocked by a remark from a colleague, who said that occurrence of reflux of a previously healthy AAGSV after standard endovenous great saphenous vein (GSV) ablation may be higher than after surgical crossectomy. My own 8-year results had junction recurrence rates below 12% but were obtained with laser crossectomy. Due to this argument, we decided to find out what the difference is,” Ragg said.

He continued: “When we started with venous lasers in 1999 as early pioneers, I had no other idea than to start GSV closure right from the femoral level, equivalent to surgical flush ligation, with total vein compression by precise coaxial perivenous local anaesthesia (CPLA) manually injected with a 200mm G21 needle. Instead of a constant pullback rate, fibre pullback was done according to wall reaction in order to place as much energy as possible, but below wall disruption and below pain level (PAWR technique).”

According to Ragg, most later-on laser users preferred to ablate with a “safety distance” to the junction in order to prevent femoral EHIT (endovenous heat-

induced thrombosis), and a less precise “tumescent anaesthesia”. This method became a standard, as it was fast and easy to perform.

The aim of the randomised study was to compare infra-epigastric to femoral-level laser ablation, using identical device and techniques. 240 Johann Chris Ragg consecutive patients with GSV insufficiency (CEAP C2–C6; diameters 6.5–17.8 mm) were selected with the criteria of 1) reflux > 1,000 milliseconds from the saphenofemoral junction (SFJ, Valsalva test) 2) non-refluxive AAGSV and 3) no other refluxive branch of the SFJ undergoing endovenous laser ablation (EVLA; 1470nm, radial fibre, 50–80 J/cm) with CPLA. Participants were randomised to one of two groups: group A underwent laser crossectomy—defined as EVLA starting at the femoral vein level—while patients in group B were treated with EVLA starting below the epigastric vein junction. Follow-up including ultrasound was performed at day one, day 14 and after one, six, 12, and 24 months.

EVLA at different power settings found to have no significant impact on pain scores and occlusion rates There is no significant difference in pain and recanalisation for patients undergoing endovenous laser ablation (EVLA) at different power settings, according to the results of a new randomised controlled clinical trial. This investigation was conducted following a previous morphological study, which showed a difference in venous wall damage when these power settings were altered.

F

indings of the trial were presented at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland)

by Denis Borsuk (Chelyabinsk, Russia), who described laser ablation as the “gold standard” of endovenous treatment, “as well as radiofrequency”.

A previous study on the association of different EVLA power settings with increased levels of vein wall damage and tissue depth penetration—conducted at the Clinic of Phlebology and Laser Surgery, Chelyabinsk, Russia and Department of Surgery, South Ural State Medical University, Chelyabinsk, Russia—discovered that using the same linear endovenous energy density (LEED) at around 70 J/cm³ and increasing power from 5W to 7W leads to a rise in venous wall damage from 25.7% to 37.9%. Moreover, an increase

Denis Borsuk

in EVLA power from 7W to 10W produced a 17.6% increase in damage (from 37.9% to 55.5%), representing a major difference.

In response to the findings of this study, Borsuk and A. A. Fokin

Presenting the results of the trial, Ragg commented: “Primary GSV occlusion was obtained in all cases, but with significant difference in the morphology. Using ablation from femoral level (group A), the outlet of AAGSV was covered in 118/120 cases (98.3%). At one-month follow-up, 102 of the 120 patients in this group showed no stump at all (85%). 18/120 (15%) had minor stumps of 5–17mm length, mean 11.5mm. More than stump length, stump diameter was characteristic, measuring 18–29% of the previous native diameter in group A, in 17/18 cases (94.4%) presenting a run-off from the inferior epigastric vein. In group B, the entry to the AAGSV was covered in only 13 of 120 cases (10.8%). There were much larger GSV vein stumps present in all of the 120 patients, measuring 8–31mm in length, mean 23mm, and diameters of 55–87% of the native size. In both groups, there were no adverse effects and, in particular, no EHIT. Within the two-year follow-up, AAGSV insufficiency was recorded in five of the patients (4.2%) after laser crossectomy (group A) and 26 of the patients (21.7%) in group B (p>0.01). All refluxive cases were related to AAGSV with pre-treatment diameters of 5.5mm or more. Visible AAGSV varices were seen in 1/120 cases (0.8%, group A) versus 4/120 (3.3%, group B). Of these cases, none were symptomatic.

Ragg concluded: “If pressure stress or venous hypertonus at the SFJ is the problem, GSV closure will transfer pressure to the next large descending branch.

Although it might take several years until clinical manifestation, it makes sense to include the AAGSV entry in the ablation, in particular when AAGSV diameter is above 5.5mm. Standard ablation starting below the epigastric junction results in five-fold rates of later-on AAGSV reflux compared to laser crossectomy.”

Furthermore, Ragg emphasised that “it is clear that laser crossectomy is superior to standard infra-epigastric ablation, but further ultrasound-based studies should follow, to clarify AAGSV vulnerability”.

(Chelyabinsk, Russia) predicted that a similar difference in pain score and occlusion rate could be measured with the use of 5W, 7W and 10W power settings. As with the previous trial, LEED would remain the same at around 70J/ cm³, allowing Borsuk et al to compare the clinical effects of these settings.

Today we have more modern devices, but you will never find better results in terms of pain score and occlusion rates.”

Discussing the method of the study during his presentation, Borsuk said: “We began our clinical trial when we randomised 154 patients; we used radial fibres, water-specific laser, and of course an automatic pull back device. Patients were divided into three groups; our primary endpoint was the occlusion rate and secondly the pain score.” Follow-up was also scheduled for one day, seven days, two months and six months after the procedure, with pain scores measured at all visits except for six months.

The trial had an inclusion criteria of patients with incompetent great

saphenous veins (GSV)—defined as reflux of more than 0.5 seconds—and no history of interventions. Alternatively, patients with GSV of over 2cm in diameter, acute deep vein thrombosis (DVT) or superficial vein thrombosis (SVT), and a number of other conditions including pregnancy and arterial insufficiency, were excluded.

All three groups were comparable for parameters such as diameter of the GSV (median of 10mm), amount of anaesthetic required (median of 375ml) and CEAP classification (p>0.05).

At day one of follow-up, pain was rated by patients in the 5W group as 0, 7W as 0, and 10W as 0.5 (p=0.355).

No difference in pain was reported, according to the results, at one week and two months (one week p=0.317; two months p=0.569), while the administration of painkillers showed no difference between groups.

Borsuk explained the results further: “The study is not finished yet, but already we can say that it is impossible to find a difference between pain scores, while occlusion rates are very high. This shows you that our methods have reached their peak, and it is difficult to find something new in our market. Today we have more modern devices, but you will never find better results in terms of pain score and occlusion rates.” He concluded: “I can say EVLA with different power settings can give us very low pain syndrome in all groups, even with different levels of damage to the venous wall.”

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November 2019 | Issue 12

Compression therapy

Evidence-based news in graduated compression for healthy subjects Sergio Gianesini Comment & Analysis While compression therapy is one of the treatment options for patients suffering with venous insufficiency and chronic wounds, this could also present benefits for healthy subjects. Following his presentation at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland), Sergio Gianesini (Ferrara, Italy) cuts through the noise of “fake news” to review recent studies on graduated compression.

G

raduated compression stockings (GCS) have demonstrated scientific validity in the management of impaired venous and lymphatic drainage of the lower limbs.1 Proper compression has also been validated in healthy subjects exposed to prolonged occupational standing2 and conditions associated with oedema, such as pregnancy3 and prolonged flights.4 At the same time, the market of compression garments for sportsmen has been increasing, with the global compression wear and shape market expected to reach US$5.576 million by 2022. However, fake news often miscommunicates the key message of public compression awareness, which is also disrupted by the general lack of data collection regarding compression in healthy subjects.

In the last few years, our research group has focused on collecting data on this topic, mainly pointing out the role of GCS in lower limb volume and perceived exertion control for those sitting, standing and walking.

In a first investigation, 24mmHg below-knee GCS (20–30mmHg class) were compared with no compression in a standardised walk of 30 minutes. In order to standardise the participant’s physical activity, the validated Tanaka equation was used during cardiac monitoring on a treadmill, consisting of, as per the definition, 70% of an individual’s estimated maximal heart rate (208 – 0.7 x age).5 Lower limb volume was calculated by tape measurement according to the truncated cone formula,6 while the perceived exertion was assessed by the validated Borg scale (six, no effort; 20, maximum effort).7 The results showed that walking for 30 minutes at a standardised pace without GCS leads to no significant lower limb volume change, while using 24mmHg below-knee GCS is associated with a significant reduction by approximately 4%. Moreover, the use of this kind of compression leads to a significant

decrease in perceived exertion (from 13 to 11 at the Borg Scale). The conclusion of this work is that specific analysis of the graduated pressure level is able to positively impact the perceived exertion.

We were not able to find literature related to the difference between continuous and intermittent walking in terms of leg venous drainage. For this reason, we planned another investigation using the model of a golf player’s intermittent walk. Indeed, golfers are often walking toward the golf ball, stopping before shooting it, then starting to walk again. The study population was randomised to sham stockings, 18mmHg below-the-knee stockings and 23mmHg below-the-knee stockings. The results showed that walking for 18 holes wearing sham stockings leads to a significant increase in lower limb volume (5%).

In the 18mmHg group, a nonsignificant 1% volume reduction was observed. In the 23mmHg group, leg volume significantly decreased by

about the performance of GCS and the potential impact of lower limb shape, we assessed in another investigation lower limb volume variations after 30 minutes of sitting, standing and standardised walking on a treadmill with and without 16–20mmHg below-knee GCS. Interface pressure measurements were performed in B (ankle point of minimum girth) and B1 (area at which the achilles tendon changes into the calf muscles).10 The outcomes demonstrated that 16– 20mmHg GCS are able to significantly decrease the lower limb volume after 30 minutes of sitting, standing and walking.

Interestingly, among the three different conditions, only after 30 minutes of walking using GCS was the extracellular fluid significantly reduced, as revealed by the bioimpedance analysis.

Even more interestingly, the interface pressure analysis showed that more than one third of interface pressure profiles present a more progressive (less pressure in the ankle) than graduated gradient, following the different lower limb shape.11 Previously published data show that progressive profiles are actually exhibiting an even more pronounced effect on the ejection fraction improvement,12 while present data confirm a similar effect on total lower limb volume reduction.11 A final investigation stimulated us to perform another study dedicated to the volume variations of different leg segments with and without GCS. This work was carried out in the context of a much larger data collection run during flights. Indeed, the topic of GCS use during prolonged flights remains an area in need of further investigation, with different recommendations currently being given by a number of different guidelines.13 The study involved the evaluation of the different leg segment volume variations after four hours of flight, comparing 15–20mmHg below-knee GCS to a non-graduated normal ankle sock. GCS use was associated with no significant lower limb volume variation, demonstrating the oedema formation

At the same time, education of healthcare professionals and patient compliance related to compression is in need of improvement.”

4%. Perceived exertion was assessed

by Borg’s scale, and in the 23mmHg group—unlike the 18mmHg cohort— there was a significant reduction.

Interestingly, the 23mmHg group included a sub-population using footless GCS, which showed no significant difference with the group using 23mmHg GCS covering the foot, both in terms of limb volume and perceived exertion.9 These data underline the importance of proper compression dose selection in order to positively impact the perceived exertion during intermittent walking calf pump activation, a model that is similar to normal everyday walking activity.

With the aim of understanding more

control. Normal ankle sock use was associated with a significant increase in lower limb volume (5.2%). Interestingly, the different leg sectors showed heterogeneous volume changes, both in the GCS and sock group, demonstrating that the mechanism of fluid shifts is still to be fully elucidated, both with and without GCS on.14 In conclusion, investigations like the ones reported here will help us to develop a better understanding of GCS performance in different physiological conditions, paving the way for a better use of the compression tool in sportscience and pathological scenarios.

Indeed, the world of sport is in need of

more homogeneous and reliable data on compression than what has already been reported.15 At the same time, education of healthcare professionals and patient compliance related to compression use is still in need of improvement, and what has been reported here could help with this process.16 Finally, fundamental care from educational, scientific and institutional bodies must be focused on counteracting fake news regarding the potential benefits of compressive items that have not been properly certified. Indeed, one of the main topics during the upcoming v-WINter 2021 Dubai meeting will be the creation of an international consensus for the creation of a booklet dedicated to patient fake-news-free information; a document that will surely include a fundamental compression tool.

Sergio Gianesini is a surgeon at the University of Ferrara, Ferrara, Italy and assistant professor at USUHS University (Bethesda, USA). He is president of the venous-lymphatic World International Network foundation (v-WIN), vice president of the International Union of Phlebology (UIP), associate-editor of International Angiology Journal and editor of Phlebology Journal.

References: 1. Rabe E, Partsch H, Hafner J, et al. Indications for medical compression stockings in venous and lymphatic disorders: An evidence-based consensus statement. Phlebology 2018;33:163-184.

2. Amsler F, Blättler W. Compression therapy for occupational leg symptoms and chronic venous disorders: a meta-analysis of randomised controlled trials. Eur J Vasc Endovasc Surg 2008; 35:366-72.

3. Gray G, Ash AK.A survey of pregnant women on the use of graduated elastic compression stockings on the antenatal ward. J Obstet Gynaecol 2006;26:424-8.

4. Clarke M, Hopewell S, Juszczak E, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2006:CD004002. Review.

5. Tanaka H, Monahan KD, Seals DR. “Age-predicted maximal heart rate revisited”. J. Am. Coll. Cardiol.

2001; 37 :153–6.

6. Kaulesar Sukul DM, den Hoed PT, Johannes EJ, et al.

Direct and indirect methods for the quantification of leg volume: comparison between water displacement volumetry, the disk model method and the frustum sign model method, using the correlation coefficient and the limits of agreement. J Biomed Eng. 1993;15:477-80.

7. Chen MJ, Fan X, Moe ST. Criterion-related validity of the Borg ratings of perceived exertion scale in healthy individuals: a meta-analysis. J Sports Sci. 2002;20:87399.

8. Gianesini S, Mosti G, Sibilla MG, et al. Lower limb volume in healthy individuals after walking with compression stockings. J Vasc Surg Venous Lymphat Disord. 2019 Jul;7(4):557-561.

9. Gianesini S, Tessari M, Menegatti E, et al. Comparison between the effects of 18- and 23-mmHg elastic stockings on leg volume and fatigue in golfers. Int Angiol. 2017 Apr;36(2):129-135.

10. Partsch H, Clark M, Bassez S, et al. Measurement of lower leg compression in vivo: recommendations for the performance of measurements of interface pressure and stiffness: consensus statement. Dermatol Surg 2006; 32: 224-32.

11. Gianesini S, Raffetto J, Mosti G, et al. Graduated Compression Lower Limb Volume Control in Different Muscle Pump Activation Conditions and Related Limb Shape Impact. J Vasc Surg VL 2019;7(2):295-6.

12. Mosti G, Partsch H. Compression stockings with a negative pressure gradient have a more pronounced effect on venous pumping function than graduated elastic compression stockings. Eur J Vasc Endovasc Surg. 2011 Aug;42(2):261-6.

13. Gianesini S, Obi A, Onida S, et al. Global guidelines trends and controversies in lower limb venous and lymphatic disease: Narrative literature revision and experts’ opinions following the vWINter international meeting in Phlebology, Lymphology & Aesthetics, 23-25 January 2019. Phlebology. 2019 Sep;34(1_ suppl):4-66.

14. Gianesini S, Mosti G, Raffetto JD. Case-control evaluation of the impact of below 20 mmHg elastic compression stockings on lower limb volume serial variations in standardized flights. Phlebology. 2019 Sep 5:268355519873527.

15. Engel FA, Holmberg HC, Sperlich B, et al. Is There Evidence that Runners can Benefit from Wearing Compression Clothing? Sports Med. 2016 Dec;46(12):1939-1952.

16. Kankam HKN1, Lim CS2, Fiorentino F, et al.

Summation Analysis of Compliance and Complications of Compression Hosiery for Patients with Chronic Venous Disease or Post-thrombotic Syndrome. Eur J Vasc Endovasc Surg. 2018 Mar;55(3):406-416.

Issue 12 | November 2019

Compression therapy

Fluorescence lymphography proven to be suitable for measuring the efficacy of intermittent pneumatic compression Indocyanine green dye (ICG) fluorescence lymphography represents a suitable method of providing information on the effectiveness of intermittent pneumatic compression (IPC) during the treatment of leg oedema (an excess of fluid around the limb), according to a study conducted with patients after surgery. Moreover, IPC was compared to other modalities for the therapy of limb oedema, including manual lymphatic drainage and bandaging.

RESULTS OF THE trial, in addition to an analysis of its findings, were presented at the International Union of Phlebology chapter meeting (UIP 2019; 25–27 August, Krakow, Poland) by Marzanna Zaleska (Polish Academy of Sciences and Central Clinical Hospital MSW, Warsaw, Poland), who explained that “tissue oedema develops with the insufficiency of both the venous and lymphatic systems”.

Zaleska, who conducted the investigation with Waldemar Olszewski (Central Clinical Hospital MSW, Warsaw, Poland), also underlined that “the oedema which develops with venous stasis affects lymphatic flow, while lymphatic stasis affects the venous capacity, so these two situations should be treated and excess fluid should be removed”. The aim of compression therapy is to move mobile oedema tissue fluid towards the extremities, where it can be absorbed, while the effectiveness of a compression method can be evaluated according to changes in limb circumference or volume.

However, as Zaleska reminded those in attendance, these methods do not show where oedema fluid has been moved, nor do they reveal whether there is a post-compression oedema fluid backflow for patients in an upright position. “All of this necessitates the visualisation of fluid movement,” Zaleska argued,

detailing the several methods currently available for monitoring the condition of both the lymphatic and venous systems; these include lymphoscintigraphy, which traces areas in which there is an accumulation of fluid, and X-ray phlebography.

“Our aim was to visualise oedema fluid movement during high-pressure pneumatic compression, using ICG fluorescence lymphography,” said Zaleska, who outlined that researchers “investigated patients with lymphoedema of the limbs after hysterectomy and patients with venous leg ulcers and oedema”. In addition to this, ICG fluorescence lymphography was used to

Our aim was to visualise oedema fluid movement during high-pressure pneumatic compression, using ICG fluorescence lymphography.”

11

visualise tissue and oedema fluid flow during manual drainage and bandaging.

As part of the study, 20 patients with post-surgical lymphoedema of lower and upper limbs, 10 patients with post-thrombotic leg oedema, and five cases with venous ulcers were enrolled, with the investigation carried out across three treatment groups: i) manual lymphatic drainage (thumb or hand); ii) intermittent pneumatic compression (eight-chamber sleeve, each chamber inflated to 50, 80, 100, and 120mmHg for 50 seconds); iii) bandaging generating interface pressure of 40–50mmHg. For each type of compression, ICG fluorescence lymphography was performed at a known force.

The findings of the investigation demonstrated that a threshold pressure of 80mmHg in the compression is needed to move oedema fluid, and over 40mmHg for tissue fluid. Furthermore, ICG fluorescence lymphography was successful in demonstrating that IPC is an effective therapy of limb oedema.

Zaleska commented: “These are pictures before and after compression, and you can see that even after one minute of compression there is less dye, which means there is less fluid. Before IPC, we measured fluorescence intensity in this area and it was 62%, and after three minutes with 50mmhg the fluorescence intensity decreased to 42%. After additional minutes with higher compression, the fluorescence intensity decreased to 36% and 34%, so the compression was effective.”

As well as visualising the accumulation of fluid in one area of the limb, ICG fluorescence lymphography was also able to show this accumulation of fluid along the whole limb, from the foot to the groin. “As you can see, some fluid was moved from the foot and calf to the knee (origin) and to the thigh. We can also see that some fluid moved to the proximal part of the limb,” Zaleska added. These observations point to the need for ICG fluorescence lymphography before and after compression therapy in each patient.

Device for managing deep vein reflux wins TCT-Shark Tank Innovation Competition At the 2019 Transcatheter Cardiovascular Therapeutics (TCT) meeting (25–29 September, San Francisco, USA), InterVene won the TCT-Shark Tank Innovation Competition for its novel endovenous system (BlueLeaf) for forming valves in patients with deep vein reflux and/or chronic venous insufficiency. The award, which is supported by the Jon DeHaan Foundation, means that the company receives US$200,000 to further develop their device.

UPON RECEIVING the award, Fletcher Wilson— InterVene’s founder and CEO—said that he and his colleagues wanted to develop a new approach for managing deep vein reflux, because the condition has such an effect on patients. “When the disease progresses to ulceration, quality of life deteriorates.

Also, the cost impact is huge. To put it into perspective, 15 billion is spent directly on venous ulcers each year—that is one out of every US$200 spent in the entire US healthcare system. Therefore, venous ulceration is a big problem,” he added.

According to Wilson, current approaches to deep vein reflux are limited with patients being “stuck with compression therapy and wound care”. Furthermore, he said, previous attempts at addressing the problem have not been successful with, for example, implants being associated with thrombosis. Therefore, InterVene sought to develop a minimally invasive method that did not require an implant. Wilson commented: “Our approach is to form a valve out of the vein wall itself. Really, what we are trying to do—as much as possible—is to

mimic natural physiology.” The BlueLeaf system is used in conjunction with intravascular ultrasound (IVUS) and is capable of creating multiple valves per procedure.

Wilson reported that in a feasibility study (INFINITE-OUS) of 13 patients, the procedure was successful in nearly all patients (12). Of the patients for whom seven-month data were available (10), the mean revised venous clinical severity score (rVCSS) was 4.9 and eight patients had a more than fourpoint improvement.

Speaking about winning the TCT-Shark Tank Innovation Competition, Wilson said: “It was an honour to even be able to participate in an event like this. The panellists have been involved in such important medical innovations that have touched countless lives, so hearing their feedback and positive response was both helpful and validating.

I also think this win says something more broadly about the venous interventional space in general. A peripheral venous company winning at TCT would have been very unlikely a decade ago, and I think

Source: CRF

it validates that the cardiovascular community is starting to realise how important venous is, and how many patients are out there in desperate need of better solutions. The generous award money will support our US Investigated Device Exemption (IDE) trial, continued product development, and building out and maintaining our team.”

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12

November 2019 | Issue 12

Interview

Profile

John Kaufman

As course director of The VEINS at VIVA 2019 (2–4 November, Las Vegas, USA), John Kaufman tells Venous News how the field of interventional radiology (IR) has transformed over the years and highlights key areas of innovation to look out for in the future.

What inspired you to enter the field of medicine and how did you first become interested in interventional radiology as a specialty?

I went in to both medicine and radiology because of my father, Seymour Kaufman. He trained during World War II in an accelerated US Army programme; remarkably, he had his MD by the age of 21. He really loved what he did, and in high-school I would develop X-rays for him in his office on Saturdays. Radiology and interventional radiology took a little longer to figure out—I was a rebel so I started in surgery. Over time I realised that my father was smarter than I had thought, and radiology was the way to go. In my first year of diagnostic residency I rotated onto “Special Procedures” with the late, brilliant Alan Greenfield. He started me on the path to IR and I never looked back.

As a trainee doctor, which figures in the IR field were some of your key mentors?

I think almost everyone I have interacted with in this specialty has given me something that I still carry today. Patients, fellows, nurses, technologists, support staff, administrators, physician colleagues (from IR and other specialties), professional society staff, and many industry partners have all mentored me in their own ways. Everyone has something to teach you. Some who stand out as having been particularly tolerant of me are Alan Greenfield, John Guben, Jim Parker, Michael Bettmann, Greg Walker, Stuart Geller, Arthur Waltman, Jan Durham, Peter Mueller, Kathy Krol, Barry Katzen, Gary Becker, Josef Rosch, Fred Keller, Matt Mauro, and Anne Roberts. But there are many, many more.

During your time as an interventional radiologist, what have been some of the major changes to the field and how has this impacted upon your practice?

I have been doing this long enough that my answer includes the availability of such common technologies (today) as stents, microcatheters, volumetric CT, and high-resolution digital subtraction angiography (DSA).

However, I think the biggest changes have not been the new technologies. The first major change is that imageguided procedures have become mainstream, such that medicine without them is now inconceivable. Take the Transjugular intrahepatic portosystemic shunt (TIPS) procedure for complications of portal hypertension, developed by Josef Rosch from my institution; modern hepatology cannot function without it. The second major change is the broad application of the scientific method when bringing new technologies and procedures forward. Although the process is now slower than in the past, it is the right way to move ahead. The third is the recognition that the patient is the focus, not the technology or the physician or their specialty.

The validation of image-guided interventions has led to adoption by many specialties that are all equally dedicated to their patients. We can all work together for the common goal of improving patient outcomes. This the core principle behind all that we do at VIVA, and I hope one that all specialties will ultimately embrace.

How great a challenge was it to gain recognition for IR as a primary specialty

in the USA?

Change is a fascinating process in general, and always seems more obvious in retrospect. The transition from sub-specialty of diagnostic radiology (DR) to a primary specialty followed many of the classic steps of implementing major changes; refinement of the message, initial champions, engagement of key stakeholders, early adopters, and all that follows.

Many of the challenges were internal to IR and DR as would be expected, and these were the most important to address up front. It is really hard to convince the American Board of Medical Specialties (ABMS) that something is a legitimate primary specialty, and that the benefit to patients outweighs all of the logistical, bureaucratic, and economic burdens that specialty status imposes upon society. In the end, it was the support of all but one ABMS specialty that encouraged us to bring this to fruition. The immense popularity of the new IR residencies and the high quality of the candidates has been very gratifying to see.

What made you decide to move across the country—from Harvard Medical School to Portland, Oregon—after spending so much of your personal and professional life in Boston?

The Dotter Institute and the Pacific Northwest. For me, it was a great professional move in terms of the people, history, and potential here, and it just gets better every year. For our family, it matched our interests and lifestyle. We do miss being closer to family, but my wife has never looked back!

What are some of the key areas of innovation and research that you are keeping an eye on, especially in your role as editor for the American Journal of Radiology?

We are all watching machine learning and artificial intelligence (AI) with intense interest. On the face of it, one might assume that proceduralists may be less impacted than imagers, but AI will become integral to

The immense popularity of the new IR residencies and the high quality of the candidates has been very gratifying to see.” our decision making processes before, during, and after interventions. It is less likely that computers will do the actual procedures; instead, they will analyse images, laboratory results, and symptoms. That being said, we will rely on AI for vast segments of our non-procedural practice. Another area that we should all be watching closely is outcomes research. Proving that image-guided procedures provide better outcomes at less expense and with higher patient acceptance than traditional open

procedures requires solid scientific work. The recent controversy over paclitaxel is just one example of how easy it is to focus on the outcomes that interest us the most. In the venous world, we will need to prove that all of the stents that we are now placing lead to improved outcomes.

As course director of The VEINS at VIVA, what are you looking forward to most at this year’s event?

The VEINS at VIVA meeting is even bigger this year than last. Raghu Kolluri is literally a force of nature, and the result is a great programme with high-level speakers that covers the full spectrum of venous diseases.

This year we have added an all-star multidisciplinary scientific committee—including Suman Wasan, Suresh Vednatham, and Lowell Kabnick—who have enhanced the content tremendously. But to answer your question, what I am looking forward to most is learning a lot.

Issue 12 | November 2019

Interview

13

Fact File

Qualifications

1978 BA, Yale University 1982 MD, Boston University School of Medicine 2010 MS, Harvard School of Public Health

Academic Appointments (selected)

1997–2000 Associate professor of radiology, Harvard Medical School 2000–Present Professor of interventional radiology, Dotter Interventional Institute, Oregon Health & Sciences University 2003–Present Professor of surgery, Division of Vascular Surgery, Oregon Health & Sciences University 2005-Present Frederick S. Keller endowed chair of interventional radiology, Dotter Interventional Institute, Oregon Health & Sciences University

Professional Appointments (selected)

Are there any especially memorable cases which stand out to you from your time as an interventional radiologist?

We all cherish the saves—the patients that we somehow pull back from the brink. I also think a lot about those that I have lost, or somehow failed. I feel that I owe it to them to not forget; if there can be any good in their sacrifices, it is trying not to let it happen again. Finally, I really enjoy the patients that I work with over time who I get to know as people, rather than conditions or diseases. This is the truly magical side of IR.

Could you describe the proudest moment of your career?

That is easy: any time I am called out as the father of Claire Kaufman, MD. That supplanted hanging my medical school diploma on the wall next to my father’s.

It is fantastic, truly awesome, and she is going to make me look like a back-bencher.

If you could give any advice to a new IR specialist graduating from medical school today, what would you say?

The best part of image-guided interventions is yet to come. Keep an open mind, think beyond the lesion, and collaborate. This space is going to remain one of the most exciting, innovative aspects of medicine for a long time. Much of what you learn and do when you graduate will be replaced with new procedures within 10 years; most of which you cannot even imagine right now. This is hard work, but it is worth it!

What are some of your hobbies and interests outside of medicine?

This will be a pathetically short answer—my continually expanding family of people and dogs, cooking (especially long complicated recipes that involve pasta), good wine, and more recently roasting coffee. I would also fly-fish if I could find the time.

1983–1985 General medical officer and director of emergency medical services, W.W. Hastings Indian Hospital 1998–2000 Fellowship director, vascular/ interventional radiology, Massachusetts General Hospital 2003–Present Chief of vascular and interventional radiology, Dotter Interventional Institute, Oregon Health & Sciences University 2012–Present Director, Dotter Interventional Institute, Oregon Health & Sciences University 2017–Present Chair, Charles T. Dotter Department of Interventional Radiology

Offices (selected)

2003–2005 Chair, Council on Cardiovascular Radiology and Intervention, American Heart Association (AHA) 2008–2009 President, Society of Interventional Radiology (SIR) 2016-2018 President, VIVA Physicians 2018–Present Governor, American Board of Radiology

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November 2019 | Issue 12

Venous thromboembolism

Decreased risk of recurrent venous thromboembolism in morbidly obese patients with Xarelto revealed Real-world evidence has been published in Thrombosis Research confirming that Xarelto (rivaroxaban) reduces the risk of recurrent venous thromboembolism (VTE) in morbidly obese patients, with its effectiveness and safety similar to that of warfarin. According to the findings of the research, patients taking Xarelto also had significantly reduced healthcare resource utilisation (HRU) and total medical costs compared to those taking warfarin, supporting the results of other studies into the efficacy of Xarelto.

APPROXIMATELY 40% OF the US population have obesity, while 8% have morbid obesity, increasing their risk of VTE by two to six times. Typically, morbidly obese patients are treated with older anticoagulants and require more supervision than patients of a normal weight. In addition, morbidly obese patients are often underrepresented in Phase 3 studies.

“This is the first large-scale, realworld study to evaluate a direct oral anticoagulant (DOAC) in morbidly obese patients with VTE, and the first to identify healthcare resource utilisation and medical costs in this population,” said Alex C Spyropoulos (Hofstra University, New York, USA).

He added: “We now know from this research that rivaroxaban is as effective and safe as dose-adjusted warfarin when treating morbidly obese patients, without the need for routine anti-Xa measurements, and with significantly lower healthcare resource utilisation.

Physicians should feel confident in prescribing rivaroxaban for managing VTE in this population.”

In 2016, the International Society on Thrombosis and Haemostasis (ISTH) published a guidance statement recommending against DOAC use in morbidly obese patients, based on limited clinical data and concerns about available pharmacokinetic/pharmacodynamic (PK/PD) evidence from another DOAC that suggested a decrease in drug levels with increased body weight. Published data for Xarelto, on the other hand, discovered that the medicine’s PK/PD were not meaningfully influenced by body weight.

Over 5,000 patients with morbid obesity (BMI of ≥40) were included in the study, with half receiving Xarelto and half receiving warfarin. Moreover, there were 2,890 matched pairs in the intentto-treat (ITT) analysis and 2,832 pairs in the on-treatment analysis.

Findings of the study showed that the risk of recurrent VTE was not significantly different between Xarelto and warfarin (16.8% vs. 15.9%; Odds Ratio [OR]: 0.99; 95% confidence interval [CI]: 0.85 to 1.14; p=0.8443), although there were significantly fewer major bleeding events for those taking Xarelto compared to those taking warfarin (1.8% vs. 2.5%; OR: 0.66; 95% CI: 0.45 to 0.98; p=0.0388).

Xarelto was also associated with significantly lower HRU compared to treatment with warfarin, with hospitalisations occurring in 35.1% and 38.6% respectively (OR: 0.86; 95 percent CI: 0.77 to 0.96; p=0.0057).

In addition, treatment with Xarelto yielded significantly lower total medical costs, though total healthcare costs (including total medical costs and pharmacy costs) were similar between groups. Average total medical costs (per person, per year) were US$2,829 lower with Xarelto compared to warfarin (US$34,824 vs. US$37,653; p=0.0201), which were mainly driven by hospitalisation costs.

The results of the study are consistent with data across body weights from the EINSTEIN DVT and EINSTEIN PE randomised clinical trials (RCTs), which were the Phase 3 registration trials for Xarelto in VTE (DVT and pulmonary embolism (PE)).

Additionally, this real-world VTE study complements the only other large-scale, real-world study of over 7,000 patients with nonvalvular atrial fibrillation (NVAF) and morbid obesity where consistent effectiveness, safety and reduction in healthcare and total medical costs with Xarelto were shown.

Furthermore, the safety and effectiveness demonstrated in this study align with what was observed in ROCKET AF, the Phase 3 registration trial for Xarelto in NVAF.

Issue 12 | November 2019

Augmented reality in phlebology practice: Is it essential?

Anelise Rodrigues Comment & Analysis Like many other industries, the shape of healthcare and medicine is being transformed by the emergence of new technologies.

Phlebology, as Anelise Rodrigues (Culabá, Brazil) explains, is no different. While there are still concerns with the potential limitations and complications of implementing a new system for treating veins—addressed by Rodrigues in her article—augmented reality (AR) could also represent the future for venous specialists.

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n this modern age, technology has become so intertwined with our own lives that we no longer notice how embedded it is in our day-to-day activities. Furthermore, it is accepted that in just a few years, many of today’s jobs will not even exist. When it comes to medicine, the situation is no different; each day there is something new going on, and to row against the stream does not seem to be the best way of navigating the waves of technological change.

My father is a vascular surgeon, and when I was a child I would to go to his office after school. I remember being amazed when he would pinch what I would see as pure skin, and all of a sudden those small purple veins would vanish. Sometimes he would miss one spot or another, but in the end the results were very good.

I grew up and became a vascular surgeon myself, and as easy as it was for me to get the needle inside small purple veins, getting to the feeder veins (especially when treating patients with darker skin) was not so easy. The phleboscope came to help me with the struggle of puncturing and marking those hidden veins only he could see, and together with white skin markers it was the top tool of my practice for some time.

Some years later, when I was first introduced to AR in a visit to the Vascular Institute of New York (New York, USA), I kind of hated it; the imaging was different from what I used to get from the phleboscope, and I lost punctures of veins I could see with my naked eye. I was then pretty sure that this “new device” was not useful at all and went back to my comfort zone. After becoming accustomed to it though, during a fellowship at Clinica Miyake (Sao Paulo, Brazil), I knew that I could not run from AR anymore.

It took some work to finally be able to correlate the AR image with the location, size and deepness of the vessels. In the very beginning, before each puncture,

I would double check the vein with the phleboscope, and even with an ultrasound, to correlate the AR images to those I was already familiar with.

After a while, and with a bit of practice, I realised how amazing it could be.

In 2006, Kasuo Miyake et al published an article entitled “Vein imaging: a new method of near infrared imaging, where a processed image is projected onto the skin for the enhancement of vein treatment,” describing the use of AR for vein treatment. Since that first publication, many improvements have arrived and the tool has been incorporated as part of many phlebologists’ daily routine.

When the work was published in 2006, it was proven that AR could identify veins that were invisible to the naked

Augmented reality eye and too shallow for ultrasound detection—in other words, it could easily identify hidden feeder veins. Today, some high frequency US transducers can also identify and measure those veins. The AR devices emit a near infrared light, which is absorbed by the blood and reflected by adjacent tissues. The information is captured, processed and projected onto the skin surface in real time.

Real time imaging is especially useful when performing transdermal laser and CLaCS (Cryo-Laser Cryo-Sclerotherapy).

It allows us to observe the vessel’s immediate response, its spasm, and the effectiveness—or not—of our laser settings, and helps us to find the best spot for puncture after lasing, even on darker skin. Moreover, the technology allows us to always select the best projection colour for each skin tone, ensuring that we can see the image in all patients.

There are a few AR devices available, but the better the equipment, the faster its image processing and lesser the parallax effect (the difference we find between the vein’s real position and the projection we get from the device onto the skin).

Nevertheless, there are a few easy tricks for punctures, such as aligning the needle image to the vein image, which help us to overcome this drawback.

Some of the main advantages of AR compared to the phleboscope are the possibility of having both our hands free, a larger visual field for treatment and, in addition to these aspects, the fact that it does not get in contact with the skin. That last part is particularly useful when performing sclerotherapy or any procedures that involve vein puncture, where contact with the skin may result in blood contaminating our equipment.

As AR devices are able to show us virtually every reticular vein on patients’ legs, a huge concern among many phlebologists is the unadvised sclerosant injection in normal veins. We have to be reasonable and keep in mind that we cannot inject everything we see,

We all know that there are many ways of getting good results without AR, but we cannot deny all of the developments we are facing.”

15

but only the unhealthy veins. To know which veins to treat, we must focus on identifying tortuous veins and feeder veins that might act as sources of the patient’s complaints. Also, you should check the direction of the blood flow of the veins connected to a telangiectasia, thus avoiding drainage veins, while the use of a high-frequency ultrasound is a helpful tool when in doubt. Ultimately, we must know the pathologies we are willing to treat before we do so.

Apart from that which we have already mentioned, patients tend to be very fond of new technologies, and most of them find this imaging amazing, not to mention that every patient (including ourselves) prefers to get their veins catheterised with a single puncture instead of several of them. Suffice to say, happy patients spread the word.

When we talk about implementing new technologies in our practices, the first thoughts we come up with are always the same: “It is too expensive” or “I don’t need to spend so much money on this.”

We know that the available AR devices are not cheap. However, if we think of it as an investment that adds value and quality to our practice, and the profit it can bring to our businesses, then the scales will probably shift the other way.

Of course, when deciding whether or not to acquire and implement this technology, the focus of your practice and professional situation must always be taken into account. If you are a vascular surgeon whose main practice is arterial, then perhaps it is not the most appropriate tool to conisder. That being said, for those who have thought or are thinking about having phlebology as their main activity, and are looking for the best aesthetic outcomes, I believe the use of AR is highly useful and, at some point, there will be no way to avoid this movement.

We all know that there are many ways of getting good results without AR; we have practiced this way for many years and continue to do so. Nevertheless, we cannot deny all of the developments we are facing; especially the fact that AR can facilitate and optimise our treatments, saving us precious time and helping us to avoid failures that could result from not treating hidden veins.

If it is essential or not may be more of a personal choice, based on each physician’s needs, patients, budgets, and also on the kind of results desired. Even though it may sound superfluous today, I really believe that in the near future every phlebologist will have at least one AR device to call “mine”.

Anelise Rodrigues is a vascular surgeon dedicated to the treatment of varicose veins. She graduated from Campinas State University (UNICAMP; Campinas, Brazil) in 2003 and has been a Brazilian Medical Association Certified vascular surgeon since 2008.

Furthermore, Rodrigues is a member of the Brazilian Angiology and Vascular Surgery Society (SBACV) and American Venous Forum (AVF), as well as a former fellow at Barcelona University, Barcelona, Spain.

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November 2019 | Issue 12

New guidelines

Updated venous thromboembolism guideline for cancer patients unveiled

by ASCO An updated guideline on the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer has been unveiled by the American Society of Clinical Oncology (ASCO) in its Journal of Clinical Oncology. An expert panel convened by ASCO reviewed evidence—including randomised controlled trials (RCTs) and meta-analyses of RCTs—from the period between 1 August 2014 and 4 December 2018, before providing a list of findings and recommendations.

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atients with cancer are at a higher risk of developing VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), than those without cancer, and have higher rates of VTE recurrence and bleeding during VTE treatment. Consequently, VTE is an “important cause of morbidity and mortality” among cancer patients.

According to the review, two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer patients confirmed the efficacy of edoxaban and rivaroxaban, but found they could be associated with an increased risk of bleeding compared to low-molecularweight heparin (LMWH). Two additional RCTs underlined the potential benefits and side effects of DOACs for thromboprophylaxis in ambulatory cancer patients at a higher risk of VTE. Co-chaired by Nigel S Key (Chapel Hill, USA) and Anna Falanga (Bergamo, Italy), the panel’s systematic review included a total of 35 publications (26 meta-analyses and nine RCTs) on VTE prophylaxis and treatment, and 18 publications on VTE risk assessment (six included multiple types of cancer, while 12 focused on individual cancer types).

In addition to Key and Falanga, 15 additional authors worked on the project.

Speaking to Venous News about the importance of these guidelines, Key

updated ASCO guidelines reflect the new evidence from clinical research showing the efficacy of new anticoagulant drugs for VTE management in oncology.

The addition of some DOAC to our armamentarium to prevent and treat cancer-associated VTE expands our choice and allows the possibility to personalise treatment based on patient characteristics and type of cancer.”

The updated guideline addresses six clinical questions:

Should hospitalised patients with cancer receive anticoagulation for VTE prophylaxis?

Should ambulatory patients with cancer receive anticoagulation for VTE prophylaxis during systemic chemotherapy?

Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?

What is the best method for treatment of patients with cancer with established VTE to prevent recurrence?

Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?

What is known about risk prediction and awareness of VTE among patients with cancer?

In response to the first clinical question,

This iteration of the ASCO guidelines on VTE prevention and treatment reflects an evolving evidencebased set of recommendations.” comments, “This iteration of the ASCO guidelines on VTE prevention and treatment reflects an evolving evidencebased set of recommendations on a common problem in a challenging patient population. Perhaps the greatest advances are the recommendations to consider certain oral direct factor Xa inhibitors for the treatment of VTE and for VTE prevention in higher risk cancer patients.”

Falanga is in accordance, adding, “The

“Should hospitalised patients with cancer receive anticoagulation for VTE prophylaxis?”, ASCO’s guideline states that hospitalised patients who have active malignancy and acute medical illness, or reduced mobility, should be offered pharmacologic thromboprophylaxis in the absence of bleeding, while patients with active malignancy but no additional risk factors may be offered pharmacologic thromboprophylaxis. However,

Anna Falanga

pharmacologic thromboprophylaxis should not be offered to patients admitted for minor procedures or chemotherapy infusion, nor patients undergoing stemcell or bone marrow transplantation.

On the subject of whether ambulatory patients with cancer should receive anticoagulation for VTE prophylaxis during systemic chemotherapy, a new addition to the guideline is that high-risk outpatients with cancer may be offered

preferred. Patients with active cancer, including those with metastatic disease or persons receiving chemotherapy, should receive anticoagulation with LMWH, DOACs or vitamin K antagonists (VKAs) beyond six months.

Responding to expert opinion in the absence of randomised trial data, uncertainty towards short-term benefits, and evidence of long-term harm from filters, ASCO has recommended against the insertion of a vena cava filter for patients with established or chronic thrombosis. Additionally, the guideline asserts that filter insertion has no role for primary prevention or prophylaxis of PE or DVT, though a vena cava filter may be offered as an adjunct to anticoagulation in patients with progression of thrombosis.

Incidental PE and deep vein thrombosis should be treated in the same manner as symptomatic VTE, according to ASCO. Answering the question of whether patients with cancer should receive anticoagulants in the absence of established VTE to improve chances of survival, anticoagulant use is not recommended to improve survival in patients with cancer without VTE. Finally, the guideline addresses what

The addition of some DOAC to our armamentarium to prevent and treat cancer-associated VTE expands our choice and allows the possibility to personalise treatment based on patient characteristics.” thromboprophylaxis with apixaban, rivaroxaban or LMWH. Patients with multiple myeloma receiving thalidomide or lenalidomide with chemotherapy should be offered pharmacologic thromboprophylaxis, according to the guideline.

For cancer patients undergoing surgery, it is recommended that all persons with malignant disease undergoing a major surgical intervention receive perioperative VTE prophylaxis with either unfractionated heparin (UFH) or LMWH, unless they present a high bleeding risk or other contraindications.

Prophylaxis should be commenced preoperatively and continue after surgery for at least seven to 10 days, while extended prophylaxis with LMWH, for up to four weeks, is recommended for cancer patients undergoing major open, laparoscopic abdominal or pelvic surgery.

Regarding the best method of treating cancer patients in order to prevent VTE recurrence, a number of recommendations are included in the guideline. Initial anticoagulation may involve LMWH, UFH, fondaparinux, or rivaroxaban, though LMWH is preferred over UFH for the initial five to 10 days of anticoagulation for patients with newly diagnosed VTE. For long-term anticoagulation of six months, it is stated that LMWH, edoxaban, or rivaroxaban are more effective and therefore Nigel S Key

is known about risk prediction and awareness of VTE among patients with cancer, recommending they be assessed for VTE risk initially and periodically, particularly when starting systemic antineoplastic therapy or at the time of hospitalisation. At the same time, individual risk factors do not reliably identify patients with cancer at high risk of VTE. ASCO argues that oncologists should educate patients regarding VTE, particularly in settings that increase risk, such as major surgery and hospitalisation.

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November 2019 | Issue 12

Deep vein thrombosis

Most reinterventions following treatment of iliofemoral DVT could be due to “preventable factors” Analysing the results of a retrospective, single-centre cohort study conducted at Guys and St Thomas’ Hospital, London, UK, Anna Pouncey (Guys and St Thomas’ Hospital, London, UK) emphasised that over 50% of cases included in the investigation could have been avoided. When questioned about how the findings of this study will impact practice, Pouncey said: “We now have a lower threshold for investigating and checking if a patient is showing signs of restenosis.”

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resented at the European Society for Vascular Surgery annual meeting (ESVS 2019; 24–27 September, Hamburg, Germany), this study into risk factors for patients requiring a reintervention, following treatment for acute iliofemoral deep vein thrombosis (DVT), was based on a classification model that highlighted technical, flow-related and haematological causes of restenosis and re-occlusion.

Furthermore, Pouncey also offered a costeffectiveness analysis of interventions for the treatment of iliofemoral DVT and subsequent postthrombotic syndrome (PTS), suggesting that either pharmacomechanical thrombectomy (PMT) or catheterdirected thrombolysis (CDT) may present benefits over oral anticoagulation.

Classification of risk factors for reintervention

“The aim of our study was to develop a classification system for why patients require a reintervention, identify the individual risk factors associated with them, and examine patient outcomes following reintervention,” said Pouncey, as she outlined the objectives of St Thomas’ investigation.

As part of the study, 135 patients who had undergone successful lysis for acute symptomatic iliofemoral DVT—between 2013 and 2017—were identified, with 33% of these patients requiring a reintervention.

In addition, patient notes were evaluated for risk factors (including the haematologist’s assessment of their anticoagulation status), while a retrospective venographic assessment was also performed with the support of two independent specialists.

Focusing on the data, Pouncey revealed that 54% of patients (who had undergone a reintervention) had a technical error identified, which could have been a lack of stenting in the presence of residual disease, a failure to extend the stent distally (missing inflow), a failure to extend the stent proximally (missing outflow), or device failure such as stent fracture. However, Pouncey noted that “very few technical issues were related to device failure”. Around 44% had a flow-related issue, which would entail scarring or an occlusion of the femoral, profunda, or popliteal vein, and 35% had a haematological issue, such as non-compliance with anticoagulation or inappropriate dosing.

Of all the cases included in the study, 29% were multifactorial, with a significant amount of overlap between technical and flow-related issues. Comparing this to the cohort who maintained their vessel patency, Pouncey commented: “We can see that very few of these patients had any technical issues, all had good flow, and only one had a haematological issue.”

Looking next at patient factors, or individual risk factors associated with reintervention, it was stated that the only relevant variable was a younger patient age,

Anna Pouncey

Anticoagulation compliance is essential, and there is a role for surveillance so that you can reintervene prior to occlusion and have a greater chance of success.” although these patients were associated with a greater prevalence of inferior vena cava (IVC) thrombosis.

In terms of flow-related factors, profunda occlusion, femoral occlusion and stenting across the inguinal ligament were all considered important, while the patient was three times more likely to require an intervention if they were non-compliant with anticoagulation. “When we performed multivariate analysis, the three factors that came out as dominant were IVC thrombosis, stenting across the inguinal ligament and anticoagulation non-compliance,” Pouncey asserted.

Patient outcome data showed that the median time to reintervention was 45 days, and 45% of cases were reintervened on during the first six weeks. There was an intervention success rate of 67%, although this was much higher in cases where a reintervention was performed prior to total vessel occlusion. Regarding the incidence of PTS, it was found that the need for reintervention doubled the risk, with 32% of patients in the reintervention group developing PTS compared to only 14% in the cases that remained patent.

In summary, Pouncey said: “Anticoagulation compliance is essential, and there is a role for surveillance so that you can reintervene prior to occlusion and have a greater chance of success.

Last of all, you have a greater risk of poor patient outcome if you have to reintervene, so try to get it right the first time.”

A cost-effectiveness analysis of interventions

“We all know that iliofemoral DVT and the subsequent incidence of PTS carries a significant financial burden,” commented Pouncey, “and if you perform an interventional treatment to expedite thrombus removal, you will hopefully reduce the patients’ symptoms and mitigate post-thrombotic syndrome.” However, the investigator also accepted that this comes with “a higher risk of bleeding” as well as a greater cost. Moreover, there is only a modest health benefit to this intervention (a 10% reduction in moderate to severe PTS) according to the ATTRACT trial.

Despite these findings, PMT is currently used in the UK, albeit under special measures due to there being “a paucity of data to support its use”, according to Pouncey.

“We aimed for an NHS-based cost-effectiveness analysis for treatment of iliofemoral DVT and specifically wanted to look at all anticoagulation vs. percutaneous interventions,” she said.

In order to perform the cost-effectiveness analysis, a patient health states model was created; a front-end decision tree was used to model the acute DVT veins and any complications that could happen, while a backend Markov model was alsoused to model the long-term patient outcomes, namely the severity of PTS. Analysis was conducted through a lifetime horizon with death as the absorbing state, while slightly increased mortality rates following DVT were also accounted for.

Pouncey addressed the sourcing of data and explained that “for patient outcomes, we used the results of the ATTRACT trial, as well as for the proportions of patients in each health state over time”. She added: “For our utility estimates we used the best available published literature and for our costing sources, we used the UK NHS national tariff workbook, published scientific literature and local data from our team at the St Thomas’ Trust.”

The results of the analysis, which accounted for a stenting rate of 80%, were in some ways unsurprising, demonstrating that oral anticoagulation is far cheaper than CDT or PMT. However, the main results of the model established as part of the investigation at St Thomas’ Hospital showed that both CDT and PMT were dominant over oral anticoagulation. Concerning the findings, Pouncey commented: “What this means is that over a lifetime, the mean cost for the interventional treatments was cheaper than oral anticoagulation and the patient quality of life was higher too. So we looked into this a bit further, and what we found was that the increased cost is offset by a long-term cost benefit in the reduction of moderate to severe PTS. Moderate and severe PTS also have much higher healthcare costs over the long-term.”

In response to these results, the robustness of the model was assessed univariate and multivariate sensitive analyses. This revealed that costing is most sensitive to age, stenting and hospitalisation for severe PTS and that clinical effectiveness is more sensitive to major bleeding rates than pulmonary embolism (PE). That being said, significant parameter uncertainty was also found, reflecting the quality of data which was put into the costeffectiveness model.

Pouncey concluded: “CDT and PMT may be costeffective over oral anticoagulation, due to a reduction in the severity of PTS, however there is still uncertainty and we need to address this before drawing further conclusions. This can be achieved with more robust data on intervention outcomes, as well as a better understanding of the cost and lifetime impact of severe PTS.”

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November 2019 | Issue 12

Market watch

Product News PIUR Imaging launches wireless tomographic ultrasound system

PIUR Imaging has launched a portable version of its tomographic ultrasound system to the European market. The new CE-marked PIUR tUS Infinity is a small, wireless version of its tomographic ultrasound solution that turns any standard ultrasound into a high-resolution tomographic imaging device.

It consists of a small video box that connects to the video output of third-party ultrasound scanners, and a patented sensor-based tracking unit that attaches to any linear probe. Both units

PIUR Imaging Infinity

connect wirelessly to a standard laptop to transmit real-time 2D ultrasound images and information about transducer movement. An AI-based reconstruction algorithm turns this information into ultrasound volumes that can be analysed, stored, and shared similar to CT or MR scans.

The technology separates ultrasound acquisition from image analysis, and can help to increase patient-throughput in busy scanning rooms. The PIUR software provides volume rendering of vein maps, varicose veins, and tools for calculating carotid plaque parameters, such as plaque volume, volumetric stenosis, and 3D grey-scale median.

Non-vascular applications include thyroid and nerve imaging.

RE-SPECT trial establishes efficacy of Pradaxa for treatment of CVT patients

Boehringer Ingelheim has announced the publication of primary analysis from RE-SPECT CVT, the first exploratory, prospective, randomised controlled study of a NOAC in patients with blood clots in the veins or venous sinuses of the brain. The trial investigated the safety and efficacy of Pradaxa (dabigatran etexilate) and dose-adjusted warfarin in patients with cerebral venous thrombosis (CVT).

RE-SPECT CVT is a prospective, randomised study, assessing the safety and efficacy of dabigatran etexilate and warfarin in patients who suffer from CVT. The open-label study involved 120 patients from nine countries and looked to evaluate the suitability of dabigatran etexilate and warfarin for the treatment and secondary prevention of blood

clots in the veins or venous sinuses of the brain. Patients aged ≥18 years with a confirmed diagnosis of CVT (with or without haemorrhagic stroke) were randomised to receive either warfarin or dabigatran etexilate.

According to a statement, the results provide an insight into the role of anticoagulation in patients with CVT of mild-moderate severity. In the study, there were no recurrent venous thromboembolism (VTE) events in either treatment group. The trial also found that the rate of bleeding was low, with two patients in the warfarin arm (3.3%) and one (1.7%) in the dabigatran arm developing a major bleed. There was no mortality in either treatment arm in this study.

“CVT, which affects predominantly young patients and women, can cause death and disability. Patients who survive the acute phase of CVT may suffer recurrent venous thrombosis.

To prevent that, the usual clinical practice is to prescribe vitamin K antagonists (VKAs, such as warfarin).

VKAs present limitations in terms of safety, dosing, reversibility and patient preference,” said Professor José M Ferro, director of the Department of Neurosciences and Mental Health at Hospital Santa Maria in Lisbon, Portugal, and chair of the RE-SPECT CVT Steering Committee.

the peer-reviewed Journal of Vascular Access (JVA).

Results of an independent, singlecentre study demonstrated successful use of the Surfacer system in placement of haemodialysis catheters for patients with central venous obstruction involving one or more central veins.

The mean time for placement and associated fluoroscopy was 13.3 and 3.7 minutes, respectively.

“The Surfacer system continues to be a safe and effective solution for accessing obstructed central veins,” states Dirk Hentschel, co-author of the publication and physician proctor for the company’s US Food and Drug Administration (FDA) approved Investigational Device Exemption (IDE) clinical study. “This is of particular concern and importance for haemodialysis patients who are prone to life-threatening obstructions at vital access points.”

The newly published study in JVA adds to the growing body of evidence demonstrating the Surfacer system is a safe and reliable option for achieving right-sided central venous access and a viable means to preserving secondary central veins.

Additional evidence resulting from the successful use of the Surfacer system for haemodialysis patients awaiting the creation and/or maturation of an arteriovenous (AV) fistula was also recently reported in Hemodialysis International.

The company recently filed a de novo request for the Surfacer system with the FDA based on the positive

Bluegrass Surfacer

“The trial showed that the risk of recurrent VTE in CVT patients of mild to moderate severity under anticoagulant therapy with dabigatran for six months was low and associated with few major or clinically relevant bleeding events.”

Additionally, the trial aims to further the understanding of the safety profile of dabigatran, which has been documented in the extensive RE-VOLUTION trial and registry programme.

Bluegrass Vascular announces publication of positive clinical results for Surfacer system

Bluegrass Vascular Technologies (Bluegrass Vascular) has announced the publication of positive results associated with the clinical use of the Surfacer Inside-Out access catheter system in

clinical results of the company’s SAVE-US pivotal trial. The company anticipates that the FDA will grant the request and the Surfacer system will be commercially available in the USA in 2020.

VEST external stent demonstrates low event and disease rates in two prospective trials

Clinical data presented at the 2019 European Cardio-Thoracic Surgery (EACTS) annual meeting (3–5 October, Lisbon, Portugal), from two prospective trials of the VEST external stent for vein grafts during coronary artery bypass surgery (CABG), showed low major adverse cardiac and cerebrovascular events (MACCE) rates up to three years, excellent patency rates and a significant

reduction in the progression of vein graft disease.

David Taggart (John Radcliffe Hospital, Oxford, UK) presented the results of the VEST III trial at the late breaking clinical trials session. VEST III is a randomised controlled trial that enrolled 184 patients in 14 centres across Germany, Austria, Israel and the UK. At two years, the trial met its primary and secondary endpoints, showing superior perfect patency rates (Fitzgibbon I) of externally stented vein grafts compared to the control group (66.4% vs. 53.6%, p value=0.02) and a highly significant reduction of 25% (p value <0.001) in both intimal area and thickness assessed by intravascular ultrasound (IVUS).

“The results of the VEST III trial confirm our previous observations regarding the bio-mechanical effects of external stenting,” said Taggart. “This

VEST stent

is another milestone in our ongoing efforts to improve coronary surgery and patients’ quality of life. As the principle investigator of the first-in-human VEST I trial in 2011, and someone who has closely followed the evolution of this technology in the last 10 years, it is very satisfying to see how the combined effort of surgeons, scientists and innovators has led to a technology with high clinical impact.”

Luca Weltert (European Hospital, Rome, Italy) presented interim results from a study that evaluated angiographic and clinical outcomes in 51 patients.

The majority of patients underwent off pump CABG (77%) and all vein grafts were supported with the VEST external stent. CT angiography was performed at one year and patients were prospectively followed every six months for MACCE. Although the average age of the study cohort was 73.5, with 32% of patients having had a prior primary coronary intervention (PCI), at average follow-up of 3 years, MACCE rates were 2% with only one patient requiring revascularisation to a de novo coronary lesion. At one year, CT angiography demonstrated 100% patency of the VEST externally supported vein grafts.

“It is very encouraging to see that “real world” data support the evidence from randomised trials,” said Weltert.

“Very often, we see big gaps between clinical results of randomised cohorts, which are highly selective in nature, and the results in our day-to-day practice.

Our interim follow-up data show that at 3 years, clinical and angiographic results are superior compared to those observed in published randomised trials.”

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November 2019 | Issue 12

Market watch

Product News Industry Omar Ishrak to step down as Medtronic CEO next year Omar Ishrak, Medtronic’s chairman and CEO, is to retire on 26 April 2020, following the end of the company’s current fiscal year. Also, the Medtronic Board of Directors has announced key leadership appointments as part of its multi-year, leadership succession planning process. A press release reports that these announcements will ensure a smooth and successful transition in leadership across the company.

The Board of Directors has unanimously appointed Geoff Martha, currently executive vice president (EVP) of the company’s Restorative Therapies Group (RTG), to assume the newly created role of Medtronic president and become a member of the Medtronic Board of Directors, effective 1 November 2019. He will also succeed Ishrak as Medtronic CEO, effective 27 April 2020.

As president, according to the press release, Martha will lead Medtronic’s operating groups and regions. Brett Wall, president of Medtronic’s Brain Therapies division, was appointed EVP

and group president of RTG, succeeding Martha, effective 1 November 2019.

At the start of Medtronic’s next fiscal year, on 27 April 2020, Ishrak will assume a new position of executive chairman. He will provide counsel and guidance to Medtronic’s leadership, oversee CEO succession, and drive the ongoing successful execution of Medtronic’s long-term strategic plan.

These changes, according to a statement, are designed to ensure a smooth transition, continuity of leadership and a continued focus on delivering Medtronic’s innovation strategy and financial performance.

Ishrak commented: “We have announced leadership changes that meet both the Board’s objective of executing a thoughtful leadership transition as well as my personal desire to begin transitioning my duties as CEO to a new leader coinciding with the start of our next fiscal year.

“This plan and its timing enable Geoff and I to partner on achieving Medtronic’s key financial performance goals as well as delivering on our critical pipeline milestones, including

Omar Ishrak

several important product launches.

“Leading Medtronic as CEO is an honour and a privilege, and I know that Geoff is the right leader to take Medtronic to the next level of its growth and evolution. Geoff is a resultsoriented, dynamic, and innovative business leader who is passionately committed to our mission, the advancement of our growth strategy and the development and diversity of our people. I am confident he has the right track record, commitment, vision and judgment to lead our company.”

Scott Donnelly, Medtronic’s lead director, and chairman, president and CEO of Textron, said: “As Omar approaches the company’s mandatory

executive officer retirement of 65 years of age next year, we have ensured Medtronic has the right leadership at the right time to advance its mission and deliver shareholder return through a seamless transition. The Board is extremely grateful to Omar for his outstanding leadership—as the company’s annual revenues have doubled and its market capitalisation has increased by more than US$100 billion during his tenure.

“We are confident Omar’s contributions to Medtronic will continue as executive chairman. The Board’s succession planning process prioritises developing leaders from within the company, and we are pleased that we could advance Geoff and Brett for these roles. During his time at Medtronic, Geoff has demonstrated his unique ability to lead, innovate and drive results, and the Board has full confidence in him and his ability to take Medtronic into its next chapter of growth.”

Wall, new EVP and group president of RTG, also made a statement, highlighting restorative therapies as the forefront of the company’s innovation agenda: “It’s my absolute privilege to lead this group, which has an incredibly strong leadership team and more than 14,000 dedicated and passionate team members around the world.”

Calendar of events 2–4 November The VEINS at VIVA Las Vegas, USA

19–23 November VEITHsymposium New York, USA

www.vivaphysicians.org

www.veithsymposium.org

4–6 November Wounds UK Harrogate, UK

27–29 November The Vascular Societies’ Annual Scientific Meeting Manchester, UK

www.wounds-uk.com

www.vascularsociety.org.uk

7–10 November AVLS: American Vein and Lymphatic Society Phoenix, USA

5–7 December French Society of Phlebology Paris, France

www.avlscongress.org

2019 | Issue

11

Oliver Lyons:

rapy for Pharmacothea 4 lymphoedem Page Efthymios

Avgerinos:

sPE interim SUNSET Page 12 outcomes Kurosh Parsi:

Profile

Page 10

“Fascinating nonvision” of cose invasive vari nt vein treatme rapy with echothe at EVF discussed

sity as high-inten also known venous ERAPY— addition to ECHOTH —is a recent new device a focused ultrasoundoptions, with a l veins in to treat superficia r (Melk, disease treatment technique . Alfred Obermaye applying the findings at ive procedure his initial non-invas first presented m (CX; 15–18 Austria), who Cross Symposiu to the delegates an update the 2019 Charing Forum UK), gave April, London,year’s European Venousnd), stating this Switzerla attending t veins Zurich, June, d insufficien y (EVF; 27–29 lly obliterate , completel successfu ultrasound R trial “we have group following primary endpoint sity focused Medical IPC-SUPE had the IPC or control esults of the using high-inten (DVT) being National Research clinical trial is highe European Russian behind orally.” at the Pirogov the idea nd) two-centr atic deep vein thrombos extracorp . were presented Zurich, Switzerla r presented asymptom (HIFU), describing Obermaye University June, duplex ultrasoundmet a range of inclusionage ultrasound achieves s without (EVF; 27–29 the revealed by d that IPC in the trial intensity focusedng vision” of procedure site ts to be over have Venous Forum who emphasise rates of leg participan surgical Patients enrolled and it as a “fascinati incisions, required all tive VTE

by Kirill Lobastov, without increasing ly, I have system ia, catheters, criteria, which a high risk of postopera outcome 2 “Previous the exclusion anaesthes The HIFU on page a beneficial bleeding. He added: of 11 or more Continued , or scarring. of 40, present of 11 or more. In addition,acute DVT at or infections and Caprini scores with skin injury of patients with of postoperative VTE, Caprini scores trial removed those and a range reported that infections for the high risk of patient.”

IPC. of this kind was criteria lower limb soft tissue contraindications to have an extremely 2 be in about 50% on page d by Lobastov, baseline, that would Continued it can be foundthe study, as underline other conditions safety of Cardinal700 and The aim of SCD both the efficacy he Kendall to determine l IPC device—t n of postoperative preventio Health’s sequentia r—for the Series Controlle

for ssion (IPC) that tic compre has revealed rative tent pneuma m (VTE) e of postope there is tion of intermit thromboembolis that the incidenc on the applica concluded risk of venous axis reduces A new study with a high d prophyl PREVENT trial, which patients e care unit. the and standar surgical those of to an intensiv of 400 ation of IPC admitted a combin findings differ from a sample size for those patients. With d into either an VTE. Theseto the use of IPC the VTE in high-risk were randomise by no benefit ts, who major surgery, of conducted participan

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26–28 January Conference of the French Society for Wound Care Paris, France

www.bsir.org

www.cicatrasions2020.org

23–25 January CACVS: Controversies and Updates in Vascular Surgery Paris, France

28–31 January LINC: The Leipzig Interventional Course Leipzig, Germany

www.cacvs.org

www.leipzig-interventional-course.

26–27 February Wound Care Today Milton Keynes, UK www.woundcare-today.com

3–6 March AVF: American Venous Forum Amelia Island, Florida, USA www.veinforum.org

com

www.sf-phlebologie.org

September

trates l demons SUPER tria intermittent of sion benefits compres pneumatic VTE patients isk h-r hig for

5 December Vascular Anomalies Special Interest Group Forum 2019 London, UK

Venous News is a trusted, independent source of news and opinion in the vascular and endovascular world.

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Issue 12 | November 2019

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