Vascular News EU

June

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While CX audience deems paclitaxel not dangerous, vascular pathologist says establishing “truth takes time” Delegates of the Charing Cross Symposium (CX; 15–18 April, London, UK) voted against the notion that there was a demonstrable danger in any organ of the body attributed to circulating paclitaxel. These polling results, with a 67% majority, came after vascular pathologist Elena Ladich (Hollywood, USA) presented insights from new analysis on the effects of paclitaxel on human tissue and organs. In a CX Highlight Session, the FDA confirmed their Individual Patient Data (IPD) review panel set to take place this June, and called for more transparent data release from industry, as a range of speakers explored the ramifications and potential resolutions four months on from the Katsanos et al metaanalysis published in the Journal of the American Heart Association (JAHA). Experts, representatives of regulatory bodies and other stakeholders scrutinised the current controversy surrounding paclitaxel, discussing the idea of a “trade-off” wherein drug efficacy may necessitate potential adverse events for paclitaxel-eluting technology.

Elena Ladich

T

he session was chaired by Roger Greenhalgh with moderators and CX Executive Board members Gunnar Tepe, Andrew Holden and Thomas Zeller.

Ladich, whose presentation closed the session, spoke on the effects of paclitaxel on the artery wall, drawing from her experience and observations with human autopsies, directly examining human tissue of patients who had received paclitaxel treatments.

Ladich explained that there are known local and downstream effects of paclitaxel-eluting technology, with “rare case reports” describing local aneurysms, localised hypersensitivity, downstream vasculitis and panniculitis.

She added that “a proportion of the drug and excipient coating are known to embolise distally”, posing the question, “should we be concerned about the potential shower?”. Drawing from her own experience and observations with human autopsies, Ladich has examined the tissue of patients who were treated with paclitaxel, analysing whether any toxicity damage to organs could be found in the body, but could find no such evidence.

“To date,” Ladich stated, “there are no published reports of autopsy findings of specific organ toxicity in humans treated with drug-coated balloon”, adding there are Continued on page 4

Kim Hodgson:

Profile

Page 26

Page 29

EVAR funding threatened, while strategy for safe, cost-effective repair is “just around the corner” The durability of endovascular aneurysm repair (EVAR) is in the limelight as the UK vascular community awaits the final aortic aneurysm guidelines from the National Institute for Health and Care Excellence (NICE), set to go against widespread endovascular practice in recommending open repair over EVAR. In May 2018, the aortic clinical guidelines committee chaired by Andrew Bradbury (Birmingham, UK) released a draft guidelines document, which suggested with its recommendations that EVAR procedures do not justify national funding from the UK National Health Service (NHS)—instead encouraging a return to open surgical aneurysm repair.

THIS WAS THE topic of discussion at a Charing Cross Symposium (CX; 15–18 April, London, UK) Highlight Session, in which Tara Mastracci (London, UK) argued for EVAR as “standard of care”. Mastracci’s argument stood in contrast with the NICE aortic draft guidelines, as did a range of speakers’ in the session who set out key arguments Continued Continued on on page page 82

4

June

While CX audience deems paclitaxel not dangerous, vascular pathologist says establishing “truth takes time” Continued from page 1

“no causal links or mechanism to explain the reported association of paclitaxel in the lower limbs and patient mortality.” Nevertheless, despite this lack of evidence in autopsy—which Ladich calls “the ultimate quality assurance tool to assess complications in patients”—she stressed that “this does not mean a potential damaging effect does not exist.”

“Truth takes time,” Ladich said, and argued that the Katsanos et al mortality data and the US Food and Drug Administration’s letter to healthcare providers in March indicate that further investigations are needed.

Polling at the close of the session revealed that 85% of CX delegates believed “no danger has been demonstrated in any organ of the body that is attributable to circulating paclitaxel”. This conviction was further consolidated, when attendees were asked: “Have we established that there are substantial levels circulating in arteries used for reducing restenosis?”—68% of respondents said no.

The potential problem: What do we know?

The Highlight Session began with a summary of the key messages from the recent Vascular Leaders Forum (VLF; 1–2 March, Washington, DC, USA) by Gary Ansel (Columbus, USA). He told CX delegates that a central discussion point was whether a “protective benefit” with plain percutaneous transluminal angioplasty (PTA) could explain the higher mortality seen with paclitaxel devices in the meta-analysis. Ansel commented there was “no mechanistic signal to date” for such a benefit but, potentially, risk factors may be more frequently identified—and thus modified—in PTA patients because they are seen more often and undergo more interventions than those who receive paclitaxel devices.

“This [peripheral arterial disease] population dies at a very high rate during the five years after a procedure.

We should be focused on how we stop these patients from dying. From my standpoint, these patients should be followed much more closely for their general medical condition. We have to make sure these patients are not having infections or different oncology problems.

We need to change this mortality rate with much more aggressive risk factor modification,” Ansel noted.

The lack of mechanistic signal was one main criticism levelled at the Katsanos et al meta-analysis findings. Defending his methodology and conclusions,

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Issue

19 82

Paclitaxel-eluting devices

Misti Malone

Konstantinos Katsanos (Patras, Greece) told CX delegates that the increased risk of death reported in the metaanalysis following the application of paclitaxel-eluting devices in the femoropopliteal artery was consistent and significant across multiple statistical analyses. “We are mathematically 99% certain of this significance,” Katsanos stated emphatically, pointing to results of a trial sequential meta-analysis. He added, “every trial is only as good as its methodology. […] The key message here is not a smoking gun—it is the consistency of the findings.

You see here the consistency of the mortality signal, and this I would say is the main take-home message.”

Mårten Falkenberg (Gothenburg, Sweden), investigator of the SWEDEPAD registry-based randomised controlled trial, reported on the status of the trial, which ceased enrolment in the wake of the JAHA meta-analysis. He told the CX audience that despite keeping up with the ongoing international conversation, the investigators were still trying to determine the best course of action, but no obvious consensus has emerged. Falkenberg further disclosed the reason for the investigators’ decision to

Editorial contribution:

Jessica Thompson, Suzie Marshall, Dawn Powell, Jocelyn Hudson, Angela O’Neill

interrupt the trial was directly in response to the Katsanos et al publication’s conclusions, rather than any own observations. Meanwhile, the future of SWEDEPAD will be determined “based on the recommendations of our clinical events committee,” said Falkenberg.

Jonathan Michaels (Sheffield, UK), chair of the steering committee for the BASIL-2 and BASIL-3 trials, spoke about the halting of enrolment into the latter trial, which was set to expand on BASIL-2’s investigation of paclitaxel treatments for claudicants by examining the therapy in patients with critical limb ischaemia (CLI).

However, BASIL-3 enrolment ceased following the Katsanos et al meta-analysis in order to review the ethics of continuing to treat patients with this drug. Michaels queried if there was an “innocent explanation” for the mortality signal. Like Ansel, he suggested a “plausible” reason for the observed increased mortality may be related to a greater follow-up frequency in patients treated with PTA, for whom potential comorbidities may be more likely to be diagnosed. Meanwhile, both Michaels and principal investigator Andrew Bradbury (Birmingham, UK) expressed their hopes to restart recruitment, although the unanswered questions surrounding paclitaxel present “serious challenges” for the trialists. Speaking from the floor, Bradbury further argued that a distinction “must be made” between claudicants and CLI patients as the risk profile varies drastically between the two. “For claudicants, treatment is about enabling the patient to walk further.” With CLI, Bradbury added, “the risk

A distinction must be made between claudicant patients and critical limb ischaemia patients, as the risk profile varies drastically between the two.” weigh-up” instead hinges on improving quality of life in end-stage peripheral arterial disease, for which effective treatment may be worth a potential increased late mortality risk.

Responding directly to Bradbury’s comments concerning CLI, Zeller noted that teasing out an association of increased mortality would be more difficult in a CLI patient cohort, due to the “higher background noise” caused from greater overall mortality rate in this patient population compared to less ill patients. Bradbury further said “we cannot assume that Katsanos’ findings

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6

June

While CX audience deems paclitaxel not dangerous, vascular pathologist says establishing “truth takes time” Continued from page 4

apply to CLI patients.” Expressing his personal view, he told attendees that the BASIL and SWEDEPAD trials “represent a unique opportunity to settle the question with regard to CLI”. Indeed, speaking to this point, US FDA representative Misti Malone (Silverspring, USA) suggested that regulatory bodies may be able to make such a distinction between claudication and CLI, and pointed out that the FDA has currently not recommended the halting of paclitaxel trials.

Following the talks from Falkenberg and Michaels, CX delegates responded to the question, “Do you agree with BASIL-3 and SWEDEPAD to recommend stop using paclitaxel products at this moment?”, with a slight majority of 52% in agreement. A similar split was seen again as 53% voted for the motion “Do you suspect that the finding of Dr Katsanos is correct?”.

The methodology and statistical validity of the metaanalysis outcomes were comprehensively described by statisticians and regulatory authorities. Overview of the meta-analysis’ statistical analysis was provided

by Jon Deeks (Birmingham, UK), statistician of the BASIL-3 trial, and Sue Duval (Minneapolis, USA), one of the two independent, academic statistical advisors to the VIVA independent patient data (IPD) review.

Deeks suggested that many of the studies used in the meta-analysis by Katsanos et al were “inadequate” in terms of the raw data, and that the reporting of the trials was “suboptimal”. However, Deeks acknowledged “statisticians are never satisfied with the data”. Polling following this statistical discussion showed a slight shifting in favour of believing that there is statistical evidence currently indicating a real increased mortality from the use of paclitaxel on a balance of probabilities: 57% to 43%.

Malone gave the FDA position, and announced the IPD review panel to take place on 19–20 June this year.

Hazel Randall (London, UK) of the UK Medicines and Healthcare products Regulatory Agency (MHRA) relayed the working process of the expert advisory group created last month, which is due to release its final recommendations for paclitaxel use “in the next few weeks”. Both regulatory bodies received considerable support from audience polling, with 68% believing the authorities were “reacting appropriately”. This result was quite decisive in comparison to the less unifying answers of previous polling.

Lessons from the paclitaxel pioneers and other disciplines

CX delegates heard from Ulrich Speck (Berlin, Germany), who spoke of his early work to enable the drug to coat the balloon, resulting in the plethora of devices available today. It was evident from Speck’s account that from the outset, the cell-killing effects of paclitaxel were

known. “Of all the drugs tested in the swine model, none were as effective as paclitaxel,” Speck stated.

Speaking on the pharmacokinetics of paclitaxel, Lindsay Machan (Vancouver, Canada) gave a description of the early application to stents, which was incorporated to address the issue of in-stent restenosis. The choice of paclitaxel was reliant upon its observed “powerful” ability to inhibit cytokine-induced migration of cartilaginous cells, which Machan explained cannot grow when more than 2mm away from a capillary.

Providing an oncological perspective, Erica Mayer (Boston, USA) detailed the use of paclitaxel as a primary therapy in cancer care. Notably, Mayer referred to paclitaxel as “one of our most commonly used treatments” in breast cancer patients, and even reported its safe, effective use in the second and third trimester of pregnancy. “We think it is safe enough to give to

controversy over a decade ago, in which a potential association with increased mortality was discussed for paclitaxel in the coronary arteries, Scheller said this 2006 “firestorm” is the “perfect blueprint” for the current paclitaxel debate. Ultimately, however, Scheller reported that the coronary community concluded that the stent design and coating technology is “more important” than drug selection in these arteries, and drug-eluting devices are in continued use.

Commenting on these lessons, Greenhalgh summarised that even though the early users of paclitaxel were “fully aware that the drug was cytotoxic, it has been used in oncology since”, iterating that its use in vascular applications was “always known to damage the artery wall in some way, which discouraged the restenosis process”.

At this stage, 85% of the audience agreed with this sentiment, answering the poll: “Do you think that those who used paclitaxel in the early days were quite aware that paclitaxel kills cells?”. A follow-up question elaborated: “If you accept that the pioneers knew that paclitaxel would kill cells, do you think that they always aimed to have a balance between achieving less restenosis in the patients’ interest without increasing mortality?”. The result of this query was 72% in favour, capturing the audience support for the idea that there may exist a trade-off in the use of

On the one hand, paclitaxel contributes to greater patency in the lower limbs, but on the other hand, there is an alleged increase in death.” our pregnant patients”, Mayer told the CX audience.

Furthermore, she pointed to the significant difference in dosing: a higher-dose drug-coated balloon reportedly providing 0.55% of an average dose given in a weekly breast cancer regimen over 12 weeks.

Finally, Bruno Scheller (Homburg/Saar, Germany) outlined the lessons learned from paclitaxel use in coronary arteries, comparing the drug to its alternatives, sirolimus and everolimus. Referring to a similar

BIOPACT-RCT to compare drugcoated balloons in head-to-head

The BIOPACT randomised controlled trial (RCT) will compare the safety and efficacy of the Passeo-18 Lux drug-coated balloon (Biotronik) versus Medtronic’s IN.PACT Admiral.

THE TRIAL WILL will be led by Koen Deloose (AZ Sint-Blasius Hospital, Dendermonde, Belgium) as principle investigator, and plans to enrol up to 302 patients across multiple European centres.

BIOPACT-RCT has received approval to being enrolled at several sites in Belgium, and expects further

Issue

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Paclitaxel-eluting devices

approval for sites in Switzerland, Austria and France.

Patients included will have a Rutherford classification of 2–4, with a maximum lesion length of 18cm in the femoropopliteal arteries, and will be randomised 1:1 for treatment with either the Passeo-18 Lux or IN.PACT Admiral drug-coated balloon (DCB).

paclitaxel. “On the one hand,” Greenhalgh summarises, “paclitaxel contributes to greater patency in the lower limbs, but on the other hand, there is an alleged increase in death.” Extensive discussion followed on whether there exists a causative action as the drug circulates within the body, or whether this is “merely an association”. Overall, there was near unanimous support from speakers, audience and the regulatory bodies on the position that while an association may exist, further investigation is required.

In a press release, Deloose comments: “Although we have already a lot of safety and efficacy data available on the Passeo-18 Lux through the BIOLUX P-I, P-II and the ongoing BIOLUXP-III trial, a more in depth, head-to-head comparison with today’s market leading DCB will offer more answers about the relative performance of DCBs and potential class effects—especially related to the ongoing debate on DCBs safety concerning a signal of increased longterm mortality with paclitaxel-coated devices, based on the publication of Katsanos et al in the Journal of the American Heart Association, and the FDA- and CIRSE-statements about additional patient level data, also in the longer run, are essential.”

8

June

Issue

19 82

Abdominal aortic aneurysm guidelines

EVAR funding threatened, while strategy for safe, cost-effective repair is “just around the corner” Continued from page 1

against the NICE committee’s proposed recommendations.

Explaining how the clinical guidelines committee had arrived at these conclusions, Bradbury outlined the strict decision-making pathways laid out

by NICE for its advisory committees.

These, he stated, ensure that long-term, randomised controlled trial data—and UK-based data in particular—are favoured over other evidence, with the reasoning that this implies the data are more directly applicable to an NHS setting. It was this principle that made the EVAR 1 and EVAR 2 trials a major contributing resource for the clinical guidelines committee, with its significant 15 years of long-term follow-up of abdominal aortic aneurysm patients.

EVAR 1 compared endovascular repair to open repair of abdominal aneurysms in patients who were fit for open surgery. At the time of enrolment for this trial, in the 1990s, EVAR provided a novel treatment option for these patients, and although the technology was in its early stages, the vascular community was increasingly appreciating the potential of a minimally invasive treatment for patients who were unfit for open surgery. At 30 days, EVAR 1 showed that endovascular repair resulted in an early superiority over open repair. This superiority was maintained for over six years, as observed in longterm follow-up, but results thereafter started to suggest the trend could be going against EVAR. At 10-year followup and beyond, this suspicion was confirmed, reporting late catch-up in mortality for the EVAR arm. Outlining the issues of this early endovascular trial at the CX Highlight Session, Fiona Rohlffs (Hamburg, Germany) described how EVAR fell behind, due to aneurysmrelated and all-cause mortality—mainly due to secondary sac rupture, from which two of every three patients would die.

“We see that of course initially there was a benefit for EVAR, but EVAR compared inferiorly to open surgery during followup—especially in the period after eight years. The cause of this was mortality from secondary rupture in this group,” said Rohlffs.

A panel at the CX Highlight Session, which included Roger Greenhalgh, Rohlffs, Maarit Venermo (Helsinki, Finland), Lois Kim (Cambridge, UK) and David Epstein (Granada, Spain), who together presented new analyses based on the EVAR trials and a current series experience by Venermo in Helsinki, then highlighted a key issue with the long-term EVAR data. It was identified that post-EVAR surveillance in terms of follow-up protocol had fallen short, described by Greenhalgh and by Venermo as “suboptimal”. “In EVAR 1, patients failed to turn up for their follow-up appointments,” explained Greenhalgh, “and this is the main reason why

reintervention was not performed.” The failure of follow-up ultimately led to the “inevitable outcome”, that EVAR was not cost-effective based on the protocol and practices of 1999–2004 data.

Presenting more recent EVAR practice data from 2010–2011, Greenhalgh noted, that a predisposition of certain patients to rupture was identified in a “cluster”. This cluster held a range of issues, including type I endoleak and type II endoleak with sac expansion, migration and kinking of the stent graft. Importantly, Rohlffs pointed to Wyss et al, who showed in 2010 that most patients had sac expansion before rupture of the aneurysm sac. Nevertheless, though centres were reportedly warned of the risks following EVAR, many patients failed to adhere to surveillance protocols and were lost to follow-up.

Indeed, Rohlffs showed that the initial 90% follow-up retention in the first six months of EVAR 1 had dropped to only 10% of all survivors at nine years.

Underlining that this problem is not restricted merely to the UK, Venermo presented similar numbers from her data, showing a 90% follow-up in the first six months, which dropped to 40% of survivors in its ninth year. “You can see this situation in the Finnish series, as only 40% at nine years came back for annual CT scan,” Venermo said, “and this is for many reasons: it is because of a lacking engagement of the patients with the surveillance, but also sometimes it is a certain decision of the patient.”

Therefore, in collaboration with a statistical team led by Michael Sweeting (Cambridge, UK), a discrete event simulation predictive model was produced by Kim, in order to model alternative outcomes of follow-up scenarios. The scenarios supposed a range of follow-up strategies, including a scenario assuming “perfect follow-up” in the EVAR trials, and application of various guidelines for follow-up, such as those of the European Society for Vascular Surgery (ESVS). A fifth option was to curtail follow-up at five years, and simulate the recommended protocol, as recently proposed by NICE. A final scenario assumed a novel strategy, based on the 2018 study of Grootes et al in the British Journal of Surgery, which examined the risk of rupture and rupturepreventing reinterventions following endovascular abdominal aortic aneurysm repair. A co-author of this study, Venermo commented: “We tried to figure out if it was possible to predict rupturepreventing interventions and secondary sac ruptures on the basis of sac diameter and changes in diameter.”

Venermo showed a series of trajectories, which outlined sac diameter over time of follow-up, grouped by type of event. These trajectories of annual sac diameter change were first described by

Maarit Venermo

Sweeting. For patients in whom there was no rupture nor any rupture-preventing reinterventions, Venermo showed that, for the EVAR trials as well as in the Helsinki cohort, “we can see a decreasing trend in sac diameter.” For patients who underwent rupture-preventing reintervention with no subsequent rupture during a 10-year follow-up, he said: “Actually, the sac diameter decreased or increased slightly but, in the end, it remained pretty much the same.” Finally, for patients who experienced a secondary sac rupture, the trajectories showed a “clearly increasing trend in maximum sac diameter.”

I think we can all agree that we need lifelong surveillance after EVAR—but it has to be patient-friendly, simple and safe.”

Venermo summarised in accordance with her colleagues, saying, “Indeed, current EVAR follow-up protocols are suboptimal. It is too heavy, it is expensive and patients do not follow or engage with it. I think we can all agree that we need lifelong surveillance after EVAR—but it has to be patient-friendly, simple and safe.” Greenhalgh further highlighted that sac expansion, “with great accuracy, was a prediction of imminent secondary sac rupture occurrence within two years.”

The group then took the next step from these findings, and established whether recent advances in technology may have presented new potentials for alternative and more flexible, yet reliable, follow-up and surveillance protocols. They worked on the assumption that sac diameter would be able to be monitored at home, by the patient, in the community— thereby dispensing of the need for a visit

to the hospital to undergo an annual CT scan. It was argued by the panel that this would present a patient-friendly option, and Greenhalgh subsequently presented the audience with a hand-held device that could perform this task: a mobile, light-weight device which could be used by the patients themselves—in combination with a smartphone—to perform a Doppler ultrasound scan of the aortic diameter. This, Greenhalgh said, is a technology that will come to “revolutionise” aneurysm care.

The use of a hand-held monitor, to increase follow-up retention and perform rupture-preventing reinterventions in patients whose aneurysm sac had been identified to be at risk of rupture, was then incorporated as a factor in the novel proposed surveillance strategy.

Health economist Epstein concluded from the panel that the novel strategy, as analysed by Kim in a discrete event simulation, presented “not the most clinically effective,” but rather “the most clinically effective option at a cost that is affordable within the context of the NHS”. As such, the findings of this multi-disciplinary group respond directly to the claim of the NICE aortic guidelines that reverting back to open repair and restricting EVAR funding presents lower cost per quality-adjusted year. “Now,” Greenhalgh maintained, “it is necessary to show that this simulated event can be created in the real world—using a simple and mobile device in combination with a smartphone.”

Polling at the close of the session revealed that the CX audience agreed, with 82% responding they believe that “By tracking sac growth after EVAR, EVAR will be more clinically effective and at lower cost than occurred in the EVAR trials”. Throughout this CX Highlight Session, signals were sent to the vascular community not to withhold EVAR when “around the corner,” Greenhalgh said, “is a cost-effective way of ensuring EVAR can be performed with long-term safety, with more patienttailored methods.”

10

June

Vascular recruitment a “universal problem”: The global perspective Across the globe, vascular recruitment is struggling. This was the reason why delegates convened for a Charing Cross Symposium (CX; 15–18 April, London, UK) Highlight Session dedicated to the topic, where representatives from three continents explained exactly how and why the vascular specialty is experiencing this decline in physician numbers, and what the international community can do about it.

T

revor Cleveland, president of the British Society of Interventional Radiology (BSIR) and the session chair, summarised the key takeaways from the afternoon’s discussion to Vascular News: “Everybody recognises recruitment is a problem. There is a lack of exposure of students and trainees to vascular procedures early on; if you show them what you are doing, they get enthused by it and stay on. Getting that exposure in medical students and junior doctors is crucial. Also, the reality of it is that we have an ageing population of operators, who we are going to lose quite a lot of—so we have a numbers problem.

There is a problem getting people in; there is a problem with the numbers going out. Then there is also a difficulty with those doing it having an unenviable work-life balance.”

Hans-Henning Eckstein (Munich, Germany) kicked off the session by outlining ways in which medical students can be attracted to vascular surgery.

He said that vascular specialists need to target medical students earlier on in their undergraduate years, pointing to the declining attractiveness of vascular surgery between the first year

Issue

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Vascular surgery workforce

of medical school (where 34.4% said they would be interested in a vascular career) and the last (where this figure was 15.5%). One reason for this, he explained, is a generational difference in attitude to work. Eckstein pointed to the work-life balance of vascular surgeons, saying that potential recruits possibly believe the specialty would “require too many sacrifices” from them. In addition to lifestyle issues, he told the CX audience to “keep in mind that currently, approximately 70% of all medical students are female”, saying that the stereotypical image of surgery as a masculine discipline had to be changed.

Providing an overview of vascular recruitment in Europe, European Society for Vascular Surgery (ESVS) president Henrik Sillesen (Copenhagen, Denmark) voiced many of the same concerns.

“Vascular recruitment is not as easy as it used to be” he remarked. “It is still OK for big university centres, but it is certainly challenging outside those, in smaller, more rural centres”. He went on to say that the training is “regulated in several [European] countries to a point that is ridiculous”. He then detailed educational, organisational, economic

Sophie Renton

and personal factors which are affecting vascular recruitment, such as whether or not the specialty is housed in its own department, or if it pays well. One of the more important educational factors, he said, was whether or not the students would have the opportunity to learn endovascular techniques in the vascular department—Cleveland returned to this point later on to say that overall, the older generation of vascular surgeons are those providing the open procedures. As they retire, the newer generation are less

There is a lack of exposure of students and trainees to vascular procedures early on.” confident in those procedures, a point made by European Board of Vascular Surgery (EBVS) president Armando Mansilha (Porto, Portugal) when he reviewed the reasons why candidates are not successful in the EBVS exam.

To improve recruitment, Sillesen said, “it is important to create a good working environment, with reasonable hours and vacation time”. He called attention to the six weeks’ paid leave offered to physicians in Northern Europe, and that institutions should provide “good opportunities for education, research and travel”.

Michel Makaroun (Pittsburgh, USA), Society of Vascular Surgery (SVS) president, stepped up to the podium to provide the North American angle. He agreed with previous speakers concerning the dearth of future vascular surgeons, calling it a “universal problem”. The two “major problems” in vascular recruitment in the USA, he said, were a significant shortage of vascular surgeons and the maldistribution of workforce.

To the latter point, he echoed Sillesen’s sentiments, saying that vascular specialists were concentrated in urban

Coil embolisation improves EVAR results for high-risk patients

Coil embolisation for at-risk patients during endovascular aneurysm repair (EVAR) is a safe and reproducible procedure. This was the conclusion of Dominique Fabre (Le Plessis Robinson, France) in a presentation at the Charing Cross Symposium (CX; 15–18 April, London, UK).

FABRE PRESENTED THE results of the prospective, dual centre, randomised, comparative and open SCOPE 1 (sac embolisation per EVAR) study, for which he is the principal investigator, concluding that the procedure was statistically effective in terms of decreasing the number of

areas. An SVS survey in 2017 found that only 6% of respondents practice in a rural setting, defined as having a population of fewer than 100,000. “The vascular specialty has the highest anticipated need of all specialities, but we are not producing enough vascular surgeons to get a significant increase in numbers,” Makaroun told attendees. Currently, 42% of US vascular surgeons are over the age of 55, and “the majority are trying to retire as soon as possible”, Makaroun said. He added that current training pathways in the USA are “not adequate to address the issues”, but that a task force on alternate pathways is studying the problem.

Alberto Muñoz (Bogotá, Colombia), president of the World Federation of Vascular Societies (WFVS), provided the South American perspective on training pathways: “We have training programmes in most of our countries, and it is important to note that in most of the countries, general surgery training is

endoleaks at one and six months.

The study investigators set out to compare the effect of coil embolisation when added to endovascular aneurysm repair, splitting 91 patients into two groups: those treated with EVAR alone (45 patients), and those treated with EVAR and coils

required. We have issues with migration, as in some countries it is mandatory to have general surgery certification.”

Following the SVS 2018 annual meeting (20–23 June, Boston, USA), where it was reported that the USA had 1.4 vascular surgeons per 100,000 people, the WFVS decided to carry out their own investigation. According to their calculations, across the entirety of South America, there is an average of one vascular surgeon per 94,793 people.

However, there have been no studies, Muñoz said, evaluating the expected need for vascular surgeons in the region.

Mansilha told the CX audience that, for EBVS, it was crucial to have “European standards of training and education for vascular surgery”. At CX on Monday, the EBVS announced the approval of a document delineating their training programme and its requirements, which Mansilha outlined. He stressed his belief in the importance of having a standard, European exam for vascular surgeons “not only for prestige, but also to consider the minimal requirements in Europe to facilitate the free exchange” of physicians.

(46 patients).

No complications, spinal cord ischaemia, colonic ischaemia or migration were observed in either group, and Fabre reported a 100% success rate.

For all time points (one, six, 12 and 24 months), the number of endoleaks was lower in the cohort treated with EVAR and coils than those treated with EVAR alone, leading the triallists to conclude that freedom from endoleak was significantly improved by the addition of coil embolisation. The total number of reinterventions was also lower with coil embolisation: 10% compared to 18%.

Fabre advised the CX delegates that coil embolisation for high risk patients must be discussed for each EVAR case “to improve the postoperative and mid-term results”.

12

June

Issue

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Thoracic endovascular aortic repair

Design of Valiant Navion “improves upon current-generation TEVAR” Reporting 30-day clinical results of the complete Valiant Navion (Medtronic) cohort, Fabio Verzini (Turin, Italy) told delegates at the Charing Cross Symposium (CX, 15–18 April, London, UK) that the acute performance results for the thoracic endovascular aortic repair (TEVAR) device are encouraging, with no access or deployment failures in tortuous anatomy. According to Verzini, the benefit provided by Valiant Navion is an improved design compared with current-generation TEVAR devices.

VERZINI EXPLAINED THAT the Valiant Navion system was designed to address the challenges of current-generation TEVAR devices, such as a need to “reduce movement and manipulations in the arch, enhance conformability/apposition to complex anatomy, expand stent graft configuration options, and have a lower crossing profile to expand patient applicability”.

Therefore, Valiant Navion has a low-profile delivery system (to expand patient applicability), broader size options (to tailor treatment to a patient’s anatomy), and is flexible and conformable to enhance the seal.

Additionally, the device is available in two configurations: “FreeFlo”, which has a 2cm landing zone, allows perfusion into the proximal vessels, and a tip-capture mechanism; and “CoveredSeal”, which has a 2.5cm landing zone, is designed to completely cover the proximal end, and (like the FreeFlo configuration) has a tip-capture mechanism.

In the study, 100 patients, 40 of whom were women, underwent TEVAR with the device. Of these, 73.7% had high access artery tortuosity and 86.5% had high thoracic aorta tortuosity. Furthermore, the mean fluoroscopy time was 12.1±9 minutes—which Verizni said was “very short”—and 49% of patients received percutaneous access. There were no access or deployment failures.

The rate of perioperative mortality was 2%, the endoleak rate was 4.3%, and the rate of secondary

procedures was 2%. Verizni commented that the 30-day rate of major adverse events was 27% but this was “in the expected range” for TEVAR and there were no major, disabling, neurological events. Of the minor strokes that did occur (two hemispheric strokes and two posterior strokes), all were resolved (with antiplatelet therapy where appropriate).

Summing up his presentation, Verzini stated that “Valiant Navion’s design improves upon current generation TEVAR,”. He added: “The acute performance is encouraging; there were no access or deployment failures, procedure and fluoroscopy times were low, and endoleaks were rare with low rates of secondary procedures.”

The Valiant Navion is both US Food and Drug Administration (FDA) and CE mark approved for all lesions of the descending thoracic aorta: aneurysms, dissections, transections, aortic intramural haematoma, and penetrating aortic ulcers.

There were no access or deployment failures, and endoleaks were rare.”

Fabio Verzini

Live case of challenging thoracic endovascular repair demonstrated using virtual reality at CX

Tilo Kölbel’s team, led on-site in Hamburg, Germany, by Giuseppe Panuccio, successfully performed a thoracic endovascular aortic repair (TEVAR) on a 77-year-old female patient with American Stroke Association (ASA) class III, and multiple aortic aneurysm disease with multiple aneurysms. The live case was viewed by delegates at the Charing Cross Symposium (CX; 15–18 April, London, UK) with virtual reality 360° video.

T

he introduction of this visual presentation allowed Kölbel to control the angle and direction of the camera from his seat on the moderating panel at CX, with the ability to show the audience each corner of the operating room in real time. Through discussion of the planning and technique, the procedure demonstrated best practice for minimising stroke from TEVAR. “In the aortic arch,” the operators noted, “the thoracic aortic aneurysm is approximately 5cm, and the additional abdominal aortic aneurysm is approximately 4cm.” The team planned the technical procedure to use a twocomponent Valiant Navion (Medtronic) endograft for the thoracic aneurysm, covering 286mm of aortic arch. “We have a difficult access, because the access vessels are compressed on both sides, so

we decided to get our main access on the right side due to the patient’s urostomy and femoral distal bypass on the left side,” they explained, adding that the patient had high-grade stenosis of the right internal iliac artery. As operators had determined the patient was at high risk for spinal cord ischaemia, she received cerebrospinal fluid drainage pre-procedurally, “and we are planning on treating her internal iliac stenosis on the right side.”

The flexibility of the 360° camera allowed for a degree of virtual reality, as viewers were immersed into the Hamburg operating room. Kölbel turned the camera to show the preparative work, as operators and assistants assembled their tools.

Importantly, as pointed out by Kölbel, flushing of the device with CO2 was performed for two minutes, followed by standard saline flushing. This technique

has been highlighted by the Stroke from Thoracic Endovascular Procedures (STEP) study collaborators as a preventative measure to reduce risk of stroke from air embolisation. Chairing the session, Roger Greenhalgh similarly commented “it is important to note that every effort is now being made to exclude air from the system before devices are put into the patient—as that itself can be the cause of stroke by air blockage.” This is a finding presented

by Kölbel and Fiona Rohlffs (Hamburg, Germany) at last year’s CX. Panucci and the rest of Kölbel’s team swiftly and successfully completed the aortic arch repair, deploying both devices in their planned landing zones. Stéphan Haulon (Le Plessis-Robinson, France), co-moderating from the panel, pointed to the importance of large overlaps between multiple devices in this type of procedure.

“This is routine now, but a bit different to what we were doing ten or fifteen years ago”, Haulon said. In aneurysmal disease, it has been learned that the diseased aorta will grow not only in diameter, but will continue to grow over time in length as well, as Kölbel commented: “So you need some additional length in order to avoid device separation: when we can, we plan at least three stents’ overlap.” Greenhalgh further added that this is a “very important matter: the anatomy and the dimensions at the time of deployment are not necessarily the dimensions in the follow-up period, and what fits perfectly in the beginning may not always stay that way.” The use of monitoring for these patients is thus significant to ensure long-term durability.

“This is an illustration of how to get the best results, and what the experts are saying”, Greenhalgh concluded.

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Multicentre dataset reveals the added value of diffusionweighted imaging in TEVAR practice

Thoracic endovascular aortic repair

Novel data from the Stroke from Thoracic Endovascular Procedures (STEP) study have provided insight into current practice of thoracic endovascular aortic repair (TEVAR), and the future role of diffusion-weighted magnetic resonance imaging (DW-MRI) in reducing stroke from endovascular repair.

The STEP multicentre dataset was presented in a Charing Cross (CX) Highlight Session, chaired by study investigator Roger Greenhalgh, and featuring a panel of moderators involved with the study— including Tilo Kölbel (Hamburg, Germany), Stéphan Haulon (Le Plessis-Robinson, France), Fiona Rohlffs (Hamburg, Germany), Hugh Markus (Cambridge, UK), Heinz Jakob (Essen, Germany) and Gustavo Oderich (Rochester, USA).

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aking a collaborative approach to investigating stroke risks associated with thoracic aortic repair, STEP is an independent, allencompassing, open and interdisciplinary study aiming to provide best practice for endovascular procedures, ultimately lowering the risk of cerebral embolism.

The STEP investigators have reported that “currently, better evaluation is needed” in terms of cerebral infarction and cognitive function after performing thoracic endovascular procedures. “There should be a better way to quantify what happens to the brain from cerebral infarction, embolism, haemorrhage and even thrombus,” Rohlffs said in an introduction of the session at CX. For this reason, she explained, the STEP collaborators worked to pool experience from participating centres in the USA and Europe.

Summarising the major conclusions presented last year at CX, Rohlffs stated that with the pooled experience and multidisciplinary guidance from specialists in neurology, interventional

STEP collaborators panel

cardiology, cardiothoracic surgery and neuroradiology, “we learned that imaging is a crucial tool for us to evaluate stroke after the procedure, as well as silent brain lesions that can occur after TEVAR.” The main aim of STEP, noted Greenhalgh, is to investigate “what infarctions there are, the type of infarctions after the procedure, and whether surgical technique can improve”.

It was highlighted that, as surgeons trying to recognise clinical stroke may underdiagnose this condition, the potential value of introducing DW-MRI was evaluated in phase two of the STEP collaboration.

This potential value, the panel explained, lies in the ability of DW-MRI to recognise whether a lesion appearing in follow-up imaging is associated with the procedure itself, while also providing a means to monitor the outcome and improvement in the long-term. From the panel, Markus noted that what is “really exciting” about DW-MRI in this area, is clear “when looking at it for improving surgical endovascular technique”.

We should press upon the funding bodies of our hospitals and institutions, that [thoracic endovascular aortic] procedures should include funded DW-MRI.” Among the STEP operators, three centres (Hamburg, Germany; Paris, France; and the MayoClinic, USA) were able to provide new data on the use of DW-MRI post-TEVAR procedures, involving zone 0, 1, 2 and 3 of the aortic arch. The total series of 37 cases combined from these centres presents the “largest global experience” to date, Greenhalgh noted.

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According to Kölbel, “the biggest difference to what is already known is that these cases include a large number of very proximal landings—with a significant zone 0 and zone 1 percentage.

It is important that MRI is done within a certain post-procedural time frame, and we were able to keep to the range of two to eight days, with the exception of only one patient.” He added, this suggested time frame of up to eight days was established with advice from Markus.

Haulon expanded on the finding that a high proportion of cases were performed in the most proximal landing zones: “What was interesting about this dataset was that in less than three months, we managed to gather over 20 cases with proximal landing in zone 0 and 1, equating to almost 60% of the entire cohort.”

A second unanticipated result was the key finding that, while new lesions were seen on DW-MRI in 80% of zone 0 cases, “63% of zone 3 patients were found to have new lesions on DW-MRI”, Haulon highlighted. These new lesions were seen despite the investigators’ use of preventative measures, including carotid clamping and, notably, CO2 flushing of the device systems before the standard saline flush. The latter technique was introduced by Kölbel and Rohlffs, whose work suggests the CO2 flush of stent grafts may help reduce air embolisation during TEVAR. However, through a survey of collaborators regarding current practice, the limitation for DW-MRI funding was brought to light, as the majority of centres were unable to make use of the imaging modality. “We found that in the US centres where STEP collaborators operate, they cannot get funding for DW-MRI,” Greenhalgh explained.

“However, perhaps the institutions could be persuaded, that if they perform this scan in the postoperative period, it can be recognised whether infarcts seen on imaging were present prior to the procedure.” As a result, an argument for funding could be made, as centres could distinguish between procedurally associated harm and pre-existing lesions.

Nevertheless, Markus warned that despite the “interesting findings” of the study and potential for DW-MRI to improve endovascular practice, “it remains important to have cognitive testing, to determine the impact thoracic endovascular repair may have on the patient.” This was elaborated on by Greenhalgh, who pointed to the fact that “some cognitive symptoms of neural damage may appear, even without visible DW-MRI lesions.”

Both Markus and Greenhalgh remarked that future investigation will require a larger number of patients—both for improved understanding of the value of DW-MRI and current TEVAR practice, as well as to ensure adequate power in the analysis of cognitive testing data.

Concluding the session, Greenhalgh argued: “DW-MRI should be a standard of care—by which I mean that whether open or endovascular, we should press upon the funding bodies of our hospitals and institutions, that the procedures should include funded DW-MRI.”

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Study argues ambulatory officebased treatment is possible for high-risk patients

risk. The risk factors analysed were age ≥80 years old, serum creatinine ≥2mg/dL or end-stage renal disease, ejection fraction (EF) ≤39%, and American Society of Anaesthesiologists (ASA) classification of 3 and 4.

For patients who were ≥80 years old, the reintervention rate at one year was 21% vs. 38% in the

younger group (p=0.04). Of these, 18% were officebased and 1.4% were hospital-based for older patients, compared to 29% office-based (p=0.03) and 4% hospital-based reinterventions (p=0.18) among those of a younger age. No patients required a bypass.

A comparison between those with renal impairment and those with adequate renal function found a reintervention rate of 12% among high-risk patients, and 36% in the lower-risk group (p=0.01). All patients at higher risk had the repeat procedure performed in hospital, while only 4% of patients with adequate renal function were hospital-based (p=0.21); 14 of the 297 reinterventions in the low-risk group required a bypass.

Reintervention rates for patients with impaired cardiac function—defined as an EF ≤39%—was 31% compared to those with adequate function at 34% (p=0.44). Only one of five reinterventions was office-based for those with impaired cardiac function, versus 84 of 105 cases among lower-risk patients (p=0.22). Two patients with EF ≤39% had a bypass vs. 12 of those with EF function ≥39%.

Outcomes for patients with an ASA classification of 3 and 4 were compared to those with a classification of 2, and showed a reintervention rate of 12% among those at higher risk vs. 34% among the lower-risk group (p=0.44). Numbers of bypasses were the same in each group as for those among the high and low-risk cardiac function patients. The mortality rate was zero and there were no major amputations among any of the groups selected for comparison.

Limitations of the data analysis were that it was retrospective and single-centre, and based on a single surgeon performing >15,000 endovascular arterial procedures. However, Ascher concluded: “Appropriately selected high-risk patients can benefit from office-based endovascular arterial procedures,” adding, “ideally, office-based arterial endovascular procedures in highrisk patients should be further validated by a large multicentre prospective randomised study.”

the USA as “amazing”. In France, the rate of ambulatory treatment for peripheral arterial disease (PAD) using endovascular repair was about 11% in 2018. In the UK, almost 30% of procedures for the same indications are performed in an outpatient setting.

European guidelines, in place since 2003, recommend overnight observation after a percutaneous transluminal angioplasty (PTA) procedure. The French Society of Vascular and Endovascular Surgery (SCVE) in 2019 released the first guidelines for outpatient management in France, providing help to physicians on how to deal with legal issues. Concerns about how to deal with complications is one of the issues that may be Yann Gouëffic affecting the development of outpatient endovascular intervention, he suggested. Other factors are economic and clinical.

Economic factors, he said, may be related to regulatory issues, but also to the need to demonstrate societal cost-effectiveness. Clinical issues relate to the need to demonstrate the safety and efficiency of ambulatory management, the benefits of different devices, and whether it is possible to perform manual compression.

Gouëffic said: “Further evidence is required to ensure the clinical, legal, and medical economic value of outpatient management.” He described three trials that are aiming to do so.

One, the Freedom registry, has been set up to demonstrate the feasibility of same-day discharge after manual puncture point compression in patients treated for PAD by endovascular technique with a 5F sheath femoral

approach. So far, 111 of the 150 patients to be included in the trial have been recruited.

A second, the STEP study, is a randomised trial comparing two arterial devices to assess their value in outpatient management.

At the time of the presentation, only one patient remained to be enrolled, with 229 of the required 230 patients already recruited.

Gouëffic also outlined details of a medical economics study, the AMBUVASC trial, which has finished recruiting patients. This is a French multicentre randomised controlled trial to evaluate the efficiency of outpatient versus hospital PAD intervention.

“We have no medical economic study available to assess the cost-efficiency of outpatient [treatment]. The objective of AMBUVASC is to compare the utility cost of conventional hospitalisation versus ambulatory hospitalisation using an arterial closure device.”

The primary endpoint of the study is the incremental cost-effective ratio (ICER). This describes the extra cost per one additional unit of patient outcome, and consists of a cost utility and a cost-effectiveness analysis. Quality adjusted life years (QALYs) are also used to measure ICER. Secondary endpoints include safety, complication rates, functional improvements, and time taken to return to employment.

A vote at the end of the audience discussion that followed indicated that 63% among the audience would recommend ambulatory treatment for their own patients with PAD.

Office-based lower extremity arterial interventions are feasible, safe, and cost-effective, and provide high levels of patient satisfaction. Enrico Ascher (Brooklyn, USA) presented data that “challenge the dogma that high-risk patients should not be offered office-based endovascular infrainguinal arterial procedures”. He was providing a US perspective on ambulatory interventions at CX Symposium 2019.

ASCHER CITED STUDIES that show patient satisfaction levels with outpatient care of 99%, and listed its other advantages as improved physician efficiency, due to multitasking, better reimbursement levels, and increased independence for practitioners because hospital administrators are “cut out of the equation”.

He also highlighted his own data series, collected from 2014–2018 and based on 8,336 cases. There were no procedure-related deaths, and only one case required an emergency transfer. The complication rate was 1.3%, and death rate at one month was 0.15%. Among the patients excluded were those who weighed >180kg, had advanced chronic obstructive pulmonary disease (COPD) or disabling spine stenosis (and therefore could not remain supine), as well as unstable psychiatric patients.

From 2014–2018, there were 576 arterial interventions, with zero cases of embolisation, retroperitoneal bleed, and acute stenosis, and six cases of puncture site stenosis.

A review of the arterial patient selection criteria revealed that lesion type or location did not play a factor in patient selection, and that eligible patients were given

Europe needs guidelines for outpatient endovascular repair European guidelines should do more to promote the use of ambulatory endovascular peripheral interventions and to support physicians wishing to set up an outpatient centre, said Yann Gouëffic (Nantes, France) at the Charing Cross Symposium (CX; 15–18 April, London, UK).

“D

RGs [device-related guidelines] should be revised to promote outpatient [care], and guidelines should be released to help vascular interventionalists to organise their practice in the most appropriate and safe conditions,” he said. And he echoed Enrico Ascher’s conclusions, pointing out: “Outpatient management is safe and efficient. We know that it works.”

Gouëffic presented the European perspective on how ambulatory treatments are moving on in the field of arterial disease, outlining how practice differs across different European nations, “according to the type of DRG in each country, and according to the type of vascular interventionalist”.

He described the growth of office-led intervention in

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Endovascular procedures

a choice to have their procedure done in the office or in the hospital. Arko pointed out: “You would think that we would select patients with easy lesions, but that was not true.”

The data were then further evaluated by comparing findings in high-risk patients with those of more average

[These] procedures in high-risk patients should be further validated by a large multicentre prospective randomised study.”

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Medical therapy

ACTION trial finds ACT-guided heparinisation increases patient safety Implementing a method of heparinisation guided by activated clotting time (ACT), with a goal of 200–220 seconds, provides a “promising” increase in safety and may decrease risk of thromboembolic events, while not increasing bleeding complications. Presenting the findings of the pilot ACTION trial, Arno Wiersema (Hoorn and Amsterdam, The Netherlands) stated he and his colleagues “believe it is time to upgrade one of the foundations of vascular surgery to optimise patient care and to prove that ACT-guided heparinisation results in far fewer thromboembolic complications.”

“T

he success of open and endovascular arterial interventions depends on a delicate balance between coagulation and anticoagulation”, said Wiersema at the Charing Cross Symposium (CX; 15–18 April, London, UK).

“Ever since its introduction in clinical practice 70 years ago, unfractionated heparin has been administered during these non-cardiac arterial procedures to prevent thromboembolic complications.

A major disadvantage of this use of heparin is that it could increase bleeding complications, as extensive surveys have shown that almost all vascular surgeons and interventional radiologists use a standardised bolus of 5,000IU of heparin during non-cardiac arterial procedures.” This is in sharp contrast to cardiac interventions, noted Wiersema, where heparin is used in higher dosages. “As surprising as it may seem, only one randomised controlled trial (in 1996) has been performed on the benefit of heparin, comparing a group with heparin to a group without heparin as prophylactic antithrombotic.”

The fact that no other study has since been performed on this subject despite the wide uptake of heparinisation is, to Wiersema and his colleagues, reportedly “astonishing”. For this reason, the ACTION trial was designed to examine the benefits of heparinisation guided

by ACT, with the hypothesis that fewer thromboembolic complications and no increase in bleeding complications would be observed.

“The final goal of ACT to strive for,” commented Wiersema, “was set at 200 to 220 seconds. To reach those ACT values, a starting bolus of 100 units per kilogram was used and additional doses were set at 60 or 30 units, depending on the actual ACT.” He added that a protocol was instituted for the use of protamine at the end of the procedure, to decrease the incidence of bleeding complications.

In terms of the results, “ACT-guided heparinisation ensured the vast majority of the patients of adequate and safe anticoagulation. Almost all patients in our pilot-study reached an ACT of more than 200 seconds after the first bolus.”

The mean dose of heparin needed to maintain this optimal anticoagulation was roughly twice the bolus of 5,000 units. While the incidence of bleeding complications was not increased, a “promising trend” of decrease in thromboembolic complications was observed, falling from 11% to 6%. For the subgroup of open AAA repair this decrease was even more profound: a reduction from 22% to 7%.

Wiersema emphasised the importance of establishing the added value of ACT-guided heparinisation “once and for all”, stating: “We are on the verge

It is time to upgrade one of the foundations of vascular surgery to optimise patient care.”

Metformin associated with reduced AAA diameter growth in diabetic US veterans A study published in the Journal of Vascular Surgery by Nathan Itoga (University of Stanford, Stanford, USA) and colleagues has identified a 20% decrease in yearly growth rate of abdominal aortic aneurysm (AAA) for patients with diabetes mellitus who were prescribed metformin, compared to diabetic patients without metformin. The findings have provided new leads to further understanding of what the investigators call “the paradoxical relationship” between diabetes mellitus and AAA disease, which they note remains “controversial and poorly understood”.

THE RETROSPECTIVE COHORT study analysed 13,834 patients treated in the Veterans Affairs Health Care System in the USA, between 2003 and 2013. Patients included had diabetes mellitus and AAA disease, and had undergone a minimum of two radiographic imaging sessions separated by at least one year, documenting the presence and diameter of an abdominal aortic aneurysm.

The median number of scans per patient was four, and Itoga et al included a sample size of 58,833 radiographic records—of which 55.4% were ultrasound images, 43.3% were CT scans, and 1.3% were MRI scans.

Itoga and colleagues found that for the entire cohort, the mean growth rate of the aneurysm was 1.4±2mm per year as analysed by multivariate linear regression (referred to as model one). Using a multivariate mixed-effects model with random intercept and random slope, referred to as model two, the investigators saw a slightly smaller aneurysmal growth rate of 1.3±1.6mm per year for the entire cohort.

The unadjusted mean rate of AAA growth, they write,

was 1.2±1.9mm per year for the metformin prescribed group, while those without metformin saw a growth rate of 1.5±2.2mm per year (p<0.001). This, the authors note, constitutes a 20% decrease in growth for patients prescribed with metformin—a decrease which “remained significant when adjusted for variables relevant on AAA progression”.

As aneurysms grow in size, the risk of rupture increases, and the authors note that AAA disease management guidelines recommend elective surgery to intervene when aneurysm diameters reach 5cm in women or 5.5cm in men. However, Itoga et al indicate that “although the introduction of endovascular aneurysm repair has significantly reduced the risk for periprocedural morbidity and mortality,” methods of slowing aneurysmal growth need to be further developed and better understood.

Similarly, Itoga et al note that despite over 60 years of “worldwide use” of the drug, the exact mechanism of how metformin works in management of diabetes “remains

Arno Wiersema

of receiving a large grant to perform an international randomised controlled trial for ACT-guided heparinisation during open AAA repair. This trial is starting in The Netherlands, Hamburg (Germany) and Copenhagen (Denmark), and we are more than happy to include other major vascular centres around the world. We need only 748 patients in five years to prove a reduction for the combined incidence of thromboembolic complications and mortality from 19% to 11%. If this method is proven to be better during open aortic aneurysm repair, it can be directly incorporated for all our other procedures.”

Concluding, Wiersema said “the ACTION pilot showed that ACT-guided heparinisation increases patient safety and looks very promising as a method to decrease thromboembolic complications, without a relevant rise in bleeding complications.”

incompletely understood”.

“Unfortunately, even though most AAAs are identified at an early stage of the disease, no medical intervention [...] has proved effective in limiting progressive diameter enlargement or eventual rupture”, write the authors, in their background and motivations for this large cohort study.

Pointing to two smaller studies, they explain that the link between reduced rates of AAA progression and diabetes is one that has been made elsewhere, but “validating this association in a larger population has proved challenging in that AAAs are less prevalent in diabetic patients”.

The US Department of Veterans Affairs Health System therefore represented the “ideal cohort” due to its size, and prevalence of diabetes (25%) as well as smoking and other cardiovascular disease factors.

The results of this study “provide further support for the hypothesis associating diabetes with AAA suppresion”, with the authors adding that the data demonstrate “for the first time in a population-based study, that metformin prescription is associated with an additional reduction in AAA enlargement rate beyond that associated with the presence of diabetes itself.”

Looking to future studies, the authors recommend “prospective clinical trials to test the ability of metformin to suppress AAA disease in both diabetic and non-diabetic patients.

Validating this association in a larger population has proved challenging [...] in diabetic patients.”

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Conference coverage

Tomographic 3D ultrasound imaging “the way forward” for vascular surgeons

Steven Rogers (Manchester, UK) presented the case for using contrast-enhanced tomographic 3D ultrasound imaging for peripheral arterial disease, stating at the Charing Cross Symposium (CX; 15–18 April, London, UK): “Our surgeons certainly prefer the 3D vessel mapping to a 2D vessel map.”

ACCORDING TO ROGERS, tomographic 3D ultrasound imaging is a minimally invasive technique that can be performed “with relatively little experience.

It is fast, it is inexpensive, it can be reimbursed, and potentially it is becoming more clinically valuable; perhaps it is the way forward.”

Rogers presented details of a currently enrolling study to investigate the use of contrast-enhanced ultrasound imaging in below-the-knee vessels for patients with peripheral arterial disease. To date, Rogers and colleagues have recruited 100 patients (414 arteries). Included patients have undergone an angiogram, followed within a week by a tomographic ultrasound scan from the popliteal artery to the toes.

Rogers told delegates that they chose to image belowthe-knee arteries as he says “standard duplex is good enough for the femoropopliteal segment”, and the investigators wanted to “address the areas where it is weak”.

To perform the scan, the physicians begin with a two-dimensional ultrasound image. Pointing to an image visualised on screen, Rogers said: “I defy anybody to give me a diagnosis from this standard contrast 2D image.” Explaining the next steps, he

continued: “We compute that [two dimensional image] into the third dimension; then we can rotate it and review it from any angle. We can also see collateral vessels that feed the muscles, and we can see potential areas of disease.”

To assess the reproducibility of the tomographic ultrasound scan, Rogers explained that they set out

This imaging tool is complementary [to current imaging techniques] rather than offering a replacement right now.” to determine the degree of intraoperative observer agreement when making diagnoses based on the images.

He reported finding a high degree of agreement, and added that as “the confidence intervals are relatively narrow, we know there is a degree of precision in its

reproducibility”.

However, Rogers did acknowledge some limitations of this imaging modality. As this is an ultrasound technique, he admitted that “we are still constrained by the sonic constraints of ultrasound”, and said for this reason “deep vessels in particular are challenging, as are calcified vessels”. Notwithstanding these restrictions to its use, Rogers believes the minimallyinvasive, 3D mapping technique “may well be a go-to test in the future arsenal for vascular physicians”, although “there is still a long way to go”.

Session chair Robert Morgan (London, UK) asked Rogers whether this imaging tool was an ultrasound machine “just for vascular imaging”, or if it is “a general ultrasound machine with tomographic capabilities?”.

Rogers replied: “It is a bolt on, basically. You need a normal duplex instrument with contrast options, and it works by screen capture, so you just plug in an HDMI cable. At the minute, it is a separate system— the current system is £44,000, they have just launched the second generation device, which costs £9,000 and plugs into a standard laptop.”

After summarising, “The point is to find if we have got a binary restenosis; a residual or a current stenosis that is haemodynamically significant”, moderator Andrew Holden (Auckland, New Zealand) questioned whether Rogers was confident that the technique would enable him to “differentiate between a 30–40% residual as compared to a 70% residual with the imaging data”.

On this point, Rogers was clear: “We can certainly measure the percentage, whether it is 30%, 40% or 70%;” he added: “I think the key here is that we can use it to go back and re-target the duplex and take the velocity shift across a particular area of interest, so this imaging tool is complementary [to current imaging techniques] rather than offering a replacement right now.”

ADVERTORIAL SPONSORED BY LOMBARD MEDICAL

Treating challenging aneurysms in complex anatomy with Aorfix The PYTHAGORAS trial provided the first long-term data from an endovascular aneurysm repair (EVAR) cohort to include a majority of highly angulated infrarenal necks, showing favourable results at five years for treatment in this group using Lombard Medical’s Aorfix stent graft. Following the results, which were published in the Journal of Vascular Surgery, consultant vascular surgeon Darren Morrow speaks to Vascular News about his experience using Aorfix at the Norfolk and Norwich University Hospital in Norwich, UK.

Your centre has been using Aorfix for over a decade.

What type of anatomies have you seen in that time, and how does that compare to the PYTHAGORAS cohort?

At the Norfolk and Norwich University Hospital we have been using the Aorfix stent graft for patients with challenging aneurysm anatomy since 2007. We have recently analysed the results of all the 127 cases we performed between 2007 and 2017, including 63 patients (50%) with a severely angulated neck

(≥60 degrees) and 64 patients (50%) with tortuous iliac arteries. In the PYTHAGORAS study, 69% of patients had a severely angulated neck.

What results have you observed in this analysis?

Our primary success rate in excluding the aneurysm was 80%, and our primary assisted success rate was 98%. We had no limb occlusions. Our 30-day and one-year all-cause mortality rates were 1.6% and 6.3%, which are very similar to those in PYTHAGORAS.

After a mean of five years of follow-up, 97 patients (76%) had a stable or shrinking sac, while seven patients had a type 1 endoleak, of whom two died before reintervention.

Our sac expansion rate is higher than that seen at five years in PYTHAGORAS, possibly because half of our patients have been followed up beyond five years.

Darren Morrow

What are the key lessons learned from your experience, and what do you think will be important next steps for these studies?

It will be important for centres such as ours to collect follow-up data for 10 years and beyond, to determine the durability of the device. particularly in severely angulated necks. Such necks

We have been using the Aorfix stent graft for patients with challenging aneurysm anatomy since 2007.”

Aorfix (Lombard Medical)

are more common in women. and a stent graft with better long-term outcomes therefore has the potential to positively influence the cost-effectiveness calculations for abdominal aortic aneurysm screening in women.

Twenty-three patients (18%) required a proximal extension cuff to exclude a type 1 endoleak during the index procedure. This need was more common in those with a severely angulated neck, as well as at the beginning of our learning curve. As we gained experience, however, we learned to be more aggressive in positioning the troughs of the fishmouth closer to the renal arteries. This was later facilitated by the new Intelliflex delivery system (Lombard Medical) which allows for a more predictable deployment. I would strongly recommend familiarising yourself with the device by also using it in non-challenging anatomies.

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Endovascular repair

Endovascular repair matches open surgery for treatment of men with complex but low-risk aortoiliac disease using balloonexpandable covered stent Endovascular repair shortens hospital stay and has comparable outcomes to open surgery when balloon-expandable covered stents are used to treat low-risk male patients with complex aortoiliac lesions, new data show. Michele Antonello (Padua, Italy) described some of the study’s key results during a presentation at the Charing Cross Symposium (CX; 15–18 April, London, UK), concluding that the Gore Viabahn VBX stent-graft used has good flexibility, accurate deployment and a customisable diameter.

ANTONELLO AND COLLEAGUES conducted a single-centre retrospective review of the outcomes in 114 patients with a mean age of 61.4 and TransAtlantic Inter Society Consensus II (TASC) lesions class C or D created between 2008 and 2017. Those with associated aortic aneurysm or lesions involving the entire infrarenal aorta were excluded.

The review found that patients who underwent endovascular surgery had, at 30 days after their procedure, spent less than a third of the time in hospital than those who had open surgery. Primary patency rates were similar at five years for men, but worse for women.

At 30 days, the endovascular repair group had spent a mean of 2.6 days in hospital and a mean of 0.1 days in intensive care, compared to a mean of 8.5 days in hospital and a mean of 0.9 days in intensive care for those who had open surgery. The primary patency rate at five years was 87.3% for the open surgery repair group versus 81.4% for endovascular repair.

In a subgroup aged ≤60 years, primary patency at five years for those who had open surgical repair was 84.7% vs. 75% among those who underwent endovascular repair. The only predictor of negative patency was female gender in the endovascular repair group.

Endovascular repair can be considered to have comparable outcomes to the open surgery approach, while shortening hospital stays.”

Michele Antonello

The authors concluded that in cases of severe aortoiliac obstructive lesions in low-risk and young male patients, endovascular repair can be considered to have comparable outcomes to the open surgery approach, while at the same time shortening hospital stays.

For female patients, however, open surgical repair remains the reference

standard of treatment.

Antonello commented: “These balloon expandable stents are extremely precise.” He added: “The most important feature is that you can customise your diameter,” elaborating that this allows the physician to adapt the stent to the required diameter of each specific vessel.

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Off-the-shelf T-branch saves lives in emergency cases An off-the-shelf endograft for the treatment of thoracoabdominal aortic aneurysms (TAAA) provides a safe and straightforward solution for a wide range of patients—including emergency cases.

Data for the Zenith T-branch endograft were presented by Martin Austermann (Münster, Germany) in a Podium 1st Session during the Charing Cross Symposium (CX; 15–18 April, London, UK).

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ontextualising this study, Austermann explained to the audience that “Open repair of thoracoabdominal aneurysms is, even in high-volume centres, still associated with significant mortality and morbidity. Using an endovascular approach could reduce mortality and morbidity by avoiding cross-clamping and reimplantation of the renovisceral vessels.”

Endovascular repair is increasingly used to treat patients with TAAA, but manufacturing customised stents can take up to eight weeks, limiting its use in urgent cases. Austermann told CX delegates that, although custom-made fenestrated and branched endovascular aneurysm repair (EVAR) devices had been well established for the last 15 years, the waiting time for the custommade devices “excludes a remarkable number of patients with very big, ruptured or symptomatic aneurysms”.

The Zenith T-branch endograft was launched by Cook Medical in September 2012 as an immediate solution for patients with any type of TAAA. The endograft has four downward-facing cuffs for the renal and visceral arteries, and can be further extended at the proximal end with tapered off-the-shelf components, enabling interventionists to accommodate individual patient anatomies. A distal, bifurcated graft is available in four lengths. Previous studies have suggested that it is suitable for around half of patients otherwise treated with custommade endografts.

The presentation gave the short-term results of this post-market, multicentre, observational study evaluating the use of the T-branch endograft in routine clinical care. Eighty patients from two sites in Germany and one in Sweden were enrolled in the study between September 2012 and November 2017, with 96% of them treated for aneurysms, and 4% of them for dissections. Half of the procedures were performed in a staged fashion. The primary outcome was procedure-related mortality and morbidity at 30 days. Secondary outcomes included longer-term mortality and morbidity, patency of the graft and bridging stents, device integrity, and aneurysm growth.

The technical success rate was 100%.

There was one death within 30 days, and there were no ruptures or conversions to open repair.

Elaborating on these positive, preliminary results, Austermann said this was particularly notable as the

patient population was “very ill”. Most of the patients (38%; 29/77) treated for aneurysms (so most of the patients enrolled in the study) were Type II on the Crawford classification. Thirty-four per cent (26/77) were designated Type IV, and a further 18% (14/77) were designated Type III, with the remaining 7% (5/77) a Type I. Therefore, the majority of patients had “very extensive disease”.

Austermann also emphasised the fact that 25% (20 patients) were symptomatic or contained ruptures, and 30% had a renal impairment or a severe cardiac disease.

Given the added complications of treating “such a sick patient group”, Austermann highlighted that treating all patients through endovascular means, even when secondary interventions were necessary, was “impressive”.

After one-year follow-up, the freedom from all-cause mortality was above 90%;

Thoracic endovascular aortic repair freedom from secondary interventions at one year was 87.7%. Austermann stressed that “most of the patients [92.3%; 24/26 patients] showed a decrease in aneurysm size of more than 5mm [at one year]; most of the rest [7.7%; 2/26 patients] had no changes in size, and there was no increase in this group of patients”.

The T-Branch design gives the tool a broad applicability, including for urgent cases, Austermann said. “Planning the procedure is easy, and implantation is very safe and straightforward. In emergency cases, the use of T-branch saves lives,” he added. Detailing the “obvious” advantages of the Zenith T-branch endograft, Austermann elaborated: “We have no waiting time, and the applicability is very good. About two-thirds of our patients [63%] can be treated with this device, shown by Timothy Chuter’s group [Nottingham, UK] and also our group. The planning is relatively easy; you have to locate the target vessels, and it should match the pattern of the T-branch—then you can use it.

“The implantation is very safe and stress free—you can do everything stepby-step. It is also a very forgiving device, because implantation as well as planning does not have to be too exact. The only mistake you can make is to place your endograft too low, as then you can run into problems.”

During implantation, the interventionist gains access both through the groin and through the left axillary artery. When questioned on this approach, Austermann

It is a very forgiving device, because implantation as well as planning does not have to be too exact.”

Martin Austermann

21

said: “In our centre, we always come from the left axillary artery, but I know others sometimes go from the right side.

I just much prefer the left side.” On gaining access to the vasculature, the physician places the graft and closes the access site in the groin. “We then have all the time we need,” Austermann said, “to connect and attach all the target vessels to the cuffs.” Austermann explained that, in his experience, this minimises the risk for spinal cord ischaemia.

Spinal cord ischaemia was also the topic of discussion following Austermann’s presentation. The shortterm results included a 12% neurologic event rate, encompassing strokes and spinal cord ischaemia. Responding to a query concerning the use of a spinal drain, Austermann said that he had reviewed his own data from 2014 and 2015, and observed a 5% complication rate following EVAR, which he attributed largely to spinal cord drainage: “When comparing between those who had spinal cord drainage and those who did not, we saw a significant difference in complication rate.” He therefore decided in 2015 to only perform spinal cord drainage post-operatively, when necessary, reporting a more recent complication rate of 2%: “So we have lowered this [complication rate],” he stated.

An additional questioner also remarked on the three strokes reported in this patient population, and asked Austermann if he had noticed any difference in the rate of strokes between patients with left or right brachial access.

Austermann expanded that he did not find an association between access direction and stroke rate. He also added that these strokes were “all minor”, although he acknowledged that this is “a potential issue”.

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June

Appropriate follow-up of patients after endovascular procedures

Marianne Brodmann Comment & Analysis Marianne Brodmann outlines follow-up and surveillance protocols after endovascular treatments for peripheral arterial disease (PAD), arguing for a standardised approach to ensure best practice for patients who have gone through peripheral endovascular procedures.

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ndovascular procedures have become a key element of treating patients with PAD, either with intermittent claudication or critical limb ischaemia. Nevertheless, there is currently no standardised approach and no general- or guidelines-derived recommendation for how to do this. The follow-up after these procedures is often dependent on facility resources, such as available manpower and equipment, or geography (urban versus rural).

What is the rationale of surveillance after endovascular procedures?

It is important to accurately implement preventative strategies to avoid other

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Lower limb interventions

cardiovascular events and disease progression in a patient cohort with a high risk of morbidity and mortality, while also avoiding recurrence of symptoms and the need for repeat revascularisation. The importance of this is amplified by the fact that we are facing an increasing disease burden of PAD patients needing treatment. In 2008, >98,000 endovascular procedures and >86,000 surgical revascularisations were performed for lower limb arterial disease in Germany alone, illustrating the burden of peripheral revascularisation interventions in Europe.

For a standardised approach to surveillance, we need to discuss several questions. What should we offer and how

should we do it? Is follow-up with anklebrachial index (ABI) alone enough, or should we also perform duplex ultrasound? What are the timeframes to do this? Another important question is, who should perform the follow-up?

One simple key element is the clinical follow-up. This also means that we should create awareness among patients about the symptoms that occur in revascularisation failure, and when immediate contact to vascular specialists is indicated.

With regards to imaging techniques, which help us to detect restenosis either in the immediate or long-term follow-up, duplex ultrasound is the most applicable.

It is non-invasive and widely available, and can be repeated over time to detect subclinical and abnormalities. It has therefore become the first-line technique for follow-up. Duplex ultrasound surveillance has been reported to predict severe in-stent restenosis with a specificity of >90%.

Functional tests such as ABI or toebrachial index (TBI) can further help to optimise surveillance of the lower limbs.

Computed tomography angiography (CTA) and magnetic resonance angiography are mostly limited to the confirmation and investigation of duplex ultrasound findings, but can be performed straight away in urgent cases.

In cases of recurrent claudication, treadmill test with post-exercise ABI can assess the functional severity.

However, ensuring follow-up after endovascular procedures will also serve

Stress hormones associated with perioperative risks in revascularisation for CLI patients

A study published in the Journal for Vascular Surgery has found that levels of certain stress hormones—namely, epinephrine and cortisol—were independently associated with an increased risk of perioperative major adverse cardiovascular events. A subanalysis of the SPINACH study by Yoshimitsu Soga and colleagues at multiple centres in Japan revealed this association in a cohort of patients with critical limb ischaemia (CLI) undergoing surgical and endovascular revascularisation.

SOGA ET AL note that while patients with CLI who require revascularisation are “well known” to suffer from poor prognosis and outcomes, and a range of risk factors including age, comorbidities and disease progression are well-documented, no detailed reports have been submitted on the potential impact of stressrelated hormones on CLI prognosis. The SPINACH study therefore set out to investigate this relationship, analysing 467 patients by measuring their levels of four stress-related hormones before undergoing a revascularisation procedure. The measured hormones were epinephrine, norepinephrine, dopamine and cortisol, and the primary endpoint was perioperative major cardiovascular events (including all-cause mortality, myocardial infarction and stroke) within 30 days following the procedure.

The endpoint of perioperative major adverse cardiovascular events (pMACE) was met in 21 patients (4.5%), with an initial crude comparison indicating that patients with pMACE had a higher level of epinephrine, dopamine and cortisol compared to those without pMACE. Investigators then applied propensity score matching to control for potential confounding.

Matching 20 pMACE patients with 192 non-pMACE

patients, this result remained significant for levels of epinephrine and cortisol, but not dopamine.

Epinephrine and cortisol were independent of each other in their association with increased risk of pMACE, as was confirmed by multivariate analysis, while a Cox proportional hazards regression model revealed that both hormones were associated with 30day mortality but did not extend into a long-term risk association.

Overall, “patients with pMACE had, in brief, a poorer general condition and more severe limb status,” the authors note in their results. The pMACE group saw a higher prevalence of regular dialysis (81% vs. 52%; p=0.02) and heart failure (48% vs.

17%; p<0.001) as well as a lower body mass index (20.1±3.3kg/m2 vs. 22±3.5kg/m2; p=0.02) and lower left ventricular ejection fraction (50%±18% vs.

61%±12%; p=0.01).

After propensity score matching, Soga et al observed “no remarkable intergroup difference in baseline characteristics”. Levels of epinephrine, at 54.3pm/ ml in the pMACE group vs. 31.5pg/ml in the control arm (p=0.002), and cortisol (15.8µg/dl vs. 13.5µg/dl; p=0.006) were still significantly higher in the former

to prevent disease progression. Regular monitoring for risk factor modification, exercise training and medical therapy is a must. Even in patients with intermittent claudication, disease progression to chronic limb threatening ischaemia may be underestimated. In a meta-analysis of studies conducted between 1990 and 2015, 21% of patients with intermittent claudication were diagnosed with chronic limb threatening ischaemia during a five-year follow-up period, and 4%–27% of them suffered amputations.

How often should we do it?

There should be an immediate postprocedural follow-up the day after the procedure, to gain insight into the procedural success achieved. To detect early restenosis, the next follow-up should be performed one month later, and thereafter in a six month period up to one year. Long-term follow up should be performed annually. As for who should carry out the followup, this should be performed by the people taking care of patients with vascular disease, whether they are general practitioners or cardiovascular specialists, such as cardiologists, vascular physicians or vascular surgeons.

The appropriateness of who carries this responsibility will vary, according to the management of patients in different individual countries.

Marianne Brodmann is a vascular specialist at the Medical University of Graz, Austria.

group than for the patients who did not suffer from pMACE. The authors note that they subsequently investigated the independence of the two hormones, finding the association to be independent both before and after matching. A supplementary analysis showed that haemodialysis, lower body mass index and decreased left ventricular ejection fraction were associated with circulating epinephrine levels, whereas foot infection was associated with circulating cortisol levels.

“Stress is induced not only by medical illness or invasiveness but also by mental disturbances, including anxiety and depression, and it has been reported that such mental and emotional stress is also strongly associated with hypertension and the progression of arteriosclerosis,” the investigators write. However, the discussion acknowledges that causes of stress, or stressors, are difficult to identify, as these will vary greatly between individuals. Furthermore, the authors point out that the body’s reaction to stress also differs according to how the stress is experienced, possibly influencing the secretion of hormones. Elaborating on the limitations of the study, Soga et al report “it was difficult to accurately quantify and to correct the extent of invasiveness,” suggesting that patients meeting the primary endpoint of perioperative adverse events may in fact have been exposed to unidentified greater physical stress. However, they maintain: “Irrespective of the cause [of adverse events], exposure to stress would have an adverse effect perioperatively, and even minor interventions to reduce stress may be effective.”

The investigators therefore suggest that proactive pain alleviation and a management strategy for emotional stressors “may prove to be useful”, and conclude: “We believe that this report is significant as it is the first to describe the relationship between stress-related hormones and clinical outcomes in patients with CLI who underwent revascularisation.”

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June

Proximal neck sealing may lower risk of inducing neck dilatation

Endovascular aneurysm repair (EVAR) using proximal polymer sealing does not seem to induce neck dilatation like other endografts, concluded Hence Verhagen (Rotterdam, The Netherlands) at Charing Cross (CX; 15–18 April, London, UK).

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hroughout his talk, Verhagen alluded to an array of studies that illuminate the issue of durability in EVAR. Specifically, he stated: “We know that the most common failure mode of EVAR is loss of proximal seal. This is especially seen in implants in attachment zones that are aneurysmal. So basically, a wide neck is a durability issue for EVAR.” Taking a global perspective, Verhagen pointed to an international study, which reported that wide necks evoke a three-fold greater increase in type Ia endoleaks, and a five-fold greater risk of aneurysm rupture and increased mortality. Moreover, a recent systematic review published this year indicated that sac expansion was 10.07 times more likely in wide neck aneurysm, with rupture 5.1 times more likely.

“All the bad things happen more often in wide neck patients,” Verhagen said.

According to Verhagen, the most common failure mode of EVAR in wide necks was loss of proximal seal due to progressive dilatation of the neck. “It is not migration, but a progressive dilatation.” As Verhagen and his team found a yearly rate of neck dilatation between 4%–6%, he said: “This continuous outward radial force by self-expandable stent grafts may play an important role here.”

Addressing the CX audience, Verhagen put

forward: “There is one different graft from the others; that is the Ovation graft.” Acknowledging that the graft contains a polymer ring that can be filled, he suggested that after implementation, “there is basically no radial force left on the aneurysm neck, leaving no outward force”.

ENCORE: Five-year results

In patients that have been treated so far, Verhagen said that the Ovation graft has demonstrated no dilatation up to five years in the neck—in contrast to most self-expandable stents. Thus, Verhagen and his team hypothesised that patients can be treated safely and durably, even with the largest Ovation device (Endologix). A retrospective analysis of six prospectively enrolled studies known as ENCORE

This analysis suggests that Ovation is a durable EVAR option, even in wide neck anatomy.”

(Effectiveness of custom seal with Ovation: Review of the Evidence) included 1,296 patients and had a mean follow-up of three years.

Between the study group and the control, Verhagen reported no difference in all-cause mortality or abdominal aortic aneurysm-related mortality through to five years. He further said: “We see no difference in rupture; we see no Hence Verhagen difference in conversion.

There is a difference in type Ia endoleak, but in contrast to all the selfexpandable stents, these type Ia endoleaks appear on the first postoperative CT, which probably has a lot to do with sizing, more than anything else. After that, there was no type Ia endoleak during the next five years. Proximal reintervention followed the same rule; after 30 days there were no reinterventions for proximal reasons.”

In conclusion, Verhagen noted that endovascular aneurysm repair using proximal polymer sealing “does not seem to induce neck dilatation like other endografts.” Moreover, in contrast to self-expanding EVAR devices, Verhagen stated that patients treated with the largest size Ovation do not suffer from more complications than those treated with standard diameter devices. “So this analysis suggests that Ovation is a durable endovascular aneurysm repair option, even in wide neck anatomy,” concluded Verhagen. He lastly acknowledged that further investigation is needed to understand why Ovation follows a different clinical course.

Endoanchors add to therapy options for aortic aneurysms Using endoanchors (Heli-FX, Medtronic) to fix and seal endovascular aortic grafts is safe and effective for short-neck abdominal aortic aneurysm (AAA) patients, two-year data from the ANCHOR global registry have shown. Frank Arko (Charlotte, USA) presented the findings at Charing Cross (CX; 15–18 April, London, UK) in a Podium 1st Session, confirming a high success rate for the procedure. “The goal of contemporary AAA therapy is the long-term durability of the repair. Surgical repair does this very well. Can we simulate and get those same results with endovascular repair, with the addition of endoanchors? I tend to think so, and I think that today would also suggest that as well.”

THE ANCHOR REGISTRY is a prospective multicentre study in the USA and Europe. Of 584 patients in the primary arm, 100 had short neck indications, at <10mm, and 70 were evaluated for one-year outcomes. Twoyear outcomes on the first 38 of these patients were made available during CX. Arko explained: “The ANCHOR registry has now evolved into only evaluating these short necks. You have to have a neck diameter somewhere between 19mm and 32mm, with angulation less than 60. It is truly an off-the-shelf approach, femoral only. The maximum size that you have to put in is the size of the Endurant [Medtronic], which is 20F. The endoanchors are actually placed within a 16F sheath.”

In all, 73% of subjects were male and mean age was 71.3 years. Arko said: “They were a sick group of patients; 93% were ASA Class III or IV; 17%

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Endovascular device trials

presented symptomatically, so they had an increased risk of morbidity and mortality, and 31% were either urgent or emergent cases, requiring an off-the-shelf solution for management. It is a relatively aggressive or hostile anatomy—average neck length was <7mm, aneurysm size 5.8cm, angulation at 20.6 degrees and the diameter of the neck was borderline, some people would say, at 26mm in diameter.”

At the time of the original implant, the average duration of the procedure was 148 minutes, average time to implant endoanchors was 17 minutes, and average fluoroscopy time was 35 minutes. The average number of endoanchors implanted was 5.5.

Procedural success rate was 97.1%, with a 2% risk of type 1a endoleak at one year. “But,” Arko pointed out, “when you followed those patients up to two years, the risk of type 1a endoleak in these very hostile neck anatomies was 0%, and the

Frank Arko

risk of migration was 0%. And most people would consider the size of the aneurysm at long-term follow-up to be a true marker of complete exclusion of the aneurysm, with more and more data to suggest that regression of the aneurysm sac is probably the most important data that we look at.”

At one year, nearly half of the patients had regressed (44%), with 56% remaining stable. At two years, sac regression increased to 65%, and 35% remained stable, with no aneurysms increasing in size. Two-year freedom from all-cause mortality was 86.7%, and freedom from anerusym-related mortality was the same at one- and two-year follow-up, at 94.3%, with 96% freedom from secondary endovascular procedures and 100% freedom from aneurysm rupture.

Arko concluded: “At two-years’ follow-up, we have excellent clinical outcomes from a complex, short neck cohort, with no type Ia endoleaks, 65% sac regression, and only one proximal neck-related secondary procedure through two years.” He added: “It should be added to the armamentarium of any vascular surgeon treating this type of patient’s condition. There probably needs to be in this hostile neck anatomy a variety of different therapies offered to the patient.”

In a vote at the end of the session on whether physicians would support the use of endoanchors as a primary intention for short proximal necks based on the data, 54% said “yes” and 46% said “no”.

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Endovascular device trials

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IN.PACT Pacific finds lower profile platform as effective for drug delivery Interventionalists can confidently use lower profile drug delivery platforms, based on data that shows 0.018-inch guidewire devices are non-inferior to 0.035-inch guidewires. In a Podium 1st presentation at the Charing Cross Symposium (CX; 15–18 April, London, UK), Andrew Holden (Auckland, New Zealand) said: “At 90 days, we can see that the 0.018-inch IN.PACT Pacific device is certainly noninferior to the [0.035-inch] IN.PACT Admiral device—the device with so much five-year follow-up data. What this means is we can have confidence transposing all the published data from 0.035-inch technologies to these newer low-profile 0.018-inch devices.”

RANDOMISED CONTROLLED trials and real-world registries have established a patency advantage in the femoropopliteal segment for drugcoated balloons (DCB) with an 0.035inch guidewire compatible platform.

But Holden pointed out: “There are a lot of clinicians who would like to use lower profile, 0.018-inch guidewirecompatible devices,” and he listed the clinical advantages. “The profile is smaller and that reduces access sheath size and bleeding risk,” he said. “And that is often very relevant, particularly in elderly female patients with small calibre vessels. Lower profile means we have better deliverability and crossing ability, and we can just use one guidewire to cross lesions above and below the knee.”

Researchers created arterial injuries in swine models using angioplasty and stenting, and treated 30 days later with a DCB or drug-eluting stent. They then assessed restenosis rates using quantitative vessel analysis (QVA) and optical coherence tomography (OCT) imaging at 60, 90 or 120 days posttreatment, and also measured tissue levels of drug at the terminal timepoint.

Firstly, the performance of two 0.035-

inch compatible guidewire devices, the IN.PACT Admiral (Medtronic) and the Stellarex (Phillips), were compared: “At various timepoints, both 60 and 90 days, there is a significant reduction in restenosis with the IN.PACT Admiral compared to the Stellarex, and this is not surprising given the higher input dose with the IN.PACT Admiral. The tissue concentrations that were obtained at the terminal timepoint also showed that there

was higher tissue dose of paclitaxel with the IN.PACT Admiral.”

The investigators also looked at two 0.018-inch guidewire compatible devices—the Pacific (Medtronic) and the Ranger (Boston Scientific); this comparison extended the timepoint to 120 days. “The Pacific was trending towards a lower restenosis rate with QVA and OCT compared to the Ranger at 60 and 120 days. It did not reach

Andrew Holden

MIMICS-2 trial data show helical stents provide durable treatment of diseased femoropopliteal arteries Data from the MIMICS-2 trial show the BioMimics 3D stent (Veryan Medical), which mimics natural vascular curvature, remains safe and effective for patients with symptomatic atherosclerotic disease of the femoropopliteal arteries two years after implantation.

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rincipal investigator Timothy Sullivan (Minneappolis, USA) presented the two-year findings at the Charing Cross Symposium (CX; 15–18 April, London, UK) in a Podium 1st Session.

He explained: “We know that swirling flow creates increased wall stress in the arterial wall, which is atheroprotective, and this is especially important in the superficial femoral artery where, under normal circumstances, shear stress is quite low. The use of a helical stent produces swirling flow and increased wall shear stress.”

MIMICS-2 is an international investigational device exemption (IDE) study to evaluate the safety and efficacy of the BioMimics 3D stent system in patients undergoing endovascular intervention to relieve obstructive or occlusive disease in the femoropopliteal artery. The three-year, prospective, single-arm trial is tracking outcomes in 271 subjects with a mean age at baseline of 68.4 years, across 43 sites in the USA, Germany and Japan.

About 50% of patients had diabetes mellitus, and the majority were in Rutherford category 3 and 4: “These

were patients with significant clinical symptoms related to lower extremity arterial claudication and a baseline ankle-brachial index of 0.7, representing patients that we all would treat in our clinical practice, typically with lower extremity intervention following a trial of exercise therapy.”

Device and technical success rates were 100%.

The primary safety endpoint of freedom from major adverse events (death, major amputation, or clinically driven target lesion revascularisation [CD-TLR]) at 12 months was achieved for 99.6% of subjects.

I will be using [the stent] with the confidence that restenosis is going to be minimal. The results shown are pretty amazing after two years.”

statistical significance, but there was a positive trend.”

Holden told Vascular News that the lower stenosis rates found with Pacific compared to Ranger could also be explained by the higher input dose for the Pacific balloon. The dissolution rates with paclitaxel for all the devices are pretty much the same so if you have a higher input dose at the start you are likely to see a pronounced, more prolonged restenosis effect.” However, “both platforms performed extremely well in terms of preventing re-stenosis,” Holden said A comparison between the IN.PACT Pacific and the IN.PACT Admiral—the 0.018-inch and the 0.035-inch devices from the same company—by QVA and OCT found comparable performance in terms of restenosis. Holden said: “This implies that the data we have from the 0.035-inch database can be translated to the 0.018-inch platform.”

He concluded: “We certainly could show that the 0.018” guidewire devices were non-inferior to the 0.035” devices.

Although this is a pre-clinical study, it is one that really does have clinical relevance.”

At 24 months, freedom from CD-TLR was 84.2% and “compares quite favourably to that at 12 months, which was 89%”, said Sullivan. “The [Kaplan-Meier] curve really starts to flatten out at about 360 days, without much loss in clinically driven-TLR.” This performance at two years is similar to that of drug-eluting stents (DES) and drug-coated balloons (DCB), despite the MIMICS-2 subject cohort including a greater proportion of challenging cases than those in pivotal DES and DCB trials.

Imaging confirmed there were no cases of stent fracture in any of the MIMCS-2 subjects, including those who have reached three-year follow-up. Sullivan concluded: “Swirling flow with this BioMimic stent creates increased shear stress at the vessel wall, which is atheroprotective without the use of an antiproliferative drug.”

The positive outcomes were achieved independent of lesion complexity—at the start of MIMICS-2, 45.9% of subjects had moderate to severe lesion calcification.

The Kaplan-Meier estimate of survival from CD-TLR at 24 months for those in this group was 85.5%.

Sullivan told Vascular News: “What these data tell me is that, in complicated patients with very calcified lesions […] when a device becomes available for general clinical use in the USA, I will be using it for long lesions, for calcified lesions […] that I might have otherwise have gone to one of the other treatment algorithms, with the confidence that restenosis is going to be minimal. The results shown are pretty amazing after two years.”

The other MIMICS-2 principal investigators are Thomas Zeller (Bad Krozingen, Germany) and Masato Nakamura (Tokyo, Japan).

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Interview

Profile

Kim Hodgson

The president-elect of the Society for Vascular Surgery (SVS), Kim Hodgson, begins his year as SVS president in 2019. In this profile interview with Vascular News, Hodgson discusses his career and research interests, how he came to be involved in the SVS, and what his goals are for the coming year.

Having started in biochemistry as an undergraduate student, why did you decide to become a medical doctor, and what led you to vascular surgery?

My interests have always tended towards the biological sciences so my pursuit of medical training following college just seemed like a natural evolution. After briefly flirting with Psychiatry, it was Surgery that captured my attention, and once in residency, Vascular Surgery that provided me with the right mix of technical challenges and opportunities for intellectual growth.

Who were/are your mentors in the vascular field, and how did they shape your career?

Vascular Quality Initiative, the publication of Clinical Practice Guidelines and Appropriate Use Criteria, the formation of a Quality Council, and the development of a vascular services certification programme with the American College of Surgeons. These initiatives are all coming together nicely, providing an opportunity for the SVS to distinguish itself and its members as leaders in the delivery of the right vascular care, at the right time, in the right site of service, and by those who have been properly trained and who are monitoring their indications and outcomes. The time is right for an overarching certification programme, which is currently in development, and my goal is to continue to shepherd that process along.

As a General Surgery resident in Albany, USA, Alistair Karmody and Dhiraj Shah introduced me to the challenges and rewards of a career in Vascular Surgery.

My fellowship training with David Sumner honed those skills and introduced me to the scientific method and the art of writing. My contemporary mentors, Alan Lumsden and Ken Ouriel, teamed up with me to educate and train vascular surgeons about the need to embrace endovascular therapies.

What do you most look forward to at the upcoming Vascular Annual Meeting?

How did your work with the Society for Vascular Surgery (SVS) develop over the years?

My current research focus is clarifying the mortality signal around the use of paclitaxel devices in peripheral arterial disease (PAD). As the leader of the SVS Paclitaxel Safety Task Force, a seasoned team of trialists, statisticians, and vascular surgeons, we are exploiting the unique power of the SVS-VQI to evaluate this critical question with real-world data.

My entrée into the SVS was my endovascular skillset, a relative rarity among vascular surgeons at that time.

Working in a smaller institution without the rigid specialty politics typically present in the more storied programmes, I was able to enter the endovascular arena very early in my career when only common iliac artery plain angioplasty was being performed and evolve with it. There was great opposition from the leaders of vascular surgery at that time to incorporating endovascular training into vascular surgery fellowship programmes, but the need to do so was recognised by some—as was my ability to contribute in that way.

So began a decade of organising endovascular skills postgraduate courses for members at the Vascular Annual Meeting (VAM), as well as initiatives to promote endovascular training in our fellowship programs and the vascular surgeons’ role in the delivery of endovascular care, all of which ultimately saved Vascular Surgery from extinction. When the need for a maintenance of certification self-assessment became apparent in the mid-2000’s, I was given the opportunity to expand on my service to the SVS and produced the inaugural edition of the Vascular Education and SelfAssessment Program (VESAP), followed over the next six years by the two editions which I co-edited with John Eidt. From there, I was elected to the SVS Executive Committee in the position of treasurer, followed by my ascension to the vice-president role in 2017 and president-elect in 2018.

As president of the SVS, what are your main goals and how do you hope to realise them?

Over the past several years, the SVS has made substantial investments to promote various facets of overall quality, including the development of our

An exciting new addition to the VAM this year is an SVS Foundation Gala: a new opportunity for vascular surgical colleagues to socialise, be entertained, and support the SVS Foundation at what will become our annual SVS Foundation auction of a variety of member artwork and other donated items and services.

What are your current research interests?

In the last year, which research paper(s) have you found particularly interesting, and why?

The Katsanos meta-analysis which first raised the alarm about a possible paclitaxel mortality signal has certainly been the most provocative publication of late, since it could undermine a promising therapy for PAD. While his meta-analysis is not without its limitations and criticisms, now that the question has been raised there will be no comfort using these devices, receiving these devices, or advancing the development of these devices, until the matter is conclusively resolved.

What do you think are the main challenges facing the vascular field?

Having witnessed the birth of vascular surgery, I am now bearing witness to the birth of its first offspring: the various facets of vascular surgery that are rapidly becoming our sub-specialties. The field has become so broad that we are now encountering vascular surgeons who only practice relatively small aspects of the field.

This will have a profound impact on how we train vascular surgeons in the future, and how and where our vascular patients receive their care. Our other main challenge is our loss of distinction among the vegetable soup of physicians now claiming to be specialists in treating vascular disease. Though we have the distinction of being the only specialty capable of delivering comprehensive vascular care, we need to demonstrate that this equates to better therapeutic decisions, outcomes, and cost-effectiveness.

The time is right for an overarching certification programme, and my goal is to shepherd that process along.”

What new advances and developments do you hope to see in the field over the next five years?

We need to reach clarity about the proper role for endovascular and open surgical revascularisations in an accountable care world. Clearly an endovascular-

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Fact File

else will be happy to step in and do so for us—and I bet we will not like the form it takes.

Could you tell us about a particularly memorable case you have had, and what you learned from it?

Most of our patients have created their own disease through socially irresponsible behaviours, which gives us a little insulation from guilt if their outcomes from our treatment are sub-optimal, which they eventually will be. These are the bulk of our patients and they all blur together because their dismissal of recommended lifestyle changes means that their clinical course over time is predictably poor. The patients that distinguish themselves in my memory are the innocent victims of an accident whose life or limb I have been able to save, or the patients who actually listened to my warnings and quit smoking. In contrast to the unreformed group, these patients generally do well, and make me feel great for what I have been able to do for them when I see them in follow-up.

What advice would you give to physicians and vascular specialists who are at the beginning of their career?

first approach for all is wasteful, if not harmful, to patients with severe disease, surgical options, and a reasonable life expectancy. This is especially true now that the use of paclitaxel devices is in doubt. While we prefer not to acknowledge it, or to point the finger at one of our competing specialties, a not-insignificant amount of vascular “care” being delivered today brings little value to the patient, yet significant cost to our healthcare system. Though some of this “care” may be provided with the best of intentions, we all know that some is also simply performed for personal gain. We need a Vascular Centers Certification programme, such as the SVS is working on with the American College of Surgeons, to ensure not just good outcomes, but appropriate indications in the first place. If we do not step up to the plate and regulate ourselves, someone

You are entering a career that will likely span over 30 years; do not expect to be practising the same vascular surgery at the end of your career that you have been trained to practice today. Keep your mind open to potentially new therapies, but do not jump on every bandwagon without careful consideration about what is best for your patients. Rarely is the hype around a new therapy proportional to the value it brings to the patient or the healthcare system.

Outside of work, what are your interests and how do you most like to spend your time?

My principal interests outside of medicine are travel and photography, which I originally embraced in my youth as a shared hobby with my father in the days of darkrooms and chemicals.

Having travelled to and photographed all seven continents I have abundant material to work on for years to come. Much of my work is done in my home office surrounded by my pet toucan Gizmo and parrots Hooter, Harley, and Yodi.

Current professional appointments

2010–Present: Associate Program Director, Vascular Surgery Residency Program, Southern Illinois University School of Medicine (Springfield, USA) 2009–Present: David S. Sumner Professor of Vascular and Endovascular Surgery, Southern Illinois University (Springfield, USA) 1999–Present: Chairman, Division of Peripheral Vascular Surgery, Southern Illinois University School of Medicine (Springfield, USA) 1998–Present: Professor of Surgery, Section of Peripheral Vascular Surgery, Southern Illinois University School of Medicine (Springifield, USA) 1987–Present: Director of Non-Invasive Vascular Laboratory, Memorial Medical Center (Springfield, USA)

Society for Vascular Surgery appointments (selected)

2018–Present: President-Elect 2017–2018: Vice President 2015–Present: Foundation Board of Directors 2014–2017: Treasurer 2014–2017: Finance Committee Chair 2014-2017: CoEditor-in-Chief of VESAP-3 2011-2014: CoEditor-in-Chief of VESAP-2 2011–2012: SVS Vascular Chairs Committee Chair 2008-2011: Editor-in-Chief of VESAP-1 2007–2016: Education Council as VESAP Editor-in-Chief

Other society appointments (selected) 2004–2008: Communications Committee Chairman, International Society for Vascular Surgery 2003–2006: Specialty Society Governor, American College of Surgeons 2000–2005: Programme Committe, The American Association for Vascular Surgery 2002–2003: President, Society for Clinical Vascular Surgery (SCVS)

Awards (selected)

2014–2018: SIU Department of Surgery Teaching Award, Resident Teaching Award 2011: Society for Vascular Surgery Volunteerism Award 2009: Recipient of the David S. Sumner, M.D. Endowed Chair in Endovascular and Vascular Surgery 2006: Senior Researcher of the Year 2005– 2006, Department of Surgery, SIU School of Medicine

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The impact of paclitaxel concerns on vascular access

At the 2019 Charing Cross Symposium (CX; 15–18 April, London, UK), a section of the programme highlighting drug-coated balloon trial updates ended with a panel discussion on whether peripheral vascular disease data are applicable to vascular access, following recent concerns surrounding paclitaxel. The discussion sparked interest from delegates, with an audience poll making it clear that physicians want more data in order to determine the place of drug-coated balloons in vascular access, in light of debate surrounding paclitaxel use in the femoropopliteal artery.

Nicholas Inston (left) chairs the CX Vascular Masterclass panel

T

he session had started with Panagiotis Kitrou (Patras, Greece) presenting the latest update on the Lutonix AV Global Registry and investigational device exemption trial, Qizhuang Jin (Beijing, China) presenting the results of a study of haemodialysis arteriovenous fistulae stenosis treated with Aperto (Cardionovum), and Andrew Holden (Auckland, New Zealand) discussing baseline data from the full cohort of the IN.PACT AV trial.

Following these presentations and the panel discussion, moderator Nicholas Inston (Birmingham, UK), asked the audience two questions; first, if they will continue to use drug-coated technology in their practice, and second, whether they believe more data are needed. While very few delegates voted for either continuing or ceasing use of drug-coated technology, there was consensus that more data is needed in order to determine the place of drug-coated balloons in vascular access treatment.

The panel was made up of Panagiotis Kitrou, Andrew Holden, Robert Jones (Birmingham, UK), Kate Steiner (Stevenage, UK), Domenico Valenti (London, UK) and Qizhuang Jin. Based on the discussion, it was clear that the Katsanos et al meta-analysis has had an impact on clinical practice in the field of vascular access. Jones, for example, mentioned that in his hospital in Birmingham, UK, a randomised trial on fistulas was “paused” and that drug-coated technology has been removed from the hospital. “I cannot see us starting to use them again any time soon,” he commented.

Holden expressed his opinion, saying it was a

“shame” that a randomised trial had been stopped, and asked the question: “In what other format would you want to be looking at this than in a clinical trial?”.

Steiner had questions about elements missing from the available data: “As well as the older patients that we treat, we do treat young patients who are going to have a transplant and probably are going to do relatively well.” She then asked the other panellists: “How do we feel about treating that patient population, in which there is a proven benefit? With that population I think it is a bit more of a difficult discussion to have.”

Holden commented: “All you can do is discuss it with patients and say here are the data. I hope that we get more information and that it changes the discussion a bit.”

There was agreement in the room, however, that presenting data to the patient and leaving the final decision up to them often leads to the question “What do you think?” in the hope that they will receive a definitive, straightforward answer.

Kitrou remarked that “here are many assumptions that we can make. We have been discussing this over and over again”, alluding to the fact that the need for new data is becoming increasingly apparent.

At the end of the session, after a show of hands from just about all delegates, Inston concluded that “It looks like people want more data.”

Looking forward, upcoming randomised controlled trials—some of which are company and others which are investigator initiated­—may be able to shed light on the questions surrounding these concerns.

The role of surveillance in thrombosis treatment As part of the Charing Cross Symposium (CX; 15–18 April, London, UK) Vascular Access Masterclass, Colin Deane (London, UK) considered the role of surveillance in thrombosis, asking whether there exists a test that is simple, safe, precise and timely. While it has been established that using angioplasty, stenting or surgery to treat thrombosis associated with stenosis is effective and that intervention is effective in reducing morbidity, questions remain regarding surveillance.

THE FOCUS OF Deane’s presentation was measuring access flow by ultrasound, beginning with an overview of his early personal experience using this technique during his post-doctoral studies in Philadelphia, USA. This involved ultrasound measurement of flow in comparison with status and dynamic pressure and looked at it with a technique that used M-mode colour flow in grafts and fistulae at zero, five and 10 months.

Deane then went on to describe the King’s College London dialysis access surveillance programme using a Zonare Z.One ultrasound scanner (Mindray). The flow was measured in the inflow artery, and then an ultrasound examination of the circuit was carried out for stenosis and thrombus in false and true aneurysms.

Flow and stenosis were then graded on a traffic light system and e-mailed to the access team for action. Surveillance was then reset for the following intervention.

This is going to be best where people are interested in it, trained and understand the clinical problem.”

Deane elaborated on the traffic light grading system they used to grade the surveillance findings, noting that all ‘Green’ scans had a six-month follow-up arranged, and represented flows either >600ml/min or which showed no reduction since the last scan, and in >50% of which no stenosis was identified.

‘Amber’ scans, representing a drop in flow rate >20% but flows still >1,000ml/min or unchanged flows of >600ml/min, had a three-month follow up arranged and, finally, ‘Red’ scans were assumed to require action and thus no follow up was arranged. These represented flows of <600ml/min with or without stenosis.

Deane further noted a few issues that arose during the programme, namely flow measurement errors Continued on page 30

June

Endovascular options gain ground in creation of haemodialysis lifelines Dimitrios Karnabatidis Konstantinos Katsanos Panagiotis M Kitrou Comment & Analysis Until recently, creation, maintenance and restoration of vascular access function was entirely performed by open surgical methods.

However, it is becoming apparent that endovascular management is a valid treatment option and a comparable alternative to the open surgical one, write Dimitrios Karnabatidis, Konstantinos Katsanos and Panagiotis M Kitrou from Patras, Greece, who are organising the first Endo Vascular Access (EVA) Meeting on the topic on 21–22 June 2019, in Patras, Greece.

V

ascular access constitutes the “lifeline” for haemodialysis patients. Until recently, creation, maintenance and restoration of function (when thrombosis occurred) was performed by open surgical methods.

However, it is becoming apparent, verified even in the most recent surgical and interventional guidelines for vascular access, that endovascular management is a valid treatment option and a comparable alternative to the open surgical one.1–3 In the last decade, there has been a continuous development of novel endovascular tools and devices (some of which were initially tested in the arterial vascular bed) that have made the endovascular approach faster and more appealing. Different types of wires and catheters, low profile devices, highpressure balloons, drug-coated balloons, scoring balloons and covered stents have improved patency rates, and in many cases circuit survival.4 Each of these devices offers an additional option to the operator. High-pressure balloons have revolutionised vascular access treatment, mainly because stenosis in this specific vascular field is characterised by an aggressive fibromuscular thickening that

needs high pressures of up to 40atm, in many cases, to enable treatment. Drugcoated balloons have allowed for more extensive use of high-pressure balloons by decelerating the effect of restenosis.5,6 Covered stents offer a valid bail-out option in cases of persistent stenosis or elastic recoil; pseudoaneurysms; and ruptures—and there is Level 1 evidence supporting their use as a primary option for the treatment of venous graft anastomotic stenosis.7 When thrombosis occurs, endovascular treatment with thrombolysis, thrombectomy or, in many cases, a mix and match of these procedures offers quick, safe and efficient ways of blood flow restoration. It also allows the patient to return immediately to haemodialysis without the need for central venous catheter placement.8 Several thrombectomy devices are available on the market and there is already extensive clinical experience with these devices. An important benefit of endovascular treatment is that it offers the ability to perform, in the same setting, both declotting and treatment of the underlying stenosis, which in the majority of cases is the reason for thrombosis.

The role of surveillance in thrombosis treatment Continued from page 29

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and changes, the interpretation of stenosis, practical problems such as whether the scan window was to fit in with dialysis or transport, and resource issues including having to stop the programme for two years

“EndoAVF”, a major advancement

Lately, there has also been a major advancement in the vascular access field with the endovascular creation of AVF. This innovation occurs in a scenario where the gold standard (open surgery) has a failure rate of more than 50%.

With two systems already available on the market (WavelinQ [BD] and Ellipsys [Avenu]) and with evidence detailing their benefits beginning to mount, patients will have the opportunity to have their fistula created without the need for surgical cut-downs, incisions and sutures, which are largely responsible for failure of maturation and future stenosis.

Being available via a 4F radial or “wrist” access or under ultrasound guidance, these fistulas are created in the deep venous system. “EndoAVF” provides additional vascular access creation sites (two when WavelinQ is used and one when Ellipsys is employed) and could conceivably become the primary option for fistula creation. The reason for this is that “endoAVF” does not implicate the superficial venous system, which is the

We feel that there is a need to help disseminate education and awareness in this area.” system used in the open surgical fistula creation. Additionally, in case of failure, conditioning of the superficial outflow veins of the arm may occur facilitating faster surgical fistula maturation.

Even though there is a growing role for endovascular vascular access management, centres performing these procedures remain low. We believe it is important for all specialties involved to understand the benefits that endovascular approaches provide to haemodialysis patients. Meetings on the specific subject remain highly “open surgery oriented and those with broader audiences sometimes combine vascular access treatment with venous disease. We feel that there is a need to help disseminate education and

due to a lack of funding.

According to Deane, the resolution of a large number of studies on this topic remains “elusive” and that due to the complexity of flow, surveillance remains “controversial”. He mentioned in particular two studies from 2019 which argued for and against the idea that vascular access surveillance in mature fistulae is worthwhile.

Deane posited that there are some questions that remain regarding surveillance of thrombosis. Firstly, the relationship of change in flow and degree of stenosis is complex and

Colin Deane

awareness in this area, particularly among nephrologists on the endovascular pathway/service they can provide to their patients. Endovascular therapists, either interventional radiologists, vascular surgeons or interventional nephrologists would also gain from staying current with developments in the field with a view to improving the care available to haemodialysis patients. In light of the current developments in this field, hospital multidisciplinary team meetings should involve endovascular specialists and congresses on the specific subject should be geared towards a multidisciplinary approach. It is in this context that the EVA (Endo Vascular Access) Meeting was created—its content is specifically designed to focus on the treatment options that the endovascular approach offers to haemodialysis patients. From EndoAVF, trial updates and treatment of symptomatic central venous stenosis to central venous catheters and background development, the EVA Meeting presents a multidisciplinary faculty of physicians from around the globe. The first EVA Meeting will be held in Patras, Greece on 21–22 June 2019.

Dimitrios Karnabatidis is a professor of interventional radiology, Patras University Hospital, Patras, Greece.

They are also directors of the EVA meeting. Konstantinos Katsanos and Panagiotis M Kitrou are assistant professors of interventional radiology.

References 1. Dariushnia SR, Walker TG, Silberzweig JE, et al. Quality improvement guidelines for percutaneous image-guided management of the thrombosed or dysfunctional dialysis circuit. J Vasc Interv Radiol. 2016;27(10):1518–30.

2. Ibeas J, Roca-Tey R, Vallespin J, et al. Spanish clinical guidelines on vascular access for haemodialysis.

Nefrologia. 2017;37 Suppl 1:1–191.

3. Schmidli J, Widmer MK, Basile C, et al. Editor’s Choice – Vascular Access: 2018 Clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55(6):757–818.

4. Kitrou P, Papasotiriou M, Katsanos K, et al. Recent developments in endovascular interventions to sustain vascular access patency in haemodialysis patients.

Nephrol Dial Transplant. 2018.

5. Trerotola SO, Lawson J, Roy-Chaudhury P, Saad TF, Lutonix AVCTI. Drug coated balloon angioplasty in failing AV fistulas: A randomized controlled trial. Clin J Am Soc Nephrol. 2018;13(8):1215–24.

6. Kitrou PM, Papadimatos P, Spiliopoulos S, et al. Paclitaxel-coated balloons for the treatment of symptomatic central venous stenosis in dialysis access: Results from a randomized controlled trial. J Vasc Interv Radiol. 2017;28(6):811–7.

7. Haskal ZJ, Trerotola S, Dolmatch B, et al. Stent graft vs. balloon angioplasty for failing dialysis-access grafts. N Engl J Med. 2010;362(6):494–503.

8. Kitrou PM, Katsanos K, Papadimatos P, et al. A survival guide for endovascular declotting in dialysis access: Procedures, devices, and a statistical analysis of 3,000 cases. Expert Rev Med Devices. 2018;15(4):283–91.

dependent on flow, site of stenosis and artery diameter. Additionally, he questioned whether there is an optimal interval for surveillance, and whether one-size-fits-all is effective. Finally, he remarked that costs remain a question related to surveillance.

After giving a brief overview of some “exciting” new technology in this field, Deane concluded: “This is going to be best where people are interested in it, trained and understand the clinical problem.”

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Paclitaxel devices in dialysis access: Should we be concerned?

Robert Jones Kate Steiner Nicholas Inston Comment & Analysis A Vascular Access Masterclass panel discussion at the recent Charing Cross Symposium (CX; 15â&#x20AC;&#x201C;18 April, London, UK) considered the use of paclitaxel devices in vascular access (see article on page 29). Here, for Vascular News, Robert Jones, Kate Steiner and Nicholas Inston explore questions arising from this dialogue, as well as the key take-home messages for vascular access specialists.

PACLITAXEL DEVICES HAVE been used in the maintenance of dialysis access. The predominant use is that of drug-coated balloons (DCB) and drugeluting stents (DES). These devices are still in evaluation with a number of large multicentre global trials in progress.

A recently published meta-analysis using data from peripheral vascular disease (PVD) studies has raised concerns regarding inferior survival in patients treated with paclitaxel-eluting devices. The meta-analysis published in the Journal of the American Heart Association analysed 28 randomised controlled trials (RCTs), including 4,432 patients of paclitaxel balloons versus plain balloon angioplasty.1 The analysis demonstrated significant increase in mortality at two years, further increasing at five years in the paclitaxel group versus control.

Whilst it is recognised that none of the trials were powered to examine mortality, the association has been robustly presented and has led to much debate internationally regards the safety of these devices and how to approach their continued use. Neither the paper in question nor any other study has been presented which addresses whether this effect should be a concern in an arteriovenous (AV) access population and whether data from use in PVD is applicable to patients with renal failure and on dialysis.

Are the data from the metaanalysis relevant to dialysis patients per se?

Whilst similarities between dialysis and PVD patients exist, such issues as higher rates of hypertension and diabetes, for example, there are fundamental differences related to the use of DCB between the groups. An immediate difference is the application in vascular

access is almost exclusively for venous stenosis and not arterial atherosclerosis.

This may be relevant although the cause of increased mortality with paclitaxel in PVD has not been offered to date.

Dose has been implicated with the increased mortality rates and hypothesised to be associated with higher dose devices, but lower dose DCBs are currently available for use in AV access. However, this argument remains nebulous in the sense that a threshold dose has not been estimated and it is likely this will not be possible. In other words, what is a safe dose of paclitaxel and is any association with mortality indeed dose related at all?

In cancer studies where paclitaxel has been used as a chemotherapeutic agent in much higher intravenous doses, no increased mortality was demonstrated.

The benefits [of paclitaxel] demonstrated to date outweigh the possible risks.â&#x20AC;?

Although it is recognised that the majority in the paclitaxel group died from cardiovascular and respiratory causes, these are also common causes of death in renal failure patients.

The PVD data also included drugeluting stents which are not applicable to AV access. A large randomised trial of DCB versus plain balloon has been published recently which demonstrated many benefits of using DCB in dialysis fistula stenosis, including statistically superior patency at 240 days and a lower number of reinterventions in the DCB group in the two year follow-up. Whilst no significant differences in mortality

between the groups at two years have been presented, five-year data are lacking.

An important consideration in both patient groups is the consequence of not using a DCB. In PVD where the use is for claudication, the risks of not using a DCB may be increased disease but not decreased survival. In dialysis patients, the consequences are loss of autologous access and progression to reliance on a central venous catheter for dialysis.

Dialysis with a central venous catheter has been shown to have a significantly higher risk of death than AVF. 2,3

What would be required to assure the safety of paclitaxel devices in dialysis access patients?

Patient level data from the PVD metaanalysis would further help to untangle this debate in general, but to date have not been published. Mortality data from the already presented and published AV access DCB trials would be a good starting place in terms of safe and continued use of DCBs in the AV access setting.

In some countries DCB trials have been suspended until regulatory bodies issue specific usage advice. It is assumed that increased data in vascular access use will be required.

Further data generation is problematic as some DCB studies have been paused resulting in a lack of data generation.

The trial data from the IN.PACT AV trial will be available later this year. Data from the Lutonix (BD) study showed mortality at 24 months that was lower in the treatment group than that expected for haemodialysis patients and not significantly different than the control group. This may add to the data required but may be not enough to provide total reassurance. Other studies such as the UKbased PAVE trial has finished recruitment but longer term mortality data from this and other trials will not be available for some time.

What are the implications to patients going forward as well as those who have already been treated with paclitaxel devices?

A key issue is what to inform patients who have already had a paclitaxel device in the last few years. Regulatory departments have not provided robust guidance and recommendations have largely been left to the individual practitioner or healthcare institution for risk-benefit assessment. In many areas this has understandably led to a halt in the use of these devices. The issue of consent is difficult. Patients must be made aware that data for the PVD cohort that have been linked to higher late mortality and informed consent process must include this. The evidence for the benefits of DCB studies in access are still awaited, so the approach to consent remains somewhat unbalanced.

Whilst this would be one way to address continued use and providing patients with information and choice, it is arguably a minimum standard of practice.

In a trial setting these data are essential

yet likely to be challenged by ethical committees.

Take-home messages

The mortality link with paclitaxel studies remains an association with no causation being defined and is to date specific to PVD patients. To our knowledge this association has not been demonstrated in AV access treatments although lack of analysis is recognised. Dose related effects seem unlikely and cannot reliably be used to justify proceeding with use of DCB in vascular access without a degree of caution. Differences in drug delivery and usage do not have an easily explainable basis that justify safety beyond speculation.

The continued use of paclitaxel technology in AV access will remain controversial for some time without further data and without guidance from regulatory bodies. It is acknowledged that the US Food and Drug Administration has not as yet banned these devices and several international societies have issued statements in support of continued and cautious application. Whilst there is no evidence to support or refute the association between late mortality and paclitaxel-coated balloon use in AV access interventions, the questions still remain. The overall feeling is that DCB and paclitaxel is not only safe in vascular access, the benefits demonstrated to date outweigh the possible risks.

Despite this impression the lack of patient-specific cause of death in the cited studies of the meta-analysis it is difficult to definitively state this. The cause of death is consistent with those seen in both PVD and vascular access groups and if medicolegal challenges of death following DCB use occur the data to date may be difficult to defend.

As in all clinical scenarios the risk and benefit must be compared. For a vascular patient the risk of losing an autologous vascular access and converting to a central venous catheter is not comparable to a PVD patient with claudication. This must be carefully considered if data are to be applied across disease states.

Robert Jones is a consultant interventional radiologist at the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. Kate Steiner is a consultant interventional radiologist at East and North Hertfordshire NHS Trust, Lister Hospital, Stevenage.

Nicholas Inston is a consultant renal transplant and vascular access surgeon at the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. References 1. Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: A systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(24):e011245.

2. Dhingra RK, Young EW, Hulbert-Shearon TE, Leavey SF, Port FK. Type of vascular access and mortality in US hemodialysis patients. Kidney Int. 2001;60(4):1443-51.

3. Ravani P, Palmer SC, Oliver MJ, Quinn RR, MacRae JM, Tai DJ, et al. Associations between hemodialysis access type and clinical outcomes: A systematic review. J Am Soc Nephrol. 2013;24(3):465-73.

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Positive AV fistula outcomes following intraoperative pharmacological intervention using a perivascularly delivered sirolimus formulation

Intraoperative perianastomotic delivery of sirolimus is feasible, according to Sriram Iyer (Lenox Hill Hospital, New York, USA). Based on preliminary data from 56 arteriovenous fistula (AVF) patients treated with intraoperative perivascular sirolimus, there are no safety concerns, and, using hard clinical endpoints, there is a strong efficacy signal measured by maturation success and suitability for dialysis at six months. In addition, the data show some consistency, with minimal variability and durability of treatment effect.

A

ccording to Iyer, “The reason why you want to use sirolimus is because the molecular rationale is very well understood”. He adds: “Unlike sirolimus, paclitaxel is a cytotoxic drug.

Sirolimus is cytostatic, and that difference may translate into a useful effect on the safety profile which we can successfully harness.”

Iyer mentioned that there is also a clinical rationale behind a stent-based endovascular sirolimus delivery.

“Over six million coronary stents have been sold worldwide using the sirolimus molecule and we have very long-term longitudinal follow up,” he said.

Iyer described that 30 patients were studied in a Phase 2 trial, involving two sites and two surgeons.

Twenty-two of the patients were radio-cephalic, and eight of them were brachio-cephalic. Safety, efficacy and pharmacokinetics were the endpoints and patients were followed up at two, four, six, and eight weeks, and three, six, nine and 12 months.

He then went on to describe the current, ongoing, Phase 3 prospective randomised single-blind trial that is being conducted in multiple centres across the USA. He commented: “The first patient enrolled by every surgeon at every site definitely got the drug product and is termed an open-label subject. Once that subject is enrolled

the trial enters the randomised phase which is where it is right now. The patients were randomised 1:1, with controls receiving a plain AV fistula, and the treatment patients getting a local sirolimus delivery.”

Thirty patients were included in Phase 2. These patients had a mean age of 51 (25–77) and 60% were male. Twenty per cent had diabetes, and all patients were on dialysis. In Phase 3, there were 26 patients, with a slightly higher mean age of 62 (30–91). Seventy-seven of these patients were male, and 69% were diabetic. Ninetyfive per cent of these patients were on dialysis.

In the composite cohort of 56 patients, the mean age was 56 (25–91), 58% were male, 43% were diabetic, and 98% were on dialysis. “Importantly, this [last figure] is a key strength of the trial as it shows how almost all of these patients were on dialysis at the time the fistula was created except one so that allows us to assess the success of the treatment using hard clinical endpoints.”

Iyer commented: “The maturation success using very robust clinical definitions was more than 80%.” Indeed, the figure was 87% in the Phase 2 group, 85% in the Phase 3 open label group, and therefore 86% across all patients.

Additionally, he explained that “use at six months comes close to about 80% as well,” based on figures of

76% in the Phase 2 group, 81% in the Phase 3 group, and 78% overall.

Iyer presented the outcomes of 56 AVF patients treated with sirolimus—30 from the Phase 2 and 26 from the Phase 3. In terms of safety, he noted that there was no risk of systemic immunosuppression, and that were were no problems with wound healing and no risk of infection. Finally, he noted that there was no increase in fistula thrombosis within six weeks.

“By day 90, 69% of the sirolimus-treated fistulae could be used for two-needle dialysis. The usual number in the USA by 90 days is 20–25% and that is important because 80% of all patients in the USA start dialysis on a catheter and the quicker you can use the fistula the quicker you can get rid of the catheter”, Iyer commented. He concluded: “There are two things I want to point out here. One is the internal consistency of the data and two, these 26 patients in the open label represent the output of 26 separate surgeons across the USA addressing also the issue of variability.”

Iyer recently presented these data at the Charing Cross Symposium (CX; 15–18 April, London, UK), where he revealed that the US Phase 3 randomised AVF trial is “nearing enrolment completion,” adding, “we should have results on this trial next year.”

More patient-reported evidence might help to “individualise” vascular access care “If we perhaps had more patient-reported evidence it might help us give a more balanced view to patients and be able to individualise their care,” concluded Melanie Field (University Hospital Birmingham, Birmingham, UK) at the Charing Cross Symposium in London, UK (CX; 15–18 April).

Melanie Field

ACCORDING TO FIELD, there is an increasing focus on achieving the “right access for the right patient at the right time” and one of the main questions is whether it is possible to get patients more involved in that in order to help clinicians to make the best decision.

Field explained that patient-reporting was originally split into just patient reported experience measures (PREMs) and patient reported outcome measures (PROMs). She expanded on this by detailing that while PREMs are divided into relational factors, such as being listened to, and functional factors, such as facilities, PROMs are “more about things like pain and bleeding”.

She commented on this division and categorisation of patient reporting: “There has been a growing awareness that splitting things up arbitrarily is probably not the most logical way to go and the

healthcare intervention.

Field then went on to describe a number of tools that exist to assess patient-reported outcomes, including generic tools such as the SF-36, which assesses multiple items across many domains, including physical function, mental health, and emotional status, and also a number of condition-specific tools such as the Oxford hip and knee scores and the EQ-5D-5L. In the vascular access space, Field noted that there exists a Vascular Access Questionnaire, which is currently under initial development work in Canada.

Seventeen different items, including bleeding, pain, infection, and swelling, are ranked on a scale of zero to four in relation to their extremity and then summed from 0–68. The resulting composite score from the questionnaire is used to examine the impact of access

focus now has changed more to patientcentred outcome measures (PCOMs).”

Traditionally, Field described, clinicians have always collected “hard outcomes” such as infection rates, mortality, and complications, and use those as a way of comparing different operations or different treatment strategies. However, “although very useful, there may be other outcomes that matter to the patient just as much that we should also really be considering,” she commented.

Field mentioned that patient reporting has been used successfully in a number of areas of medicine. For example, it has been shown to improve survival and quality of life in oncology patients, and has been used in conjunction with hip and knee surgery in order to guide treatment. It has also been used as an adjunct to determining “value” in a

in the last four weeks, with a lower score denoting a better outcome.

According to Field, the literature suggests an overall pattern that arteriovenous fistula use gives better quality of life and health status scores and there is a suggestion that central venous catheter use correlates to lower scores.

However, “It is hard to differentiate other aspects related to dialysis that could have impacted access choice,” and asks the question: “Are all aspects equally weighted by all patients?”

Field believes it is important to put more of an emphasis on effective patient reporting going forward as “patients are often quite reticent to tell us the exact reason why they do not want a fistula,” concluding: “I think we have to give them the right to actually give us a really decent explanation as to what it is that they want to change or why they do not want a fistula,” She suggests that patient reporting may help clinicians as it “may help to open the dialogue with the patient about what is important to them in terms of their vascular access” and hopes that “with more data we might be able to help people make a better decision or decision that works better for them in terms of the right access at the right time”.

She continues: “Possibly we could even then work on developing some patient decision making tools that would then would then give some of the autonomy back to the patient in terms of making those decisions.”

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BIBABriefings

BIBA Insights

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FDA letter may lead US physicians to use fewer drug-coated balloons Following a letter from the US Food and Drug Administration (FDA) that advised against the use of paclitaxel devices in most patients with peripheral arterial disease, according to a new survey, most (68%) US-based physicians think that they will use fewer drug-coated balloons this year than they did last year. A previous survey, conducted just after the Katsanos meta-analysis was published (December 2018), found that only 55% of US-based physicians thought that they would use fewer of these devices.

Source: BIBA MedTech Insights

A

fter the publication of the Katsanos meta-analysis (December 2018), the FDA performed a preliminary analysis of the long-term follow-up data of FDAapproved paclitaxel devices. As reported in the FDA letter (published March 2019), this analysis showed higher mortality in patients who were treated with paclitaxel-coated devices than those treated with uncoated devices.

Furthermore, the letter says: “For most patients, alternative treatment options to paclitaxel-coated balloons and paclitaxel-eluting stents should generally be used until additional analysis of the safety signal has been performed”.

However, it says physicians may believe that the benefits of paclitaxel devices outweigh the apparent risks “for some individuals at particularly high risk for restenosis”.

Subsequent to this letter, BIBA MedTech surveyed 275 physicians about their anticipated use of paclitaxel devices in the femoropopliteal arteries this year (vs. their actual use last year). Of these, 60% were from Western Europe, 17% were from North America, and 23% were from other regions.

Overall, 45% of respondents anticipated using fewer drug-coated balloons this year compared with how many they used last year. However, when the results for the subgroup of US respondents were reviewed, the proportion who report that they anticipate using fewer drug-coated balloons increased to 68%. A similar trend was seen with drug-eluting stents—66% of US-based physicians believe they will use fewer stents this

Source: BIBA MedTech Insights

year compared with 39% of respondents overall. Among Western European respondents, 50% think they will use fewer drug-coated and 42% say they will use fewer drug-eluting stents.

Impact of Katsanos metaanalysis vs. impact of FDA letter

In early January 2019, as reported in the last issue of Vascular News, BIBA MedTech conducted a survey of 107 physicians to determine the immediate impact of the Katsanos meta-analysis. In this survey, 46% of physicians were from Western Europe, 25% were from North America, and 29% were from other regions. The number of US physicians in this first survey who thought they would use fewer drug-coated balloons was considerably lower than in the second survey: 55% vs. 68%, respectively. See Figure 1. Similarly, the proportion of US physicians who think their use of drug-eluting stents will go down this year was lower in the first survey: 36% for post-Katsanos survey vs. 66% for the post FDA survey. Of note, for Western European physicians, their anticipated use of both drug-coated balloons and drug-eluting stents remained relatively stable between the two surveys: 49% vs. 50% for drug-coated balloons and 40% vs. 42% for drug-eluting stents, respectively.

Between the Katsanos meta-analysis being published and FDA letter being published, several companies released patient-level data for their paclitaxel devices and various conferences held special sessions reviewing the safety of paclitaxel devices. In particular, a

highlight of the 2019 Charing Cross Symposium was the “Paclitaxel: The last word” session (see page 1). Therefore, the increase in the number of US physicians anticipating a drop in the number of paclitaxel devices that they use could be the result of several factors.

However, that such an increase was not observed among Western European physicians does suggest that the FDA letter has had an influence on the attitudes of the US physicians (given that the FDA only regulates the US device market).

Of note, this does not mean that the FDA letter has not had any influence on Western European physicians. In fact,of respondents who think that they will use fewer paclitaxel devices this year (in the second survey), 68% of US physicians and 74% of Western European physicians say that their decision is a “direct result” of the FDA letter. Furthermore, only 43% and 60%, respectively, say that the Katsanos meta-analysis directly affected their anticipated use of devices this year.

Alternatives to paclitaxel

In the post FDA letter survey, if they stated they would use fewer paclitaxel devices, respondents were asked what

they would use as alternative treatments.

Of 95 respondents overall, most (68) said that they would use plain old balloon angioplasty rather than drug-coated balloons. The remaining respondents said that they would use speciality balloons (10), bare meta stents (eight), interwoven nitinol stents (six), and other methods (3). See Figure 2.

Regarding alternatives to drug-eluting stents, 72 overall, 38 would use bare metal stents, 21 would use interwoven nitinol stents, five would use plain old balloon angioplasty, three would use speciality balloons, and five would use other methods.

68% of US physicians and 74% of Western European physicians say that their decision is a ‘direct result’ of the FDA letter.”

BIBA Briefings BIBA Briefings provide in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America. The platform also reviews data and news.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact Merveille Anderson merveille@bibamedical.com

34

June

CX highlights: Acute Stroke Challenges This year, the 2019 Charing Cross Symposium (CX; 15–18 April, London, UK) opened with the Acute Stroke Challenges programme; the session, which was chaired by Barbara Rantner (Innsbruck, Austria), Hugh Markus (Cambridge, UK) and Ross Naylor (Leicester, UK), featured five CX debates, covering carotid challenges, intracranial thrombectomy, and stroke after cardiac surgery.

The debates

In the first debate of the session, 73% of the audience voted against the motion:“It is reasonable to offer urgent carotid endarterectomy (within the first 48 hours) in patients suffering a minor stroke.” Sofia Strömberg (Gothenburg, Sweden), who presented the case against the motion, reviewed the potential issues of performing endarterectomy in this timespan: increased risk of recurrent stroke and the risk of the surgical procedure.

She outlined data pointing to this increased risk, and argued that, as a result, delaying the procedure to two days post stroke is a safer treatment option.

Clement Darling III (Albany, USA), in his bid to get the audience to vote in favour of the motion, outlined a range of studies and argued that the higher risk observed in this time window may be due to other factors such as procedure timings, patient selection and surgeon experience. However, he said, offering the procedure within the 48-hour window is “absolutely reasonable”.

The real question, he maintained, was how other factors may influence the outcomes of carotid endarterectomy.

The second debate of the Acute Stroke Challenges session saw the audience vote in favour of the motion— “the majority of patients with asymptomatic carotid disease do not benefit from carotid interventions”— with 76% voting in favour vs. 24% voting against.

Ross Naylor (Leicester, UK), who was speaking for the motion, said: “The vast majority of patients with asymptomatic carotid disease will never benefit from a one-size-fits-all approach to treatment.” He urged that “we [physicians] need to be more selective, and identify the high risk for stroke patients, and then offer surgery or stenting”. Alun Davies (London, UK) argued against the motion, and stated that carotid endarterectomy decreases the risk of stroke, and that its “results are improving with time”. He added that it is “undoubtedly a cost-effective strategy”.

For CX Executive Board member Hugh Markus, this debate was a particular highlight of the Acute Stroke Challenges. Describing the debate as “excellent”, he told Vascular News: “In the end, perhaps both [speakers] concluded that, in certain patients, if you can select those that are very high risk, it is worth operating, but in the majority of other patients it may not be.”

Davies had better luck in the third debate, in which 64% of the audience agreed with him that carotid revascularisation (with surgery or stenting) was not safe to be performed early after thrombolysis. This result was despite his opponent Maarit Venermo (Helsinki, Finland) raising some chuckles from the audience when she cited a paper in support of her argument that carotid revascularisation in this setting was safe, on which Davies was an author. Davies countered playfully with a series of research articles to back up his point of view.

In the following discussion, Venermo maintained that the best timing is between two and seven days following thrombolysis. She cautioned against delays because of the potential for strokes to occur: “I do not think it is wise, because we never know what happens to these patients while we are waiting.” Davies stated that he would wait for a minimum of 72 hours.

In the fourth and final debate of the carotid challenges section, 75% of the CX audience voted against the motion that newer technologies and innovations have made carotid artery stenting as safe as carotid endarterectomy in the first 14 days after a transient ischaemic attack or stroke. Peter Schneider (Honolulu, USA), who was arguing for the motion, commented:

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Conference coverage

“There is an increased risk of stroke [with stenting] in recently symptomatic patients but that is using outmoded devices. Proximal protection is better and proximal protection with reversed flow (i.e. transcarotid artery revascularisation or TCAR) is even better than that because it avoids the arch and has better particle capture.

TCAR is as safe as endarterectomy even in patients who are recently symptomatic”.

Naylor countered this view by saying the evidence for TCAR “was not there across the whole generality of stroke patients”. While he “suspected” there would be “more equipoise” between stenting and endarterectomy in the future, at present, the evidence still favours surgery “for the vast majority of symptomatic patients undergoing intervention within seven to 14 days”.

However, the closest vote of the debate was the one in which Jan Kovac (Leicester, UK) and Andrew

Intracranial thrombectomy is one of the huge advances in stroke care at the moment.”

Intracranial thrombectomy

The debate on intracranial thrombectomy was part of a whole session dedicated to the procedure. Markus, who was chairing the session, called intracranial thrombectomy “one of the huge advances in stroke care at the moment”. Outlining its significance, he said “for every three patients we treat, we can cure one, so it is a massive treatment effect. It has transformed stroke care.”

In a keynote lecture, David Hargroves (Kent, UK) reviewed what thrombectomy trials “really tell us”, and how the findings can be implemented into routine clinical practice. In light of DAWN and DIFFUSE-3, he said that there is a strong evidence basis for thrombectomy and that this treatment should be available to all patients. Additionally, Hargroves posited that regional and countrywide networks are required to deliver and achieve its 10% potential reach. However, he said, caution is needed when reorganising stroke services, so as not to destabilise the ‘core’ business and therapeutic benefit of organised care, closest to home.

The session was moderated by Barbara Rantner.

Thomas Liebig (Munich, Germany) looked at the use of virtual reality in thrombectomy training. He described his own training as similar to that of learning to drive a car, and contrasted it with the simulator experiences of pilots who must demonstrate their competencies in a virtual environment. Liebig pointed out that skilled performance is difficult to characterise, and then outlined his work with University College Cork (Republic of Ireland) to develop surrogate parameters for performance metrics that can be used in a simulator.

The findings, he said, “have the potential not only for training purposes” but, in a nod to the earlier debate on intracranial thrombectomy, could also allow us to “discriminate between a person who can do the procedure and those who should be doing something else”.

Acute Stroke Challenges took place in the Pillar Hall Learning Centre

Clifton (London, UK) discussed whether intracranial thrombectomy should be limited to neurointerventionists.

Kovac (a cardiologist), whose proposition was that it should not be limited to neurointerventionists, won the debate with 57% of the vote, but a substantial minority (43%) supported Andrew Clifton’s arguments that the procedure should be limited to neurointerventionists.

While Clifton argued that experience and proper training leads to “appropriate patient selection [and] faster, safer procedures with fewer complications”, Kovac said that, given the magnitude of the potential clinical and economic benefits of mechanical thrombectomy, a “collaboration of various interventional specialists is desirable to deliver this therapy to a wider population”.

Acute Stroke Challenges panel after the first debate

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June

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Wound care

The benefit of early anklebrachial pressure index measurement for vascular wound care

CX Executive Board member Una Adderley (Wakefield, UK), director of the National Wound Care Strategy Programme for the National Health Service (NHS) England, spoke at the Charing Cross Symposium (CX; 15–18 April, London, UK), on the challenge of anklebrachial pressure index (ABPI) for managing vascular disease.

Adderley argued for the benefits of introducing ABPI assessment, claiming the data support that a significant majority of amputations due to chronic vascular disease could be prevented with its use.

ADDERLEY TOLD CX delegates attending the wound care session that an “accurate diagnosis is the foundation of any treatment decision”. The ABPI is, she argued, a “relatively accurate” test for arterial insufficiency—“more valid and reliable than pedal pulse palpation and more portable than duplex scanning”.

Furthermore, Adderley pointed to literature that raises issues of interpretation with other diagnostic methods, such as peripheral pulse palpation.

In addition to allegedly inaccurate diagnostic tools, Adderly directed the audience’s attention to an All-Party Parliamentary Group report on vascular and venous disease in the UK, which highlighted that “every two hours, a patient in England loses their leg due to complications” related to peripheral arterial disease. Adderley described this as an opportunity for improvement, telling the audience at CX: “With early arterial assessment, 80% of these amputations would be prevented”.

Adderly then commented on what she perceived as the “suboptimal use of compression for venous leg ulceration”.

Citing support from articles published in Journal of Wound Care and Journal of Tissue Viability, she informed attendees that in north-east England, 23.6% of leg and foot ulcers are not assessed using Doppler ultrasound, and 46% of venous leg ulcers in the same region are not in compression.

Data from an individual English healthcare district evidenced that 33.6% of leg ulcers are not assessed using Doppler ultrasound, and 25% of venous leg ulcers are not in compression.

Using these data as evidence of a problem with the management of vascular disease in England, Adderley said that the solution was the early use of the ABPI measurement. She called for a service redesign, emphasising, in her eyes, what the benefits would be: “Opportunities for deliberate practice, access to equipment, and knowledge re-interpretation”.

With early arterial assessment, 80% of these amputations would be prevented.”

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The increasing importance of interdisciplinary wound care

ular ss nges

Keith Harding Comment & Analysis Keith Harding advocates for the increased involvement of medical staff in the treatment of patients with wound healing difficulties, as the number of chronic wounds seen in hospitals is on the rise. He argues that wounds “do not receive the attention they deserve”, and that patients are suffering as a result. Currently, he says, the majority of patients are seen by nurses, but additionally require input from specialists working across a wide range of disciplines.

Harding believes that “there is no question that [vascular surgeons] have a significant amount to contribute to the management of patients with a range of wound problems”, and sets out his supporting arguments here.

I

t is increasingly recognised and accepted that wounds are both common and expensive in clinical practice. Recent publications have suggested that up to 10% of the National Health Service (NHS) expenditure in the UK is directed towards treating patients with wound healing difficulties.

Although the cost of the products used to affect wound healing is significant, the majority of the costs are driven by the inefficient, fragmented and haphazard way in which services are provided to patients with wounds.

In recent years, in most parts of the world, patients with wounds and wound healing difficulties are often seen as something that medical staff do not get involved in. This is because wounds are seen as a trivial problem that is delegated to nurses and other healthcare professionals, rather than something that merits the attention of medical staff. This has resulted in a greater focus on wound management and wound dressings rather than wound healing.

The wounds seen in clinical practice are caused by a wide diversity of clinical problems and conventionally divided into acute and chronic wounds. Chronic wounds are increasing in number because of changing demographics in western societies and it is recognised that although not all of these chronic wounds will heal, they do not receive the attention they deserve. In considering patients with leg ulceration, although most studies would suggest that by far most common underlying condition is venous disease, it should be recognised that there is a wide diversity of underlying diseases that can produce chronic ulceration of the leg. It is important, therefore, to

recognise that a diagnosis has to be made as to that underlying condition, and once this has been undertaken an appropriate treatment regime should be offered to those patients. In patients with venous ulceration, there is increasing evidence that the role of surgery to correct the underlying venous disease may have a significant impact on healing.

Despite this, in most healthcare settings, these patients are seen by nurses, who spend a considerable amount of time working on the choice of dressings and bandages to treat these wounds.

Keith Harding

Wound care Similarly, patients who develop pressure ulceration, which can be caused by a wide variety of medical conditions, may require the input of geriatricians, dermatologists, rehabilitation physicians, plastic surgeons, microbiologists, neurologists and spinal cord injury specialists. An increasingly important problem is that of diabetic foot disease— here, is it the role of the diabetologist, the vascular surgeon, orthopaedic surgeon, or microbiologist?

For vascular surgeons, there is no question that they have a significant amount to contribute to the management of patients with a range of wound problems, as common sense would suggest that no wound will heal if abnormalities in the vasculature are not addressed. In patients with arterial disease, there is no prospect for healing if there is insufficient blood supply or tissue oxygenation. In patients with venous disease, then surgical correction, where feasible, is an important aspect of assisting healing and preventing recurrent ulceration occurring. Similarly, there are many other wound situations where vascular intervention is a cornerstone of good care.

Unfortunately, even if the vascular supply and venous return from a wound is optimised, that still does not necessarily result in the healing of that patient’s wound. There are a number

37

of issues associated with infection, offloading, oedema control and the impact of various drugs on wound healing that require the input of a range of clinical expertise.

The biggest driver of change in wound healing over recent years has been from industry, which has developed a number of new and novel approaches to affect wound healing. These approaches do, however, lack a robust evidence-base on which clinicians can make decisions to treat patients with proven effective interventions. It is important to appreciate that many patients require a range of interventions to affect closure of their wound problems that include, but are not exclusively focused on, the choice of dressings, bandages, mattresses and other devices. In addition to these interventions, there is a potential role of drugs, surgery and—if we follow the trends that are seen in the USA— biological approaches to healing which will be the next big advance in terms of treatment options that have failed for patients with wound healing difficulties.

Keith Harding is the professor of Wound Healing in the School of Medicine at Cardiff University, Cardiff, Wales, and works at the Skin Research Institute of Singapore. His clinical practice is exclusively focused on treating patients with complex wound healing problems.

For vascular surgeons, there is no question that they have a significant amount to contribute to the management of patients with a range of wound problems, as common sense would suggest that no wound will heal if abnormalities in the vasculature are not addressed.”

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June

Regionalisation of ruptured abdominal aortic aneurysm is safe and cost-effective Clement Darling III Comment & Analysis Clement Darling III discusses how the regionalisation of ruptured aneurysm repair to tertiary care centres equipped for both endovascular and open repair has helped decrease the overall mortality of these “gravely ill” patients by approximately 20%.

F

or over five decades, mortality for ruptured abdominal aortic aneurysm (rAAA) has remained unchanged. Without surgical repair, a ruptured aneurysm is a universally fatal event. For many years, mortality for rAAA has remained unchanged, reported between 35% and 70%.

Endovascular aneurysm repair (EVAR) for rAAA has expanded, with multiple recent reports documenting lower short term morbidity and mortality in patients treated with EVAR instead of open repair. Frank Veith and Takao Ohki were the first to perform EVAR for ruptured aneurysm in the USA. In the collective world experience published in 2008, over 1,000 cases has been performed globally, with a mortality of around 22%. This allowed for an emerging model of care delivery in the transfer of patients with ruptured aneurysms to centres with the necessary expertise and infrastructure in place to adequately deal with this lethal pathology. Several centres have published experiences developing a multidisciplinary approach to expedite EVAR for ruptured aneurysms. Our group, as well as others, have undertaken a strategy of regionalisation of ruptured aneurysm care based on the realisation that it is more efficient to transfer patients to a centre with an infrastructure that allows for early identification and seamless expeditious transfer. Our goal was to have a waiting time of less than half an hour between arriving at the receiving hospital’s emergency room and the beginning of the procedure.

Our system was based on the current US model for trauma care delivery. The American Trauma Society led the fight for nationwide quality trauma care.

Its foundational goals were to prevent injury and trauma and when trauma occurred, to ensure the victim be cared

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Abdominal aortic aneurysms

for “by the right people, in the right place, at the right time.” Our goals as vascular surgeons and providers of regional vascular care should be no different. One reason that rAAA mortality has been unchanged in the last 50 years may be that many regions do not have a cohesive system to deal with this highly lethal problem. As we branched out to provide vascular surgery coverage for more than 16 hospitals over a 100-square mile area in upstate New York, we started to regionalise vascular emergencies for efficiency and to streamline delivery of emergent vascular care.

Courtney Warner, one of our vascular surgeons, recently examined the outcomes of regionalisation for care of ruptured aneurysms. We performed a retrospective study of all ruptured aneurysm patients treated by our vascular group in New York state. During the study period, we

and looked at outcomes such as 30-day perioperative mortality and if patients died during transport. A total of 451 patients with rAAA were treated over this period. Most (71%) presented initially to a community hospital. Of these, 133 (41%) were treated at the community hospital, and 59% were transferred to the academic tertiary care medical centre. The mean time from diagnosis to patient transfer to the medical centre was 1.2 hours.

There was no significant difference in demographics. Patients were more likely to undergo EVAR at the tertiary care medical centre: 94% of patients treated at community hospitals underwent open repair, whereas in the tertiary care centre just 38% did, with the remaining 62% undergoing EVAR. At the community hospitals, 30-day mortality was 46%.

Among the transferred patients, the overall 30-day mortality was 27%.

At the medical centre, EVAR was associated with a lower 30-day mortality rate compared with open repair (20% to 37%; p=0.001), and most importantly transfer did not negatively influence mortality (20% for patients at the medical centre undergoing EVAR and 20% for patients transferred to the medical centre). Therefore, all ruptured aneurysm mortality at the tertiary care centre was 20% lower than the community hospitals (27% vs. 46%; p<0.001).

We have developed an educational system to assist emergency room doctors with rapid diagnosis of ruptured aneurysm and set up a “hub and spoke” system similar to a trauma network.

Developing this system required negotiation with numerous hospital emergency departments and emergency medical technicians to transfer these patients immediately. Since we work at many of these community hospitals, we realise that most if not all do not have 24-hour in-house anaesthesia. Many times it takes up to two to three hours to have an operating room ready. This was not acceptable for patients with ruptured aneurysms. The concept of scoop and run was used to deliver these patients, both stable and unstable, to our tertiary care facility. Since only about 75% of patients

Regionalisation of ruptured aneurysm repair to tertiary care centres equipped for EVAR and open repair decreases overall mortality by approximately 20%.” developed a multidisciplinary team consisting of surgeons, emergency physicians, anaesthesiologists, nurses and radiology technicians. If a patient was suspected of having a ruptured aneurysm, the vascular surgery on-call team was alerted and the patient was either transferred to the tertiary medical centre or stayed at the community hospital to be operated on by one of our board certified vascular surgeons.

We evaluated our 13-year experience

during this time period had anatomy amenable to EVAR, the staff needs to be flexible and comfortable with both endovascular repair and open repair.

Importantly, the hospital has to invest in a significant amount of infrastructure for aortic grafts, fixed radiologic units, wires and catheters, as well as staff, such as vascular trained nurses, intensivists and the back-up of general surgery, cardiology and other supporting services to take care of these gravely ill

patients.

There have been reports by Matthew Mell and colleagues who demonstrated that in a large, nationwide inpatient database, the survival of transferred patients treated with EVAR for ruptured aneurysm was eclipsed by the increased mortality of the transfer process; however, they found that some patients lose their window of opportunity because the transferring hospital had delays in finding an accepting physician in the hospital— thus delaying definitive treatment. In our system there is one number that each emergency room can call, the patients are accepted automatically, and the vascular emergency team is notified in advance. In most cases, the scans can be reviewed before the patient arrives in order for us to designate which operating room the patient should go to; whether it will be an open repair or an endovascular repair. This allows for a smooth, expeditious transfer of patients out of these community hospitals to the tertiary care centre. We strongly believe that this is why our results differ from those seen by Mell and others. Interestingly, in a separate dataset of 82 patients with ruptured aneurysms over a two-year period, our group found that the cost margin was positive for the hospital for patients with open and/or endovascular repair (11% vs. 4% respectively); with open repair having a better positive margin than endovascular due to the cost of the grafts, in spite of the increased length of stay. Again, we would strongly argue, that in hospitals not prepared for the complexity of rAAA, they will lose money. However, if you create an infrastructure that can support the expeditious diagnosis, transfer and comprehensive care of these critically ill patients, the results will not only be better, but also more cost effective.

In our experience, regionalisation of ruptured aneurysm repair to tertiary care centres equipped for EVAR and open repair decrease overall mortality by approximately 20%. Patients tolerated transfer well, even those that were unstable. Transfer did not negatively impact mortality at our tertiary care centre, and this highlights the importance of infrastructure, treatment algorithms, and coordination with community hospitals and emergency medical technicians to encourage expeditious patient triage to specialised centres that offer 24/7 coverage, surgery, anaesthesia and intensive care.

Currently, the Society for Vascular Surgery and the American College of Surgeons are working together to develop standards and possible accreditations of centres capable of caring for ruptured abdominal aortic aneurysms and other vascular emergencies.

Clement Darling III is chief at the Division of Vascular Surgery, Albany Medical Center Hospital; he is also director of the Institute for Vascular Health and Disease, Albany Medical Center, Hospital, USA.

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June

Nikolai L Volodos: Developing endovascular repair in the Soviet Union Alexei Svetlikov Yulia Valentinovna Kalashnikova Comment & Analysis Until quite recently, a great part of the international surgical community was not aware of the outstanding scientific and practical achievements of professor Nikolai L Volodos in the field of invention and clinical application of vascular stent-grafts, and this article by Alexei Svetlikov and Yulia Valentinovna Kalashnikova serves to describe in detail how this development took place.

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olodos was born on 15 May, 1934 in Belarus and in 1950 he moved to Ukraine, where he graduated from Odessa Medical Institute in 1958. From 1962 to 1965 he studied thoracic and abdominal surgery at the postgraduate faculty of Kharkov Medical Institute, guided by famous professor Alexander Alexeeviych Shalimov, who he considered his main teacher. In 1965—when he was only 31 years old—Volodos was appointed to the post of head of the Vascular Surgery Department of the Kharkov Medical Institute. In 1992, he founded the Kharkov Centre of Cardiovascular Surgery, and resided as its first director. Volodos was also a visiting professor at several foreign institutions, and shared his experiences in a generous manner throughout his career. He worked in Paris, France with professors Christian Cabrol and Iradj Gandjbakhch of Pitié-Salpêtrière hospital, at the thoracic and cardiovascular surgery clinic (1992, 1999, 2004, and 2011), as well as at the Thoracic Surgery Department of Vienna University Clinic in Austria. Volodos also spent some time in the USA, visiting professor Bruce W Lytle at the Thoracic and Cardiovascular Surgery Clinic of the Cleveland Clinic in 1997 and 2000.

The original development of a large vessel endoprosthesis replacement method came as a surprise to most foreign specialists. This method had been studied on models, in experiments and in the clinic within the former Soviet Union. The distinctive feature of this project was that when creating the tools for experiments, and then for use in the clinic, the only devices used were those that had been developed by native specialists, specifically for the national medical industry enterprises of the Soviet Union and its military industrial facilities—no imported devices were used at all.

Volodos thought that this fact pointed to huge possibilities, considering the large creative intellectual potential, of the former Soviet Union as well as modern Russia, in realisation of such projects.

A more than 30-year-old project of stent graft engineering was performed “from scratch” due to the available peculiar cooperation of scientific and technical institutions and teams in supporting medicine. Support is here defined in a wide sense—from performing medical projects for creation and development of new treatment methods or improvement of existing ones, to providing medical institutions with new equipment.

As is already well known, a stent grafting method assumes using an integral complete self-fixing synthetic prosthesis—unlike “bare” spring-stents, intended to keep vessel diameter after angioplasty. By the start of Volodos’ team’s work, there was no such prosthesis

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Endovascular aneurysm repair

in the world. The difference of the project realised by Volodos and his colleagues was that the main purpose of it was simply the creation of a self-fixing synthetic prosthesis as the key element in stent grafting.1 It was necessary to develop a structure that, once introduced into the prosthesis, would give it the ability to self-fix. For this purpose, they invented, developed, and searched for the radial Z-shaped spring that gave the prosthesis the ability of self-fixing once it was sewn into the prosthesis lumen. So, for the first time in world practice, a real self-fixing synthetic endograft was created. A similar Z-shaped structure was registered in the USA five months after the patent had been registered in the USSR, and it was named the Gianturco stent. One gets the impression that this patent was simply copied. During the Cold War, the adversaries on each side of the so-called Iron Curtain did not respect each others’ patents—a fact that Volodos’ innovation may have suffered from.

From springs to balloons: Developing the prosthesis design

Many technical works were performed in the Institute for Low Temperature Physics and Engineering (ILTPE)

Nikolai L Volodos

of the National Academy of Sciences of Ukraine, headed by Boris Ierimeevich Verkin as director, who was Volodos’ patient and friend. The project would not have been clinically implemented without him as the director of the Institute—with its technical, material and professional capabilities—due to his personal concern and wish to help Volodos in making his dream of the remote aortic prosthetics come true. Verkin established a special group at the ILTPE dealing with remote endoprosthetics, and every Monday he held telephone conferences on this issue.

Nikolai Volodos’ team, together with research and development institutes, studied the function of newly created self-fixing synthetic endograft in models, including segments of cadaveric aorta, as well as the conditions of blood pulsatile flow. Radial force parameters required for safety fixing of a spring and a graft in a vessel in the conditions of blood pulsatile flow were studied.2 Yulia Valentinovna Kalashnikova joined the team of professor Volodos in August 1983, when she graduated from Kharkov National University with a degree in biophysics. When she started her work with this team, the spring prosthesis studies in dogs had been carried out at full speed. Those were springs using ferrous metal, as stainless steel was not yet known at the time. The investigators incubated prostheses with the springs sewn-in in saline solutions to simulate blood composition and monitor the oxidation of metal.

Rust put by the ferrous metal on the prosthesis tissue was frequently observed. In order to intensify the experiment, the spring was boiled in these solutions.

First, Volodos’ team was searching for a method to isolate the spring from the blood flow to prevent potential toxicity due to metal oxides. The spring was covered by metallising: silver, gold, different alloys, and latex rubber and glue compositions. When medical stainless spring wires were developed, the problem was solved. At Volodos’ request, 40КХН10МТЮВИ stainless steel wire was manufactured in Moscow exclusively for his team by the Bauman Moscow State Technical University at their pilot production.

Toxicity studies of this steel were performed again, and it was proven that it caused no harm to the human body. Biological investigations demonstrated good biocompatibility of the stainless wire with the body tissues. Microscopic histological studies of changes in the vascular wall, in the contact area with the stainless steel spring, and in the contact area of the prosthesis with the spring sewn in, showed that indicated changes were consistent with those observed in the synthetic prosthesis implantation.

Some questions arose: what effect was the spring having on the prosthesis tissue? Would it not disrupt the prosthesis after full disclosure of the spring?

Tear strength of the prosthesis tissue was tested using specialised equipment. It was shown that, in comparison with the zigzag radial spring, the force needed to start prosthesis tissue tearing was 100 times more than the spring force.

Here was another problem concerning the tissue of the prosthesis. When calculating the intrinsic area of the compressed prosthesis, it turned out that the tissue of the crimped prosthesis occupied the most part of this area. The scientists tried to reduce the thickness of the tissue by smoothing the crimp with an iron, but tear strength tests nevertheless showed that the tissue of the prosthesis lost its properties and was not able to stand spring radial force. Volodos and the team began stretching the crimps without any hightemperature exposure using specialised bend formers at the temperature up to 40ºС resulting in no significant reduction in prosthesis tissue resistance.

Simultaneously, tear strength test of the cadaveric aorta was performed. It was proved that cadaveric aorta was able to stand the radial force of that 8–10 times exceeding the spring force.

There were also experiments in flush tests of prostheses with springs (hereinafter referred to as an

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X-ray of first canine with stent graft implant (1984)

endoprosthesis) to see how the endoprosthesis would behave in the vessel affected by the blood stream. At the first stage, water hammer tests were performed under different pressures in the system without a pulsatile flow. Endoprosthesis could stand the water hammer under pressure of 200–250mmHg. First, glass models were used, followed by the fixing tests of the endoprosthesis inside the cadaveric aorta in order to bring the experiment closer to the real conditions in which the endoprosthesis would be used in the human body. The next stage involved the experiments using pulsatile flow and heart-lung machine. No shifts of the prosthesis along the aorta were observed even with the capacity of six litres per minute. The impact of increased pressure of up to 400mmHg was studied in pulsatile flow, and it showed no shifts of self-locking prosthesis even when the aortic pressure was high which was impossible inside the living human body.

Thus, the self-locking synthetic prosthesis placed in the patient’s aorta and exerting pressure on the aortic wall using a fixing element (stent) was shown to resist to flushing by the blood stream. The results of the experiments were subsequently used by Nikolay Emmanuilovich Terniuk for theoretical calculations of radial stiffness of the zigzag spring. Together, these experiments and theoretical calculations created the basis for estimating the use of fixing elements, including nomograms, produced for such purposes.

The subsequent development of the balloon catheter required the invention of the device protecting the syringes from destruction due to high pressure produced in the balloon catheter, thereby increasing the doctor’s operational safety.

The first endoprosthesis procedure

After the examination of spring radial force, a number of experiments were conducted on large dogs which demonstrated good functioning and implantation of the endoprosthesis. It was the first experimental system which had very long mainlines of fluoroplastic, with complicated and heavy devices connecting to the system. The whole endoprosthesis system was formed inside the filling part which was subsequently pushed into the transportation unit through clamp

Endovascular aneurysm repair

41

coupling. Later it was found that the long length of pathology, and anatomic data were subjected to a kind those fluoroplastic mainlines produced high resistance of “mathematisation”. The method drove development and required great physical efforts to mount the of new diagnostics methods, and made it possible to endoprosthesis. This system allowed Volodos—for treat patients with aortic dissection and disruption, who the first time ever in the world—to perform an earlier were doomed to die. It was the precondition to endoprosthetic replacement using this method in develop new methods of replacement with fenestrated, the clinic for iliac artery, as well as abdominal and branched, and chimney prostheses, as well as the thoracic aorta replacement. sandwich-methods of Armando Lobato. Stent grafting The method of stent grafting procedure then was also the basis for a new chapter of endovascular continued to progress, as a combined (hybrid) methods in treatment of heart valves pathologies, with endovascular and open repair of aortic arch aneurism endovascular replacement of heart valves. was developed and applied, again for the first time.

The achievements of professor Nikolai Leontyevich The method was also used in urgent conditions for Volodos include the following: emergency pathology treatment—massive pulmonary Development and manufacture of the prosthesis fixing haemorrhage at aortobronchial fistula. element, i.e. a Z-shaped spring Abovementioned interventions were performed Study of its properties, primarily, radial force five to seven years earlier than they were applied Development of the endoprosthesis abroad. However, it so happened that the literature Study of its behaviour in cadaveric aortic lumen under showed that the method was just about developed conditions of pulsatile flow and originally applied by foreign authors, despite Development of the endoprosthesis diameter matching being five years after the work of Volodos. His system depending on the diameter of the vessel developments, despite many modern publications including nomogram formation in national and foreign journals, was kept in the Development of the delivery system background until recent years.

Development of the special balloon catheter for the Since 2012, due to the principal position of some prosthesis settling in foreign scientists, including Krassi Ivancev (UK, Development of endoprosthesis replacement method London) and Martin Björck (Uppsala, Sweden), Carrying out of the experimental study in animals recognition of Volodos’ contributions have increased. including morphological changes in aorta and Since 2013 with Edward Dietrich in Phoenix, USA, endoprosthesis several large historical sessions were performed within Clinical use of endoprosthesis for various bloodstream leading international congresses, where Volodos’ work segments (including endovascular aneurysm repair was officially document-supported.

(EVAR) and thoracic endovascular aortic repair The important role of Sebastian Debus (Hamburg, (TEVAR) Germany) and Arkadiusz Jawien (Bydgoszcz, Poland) In recent years, we were lucky enough to work in international recognition of closely with professor Volodos.

Volodos’ achievements must also Anyone who knew him saw be emphasised. Finally, in Porto, his incredible internal force, Portugal, and the European Society modesty and decency of the for Vascular Surgery (ESVS) annual unbroken person. meeting in 2015, Volodos became Until his last days, Volodos an honourary member of the ESVS continued to work to the “in recognition of outstanding extent that he could, keeping contribution […] to the development in touch with leading foreign of endovascular surgery, particularly, specialists, and staying in performing the first in the world the know of the newest procedure of endovascular stent information on endovascular graft implantation on May 4, 1985.”3 techniques and cardiovascular Two weeks after his death, Volodos surgery. The millions of was also awarded an honorary lives saved thanks to the membership of the Society for technologies invented by Vascular Surgery (SVS).

Volodos and others serves as At the initial stage of the project, monument for his work with Volodos attempted to enable the his colleagues. release of national endografts and We will have to understand delivery systems in the Soviet Union. and acknowledge the Though they were close to perform phenomenon of Volodos and this task, the disintegration of the his team. We are certain of Soviet Union occurred at the clinical the need for preservation and trials stage. The attempt to realise Yulia Valentinovna Kalashnikova historical memory of him and this task for Ukraine in the following preparing a device for an his achievements, because years was unsuccessful. Volodos endoprosthesis flush test the personality of Nikolai continued to hope for the rest of his Leontyevich Volodos is the career, that a competitive self-fixing endograft and its greatest example of devotion to science and medicine, delivery system made in Russia would be created to strength and courage, humanity and belief in oneself. realise the method that was first created in the Soviet Alexei Svetlikov, ESVS councillor, is at the Department Union. In his opinion, Russia had the opportunity and of vascular surgery of the Memorial LG Sokolov ability to create specialised industrial facilities for Clinical Hospital No. 122 and the North-Western production of these devices. Volodos considered it Medical University named after II Mechnikov, in St abnormal that stent-grafting continued to be performed Petersburg, Russia. in Russia using systems created by import companies, paying for labour of foreign specialists contributing to Yulia Valentinovna Kalashnikova is at the Kharkov intellectual development of this method abroad.

Centre of Cardiovascular Surgery in Kharkov, Ukraine.

Looking back at 30 years’ application of the stent References grafting method, it should be noted that it was the 1. V olodos NL, Shekhanin VE, Karpovich IP, et al. A self-fixing synthetic new chapter in endovascular surgery relating to aorta blood vessel endoprosthesis. Vestn Khir Im I I Grek. 1986; 137(11): 123–125. and large diameter vessels with its specificity and 2. S vetlikov AV. Unknown pages in the history of vascular stent-grafting Journal of Vascular Surgery. 2014. 59:865–868. features. It modified the treatment scheme for aortic 3. B jörck M. The Fall of a Giant: Professor Nicolai Leontyevich Volodos, May and large vessel diseases. It forced us to revaluate 15, 1934–April 3, 2016. European Journal of Vascular and Endovascular Surgery.

Vol. 52, Issue 1, p. 3–4. and clarify anatomy of thoracic and abdominal aortic

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Endovascular aneurysm repair

EVAR with an iliac branch endoprothesis is safe and effective Speaking at the Charing Cross Symposium (CX; 15–18 April, London, UK), Fabio Verzini (Turin, Italy) reported that endovascular aneurysm repair (EVAR) with an iliac branch endoprothesis (Gore) is safe and effective.

He added that the procedure was associated with improved quality of life in the short term and walking capacity was preserved.

“WE KNOW THAT if we perform EVAR, we wither have to occlude the iliac artery or to preserve it with an iliac branch. But if we do occlude the iliac artery, according to one paper, the risk of vascular complications is between 29% and 36%. Using a device to preserve the iliac artery is associated with favourable results [in terms of morbidity and mortality],” Verzini commented. He added that morbidity and mortality were not the only clinical outcomes of relevance in this context “as we need to have patient-reported outcomes”.

Therefore, the aim of the present study was not only to confirm previous findings of EVAR with an iliac branch endoprothesis but also to “know what the patients think” about the procedure.

In the prospective, multicentre, single-arm study, 102 patients (mean age 75; all male) underwent EVAR with a minimally invasive iliac branch endoprothesis.

The clinical endpoints were mortality, aneurysm-related mortality, the rate of reinterventions, and patency; the

Fabio Verzini

patient-reported outcomes were quality of life, walking ability, and erectile function.

The average procedure time was 147 minutes with an average fluoroscopy time of 41 minutes.

Additionally, 75% of patients underwent the procedure via percutaneous access and 59% received local/regional anaesthesia. Overall, the technical success rate was 100%. At 30 days, mortality was 1% as was aneurysmrelated mortality and the rate of iliac artery occlusion.

Overall, 36% of patients had an endoleak, but, of those with an endoleak, only one had a type 1c endoleak. By one year, 3% of patients had died with no aneurysmrelated mortality at this time point.

Furthermore, quality of life—as measured by

the EQ5D score—was significantly improved at one month compared with baseline levels: 78±13 vs.74±16, respectively (p=0.035). At one-year followup, quality of life scores had decreased but were still improved compared with baseline levels (although not to significant extent). Additionally, the percentage of patients without erectile dysfunction increased from 49% at baseline to 62% at one year (p=0.037).

Concluding, Verzini reported: “Aortoiliac endografting with the Gore iliac endoprothesis is safe and effective.

Quality of life is positively affected by the intervention in the short term, walking capacity is preserved at one year, and erectile function is impaired in this elderly population and is slowly decreasing during follow-up.”

Late rupture after EVAR is rare but incidence is increasing, study finds Vincenzo Brizzi (Bordeaux, France) presented at the Charing Cross Symposium (CX; 15–18 April, London, UK) the 10-year results for late rupture after endovascular aneurysm repair (EVAR) at his centre (Groupe Hospitalier Pellegrin, Bordeaux, France). These showed that late rupture was a rare event—accounting for 15% of all ruptured aneurysm cases during the 10-year period—but indicated that there had been a slow increase in incidence to the extent that it had reached 28% by 2018.

B

rizzi noted that the concern over the long-term results of EVAR was “clear”, commenting that the recent European Society for Vascular Surgery guidelines recommend operators take into account a patient’s ability to comply with the frequent lifelong surveillance that is required with the endovascular procedure when reviewing potential treatment options. He added that part of this concern related to studies showing that “the risk of death from aneurysm rupture [following EVAR] is persistent over time”.

To further explore the long-term outcomes after EVAR, Brizzi and his colleagues performed a retrospective study of the incidence of patients presenting with late rupture after EVAR—defined as >30 days after the procedure, as confirmed by computed tomography (CT)—at their centre. Their aim, Brizzi commented, was to “report the incidence, identify the causes, and evaluate the management” of late rupture. He explained that in-hospital

mortality rather than 30-day mortality was the primary endpoint because “we noticed that, sometimes, patients stay in the hospital for two or three months without ever leaving the hospital before dying” and, therefore, in-hospital mortality would give a “more precise idea” of the mortality related to late rupture than would 30-day mortality.

Of 140 cases of ruptured aneurysm that presented between 2009 and 2018 (the study period), 121 (86%) were identified as late ruptures after EVAR. The incidence, Brizzi observed, appeared to slowly increase over time—ranging from 0% in 2009 to 28% in 2018. He stated, that although the presumption might be that the late ruptures related to early-generation devices, only one of the late ruptures was associated with such a device and most of the ruptures occurred in the last four or five years (when a newergeneration device would have been used). The mean time between the EVAR procedure and late rupture was 54

months (with a peak during the second after the procedure).

Sixty-six per cent of patients with late rupture post EVAR had a type 1 endoleak but Brizzi noted that determining whether this was a cause or an effect of aneurysm evolution was difficult to determine. Additionally, 33% of cases of late rupture were related

The risk of death from aneurysm rupture is persistent over time.” to a “violation of instructions for use” (ranging from poor device selection to the patient having a short neck).

In terms of management, 14 patients received endovascular repair (12 with proximal or distal extension and two undergoing relining) and four underwent

surgical repair (three partial expansions and one lumbar artery ligation). The inhospital mortality rates for these patients were 28.5% and 50% respectively. These findings, Brizzi stated, indicated that “a new endovascular procedure is often possible” but “sometimes conversion is the only option”. Overall, in-hospital mortality was “still high” at 42.8%.

Summarising the findings, he said: “Late rupture after EVAR is a rare but an increasing complication. Respect of instructions for use at the time of index EVAR and lifelong tailored surveillance seems to be essential for long-term success.” He added that “tailored” surveillance was important because the first CT scan after EVAR could be used to identify those at high risk of rupture (<10mm proximal or distal sealing and/ or endoleak) and should receive more frequent surveillance. Thus those at lower risk for rupture could receive less frequent surveillance, reducing costs and the risks of complications related to radiation/contrast exposure.

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Data show good results in high-risk aneurysm patients with F-BEVAR after careful selection Results from a large, single-centre data review in France provide critical information regarding patient selection and expected outcomes in the most difficult of endovascular aortic aneurysm repairs.

The study was published in the Journal of Vascular Surgery, with the findings recently highlighted by the Society for Vascular Surgery.

PARAVISCERAL AND THORACOABDOMINAL aneurysms are the most challenging cases for vascular surgeons. The combination of patient co-morbidity and complex paravisceral aortic anatomy mandates utmost surgical judgment, technical skill and a multidisciplinary approach to achieve acceptable outcomes.

While open surgical repair has been the standard of care, advances in endovascular techniques offer hope to those considered too high-risk for traditional open surgery.

Previous research suggests advanced age, history of congestive heart failure, aneurysm diameter and chronic renal insufficiency are the most important risk factors determining the outcomes for infrarenal endovascular aneurysm repair. Limited data exist with regards to more complex proximal repairs given the few reports for fenestrated and branched endovascular aneurysm repair (F-BEVAR).

As reported in the May 2019 edition of the Journal of Vascular Surgery, researchers from Lille, France led by Stéphan Haulon, reviewed their prospectively collected single-centre data involving 468 highrisk patients with pararenal or thoracoabdominal aneurysms treated with F-BEVAR from 2004 to 2016.

The clinical and anatomic characteristics of the cohort included: Age: 72 years (range 65–77 years) Male sex: 94% American Stroke Association (ASA) class 3 or 4: 95% Diameter: 58mm (range 54–64) Type 1–3 thoracoabdominal aortic aneurysm: 47% Type 4–5 thoracoabdominal aortic aneurysm: 53% Technical success for target vessel stenting was 99%.

Their early results included: 30-day mortality: 5% Spinal cord ischaemia: 4% Postoperative dialysis: 4% (0.8% long-term) The median follow-up was 29 months with a five-year survival rate of 60%. Freedom from vessel occlusion and secondary procedures were 90% and 70% at five years, respectively.

Early mortality was associated with procedure time, aneurysm diameter and chronic renal insufficiency. Mortality during the first 24 months

This mandates that high-volume centres be prepared to invest in the incrementally complex learning curve that this technology and these patients demand.”

iCARUS three-year results demonstrate safety and efficacy for covered stent in atherosclerotic iliac artery Three-year data from the iCARUS study have been published by John Laird (Adventist Heart & Vascular Institute team at St Helena Hospital, USA) and colleagues in the Journal of Vascular and Interventional Radiology (JVIR). The study investigated the safety and efficacy of the iCAST Covered Stent (Atrium Medical) used in atherosclerotic iliac artery lesions and has demonstrated the device’s “sustained clinical benefit out to three years.”

T

he iCARUS trial was a singlearm, prospective, multicentre study with 152 patients enrolled across 25 sites in the USA and Germany.

Included patients had lifestyle-limiting claudication or ischaemic rest pain, with a Rutherford category of 2–4. Criteria further included presence of de novo and/or restenotic lesions in the common and/or external iliac arteries. Lesions were <110mm long and 5–12mm in diameter, with at least 50% stenosis by visual estimate.

The primary endpoint in the study was a composite of all-cause mortality within 30 days, target lesion revascularisation within nine months or restenosis of the iliac artery detected on duplex ultrasound or angiography

at nine months. Secondary endpoints included major adverse vascular events, primary patency, freedom from target lesion revascularisation and clinical success.

The investigators report device and acute procedural success was achieved in 98.7% and 92.7% of cases, respectively. The nine-month composite primary endpoint was observed in 8.1% (10/123), which Laird et al note was below the performance goal set at 16.57%. Primary patency at nine months, “defined as continuous flow without revascularisation, bypass of target limb amputation,” was reported in 96.4% of patients, and freedom from target lesion revascularisation at nine months was 97.2%. At three

Stéphan Haulon

was also associated with more extensive, Type 1-3 thoracoabdominal aortic aneurysms.

“Our findings suggest that F-BEVAR can be performed in high-risk patients with excellent technical success, low 30-day mortality rate, and low rates of spinal cord ischaemia and permanent dialysis,” noted Haulon. “Additionally, our five-year survival rate of 58% is similar to other series, with the majority of deaths attributed to non-device and nonaorta-related causes.”

“The strength of this study lies in the large cohort of prospectively collected patient data, extensive followup and systematic approach to preoperative planning, execution, and surveillance,” Haulon noted. “Because the study covers a 12-year experience, there has been a transformation in practice and techniques over time.”

“We believe these procedures can be offered safely, even in high-risk patients; however, this mandates that high-volume centres be prepared to invest in the incrementally complex learning curve that this technology and these patients demand,” Haulon said.

years, freedom from target lesion revascularisation remained significant at 86.6%.

The benefit of covered stents Discussing the choice between different stent designs, the authors write that “whereas self-expanding stents are flexible and may induce less stress to the vessel, they may have less predictable deployment compared with balloonexpandable stents,” which Laird et al point out have greater radial strength— providing an advantage for ostial or calcified lesions. Expanding on the benefits of the iCAST device design, they add that a covered stent offers “the additional theoretical advantage of excluding complex atherosclerotic plaque and potentially reducing the risk of atheroembolism during the treatment of complex iliac lesions.”

The iCAST stent employs an expanded

[Selfexpanding stents] may have less predictable deployment compared with balloon-expandable stents.”

polyetraflouroethylene (PTFE) cover, encapsulating the 316L stainless steel frame. This expanded PTFE “may also serve as a barrier to subsequent neointimal ingrowth,” the authors hypothesise, “reducing the likelihood of in-stent restenosis.”

In discussion of the results, Laird et al further state that “PTFE covering was also associated with significantly increased luminal dimensions after stent placement, which may contribute to long-term patency,” and add that the cover “may serve as a barrier to smooth muscle cell migration, and thus covered stents may be associated with decreased intimal hyperplasia.”

Early clinical success was seen in 88.7% of subjects at 30 days with sustained clinical benefit in 72.4% of subjects at three years, and Laird et al conclude the iCAST stent remained safe and effective through to three years.

In discussion of the study limitations, they point to the lack of patency data confirmed by imaging beyond the initial nine months, with long-term effectiveness instead being based only on rate of reintervention. “Although the three-year clinical outcomes of the iCARUS study are promising, further studies are needed to evaluate the long-term effectiveness of iliac covered stents,” the authors state.

The iCAST Covered Stent is sold outside the USA as the Advanta V12 Stent (Atrium Medical).

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Product News Tack Endovascular System launches in USA, first commercial use announced

Intact Vascular has announced the first commercial use of its Tack Endovascular System in multiple sites across the USA. Recently FDA-approved for above-theknee interventions, the first-of-its-kind dissection repair device is implanted post-angioplasty to resolve dissections in patients with peripheral arterial disease (PAD).

“Dissections are an unavoidable consequence of balloon angioplasty. Now, with the Tack Endovascular System, we have an effective minimal metal solution to treat dissections above-the-knee, further improving our angioplasty outcomes,” states Nicolas W Shammas, founder and research director, Midwest Cardiovascular Research Foundation in Davenport, USA. “I am extremely pleased with my experience using Tack implants and believe this device will facilitate better care for my PAD patients.”

Balloon angioplasty, whether performed with plain or drug-coated balloons, inherently injures the vessel wall, creating dissections that may inhibit blood flow and promote thrombosis formation.

Despite the prevalence of dissections, they are frequently underdiagnosed and left untreated, often leading to further

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Market watch

complications and compromised patient outcomes.

“The Tack Endovascular System brings us unique clinical and economic advantages in the office-based-lab setting.

With six implants pre-loaded into a single delivery system, physicians can quickly and easily provide precision dissection repair along the vessel length,” stated John Rundback, vascular and interventional radiologist and partner at the New Jersey Endovascular & Amputation Prevention Services, LLC in Teaneck, USA. “This minimal metal therapy complements balloon angioplasty and avoids the complications a larger metal stent may cause, thereby preserving future treatment options.”

“In striving to provide the best care for patients, we actively seek new ways to improve the results of balloon angioplasty,” said Ehrin Armstrong, interventional cardiologist and director of

Tack Endovascular System

Interventional Cardiology at the Rocky Mountain Regional VA Medical Center in Denver, USA. “Based on my clinical experience using the Tack Endovascular System, I anticipate this targeted therapy will become standard of care for postangioplasty dissection repair.”

Surmodics Sublime guide sheath receives FDA 510(k) approval

Surmodics has announced it has received US Food and Drug Administration (FDA) 510(k) clearance for its Sublime guide sheath.

The highly flexible, proprietary Xtreme braid-reinforced Sublime sheath is designed to resist kinking and maximise strength while retaining a low profile.

The sheath will be available in 5F and 6F diameters, and 120cm and 150cm lengths. The entire working length of the guide sheath is Serene hydrophilic coated to provide a lubricious surface.

It is preloaded with a dilator and has a haemostasis valve with side arm for flushing. The dilators are available with .018” and .035” guide wire compatibility.

“Surmodics continues to make progress in the development of clinically important and innovative technologies,” said Gary Maharaj, Surmodics president and chief executive officer. “Our Sublime guide sheath will set a new standard for performance and enable the delivery of lower extremity interventions from the radial artery.”

Radial artery access has been widely adopted for use in coronary procedures

where devices have been developed to accommodate that need. The Sublime guide sheath is intended to introduce therapeutic or diagnostic devices into the vasculature, excluding the coronary and neuro-vasculature. Radial access offers many benefits relative to femoral access including reduced puncture site bleeding complications, earlier ambulation, reduced length of hospital stay, and lower healthcare costs.

The development of the Surmodics Sublime guide sheath is a step forward in the company’s strategy to be a provider of whole-product vascular solutions, including a family of radial access products. Surmodics has complete capabilities for design, development and high-volume manufacturing of a wide variety of highly differentiated balloon catheter and specialty catheter solutions.

Avinger receives FDA clearance for Pantheris SV

Avinger has announced that the company received 510(k) clearance from the US Food & Drug Administration (FDA) for its Pantheris SV (small vessel) image-guided atherectomy system.

Avinger is a developer of imageguided, catheter-based systems for the diagnosis and treatment of patients with peripheral arterial disease (PAD).

Pantheris SV, a product line extension of the company’s Lumivascular imageguided atherectomy platform, is expected to expand the available market for the product line by up to 50% and allow the company to address a larger portion of the

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Market watch Bloodstream infection is the second leading cause of death and a leading cause for hospitalisation in haemodialysis patients, with catheters causing the majority of these infections.

Product News estimated US$500 million atherectomy market. Designed with a lower profile and longer length than Pantheris, the small vessel device is indicated for the diagnosis and treatment of PAD in small vessels (2mm–4mm in diameter). The new device incorporates key improvements introduced to the platform with the launch of the next-generation Pantheris system in June 2018, including a stiffer shaft for increased pushability, a refined OCT imaging system, and an enhanced cutter design.

Pantheris SV

Pantheris SV received CE marking in October 2018 and the first patients were treated with the device in Germany in November. The company intends to initiate a limited launch of the device in several sites in the USA when commercial product is available. Distribution is expected to be expanded as the company gains additional clinical experience, builds product inventory, and receives purchasing approvals in new Lumivascular sites.

“We are excited to receive US premarketing clearance for Pantheris SV, which we believe could expand our addressable market for atherectomy procedures by as much as 50%,” says Jeff Soinski, Avinger’s president and CEO. “With the clearance of this new device, we are well-positioned to build on the positive momentum we have seen in our Pantheris business since the introduction of the nextgeneration system in 2018. Following our anticipated limited launch, we plan on leveraging our growing commercial infrastructure and installed base of Lumivascular accounts to efficiently scale up the introduction of Pantheris SV and drive growth of the product family in the second half of 2019.”

Jaafer Golzar, Avinger’s chief medical officer and a highly experienced interventionalist treating patients with small vessel disease, comments, “This product line extension represents a significant advancement for patients with PAD, in particular those suffering from the complications of small vessel disease. Treating small vessels presents a number of challenges and physicians have had a limited set of minimally invasive tools that can provide safe and effective outcomes for this high-risk patient population. Pantheris SV uses a combination of directional atherectomy with onboard image-guidance to provide several potential clinical advantages, including an enhanced safety profile, the ability to maximise luminal gain without causing vascular injury, and precise vessel measurement capabilities.”

Lumivascular technology allows

physicians to see from inside the artery during an atherectomy procedure with optical coherence tomography (OCT).

With the Lumivascular approach, physicians can more accurately navigate their devices and treat PAD lesions, thanks to the real-time OCT images generated from inside the artery, without exposing healthcare workers and patients to the negative effects of ionising radiation.

Pursuit Vascular gets CE mark for ClearGuard HD haemodialysis catheter caps

Pursuit Vascular, manufacturer of ClearGuard HD Antimicrobial Barrier Caps, has announced that the company has received both (CE) mark and Medical Device Single Audit Program (MDSAP) certificates for its haemodialysis catheter caps, paving the way for launch in international markets.

The CE marking confirms that the device meets the requirements of the European Medical Devices Directive, which now allows Pursuit Vascular to commercialise their catheter caps in the European Union and other CE mark geographies. The MDSAP certificate demonstrates compliance with regulations in Canada, Australia and Brazil. The company is pursuing applications to market in these countries to facilitate launch of ClearGuard HD caps internationally later this year.

“The CE mark and MDSAP approvals are significant accomplishments for Pursuit Vascular as it allows the company to expand sales to Europe and other key international markets,” said Doug Killion, president and CEO. “We look forward to working with hospitals and physicians in these countries to bring this lifesaving technology to more patients worldwide.”

The company has seen rapid uptake of the catheter caps in the USA following publication of landmark clinical studies demonstrating a ~70% reduction in bloodstream infections in patients using ClearGuard HD caps versus patients using standard caps or needleless connectors. The cap is the first and only device available for sale that kills infection-causing microorganisms inside a catheter hub between dialysis treatments.

PolarCath Balloon Dilation System

NuCryo Vascular announces Series B financing and launch of Extended PolarCath catheter

NuCryo Vascular, the manufacturer and marketer of the PolarCath Balloon Dilatation System, announced today that the company is raising a Series B round of financing and is launching its Extended PolarCath Balloon Dilatation Catheter.

The Series B financing will provide the necessary working capital to support the expected rapid growth of the PolarCath Balloon Dilation System while reaching corporate profitability in 2019. “Our supply chain has been optimised to meet our growing forecast, so the Series B financing round is critical as we prepare to scale in 2019,” said Kevin Beedon, general manager and executive vice president of NuCryo Vascular. “Scaling the operation will allow us to meet the growing demand for our system while lowering costs for our customers.”

The company is also launching its PolarCath Extended Catheter. “The extended catheter launch is a huge milestone for NuCryo Vascular as it not only improves the efficiency of our internal manufacturing process, but it also reduces inventory and costs to our expanding and loyal customer base,” stated Tri Tran, manager of operations for NyCyro Vascular. “The extended catheter launch improves our manufacturing capacity by nearly 50 percent, which is critical as we ramp up to meet the increased demand.”

The PolarCath Peripheral Dilatation System received US Food and Drug Administration (FDA) clearance in 2002 to dilate stenosis in the peripheral vasculature (iliac, femoral, popliteal, infrapopliteal, rena and subclavian arteries) and for the treatment of obstructive lesions of polytetrafluoroethylene (PTFE) access grafts or arteriovenous dialysis fistulae.

The PolarCath System is also indicated for post-deployed stent expansion of selfexpanding peripheral vascular stents.

“I am very excited for the PolarCath Extended Catheter as it provides a safe and effective anti-restenotic alternative to other currently available treatment options,” said Van Crisco, an interventional cardiologist from First Coast Heart & Vascular Center (Jacksonville, USA). “The extended

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catheter will not only make an already easy-to-use system easier, but by lowering the cost to the customer, it enhances the position of the PolarCath system in my peripheral treatment algorithm in the hospital as well as the office-based lab.”

The system is an angioplasty balloon that combines mechanical angioplasty and precise cryotherapy for the treatment of peripheral arterial disease. The PolarCath balloon has been used in over 270,000 procedures since its initial launch in 2002.

BD announces launch of UltraScore 014 Focused Force PTA Balloon

BD has announced the launch of their UltraScore 014 Focused Force percutaneous transluminal angioplasty (PTA) Balloon. This marks the first scoring balloon with sheath compatibility as small as 4F on the US market.

The UltraScore balloon is intended to dilate stenoses in the iliac, femoral, ilio-femoral, popliteal, infra-popliteal and renal arteries and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulae. This device is also recommended for post dilatation of balloon expandable stents, self-expanding stents, and stent grafts in the peripheral vasculature. UltraScore is designed to longitudinally fracture plaque at lower inflation pressures compared to standard PTA and may allow for more controlled plaque fracture and less vessel recoil, even in calcified lesions. With the addition of the 0.014” guidewire platform, the device is available in both 0.014” and 0.035” solutions with sizes ranging from 2mm to 8mm in diameter and up to 300mm in length.

“The deliverability, ease of use and expansion of the vessel with UltraScore Focused Force PTA Balloon are excellent,” commented William Bachinsky, director of the Cardiac and Vascular Interventional Program at UPMC Pinnacle. “The addition of UltraScore 014 Focused Force PTA Balloon will fit right in with our treatment algorithms for popliteal and infrapopliteal lesions.”

Both UltraScore 035 and UltraScore 014 devices are CE marked and have received 510(k) clearance by the US Food and Drug Administration (FDA).

Misonix to acquire Solsys Medical for approximately US$97 million

Misonix, a provider of minimally invasive therapeutic ultrasonic medical devices, has announced that it has entered into a definitive agreement with Solsys Medical, a regenerative medical company and allograft producer, to acquire Solsys in an all-stock transaction valued at approximately US$97 million.

Solsys markets an advanced wound care product under the brand name TheraSkin, a cellular and tissue-based product for regenerative wound healing designed to help healthcare professionals treat difficult-to-heal chronic wounds.

TheraSkin is a clinically proven, minimally manipulated, living human split-thickness skin allograft that is cryopreserved to retain living cells and

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The versatility in applications and sizes of TheraSkin reduces product waste and helps drive operational efficiencies to better manage total cost of care and quality outcomes needed to treat difficult to heal and chronic wounds. TheraSkin has been applied to over 100,000 wounds supported by multiple clinical studies.

The planned acquisition of Solsys substantially broadens Misonix’s addressable market through wound care solutions that are complementary to its existing products. In calendar 2019, Solsys is expected to achieve sales of approximately US$32 million. In fiscal 2020, the pro forma company is expected to generate over US$80 million in sales.

The combined company anticipates top line revenue growth in excess of 20% per annum over the next several years.

New update on Phase III clinical trials of REX-001 cellbased therapy for critical limb ischaemia

Rexgenero, a regenerative medicine company working to develop cell-based therapies to treat critical limb ischaemia (CLI), has presented an update on its two Phase III SALAMANDER trials being conducted across Europe for its lead development programme REX-001 to treat CLI in patients with diabetes.

During Rexgenero’s presentation at the Cell and Gene Therapy Meeting on the Med (23–25 April, Barcelona, Spain), organised by the Alliance for Regenerative Medicine (ARM), Joe Dupere provided an update on the Phase III programme with REX-001. Dupere, who is CEO of Rexgenero, announced that 12 of the 25 planned trial sites are now open and treating patients in Spain, Austria, Portugal, Poland, Czech Republic, and Hungary, with additional hospitals expected to be initiated by the end of the year in three additional countries.

REX-001 consists of bone marrowderived white blood cells extracted from the patient (autologous) and has shown efficacy in 80% of patients in Phase II and I/II studies. The company is planning to treat 138 patients in two Phase III SALAMANDER trials. The presentation highlighted encouraging clinical improvements in two patients treated in Spain with REX-001 out of protocol, as they did not meet the trial criteria.

Commenting in a company press release, Dupere states: “We are at a hugely exciting time for the company and, more importantly, for patients with CLI, as our Phase III trial sites for REX-001 are now treating patients in many countries including Spain. With our Spanish heritage, the location of ARM’s Meeting on the Med is particularly significant for Rexgenero. We are on track to open further clinical trial sites across Europe.”

Cook Medical releases patient-level data from Zilver PTX paclitaxel-eluting stent study

Cook Medical has released deidentifiable patient-level data from a clinical trial of its Zilver PTX peripheral paclitaxel-eluting stent.

The move comes a month after the US Food and Drug Administration (FDA) said that its preliminary review of longterm follow-up data found a “potentially concerning signal” of increased long-term mortality in people with peripheral arterial disease (PAD) who were treated with paclitaxel-coated devices compared to those treated with bare devices.

Cook Medical says it is releasing the data to encourage further collaboration with researchers to improve treatment of PAD. The company website states: “In the spirit of full transparency, Cook Medical is providing our extensive long-term data on Zilver PTX, our drug-eluting stent. Zilver PTX is a paclitaxel-coated stent that was approved by the FDA in 2012 through the premarket approval process.”

The Zilver PTX randomised, controlled trial followed 479 patients over five years in the USA, Germany and Japan.

Cook Medical stated it is the first company with paclitaxel devices to make its de-identifiable patient-level data publicly available.

“We will continue to support our customers and their patients by sharing what we have discovered from our research and data in the area of paclitaxel,” vascular division vice president Mark Breedlove said in a press release.

Last September, Cook Medical said that it won FDA approval for a smallerdiameter version of its Zilver PTX peripheral drug-eluting stent.

Surmodics provides update regarding TRANSCEND clinical trial

Surmodics has announced the company has now resumed patient enrolment into its TRANSCEND clinical trial, and is nearly 75% of the way to its goal of 446 randomised patients.

Patient enrolment in TRANSCEND, the pivotal clinical trial for the SurVeil drug-coated balloon (DCB), was temporarily paused following the March 15 publication of a US Food and Drug Administration (FDA) letter to physicians. The letter included an update on the Agency’s preliminary analysis of a potentially concerning signal of increased long-term mortality with paclitaxelcoated devices and recommended that physicians consider alternative treatment methods until additional analysis has been performed.

“Immediately following publication of the March 15 FDA communication, we reached out to the Agency seeking guidance on the recommendations and the impact on TRANSCEND,” says Gary Maharaj, Surmodics president and CEO.

“Following multiple conversations, we have taken several actions in response to the Agency’s recommendations, including updates to investigator communications, patient Informed Consent Forms (ICF), and data safety review and patient follow-up procedures. A number of our trial sites have already secured IRB or Ethics Committee approval of the updated ICF and are actively enrolling and randomising patients.”

The TRANSCEND randomised trial will evaluate the SurVeil DCB for treatment of peripheral arterial disease (PAD) in the upper leg compared to a commercially available DCB treatment.

The results of the trial will also include long-term, patient-level data out to five years. The company continues to assess the impact of the March 15 FDA communication on its expectations regarding the timing of completion of patient enrolment in the TRANSCEND clinical trial and related regulatory approvals for the SurVeil DCB. “Patient safety is the top priority in every study, so pausing trial enrolment while implementing the recommendations from the FDA was in the best interest of both our patients and this trial,” said William Gray, the national co-principal investigator of the TRANSCEND study. “We are pleased to see many sites enthusiastically resuming enrolments. The TRANSCEND trial comes at a critical time in the endovascular field and will provide important safety and efficacy data for the next generation SurVeil DCB as it compares to the Medtronic IN.Pact DCB and will ultimately be useful for physicians and the patients that they treat.”

Positive outcomes of Eluvia drug-eluting stent in IMPERIAL sub-analyses

Boston Scientific has announced results from sub-analyses of the IMPERIAL clinical trial for the Eluvia DrugEluting Vascular Stent System at the 41st Charing Cross (CX) Symposium (15–18 April, London, UK). Data demonstrated that the efficacy and safety performance of the polymer-coated Eluvia drug-eluting stent does not appear to be affected by challenging lesions, defined as being severely to moderately calcified or completely blocked within the superficial femoral and proximal popliteal arteries.

One of the analyses from the global, randomised controlled IMPERIAL trial, which evaluated the Eluvia drug-eluting stent (DES) in patients with symptomatic peripheral arterial disease, assessed outcomes of patients diagnosed with moderate to severely calcified lesions.

Highlights of the findings include: A primary patency rate—a measure of the target vessel remaining unobstructed at 12 months—for patients diagnosed with moderate to severe lesion calcification of 89.2%; A low rate (2.8%) of target lesion revascularisation in study participants with moderate to severe lesion calcification at 12 months; A low rate of stent thrombosis (1.1%) for patients treated with the DES who were diagnosed with moderate to

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severe lesion calcification.

“Our analysis demonstrated the Eluvia stent is a highly effective treatment option for some of the most complex lesion classifications commonly associated with femoropopliteal disease,” said Frank Vermassen, Ghent University Hospital, Gent, Belgium, an investigator in the IMPERIAL trial who presented the data at CX. “The findings underscore the ability of this stent to successfully treat varying lesion characteristics, and its performance will continue to be observed in ongoing patient follow-up.”

Investigators also analysed the safety and performance of the DES for patients diagnosed with having 100% blockage— or chronic total occlusions—at the target lesion and found that these patients experienced 83.9% primary patency at 12 months.

“The data presented today adds to the clinical evidence supporting the Eluvia Stent System as a viable first-line treatment option for patients suffering from debilitating peripheral artery disease,” said Ian Meredith, executive vice president and global chief medical officer, Boston Scientific. “Designed with a controlled release of the lowest possible drug dose to seek the best clinical outcomes, we believe the Eluvia stent can become a preferred therapy option and look forward to continued clinical successes with this product.”

The Eluvia Stent System received approval from the US Food and Drug Administration in September of 2018 and CE mark in February of 2016.

Reflow Medical completes enrolment in the Wing-IT IDE CTO clinical trial

Reflow Medical has announced the completion of enrolment in its WingIT investigational device exemption (IDE) trial; a prospective, multicentre, nonrandomised study evaluating the ability of the Wingman catheter to cross chronic total occlusions (CTOs) in peripheral lesions after failed guidewire attempts.

Eighty-five patients with advanced peripheral artery disease enrolled in the Wing-IT trial were evaluated at 12 centre in the USA, Germany, and Austria.

John R Laird of Adventist Heart and Vascular Institute, St. Helena, USA, is the principal investigator for the study.

“We would like to express our gratitude to the participating patients, physician investigators, research staff and employees. Their efforts have made it possible for us to reach this major milestone,” says Laird.

The Wingman Crossing Catheter uses an extendable beveled tip that creates a channel to help penetrate, or cross, the occlusion. This enables further treatment of the lesion with therapeutic devices.

Isa Rizk, chief executive officer of Reflow Medical, commented, “Our goal is to expand the physician’s ability to treat CTOs, which often develop in patients with advanced peripheral arterial disease. Facilitating CTO crossings helps physicians avoid amputations or bypass surgery, which directly correlates to better long-term outcomes.”

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June

Issue

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Events

Calendar of events 23–24 May Critical Issues in Aortic Endografting

Liverpool, UK W critical-issues-congress.com

24 May PNEC: Pacific Northwest Endovascular Conference

Seattle, USA W pnec-seattle.org

23–25 June Complex Cardiovascular Catheter Therapeutics: Advanced Endovascular and Coronary Intervention Global Summit (C3)

Orlando, USA W c3conference.net

27–28 June BSET: British Society of Endovascular Therapy annual meeting

Wotton-under-Edge, UK W bset.co.uk

5–7 June I-MEET

Nice, France W imeetcongress.com

27–29 June 2019 Northeast National Conference

Stamford, USA W kent.edu/cpm/2019NNC

11–12 June LINC Mount Sinai 2019

New York, USA W lincmountsinai.org

15–19 August ANZSVS Annual Scientific Meeting 2019

Adelaide, Australia W anzsvs.org.au

12–15 June SVS Vascular Annual Meeting

National Harbor, USA W vascular.com

7–11 September CIRSE: Cardiovascular and Interventional Radiological Society of Europe

21–22 June Endo Vascular Access (EVA) Meeting

Patras, Greece W evameeting.com

Barcelona, Spain W cirse.org

23–27 September ESVS: European Society for Vascular Surgery annual meeting

Hamburg, Germany W esvs.org

25–29 September TCT: Transcatheter Cardiovascular Therapeutics

San Francisco, USA W crf.org/tct

10–11 October 2019 Pacific Northwest Vascular Society Annual Meeting

Vancouver, Canada W pacificnwvascular.org

30 October–2 November Controversies in Dialysis Access (CIDA)

San Diego, USA W dialysiscontroversies.org 31 October–2 November Aortic Summit 2019

Lugano, Switzerland W aorticassociation.org 31 October–3 November CEC: China Endovascular Course

Beijing, China W topcec.com

4–7 November VIVA: Vascular Interventional Advances

Las Vegas, USA W vivaphysicians.org 19–23 November VEITHsymposium

New York, USA W veithsymposium.org 17–18 November EVTM: Endovascular Trauma Management Symposium

Denver, USA W jevtm.com/evtm-symposium 27–29 November The Vascular Societies’ Annual Scientific Meeting

Manchester, UK W vascularsociety.org.uk

4–6 December 9th Munich Vascular Conference

Munich, Germany W Mac-conference.com 5–7 December The Verve Symposium

Sydney, Australia W vervesymposium.com

June 2015

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Issue 66

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Janet Pow Profile

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94.4% primar a the 12-mo the open repair d a strong benefit for liteal artery and aged them showed a agreed that months, s showe trial results in women nine VE trial encour y analysi at The at the strateg IMPRO erthe often. scular with Eluvia tion rate the charact EVAR more the endova , patency rate at baseline, revascularisa Continued on page 2 to perform similar with men. the fact that , Imperial College data target lesion compared groups were 3.6% two latest Janet Powell the the nt in each istics of presented three-quarters idual patie diate manLondon, UK, with almost VE (Imme aneurysms Pooled indiv : s men. “The from the IMPRO with rupture large with outcome the 12-month group being the patient trial that were also very group being data agement of presented in this trial scular repair) from the Ron Balm ers in each Open vs. endovaar outcomes followmeta-analysis average diamet said. The principal outcomes from the she reported one-ye ty and endovascular patient data over 8cm,” trials of strategy of individual e was mortali controlled of ruptured ing either a one-year outcom es were reintervenrandomised or open repair The Dutch AJAX outcom repair first related three d aneurysms; the sm. secondary ge, healthaortic aneury rupture y 2013), the l benefit abdominal hospital discharquality-adjusteds of Surger no surviva tions, (Annal strate 2015) S trial , costs, for ruptrial (EJVE results demon ess. quality-of-life scular strategy er, French ECAR trial. cost-effectiven for the endova at one year. Howev IMPROVE life-years and Powell noted that were sm and the UK for the all trials that tured aneury l At CX 2015, rst strategy answer the “These were s with a clinica designed to aneurysms an endovascular-fi on patient In the trial was with a patient of ruptured performed d aneurysm. what to do management discharge ncy room of rupture question of mortality patients faster and it is suspicion s to the emerged abdomidoes offer trial the 30-day imately who present quality of life the AJAX sis of rupture was approx with better these factors with a diagno sm. “What we had ective. Both in both groups it was 22% and in also cost-eff and clinical nal aortic aneurythat using an endory for patient heard.

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