Vascular News 78 – June 2018 US Edition

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NICE draft guideline casts shadow over EVAR for unruptured aneurysms

Bijan Modarai:

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The UK’s National Institute for Health and Care Excellence (NICE) has issued draft guidance on abdominal aortic aneurysm (AAA) diagnosis and management. The most notable recommendation within the guideline is related to repairing unruptured aneurysms where the guideline states that patients should not be offered endovascular repair (EVAR) if open surgical repair is suitable.

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his latest draft guideline issued in May is for consultation and will update NICE technology appraisal guidance 167 which was published in February 2009. According to NICE, the guideline aims to improve care by helping people who are at risk to get tested, specifying how often to monitor asymptomatic aneurysms, and identifying when aneurysm repair is needed and which procedure will work best.

On monitoring the risk of rupture, NICE recommends that patients with an asymptomatic AAA be offered surveillance with aortic ultrasound every three months if the AAA is 4.5–5.4cm or every two years if the AAA is 3–4.4cm.

When it comes to repairing unruptured aneurysms, the guideline suggests that physicians should consider aneurysm repair for people with an unruptured AAA if it is symptomatic, asymptomatic and 5.5cm or larger, or asymptomatic, larger than 4cm and has grown by more than 1cm in one year. But add that patients meeting these criteria should be offered surgical repair unless there are anaesthetic or medical contraindications.

As for EVAR for repairing unruptured aneurysms, the instructions in the draft guideline are clear: “Do not offer endovascular repair (EVAR) to people with an unruptured infrarenal AAA if open surgical repair is suitable. Do not offer EVAR to people with an unruptured infrarenal AAA if open surgical repair is unsuitable because of their anaesthetic and medical condition. Do not offer complex

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New CMS reimbursement code “severely underpays” for drug-coated balloons

EVAR to people with an unruptured AAA if open surgical repair is a suitable option, except as part of a randomised controlled trial comparing complex EVAR with open surgical repair. Do not offer complex EVAR to an unruptured AAA if open surgical repair is unsuitable because of their anaesthetic and medical condition,” they state.

In an effort to explain how NICE comes to these recommendations, the rationale within the document indicates that there is “no evidence that EVAR for people with an unruptured infrarenal AAA provides long-term benefit compared with open surgical repair. While EVAR is associated with fewer

perioperative deaths, it has more long-term complications, and these complications mean that people will need further procedures. There is some evidence that EVAR is associated with worse long-term survival than open surgical repair.

EVAR also has higher net costs than open surgical repair. The evidence shows that, even if longterm benefits were achievable, they could not plausibly be sufficient to outweigh these costs. Open surgical repair is unsuitable for some people with an unruptured AAA because of their anaesthetic risk and/or medical comorbidities. For these people, the risks of their AAA rupturing, if no repair is attempted, have to be Continued on page 4

Drug-coated balloon (DCB) angioplasty devices have been categorised by the US Centers for Medicare and Medicaid Services (CMS) into the same billing code as plain balloon angioplasty, following the expiration of the technology’s transitional pass-through and new technology add-on payments on 1 January 2018.

The decision not to create a separate reimbursement code for DCBs comes to the surprise and disappointment of a wide range of stakeholders and advocates, from industry to public advocacy groups.

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he conflation of the two technologies into the same ambulatory payment classification has caused protests from scientists, physicians, societies, public advocacy groups and industry alike, who argue that the decision will indirectly discourage DCB use despite evidence of superiority compared to plain angioplasty.

A recent viewpoint article published in the Journal of the American College of Cardiology (JACC): Continued on page 10

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NICE guideline

NICE draft guideline casts shadow over EVAR for unruptured aneurysms Continued from page 1

balanced against the perioperative risks and long-term complications associated with EVAR. The evidence shows that the average person receiving EVAR has an uncertain chance of a small net benefit, compared with the large and certain increase in costs. Therefore, the committee agreed that elective EVAR cannot be considered an effective use of NHS resources in this population.”

Additionally, the NICE committee found that the evidence for complex EVAR was limited in quantity and quality.

However, they note that complex EVAR grafts are much more expensive than standard devices, so the difference in cost between EVAR and open surgical repair is even greater than in infrarenal AAAs. The committee also noted that the instructions for use of the grafts that are currently available do not cover complex AAAs. “Although there is currently no evidence that complex EVAR has better outcomes than open surgical repair, people with complex AAAs have higher perioperative mortality rates. Because of this, a perioperative survival benefit equivalent to that seen with EVAR for infrarenal AAAs could potentially be more influential in complex AAAs. Therefore, the committee agreed that more information would be helpful, so it recommended that the use of complex EVAR should be restricted to randomised trials.”

According to the guideline document, the committee also discussed complex EVAR for patients for whom open surgical repair is not a suitable option because of their anaesthetic risk and/ or medical co-morbidities. They agreed that, in this population, people who need complex EVAR could not plausibly have better outcomes than those who need standard infrarenal EVAR. As they had not recommended standard EVAR in this population, the committee agreed that they could not recommend complex EVAR either. Further, the committee did not recommend using complex EVAR in randomised trials in these circumstances, because it would be unethical to randomise people to a treatment with a

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high risk of perioperative death when there is no prospect of long-term benefits at reasonable cost.

“For each of these recommendations, the committee considered whether there were any specific groups that would benefit from standard or complex EVAR for unruptured AAAs. They explored groups defined by age, sex, AAA diameter and life expectancy, but there were no groups in which the benefits would outweigh the harm and costs,” the guideline states.

The guideline committee acknowledges that the recommendations on EVAR will have a large impact on practice, as EVAR is a widely performed procedure. “EVAR is currently used more frequently than open surgical repair in some areas, so a diverse group of people both within and outside the national screening programme will need to update their knowledge,” they state. On a more positive outlook, the committee believes that the recommendations will “minimise harm by reducing long-term mortality and the need for reintervention as a result of problems with EVAR. Reductions in EVAR use and subsequent EVAR-related reinterventions will lead to cost savings within the NHS”.

EVAR did not lose out all round, as the NICE draft guideline does allow for the consideration of EVAR for the repair of ruptured aneurysms, at least of the infrarenal kind. The guideline suggests that either EVAR or open surgical repair should be considered for repair of a ruptured infrarenal AAA. They advise that EVAR provides more benefit than open surgical repair for most people, especially for women and for men over the age of 70 years, and open surgical repair is likely to provide a better balance

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of benefits and harms in men under the age of 70 years.

However, for ruptured complex AAA the guideline instructs that open surgical repair should be considered, but that complex EVAR should not be offered to people with a ruptured AAA if open surgical repair is suitable, except as part of a randomised controlled trial comparing complex EVAR with open surgical repair.

According to the document’s rationale, the evidence considered by the committee showed that, compared with open surgical repair, a strategy that uses EVAR (where anatomically possible) to repair ruptured infrarenal AAAs provides a reasonable balance of benefits and costs.

Further, as the average cost-effectiveness results for EVAR were favourable, the committee discussed whether they should recommend EVAR whenever it is possible. They decided not to, for two reasons: “Firstly, there is uncertainty in the evidence for EVAR. People who had EVAR for a ruptured AAA were followed up for at most seven years.

People who had EVAR for an unruptured AAA were followed up for 15 years, and the committee noted that these data suggested that EVAR may be worse than open surgical repair in the long run. There are some signs that a similar long-term pattern may develop in trials of ruptured AAA, so it is possible that longer-term data would show EVAR to be worse than open surgical repair for people with ruptured AAA as well.

“Secondly, there was evidence that the balance of benefits and costs of EVAR varies between different groups of people with ruptured AAA. In particular, women clearly have better short-term

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survival after EVAR, whereas the evidence favours open surgical repair for younger men. Therefore, the committee recommended that either EVAR or open repair can be considered, and provided detail on the groups for which each approach is likely to be best.

“Complex EVAR is only recommended within the context of a randomised controlled trial because there is currently no evidence to support it as an option for people with ruptured complex AAA.” As for how the recommendations might affect practice, NICE maintains that they will have little impact on current practice, “as both standard EVAR and open surgery are currently offered to people with ruptured infrarenal AAA. In relation to complex EVAR, the recommendation not to use it outside of randomised trials will limit the use of a technically complex and expensive procedure in people for whom open surgery is a safe and suitable option”.

When EVAR is used, the draft guideline suggests that patients should be monitored for complications, and that they should be enrolled into a surveillance imaging programme and the frequency of surveillance imaging should be based on the patient’s risk of graft-related complications. It recommends the use of contrast-enhanced CT angiography to detect postoperative complications and further aneurysm expansion.

Finally, the draft AAA guidelines make some key recommendations for research. Firstly, it encourages research into monitoring frequencies and repair thresholds, noting that more frequent monitoring increases the chances of identifying aneurysms that have grown large enough to need repair.

“It is important to establish how often aneurysms should be monitored to keep the risk of rupture as low as possible while making the best use of NHS resources,” they state.

Secondly, the document calls for research into the effectiveness of endovascular aneurysm repair and open surgical repair of unruptured and Continued on page 6

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NICE guideline

NICE draft guideline casts shadow over EVAR for unruptured aneurysms Continued from page 4

ruptured abdominal aortic aneurysms, noting that while EVAR is a widely performed non-invasive alternative to open surgical repair, it is more expensive. “Although EVAR has been shown to produce no long-term benefit over open surgical repair in people with unruptured infrarenal aneurysms, it is less clear whether this is the same in people with unruptured or ruptured juxtarenal, suprarenal type IV, and short-necked infrarenal aneurysms. As a result, research is needed to identify how effective complex EVAR is in these populations”.

The committee also recommended research into macrolides for slowing aneurysm growth and reducing risk of rupture, metformin for slowing aneurysm

growth and reducing the risk of rupture, tranexamic acid for preventing and treating excessive blood loss during EVAR or open surgical repair and preoperative exercise programmes for improving the outcome of aneurysm repair. Other recommendations for research include the use of direct oral anticoagulants after AAA repair, transfer to specialist vascular units, permissive hypotension, and surveillance after EVAR. Finally, on surveillance after EVAR, the guideline suggests research should be conducted to determine the risks, benefits and cost implications of different surveillance protocols in patients who have undergone EVAR, as well as which device and patient-related variables can be used in a risk model to inform

amendments to surveillance frequencies and modalities.

Such research is already underway in the form of prognostic modelling, based on data from the EVAR trials and validated by a contemporary EVAR dataset from Helsinki, Finland.

Next steps

The period for consultation of the draft guideline is 16 May 2018–29 June 2018. For consultation comments, NICE is encouraging consideration of the areas that will have the biggest impact on practice and be challenging to implement and how to help users overcome challenges. The expected date for publication of the approved guideline is 7 November 2018.

Sac growth model could enable simple, safe and patientfriendly surveillance after EVAR At the Charing Cross Symposium (CX; 24–27 April, London, UK) delegates heard compelling research-in-progress from a multidisciplinary team of surgeons, statisticians and health economists that the initial aortic diameter plus annual secondary sac diameter, as measured by ultrasound close to a patient’s home, could be a new way to follow EVAR patients. Prognostic modelling, based on data from the EVAR trials, was revealed to have predictive value in identifying patients at high-risk of secondary rupture and those who were classified as low-risk. This project was funded by the UK’s National Institute of Health Research Health Technology Assessment programme.

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urrent EVAR 1 follow-up is suboptimal,” said Fiona Rohlffs, Imperial College, London, UK, who backed this statement using long-term data from the EVAR 1 trial, which was the first large randomised controlled trial conducted in the UK comparing open repair with endovascular repair of abdominal aortic aneurysms. The trial’s 15-year survival curve showed a benefit for EVAR patients in early followup, but this declined during the follow-up period of 15 years. Rohlffs called into question the surveillance schedule that was employed by emphasising data showing the proportion of EVAR patients returning for CT scan follow-up each year.

“In EVAR 1, this was 90% in the first six months, but this declined to just 10% of the survivors by year nine,” Rohlffs explained.

Maarit Venarmo (Helsinki, Finland) then presented a contemporary EVAR dataset that showed exceedingly similar losses to follow-up in the surveillance protocol with time. The Helsinki dataset comprised 417 consecutive patients who underwent elective EVAR due to asymptomatic abdominal aortic aneurysm during 2000–2015. At six-months, there was follow-up data for 90% of patients. This declined to 40% at nine years, Venarmo said. The EVAR trials and the Helsinki University series were harmonised to achieve a comparable, consistent dataset.

Further, US data from follow-up in 20,000 Medicare beneficiaries between 2001–2008, published by Andres Schanzer et al in the Journal of Vascular Surgery, showed a 50% loss to imaging follow-up by year five.

Michael Sweeting, Cambridge University, UK commented that the multidisciplinary team wanted to develop

a prognostic model for predicting future sequelae after EVAR. As background, Sweeting pointed out that the adherence to lifelong surveillance following EVAR was poor. “This is an ageing population; in the EVAR 1 trial, by six years, more than 40% of patients were aged over 80. Another reason why there might be poor follow-up is because there might be concerns about the frequent use of CT scanning (due to the radiation burden), and there is, therefore, a real need for patient-driven, safe and acceptable, truly personalised surveillance,” commented Sweeting. “Developing a prognostic model to be able to predict those who may be at high- and low-risk will help us to do that, so that we can potentially have less frequent follow-up, surveillance using different modalities (such as ultrasound) or potentially surveillance in primary care.

There is interest growing in developing prognostic models to determine long-term outcomes following EVAR,” he explained.

The aims of this research, clarified Sweeting, are to model the trajectory of aneurysm sac diameters, to develop a prognostic model using modelpredicted rates of sac growth and sac diameter in order to predict future events and to validate (in external data) its predictive accuracy.

The team developed the model using data from EVAR 1 and EVAR 2 randomised controlled trials for unruptured abdominal aortic aneurysms and validated the model using data from the Helsinki series.

Sweeting commented that prognostic models can be used to classify patients into low- and high-risk groups. “It is possible to reassess classification throughout follow-up using dynamic models. Predicted sac growth is important and outperforms observed change from

baseline. It can be used to recommend reduced surveillance (for example biannually) or alternative surveillance (such as ultrasound).”

He reported on the diagnostic accuracy of the prognostic model with sac growth in predicting events over the next twoyears to state that using the model, 40% of all patients could be classified as low risk and that it could also be used to correctly identify 85% patients who would go on to have a reintervention or rupture within the next two years. Roger Greenhalgh (London, UK), who was chairing the session, indicated that these were the key findings.

In an invited commentary, Stéphan Haulon, Le Plessis Robinson, France, endorsed the researchers’ approach regarding this data. “I fully agree that prognostic models will allow personalised follow-up and will probably provide better outcomes, if the patients that need follow-up actually get the follow-up. My concern is that after 15 to 20 years of treating aneurysms with endovascular procedures, we are still seeing a lot of secondary aneurysmal sac growth—is it because of technical issues? This is unlikely as we now have a 3D work station to properly design the endograft; access to the latest generation endografts and delivery systems that we can nicely position. However, despite this, we still have secondary aneurysmal sac growth and it is associated with an increased number of secondary procedures, an increased number of sac ruptures, and an increased inflammatory response,” he said.

Continuing, Haulon commented that EVAR is not succeeding (unlike open surgery) in treating aneurysms

“because we are not resecting the sac, or closing the side branches and because we still have thrombus inside the aneurysm sac. We probably need to monitor the sac differently and maybe future endografts should include a way of easy monitoring, such as with a mobile phone that can actually be connected to the device to tell us about diameter pressure.

“I completely concur with your findings that with prognostic models we should leave the patients who will have an uneventful follow-up alone, and really focus on those patients who are high-risk, even though they are not a majority. It is very important information because if the patient needs to go to the hospital, wait a couple of hours, see somebody different, they will not come back.

What you are suggesting is exactly what we should do.”

Greenhalgh then drew attention to “the key finding being the ability to classify 40% of all patients low risk” and its consequences. And, further, the findings that 85% of those who will have a rupture in the next two years without investigation can now be identified. So this brings a whole different attitude to the follow-up of EVAR”.

He noted that certain assumptions have been made, including that ultrasound sac diameter will be available at, or close to home; that at the vascular centre clinical and CT angiography will be performed; that modern techniques will detect the cause of sac expansion and that rupture preventing reinterventions will correct sac growth.

Summarising these data Greenhalgh said, “it turned out that many patients did not accept having to go to hospital so often. The EVAR procedure requires lifelong annual surveillance.

Lifelong surveillance has to be patient-friendly, simple and safe.

From baseline morphology and annual sac diameter, low-risk patients can be identified and no hospital follow-up is needed. Further, high risk of secondary sac rupture in two years is predicted. The threshold for criteria of vascular centre referral needs further definition.”

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Drug-coated balloons

Addressing the data deficit for drug-coated balloon use in dialysis access The first 24-month data from the LUTONIX AV investigational device exemption trial were presented at the Charing Cross Symposium (24–27 April, London, UK). These interim data show a sustained effectiveness benefit for the Lutonix drug-coated balloon (BD) and indicate that it leads to an average time to first reintervention that is four months longer than obtained with plain balloon angioplasty.

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he randomised, prospective, multicentre Lutonix AV trial was designed to assess the safety and effectiveness of the Lutonix 035 drugcoated balloon in the treatment of native dysfunctional arteriovenous fistulae. The patient cohort was a “real-world” group and the study included secondary nontarget lesions, de novo/restenotic lesions, and stents in the access circuit outside of the studied lesions. Investigators in the trial randomised 285 patients at 23 clinical sites. After predilatation to specific requirements with a plain angioplasty balloon, patients who had less than 30% residual stenosis were then enrolled and randomised 1:1 to treatment with either a drug-coated balloon or a standard matched compliant angioplasty balloon.

Kate Steiner (consultant interventional radiologist at East and North Hertfordhsire NHS, Stevenage, UK)

reported the latest data from the trial.

Emphasising the points that would resonate most with patients, she highlighted that patients in the drugcoated balloon arm had, on average, a reintervention at 11 months (318.7 mean days) as compared to patients in the control arm who had a reintervention at seven months (198.4 mean days). “Four months, or 120 reintervention-free days, is significant to the dialysis patient who already spends three days a week on dialysis,” Steiner commented.

The primary efficacy endpoint of LUTONIX AV was target lesion primary patency at 180 days. While the trial did not show a statistically significant benefit for the drug-coated balloon at this time point, further follow-up revealed that the paclitaxel drug had a significant effect on the lesion patency at later time points.

The primary safety endpoint was freedom

patency curve do the lines cross through 24 months,” she said, adding that longterm safety remains non-inferior to plain balloon angioplasty. “The Kaplan-Meier patency curves start to separate around the 90 to 100-day mark and what we see now is that they continue to remain separate; there is no time point at which the curves cross or come together. We see a 36.8% improvement out to 550 days and this continues out to a 30% improvement out to 730 days, or 24 months,” she explained.

Results Kate Steiner

from any serious adverse event(s) involving the arteriovenous access circuit through 30 days and showed that treatment with a drug-coated balloon was non-inferior to treatment with a plain balloon. Follow-up was clinically driven and took place at one, three, six, nine, 12, 18 and 24 month visits.

Steiner maintained that the long-term data suggest a sustained efficacy benefit through the 24 months. “Nowhere in the

The results were adjudicated by a core lab, an Independent Clinical Events Committee, and a Data Safety Monitoring Board.

“When we combine the LUTONIX AV trial, LUTONIX global registry (n=324), and LUTONIX post-approval study (n=213), we will have well over 800 patients going towards addressing the data deficit in dialysis access. I will predict that as we learn more about the pathophysiology of dialysis access stenosis, we will see more innovation in this area,” Steiner stated.

Drug-coated balloon is “highly effective and safe” and shows outstanding clinical improvement for patients compared to an uncoated balloon The 12-month results from the full clinical cohort of the EffPAC randomised controlled trial, were presented for the first time at the Charing Cross Symposium (CX; 24–27 April, London, UK).

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lf Teichgraeber (Jena, Germany) reported the 12-month outcomes of the Luminor paclitaxelcoated balloon (iVascular) for the treatment of superficial femoral and popliteal arteries. At 12 months, Teichgraeber noted that patency was significantly higher in patients who received drug-coated balloon therapy compared with those who received treatment with an uncoated balloon.

Target lesion revascularisation at 12 months was 1.3% (vs 17.7% in the plain angioplasty group, p<0.001).

Primary patency at 12 months was 90.3% (vs. 65.3% in the plain angioplasty group, p<0.001). Rutherford stage improvement at 12 months was 90.6% in the Luminor group (p=0.006), Teichgraeber reported.

“What is special about the Luminor drug-coated balloon, is its unique nano-coating technology, which is ultra-thin and uniform,” commented Teichgraeber, principal investigator of the study.

According to Teichgraeber, Luminor is not “just another” paclitaxel-coated balloon. As he explained it had a unique “nanotechnology coating”. “It is multilayer technology, which makes it seem very rigid.

So, you may think: ‘how does paclitaxel get off the balloon?’ But, it increases adhesion to the balloon, improves durability, improves mechanical properties, and provides fast absorption (30–60 seconds)”.

The aim of the EffPAC trial was to review how the device compared with an uncoated balloon. Patients with lesions in the superficial femoral artery or in the popliteal artery were randomised to receive treatment with Luminor (n=85) or with an uncoated balloon

Ulf Teichgraeber

(n=86). So as to include as many people as possible in the trial, prolonged percutaneous transluminal angioplasty with the same balloon was performed in cases of non-flow limiting or flow-limiting dissection (in both groups). The primary endpoint was late lumen loss at six months, with secondary endpoints including freedom from target vessel revscularisation, patency, change in ankle-brachial index, Rutherford stage, and quality of life.

At 12 months, data were available for 76 patients in the Luminor arm and for 75 patients in the uncoated balloon arm. Teichgraeber noted that, at six months, the late lumen loss was 0.14mm for Luminor vs.

1.06mm for uncoated balloon (p<0.01). However, he commented that this was “a technical endpoint” and the focus should be on clinical endpoint. “You might say it is target lesion revascularisation or patency that are most important, but I think it is more about assessing the benefit for the patient. And, therefore, the clinical result is the change in the Rutherford score,” Teichgraeber added.

He said, “what was astonishing for us as investigators was that there was strong evidence that Luminor was associated with an improvement in the Rutherford classification not only compared with baseline levels but also with the uncoated balloon.” At 12 months, 49.3% of patients in the Luminor group had an improvement of three stages compared with only 29.2% of patients in the uncoated balloon group, he reported. Furthermore, both the rate of target lesion revascularisation and patency were better with the drug-coated balloon.

Teichgraeber concluded: “The Lumnior paclitaxelcoated balloon catheter was demonstrated to be highly clinically effective and safe in inhibiting restenosis compared to an uncoated balloon. The innovation coating technology matters and is shown not only in the patency, late lumen loss, and target lesion revascularisation data but also in an improvement in the Rutherford classification. The results of the study allow direct comparison to other already-completed randomised controlled trials applying paclitaxel-coated balloon from different manufacturers to the same target vessel.”

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New CMS reimbursement code “severely underpays” for drug-coated balloons Continued from page 1

Cardiovascular Interventions calls the ruling “arbitrary” and “disappointing”, urging all who advocate for patients with peripheral arterial disease to engage on CMS decisions regarding payment.

Vascular News spoke to Mehdi Shishehbor (Case Western Reserve University School of Medicine, University Hospitals, Cleveland, USA), first author of the article, who finds the decision both puzzling and alarming. “There is Level 1 evidence from three randomised controlled trials with three different devices, showing clearly that drug-coated balloons compared to angioplasty alone is superior,” he says.

“We [Shishehbor and colleagues] are puzzled as to why the CMS would treat DCBs as being the same as angioplasty, because by not giving it a new billing code, the CMS is implying that DCBs and angioplasty are the same. We are just dumbfounded. I have no idea why they believe that.”

Although DCB treatment costs are significantly higher than angioplasty use per-treatment, Shishehbor points to higher long-term costs of reintervention rates and continued care stemming from the lower patency rates of plain angioplasty. Grouping the two under one APC billing code, the fear is that patients who are uninsured or relying on Medicare and Medicaid will not receive DCB treatment, as hospitals pay out of pocket for the higher costs of the device.

The CMS can allow innovative device technologies that are too novel to be included in regular coverage, to instead be covered over a short-term period under the transitional pass-through add-on payment and new technology add-on payment categories. This ensures patients gain access to beneficial new treatments while the CMS gather data to make a decision on its longterm ambulatory payment classification (APC), or billing code. The pass-through phase usually lasts for up to two years, and Shishehbor notes that this period is rarely extended. In the JACC article, Shishehbor et al write that the CMS “should be applauded for approving additional DCB coverage through [add-on payments], recognising the incremental clinical benefits afforded by DCB compared with traditional uncoated angioplasty for patients with peripheral arterial disease.”

As the pass-through and new technology add-on payment phase came to an end, however, the decision was made to package DCB device treatment costs into an existing

Mehdi Shishehbor

category for angioplasty—surprising professional societies, physicians, public policy organisations and medical centres who argued against the idea “out of concern over unintended patient consequences”, write Shishehbor et al. What should have been done, they argue, was to create a new APC category or assign the device to a “more appropriate APC category”.

The unintended consequences

In the long term, Shishehbor et al argue that elderly and disadvantaged patients who rely on Medicare and Medicaid will be assigned to suboptimal treatment with plain angioplasty.

“This policy in the USA affects everyone over the age of 65,” Shishehbor told Vascular News, “because the majority of these patients—male or female and regardless of race—get their insurance through the Medicare system. So every single patient over the age of 65 who relies heavily on Medicare as their insurance, which is a majority of the population, may be affected by this. It also affects those who do not have insurance, or rely on Medicaid as insurance.”

“For these patients it is very unlikely that they would receive treatment with a technology that costs five to six times more than the other technology, as the hospital would have to pay out of their own pocket in order to use it,” Shishehbor said. He added that in 2018, the uncoated balloon alternative, which physicians are likely to fall back on for these patients, “is not something that is clinically appropriate in most cases—if not all”.

Chairman of the New Cardiovascular Horizons (NCVH), Craig Walker, voiced his opposition on the change when it was proposed in 2017, and encouraged physicians to submit public comments. He

said at the time that the proposed payment structure (now implemented) “would not adequately reflect the added costs of DCB and could adversely impact access for Medicare beneficiaries given the difference in costs between a plain balloon and DCB. The clinical benefits and cost effectiveness of DCB angioplasty have been wellestablished through randomised controlled trials and large-scale, population based observational studies. CMS’ approval of both inpatient and outpatient temporary addon payments for DCB was in recognition that DCBs represent a significant clinical improvement in the treatment of PAD relative to plain balloon angioplasty catheters when compared to drug-coated balloon therapy.”

“I believe an appropriate payment structure after the expiration of these add-on payments is important to avoid patient access barriers to a technology that reduces repeat interventions for patients and healthcare costs to Medicare.”

A fee-for-service system of care

Describing the disconnect observed between the evidence of DCB superiority and the failure to designate it to a new APC category, Shishehbor explained it is due to the guidelines which inform CMS’ decisions. “The bigger issue comes down to the fact that this is really not the CMS’ fault. These are rules that are set

by Congress and by the government.”

“When CMS wants to give something a pass-through code, the rules say they need to look whether clinically, that technology offers something superior. But for the regular billing code in the second phase, there is no rule that says the CMS need to look at efficacy. They only need to look at cost.”

The CMS responded to the request that a new reimbursement code be created for DCBs, explaining that their decision is based on “a prospective payment system that relies on the principles of averaging, with some cases in an APC being more costly than others (and some being less costly)”.

These principles however, as Shishehbor maintains, are problematic. “What they [the CMS] say is they believe in the concept of averaging,” Shishehbor told Vascular News. “The idea is, sometimes physicians use angioplasty and sometimes physicians use DCBs, and over time the cost kind of averages out. That would be true if DCB and plain balloons were the same, but they are not the same. A drug-coated balloon is much more superior—not only

Pioneers of drug-coated balloon technology developing hyper-compliant balloon catheters A novel balloon catheter which seeks to adapt its shape according to existing vascular anatomy is being developed by Germany-based InnoRa, in a project led by drug-coated balloon pioneers, Ulrich Speck (Charité University Hospital, Berlin, Germany) and Bruno Scheller (University of Saarland, Homburg/Saar, Germany).

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arly data of in vitro and in vivo testing of hypercompliant balloon catheters in varying balloon lengths and with or without drug coating were presented in a poster presentation at EuroPCR (22–25 May, Paris, France) by engineer Maciej Kusmierczuk

(InnoRa, Berlin, Germany).

“Local drug delivery by drug-eluting stents and drug-coated balloons leads to a significant reduction of restenosis after percutaneous vascular therapy,” Kusmierczuk said. “A single drug-coated hyper-

from the standpoint of patency, but also from the standpoint of patient quality of life and even long-term cost, because as patients come back for reinterventions due to their lower patency plain angioplasty, this affects cost to the healthcare system.

“This principle is outlined by Congress and by the law, and that rule fundamentally is what we need to change if we want to move towards a value-based system rather than a fee-for-service system.”

The role of industry

Not alone in voicing disagreement with the reimbursement code decision for DCB devices, Sheshehbor et al’s call to action is joined by industry actors and stakeholders.

Mark Pacyna, VP and GM of the Peripheral business in Medtronic’s Cardiac and Vascular Group, recently released a statement in response to Shishehbor et al, referring directly to the article. “As discussed in the JACC article,” Pacyna says, “DCBs serve as a costeffective solution to safely and effectively treat femoropopliteal disease, while also reducing rates of reintervention. While the expiration of CMS’ transitional pass-through add-on payment for DCBs was anticipated, data has proven that drug-coated balloons offer economic and clinical value.” He concluded, “Medtronic and our collaborating partners will continue to pursue appropriate reimbursement for DCB procedures and ensure access to this proven therapy that improves outcomes and delivers long-term savings to health systems and payers.”

Shishehbor hopes that through collaborative engagements between societies, public advocacy groups and scientists, their concerns can be communicated to the CMS and influence the upcoming reevaluation of DCB reimbursement.

Regarding the role of industry partners in this collaborative response, Shishehbor comments he is aware that industry is engaging CMS on their own, “because they also believe that something has to be done”.

To his knowledge however, there is no direct collaboration between industry and people like Shishehbor, “who are advocating on behalf of my patients and on behalf of my profession” rather than for financial reasons.

However, he says, “They are fighting on the right side of the aisle, fighting for something that I believe as a scientist and as a physician, is the right thing to do. […]

Industry obviously wants these devices to be paid for by the government, and we do too.”

In this sense, he says, they are aligned.

compliant balloon covers various lumen diameters and shapes, and smoothens the injured vessel wall.” High drug transfer to the vessel wall was observed.

The four-week follow-up data of technical feasibility explored in swine indicated that the technology “may allow homogenous treatment of irregularly shaped vessel segments and long segments with variable diameters.”

Speck, whom session moderator Marc Bosiers (Dendermonde, Belgium) dubbed “the Godfather of drug-coated balloons”, has long been a leading figure of drug-coated balloon technologies along with Scheller—who also highlighted the technology earlier this year at the Charing Cross Symposium (CX; 24–27 April, London, UK).

12

June

Issue

18 78

Endovascular aneurysm repair

First case experience presented with next generation conformable EVAR device New data from the first 10 EVAR patients treated using a new conformable device, the Gore Excluder conformable abdominal aortic aneurysm endoprosthesis with active control system, were presented at the Charing Cross Symposium (24–27 April, London, UK).

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obert Rhee (New York, USA), the national principal investigator of the US investigational device exemption (IDE) trial for the device, presented site-reported, procedural data for the first 10 patients.

“One of the biggest challenges with EVAR is the sealing zone, especially in a hostile neck. The second iteration of the Gore Excluder device was designed specifically to address this issue so that the proximal neck is addressed in a fashion where the seal is allowed, without compromising the proximal neck.

This device is specifically designed to conform to an angulated neck and be adjustable so that you are able to use every millimetre of the neck,” Rhee stated.

“This next generation stent graft is the first truly ‘adjustable’ EVAR system for high-risk proximal sealing zones, such as highly angulated necks, because you are able to change the configuration and control the angle of the device to improve incomplete endograft apposition to the aortic neck. This incomplete neck apposition has been shown to increase the risk of endoleak formation after endovascular repair,” Rhee further explained.

The conformable endoprosthesis has the ability to conform to proximal neck angles up to 90° and achieve seal in short (greater than or equal to 10mm) proximal necks. It is repositionable and has a mechanism to

Robert Rhee

adjust device angulation.

Rhee maintained that cases which present possible

anatomical challenges with apposition of the graft in the proximal landing zone can be overcome by controlling the proximal angle of the device.

The US pivotal trial is designed to assess the safety and effectiveness of the new generation Excluder for the treatment of infrarenal abdominal aortic aneurysm, with the aim of gaining US FDA approval for the technology.

The study will enrol at 51 US sites. There are two arms of the study: one includes patients with short necks (patients with aortic neck angulation of less than or equal to 60˚ and infrarenal aortic neck length greater than or equal to 10mm) and another includes patients with a high aortic neck angulation between 60˚ and 90˚ and infrarenal aortic neck length greater than or equal to 10mm. The study will enrol 190 patients, with 80 patients in the short neck arm and 110 patients in the high neck angulation arm.

“Site-reported data from the first 10 patients showed that the device performed as expected.

There were no technical problems or difficulties. All the procedures were successful and there were no conversions to open repair, or additional procedures at treatment including angioplasty, stent placement, embolisation, thrombectomy, endostaples or other treatments,” Rhee said.

Providing further data, Rhee revealed that there are currently 35 patients enrolled in the study, with 32 patients in the short neck arm and three patients in the high neck angulation arm. “The 35 trial patients were successfully treated,” Rhee concluded.

How volume and endovascular aneurysm repair impact outcomes for ruptured abdominal aortic aneurysm treatment JACOB BUDTZ-LILLY COMMENT & ANALYSIS A recent study sought to evaluate endovascular treatment of ruptured abdominal aortic aneurysms, revealing some “interesting contradictions and unanswered questions”. Jacob Budtz-Lilly discusses the findings and their implications.

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his analysis of data from eleven countries and over 400 vascular surgery centres provides an update on variations in the treatment and outcomes for ruptured abdominal aortic aneurysms (rAAA) across the globe. Vascunet, an international collaboration of vascular surgery registries, coordinated the collection and cooperative analysis of data. With over 9,000 rAAA patients included, it is possible to evaluate some of the evidence from “real world” practice.

The three objectives of this study were: first, to evaluate any differences between perioperative mortality for open repair and endovascular aneurysm repair

(EVAR) for patients undergoing treatment for rAAA; second, to detect any relationship between outcomes and the number of patients treated per centre; and third, to compare outcomes between centres that either primarily used EVAR or primarily used open repair.

The results show that the use of EVAR is steadily growing, yet the vast majority (>75%) of patients with ruptured aneurysms are still being treated with open surgery. The perioperative mortality was 32.1% for open repair and 17.9% for EVAR (overall 28.8%). Looking closer and after correcting for multiple co-morbidities, the odds ratio of mortality for EVAR against open

repair was 0.38. It should also be noted that, on average, the patients who underwent EVAR were older and more heavily burdened with cardiac and pulmonary disease.

When looking at the relationship between volume and outcomes, it is clear that high-volume centres have better results (23.3%) than in lowervolume centres (30.0%). Much of this is driven by the differences in open repair. That is, it does not appear that outcomes after EVAR are different between centres of varying volume, while open repair is best performed at centres that have sufficient volume.

Finally, it is also clear from this analysis that some centres have a preponderance for treating patients with EVAR. The mortality at these centres (23.0%) was lower than that at centres that more often opted for open repair (29.7%). Furthermore, the operative mortality for EVAR was almost the same at centres of predominantly open surgery or predominantly EVAR. In other words, the reduced mortality at centres using a strategy of primary EVAR was essentially borne by the fact that they perform a greater percentage of EVAR procedures.

This study reveals some interesting contradictions and unanswered questions. EVAR appears to offer a better outcome than open surgery, yet

the proportion of patients receiving this treatment is still relatively low.

One would expect that these numbers have changed or improved since 2013, the end of the study period.

One could also speculate, however, as to the availability of EVAR in the acute setting. Indeed, many centres in this study (58.2%) treat the majority of their elective patients with EVAR, yet more often opt for open surgery in the acute setting. Other issues may also play a role in this finding.

The choice of treatment is obviously dependent on which service is available or offers acute vascular care. This is also further influenced by various local geographical limitations and local hospital agreements. Nonetheless, the findings from this study should be borne in mind in future considerations of acute vascular care. EVAR may yield better outcomes, but its utilisation appears lacking for whatever reasons.

If centres intend to continue using open aortic repair for rAAAs, then centralisation to centres of high volume may be the best strategy.

Jacob Budtz-Lilly is a vascular surgery consultant at Aarhus University Hospital, Aarhus, Denmark and Uppsala University, Uppsala, Sweden.

14

June

Issue

18 78

Drug-eluting stents

Paclitaxel-eluting stent loses BATTLE against bare metal stent The BATTLE trial has failed to show the superiority of primary stenting with a paclitaxel-eluting stent (Zilver PTX; Cook Medical) over bare metal stenting with a self-expandable stent (Misago; Terumo) for the treatment of intermediate length femoropopliteal lesions in patients with symptomatic peripheral arterial disease at one year.

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he trial set out to demonstrate the clinical superiority of primary stenting using a paclitaxel elutingstent when compared to using a bare metal stent in this group of patients in order to gather direct comparative data on treatment strategies in this population of patients.

“The trial highlights a need for further direct comparative data between devices and strategies for treatment of femoropopliteal lesions,” said Yann Gouëffic (Nantes, France), who presented the data for the first time at the Charing Cross Symposium (CX; 24–27 April, London, UK).

BATTLE is a French multicentre randomised clinical trial that included 181 patients who were randomised 1:1 to either receive treatment with Zilver PTX (n=86) or with Misago (n=85). The trial included patients classed as Rutherford 2–5, with de novo atherosclerotic femoropopliteal lesions of 2–14cm and a reference vessel diameter of 4–7mm.

The primary endpoint was freedom from in-stent restenosis at one year,

defined as restenosis of greater than 50% and by a peak systolic velocity index of >2.4 at the target lesion, assessed by an independent core laboratory. An independent clinical event committee adjudicated adverse events.

There are currently several different options for treating TASC A and B lesions, Gouëffic said, including bare metal stents, drug-eluting stents, drugcoated balloons and covered stents.

However, there are few head-to-head randomised data completed so far to compare the safety and efficacy of devices for femoropopliteal lesion treatment.

Data from the ZILVER PTX randomised controlled trial showed that the paclitaxel-eluting Zilver PTX fared better compared to a bare metal stent. This data from the second arm of randomisation of Zilver PTX trial, Gouëffic explained, led to the hypothesis that Zilver PTX would prove superior to the bare metal Misago stent and subsequently the BATTLE trial was designed as a superiority trial, rather than

non-inferiority.

In the BATTLE trial, the patient population at baseline showed similar mean lesion lengths and reference vessel diameters, with intermittent claudication present in 79% of patients in the Zilver PTX arm and 82% in the Misago arm.

Technical success was 100% in both arms.

At one year, 82 patients completed the follow-up in the Zilver PTX group and 78 in the Misago groups. The mean lesion length in both groups was 7.3mm.

In total, three deaths were observed at one year, but they were not related to the device, or the procedure. Clinical outcomes were similar between both groups at one year in terms of Rutherford stages and primary sustained clinical improvement.

At one year, the primary endpoint of freedom from in-stent restenosis based on the Kaplan-Meier estimation was reached in 51 of 82 Zilver group patients (90.3%) and in 51 of 78 Misago group patients (85.7%; p=0.36).

The trial did not show a significant benefit for the paclitaxel-eluting stent with regard to secondary endpoints either. Patency rate was 84.2% vs.

81.6% (p=0.41) for Zilver PTX and Misago, respectively; target extremity revascularisation was 4.9% vs. 3.8% (p=0.52) and notably, target-lesion revascularisation rates were 8.8% vs.

Yann Gouëffic

8.9% (p=0.91), respectively, at one year.

No difference was seen between the treatment arms in Rutherford stage at baseline or at one year. Finally, there was an 88.6% clinical improvement in the Zilver PTX arm vs. 85.3% in the bare metal stent arm (p=0.56).

Due to the fact that BATTLE was designed as a superiority trial, the investigators were not able to conclude that these two devices are equivalent.

“Further, these results are not applicable to all drug-eluting stents,” Gouëffic pointed out, “as future generation devices may cause the field to change.

More data on the advantages of drug-eluting therapy in comparison to bare metal stents are still required, to define the strategy for the treatment of intermediate length femoropopliteal lesions,” Gouëffic maintained.

Angiolite BTK drug-eluting stent is safe and feasible for treating below-the-knee lesions Kim Taeymans (Antwerp, Belgium), speaking at the Charing Cross Symposium (24–27 April, London, UK), revealed six-month outcome results for the Angiolite BTK drug-eluting stent (iVascular). She reported that the device was “safe and feasible” for the management of below-the-knee lesions and that it had a positive effective on wound healing.

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aeymans noted that the goals of treating lesions that are below-the-knee are relieving ischaemic rest pain and “avoiding terrible wound problems”. She added: “After successful recanalisation in long, diffuse lesions, with plain balloon angioplasty, you can go for plain balloon angioplasty or drug-coated balloons in patients. But, the role of drug-coated balloons in this context is debatable. We do think, however, there is a role for drug-eluting stents in short focal or medium length lesions.”

Therefore, the aim of the present study was to review the use of the balloon-expandable Angiolite BTK drug-eluting stent as a bailout device in belowthe-knee procedures. Regarding this device, in the single-centre, physician-initiated, prospective, real-life study, 50 patients with below-the-knee lesions were enrolled; all lesions had a Rutherford classification of 4–6. The primary endpoint was safety and feasibility at six months and the absence of clinically-driven target lesion revascularisation at 12 months. Second endpoints included technical success (defined as <30% residual stenosis), clinical success (defined as no serious adverse events by six months), primary patency, secondary patency, and improvement in Rutherford classification.

Regarding the Angiolite BTK drug-eluting stent,

Kim Taeymans

Taeymans reported that it has “a specific open cell design” and is made out of cobalt chromium— making the device “very flexible”. As well as

being coated with sirolimus, it has a fluoropolymer biostable coating. Additionally, according to Taeymans, the Angiolite BTK has “a large portfolio of diameters and lengths”. Explaining why sirolimus was used rather than paclitaxel, as is usually the case with peripheral drug-eluting stents, she said the drug had better long-term patency and that “there is a lot of evidence for using sirolimus in the coronary arteries”.

Overall, 64 lesions (mean length 51.45mm) were treated. In 49 of these lesions, predilatation orballoon angioplasty was used prior to the device being implanted; primary stenting was used in the remaining 15 lesions. Technical success was 100%.

At six months, primary patency was 88%, secondary patency was 96%, freedom from target lesion revascularisation was 94%, and freedom from minor amputation was 72%. Taeymans commented that at the six-month time point, most patients were Rutherford 2—at baseline, nine patients were Rutherford 6, 23 were Rutherford 5, and 18 were Rutherford 4.

She stated that in one patient, there was a “very positive effect of revascularisation after two weeks” and that “after seven weeks, there was also most complete healing of the wound. I do have to say that it was combined with vacuum therapy.”

“To conclude, use of Angiolite is safe and feasible; it has a positive effect on revascularisation and wound healing. But, we do admit that longer term follow-up is needed to confirm the advantages of the use of the Angiolite BTK drug-eluting stent.”

16

June

Issue

18 78

Abdominal stent grafts

Majority of CX audience decides endovascular-first strategy for critical limb ischaemia is a concept without evidence In one of the Great Debates at the Charing Cross Symposium (24–27 April, London, UK) endovascular and vascular surgery titans went head-to-head to debate the contentious topic “Endovascular-first strategy for critical limb ischaemia is a concept without evidence”.

Arguing in favour of this motion were current Society for Vascular Surgery (SVS) president Clement Darling III (Albany, USA), BASIL trial principal investigator Andrew Bradbury (Birmingham, UK) and BEST-CLI trial principal investigator Matthew Menard (Boston, USA).

Against the motion were vascular surgeon Peter Schneider (Honolulu, USA), angiologist Thomas Zeller (Bad Krozingen, Germany), and interventional radiologist Andrew Holden (Auckland, New Zealand).

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vote held at the session saw 60% of the voters backing the motion “Endovascular-first for critical limb ischaemia is a concept without evidence”.

Sharpening his metaphorical scalpel, Andrew Bradbury (Birmingham, UK) insisted that the only “reasonable, logical and unbiased” conclusion that can be drawn from the existing data on surgical vs. endovascular approach is that patients presenting with critical limb ischaemia due to femoropopliteal or infrapopliteal disease and who can have vein bypass, should be offered vein bypass. Further, outside of ongoing randomised controlled trials, an endovascularfirst revascularisation strategy should be reserved for those patients who cannot have vein bypass, he said.

Referring to the BASIL (Bypass versus Angioplasty in Severe Ischaemia of the Leg) trial, the only published randomised controlled trial of endovascular treatment against bypass in critical limb ischaemia due to infrainguinal disease, Bradbury reminded the audience that the trial showed for most patients who live for more than two years, the outcome with bypass is better in terms of amputationfree survival and overall survival.

“People often say to me that BASIL is an old trial and is no longer relevant, but the question is: are the BASIL-1 endovascular outcomes still relevant? I would say very much so, and if anything, I would suggest that the results from endovascular studies now are not quite as good as what we saw in the BASIL trial for a number of reasons,” Bradbury stated.

Further, he pointed out that while the BASIL-1 infrapopliteal subgroup results do not all meet standard criteria for statistical significance, the direction of the effect consistently favours bypass and the confidence intervals rule out the possibility of clinically important effects in favour of plain balloon angioplasty over vein bypass in this subgroup.

As for whether an endovascular procedure should be done prior to bypass, Bradbury pointed to research from the European Journal of Vascular Surgery that showed clinical outcomes following primary bypass were significantly better than in patients undergoing secondary bypass after a failed endovascular intervention. It advised that prior to treating patients with clinical limb ischaemia with primary balloon angioplasty, clinicians should consider that if this approach should fail, the outcome of attempted subsequent bypass is likely to be significantly worse than if primary bypass were attempted.

Acknowledging the need for additional data, which is currently being collected in BASIL-2 and BASIL-3 and BEST-CLI, Bradbury maintained that it is clear that those patients who can have a vein bypass should have a vein bypass.

Adding to the debate in favour of bypass surgery, Matthew Menard (Boston, USA) called for an end to turf war between surgeons and endovascular practitioners. “We need all of us, collectively, to put the turf wars of the last two decades behind us and start, systematically and scientifically, to begin the process of figuring out the evolving role for open and ‘endo’ procedures,” he stated.

Choosing one word to sum up his point of view, Menard referred to “equipoise”. He said that the BEST-CLI trial showed that the revascularisation option in critical limb ischaemia that has the best value was clearly bypass surgery.

He used data from Vogel et al from a 13,000-patient metaanalysis of the endovascular approach which reports a 7% 30-day mortality, 30% 30-day rehospitalisation rate and a 24% 30-day amputation rate, and compared that with a

1,000-case analysis by Pomposelli et al which found a 0.9% 30-day mortality, 78% five-year limb salvage rate, and a 22% five-year amputation rate with open surgery.

“You have an endovascular 30-day amputation rate of 24% and a bypass surgery five-year amputation rate of 22%...

What is the matter with us? There is zero data to support an endovascular-first strategy, and it is unsound medical practice to pretend that there is,” Menard argued.

Bringing up the rear for the winning side, Clement Darling III (Albany, USA ) concluded that there is no survival benefit in the endovascular-first approach and better limb salvage in bypass surgery, which also costs the same, or less, than the endovascular-first approach. He said that bypass should be the first option in patients with significant tissue loss, and that the endovascular-first approach should be reserved for those with rest pain or shallow ulcers and those who are anatomically suited or have no vein and/or a limited life span.

Darling added that the ideal therapy should “really be effective and durable and have high limb salvage rates, low mortality and low morbidity. Unfortunately, this is not seen in the current endovascular-first approach data.”

Leading the charge for the interventionalists was Thomas Zeller (Bad Krozingen, Germany) who stated that the arguments of the promoters of surgery-first approach were mostly based on the BASIL trial—an “old fashioned, outdated and underpowered” trial. “What I have heard so far is not that much evidence to back the use of surgery as a front-line strategy for critical limb ischaemia,” he said.

BASIL randomised patients to receive either bypass or balloon angioplasty, but angioplasty is “definitely an outdated endovascular interventional method today,” said Zeller. Further, in the trial, patients were analysed on the basis of their randomisation and not on the basis of treatment, he added. Zeller explained that 15% of patients allocated to surgery did not actually undergo surgery, yet they were analysed as having been treated with a bypass.

“The crossover in the endovascular cohort is not as marked, and this indicates that even if you want to treat a patient with surgery, a relevant number of patients are unfit for open repair. This is in contrast to the endovascular approach, which can be applied to everybody,” he said.

He also questioned the data for survival benefit that was obtained from the BASIL trial, noting that the trial was powered for follow-up to the two-year endpoint and not for the five-year endpoint. “Even if the curves appear to diverge in favour of the bypass group, you have to take into account the number at risk for the analysis at five years,” said Zeller, noting that these were too small to draw definitive conclusions about the superiority of one method over the other. “[To do this] is nonsense,” said Zeller, reiterating that a post-hoc analysis based on an underpowered study could not be used to conclude anything definitive.

After dismantling the findings of the BASIL trial, he carefully constructed the argument that open surgery is not the gold standard for the treatment of critical limb ischaemia anymore by using more recent studies such as the SPINACH

(Surgical reconstruction vs. peripheral intervention in patients with critical limb ischemia) study. Iida et al found no difference in three-year amputation-free survival between surgical reconstruction and endovascular therapy in a critical limb ischaemia population. “We have, at least, comparable amputation-free survival for endovascular therapy and, at least, comparable wound healing rates for endovascular therapy. The endovascular approach is less invasive and has no intensive care unit stay. It results in faster ambulation and shorter hospital stay. It allows the optimisation of outflow (pedal arteries) and many patients need to crossover to receive this treatment due to the anatomical requirements for surgery,” Zeller concluded.

Andrew Holden (Auckland, New Zealand) maintained that to debate whether the evidence supports a surgical bypass or an endovascular-first approach “implies that both treatment modalities are in clinical equipoise”. However, said Holden, in critical limb ischaemia clinical equipoise does not exist because endovascular revascularisation is constantly evolving due to improvements in equipment, advances in the concept of vessel preparation, antirestenosis strategies and procedural improvements. New concepts are angiosome-guided interventions and new developments in intraprocedural monitoring of adequate revascularisation are some examples, he said.

Holden also pointed out that it was important to bust the myth that endovascular was “not a free pass” and that failed endovascular cases have a significantly worse outcome than those treated early with bypass.

“The vast majority of critical limb ischaemia patients is offered endovascular revascularisation first. It is important to remember that rest pain (Rutherford 4 critical limb ischaemia) often responds to revascularising single-level disease and almost never requires surgical bypass. In the small subset of patients who have a good life expectancy, large wounds and a venous conduit, it is reasonable to consider surgical bypass and we must established scoring tools to allow us to identify this subset of patients.

“The investigators of BEST-CLI and BASIL-2 should be congratulated on their endeavours. However, these trials will not significantly change clinical practice because there is not clinical equipoise between the treatments being compared and one of the therapies is continuing to improve and evolve.

There is also clearly ample evidence for an endovascularfirst approach to critical limb ischaemia in most patients, so further trials are not going to change that,” affirmed Holden.

Peter A Schneider (Honolulu, Hawaii) then picked up the endovascular baton and pointed out that the advantage of bypass relied largely upon the improved patency it conferred and that it was usually a definitive treatment.

However, bypass also had disadvantages with regard to the morbidity and mortality associated with the procedure and the time patients needed to stay in hospital after receiving the procedure. “In order to perform a bypass, there needs to be adequate vein. The procedure is typically to a single target and there can be anatomic limitations to the target site,” Schneider explained.

In 2018, there is currently Level 1 and other evidence backing an endovascular-first approach to treat critical limb ischaemia that is just as strong as the evidence for bypass, exhorted Schneider. “Endovascular interventions rarely burn bridges and surgery is not the answer in most patients. The preponderance of evidence favours the endovascular-first approach for critical limb ischaemia, and those who can do both, more often than not select endovascular first,” he concluded.

18

June

Issue

18 78

Drug-coated balloon

First BIOLUX P-III data show below-the-knee treatment with drug-coated balloon is safe at one year The safety of below-the-knee treatment with a paclitaxel-coated balloon (Passeo-18 Lux, Biotronik) was reported in a late-breaking trial session at the Charing Cross Symposium (CX; 24–27 April, London, UK) by Gunnar Tepe from the Klinikum Rosenheim in Germany.

The BIOLUX P-III trial below-the-knee (BTK) subgroup analysis showed “highly promising” 12-month safety and efficacy outcomes of infra-popliteal artery treatment in particularly advanced stage peripheral arterial disease patients.

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he BIOLUX P-III prospective, global, multicentre registry all-comers cohort enrolled any patient with an infralinguinal artery lesion that could be treated a Passeo-18 Lux drug-coated balloon; the only exclusion criterion was failure to cross the lesion with the guidewire. The primary endpoint of the study was freedom from major adverse events at six months and freedom from clinically driven target lesion revascularisation at one year.

Among the 882 patients enrolled in the all-comers cohort, 150 were treated for below-the-knee lesions. Tepe highlighted several notable baseline characteristics of this cohort, including the high number of diabetic patients at 62.7%: “If we compare this with general superficial femoral artery studies, we normally see 30–35% of patients with diabetes,” Tepe said. Similarly distinct was the percentage of patients in Rutherford 5–6 classification (39.2% Rutherford 5 and 26.7% Rutherford 6), as well as the 76.7% of patients with critical limb ischaemia. “We had a lot of patients with calcified arteries and also with long lesions,” Tepe said, with 49.1% of treated lesions being TASC C or D. For patients at such an advanced stage of disease, for whom risk of amputation is significantly higher, the results of the BIOLUX P-III BTK follow-up analysis at one year were surprising. “Below-theknee patients had more major adverse events” Tepe

Gunnar Tepe

explained, with 83.1% freedom from major adverse events at one year vs. 91% in the rest of the registry cohort, “but this was not from target lesion revascularisation”. In fact, Tepe showed that below-the-knee lesions showed similar rates of freedom from clinically-driven target lesion revascularisation compared to other patients (92.4% vs. 93.7%, respectively), as well as patency (78.8% vs. 77.7%). “Of course,” he said, “the amputation rate was difference, and that is

where the major difference is”, pointing to freedom from major amputations in 92.2% of below-the-knee patients vs. 98.5% of others.

Overall, the results were interpreted by Tepe as a “strong signal” that drug-coated balloons provide a safe and effective treatment option for below-the-knee lesions.

Discussion with audience, however, revealed doubts about the efficacy data, as the unusually low limb-loss rate for such a high proportion of advanced disease stage—and indeed an 87.5% improvement of at least one Rutherford classification category—were questioned by audience members. Thomas Zeller (Bad Krozingen, Germany) and Andrew Holden (Auckland, New Zealand) remarked on the striking Rutherford 6 percentage, of which Holden said “you would expect at least half of those patients end up with amputations”, an expectation which was not reflected in the trial data. Holden added: “We would certainly go back to the sites and make sure these data were correct”. To this point, Tepe responded that the Rutherford classification had been determined by the operators. However, “this was not a dedicated belowthe-knee artery study, and therefore for the future there needs to be a focus on below-the-knee to see what might work, and see what endpoints might be appropriate for further study,” Tepe said.

Finally, Tepe concluded: “Despite what has been discussed previously, that drug-coated balloons do not work or might even be dangerous in below-the-knee arteries, critical limb ischaemia patients seem to benefit from this treatment, and in terms of safety, data are clear: It is safe.” Indeed, Holden agreed that the safety outcomes of the trial were reassuring for drug-coated balloon therapy in critical limb ischaemia patients with below-the-knee lesions.

20

June

Issue

18 78

Stent grafts

Low early mortality and high technical success for novel thoracic stent graft A physician-sponsored investigational device exemption trial on thoracic endovascular aortic repair (TEVAR) using a new thoracic stent graft (Valiant, Medtronic), along with its initial 30-day data, was revealed at the Charing Cross Symposium (CX; 24–27 April, London, UK)

by Thomas Maldonado (New York, USA). The early results showed high technical success (94%) and low mortality (9%).

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he Valiant thoracic stent graft is currently undergoing feasibility trials as part of physiciansponsored investigator device exemption (PS-IDE) at select centres in the USA. Maldonado presented early results of the first 32 patients treated at six US sites, showing high technical success (94%) as well as good efficacy and safety profile at 30 days.

The PS-IDE trial is designed as a prospective, single-centre, nonrandomised multi- or single-arm study with five years of follow-up.

All sites use similar protocols, with intent of pooling data. Enrolment includes patients with a maximal aneurysm diameter of >5.5cm (>4.5cm symptomatic) and growth of >0.5cm in six months. In the first 32 patients, 12 (38%) were Crawford type II and 11 (34%) type III. Although endovascular approaches to thoracoabdominal aneurysmal disease provide advantages over open repair—such as improved early survival, shorter recovery period and overall less invasiveness—current device options have certain limitations, argued Maldonado. Devices for all patient

Thomas Maldonado

anatomies are not currently available “off-the-shelf”, Maldonado said, “and importantly, distal perfusion is impeded and not stageable in all cases”.

To meet clinical needs in this area, “In 2014, Patrick Kelly of the department of Vascular Surgery at Sanford Health

in Sioux Falls, USA developed a novel branched endograft for thoracoabdominal aortic aneurysms which promised to be fully off-the-shelf, requiring no customisation,” Maldonado said, “leading to the 2016 Valiant thoracoabdominal stent graft system”—a

prototype of Kelly’s multibranched stentgraft system for endovascular treatment of thoracic aneurysms.

Current data are early, but Maldonado reported that major adverse events included three events of paraplegia (9%). “It goes without saying that you are covering a fair amount of aorta here, so the graft [which extends 17cm above the coeliac artery] is perhaps not ideal for Crawford type IV aneurysms”, he explained, as it could cover significantly healthy aorta.

Maldonado suggested these results emphasise the importance of applying thorough spinal drainage protocols, rescue protocols, and careful patientselection, as well as implementing a multidisciplinary team involvement in each case and recognising the value of staging procedures.

Several sites are engaged in the Valiant PS-IDE trial, which continues to address some of the key limitations of existing technologies, and to minimise risk of spinal cord ischaemia events “an anticipated second-generation manifold device will be significantly shorter and better suited for type IV anatomy”, Maldonado concluded.

Two-year data from the VBX Flex trial show “little or no” decline in outcomes Data from the VBX FLEX trial, presented at the Charing Cross Symposium (CX; 24–27 April, London, UK), show that two years after receiving the Viabahn VBX balloon-expandable stent graft (Gore) for the treatment of complex iliac disease, 93% of patients (including those with complex disease) are free from target lesion revascularisation. These results indicate that the trial’s nine-month results, which showed that the stent graft was associated with a low rate of target lesion revascularisation, have been sustained.

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resenting the data, Michael Dake, who has recently been named vice president of University of Arizona Health Sciences, Arizona, USA, said that one of the most distinguishing characteristics of the Viabahn VBX is its flexibility. He explained that this meant patients could be treated from a contralateral approach and noted that in the VBX FLEX trial, about 20% of patients underwent intervention via this approach. “The other thing, with this device, is that there is a tremendous matrix of diameters and stent lengths.

We really have not had this before in our armamentarium. So, it gives us a lot of choice,” Dake commented.

The VBX FLEX trial was a prospective, multicentre, singlearm clinical study involving 134 patients. The trial enrolled patients with iliac disease and included those who had advanced and complex disease. The primary endpoint was a composite of major adverse events at nine months with a planned follow-up period of three years.

Nine-month data, which were

published last year in the Journal of Endovascular Therapy, found that only 2.3% of patients experienced the primary endpoint—a composite of events, including device- or procedurerelated death within 30 days, myocardial infarction within 30 days, and target lesion revascularisation within nine months. There were no device-related serious adverse events or unanticipated adverse device effects.

Dake’s presentation focused on the one-year and two-year outcomes.

He noted that at one year, the rate of freedom from target lesion revascularisation was 95.4%, with 93.1% at two years. He added that, at two years, the rate of freedom from target lesion revascularisation was more than 90% in nearly all of the subgroups, commenting that this was true even in patients who had received kissing stents (92.9% at two years). Furthermore, it was 95.3% in patients with TASC II C and D lesions.

Dake concluded: “It is a realworld study—TASC II C and D lesions, kissing stents in a high

Michael Dake

majority of patients. Kaplan-Meier indices, through two years, showed sustained effectiveness (greater than 92% in all comers).”

He added: “There has remained an unmet need for stents that can effectively repair complex, advanced iliac disease without major limitations or drawbacks. The Viabahn VBX

represents a next-generation modality that addresses this extant unmet need, with previously reported safety and effectiveness through ninemonths. At two-year follow-up, the results show little, or no, decline in outcomes compared to nine months and support its employment in the treatment of these patients.”

Thank you for helping us celebrate 40 Years of Looking Forward in style!

At CX 2018, we were delighted to welcome just over 4,000 participants from more than 80 countries.

H O L D T H E D AT E Vascular & Endovascular

Challenges Update NEW Monday–Thursday format

15–18 APRIL 2019 MONDAY–THURSDAY OLYMPIA GRAND • LONDON • UNITED KINGDOM

Aortic Challenges

Peripheral Arterial Challenges

Venous Challenges

Acute Stroke Challenges

Vascular Access Challenges

EDUCATION

www.cxsymposium.com

INNOVATION EVIDENCE

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Issue

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Critical limb ischaemia

One-year outcomes of EndoAnchor study adds ESAR— endosuture aneurysm repair—to the endovascular lexicon Speaking at the Charing Cross Symposium (CX; 24–27 April, London, UK), Frank Arko (Charlotte, USA) presented one-year results from the 70-patient short-neck cohort of the ANCHOR Registry.

Patients with an abdominal aortic aneurysm were treated with an endograft and endoanchors (Endurant and Heli-FX, Medtronic). The data showed “very good clinical outcomes in a challenging patient population”, Arko reported, and suggested a new term be added to the endovascular lexicon to name the procedure: endosuture aneurysm repair, or ESAR.

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hort-neck patients from the registry were defined as having necks of less than 10mm, with a minimum of 4mm. The proximal neck diameter was “right around 26mm, and the average neck length 7mm”, Arko said. The average aneurysm size was 5.8cm. The endoanchors were described by Arko as a “complementary option for the short-neck patient; Endurant is on label to 10mm, and with the addition of the endoanchor it allows you to treat down to a 4mm neck.”

In the overall one-year outcomes for the shortneck cohort, average duration of procedure time was 148 minutes—not “that much of an increase”, Arko commented. Patients received an average of 5.5 endoanchor implants. Technical and procedural success was high, with 88.6% (62/70) and 97.1% (68/70), respectively. Type Ia endoleak incidence was low at one year, with 1.9% which Arko mentioned is consistent with alternative treatment options including FEVAR and chEVAR. Endograft migration was 0% and need for secondary procedures at the one-year follow-up was 4.7%.

Frank Arko

“Nearly all patients had stabilisation or decreasing of the sac, with 43% decreasing in size”, Arko said. Freedom from all-cause mortality was 93%, and freedom from aneurysm-related mortality was 94.3%, with no aneurysm ruptures. “Most deaths were related to perioperative

implant procedure,” Arko added, “and as 17% of patients in the registry were actually symptomatic, these were not all elective cases.”

“In theory,” he argued, “endoanchor implants increase the seal zone and provide radial fixation, and we also believe it prevents neck dilatation in this dilating disease. For patients with neck lengths less than 10mm, the endograft plus the endoanchor for this is advantageous, because it applies for patients who present symptomatically or emergently; it is ‘off-the-shelf’ and expands patient applicability; it has very good clinical results in the ANCHOR short-neck cohort at one year; and it decreases the complexity costs and resource utilisation within the hospital system compared to alternative therapies. Finally, it really allows us to evolve our therapy and really simulate open surgical repair.”

Speaking about the technique applied in the trial, using endoanchors in combination with the stent graft for repair in this type of short-neck abdominal aneurysm patient, Arko concluded that a new term is appropriate to describe it: “We really ought to name this, and add the term to our lexicon of aneurysm therapy—and we would like to call this ‘ESAR’: endosuture aneurysm repair”.

While one-year data are promising, the study aims to follow the 70 patients for a total of five years, to determine the longer-term safety and efficacy of the endoanchor and endograft combination therapy.

Ovation is an “on-label” solution that has durable outcomes According to Sean Lyden (Cleveland, USA), the Ovation iX abdominal stent graft (Endologix) can be used within the manufacturer’s instructions for use (IFU)—i.e. on label—in many patients in whom other devices would be considered off label. He added that the ENCORE registry indicates that the device is associated with durable outcomes at five years.

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peaking at the Charing Cross Symposium (CX; 24–27 April, London, UK), Lyden reported that “violations” of instructions for use of endovascular aneurysm repair (EVAR) devices are driven by short conical and wide necks. He added that the “number one” reason for failed EVAR interventions in people who have received a device off label is loss of proximal seal, which is followed by neck dilatation, migration or “just disease progression in the aortic neck”.

Lyden reported that there are three potential solutions aimed at managing patients with complex abdominal aortic aneurysm without having to use a device off label: fenestrated EVAR (FEVAR), chimney EVAR (chEVAR), and the use of endoanchors.

Furthermore, he said, there was the Ovation iX device—describing it as a low-profile device (14F) with “broad IFU applicability”, good device deliverability, and polymer proximal sealing. The indication for the device, Lyden explained, was based on neck diameter at the proximal sealing ring and “all you need to have is a neck diameter between 16mm and 30mm”.

Lyden claimed that Ovation could be used to treat complex aneurysm anatomy that would be off label for other devices. For example, he stated

that 66% of patients initially enrolled in the Zenith Fenestrated US trial—of which, Lyden was an investigator— were excluded from the study for having unsuitable anatomy. “We were not allowed angulation, thrombus, or calcification,” Lyden reported and noted: “Some of the patients excluded would have been on label for Ovation.”

Furthermore, he observed that in the PERICLES registry—in which patients underwent chEVAR or snorkel EVAR—the rate of clinically relevant cerebrovascular events was 1.9%.

“With an infra-renal fixation device [such as Ovation], you are not going to have issues with stroke,” Lyden stated.

Additionally, according to Lyden, data from the ENCORE registry indicate that Ovation is associated with durable five-year results. This registry was a pooled retrospective analysis of prospectively enrolled studies (four of which have five-year data), comprising of 1,296 patients. Of these patients, overall, 46% had one or more complex anatomical feature—28% had a reverse taper ≥10%, 7% had a neck length of <10mm, and 14% had an external iliac artery of <6mm. He stated some of these patients would be “off label” with other devices. At five years, the freedom from rupture rate, conversion, and aneurysm-related mortality

Sean Lyden

was 99%, freedom from target Ia endoleak was 96%, and freedom from reintervention was 98%.

Summing up the data for Ovation and for chEVAR, FEVAR, and endoanchor devices, Lyden said: “Short conical necks are an issue for standard EVAR. Polymer EVAR with Ovation has broad applicability within IFU and has durable five-year outcomes. FEVAR, chEVAR, and endoanchors have added issues.”

Responding to the talk, Frank Arko (Charlotte, USA), who spoke about one-year data for endoanchors at this year’s CX, commented that he did not think that Ovation was “without the risk of endoleak and freedom from reintervention”. To which, Lyden

replied: “I do not think there is any therapy that anyone has invented that is not without long-term issues. I think the point of this discussion is that we have good five-year data. If you look at the risk of migration in ENCORE, it is actually lower than seen in the Zenith Fenestrated US trial. With chEVAR, we do not have enough data.”

Looking to the future, Lyden said enrolment had been completed in the US Food and Drug Administration (FDA) trial of the next-generation Ovation device—Ovation Alto. A key difference between this device and the current-generation of Ovation was the “elevated sealing ring”, which was moving from 13mm to 7mm.

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Interview

Profile

Tilo Kölbel

Coming from a family of medical professionals, Tilo Kölbel was destined to become one himself. He tells Vascular News about his journey to becoming a vascular surgeon, the proudest moments in his career and the research that he is currently doing, as well as his interests outside of medicine.

Why did you decide you wanted a career in medicine, and why in particular did you choose to enter the vascular field?

My medical career was guided by serendipity, mostly.

I was exposed to the medical profession throughout my childhood; with my father being an orthopaedic surgeon and my mother a general practitioner. Patients, treatments, and reimbursement issues were topics of everyday dinner conversations throughout my childhood. I never thought of becoming a physician myself until friends convinced me to sign up for the medical school admission-tests at the last minute.

Fortunately, with good marks, I gained the option to enter medical school directly.

All surgical fields I worked in were interesting and I would have been happy with a career in urology, orthopaedic surgery, or general surgery. But I chose vascular surgery because I noticed that the general surgeons I worked with during my training were overly cautious of vascular damage. So much so, that they sometimes limited surgery just to stay safely away from major vasculature. The limitations I witnessed helped me understand that vascular surgery experience would make me a better surgeon; and allow me to perform surgery as extensively as necessary.

Who have been your most important career mentors and what lessons did they teach you?

Many colleagues taught and influenced me throughout my career. Bengt Lindblad gave me confidence in operating and stimulated my curiosity for research. Mats Lindh taught me the principals of vascular interventions and shared his vast knowledge on interventional materials with me. Krassi Ivancev inspired and encouraged me to change what requires change, and that endurance can overcome most hurdles.

Martin Malina believed in my ideas and encouraged my steps forward in device-development. Sebastian Debus gave me the opportunity to co-develop a cutting-edge aortic programme and to refine treatment principles in complex aortic therapies.

But perhaps the most vital lessons come from experience.

With every case, I learn something new alongside the colleagues I have the privilege of working with.

And most importantly, my patients continue to teach me to value their health and wellbeing, and that every aortic case needs to be judged individually with respect to their needs.

How have you seen the field develop during the course of your career?

I began to follow aortic treatment techniques and principles in 2004 when I moved to the Malmö Vascular Center in Sweden. Most basic treatment principles and techniques were already established at that point—and, in all areas, refinement and technical improvements have characterised the development trend since then.

Fenestrated and branched aortic endografts have been applied to all areas of the aorta since.

A major breakthrough for proximal aortic therapies, in my memory, was the use of trans-cardiac access techniques; such as the transseptal and transapical access techniques used for structural heart interventions. At the same time, open and hybrid techniques have developed around frozen elephant trunk.

What new vascular technology are you watching closely and why?

Not all patients are suitable for endovascular repair due to anatomical reasons and certain comorbidities. I follow closely developments such as the spider-graft for thoraco-abdominal repair to improve open surgical and hybrid techniques—in hopes of offering less invasive treatments for patients who are currently contraindicated for endovascular repair. But some of the techniques and implants, especially those which promise easy solutions for complex problems—like the Multilayer Flow Modulator or simple aortic arch stents for type A aortic dissection—should be watched with caution, as the described mechanism of action may be both unproven and far too optimistic to be true.

My interest in new developments for this space is motivated by the fact that I frequently have to deal with failed previous repairs.

Aneurysm sac-filling technologies are also of interest, and I am glad to see that more companies are developing polymers that may work without a bag and independently of the main graft.

Lastly, cerebral protection devices have become frequently used tools in transcatheter aortic valve implantation (TAVI). I follow this technology with great interest as we will need to focus more on safeguarding neurological outcomes in thoracic endovascular aneurysm repair (TEVAR) in the near future.

What is the most interesting paper or presentation that you have seen recently?

In the British Journal of Surgery, AH Perera et al present a study on neurological outcome after TEVAR with a surprisingly high frequency of new silent brain infarctions, over 80%, with presentation of neurocognitive decline of the same frequency. This study uses up-to-date examination to get a realistic impression of the neurologic damage during TEVAR.

What are your current research interests?

My main research interests lie in a number of different areas: Stroke prevention in TEVAR, the role of air embolism and techniques to prevent stroke together with Fiona Rohlffs and Vladimir Makaloski.

Clinical outcomes of complex aortic arch intervention together with Nikos Tsilimparis.

Development of a new hybrid-graft for thoracoabdominal aortic aneurysm (TAAA) repair: the Spider-graft together with Sebastian Debus and Sabine Wipper.

Spinal cord ischaemia prevention techniques in porcine models together with Sabine Wipper.

Trans-femoral access for branched EVAR in TAAA with Nikolaos Tsilimparis.

False lumen occlusion techniques together with Fiona Rohlffs.

What were the aims and findings of the Stroke from Thoracic Endovascular Procedures (STEP) collaboration?

The STEP study aims to reduce the risk of stroke during TEVAR. Early goals of the initiative are to define best

practices in TEVAR; identify stroke-prevention strategies; and define meaningful outcome measures in cooperation with vascular and cardiovascular surgeons, clinical neurologists, cardiologists, and manufacturers of endografts. The main findings are that, among a group of 18 world-experts nominated by stent graft manufacturers, a significant experience with aortic arch endografting exists.

There was broad consensus in some areas like anticoagulation during treatment and the use of cardiac output reduction in proximal landing zones.

No consensus exists, presently, in revascularisation strategies of the left subclavian artery, which may play a significant role in stroke. Additional first-phase results were highlighted during the STEP-presentations at the 2018 Charing Cross Symposium.

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Interview

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Fact File

Why do you think understanding of stroke caused by endovascular procedures has been lacking?

Advancements in TAVI, TEVAR, or carotid artery stenting (CAS) treatments are usually focused on overcoming the problems and issues of older techniques, like open surgery, and on the potential advantages of new minimally invasive approaches. This is totally justified and required in order to improve patient outcomes.

At the same time, physicians and industry—both enthusiastic for these new treatments—may be biased when it comes to recognition of negative outcomes related to these new treatments. As endovascular aortic treatments are now widely established, we really need to focus on the potential down-sides of

innovations introduced, to further improve outcomes for our patients—who otherwise significantly benefit from new minimally invasive treatment options.

What is the most memorable case you have had?

I will never forget the case of a patient, who I treated for an asymptomatic penetrating atherosclerotic ulcer (PAU) in the aortic arch with a branched arch graft, who suffered a stroke during the operation. It is memorable because I could see air bubbles being released in the aortic arch on digital subtraction angiography (DSA).

And I remember watching the bubbles travel up the innominate artery. I did not know how to react at that time. I may have been able to avoid the stroke by closing the vessel loop at the carotid artery, but I was not prepared for that situation and the patient suffered a life-changing stroke.

What are some of the proudest moments in your career?

The proudest moment in my career was the first insitu bending case we performed in 2007 in Malmö.

A 66-year-old woman required a TEVAR with an unfavourable steep arch, so that a bird-beaking of the stent graft was likely to occur. We used a newly developed technique of modifying a standard graft so that the inner-curvature could be shortened using a sliding knot, a Bowden-cable mechanism, and a release mechanism. For the first time, we were able to remotely change the stent graft position in the aortic arch through femoral access! For me, it was the most fascinating experience to see a new idea and theory, that worked on the bench, be transferred into practice by simple side-table modification. Since this case, all introductions of new techniques at our centre have been proud moments. A few that come to mind are: the first transapical TEVAR, the first trans-septal throughwire case, the first Candy-plug, the first Knickerbocker, and the first trans-femoral branched endovascular aneurysm repair (BEVAR) case.

Other moments that I cherish are to see colleagues develop and grow to become leaders in their specialty.

Recently my colleague, Nikolaos Tsilimparis, was offered a professorship at the Ludwig Maximilian University (LMU) of Munich. This may be a big loss for our team and I will miss Dr Tsilimparis, but the move also serves to distinguish our German Aortic Center in Hamburg, Germany.

What advice do you hope your mentees/ students will always follow?

Do not believe your teachers too much and question dogmas in your textbooks. Do not be afraid of trying something different if you are convinced of it and do it with respect for your patients’ wellbeing.

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

My main interests outside medicine are to spend time with my wife and my children. I enjoy travelling and I like all kinds of fishing and outdoor activities. In the autumn, I enjoy mushroom picking—especially when in Sweden. I like swimming, skiing, tennis, and any kind of board-game like chess or go.

Current appointment

Head of the German Aortic Center, University Heart Center Hamburg, Germany

Professional career

2009 - 2014 Senior consultant for Vascular

Surgery and Head of

Endovascular Therapy, University Heart

Center Hamburg, University

Hospital Eppendorf, Germany 2008 - 2009 Consultant for vascular

surgery and interventional

radiology at the Vascular

Center Malmö-Lund, Malmö

University Hospital, Sweden 2007 Board certified specialist in

vascular surgery, Sweden 2006 Full-time occupation at the

endovascular section of the Vascular Center 2005-2007 Staff-member at the Vascular Center Malmö-Lund 2004 Fellowship: Vascular Center

Malmö-Lund, Malmö

University Hospital, Sweden.

2003 Board certified specialist in general surgery 1996 – 2003 Residency and fellowship in

surgery (general and

trauma surgery) Sankt Gertraudenkrankenhaus,

Humboldt University, Berlin, Germany

Education

2015 Professor of Surgery at

University of Hamburg, Germany 2012 Guest Professor at Huazhong

University of Science and Technology, China 2011 Associate Professor for

Vascular Surgery at the

University of Hamburg, Germany 2009 Associate Professor for

Vascular Surgery at

the University of Lund, Sweden

Editorial Board appointments

Journal of Endovascular Therapy (since 2012) Gefäßchirurgie (since 2014) Gefäßmedizin Scan (since 2014)

June

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Abdominal aortic aneurysm

Data support targeted screening of first-degree relatives of aneurysm patients as a “valuable alternative” to population screening

27

A new study suggests that the familial risk of abdominal aortic aneurysm is much higher than previously thought and this excess risk is highest both in female relatives and in relatives (of any sex) of female patients. According to Hence Verhagen (Rotterdam, The Netherlands), who presented the study at the Charing Cross Symposium (CX; 24–27 April, London, UK), these findings indicate focusing screening on first-degree relatives of aneurysm patients may be a more effective approach.

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erhagen observed that a recent UK study found that, following the introduction of a populationbased screening programme for men aged >65 years, the incidence of aneurysm was “lower than expected”. He added: “To raise efficacy, screening of subpopulations at high risk—i.e. targeted screening—may be a better alternative.”

One subpopulation may be people with known family history of aortic aneurysm, with Verhagen noting that 20% of aneurysm patients have a positive family history. “The majority of the studies looking at this have been directed at finding aneurysms in male relatives of mostly male patients. Very little is known about the risk for female relatives or if there are different familial risks for female and male aneurysm patients,” he commented.

Therefore, the aim of the present study was to evaluate the risk of aneurysm in relatives of aneurysm patients with a specific focus on the risks for female relatives and those associated with female patients. Verhagen explained that it would address three key questions: would family screening of aneurysm patients’ relatives reveal a specific category of patients at risk of aneurysm? Do female relatives of aneurysm patients have a higher risk than male relatives of developing an aneurysm?

And, do relatives of female aneurysm patients have a higher risk of developing an aneurysm?

In the cross-sectional, observational, single-centre study, aneurysm patients were interviewed using a family history questionnaire. A familial aneurysm relative was defined as someone who had at least one first-degree relative with an aneurysm.

Of 590 patients interviewed, 22 had a family member who was also participating in the survey; therefore, only the first diagnosed aneurysm patient was included.

After excluding patients with a relative already in the study, data were available for 568 patients. Of these, 128 (23%) had a relative with an aneurysm. In this familial aneurysm group, 68% had one relative with an aneurysm, 23% had two relatives, and 9% had three or more relatives.

Verhagen reported that, overall, the relatives of patients in the study had a 6.4% risk of aneurysm. However, when patients were analysed by sex, relatives of a female patient had a 9% risk of aneurysm and relatives of a male patient had a 5.9% risk of aneurysm.

“If you are male with a relative with an aneurysm,” Verhagen said, “your risk is 1.7 times that of a person without such a relative. If you are female, it is 2.8 times that risk.” Furthermore, the study showed that the risk of aneurysm in men with a

Hence Verhagen and Jennifer Ash

relative who is a female aneurysm patient is 11%; this risk is two times the aneurysm risk of the general population. However, women with such a female relative have a 7% risk—5.5 times the risk of aneurysm seen in the general population.

Commenting that recommendations for family screening vary, Verhagen stated: “Our data support targeted screening of all first-degree relatives of aneurysm patients, irrespective of sex. To increase efficiency, screening family members of aneurysm patients may be a valuable alternative to population screening.” He added that starting screening at the age of 50 “seems reasonable”, as 7% of aneurysm patients worldwide are younger than 60 years and “no data exist on growth rate in familial abdominal aortic aneurysm”.

The significance of LUCY trial is “the non-significance”

Following Verhagen’s presentation, in the same “EVAR in women controversies” session at CX, Jennifer Ash (Champaign, USA) outlined the early results of the LUCY study—the first prospective study to specifically evaluate endovascular aneurysm repair (EVAR) in women. She stated that, in the study, women had similar 30-day outcomes to men.

According to Ash, women have

historically been under-represented in EVAR trials as they “only represent 10% of patients enrolled in EVAR investigational device exemption (IDE) trials”. Therefore, the aim of LUCY was to provide further data in this area, with Ash commenting: “The reason this trial was called LUCY was because, as some people may know, the famous US comedian Lucille Ball actually died of a ruptured aneurysm.”

In this prospective, multicentre study, men and women were enrolled in a 2:1 ratio (149 men and 76 women). The primary endpoint was the rate of major adverse events within 30 days of the procedure. EVAR was performed with the Ovation stent graft (Endologix).

Ash noted that the vascular characteristics of the female patients were “pretty routine” for what is seen in clinical practice female patients. She observed that, as has been seen in previous studies, women had significantly more complex anatomy—for example, juxta-renal angle was significantly increased (26.6±19.2 vs.

23.1±3.1; p<0.01). Also, proximal neck length was decreased in women but not to a significant extent.

Ash stated: “The significance of this trial is essentially the non-significance as, at least in this trial, there was no

significant difference when it came to procedural outcomes between men and women.” She added that there was also no significant difference between groups in terms of major adverse events. This included all-cause mortality, renal failure, and respiratory failure. Furthermore, there were no stent occlusions in either group and there were no stent migrations. “The women actually fared a bit better than men in terms of type Ia endoleak, which is a little surprising given that access was perhaps a little more hostile in the female population,” Ash said.

She concluded: “What we know is that women traditionally have a limited eligibility for endovascular repair and worse outcomes. LUCY is the first prospective study to specifically evaluate EVAR in women, head-to-head with their male counterparts, and we found at 30 days that—at least in this trial—women and men experience similar outcomes after EVAR, both procedurally and in terms of adverse event rates.”

The findings of LUCY were supported by a study from Chiara Mascoli (Bologna, Italy) and colleagues. Presented by Mascoli immediately after Ash presented LUCY, this study reported encouraging results for the use of new-generation EVAR devices in women.

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Endovascular aneurysm repair

EVAS is associated with higher long-term survival than EVAR A recent study sought to investigate whether endovascular aneurysm sealing (EVAS) might be associated with a difference in mortality compared to endovascular aneurysm repair (EVAR). Marc Schermerhorn (Boston, USA) presented the three-year data for the first time at the Charing Cross Symposium (CX; 24–27 April, London, UK), showing a 41% difference in overall mortality rates between EVAS and EVAR patients—a number that increases to 50% for patients for >5.5cm aneurysm diameters.

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he retrospective, propensityweighted study compared long-term survival for the Nellix EVAS system (Endologix) with traditional EVAR, including 333 EVAS patients from the system’s US investigational device exemption (IDE) trial as well as 15,431 EVAR patients from the Society for Vascular Surgery Vascular Quality Initiative (VQI). All patients were treated between 2014 and 2016, and were propensity weighted for abdominal aortic aneurysm size, patient demographics and cardiovascular risk factors. Schermerhorn and colleagues also applied inverse probability weighting to compare risk-adjusted long-term survival, using KaplanMeier. “There were certain things that we were not able to control for, like neck length or neck angulation”,

Schermerhorn said, “but most of the import factors were pretty wellcaptured”.

The primary outcome was overall survival, and a secondary analysis stratified overall survival by aneurysm diameter. At three years, the primary outcome showed a 41% lower risk of mortality for patients in the EVAS group with a 93% survival for EVAS patients vs. 88% survival with EVAR (hazard ratio 0.59 [0.38—0.92] p=0.02). Secondary analysis identified the particular survival benefit of EVAS in patients with vessel diameters >5.5cm, as EVAS patients with these larger aneurysms experienced a 50% higher rate of three-year survival as those treated with EVAR (hazard ratio 2.01, p=0.01).

However, for patients with smaller aneurysms of >5.5cm, “we actually

Marc Schermerhorn

found no survival differences”, Schermerhorn pointed out, suggesting that this may be related to thrombus: “Smaller sacs have less volume to thrombose, and this may be why we see an increase in mortality with EVAR in larger diameters.”

“There is an inflammatory process that may be compounded by thrombus within the aneurysm, and we know that if we obliterate that space, that can mitigate it somewhat in the short term. There are several hypotheses in terms of how sac obliteration

can impact that, and any number of possibilities may potentially explain the differences we saw.”

The study hypothesis was based on previous studies showing an association between sac behaviour (regression, stability or expansion) and long-term mortality, which persisted in patients without endoleaks and was not modified by reintervention. “It led us to question if there might be a survival difference in late mortality with active sac management using EVAS compared to EVAR,” Schermerhorn said, as “EVAS minimises the potential for thrombus to form in the sac area and dramatically minimises the chance for a type II endoleak.” Noteworthy in the data was the stability of mortality difference over time in the three years, Schermerhorn said. “We see that there was some early separation of the curve, and they continue to separate.” Longterm follow-up will reveal whether this trend continues.

Concluding his presentation on the outcomes, Schermerhorn said the results “certainly makes us wonder if we should apply this technique of active sac management more broadly— at least in experimental settings.”

Latest generation of EVAR devices reduces iliac limb occlusion rates to under two per cent One-year data from the latest generation of EVAR devices may help to expand the patient population that is eligible for the procedure by accommodating a wider range of aorto-iliac anatomies. Data are emerging that these devices have a rate of iliac limb occlusion of less than 2% and this compares favourably with the rates obtained for previous generations of stent grafts, delegates at the Charing Cross Symposium (CX; 24–27 April, London, UK) heard.

M

auro Gargiulo, Bologna, Italy, presented on the risk factors for iliac limb occlusion and one-year data with the latest generation EVAR devices. “The incidence of iliac limb occlusion at one year in the second to third generation endografts typically ranges between 3.4–4% in the literature. However, with the graft and material-related causes becoming obsolete, in effect the rate of iliac limb occlusion is coming down,” he reported.

Limb dysfunction, often present to the tune of 27%, is one of the main causes of reintervention in the follow-up of endovascular repair. Iliac limb occlusion represents the third most frequent cause of reintervention after EVAR and the anatomical severity of iliac arteries is one of the main risk factors for iliac limb occlusion.

Younger-aged patients, graft limb kinking and poor outflow are all factors that confer greater risk of limb graft occlusion. The factors that predispose endograft limb occlusion after endovascular aortic repair include the angle of the iliac arteries, calcification and endograft limb oversizing.

The latest generation of low profile devices includes the Incraft (Cordis, now Cardinal Health) Ovation (Trivascular), Excluder C3 (Gore) and Zenith Alpha (Cook Medical). Safety and effectiveness data from Incraft show no limb thrombosis at 12 months and a rate of 1.9% at 24 months with only one occlusion at day 666; outcomes from an Italian study of Ovation reveals an iliac limb occlusion rate of 0.6% at 30 days, and no

Mauro Gargiulo

instances at one year. Data from the new Gore Excluder C3 stent graft from the European module of the Global Registry for Endovascular Aortic Treatment (GREAT) shows 12-month iliac occlusion rate of 0.7%, Gargiulo reported.

He then elaborated on results on the Zenith Alpha

abdominal endograft performance in abdominal aortic aneurysm with severe iliac anatomies. An analysis from an Italian National Registry which collected data from September 2015 to November 2016 at 14 Italian Vascular Surgery Units reported on the primary endpoints being technical success, 30-day mortality, 30-day endograftrelated reintervention, 30-day endoleak and 30-day iliac artery complications. The secondary endpoints included short-term limb occlusion, short-term endograft-related reintervention, and short-term abdominal aortic aneurysm-related mortality.

“In order to evaluate endograft performancerelated to iliac anatomy, we divided the sample into two main groups, one with patients with hostile iliac anatomy (n=26) and another with patients who had suitable iliac anatomy (n=236). Results from the study of 274 patients, of which 262 had valid data, revealed a technical success rate of 98.5% and 30day mortality rate of 1.5%, with a procedure related mortality of 0.3%. “There was one case of endograftrelated re-intervention and no cases of 30-day iliac complications,” Gargiulo stated. Regarding the primary endpoint, there were no iliac complications in this group of patients. In the short-term, we had 1.5% iliac limb thrombosis, and the overall limb occlusion rate was 1.5% at one year. The subgroup with severe iliac arteries disease did not have significant differences in their primary and secondary outcomes from the group with the more suitable anatomy.

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“Promising” initial results for sirolimus-eluting bioresorbable scaffold in DESappear trial

Drug-eluting scaffold

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The sirolimus-eluting bioresorbable peripheral scaffold system (Prava; Elixir Medical) is designed to treat stenoses and occlusions in the superficial femoral artery. Prava was first implanted in October 2016 and will be clinically evaluated in the DESappear trial that has currently enrolled 21 patients at 11 sites in Austria, Belgium, Germany and New Zealand.

“T

he initial results have been very promising with one target lesion revascularisation performed at the 12-month follow-up interval,” said Andrew Holden (Auckland, New Zealand) who presented an update on the trial at the Charing Cross Symposium (CX; 24-27 April) in London, UK. The DESappear (Drug Eluting Scaffold) study is a prospective, multicentre, single-arm safety and performance study. The investigators plan to enrol 60 patients across Europe and New Zealand. The coordinating investigators are Marc Bosiers (Dendermonde, Belgium) and Dierk Scheinert (Leipzig, Germany). The key inclusion criteria are symptomatic claudication (Rutherford 2–4) and vessel diameter of ≥5mm to ≤6mm. The patients will be followed for clinical assessment and imaging using duplex ultrasound follow-up at 30 days, six months, one, two and three years.

The primary safety endpoint is a composite of freedom from perioperative death through 30 days and freedom from major adverse limb events defined as the occurrence of major amputation, thrombectomy or thrombolysis, or major open surgical revascularisation through six-month follow-up. The primary effectiveness endpoint is primary patency defined as freedom from restenosis (>50% diameter reduction defined by duplex ultrasound) or clinically-driven target lesion revascularisation through six months.

The drug-eluting scaffold is a poly L-lactic acid-based polymer scaffold incorporating sirolimus (rapamycin) with around 17µg sirolimus per mm of scaffold length. Over four weeks, about 30% of the drug is eluted, with 90% of the drug eluted at six months. The scaffold degrades in six months with near complete resorption at one year.

“The scaffold is made up of sinusoidal rings connected by ‘S’ links for flexibility. It is balloonexpandable, has low recoil, radial strength and a single pattern for 5mm and 6mm scaffold diameters.

It comes in 18, 37 and 57mm scaffold lengths,” reported Holden.

Holden was not able to provide substantial patency data at 12 months, but noted that all the patients who have reached the follow-up have patent vessels.

“It is very early days and there is

limited trial data, unfortunately, but the data presented can show you the concept of a different bioabsorbable

balloon-expandable scaffold for the superficial femoral artery segment with sirolimus elution,” said Holden.

Andrew Holden

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Radiology safety

Radiation protection more important than positioning during thoracic procedures The 2018 Charing Cross Symposium’s (CX; 24-27 April, London, UK) Thoracic Aortic Controversies programme hosted a debate, which saw 59.6% of the audience vote against the motion that traditional radiological positions on the right side of the patient, during thoracic procedures, are beneficial for radiation safety and offer superior workflow and access. The audience, therefore, supported the arguments of Joost van Herwaarden (Utrecht, The Netherlands) and Eric Verhoeven (Nuremberg, Germany)—both of whom were debating against the motion.

S

peaking for the motion were Tilo Kölbel (Hamburg, Germany) and Timothy Resch (Malmö, Sweden).

Kölbel commented that, historically, right-sided access—compared with left-sided access—has been linked to an increased risk of stroke. However, he called this “old dogma” that has not been proven; in particular, according to a study by Kölbel and colleagues, the stroke rate associated with right brachial access during branched endovascular aneurysm repair (BEVAR) is in line with that seen in the literature for the treatment of thoracic and thoracoabdominal aneurysms.

Expanding on the “for the motion” argument, Resch claimed that an operator switching to a left-hand access was “an individualist approach” because it meant that all of the other members of the team are on the right-hand side while only the operator is on the left (and therefore, exposed to all of the radiation on the left-hand side).

Furthermore, he added that a study by Kado et al showed that operator discomfort was considerably increased when a left radial approach was used: 22% vs. 4% for the right radial approach (p=0.017). “You think that might not be important but the most common reasons for an interventional surgeon to retire or take sick leave is a musculoskeletal disorder”.

As part of his “against the motion” arguments, van Herwaarden told the audience that they should not accept that the C arm is on the left side of the patient “because you can build it yourself”. He added that, at his centre,

Joost van Herwaarden and Eric Verhoeven

switching access sides resulted in different levels of radiation exposure depending on the procedure that was required. Acknowledging the potential for access site complications, van Herwaarden stated “if it was my arm, I would prefer complications on the left side. I think most patients would” (because they are likely to be right handed). Countering this argument, Resch said: “I would not want to tell the patient that I want to practice using my left hand, so I will stand on the left side. I would tell

them that I am very skilled with my right hand and I will stand on the right side.”

Verhoeven, following on from van Herwaarden, said that the real issue was not side you stand on but how much protection you use. He added that a confounding factor in previous studies that indicated that the left-hand side was associated with more radiation may have been the lack of a protective shield on the left-hand side, noting “modern hybrid operating rooms have protective shields on both sides”.

A study, Verhoeven reported, showed that brain tumours in interventionalists occurred significantly more frequently on the left-hand side than on the righthand side—indicating this is related to the traditional radiological positon of being on the right-hand side of the patient. “So why would you not be practical and stand half the time on the right and half the time on the left?” he commented.

Summing up his arguments, he said; “Scientific data are not sufficient; protection is more important than which side to be on, and the left side position has its advantages.

I do not think it is a bad idea to switch positions.”

However, there were two points which all four debaters—irrespective of whether they were for or against the motion—universally agreed upon: the need for operators to be aware of radiation exposure during procedures, and that steps need to be taken to minimise exposure.

Deficiencies in operator behaviour: Premature atypical malignancies in high-volume operators BIJAN MODARAI COMMENT & ANALYSIS In this article, Bijan Modarai outlines recent research on the effects of radiation exposure in high-volume interventionalists, why a future with alternative modalities to X-ray guided procedures is an exciting prospect, and what safety measures could make a difference in the meantime.

I

n recent years, alarming and emotive reports of cancer diagnoses made in high-volume interventionists at a relatively young age have focused attention on the deleterious effects of occupational radiation exposure. The fact that even the low doses absorbed during fluoroscopically guided procedures can induce DNA damage, triggering inherent reparative mechanisms within the cell, are now beyond doubt and our group has shown this to be the case in both patients and operators after endovascular aortic procedures. These studies also suggested the fact that operators may have differential sensitivity to the same exposure dose. DNA repair pathways

are error-prone and can lead to genomic instability and cytogenetic damage after chronic radiation exposure. In the absence of long-term studies in large cohorts of health workers, however, a definitive link between exposure and malignant transformation remains difficult to prove.

Our bodies are continuously bombarded by low-dose environmental radiation and in the UK, for example, an individual would accumulate approximately 2mSv of natural background exposure per year.

Flying at altitude increases this exposure, with a 10 hour flight accounting for an extra 50μSv. A link between low dose exposure and cancer may be emerging with a recent publication showing an

increased incidence of cancer in pilots who have the highest cumulative air hours and large dose exposures before the age of 40. Our recent studies monitoring realtime radiation exposure have measured an average dose of approximately 70μSv to exposed body parts after a complex endovascular aneurysm repair. A highvolume operator, performing 50 cases per year, for instance, would incur a significantly raised dosage over that time.

A modern day vascular trainee in their early 30s would be at risk of accumulating the aforementioned yearly dose for more than 30 years, with consequences that are unknown at present but may become apparent as our understanding of the ill effects of chronic exposure improves.

Real-time monitoring has allowed linkage of operator behaviours that account for the highest dose exposure.

Protective manoeuvres during digital subtraction angiography (DSA) appear to be particularly important. Left lateral angulation of the C-arm, distance of the operator from the table and the “air gap” between the detection plate and the patient’s body are independent predictors of radiation exposure during DSA. The operators who were studied remained tableside for the majority of DSA runs, significantly increasing their absorbed dose. Perhaps a paradigm

shift in strategies that ensure minimal exposure throughout the procedure is required. A non-operating “spotter”, delegated with prompting the operator to instigate optimal protective manoeuvres for themself and the rest of the team, particularly during the more critical steps of the procedure when focus on radioprotection may wane, could prove highly effective in reducing dose.

A definitive link between low-dose chronic radiation exposure and cancer remains to be demonstrated, but the mere fact that exposure can trigger DNA damage should motivate all, and in particular young and training vascular interventionists, to optimally protect themselves. The promise that one day we may circumvent the use of X-rays during procedures, instead using modalities such as electromagnetic guidance, for example, is exciting.

Until then, encouraging radiation safety behaviours, ensuring optimal room set up and insisting on maximal shielding is of paramount importance.

Bijan Modarai is a senior lecturer in Vascular Surgery at King’s College London and honorary consultant Vascular Surgeon at Guy’s and St Thomas’ NHS Foundation Trust. as well as a senior fellow at the British Heart Foundation

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Vascular access

High technical success and low complications with everlinQ in study and real-world experience Experience from multiple clinical studies and real-world use of the everlinQ endoAVF system (TVA Medical) globally has shown high technical success with low complication rates, high cannulation success and high patency rates with low interventions.

T

he data were presented by Tobias Steinke (Dusseldorf, Germany) during the Vascular Access Masterclass at the Charing Cross Symposium (CX; 24–27 April, London, UK).

According to Steinke, even with over 50 years of arteriovenous fistula use, 20– 60% of arteriovenous fistulae still fail to mature, and 80% of patients start dialysis on a central venous catheter. As to why they fail, he pointed to the flow-limiting lesions often at the site of surgery associated with maturation failure.

“To overcome this problem—surgical damage at the anastomotic site— endoAVF creation with the everlinQ might be the solution. When doing the endoAVF, we have no scar, we may have fewer interventions, higher patency rates, and by adding another site, we have more options to create an AV fistula,” he said.

During the endoAVF procedure, two thin, flexible, magnetic catheters are inserted into an artery and vein in the arm through a small puncture or incision. When placed in proximity, the magnets in each catheter attract to each other, pulling the vessels together. After confirming alignment, the radiofrequency electrode is deployed. The venous catheter, which contains the electrode, delivers a burst

of radiofrequency energy to create a connection between the artery and vein. Then, the catheters are removed.

The fistula is confirmed with arteriogram to show that arterial blood is flowing to the low-pressure venous system, creating multiple options for cannulation.

Steinke looked at data from over 300 endoAVF cases performed with the everlinQ endoAVF system globally in Germany, the UK, Paraguay, Australia and Canada. The data were from the endoAVF studies as well as non-study, real-world cases.

The pooled efficacy and safety data from 157 study patients, as well as data from 79 commercial cases, demonstrated 96.8% and 97.5% procedure success rate in the clinical study population and real-world cases, respectively. He further reported that 12% of patients experienced a procedurerelated serious adverse event in the pooled studies and 3.8% of patients in the real-world cases.

In the pooled studies, time to cannulation was two months, only 14.6% of pre-dialysis patients initiated dialysis with a central venous catheter, and twoneedle cannulation was 74.8% at six months. Ninety per cent of patients in the real-world cases were successfully

Tobias Steinke

cannulated by six months.

Additionally, at 12 months, 74.8% primary patency (unobstruction without additional intervention); 79% secondary patency (unobstruction) and 98.2% functional patency (durability post-cannulation) was reported in the clinical study patients.

Newer data are showing that the endoAVF procedure potentially has better outcomes than the surgical approach.

“The latest data show that the patients in the NEAT study, which were compared to propensity-score

matched surgical AVF cohort from the United States Renal Database System, have less intervention rates than the endoAVF patients,” Steinke explained.

He showed that one month after the fistula was created, 50% of surgical arteriovenous fistula patients needed an additional intervention, compared with only 15% of endoAVF patients.

Further, at one year, 85% of surgical arteriovenous fistula patients have had an additional intervention compared to only 38% of endoAVF patients.

Further, a separate presentation at ISPOR 2018 (19–23 May, Baltimore, USA) showed that compared to surgical arteriovenous fistula patients, endoAVF patients had nearly double the number of days with a functioning fistula for dialysis and spent less time using a central venous catheter (83 vs.

261 days), leading to improvements in quality-adjusted life years (QALYs) (0.574 QALYs vs. 0.548 QALYs), and needed fewer interventions (0.55 vs. 4.38), resulting in an average of 90% lower related costs (US$1,271 vs. US$13,031) in the first year after receiving an arteriovenous fistula.

“The everlinQ endoAVF system adds additional fistula options for patients and physicians. The studies, real-world experience and commercial cases show that we do have high technical success, with quite low complication rates, high cannulation success, and we have high patency with low intervention rates,” Steinke concluded.

IN.PACT AV access trial nears enrolment completion Andrew Holden (Aukland, New Zealand) presented updates of the IN.PACT AV access investigational device exemption (IDE) trial at the Charing Cross Symposium (CX; 24–27 April, London, UK), noting that the study had almost finished enrolment, with just 24 further participants needed.

T

he IN.PACT AV Access IDE trial is evaluating the safety and efficacy for up to two years of the IN.PACT AV access drug-coated balloon (Medtronic) compared to percutaneous transluminal angioplasty for treatment of de novo or restenotic obstructive lesions of native arteriovenous fistulae in the upper extremity. The study aims to enrol 330 patients with a 1:1 randomisation to either treatment.

The primary safety endpoint is serious adverse event rate through 30 days, and the primary efficacy endpoint is primary patency at six months post-procedure.

Patency is defined as freedom from clinically driven target lesion revascularisation or thrombosis of the access circuit measured. The primary endpoint is not measured at one particular day, but over a range of approximately 180 days; Holden explains that this is important, “rather than focusing on a single day with regard to the primary endpoint.”

The multicentre, randomised study is particularly exciting, Holden claims, as it “will allow us to compare an Asian, North American and New Zealand population”, having recruited patients from approximately 30 sites in Japan, the USA, and Holden’s native New Zealand. There are three principal investigators of the study from these

respective countries: Robert Lookstein (New York, USA), Hiroaki Haruguchi (Tokyo, Japan), and Holden.

The Japanese cohort “recruited extremely quickly and early”, meaning that the baseline clinical and lesion characteristics reflect the early recruitment geographic distribution, and are likely to change with full recruitment. For example, there is a dominance of radiocephalic access in the interim analysis of 105 patients presented by Holden (more common in Japan), whereas brachiocephalic and brachiobasilic access, favoured in North America, are perhaps underrepresented at this stage. Commenting on this, Holden says, “Subsequently, we have seen a much more even distribution.”

During his presentation, Holden showed a few case studies to the CX audience, illustrating the use of the IN.PACT AV access drug coated balloon in real patients.

To be included in the study, patients can only have one target lesion, or alternatively two tandem lesions less than 3cm apart, and with an overall length of the two together, totaling <10cm.

This is different to the Bard trial comparing the Lutonix

AV drug-coated balloon with a standard balloon for the treatment of dysfunctional AV fistulae (Trerotola, 2018).

However, like in the Bard trial, patients have to have good vessel preparation. Holden says, “We are learning good vessel preparation is extremely important, as it is in the peripheral arterial system.” Patients also need to have a residual stenosis of less than 30%, and the absence of a significant dissection or perforation.

There are multiple exclusion criteria. Patients could have a central venous stenosis, but that had to be adequately treated prior to treatment of the target lesion without a significant residual stenosis. Unlike the Bard trial, patients could not have, or have ever had a history of, thrombosis of the target access.

Patients who had a pseudo-aneurysm at the target site were also excluded, and patients could not have a stent in the AV access.

The IN.PACT AV access drug-coated balloon is available in diameters between four and 12mm; in the trial, balloons with lengths of 40 to 80mm were used. The device is based on the IN.PACT Admiral drug-coated balloon technology, which is FDA approved to treat patients with paripheral arterial disease (PAD) in the upper leg. The IN.PACT AV access drug-coated balloon is an investigational device and is not approved for sale in the USA, advised Andrew Holden Medtronic.

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Aortic arch

Endovascular approaches to aortic arch disease gather steam Both the Charing Cross Symposium 2018 (CX; 24–27 April, London, UK) and the recent Aorta Masterclass (1–2 June, London, UK), hosted by Brompton & Harefield, focused on current approaches to aortic arch disease.

A

t the Aorta Masterclass, Deborah Harrington, a cardiac surgeon in Liverpool, UK, showed that open aortic surgery continues to have good clinical outcomes. However, neurological injury remains a significant complication and in her view, cerebral protection strategies need to be individualised.

Speaking on multi branch arch stents, Nicholas Cheshire, Royal Brompton, London, UK, gave a comprehensive overview of the different approaches and concluded that whilst open aortic surgery is still the gold standard, there are many unanswered questions: How should you manage hypothermic circulatory arrest? What is the right cerebral protection strategy? Should you use the Carrell patch or branched grafts? What are the

appropriate measures of outcome?

The patient series for wholly endovascular approaches to aortic arch disease were far smaller than open surgery. Nonetheless, these series are growing but outcomes are yet unknown. Cheshire finished his presentation with a summary of the literature evidence.

Mario Lachat, Zurich, Switzerland, followed with a presentation on total aortic arch endovascular repair with multibranched stent grafts. He concluded that multi-branched stent grafts were feasible and safe. However, these multi-branched stent grafts were only suitable in a highly-selected patient population and less than 10% of patients with aortic arch disease were anatomically suitable. The use of multi-branched stent grafts should be reserved for patients unfit or high risk MORTALITY STROKE for open repair. AcOPERATIVE† STROKE NOTE cording to Lachat, Open Arch (n=18,286) multi-branched Englum et al 12% 8% Mild HCA & ACP >DHCA & no CP Settepani et al 5.3% 3.4% Triple ACP & Spielvogel >Other techniques stent grafts are ? Low Vol. Centre, Age & redo surgery Urbanski et al 8.8% 5.7% 5-12% 0-8% ready for prime worse Konstantinos et al 9.5% 6.2% Equivalent results to Arch Hybrid time but experience Hiraoka et al 4.7% 0% Lower stroke rate with open surgery is still very limited, Arch Hybybrid (n=1,014) with mid-term and Konstantinos et al 11.9% 7.6% Equivalent results to Open Surgery 7-12% 7-11% Hiraoka et al 7% 11.6% Higher Stroke rate with Arch Hybrid long-term results of Total Endo (n=127) between two to five Haulon et al 13.2% 15.8% Results improve with experience (7% & 10%) years of follow-up 4-13% 16% Tazaki et al 4% 16% Single branch > Triple Branch currently mostly Summary of literature evidence (Source: N Cheshire/Aorta Masterclass 2018) missing. Lachat

provided a literature review of different aortic arch branched devices including both the Cook Medical and Bolton Medical devices.

Mario Lachat also presented his initial data about the Nexus aortic arch branched device (Endospan) which is still CE mark pending. The Nexus first-in-man procedure was performed by Cherrie Abraham in Montreal, Canada. Abraham is now based in Portland, USA. Lachat’s personal experience with Nexus aortic arch branched device is 40 total endovascular arch repairs since 2014.

At CX 2018, during the CX Innovation Showcase, Andrew Holden gave the early clinical experience with the Nexus arch branched device designed for Zone 0 and 1 with a mean follow-up of 12 months. This is a prospective, open-label, non-randomised, single-arm investigational clinical study with clinical and computed tomography angiography (CTA) follow-up for five years post-implantation and independent core lab imaging review and CEC safety events adjudication. Twenty-five patients were implanted between August 2014 and December 2017.

For fourteen patients, double bypass RCCLCC-LSA was performed, usually around seven days prior to Nexus implantation and in 10 patients, a parallel graft was implanted parallel to the Nexus device in order to feed one of the supra aortic vessels. No rupture, loss of integrity, device migration or device malposition was observed. The early data for Nexus Aortic Arch Stent Graft System is encouraging with 100% technical success observed. Holden concluded that the Nexus has an excellent safety profile with no aneurysm

related death in a high-risk group. Gutter type 1 endoleaks were observed in four patients at six months and were only seen in patients implanted with a periscope in parallel to Nexus (instead of surgical bypass). One of these endoleaks resolved spontaneously and two were successfully treated, leaving one persistent endoleak at two years. Aneurysm growth >5mm was observed due to gutter endoleaks and one was resolved with coil embolisation. Re-interventions included five to resolve type II endoleak from a patent LSA (requiring a plug) and two to resolve gutter endoleak. However, Holden concluded that longer term data is needed to further study performance of Nexus Aortic Arch Stent Graft.

Martin Malina, currently on sabbatical in Copenhagen, Denmark, gave his personal experience of using chimney grafts for endovascular arch repair. Malina has used chimney grafts at a low but consistent rate over 20 years in three institutions.

Ninety per cent of his use of arch chimneys is in urgent cases: ruptures, myocotic aneurysms, complicated Type B dissection, accidental overstenting and previous surgery. His personal experience showed 100% patency for all arch chimneys and a 30-day unrelated mortality of 7% and late related mortality of 7%. Malina concluded that chimneys do work and they should be used when branched and fenestrated endografts are unavailable or unsuitable. More data on arch chimney repair is needed but patients with poor anatomy for thoracic endografts or who tolerate open repair poorly, may benefit from an arch chimney repair the most.

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TEVAR-related stroke

STEP seeks to advance patient safety after TEVAR Stroke is a major concern in thoracic endovascular aortic repair (TEVAR) and delegates from the Charing Cross Symposium (CX; 24–27 April, London, UK) heard the results of a collaborative study that pooled practice data from a number of high-volume centres in order to eventually benefit patients undergoing the procedure. A highlight of the session was the transmission of a live complex aortic case from Hamburg, Germany, that illustrated key learning points. The case was a live endovascular arch reconstruction by Nikos Tsilimparis on a patient with thrombus in the arch.

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he STEP (Stroke from Thoracic Endovascular Procedures) study was presented by the investigators Roger Greenhalgh (London, UK), Stéphan Haulon (Le Plessis Robinson, France), Tilo Kölbel (Hamburg, Germany) and Fiona Rohlffs (Hamburg, Germany).

Advisors to the STEP study are Hugh Markus, a neurologist, Simon Redwood, an interventional cardiologist, Heinz Jakob, a cardiothoracic surgeon, and Kyriakos Lobotesis, a neuroradiologist.

“The purpose of this is to share the experience this group is producing. This experience includes over 800 procedures per year, broken down into the various zones, and that data is a powerful tool. We also have the findings being illustrated by a live procedure that is taking place alongside,” Greenhalgh said.

The STEP study aims to provide best practice for endovascular procedures for the ascending aorta, aortic arch, great vessel branches and high TEVAR to lower the risk of cerebral embolism.

The group is an independent, open, interdisciplinary one that is built to learn from each other and to make TEVAR safer for patients. The STEP collaborators include Frank Arko, Carlos Bechara, Adam Beck, Dittmar Böckler, Matthew Eagleton, Dennis Gable, Stéphan Haulon, William Jordan, Tilo Kölbel, Gustavo Oderich, Jean Panneton, Geert Schurink, Santi Trimarchi, Marwan Youssef and the physicians who nominated by the manufacturers of the devices used in the procedure including Martin Czerny, Michael Dake, Ahmed Koshty and Rodney White.

The manufacturers of devices used by the 18 operators are Cook Medical; Gore; Bolton Medical (now Terumo Aortic); Jotec and Medtronic. The STEP study did not seek to compare outcomes based on the device used.

Rohlffs explained that a STEP questionnaire had been designed and sent out to gather data on experience and current practice. The questions were formulated before the data was collected.

“With regard to the experience of the 18 physicians who were surveyed, all key opinion leaders operate on each zone and the survey group has a cumulative 143 years of experience in Zone 0 interventions; 193 years in Zone 1 and 232 years in Zone 2,” Rohlffs said.

STEP results

Illuminating data on the number of procedures performed within each zone per year revealed that there were 171 procedures performed in Zone 0 (21%); 135 procedures performed in Zone 1 (17%) and 510 procedures performed in Zone 2 (62%).

Other key findings include data from the preprocedural, intraprocedural and postprocedural phases of TEVAR.

Preprocedural results

Preprocedural findings showed there was 100% consensus that an interdisciplinary team is central to the final decision for treatment strategy in Zone 0. In Zone 1 and Zone 2, this was seen as less necessary.

The physicians unanimously responded “yes” to the question: Do you apply endovascular techniques in urgent or emergency cases? This established that the endovascular approach is widely utilised among those surveyed in this setting.

There was also 100% consensus to the question of which imaging technique was preferred to visualise the pathology, with all physicians revealing that they preferred CT angiography over MR angiography.

However, there was less consensus on how long before the procedure the imaging could be performed.

Intraprocedural data

There was consensus in the survey about anticoagulation, that the procedure should be done under antiplatelet therapy and that the activated clotting time should be >250 seconds.

There was no consensus on revascularisation of the left subclavian artery, which was either done routinely or selectively. With regard to timing, revascularisation of the left subclavian artery was sometimes done in advance, simultaneously with the procedure, or on a case-by-case basis. There was 100% consensus on the use of cardiac output reduction in Zone 0, with less consensus in the other zones. There was no consensus on the technique of cardiac output reduction or embolisation prevention strategies with some physicians using carotid clamping, others using the CO2 flushing technique or minimising arch and device manipulation.

The survey findings did not show a role for filters in this context. There was no consensus on adjunctive techniques.

Post-procedural findings

All operators favoured CT angiography to visualise the stent graft at followup, but there was no consensus on the timing of the imaging. Again, there was consensus on antiplatelet therapy and

postprocedural intensive care unit stay for the Zone 0 patients, but no consensus on the other aspects.

Simon Redwood, King’s College London, UK, spoke on the topic of reducing cerebral embolisation with transcatheter aortic valve implantation (TAVI) to note that stroke remains an issue and that it is under-reported. “The risk of stroke is up to 4–5% in trials at 30 days. Trials only report major disabling strokes, yet minor strokes or transient ischaemic attacks have a two- to four-fold increase in mortality. Stroke risk is independent of operator experience and using diffusionweighted MRI, 68–99% of patients show evidence of embolisation,” Redwood explained. With regard to the timing, stroke is a procedural issue and usually occurs within 72 hours of undergoing the procedure, he said.

Alan Lumsden (Houston, USA) presented data on transcranial Doppler being a useful technique for monitoring arch interventions. Transcranial Doppler is a non-invasive technique that uses a pulsed Doppler transducer for assessment of intracerebral blood flow.

Cerebral emboli can be recognised by high-intensity transient signals (HITS).

“Real-time middle cerebral artery monitoring is the gold standard as it relates immediately to intervention. It can be used for troubleshooting established and developing procedures and identifies high-risk manoeuvres,” he said.

Markus made the point that stroke is clinically relevant and it is what matters to the patient. “[The determination of stroke] requires large numbers in studies as there are few endpoints. Surrogate endpoints such as brain imaging, imaging of emboli and cognition is often what counts,” he noted.

Operative risk of stroke and death in endarterectomy studies is assessed differently depending on the specialty of the assessor, whether the assessor was the study author, or whether it was a surgeon. This was one of the key messages that came out from Markus’ presentation: that outcomes need to be assessed independently.

Markus further commented that transcranial Doppler cannot reliably distinguish solid from air emboli—and that

the two types of emboli have very different consequences. “Transcranial Doppler emboli detection needs to be used with caution intraoperatively; post-procedure emboli are likely to be solid emboli. It provides additional information on cerebral blood flow,” said Markus.

Rohlffs further discussed how systematic exclusion of air from unpacking to deployment of the devices avoids air embolism, explaining that the amount of air released by stent grafts can by minimised in several ways. Firstly, Rohlffs pointed to the way in which the amount of air released can be influenced by the ‘flushing technique’. Secondly, she observed that the construction of the stent graft system can influence the amount of air released during the procedure.

Rohlffs maintained that synergistic effects of different approaches to reduce air release can be used, and concluded that “the amount of released air can be minimised.”

Haulon said that the STEP study has shed light on modern practice in the selected high-volume centres and that the group had learned from each other and were now ready to sit around the table to decide how they should perform these complex procedures. “We have learned about how we should design future studies and monitor results to find out what can be changed to reduce the stroke risk following complex TEVAR,” he said.

Kölbel closed the session by saying this was an area in which there was a need for logical outcome measures, as very rough outcome measures had been used so far. “Additionally, it is vital to have independent measurement of outcomes as this has been shown to have a bearing on the data. There may also be some old dogmas to kill and I look forward to further collaboration,” he told delegates.

“We have worked out some of the questions we want to see answered and advances have been made in the areas of obvious consensus. The key next steps will be designing future studies that need to be carried out in order to benefit this group of patients who are inherently at risk of stroke after TEVAR,” Greenhlagh concluded.

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Issue

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Lithotripsy

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“Fantastic” live case demonstrates potential value of intravascular lithotripsy In an exciting session at the Charing Cross Symposium (CX; 24–27 April, London, UK), the audience witnessed the demonstration of a novel treatment strategy with intravascular lithotripsy for calcified arterial stenosis. The session introduced a new programme feature of the meeting, as part of an initiative to feature live cases in illustration of what has been discussed in the presentations, giving delegates the opportunity to observe the evidence given in practice.

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iving some background to the concept of intravascular lithotripsy, Andrew Holden, Auckland, New Zealand, who performed the first-in-human intravascular lithotripsy procedure, explained, “the basic concept is to create apposition of the angioplasty balloon to the vessel wall at very low pressure to perform lithotripsy, to create microfragmentation of the calcium in both the medial and intimal layers, change the compliance of the artery and then allow the balloon to dilate out to nominal diameter at low pressure and hopefully, with a low instance of residual stenosis or dissection.”

The live case was broadcast from Bad Krozingen, Germany, with operator Thomas Zeller.

The patient was an 84-year-old female with Rutherford stage 3 claudication, with a history of coronary vessel disease and internal carotid artery stenosis.

Previously, the patient had an occlusion of the right superficial femoral artery, extending into the popliteal artery, with significant calcification that was treated with lithotripsy and drug-coated balloon angioplasty, after which she had been pain free on her right leg.

During the procedure, Zeller used lithotripsy to prepare the vessel in the patient’s left leg for drug-coated balloon angioplasty using the protocol from the DISRUPT III randomised controlled

trial which is comparing lithotripsy plus drug-coated balloon to drug-coated balloon as standalone therapy.

Providing some tips based on his experience with the lithotripsy device, Zeller placed a lot of importance on the preparation of the catheter. “In every balloon there is still some air trapped and it is important to evacuate the air from the folded balloon before you inflate it and before you try to apply the sonic pressure waves because if there is still air trapped in the balloon, the pressure waves will not be transmitted to the vessel wall,” he said.

Further, pulling from lessons learned in the DISRUPT I and DISRUPT II trials, Zeller advised that the balloon should be slightly oversized in order to improve acute outcomes. “Undersizing leads to inferior outcomes acutely and also in the longer term. Similarly, increasing the dose, i.e. doing more lithotripsy cycles in the same position, does improve the overall outcome of the lithotripsy procedure.”

Describing how the device is used by the operator during the procedure, he explained, “the device has seven markers in total. The markers at the edges represent the proximal and distal balloon shoulders and the five markers inbetween are the emitters. It is important to position the emitters in the lesion area and the balloon marker can be outside.”

Watching the case, Holden commented that the lithotripsy is a

dose that is delivered to refractory stenoses to try to improve the acute outcome, with Zeller adding, “the specific feature of lithotripsy is that you disrupt medial calcification.”

As for his strategy following intravascular lithotripsy, Zeller reported that at his centre, it is followed up with a drug-coated balloon. “That is our general strategy, because, based on what we learned from the pilot study, lithotripsy is a very good tool for achieving good acute outcomes, but in the long-term we still see restenosis development. This leads me to believe the combination of vessel preparation with lithotripsy followed by drug-coated balloon angioplasty is a logical approach to treat these lesions.

DISRUPT III will prove whether it is true or not,” Zeller stated.

Polling following the live case showed that 50% of the CX 2018 audience believes that calcified tibial vessels are best managed with a drug-coated balloon following vessel preparation during endovascular procedures. Further, 69% of the CX 2018 audience would not use a drugcoated balloon for a heavily calcified lesion without vessel preparation.

A focus on calcification

Broadening the discussion on calcification, Arne Schwindt, Münster, Germany, weighed in with his personal experience, adding, “lesions that are

unresponsive to stenting and high pressure ballooning could be treated.

We have seen acceptable clinical and angiographic outcome in rock-like calcified common femoral arteries.

Early experience shows promising results of intravascular lithotripsy in highly calcified small mesenteric and celiac branches, and has the potential to make EVAR/TEVAR/TAVI feasible in patients with poor iliac access.”

In her assessment, Renu Virmani, Gaithersburg, USA, called for a “dedicated device for calcified lesions that either cracks or removes calcified areas in order to achieve adequate vessel expansion. Probably, such lesions need drug-eluting stents rather than drug-coated balloons.”

In the end, Fabrizio Fanelli, Florence, Italy, concluded that calcium significantly increases procedural complications and that most studies have excluded severely calcified lesions from endovascular treatments.

He said that acute and long-term endovascular outcomes are inferior when severe calcium is present, and that it represents a great limitation of superficial femoral artery procedures due to vessel recoil after balloon dilatation, flow-limiting dissection related to high pressure use and a higher stent implantation rate.

“Multiple technologies are available nowadays but ‘the ideal’ is not available yet. Atherectomy devices increase the luminal gain and may also improve drug uptake. Further, vessel preparation with plaque scoring and lithotripsy do not debulk calcium, but are able to increase vessel permeability, drug absorption, and patency rate.”

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June

Issue

18 78

New innovations

Europe braces for harder times in medical device innovation while US FDA eases regulations Countries in the European Union have long been the first to receive new innovations in medical technology, as the EU’s Medical Device Directive (MDD) provided quicker routes to implementation of new devices than its equivalent in the USA, the Food and Drug Administration (FDA). However, on both sides of the Atlantic, the regulatory pace is likely to change over the next few years—in opposite directions.

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he EU is moving to replace the MDD with the Medical Devices Regulation (MDR): a more extensive regulatory document, introducing significant revisions to quality and safety standards and the range of regulated devices. The MDR was initiated in May 2017, and a three-year transition period applies. Current MDD certificates remain valid, but cannot be renewed, meaning that from 26 May 2020 onwards, all medical devices brought to market in the EU and Switzerland must conform to the MDR. While increasing demands on the standard of clinical data and safety profiles of new technology, medical device innovation in the EU is likely to see reduced speeds on the road to the CE mark.

Meanwhile, the US FDA has published its strategic priorities for the MDD-MDR transition period of 2018–2020, outlining an aim to “reduce the time and cost of generating clinical evidence, typically the most expensive and lengthy regulatory requirement for marketplace entry.” The FDA states it has adapted their policies and procedures to “faciliatate and streamline the development and approval” of clinical trials in the USA, and redistributing the data collection requirements pre- and postmarket. “By striking the right

balance between premarket and postmarket data collection we can help assure we get the right data at the right time, thereby creating incentives for timely patient access to high-quality, safe and effective technologies to improve their health and quality of life.”

Speaking on the subject in the CX Innovators Showcase at the Charing Cross Symposium (CX; 24–27 April, London, UK), Veryan CEO Chas Taylor noted that the FDA’s strategic direction is “more open and approachable,” and while it does not change the burden of proof, it “makes the system easier to navigate.” The EU MDR on the other hand, “will increase barriers to entry in Europe” with new regulation, Taylor said.

The panellists of the session, Gido Karges (Wangs, Switzerland) and Jeffrey Jump (Most-sur-Rolle, Switzerland) similarly feared that the pace of innovation in Europe will be diminished, with Jump stating that “the golden age of innovation in Europe is coming to an end.” Jump suggested “CE mark lead approval time will at least double (6–12 months)”, and claimed “the number of innovative medical devices receiving CE mark will drop down by an estimated 30%.”

Karges explained the ramifications:

“Expenditures associated with MDR compliance are enormous. Due to these costs, device developers will need to make choices about which areas of their business to remediate first. Some may decide the costs of remediation exceed the business opportunity, choosing to sell or close down certain product lines. As manufacturers decide to discontinue legacy products, suppliers go out of business, dragging other manufacturers who bought from them behind. German and Swiss health authorities predict the extinction of 30% of all medical device manufacturers.

They also expect that 50% of all medical devices will be discontinued or fail to meet the requirements. Patients might be at risk—it is a very grim outlook.”

In contrast, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) is collaborating with the US FDA to allow “globalisation” of approval studies, Taylor highlighted, in an initiative called “harmonisation by doing.” The FDA state that the initiative will see them agreeing

with the PMDA, academia and industry on internationally developed standards for global clinical trials related to cardiovascular devices, addressing “regulatory barriers that may delay timely medical device approvals in both countries.”

Jump summarised, “The FDA and other competent authorities have released new regulations and guidelines in order to decrease the burden of getting market access for innovative devices.”

“Europe is now heading in the opposite direction, particularly for innovative products. Due to the uncertainty of MDR implementation and interpretation, increased cost of compliance, fragmented distribution and divergent reimbursement policies, the 40-year old model of ‘go to Europe first’ will be challenged. Europe may have to wait for innovative medical devices to be proven safe and effective in other markets before European patients will have access to improved technologies.

I believe innovators will follow the path of least resistance and vote with their feet.”

CX showcases most promising vascular innovations The CX Innovation Showcase at the Charing Cross Symposium (CX; 24–27 April, London, UK) this year painted a global picture of vascular entrepreneurship, highlighting the controversies currently threatening the next generation of gamechanging products.

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eginning the session with innovation and regulation controversies, key opinion leaders provided a grim outlook for the future of truly disruptive technologies and products emerging from the European vascular marketplace (see above article).

Later on, discussions of peripheral, aortic, venous, vascular access, diagnostic and imaging innovations provided insight into cutting-edge developments in each of these fields.

Focusing on the introduction of the European Medical Device Regulation (EU MDR) legislation, many speakers expressing the fear that the pace and scale of vascular innovation in Europe will be diminished. Session panellist Gido Karges (Wangs, Switzerland) referred to the EU MDR as “one of the most impactful pieces of legislation”. In 2008, legislators aimed to establish a robust, transparent, predictable and sustainable regulatory framework for medical devices in the EU, improving health and safety while supporting innovation. However, in 2010, a criminal fraud case caused a public scandal that, according to Karges, meant “some politicians saw a chance to make a name for themselves, and triggered harsh reactions to isolated cases of fraud or misconduct of very few manufacturers”, providing impetus for the

EU MDR. Speakers and delegates speculated on the best ways to navigate the road to CE marks under this new regulation, which will be replacing the previous Medical Device Directory (MDD) by Spring 2020.

Coramed antioxidant premedication announced as CX Dragon’s Den 2018 winner The CX Innovation Showcase featured its annual Dragons’ Den panel, awarding Kieran Murphy this year’s winner. The prestige value attached to being recognised as the developer of the most promising

innovation in vascular medicine has allowed the three previous winners of the £1,000 prize to gain additional funding for their product.

In what Chas Taylor (Horsham, UK)—one of the competition judges or so-called ‘Dragons’—called “The best Dragon’s Den line-up” of any CX, eight innovators pitched their idea to the panel. In addition to Taylor, the panel of judges consisted of Stephen Greenhalgh (London, UK), Frans Moll (Utrecht, the Netherlands), Andrew Holden (Aukland, New Zealand), Bob Mitchell (Irvine, USA), Daveen Chopra (Santa Rosa, USA) and Alan Edwards (Ruthin, UK).

Murphy’s winning contribution was a presentation on the use of antioxidant premedication for patients, physicians, and aircraft crew. These are all people exposed to above average levels of radiation; Murphy explained how antioxidants prevent DNA damage caused by excessive radiation. Murphy and colleagues have preliminary FDA guidance, and prospective randomised human studies are positive. Murphy identified the addressable market size as approximately US$600 million a year.

The runner-up was Martin Czerny (Freiburg, Germany) with a non-occlusive TEVAR moulding balloon.

There were also two honourable mentions: one for Elchanan Bruckheimer (Petach Tikva, Israel), for his use of holography in clinical interventions, and one for Colin Henehan (Galway, Ireland) for his Tulip device.

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Drug-coated balloons

In.Pact Pacific drug-coated balloon is no better than Zilver PTX drug-eluting stent in complex superficial femoral artery disease The 13-month outcomes of the DRASTICO trial—presented by Francesco Liistro (Arezzo, Italy) at the Charing Cross Symposium (CX; 24–27 April, London, UK)—show that the In.Pact Pacific drug-coated balloon (Medtronic) is not superior to the Zilver PTX drug-eluting stent (Cook Medical) in terms of restenosis.

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iistro noted that when faced with patients with complex superficial femoral artery disease, there is a choice between “stenting them all” or using a drugcoated balloon with provisional stenting. Therefore, the aim of the DRASTICO trial, being a superiority trial, was to provide clarity on the issue. He said: “We decided drugcoated balloons would be superior to drug-eluting stents. The study sample size was powered to demonstrate a relative 50% reduction in binary restenosis provided by a drug-coated balloon as compared with a drugeluting stent. Thirty per cent was considered as the projected restenosis rate for drug-eluting stents.”

In the study, 250 patients with intermittent claudication or with chronic limb ischaemia were randomised to receive treatment with

Francesco Liistro

the In.Pact Pacific balloon (125) or with the Zilver PTX stent (125). At 13 months, the rate of restenosis was 23% for the drug-coated balloon group vs.

21% for the drug-eluting stent group (p=0.4). The rate of total occlusion was higher in the drug-eluting stent group but not to a significant extent: 18%

vs. 10% for the drug-coated balloon group (p=0.06). Additionally, there were no significant differences in the rate of clinically-driven target lesion revascularisation between groups.

Liistro and his fellow investigators also analysed the results based on whether patients had intermittent

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claudication or critical limb ischaemia; significantly more patients in the drug-coated balloon group had critical limb ischaemia than in the drug-eluting stent group (70% vs.

55%; p=0.02). In the beginning, he said, “we saw a difference between drug-coated balloons and drug-eluting stents. But, in the end, there was late catch-up for the drug-coated balloons.

This meant there was no difference between groups.”

“In a complex clinical and anatomical scenario, drug-coated balloons were not superior to drugeluting stents in terms of 13-month restenosis,” Liistro concluded. He added that a higher rate of mean lumen diameter in the drug-eluting stent “was counterbalanced” by a higher rate of late lumen loss” and that “the difference in target lesion revascularisation in favour of drugcoated balloon shows a late catch-up at 13 months”. “Of course, longterm follow-up (two to three years) is necessary for a final and more complete evaluation,” he observed.

Zeller and Moll go head to head: Does directional atherectomy pretreatment improve patency of drug-coated balloons?

Pitching Thomas Zeller (Department of Angiology, Universitäts Herzzentrum—Freiburg, Bad Krozingen, Germany) against Frans Moll (Department of Vascular Surgery, University Medical Center, Utrecht, The Netherlands), a debate on directional atherectomy pretreatment and use of constrained expansion using nitinol struts will improve patency results of drug-coated balloons resulted in a win for Moll, who was arguing against the motion. The audience voted 57.3% against, and 42.7% for.

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or context, data published in the journal Circulation and the Journal of American College of Cardiology Cardiovascular Interventions, cited by Zeller, show that, independent of lesion complexities, primary patency rates at 12 months of using a dedicated drug coated balloon range from 85.3% to 91.1%. However, Zeller argued that he believes there is still “room for improvement”, as looking at longer-term data, the difference between the benefit of using drug-coated balloon application compared to the benefit of using percutaneous transluminal angioplasty diminishes. Zeller postulated, “It could be that in the long-term, the efficacy of drugcoated balloons might be reduced.”

Zeller also proposed that directional atherectomy pretreatment reduces the rate of bailout stent use.

Directional atherectomy excises the plaque, and data from a range of journals demonstrate that bailout stent rates are significantly reduced with directional atherectomy when compared to performing drug-coated balloon angioplasty as a first-line strategy. Zeller commented, “This reduction of stent use is not shown for other atherectomy devices, so it seems to be a specific feature of directional atherectomy.”

Opposing Zeller, in a talk dubbed “provocative” by debate chair Andrew Holden (Auckland University

School of Medicine, Auckland, New Zealand), Moll argued against the motion, calling directional atherectomy pretreatment in combination with drugcoated balloon angioplasty “window dressing” (though he made a point of not referring to drug-coated balloons as such, instead labelling them cytotoxic coated balloons). Moll concluded that although atherectomy pretreatment and constrained expansion in combination with cytotoxic coated balloons will improve short-term results at follow-up in low-grade superficial femoral artery disease, for sustainable, five-year results of high

grade superficial femoral artery disease, “we need better atherectomy devices and more advanced drugs.”

Moll began his argument by explaining standard treatment—the reasoning behind the use of drug-coated balloons. He claimed that the superficial femoral artery is, “The most obstinate artery to get long-term results of recanalisation of stenosis/occlusion by endovascular techniques”, as it is the longest and youngest (from a phylogenetic perspective) artery in the human body. Current treatment for superficial femoral artery disease is aimed at preventing the body “signalling for over-reaction” (Moll’s description of restonsis) to the traumatic lesion of the media and adventitia, which would trigger early restenosis. To stop restenosis developing, the media and adventitia are “marinated and pickled” with cytotoxins. Atherectomy is an effective method of getting these cytotoxins to the media. Moll even accedes that for 20 years he has been, “a strong believer that debulking and atherectomy is the way to go.”

However, excluding the high-grade superficial femoral artery disease cases, defined as highly calcified arteries, Moll’s data show that atherectomy is not successful in highly calcified arteries. “Just like in cancer, we currently may prolong the sympotm-free interval in low-grade superficial femoral artery disease, but we cannot prolong life patency, if you call patency life extension, at five years,” explains Moll.

Following the live polling result, Zeller says of his loss: “This is what I expected—but give it two years.

Let us have this debate again in two years!” With trials promising longer-term data on directional atherectomy pre-treatment underway, the debate may not be over.

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Conference coverage

Positive data for renal denervation reignites interest in field After two studies indicated that renal denervation lowers blood pressure both with and without antihypertensive drugs, Felix Mahfoud (Klinik für Innere Medizin III, Saarland University Hospital, Homburg, Saarland, Germany) said that the PCR group was “committed to supporting the field of renal denervation”. He added that there would be further developments in the field, so interventional cardiologists should “stay tuned”.

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ahfoud’s statement, on behalf of PCR, came directly after two sham-controlled trials were presented at EuroPCR (22–25 May, Paris, France)—with both studies suggesting that renal denervation does lower blood pressure. The first of these, SPYRAL HTN-ON MED (of which Mahfoud was an investigator), explored the use of the Symplicity Spyral renal denervation system (Medtronic) in patients with moderate, uncontrolled hypertension who were taking one to three antihypertensive medications. A previous study with the first-generation Symplicity catheter did not demonstrate a significant reduction in blood pressure compared with a sham procedure in patients with resistant hypertension. According to Mahfoud, one of the lessons from this trial was that “we probably started with the wrong population” because their hypertension was too severe and perhaps could not be treated with anything.

Presenting the SPYRAL HTNON MED trial at EuroPCR, David E Kandzari (Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, USA) reported that patients were included in the study if they were stable on one to three antihypertensive medications for six weeks prior to enrolment. After a second screening visit, 80 patients were randomised to renal denervation (n=38) or a sham procedure (n=38). Follow-up visits were scheduled at one month, three month, six months, and planned 12 to 36 months after the procedure. The primary efficacy endpoint was change from blood pressure measured at baseline (at the second clinic visit) to blood pressure measured at the six-month follow-up visit.

At six months, there was a significant decrease in 24-hour ambulatory

blood pressure in terms of systolic and diastolic blood pressure in the renal denervation group compared with baseline levels. There were no significant blood pressure reductions in the sham procedure group. These findings meant that, compared with the sham procedure group, the renal denervation group had significant reductions in both 24-hour systolic blood pressure and 24-hour diastolic blood pressure: -7mmHg (p=0.0059) and -4.3mmHg (p=0.0174), respectively.

Writing in the Lancet—SPYRAL HTN-ON MED was published in the journal simultaneous to the EuroPCR presentation—Kandzari et al note that the magnitude of blood pressure decline was “clinically significant” as prior studies have shown such reductions to be associated with “both lower rates of both cardiovascular events and mortality”.

Kandzari told Cardiovascular News: “Irrespective of the level of blood pressure elevation, the extent of blood pressure reduction observed in this trial has clinical significance. Considering that hypertension is the worldwide leading cause of death and disability, if confirmed in larger study, such blood pressure reductions would have substantial public health impact.”

In the Lancet, the authors observe that the extent of blood pressure reduction with renal denervation “increased over follow-up through six months” and the reductions were present throughout the day and night. Kandzari told delegates at EuroPCR this represents an “always on” effect for renal denervation that may have particular relevance given the limitations of dosing regimens and adherence with medications.

This apparent “always on” effect may be of particular importance given the

David E Kandzari

relative prevalence of patients in both the sham procedure group and the renal denervation group who did not adhere to their medication regimens. Overall, the study investigators report in the Lancet, individual patient adherence to medication was 60% and this was “highly variable”. “We embarked on the SPYRAL HTN OFF MED study as a biological proof-of-principle study [which showed renal denervation to significant lower blood pressure in patients not taking medication]. However, the rates of nonadherence and patients’ general desire not to take medication has increasingly come to the forefront. So, there may be a role for renal denervation in the context of patients off medication,” Kandzari commented.

He concluded: “Renal denervation with the Symplicity Spyral system resulted in statistically significant and clinically relevant blood pressure reductions at six months in uncontrolled hypertensive patients compared with sham control and in the presence of commonly prescribed antihypertensive medications.” In the context of these results, further to the potential use of renal denervation being used in patients off medication, the procedure could be used to compliment drug therapy to lower blood pressure in patients with “uncontrolled hypertension despite the persistent use of medication”.

Following Kandzari’s presentation, Laura Mauri (Brigham and Women's

Hospital, Boston, USA) presented the results of the RADIANCE-HTN SOLO trial (which, like SPYRAL HTN ON MED was simultaneously published in the Lancet). This study compared renal denervation with an endovascular ultrasound system (Paradise, ReCor Medical) with a sham procedure in patients with mild-to-moderate hypertension who were off medication.

Mauri reported that, at the two-month follow-up point, renal denervation was associated with a “greater reduction in daytime ambulatory blood pressure than a sham procedure (6.3mmHg greater, p<0.001, in the intention-to-treat analysis), consistent reductions in 24hour ambulatory, office, and home blood pressure, and a high rate blood pressure control on the absence of medications.”

Both Kandzari and Mauri noted that further studies, of the respective devices, would further evaluate the safety and efficacy of renal denervation. Kandzari reported that a larger SPYRAL HTN PIVOTAL trial is ongoing—having just received investigational device exemption from the US FDA—and would further examine the use of renal denervation in patients off medication.

Additionally, he said that “a study design for a larger trial in the presence of antihypertensive therapy is in development”. Mauri stated that followup of the RADIANCE-HTN SOLO study is ongoing through three years to assess longer term safety and efficacy of the endovascular renal denervation system and that “enrolment is ongoing for a parallel blinded sham-controlled trial of patients with resistant hypertension (RADIANCE-HTN TRIO)”.

Mahfoud commented that main research topics of these studies and other studies should be intraprocedural feedback, identification of responders, and sustainability of the effects.

However, based on the available evidence, he added: “We know that renal denervation does lower blood pressure in hypertensive patients with and without antihypertensive drugs.

There is more to come, so stay tuned!”

European Vascular Surgeons in Training—Prize session At this year’s Charing Cross Symposium (CX; 24–27 April, London, UK), the European Vascular Surgeons in Training (ESVT) programme had two sessions: How to deal with complications in vascular surgery and the EVST Free Abstract Prize Session.

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n the complications session, Marina Neto (Porto, Portugal) reviewed three cases that looked at aortic and lower limb complications and the lessons that could be learnt from them. Following Neto’s presentation, Kakkhee Yeung (Amsterdam, The Netherlands) described a patient with complicated aortic dissection. Both presentations produced great discussion with the audience and with Po Jen Ko (Taoyuan, Taiwan), who was chairing.

Other topics reviewed in this session included what can go wrong with popliteal aneurysm repair, iliac complica-

tions during endovascular aneurysm repair (EVAR), and complications during haemodynamic access.

The EVST Free Abstract Prize session was a success with original studies and six case reports being presented.

Presenters came from all over Europe and there were also presenters from New Zealand, USA and Taiwan.

Natalija Bogunovic (Amsterdam, The Netherlands) received first prize for presenting a basic science study about using a new method to study genetic mutations involved in aortic aneurysms. The second prize went to

Thomas Aherne (Dublin, Ireland), who reported that his study exercise adherence in claudicants led to him changing his local protocol. The third prize was for Shanka Benaragama (Colchester, UK), who reviewed visceral artery aneurysms.

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June

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New innovation

Two-year outcomes of AcoArt I trial demonstrate safety and efficacy of drug-coated balloon in treating femoropopliteal artery disease Although the rate of in-stent restenosis lesions is low, the results of AcoArt I are promising and invite further investigation. AcoArt I was the first drug-coated balloon trial in China and demonstrated the safety and efficacy of the Orchid drug-coated balloon (Acotec Scientific) in treating femoropopliteal artery disease. It also showed the sustained durability of drug-coated balloon treatment with no late catch-up through two years. The results were presented at the Charing Cross Symposium (CX; 24–27 April, London, UK) by Wei Guo, Beijing, China.

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he objective of the study was to evaluate the safety and efficacy of the Orchid drug-coated balloon for the treatment of femoropopliteal artery disease.

The primary endpoint was angiographic late lumen loss at six months, while secondary endpoint was primary patency at 12 and 24 months as well as clinically-driven target lesion revascularisation at 12 and 24 months.

The study was carried out at 10 sites, with 200 patients randomly assigned in a 1:1 ratio to drug-coated balloon or the uncoated balloon control group. Angiographic late lumen loss at six months was measured by a blinded core laboratory., and clinical followup was conducted up to 24 months. The Orchid drug-coated balloon has a propriety

coating technology and a paclitaxel dose of 3µg/mm2.

Patients were eligible for the study if they had superficial femoral artery and/or proximal popliteal artery lesion, single target lesion, Rutherford class 2–5, successful inflow treatment and at least one infrapopliteal runoff vessel. They were excluded if they had a life expectancy of over two years, acute thrombus in the target vessel, prior vascular surgery or thrombolysis within six weeks, no adequate distal outflow, unsuccessful lesion crossing, known allergy to paclitaxel, were pregnant or breast feeding, and plasma creatinine of 150µmol/L. At six months the late lumen loss already pointed to the superiority of the drug-

Wei Guo

coated balloon, and the primary patency showed strong durability through two years.

Primary patency was defined as freedom from clinically-driven target lesion revascularisation and freedom from restenosis as determined by duplex ultrasound peak systolic velocity rate ≤2.4. The trial demonstrates strong durability over two years with superior performance in primary patency for the drug-coated balloon vs. percutaneous transluminal angioplasty (64.6% vs. 31.4%, respectively).

ArcoArt I showed significant difference in freedom from clinically-driven target lesion revascularisation for the drug-coated balloon vs. percutaneous transluminal an-

gioplasty (92.8% vs. 60.4% at 12 months, and 86.5% vs. 58.9% in 24 months, respectively). There were 15 cumulative target lesion revascularisation events in the drug-coated balloon group and 49 in the plain angioplasty group. More patients in the plain angioplasty group had revascularisation, with as many as three target lesion revascularisation events in two patients over two years, and the average time to first clinically-driven target lesion revascularisation being 307 days vs. 173 days.

Although the number of in-stent restenosis lesions is small, the superior efficacy of the Orchid drug-coated balloon was consistent in in-stent stenosis subgroups, with freedom from clinically-driven target lesion revascularisation for the drug-coated balloon vs. percutaneous transluminal angioplasty (95.8% vs. 25% in 12-months, and 87.5% vs. 25% at 24 months, respectively) and there was a similar trend in primary patency (91.7% vs. 15% at 12 months, and 54.2% vs. 5% at 24 months, respectively).

In addition, there were no significant between-group differences in the rates of death and major amputation.

NHS to fast-track SecurAcath device use

Sirolimus-coated balloon gets investors’ attention following early results of first-in-man study

Interrad Medical has announced the selection of their SecurAcath Subcutaneous Catheter Securement Device for the Innovation and Technology Payment programme by the UK National Health Service (NHS) England.

The SELUTION drug-coated balloon, developed by Med Alliance, has been gaining traction among investors since the release of its first-in-man study results earlier this year at the Leipzig Interventional Course (LINC; 29 January–2 February, Leipzig, Germany) by principal investigator Thomas Zeller of UniversitätsHerzzentrum in Bad Krozingen, Germany. The company has now raised US$37 million in an investment round to fund European commercialisation and US regulatory approval, as well as to support global clinical programmes.

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he Innovation and Technology Payment (ITP) programme is designed to remove significant barriers to the spread and adoption of new innovations and builds on the NHS commitment to support technologies that can make a real difference in patient care and outcomes. The programme delivers improvements in patient care by cutting bureaucracy for clinicians and other innovators and encouraging uptake through the NHS. The SecurAcath underwent a detailed selection process. Over 250 medical technologies applied for the programme and only four were selected. Selected innovations had to already be in use, and ready for scaling—and delivering significantly increased quality, improved efficiency and patient benefit.

Under the ITP programme, the SecurAcath will be centrally funded by the NHS. In addition, the ITP will work with other NHS organisations and partners to speed the adoption of the SecurAcath.

The SecurAcath is the only subcutaneous catheter securement device that lasts the life of the line and can dramatically decrease catheter dislodgement and migration, decrease catheter replacement costs, prevent therapy interruption, improve vessel health and preservation, reduce catheter complications and lower total cost of patient care.

In a press release, the NHS described the SecurAcath as: “A device to secure catheters that reduces the infection risk for patients with a peripherally inserted central catheter. The use of this equipment helps to reduce the time taken to care and treat dressing changes. This type of catheter is normally used in people needing intravenous access for several weeks or months in both inpatient and outpatient settings.

NICE estimate up to 120,000 people per year could be eligible.”

Interrad Medical is a privately held medical device company based in Plymouth, USA. Joe Goldberger, the company’s president and CEO commented, “We are very pleased the SecurAcath was chosen to be included in this highly select group of important innovations”, adding that he believes the device is “a perfect fit with the ITP programme goals of providing significant cost savings and improving patient care”.

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he sum consists of US$22 million equity and US$15 million in non-dilutive licensing agreements for Japan and China. The investment round was led by a significant US$20 million investment by China-based Shenzhen Salubris Pharmaceuticals.

The results of the first-in-man study demonstrated that median late lumen loss (LLL) of the target lesion, as measured by quantitative vascular angiography (QVA) at six months post-index procedure, was 0.19mm (-1.16; 3.07). The rate of target lesion revascularisation (TLR) was 2.3%— one of the lowest that has ever been reported in a drug-coated balloon first-in-man study at six months.

There were no incidences of either death or the need for minor and/or major amputations.

“These initial results from the SELUTION firstin-man study are encouraging,” commented Zeller at LINC 2018. “The findings confirm the efficacy of the SELUTION sirolimus-coated technology and they concur with previous paclitaxel drug-coated balloon studies in the superficial femoral artery. The primary endpoint has been achieved, and excellent clinical outcomes have been reported: Rutherford classification, ankle-brachial-index, walking impairment and quality-of-life assessment have all indicated beneficial patient improvement from this sirolimus technology. The study will be carried out to 24 months to confirm safety and efficacy.”

The study involved 50 patients enrolled across four German centres. Its objective has been to assess the safety and efficacy of the DCB in the treatment of lesions of the superficial femoral artery and/

or the popliteal arteries, measured at multiple time points through clinical, duplex ultrasound and/ or angiographic assessment (six-month time point only). The SELUTION first-in-man study is a prospective, controlled, multicentre, open, single-arm clinical investigation. The primary endpoint of the study is angiographic late lumen loss at six months.

Secondary endpoints include major adverse events, primary patency, and angiographic binary restenosis.

Speaking at the Charing Cross Symposium (CX; 24–27 April, London, UK), Thomas Albrecht of the Vivantes Klinikum Neukölln in Berlin, Germany, discussed the insights from the study, highlighting the use of sirolimus rather than the common paclitaxel coating on the balloon. He noted that although “paclitaxel is easier to apply to balloons and has higher tissue absorption,” the antiinflammatory sirolimus coating provides a “much wider therapeutic range and higher safety margin” as well as a “higher efficacy than paclitaxel in coronary drug-eluting stent.” Albrecht concluded that further studies are required, to confirm the findings of the trial in larger patient populations.

Med Alliance chairman Jeffrey Jump commented on the recent investment round, “We are very encouraged by the first-in-man data and investor enthusiasm for this novel sirolimus drug-coated balloon technology.” In a comment on these data following their presentation at LINC, Jump said the trial demonstrates a role for the sirolimuscoated balloon, adding that the company aims to “aggressively pursue regulatory approval in the USA, Japan and China”.

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Product News Avinger’s next-generation Pantheris Lumivascular atherectomy system gets FDA clearance

Avinger has announced that the company received 510(k) clearance from the US Food & Drug Administration (FDA) for its next generation Pantheris Lumivascular atherectomy system, the first-ever image-guided atherectomy device for the treatment of peripheral arterial disease (PAD). Lumivascular combines real-time intravascular imaging with highly effective catheters for the treatment of PAD. The new version of Pantheris received CE marking approval in December 2017, and patients have been successfully treated with this new device in Germany since that time. Avinger’s next generation Pantheris device includes a number of design improvements, including a simplified single balloon system for both apposition of the device and occlusion of blood flow, a stiffer shaft for increased pushability, a reinforced nosecone with the option for more tissue storage capacity, and an enhanced cutter design.

The company intends to launch two versions of this product (standard and extended length nosecone) into initial sites in the USA immediately, and plans to incorporate the new design into the INSIGHT IDE clinical trial currently in progress. INSIGHT is a multicentre clinical study designed to evaluate the safety and effectiveness of Pantheris for treating in-stent restenosis (ISR) in lower extremity arteries.

Distribution of the next generation Pantheris will be expanded as the company increases production and gains purchasing approvals in additional Lumivascular sites.

“We are excited to introduce the next generation Pantheris to our network of physicians here in the United States,” says Jeff Soinski, Avinger’s president and CEO. “After extensive testing by our R&D and operations teams, physician design validation, and successful initial case experience in Europe across a variety of different lesion types, we believe this next generation device will significantly improve the user experience in terms of reliability, efficiency, and ease of use across a spectrum of clinical situations.”

Barry Tedder, interventional cardiologist at St Bernards Medical Center in Jonesboro, USA, comments, “The Pantheris Lumivascular atherectomy system has allowed me to treat peripheral artery disease with more precision while largely avoiding trauma to the blood vessel during an intervention.

Unlike some other products, this technology’s performance can stand on its own but also enhance other forms of adjunctive therapy if needed, while preserving future treatment options for the patient.

As one of the first users of the initial generations of Pantheris, I have been eagerly awaiting the product enhancements incorporated into the new system, which has the promise of not only improving ease of use, but also providing a new level of operator control during the procedure.”

Atherectomy is a minimally invasive treatment for PAD in which a catheter-based device is used to remove plaque from a blood vessel. Lumivascular technology allows physicians to see from inside the artery during an atherectomy procedure by using an imaging modality called optical coherence tomography, or OCT, that is displayed on Avinger’s proprietary Lightbox console. Physicians performing atherectomy with other devices must rely solely on X-ray as well as tactile feedback to guide their interventions while treating complicated arterial disease. 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.

Laerdal Medical introduces procedure simulator system SimMan Vascular

Laerdal Medical has announced the launch of their new simulation training technology, SimMan Vascular. The company has partnered with endovascular simulator developer Mentice to produce the SimMan Vascular system, which was introduced at the Simulation User Network conference (SUN; 30 April–2 May, Schaumburg, USA).

The company states that the prevalence of diagnostic and therapeutic endovascular procedure makes it essential to have a simulation training solution in response, and that their new technology will support the multidisciplinary team training and skills practice required.

Built on Laerdal’s SimMan 3G platform with Mentice’s VIST endovascular simulation technology inside, SimMan Vascular is an integrated emergency patient and endovascular procedure simulator. The simulator can help to provide immersive training to all members of the acute care team, including: endovascular specialists, cath lab teams, interventional radiologists, resuscitation teams, and pre-hospital care providers.

It incorporates all aspects in the critical care areas of vascular trauma, acute myocardial infarction and acute ischaemic stroke.

The system provides endovascular access as well as advanced cardiovascular life support and treatment capabilities, including quality cardiopulmonary resuscitation feedback, convulsions, bleeding and wounds, RFID technology for administered medications and airway devices, and reactive eyes.

The Mentice user interface is integrated into Laerdal’s LLEAP software, allowing: The use of real clinical/operation devices Simulated fluoroscopy and a 3D colour mode A dynamic patient monitor Recognition of drug administration The simulator comes with scenarios for acute myocardial infarction, acute ischaemic stroke, and vascular trauma. All scenarios are designed with team training in mind, the company states, to help improve time management, decision making, communications, and transitions through each level of care—from the onset of symptoms to the cath lab.

Terumo Aortic launches RelayPro thoracic stent graft in Europe

Terumo Aortic have announced the European limited market release of the RelayPro thoracic stent graft system at the 2018 Charing Cross Symposium (CX; 24–27 April, London, UK).

RelayPro is a low profile, next generation device designed to expand the treatment of thoracic endovascular aortic repair (TEVAR) to patients with smaller access vessels. Utilising the same stent design, material, and Dual Sheath Technology of the proven RelayPlus with a 3 to 4F reduction in outer profile, RelayPro delivers the accuracy, control and confidence of the RelayPlus without compromising device

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integrity and durability.

RelayPro offers physicians a wide range of diameters, lengths, tapers, and proximal configurations. Available in both Bare Stent and Non-Bare Stent (NBS) versions, RelayPro can be individualised to meet the specific anatomical needs of patients.

Mark Miles, global vice president of Marketing at Terumo Aortic, said: “By combining the proven stent design and material of RelayPlus with a lower outer profile, RelayPro enables percutaneous access to treat a larger patient population. This advancement not only expands patient applicability but will help improve access site complications and ultimately reduce the burden of rising global healthcare costs.”

RelayPro is currently enrolling in multiple trials in the USA and Japan for treatment of Descending Thoracic Aortic Aneurysms, Acute Complicated Type B Thoracic Aortic Dissection, and Blunt Aortic Trauma.

IN.PACT Admiral DCB receives FDA approval for long SFA lesions

Medtronic has announced that it has received US Food and Drug Administration (FDA) approval for the IN.PACT Admiral drug-coated balloon (DCB) to treat long superficial femoral artery (SFA) lesions up to 360mm in patients with peripheral artery disease (PAD).

Approval was based on clinical data from the complex lesion imaging cohorts of the IN.PACT Global Study, including long lesion, in-stent restenosis, and chronic total occlusion (CTO) groups with lesion lengths >180mm. Across these groups, a total of 227 subjects with mean lesion lengths of 28.7±7.1cm were analysed. Data show a one-year patency rate of 89.1% by Kaplan Meier estimate at day 360, and a clinically-driven target revascularisation (CD-TLR) rate of 7.1%.

“Data from the IN.PACT Global Study demonstrate that the DCB is a safe and effective treatment option in real-world patients with lesions beyond 180mm, frequently comprised of in-stent restenosis and chronic total occlusions,” says Daniel Clair, chair of the Department of Surgery for University of South Carolina (USC) and the Palmetto Health-USC Medical Group. “More specifically, these results show maintenance of strong clinical outcomes, including a high primary patency rate and limited need for reintervention in patients exhibiting these complex, long lesions—among the most prevalent cases we see.

The FDA’s approval of this expanded indication now offers US physicians a clinically-proven endovascular therapy to address this critical patient need.”

Complex lesions, including those over 150mm, remain a significant treatment challenge for physicians.

“In conversations with physicians, a key clinical challenge raised is the ability to provide a sustainable treatment option for longer length, complex lesions.

With this approval, IN.PACT Admiral is now indicated to treat the longest lesions of any commerciallyavailable DCB or peripheral stent in the USA, providing physicians with additional confidence in using this DCB as part of their treatment algorithm,” says Mark Pacyna, vice president and general manager of the Peripheral business, which is part of the Aortic & Peripheral Vascular division at Medtronic. “In partnership with the clinical community, we look forward to continued collaboration as we work to address additional treatment challenges in PAD with this device.”

Perclose ProGlide suture-mediated closure system FDA approval

Abbott has gained FDA approval for its Perclose Proglide suture-mediated closure system. The device is designed to close access sites created by large bore

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Product News catheters, stopping the blood flow.

The ProGlide is used after the insertion of large bore catheters in catheterisation procedures in the femoral vein or artery. The device is able to close access sites ranging from about 0.07 inches to 0.32 inches in diameter, the US FDA states.

The closure system is composed of a plunger, handle, guidewire, and sheath. The device is designed to deliver a single suture to close the access sites in the femoral vein or artery following catheterisation procedures. The placement of a suture where the catheter was inserted will prevent blood flow until the access site heals.

The ProGlide is placed over a guidewire, inserting the end of the device into the blood vessel. The surgeon presses the plunger and lever on the handle of the device, which maneuver the suture to create a stitch across the access site. In some cases (three out of 10), in addition to the ProGlide stitch, pressure may need to be applied to the access site to fully stop blood flow. When catheters larger than about 0.1 inches in diameter are used during the catheterisation procedure, two ProGlide devices are necessary to close the access site.

The FDA state that the ProGlide device will seal the opening created by the catheter at the access site either with or without additional pressure applied to the stop blood flow.

Beacon Tip catheters return to USA and Canada after product recall

Cook Medical has announced that physicians in the USA and Canada are once again able to order the company’s Beacon Tip Torcon NB Advantage 5F catheter, used in angiographic procedures. In 2015 and 2016, Cook recalled all Beacon Tip catheters due to an unexpected increase in complaints.

The relaunch comes after significant testing by engineering following the global recall. A change customers will notice is a new foil outer packaging that provides a barrier against environmental factors that were identified as contributing to the recall.

“When we saw the catheters acting in unexpected ways without a clear root cause, we knew we had to recall,” says Mark Breedlove, vice president of Cook Medical’s Vascular division. “We knew the product was in high demand, and how heavily physicians relied on this product. But, patient safety comes first, period.”

After the recall, the company says they received a high volume of physician responses demanding the product. Cook Medical also explains it devoted many operational, manufacturing and engineering resources to determine the most efficient path back to market.

SoundBite receives CE mark for peripheral shockwave crossing system

SoundBite Medical Solutions has announced it has received CE marking for the SoundBite Crossing System, a novel first-in-class wire-based technology that is intended for the treatment or peripheral chronic total occlusions (CTOs) in a simpler and clinically efficient method.

“We are pleased that our notified body verified that we have objectively demonstrated the safety and efficacy in Europe of our CTO crossing technology throughbench and clinical studies,” says Marc-André Côté, director of Regulatory Affairs at SoundBite Medical, “and that we were able to demonstrate the effective tracking of our activities in an ISO 13485-certified quality management system,” adds Abderrahim Benrabah, vice president of the company’s Quality Engineering department.

CE marking indicates that the product complies with the essential requirements of the 93/42/EEC Directive and is authorised to be distributed and commercialised in the European market.

“The CE marking is the culmination of our efforts

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to engineer and manufacture a product that satisfies all the European requirements for a medical device,” says Domenic Santoianni, director of Product Development.

“The award of our first CE mark is a significant milestone for the company,” says co-founder and CEO of the company, Martin Brouillette, “and is the direct result of the tenacious efforts and exemplary dedication of our excellent team of employees.”

SoundBite Medical Solutions is a Canada-based company developing its shock wave technology in an effort to address significant unmet clinical needs within interventional vascular treatment. Through a combination of hardware and software, the technology delivers high amplitude shock wave pulses in a controllable manner through guidewires and other interventional tools, to specifically attack highly calcified and fibrotic tissue in the vascular system, while leaving healthy, elastic arterial walls unharmed.

Horizon stent graft receives CE mark

The Horizon stent graft system, developed to treat abdominal aortic aneurysms, has received CE mark.

The stent graft system is produced by Endospan, a company specialising in off-the-shelf endovascular aortic repair (EVAR).

“Horizon is a unique platform that can be used in a 14F single-sided approach, generally shortening and simplifying EVAR procedures,” says Kevin Mayberry, CEO of Endospan. “Horizon is supported by a strong cohort of pivotal trial data with over three years of follow-up to support the commercialisation effort.

In 2016, Vascular News spoke to Mario Lachat (University of Zurich, Zurich, Switzerland) at the VEITH Symposium about the concepts behind the Horizon stent graft as well as the Nexus stent graft, and whether these translate to clinical success. “Singleaccess site is a key feature of [the Horizon] device, which is really innovative”, Lachat said at the time, adding that “The results in clinical trials are very promising, and I would guess they get approval for this device based on these results very soon”.

“We are very proud to have earned CE mark in a challenging regulatory environment. Now, with CE mark in hand, we are looking forward to working with potential partners to commercialise the Horizon system for abdominal aortic aneurysm repair,” Mayberry said in a recent statement.

Endospan has also initiated the CE-marking regulatory process to market in Europe their Nexus stent graft system, an endovascular off-the-shelf system for treatmeant of aortic arch disease. While minimally invasive endovascular repair has been the standard of care for abdominal aortic aneurysm, the company states that aortic arch disease patients with aneurysms or dissections have not been as fortunate and have had little choice but to undergo open-chest surgery with its invasiveness and risks, lengthy hospitalisation periods, and prolonged recuperation.

IJN first in Asia to perform spot stenting procedure with VascuFlex Multi-LOC

Institut Jantung Negara (IJN; Kuala Lumpur, Malaysia) has become the first hospital in Asia to perform peripheral vascular intervention (PVI) using VascuFlex Multi-LOC (B Braun), a multiple stent delivery system designed for the treatment of peripheral arterial disease (PAD).

The procedure was performed by Shaiful Azmi bin Yahaya, deputy head of Cardiology Department at Institut Jantung Negara, Kumara Guruppan s/o Ganesan, consultant cardiologist at Institut Jantung Negara and Ralf Langhoff, head of Angiology and Vascular Medicine, Sankt-Gertrauden Hospital, Berlin, Germany.

VascuFlex Multi-LOC is a multiple stent delivery system that allows the doctor to deliver up to six short stents using a single device during PVI. With a single system, it enables spot stenting (placing short individual stents) only where they are necessary and helps the vessel to maintain its natural movement, especially in the moving segments of femoropopliteal region. Spot stenting procedures are capable of avoiding the complications of a “full metal jacket” concept (where the entire affected site is fully covered by a metal stent) in the vessel, which can cause stent fracture and thereby reduce the treatment’s efficacy. The multi stent delivery system could shorten procedure time and hence minimise infection risk for patients.

Data from the LOCOMOTIVE All Comers Registry on VascuFlex Multi-LOC system found it to be safe and highly effective in the treatment of PAD patients with complex and long lesions in the femoropopliteal vessel.

Clinical results showed that after six months, an overall 90% of patients with challenging conditions did not require additional intervention measures and that 100% of the individual stents were successfully released. Spot stenting via the delivery system reduced the amount of metal implantation by 50% when compared to the fullmetal jacket strategy.

RelayBranch early feasibility study begins enrolment

The first two patients have been successfully enrolled in the RelayBranch Early Feasibility study. This trial will assess the safety and efficacy of the RelayBranch Thoracic Stent-Graft system (Terumo Aortic) in patients with thoracic aortic pathologies requiring treatment proximal to the origin of the innominate artery.

Luis Sanchez, chief of the Section of Vascular Surgery and Marc Moon, chief of the Section of Cardiac Surgery, Washington University in St Louis – Barnes Jewish Hospital, performed the procedures.

The standard operative approach in patients with aortic arch pathology is a median sternotomy. The distal aspect of the arch and proximal descending thoracic aorta are difficult to expose through a sternotomy and pose an additional risk to the patient. The RelayBranch Thoracic Stent-Graft system establishes an endovascular alternative for patients requiring this type of surgical intervention. Presently, there are no commercial endovascular treatment options available for patients with thoracic arch pathologies.

Sanchez comments, “RelayBranch expands the range of endovascular treatment options for a high-risk population. We are very pleased to be able to offer an endovascular alternative to our patients.” Moon presented details of the cases at the 98th Annual AATS meeting (1 May, San Diego, USA).

The RelayBranch Thoracic Stent-Graft system consists of a main-body graft which is deployed in the ascending aorta and features two anterograde tunnels that give way to a large cannulation window. Branch grafts are then deployed within these tunnels for both the innominate artery and left common carotid artery.

The tunnels have lock stents incorporated into them which were designed to provide a secure engagement with the branch grafts and prevent modular disconnection.

This Early Feasibility study is the first US clinical trial of a double branch design for the treatment of thoracic arch pathologies.

Terumo Aortic has leveraged their NBS (Non-Bare Stent) technology in the design of the main body which features a fully covered proximal end that is clasped to the delivery system to enable an accurate deployment.

“Terumo Aortic is uniquely Terumo Aortic positioned to collaborate directly with Relay Branch

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Clinical News surgeons and address unmet clinical needs. We are excited to provide patients with a less invasive treatment option through this innovative technology,” said John Canning, CTO of Terumo Aortic.

The RelayBranch system incorporates the use of the RelayPro delivery system that is currently under clinical trial in the USA. RelayPro is a low profile nextgeneration delivery system that features a mechanical advantage mechanism allowing for a controlled and accurate deployment of the prosthesis. The RelayPro delivery system also features the company’s dual sheath and self-aligning technologies.

II BTK and TOBA III. TOBA II is investigating the combination of the Tack device with both plain and drugcoated balloon angioplasty in the arteries above the knee, and completed enrolment in March 2017. TOBA II BTK is investigating the combination of the Tack device with plain balloon angioplasty in the arteries below the knee and is actively enrolling patients. TOBA III has nearly completed enrolment in Europe and is investigating the combination of the Tack device with drug-coated balloon angioplasty, inclusive of long lesions.

TOBA BTK trial study publishes one-year results for Tack endovascular system

The first results have been announced from ENCORE, a pooled, global analysis of several prospective clinical trials and registries studying polymer endovascular aneurysm repair (polymer EVAR) using Ovation abdominal stent graft systems (Endologix).

ENCORE is a pooled, retrospective analysis of six prospectively enrolled clinical trials and registries of Ovation abdominal stent graft systems encompassing 1,296 patients, 160 centres and 339 investigators in the USA, Europe and Latin America. This contemporary analysis standardises outcome variables across each study. The data is a mix of real-world registry and controlled data, and all endpoints are presented using Kaplan-Meier survival estimates.

Median follow up across all studies was 883 days (range 30 days–five years). At five years, the ENCORE analysis included the following results for Ovation based on the available data: 1% freedom from AAA-related mortality 0% freedom from reintervention for Type Ia endoleak 7% freedom from rupture 2% freedom from conversion 4% freedom from all device-related reintervention “With ENCORE, our objective was to conduct a rigorous, global evaluation of the available Polymer EVAR clinical data, which includes nearly 1,300 patients, and to share the consolidated results with physicians worldwide,” says Matt Thompson, chief medical Ovation Graft and Delivery System officer for Endologix. “We look forward to sharing additional analyses from the ENCORE data set in the future, and we would like to thank all of the clinical investigators who participated in the underlying studies that are the basis for the ENCORE analysis.”

The TOBA BTK (Tack Optimized Balloon Angioplasty Below the Knee) clinical trial results have recently been published in Catheterization and Cardiovascular Intervention. The multicentre pilot study focused on collecting data supporting the safety and performance of the Tack Endovascular System (Intact Vascular) in patients with critical limb ischaemia (CLI) due to vascular disease below the knee.

Thirty-five patients were enrolled at six sites in Europe and New Zealand in the TOBA BTK study, which targeted diseased tibial arteries for dissection repair following plain balloon angioplasty.

The analysis of the TOBA BTK data demonstrates one-year primary patency via Kaplan-Meier estimate of 77.4%. Additionally: 93.5% freedom from clinically driven target lesion revascularisation (CD-TLR) 93.5% freedom from clinically driven target vessel revascularisation (CD-TVR) 84.5% amputation-free survival (AFS).

“The number of patients being treated for critical limb ischemia is rapidly growing, making it vitally important to optimise post-angioplasty results and minimise metal burden to improve blood flow and allow wound healing,” commented Marianne Brodmann, head of the Clinical Division of Angiology, Medical University Graz, Austria. “I believe that the Tack Endovascular System provides a promising option to treat post-angioplasty dissection in this very challenging patient population.”

The TOBA BTK multicentre pilot study was the first known industry-sponsored study designed to investigate a permanent vascular implant in arteries below the knee for focal dissection repair. The Tack implant is a first-of-its kind device for precision dissection repair following balloon angioplasty. The system is designed to help maintain vessel integrity and improve blood flow to promote healing, improve outcomes and preserve limbs. The system leaves a minimal amount of metal in the artery, reduces mechanical stress on the arterial wall and preserves future treatment options. Unrepaired dissections—which are frequent following balloon angioplasty—increase the probability of acute arterial occlusion and may continue narrowing the artery, which leads to lower long-term patency rates.

“We are very pleased with the results from the TOBA BTK study and the expanding publication of peer-reviewed clinical evidence supporting the Tack Endovascular System,” said Bruce Shook, Intact Vascular’s president and CEO. “As we previously reported, we are on track to complete our pivotal TOBA II BTK clinical study enrolment earlier than originally planned, and we are thankful to our committed investigators who are eager to have more approved therapeutic options to treat their patients with CLI.” Intact Vascular is sponsoring three clinical trials to evaluate its Tack Endovascular System: TOBA II, TOBA

First results of global ENCORE analysis using Ovation abdominal stent graft

E-xtra Design Engineering prosthesis successfully implanted for the 3000th time

The 3,000th E-xtra Design Engineering vascular implant (Jotec/CryoLife) was recently inserted successfully. The endovascular implantation was performed at Cologne University’s academic teaching hospital, Porz am Rhein hospital, Cologne, Germany, by senior consultant Thomas May and senior physician Guido Schmitz-Hagnau.

The procedure was performed on a 72-year-old patient with a thoracoabdominal aneurysm and a conventional vascular prosthesis previously implanted in the area of the infrarenal aorta.

According to a company release, based on the relevant medical information, Jotec used E-xtra Design Engineering to develop, produce and deliver a vascular implant tailored to the patient’s anatomy with four external branches and integrated bifurcation in a short space of time.

Jotec explains that E-xtra Design Engineering enables the production of individual vascular implants that are tailored to the patient’s anatomy. The necessary medical

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information and the resulting specifications are supplied by the hospital providing treatment. E-xtra Design Jotec e-xtra Engineering then checks how the individual therapy plan can be optimally supported.

An overall concept is prepared. This firstly includes the implant and, secondly, also additional measures and components that support the physician during implantation—up to and including expert surgical support.

Just 18 working days are required to produce a bespoke E-xtra Design Engineering solution as of design drawing approval. With short production times, E-xtra Design Engineering enables the individual endovascular care of complex patient anatomies for which standard implants cannot be used.

New data for biocompatible particle embolic device to slow or stop blood flow

Results and data on vascular embolic device GPX (Fluidx Medical Technology), a new proprietary in situ setting embolic agent that combines the benefits of coils, gelbeads, and other embolics, were presented at the 2018 Society of Interventional Radiology conference (17-22 March, Los Angeles, USA).

“GPX is a biocompatible particle embolic loaded in a pre-packaged syringe in a low-viscosity state. After injection into a blood vessel through a standard catheter, GPX can fill the targeted vessel and therapeutically slow or stop blood flow,” said Josh Jones, presenting author of the scientific abstract. “It is non-toxic and non-inflammatory and can be delivered through standard off-the-shelf small and large catheters. It does not rely on polymerisation or precipitation, and is designed to deliver precise control and safety for embolisation procedures.”

Therapeutic catheter-delivered embolisation is performed to stop or slow arterial or venous blood flow into certain organs or anomalies to control bleeding, treat aneurysms, seal arterial venous malformations, selectively block blood flow into specific organs and conditions (prostate, uterine fibroids…etc.), and/or to de-vascularise certain tumors to starve them of blood supply.

“The data presented today are exciting. In acute in vivo experiments, GPX was delivered with no catheter reflux and demonstrated complete vascular occlusion without crossing into the venous circulation,” said David Blossom, president of Fluidx Medical Technology. “Some other embolic devices stick to catheters during delivery which can create patient safety issues. These data show that a catheter could be left in the body, with GPX embolic material around it, for hours without risk of catheter entrapment. Because of its ease-of-use and precise control, GPX represents a promising new device to help patients in a variety of embolisation scenarios.”

Two scientific abstracts on the device were also presented earlier this year at Leipzig Interventional Course (LINC; 31 January–2 February, Leipzig, Germany).

Embolic devices include particles, coils, and liquids or glues. Particles, sometimes referred to as “beads” or “gel-beads”, are generally small polymer spheres injected thorough catheters which flow downstream with the blood flow and embolise large spaces. However, particles are hard to control, sometimes uncontrollably and unintentionally flow into non-target organs. They also typically are not radiopaque, and do not allow the clinician to create a plug.

Metallic coils can create a plug to occlude flow, but lack precision, sometimes perforating the vessel, and often require numerous expensive deployments to occlude.

Liquid embolics, including “glues”, have advantages for certain procedures, but are associated with cytotoxicity, vascular inflammation, clumping, in-vivo polymerisation and precipitation, and accidental catheter entrapment in the body that can be catastrophic for the patient.

GPX is currently under development and not FDA cleared at this time.

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Industry News Surmodics acquires thrombectomy technology assets from Embolitech

Surmodics has reached an agreement with Embolitech to acquire an innovative thrombectomy platform technology and related intellectual property with broad potential peripheral vascular applications.

Under the agreement, Surmodics will pay US$5 million up front, and additional amounts related to various regulatory milestones. The addition of this technology to the Surmodics peripheral vascular pipeline strengthens the company’s focus on developing highly differentiated whole-product solutions for its medical device customers.

“We are excited to add to our portfolio a technology that offers significant advances over the current treatment of complex, peripheral artery disease,” said Gary Maharaj, president and CEO of Surmodics.

“The Embolitech technology offers nextgeneration innovation that may eliminate the need for the use of thrombolytics, reducing the likelihood of ICU time and bleeding complications that significantly affect patient recovery and outcomes. In addition, the technology is anticipated to reduce procedure time and the need for multiple procedures, and it does not require any additional, external capital equipment.”

The Embolitech technology platform

is designed to remove difficult, organised blood clots. Surmodics will leverage its design, development and manufacturing capabilities to advance the technology platform for a variety of peripheral and vascular applications.

Surmodics anticipates recording a US$0.49 per share charge to earnings in the third quarter of fiscal 2018 related to in-process research and development expense and deal costs associated with this agreement.

Vascutek and Bolton Medical merge as “Terumo Aortic”

Vascutek and Bolton Medical, subsidiaries of Terumo Corporation of Japan, have combined into Terumo Aortic. Combining the aortic companies into a single business, Terumo looks to grow its presence in the global aortic and vascular implants market.

The new company brings together two leaders in the aortic implant market. The new identity underlines Terumo’s global growth ambitions, further to a previous US$43 million factory investment.

Calendar of events 20–23 June

25–28 September

21–22 June

17–20 October

Vascular Annual Meeting Boston, USA W www.vascularannualmeeting.org BSET Gloucestershire, UK W www.bset.co.uk 29–30 June

Critical Issues in Aortic Endografting Malmö, Sweden W www.critical-issues-congress.com 12–14 September

6th International Meeting on Aortic Diseases Liège, Belgium W www.chuliege-imaa.be 21–25 September

ESVS 32nd Annual Meeting Valencia, Spain W www.esvs.org VASSA (Vascular Society of Southern Africa) Congress Cape Town, South Africa W www.vassacongress.co.za 18–21 October

World Congress of the International Union of Angiology and 14th Chinese Capital Vascular Symposium Beijing, China W www.lua2018.org 5–9 November

VIVA 2018 Las Vegas, USA W vivaphysicians.org

TCT—Transcatheter Cardiovascular Therapeutics San Diego, USA W www.crf.org/tct

13–17 November

22–25 September

13–15 December

CIRSE Lisbon, Portugal W www.cirse.org

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Events

VEITHsymposium New York, USA W www.veithsymposium.org Aortic Surgery, Preipheral & Venous HTDI-How to do it Milan, Italy W www.aorticsurgery.it

The integrated company aims to become a world leader in driving innovation and developing devices to treat aortic disease. As a combined business, Terumo Aortic will focus on providing individualised treatments that offer clinicians more options than ever before.

Terumo Aortic will have a combined revenue of nearly US$200 million and over 1,100 employees worldwide. Its primary research and manufacturing facilities will remain in Glasgow, Scotland and Sunrise, USA. The combined offering includes advanced technologies such as surgical grafts for abdominal, cardiothoracic and peripheral applications as well as hybrid and catheter-based stent graft systems for abdominal and thoracic aortic aneurysms.

These implants have already helped to save or improve the lives of over two million patients in over 100 countries worldwide.

Vascutek and Bolton Medical have been working to consolidate and streamline their complementary offerings for the past year. Significant focus has been placed on creating an integrated research and innovation strategy that will push the boundaries of the aortic and vascular implants market.

Paul Holbrook, president of Terumo Aortic, said: “This coming together of two organisations with highly advanced technologies will be transformative for physicians and the patients they serve.

“We have woven together the products, services and expertise offered by our teams in Europe and the USA, enabling clinicians to meet the unique needs of their

patients and redefine the treatment of aortic disease.”

Med Alliance raises US$37 million to launch sirolimus drug-coated balloon

Med Alliance SA, a company developing and commercialising the first sirolimus micro-reservoir drug-coated balloon (SELUTION DCB) to treat patients suffering from peripheral artery disease, coronary artery disease, arteriovenous fistulas and grafts for end-stage renal disease, has raised US$37 million.

The US$37 million consists of US$22 million equity and US$15 million in nondilutive licensing agreements for Japan and China. The Investment Round was led by a US$20 million investment by Shenzhen Salubris Pharmaceuticals.

Kevin Ye, CEO of Salubris, highlighted the MedAlliance investment and distribution agreement: “Sirolimus’ combination of antirestenotic and anti-inflammatory properties have been proven clearly superior to first generation paclitaxel drug coatings on stents, but technical challenges have precluded the transposition of this evolution in stents to the drug-coated balloons used in reperfusion procedures. Salubris is pleased to support MedAlliance progress through this strategic investment, and we look forward working together to commercialise the company’s technology for the benefit of many millions of patients in China”.

The proceeds from the equity financing will be used to fund European commercialisation, US regulatory approval and support global clinical programmes.