Vascular News — CX 2019 Special Edition

Charing Cross Special Edition

March 2019

Vascular & Endovascular

Challenges Update Aortic Challenges

Peripheral Arterial Challenges

Venous & Lymphatic Challenges

Acute Stroke Challenges

Vascular Access Challenges

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

and introducing

EDUCATION

INNOVATION EVIDENCE

CX Challenges vascular community to focus on Evidence The Charing Cross Symposium (CX; 15–18 April, London, UK) is the longest-running vascular and endovascular global symposium in Europe, and an important source of Education, Innovation and Evidence as the vascular field in 2019 faces several critical questions and concerns. Through structured debate and presentation of data, the international forum at CX aims to drive the discussion through this year of Challenges, towards future Consensus.

T

hree CX Special Sessions have been introduced to the programme, to focus on those topics that are seen as most central to the vascular community and warrant highlighting.

With two aortic and one peripheral CX Special Sessions, as well as dedicated Podium 1st sessions to emphasise new data, CX is improving its format to optimise engaging education.

This year, the four-day programme starts with an afternoon of Acute Stroke Challenges, followed by three days of Aortic, Peripheral, Venous and Vascular Access programmes.

The last word on paclitaxel

On Tuesday 16 April, the first CX Special Session will take place to shed

light on the highly discussed 2018 suggestion of an association between paclitaxel-coated and -eluting devices, and patient mortality.

Katsanos et al created uproar and uncertainty surrounding the results of the meta-analysis of 28 paclitaxel device studies and trials. Enormous efforts have been made by societies, regulatory bodies and industry to understand the data presented in the meta-analysis claims.

CX aims to analyse the problem and attempt to point the way forward. The US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency are showing high-level interest and will be listening to the CX discussions.

Draft NICE aortic guidelines

The second CX Special Session, on Wednesday 17 April, is focused upon the durability of endovascular aneursym repair and the draft National Institute for Health and Care Excellence (NICE) aortic aneurysm guidelines. A Virtual Reality live endovascular aneurysm repair procedure will be performed to illustrate the discussion.

The draft guidelines, published in May 2018, recommended UK healthcare professionals to favour open repair for aneurysms over endovascular repair.

Subsequent debate with a dissenting majority within the vascular community has ranged from the appropriateness of outdated trials, to healthcare economics and the cost of post-endovascular repair

reinterventions. If implemented, the draft guidelines may change vascular practice in the UK significantly.

The final guidelines remain unpublished at the time of writing.

Stroke from Thoracic Endovascular Procedures

On the final day of CX, Thursday 18 April, the investigators of the Stroke from Thoracic Endovascular Procedures (STEP) study take the stage, to give new insight on an important issue in thoracic interventions.

Presenting new ideas for riskreduction with regard to stroke from endovascular procedures, one particular tool and its peri-procedural application stands out, as the benefits of using diffusion-weighted MRI are considered.

Tilo Kölbel’s team from Hamburg, Germany, will perform a Thoracic EndoVascular Repair (TEVAR) whilst risk of stroke is discussion, and how to minimise this risk.

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March 2019

CX 2019

Aortic Special Sessions focus on aortic aneurysm guidelines and endovascular stroke risks

Aortic Challenges

Podium 1st Aortic session

Abdominal Aortic Challenges 10:00–18:00 Wednesday 17 April Upper Main Auditorium

The abdominal aortic programme will host the second CX Special Session, to shed light on the status of the National Institure for Health and Care Excellence (NICE) UK aortic aneurysm guidelines. Andrew Bradbury, chair of the NICE aortic guidelines committee, will introduce the sessions with the latest news from the committee.

Stéphan Haulon, CX Executive Board Member, says the session is important, as “we need to know how endovascular aneurysm repair (EVAR) practice will evolve in the UK and outside the UK due to these guidelines.

“We will see how the randomised controlled trials, and in particular EVAR 1, were interpreted by the NICE committee and how they are interpreted by the authors of those trials. We will talk about the most recent registries and how they also impact

EVAR practice throughout the world.”

Greenhalgh similarly implores those affected by the guidelines to attend the session, and hear how the EVAR follow-up is where failure occurred, and how to correct this.

The plenary programme will be illustrated with the use of several Live and Edited Cases, as well as a cutting-edge Virtual Reality Case to demonstrate the durability of EVAR. The full day of Edited and Live Aortic Cases will run parallel to the programme in the Pillar Hall Learning Centre, and will further include the best cases from two recent meetings: Aortic Live and Paris Endovascular Aortic Course.

Among this year’s Aortic Challenges is also the vascular surgery recruitment crisis, and an afternoon session will focus on the potential pathways to increasing recruitment of young specialists as we face an ever-increasing arterial disease burden globally.

08:00–10:00 Wednesday 17 April Upper Main Auditorium

•T hirty-day clinical results of global cohort with new thoracic aortic endograft • Use of inner branches in complex aneurysms—early results of the Iberian Study • Early outcomes of post-market registry of an off-the- shelf endograft for thoracoabdominal aneurysms • New developments in fusion imaging—artificial intelligence that deforms anatomy to maintain accuracy • Early results and implication of internal iliac preservation on quality of life • EVAR plus endoanchors in the treatment of short proximal necks is a viable option: Two-year clinical results • FRONTIER IV data with a large hole closure device • The impact of polymer sealing on neck-related adverse events: Five-year results from ENCORE • Exercise for abdominal aortic aneurysm patients: Early results from the AAA Get Fit Trial • ACT-guided heparinisation during non-cardiac arterial interventions: First results of the ACTION trial • EVAS cardiovascular mortality benefit through active sac management in comparison to EVAR

Thoracic Aortic Challenges 08:00–18:00 Thursday 18 April Upper Main Auditorium

The thoracic aortic programme will be focusing on the stroke risk following ascending arch and descending thoracic aorta endografting, with a Special Session dedicated to the Stroke from Thoracic Endovascular Procedures (STEP) study. “This is very interesting”, says Stéphan Haulon, “because there is new data coming

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from the STEP study which we will share. We will see that we can actually reduce the stroke risk by having a specific workflow.” The value of diffusion-weighted MRI will be presented with expeirences from across the globe.

“We will also be talking about spinal chord ischaemia risk following extensive aortic repair during branch- and fenestrated thoracoabdominal endovascular repair”, Haulon

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reports. “A lot of experts will show how they significantly reduce the risk for spinal cord ischaemia and there is a lot to be learned from this session.”

Continuing from the previous year, hands-on activities and workshops with the experts will again be available in the Aortic Village.

“Do not miss CX 2019”, says Haulon in summary, as there is “a lot going on.”

Please contact the Vascular News team with news or advertising queries Tel: +44 (0) 20 7736 8788 Published by: BIBA Medical 526 Fulham Road London, UK SW6 5NR Tel: +44 (0) 20 7736 8788

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March 2019

CX 2019

Peripheral Arterial Challenges

Peripheral Arterial Programme: Dedicated sessions for new data and last word on paclitaxel

Peripheral Proximal Arterial Ischaemia Challenges

Peripheral Critical Ischaemia Challenges

08:00–18:00, Tuesday 16 April Upper Main Auditorium

08:00–18:00, Thursday 18 April Lower Main Auditorium

DESCRIBING THE BIGGEST questions facing the 2019 CX Periphepheral Arterial programme, CX Executive Members Gunnar Tepe (RoMed Clinic, Rosenheim, Germany), Thomas Zeller (Universitäts-Herzzentrum Freiburg, Bad Krozingen, Germany) and Andrew Holden (Auckland City Hospital, Auckland, New Zealand) focus on the use of drug-coated balloons in the superficial femoral artery, the effects of paclitaxel, and the role of drug-coated balloons in below-the-knee interventions. These central questions and more will be discussed in the Peripheral Arterial Challenges, which runs through all of Tuesday in the Upper Main Auditorium.

CX will also introduce a dedicated Podium 1st session on Thursday 18 April, presenting a record number of new data presentations into dedicated aortic and peripheral sessions. This new format for CX makes it easier for attendees to engage with the late-breaking trial results and the cuttingedge research that is most relevant to them.

“For me,” says Tepe, “Charing Cross is an educational meeting, so I bring back new ideas all the time. Secondly, when I go to CX I can expect to find data presented in an unbiased way, and there is an open discussion possible— this is really the culture that is implemented there.” Meanwhile, for Holden, “one of the highlights of Charing Cross is always live data, and I know 2019 is going to be no different—I know we are going to see a lot of new data.”

He adds that, importantly, CX provides an environment “where we can analyse and criticise new data, and reach consensus.”

CX Special Session: The last word on paclitaxel

The first of three Special Sessions is a telling of the paclitaxel story which has unfolded since

the publication of Konstantinos Katsanos et al’s meta-analysis published December 2018 in the Journal of the American Heart Association (JAHA). The authors’ conclusions are that paclitaxel use in the superficial femoral artery is associated with increased long-term mortality. These have been debated and scrutinised at every major international vascular meeting of 2019, including the Vascular Leaders Forum (VLF; 1–2 March, Washington DC, USA) which in its entirety was dedicated to discussion of the topic. The alarm and surprise of the vascular community faced with the concerning findings could be seen in the halting of ongoing SWEDEPAD and BASIL-3 trials, which used peripheral paclitaxel treatments. Nevertheless, many argued methodological flaws and incomplete datasets may have undermined the outcomes of the study, and Peter Schneider (Honolulu, USA) stated in Vascular News that the metaanalysis “prompts many questions but does not answer any.”

Starting at 11:20, this CX session will begin by defining the paclitaxel problem which Katsanos et al generated, and summaries of the discussion that has taken place at recent vascular meetings. This will be followed by talks that aim to shed light on the way forward. As regulatory bodies from the USA and Europe will be in attendance, it is clear this is a session that could have an impact on future guidelines and the daily practice of attendees.

“We shall review the evidence with our colleagues in the vascular community,” says CX Founder and former Executive Board Chair Roger Greenhalgh. “We see that it is in everyone’s interest to review the problem, and find the best way forward.”

Peripheral Techniques & Technologies 09:30–18:00, Wednesday 17 April Lower Main Auditorium The Live and Edited Cases at CX are more than a simple technology showcase session: each case has been carefully selected with the intent to illustrate central points from the plenary programmes. At CX, education is always the priority, with new and exciting ways of dissimentating information in an engaging way being developed each year. In 2019, the successful Live Cases continue, with the addition of several Virtual Reality Cases.

In the Peripheral Village, workshops will be ongoing through Tuesday 16 April and Wednesday 17 April.

The Peripheral Village is a great place to interact with the experts, while the numerous hands-on activities provide practice with techniques and tools as discussed in the sessions, or illustrated in the Live and Edited Cases.

Charing Cross Special Edition

iLegx returns to CX for two sessions in the Critical Limb Ischaemia programme, including presentations on limb-saving interventions and news in medical therapy, again in partnership with the Global CLI Society. This year, an afternoon session is also dedicated to the new iWounds initiative, covering wound management and healing related to arterial and diabetic wound treatment. Finally, two mini-symposia will focus on arterial disease in the foot.

Podium 1st Peripheral Arterial session 10:30–12:30, Thursday 18 April Lower Main Auditorium

•A ngiography alone in the lower limb: First results comparing IVUS and angiography in the leg • Two-year data from the MIMICS-2 study • The case for treating aortoiliac occlusive disease with a covered device: Early experience with new balloon- expandable endoprosthesis • Multivariate analysis of 2,400 patients using a drug- eluting stent—patency data • Final results of preclinical study comparing drug delivery on 0.018” vs. 0.035” DCB platforms • Intravascular lithoplasty: Study status (DISRUPT PAD II and III) and lessons learnt from a real-world registry • ZILVERPASS study—final 12-month and preliminary 24-month results • R EPLACE study—heparin-bonded ePTFE graft vs. ePTFE graft • First results of the MUST trial and further updates on the use of microbubbles in thrombolysis • FINNPTX final results • PORTRAIT Claudication Registry • DRASTICO study two-year results • China one-year results with drug-eluting stents in small vessels • IDE below-the-knee six-month results with Rutherford 5 patients

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March 2019

CX 2019

Venous and Lymphatic Challenges examine pathways of care

Venous & Lymphatic Challenges

Elaborating on the important questions at the heart of the Venous programme, CX Executive Board Member Manj Gohel tells Vascular News: “The theme of the meeting this year is Challenges, and we are going to be looking at all sorts of deep and superficial venous topics. In the deep venous space, one of the biggest complications and problems is reinterventions; we have an excellent army of speakers to look at reinterventions. In the superficial venous space, after the EVRA study results, the focus is really on pathways of care and meeting the challenge of getting appropriate treatments to the appropriate patients.”

Superficial venous treatments Morning, Tuesday 16 April Lower Main Auditorium

The plenary Venous programme at CX this year kicks off with a discussion of options for truncal vein treatment including foam, glue and other non-thermal treatments, the leaders and trailblazers using a range of new treatment modalities will share their insights, and pose the question of whether the superficial field is leaving thermal intervention techniques behind.

CX Executive Board Member Stephen Black comments, “What I am looking forward to is furthering the discussions of the role of the non-thermal techniques in the treatment of superficial venous disease, in particular where glue which is now gaining a lot of traction around the world—where the role of glue fits and which patients are going to benefit most

from that, over and above our experience with thermal technologies.” The Podium 1st presentation of the late-breaking VeClose trial five-year results are set to further this discussion.

Beyond superficial veins with thermal and non-thermal treatments, the CX Venous programme continues to cover a wide range of disease areas, including pelvic venous disease, lymphoedema and venous ulcerations. Last year’s CX saw a landmark trial in EVRA, which produced evidence for early intervention with ablation in the treatment of venous leg ulcers. This year, principal EVRA investigator and CX Executive Board Member Alun Davies will lead the discussion on how to maximise implementation and impact following the study outcomes.

Venous Techniques & Technologies Wednesday 17 April, Thursday 18 April Venous City

Podium 1st sessioni VeClose Extension Study five-year results Nick Morrison (Scottsdale, USA) 08:36–08:45 Tuesday 16 April Lower Main Auditorium

“The great thing about Charing Cross,” Gohel tells Vascular News, “is that there are four days of fantastic educational activity. […] There are two days of workshops where there is a great chance to meet the experts from around the world and discuss the individual techniques.” Black accords, saying, “The CX Venous programme has always been a wonderful opportunity to bring together science and learning opportunities in the Venous City, and the mixing of all the wonderful faculty that come to share their ideas and their visions. […] I learn a lot every single year from the marvellous faculty we have.”

The Venous City, which last year celebrated 10 years of venous workshops at CX, is a thriving hub of activity where cutting-edge technology and new techniques are demonstrated and discussed. This year, the venous edited cases continue to provide thoughtful illustration of key topics from the plenary programme, with a broad range of both superficial treatment cases and deep vein procedures.

Deep venous system Afternoon, Tuesday 16 April Lower Main Auditorium

The deep venous programme will explore a multitude of new devices and developments in deep vein interventions. From stents and inferior vena cava filters to the role of intravascular ultrasound and medical apps in venous care, the Tuesday afternoon provides a thorough update on this space, with audience participation and discussion of topics that affect all vein specialists, including the optimisation of treatment pathways.

“There are a lot of advances now in the deep venous space”, Black notes, and outlines some key questions currently in this space. “A number

of companies have brought their stents out into the market, and these have reached the end of IDE studies—we should be starting to know what these studies have shown and what the outcomes for these treatments will be, but in particular we need to start putting together where the respective treatments for venous patients are going to be: what is the role of deep vein stenting? How can we make sure that the appropriate patients receive the appropriate treatments? Not only in the deep vein space but in pelvic venous disease and in superficial venous disease, and of course we cannot forget that there is lymphatic involvement— we need to treat that as well.”

Charing Cross Special Edition

What is the role of deep vein stenting?

How can we make sure that the appropriate patients receive the appropriate treatments?”

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March 2019

CX 2019

New format as CX starts with Acute Stroke Challenges

Acute Stroke Challenges

Introducing a new format which begins, rather than finishes, with the half-day Acute Stroke programme, the Charing Cross Symposium starts out with an afternoon of the challenging carotid and stroke areas of vascular surgery. A great number of debates have been confirmed, building on from a similarly interactive programme with plenty of debates last year.

13:00–17:00 Monday 15 April Pillar Hall Learning Centre

CX Executive Board Member Hugh Markus (University of Cambridge, Cambridge, UK) says the debates are appreciated by both Faculty and attendees, with a great degree of engagement.

“Stroke is an important complication of a lot of interventional procedures”, Markus says. “Often there is a big division between the stroke community and the endovascular community, and at CX it is really good to see the two coming together with lots of active discussion. I particularly enjoy the debates, and I think the audience enjoys them a lot too, as there is a high level of interaction.”

The first session, co-chaired by Ross Naylor (University of Leicester, Leicester, UK) will focus on current challenges and hot topics in the carotid space, with debates on the appropriateness of carotid endarterectomy for minor stroke, interventions for asymptomatic carotid disease, and carotid revascularisation following stroke thrombolysis. Naylor reports that in his experience, “attendees of the CX Acute Stroke programme are often working vascular surgeons, who want to hear how the experts would deal with pragmatic questions that they face every day of their lives.”

Last year, Naylor noted, the debates produced

several informative consensuses on best practice for several situations common for vascular surgeons. Among others, the CX 2018 audience concluded that given the choice of surgery versus stenting for patients immediately after the onset of stroke symptoms, surgery was favoured—“although as stent technology improves, that may change”, said Naylor. “We also demonstrated that most people do not think completion assessment is beneficial, and a narrow majority agreed that surveillance could reduce risk of stroke after endarterectomy or stenting.”

Looking forward to the 2019 CX Acute Stroke Challenges, Naylor noted: “The key question I have asked several times to speakers at this meeting is a challenge to the stenters. We already know that surgery can be performed safely in the first seven days following the onset of symptoms, but we do not know the same for stenting. There is an awful lot of papers on how good new stent systems are or new protection systems are, but in asymptomatic patients. What we need to know is whether these new technologies are going to reduce the risk of perioperative stroke in patients who are recently symptomatic—because in the battle of stenting and surgery, once you get beyond 30 days there is no difference in outcomes; if these new technologies

reduce the risk of stenting in the first month, it may become the preferred choice—but right now, it is still surgery.”

“Stroke is an important complication,” Markus emphasised, “and it is often not thought about in endovascular procedures but it really matters to patients—it is a devastating disease. That is why it is important to raise awareness of it with sessions like these, and to see how we can reduce stroke rates.”

“We tried to cover a broad field of relevant topics in cerebrovascular disease in this year’s CX programme,” says CX Executive Board Member Barbara Rantner. “Since the debate of intracranial thrombectomy—who should do it and when—is very vivid at the moment, we decided to highlight that amongst our debates and cover it with a key note lecture.” Rantner adds that there will also be a series of “pro and cons” talks on relevant topics of acute stroke management, including timing, techniques and treatment of patients with asymptomatic internal carotid artery stenosis.

“Adding an interesting session with abstracts covering plaque diagnostics,” Rantner hopes “new technologies and pathways for treatment decisions will make the Acute Stroke programme attractive to a large number of CX attendees.”

New iWounds programme and village provide interdisciplinary forum for chronic wound care Wednesday 17–Thursday 18 April London Room Learning Centre THE 41ST CX Symposium continues to revitalise its format with iWounds, a new addition to the specialist areas of vascular patients. In addition to a dedicated programme on the Wednesday, the iWounds Village will feature hands-on activities and edited cases, demonstrating the innovations and techniques for wound care that are discussed in the plenary programme.

CX will feature three days of iWounds activities, starting with a session in the Venous and Lymphatic Challenges programme dedicated to venous leg ulcers, with CX Executive Board Member Alun Davies giving an update on the EVRA trial to consider implementation of its findings into practice (11:20, Tuesday 16 April, Lower Main Auditorium). Wednesday will see a half day of the iWounds programme in the morning, and the workshop starting in the iWounds village throughout the afternoon. On Thursday afternoon, the Peripheral programme hosts an iWounds session alongside the Global CLI and ilegx agendas, dedicated to treatment of arterial and diabetic wound patients.

The iWounds Village on the Exhibition Floor provides a hub for overlapping areas of peripheral and venous disease to cover wound management, for wounds caused by vascular and non-vascular conditions such as diabetes. Running parallel and in close proximity to the Venous workshop, participants are encouraged to visit both, as well as the related workshops in the Peripheral Village on the previous days.

Together, the three areas will encompass a full range of wound care and bring the challenges of chronic wound management to the forefront.

Partaking in the iWounds initiative is the American College of Wound Healing and Tissue Repair (ACWHTR) and the Association for Advanced Wound Care (AAWC), whose representatives join an international list of speakers in the iWounds programme. Attendees of the iWounds sessions will hear about wound care challenges as they appear in different healthcare systems, identifying needs for structural and patient pathway changes for these conditions. The importance of collaborative work will be emphasised, and

Charing Cross Special Edition

discussions will consider the integration of wound care into vascular services.

Another focus of the iWounds programme is on innovations in wound care, where dressings, compression wear and imaging and monitoring technology take centre stage to show the latest developments in the broad spectrum of tools for treatment of wound patients.

With the aim to reduce the number of lower limb amputations due to conditions underlying chronic wounds, this new

interdisciplinary and interspecialist initiative is based on the iLegx project, with its focus on three main strategic workstreams: interdisciplinary education, early referral pathways, and implementation of raised awareness in practice. The goal of iWounds, like iLegx, is to increase early diagnosis of the underlying conditions of tissue loss in the lower limbs, and to promote collaboration across disciplines, from the acute to long-term community services.

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March 2019

CX 2019

CX Vascular Access Masterclass to emphasise long-term access maintenance

Vascular Access Challenges

Wednesday 17 April Pillar Hall Learning Centre This year, Nicholas Inston and Domenico Valenti—Co-Chairs of the CX Vascular Access Masterclass—have put together a programme which focuses on the larger scope of vascular access for haemodialysis, with an emphasis on what happens after vascular access has been attained. “This year at Charing Cross, we are very excited to be building on from the previous year’s CX Vascular Access Masterclass,” Inston says, “and actually talking about maintenance of vascular access this year, rather than just formation of vascular access. This includes all the interventions, procedures and tricks of the trade that we use to keep vascular access going.” The full-day Masterclass starts off with a morning of talks on maintaining and optimising dialysis access, from defining the problem and preventing failures to methods for dealing with stenosis, thrombosis and occlusion.

Emphasising long-term solutions for vascular access patients is an increasingly important

focus. In 2019, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) is set to release new guidelines (see page 49); the first update of their recommendations since 2006. These have been described by the guidelines committee chair Charmaine Lok (University of Toronto, Toronto, Canada) as a “conceptual shift”, urging vascular access specialists to focus on the life-plan of the patient and making decisions based on the expected trajectory of the patient and future maintenance of the access.

Highlighting the interdisciplinary nature of the CX Vascular Access Masterclass, Inston explains that “what makes the CX programme unique in this area is that a lot of people deal with vascular access: interventional radiologists, surgeons, nurses and other staff dealing with patients at end stage renal failure, and vascular access is an increasing problem for all of those people.”

The sessions and workshops, therefore, provide a forum of discussion and exchange of expertise from many different perspectives on care for haemodialysis patients. The CX Vascular Access

CX Innovation Showcase THIS YEAR’S CX Innovation Showcase assembles an array of talent to inform the physician inventor on how to take their early-stage idea forward, from prototype to commercialisation. Course director Stephen Greenhalgh outlines some of this year’s programme highlights: “First, we hear from the Godfather of endovascular aneurysm repair, Juan Parodi, about some of the hard lessons he has learned, and Lindsay Machan, who is perhaps most widely known for his contribution to developing and commercialising the paclitaxel-coated stent. We also hear from Chas Taylor who has made not one but two successful exits in the last year with the sale of Veryan Medical to Otsuka and Novate to BTG—who has subsequently been acquired by Boston Scientific.

“We will learn about the use of artificial intelligence in vascular surgery from Tom Carrell and, more broadly, in medicine from Machan.”

Greenhalgh notes, “robotics is making a comeback and we cover this in some depth”, with an overview given by Willem Wisselink (VU University Medical Centre, Amsterdam, The Netherlands).

“The peripheral innovation section is packed with early-stage technologies,” Greenhalgh adds, “including sirolimus drug-coated balloons and infusion

catheters to deliver paclitaxel (perhaps more safely) to the target vessel.”

Furthermore, the Innovation Showcase will see a presentation of a microstent used in below-the-knee arteries by Robert Beasley (Mount Sinai Medical Center, Miami, USA) amongst “a myriad of other things”.

The Aortic Innovation section includes updates on the off-the-shelf Nexus endograft (EndoSpan) by Mario Lachat (University of Zürich, Zürich, Switzerland). Endologix chief medical officer Matt Thompson will then discuss whether Nellix (Endologix) is an example of a “failure or a phoenix”.

There are also a series of talks on Venous, Acute Stroke, Vascular Access Innovation and Diagnostic and Imaging Innovation, culminating in a talk about a next-generation wound care.

Following these presentations is a mini-symposium on the ramifications of the EU Medical Device Regulation (MDR) from different perspectives.

Highlighting the importance of this topic, Greenhalgh notes that “many believe that the EU regulation will set back medical device innovation in Europe by many light years.”

Finally, delegates will hear from previous winners of the CX Dragons’ Den, before 10 or more people step into the Den to compete for the £1,000 CX Innovation Prize.

Charing Cross Special Edition

Techniques & Technologies will take place over two days (Wednesday 17–Thursday 18 April) in the Vascular Access Village, and feature several edited cases alongside demonstrations of tools and strategies for vascular access.

The afternoon of the Masterclass delves deeper into devices and innovations, with updates on the latest trials of drug-coated and other devices used in arteriovenous fistulae, as well as discussions of grafts and stentgrafts, pharmacology, and pre-access optimisation. “I think [vascular access] is an area that industry is beginning to focus on more”, Inston says.

When treating patients requiring haemodialysis, Inston points out, “many of the problems that arise are long-term, lifetime problems for these patients, and as clinicians we have a responsibility to deal with these in the best possible way. What we are trying to do at Charing Cross is to give those who come to the CX Vascular Access Masterclass the skills and the knowledge to keep them completely up to date with what is available to patients requiring vascular access for haemodialysis.”

CX Meets Latin America 13:30–15:30 Tuesday 16 April Gallery Suite Learning Centre

THE CX SESSION with a focus on Latin America returns to showvase vascular and endovascular practice in the region. With endovascular pioneer Juan Parodi (Buenos Aires, Argentina) chairing the session, talks will update CX attendees on a range of endovascular techniques, from optimising outpatient endovascular aneurysm repair programmes to performing fenestrated and branched stent-grafting after previous surgery. The programme will allow plenty of time for debate and discussion with the audience.

CEC@CX

LINC@CX

10:30–12:30 Tuesday 16 April London Room Learning Centre

08:00–10:00 Wednesday 16 April Lower Main Auditorium

The China Endovascular Course (CEC) returns to CX for a second year of exchange with Chinese vascular experts.

CX hosts the Leipzig Interventional Course (LINC) following a successful CX@LINC session in January.

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March 2019

CX 2019

CX launches Virtual Reality Live Cases The Virtual Reality display, or 360-video, is a three-dimensional format that is completely immersive to the viewer, and allows audience members to see the case performed as if they were placed within the procedure room themselves. Using a headset provided by CX, attendees will be able to view their own smartphone screens through lenses, which provide the simulation.

Wednesday 17 April

Abdominal aortic case Stéphan Haulon, Paris, France Upper Main Auditorium Peripheral arterial case Thomas Zeller, Bad Krozingen, Germany Lower Main Auditorium Peripheral arterial case Arne Schwindt, Münster, Germany Lower Main Auditorium

Thursday 18 April

Thoracic aortic case Hamburg, Germany Upper Main Auditorium ZIV HASKAL (University of Virginia School of Medicine, Charlottesville, USA) has started ZVR, a virtual reality company with the view that this technology has a strong potential for advancing procedural medical training, by allowing the viewer to experience the entirety of a medical procedure and its environment in a way that is “far more conducive” to adopting new knowledge, as well as for updating and refreshing medical professionals

on aspects they have previously learned. Haskal and ZVR state, “For interventional and endovascular procedures, essential apsects of education and learning include awareness of the environment, i.e. assistants’ actions, fluoroscopy findings, operators’ hands, team behaviour, vital signs, and haemodynamic assessments etc.”

In an immersive virtual reality environment, these modalities of the operating room and procedural environment become available to viewers in a way that is “simply not possible” in a standard educational video or simulator. Further, Haskal and ZVR note, learners can return repeatedly to recorded content, and observe different aspects of procedures.

Haskal has explored and pioneered novel educational media for 26 years in academic medicine, currently driving the use of social media as editor of the Journal of Vascular and Interventional Radiology. In 2018, Haskal created the first virtual reality simulation of an interventional procedure, in which he taught portosystemic shunt creation (TIPS), at the University of Virginia.

Recent developments in vascular simulation technology

Virtual and augmented reality technologies have moved beyond the video gaming industry and found creative applications in an increasing number of educational settings. The field is a rapidly developing area of technology, which is now finding its feet in

the healthcare industry. Philips and Siemens recently announced their partnerships with Microsoft, to bring their medical imaging platforms to Microsoft’s newly launched HoloLens 2—a headset which allows wearers to experience a so-called “mixed reality”, an augmented reality in which medical images and data can be on display for healthcare professionals during procedures. While a primary difference between virtual and augmented reality is the level of immersion, with augmentation typically simply adding information or visualisation to the real environment rather than replacing it, both technologies have the potential to become commonplace tools for education and practice in medicine.

VR technology has a strong potential for advancing procedural medical training, allowing the viewer to experience the entirety of a medical procedure.”

“Star-studded” CX Abstract Sessions Last year’s introduction of a CX Global Stars and Rising Stars category in the Abstracts Sessions continues at CX 2019, with another increase in abstracts received which were found to be of CX Faculty-level quality. Such abstracts are awarded with the designation Rising Star for junior presenters.

T

he Global Stars are abstracts submitted by non-junior presenters, often Faculty members who are leaders in their field.

CX Abstract Sessions therefore give attendees yet another opportunity to exchange ideas and research across all levels of expertise.

The Abstract Sessions take place on all four days of CX, and are divided into the main programmes of the symposium. Meryl Davis, CX Executive Board Member, told Vascular News that last year saw a tremendous

Tuesday 16 April

•A cute Stroke Abstracts Dark Room Learning Centre • Peripheral Arterial Abstracts (Day 1) London Room Learning Centre • Vascular Access Abstracts Dark Room Learning Centre • Aortic Abstracts (Day 1) Gallery Suite Learning Centre

Wednesday 17 April

•A ortic Abstracts (Day 2) Dark Room Learning Centre

amount of abstract submissions, and a “huge increase” in the number of invited surgeons and trainees who came to speak about their topics of research.

“Across the world we have people doing a tremendous amount of work and a lot of research”, says Davis, adding that “CX is an ideal opportunity to share that with everyone else, but is also an ideal opportunity for speakers to reflect on what our results actually are—there is a lot of work that goes into preparing these abstracts, and we should respect that.”

•V enous Abstracts (Day 1) Dark Room Learning Centre • Peripheral Arterial Abstracts (Day 2) Gallery Suite Learning Centre

Thursday 18 April

• Peripheral Arterial Abstracts (Day 3) Dark Room Learning Centre • Venous Abstracts (Day 2) The Dark Room Learning Centre • Aortic Abstracts (Day 3) Gallery Suite Learning Centre

Charing Cross Special Edition

CX Vascular Malformations invites interactive discussions of most challenging cases THE CX VASCULAR Malformations programme, chaired by Krassi Ivancev (University Hospital HamburgEppendorf, Hamburg, Germany) and Fiona Rohlffs (University Hospital Hamburg-Eppendorf, Hamburg, Germany), will showcase some particularly challenging cases this year to highlight difficult or failed cases, with seemingly no easy way out. Taking a new approach to interactive audience engagement, this year’s Vascular Malformations Session at CX has set aside ample time for discussion with participants, who are encouraged to submit their own difficult cases for the session. The format allows attendees to show slides agreed upon beforehand

with the programme chairs, and share them for perspectives from the audience and experts.

The CX Vascular Malformations programme, running through the Wednesday afternoon, will include the basic background and imaging of vascular malformations, as well as management of both low-flow and high-flow malformations, and the complementary role of surgery.

Wednesday 17 April 13:30–18:00 London Room Learning Centre

16

March 2019

CX 2019

CX 2019 Floorplan

Pavilion

Exhibitors

Cook Medical

140

3D Systems Simbionix

315

EVARplanning

Orbus Neich

505

Endologix

155

Abbott Vascular

232

EVC

TBC

Penumbra

412

Getinge

170

ALN Implants Chirurgicaux

122

EVF

TBC

Pie Medical Imaging

538

AndraTec

TBC

EVT

TBC

Piur Imaging

215

TBC

F Care Systems

116

R&D Surgical

720

Gore

250/260

132

Medtronic

450

AORTIC ASSOCIATION

Terumo Aortic

240

Advanced Oxygen Therapy Inc

138

Fist Assist Devices

718

Ra Medical Systems

509

Avenu Medical

734

GE Healthcare

311

Regen Medical

134

BALTON SP. Z.O.O.

304

Huntleigh

209

Scanlan International

211

BIBA Medtech Insights

110

IDEAS

Shockwave Medical

424

402

Intact Vascular

408

Therenva

533

Laminate Medical

409

The University of Edinburgh

135

Legs Matter

136

Vascular News

110

LifeTech Scientific

523

Venous News

110

Major Sponsors BD

428

Bentley

419

Boston Scientific

228

Cydar

229

JOTEC CryoLife

440

Lombard Medical

432

Merit Medical

470

Philips

444

RD GLOBAL

238

Siemens Healthineers

150

Straub Medical

418

BIOTRONIK BSIR

TBC

BTG

212

CACVS/i-MEET/DIVINE ID

TBC

TBC

Cardionovum

716

LINC

648

Venclose

112

Clinlogix

736

LimFlow

714

VentureMed

732

Concept Medical

401

LSO Medical

220

Veryan Medical

438

ECO Microwave

208

medi

217

Vivasure Medical

Edward Lifesciences

134

Micro Medical

738

VSGBI

317 TBC

Edizioni Minerva Medica

TBC

Mรถlnlycke

134

Wisepress

725

ESVS

TBC

optimed

404

Ziehm Imaging

223

Upper Main Auditorium

Vascular Access Village

Aortic Workshop

Peripheral Workshop

Pillar Hall Learning Centre Faculty Lounge

Lower Main Auditorium

Gallery Suite Learning Centre & Dark Room Gallery level

Entrance Venous City and Venous Edited Cases London Room Learning Centre

Charing Cross Special Edition

March 2019

CX 2019 Pavilion and Major Sponsors PAVILION SPONSORS Cook Medical Booth 140

A global pioneer in medical breakthroughs, Cook Medical is committed to creating effective solutions that benefit millions of patients worldwide. Today, we combine medical devices, drugs, biologic grafts and cell therapies across more than 16,000 products serving more than 40 medical specialties. Founded in 1963 by a visionary who put patient needs and ethical business practices first, Cook is a family-owned company that has created more than 10,000 jobs worldwide.

www.cookmedical.eu Endologix Booth 155

The Endologix portfolio of AAA products is designed to address challenges and improve outcomes.

As the designers and providers of evidence-driven solutions, the world around us provides inspiration to create devices that adapt and elevate the standards for aortic intervention, because we are dedicated to our patients.

www.endologix.com Getinge Booth 170

Getinge is a global provider of innovative solutions for operating rooms, intensivecare units, sterilisation departments and for life science companies and institutions.

Based on our first-hand experience and close partnerships with clinical experts, healthcare professionals and medtech specialists, we are improving everyday life for people, today and tomorrow.

www.getinge.com Gore Booths 250, 260

Gore Medical Products Division engineers devices that treat a range of cardiovascular and other health conditions. With more than 40 million medical devices implanted over the course of more than 40 years, Gore builds on its legacy of improving patient outcomes through research, education and quality initiatives. Gore is joined in service with clinicians and through this collaboration we are improving lives.

www.goremedical.com/eu Medtronic Booth 450

Patients are at the center of everything we do—and we believe medical technology can play an even greater role in improving people’s lives. Join us in our commitment to take healthcare Further, Together.

www.medtronic.com

Terumo Aortic Booth 240

At Terumo Aortic, we understand that no two aortas are alike. We are 100% focused on the aorta, from the arch to the iliacs. With our comprehensive portfolio of surgical, endovascular and hybrid technologies and services, we help you address your patients’ unique challenges—so no patient is left behind.

www.terumoaortic.com MAJOR SPONSORS BD Booth 428

BD is one of the largest global medical technology companies and is advancing the world of health by improving medical discovery, diagnostics and the delivery of care. In 2017, BD welcomed C.R. Bard into the BD family and through this collaboration is accelerating the delivery of innovative technologies, world-class clinical education, and disease awareness programmes that are helping to transform the standard of patient care.

www.bd.com Bentley Booth 419

Bentley’s passion is the development, manufacturing and distribution of innovative implants for minimalinvasive treatments of vascular diseases.

Since market launch in 2012 we rapidly expanded worldwide. Thanks to our international network of exclusive distribution partners we are represented in more than 70 countries—in some we are already market leader.

www.bentley.global Boston Scientific Booth 228

Boston Scientific transforms lives through innovative medical solutions that improve the health of patients around the world. As a global medical technology leader, we advance science for life by providing a broad range of high performance solutions that address unmet patient needs and reduce the cost of healthcare.

www.bostonscientific.eu Cydar Booth 229

Co-founders Tom Carrell, a vascular surgeon in London and Graeme Penney, an imaging scientist at King’s College London, formed Cydar in 2012 to solve a true clinical problem: the need for better visualisation of the anatomy during endovascular surgery. Since then, Carrell and Penney have been turning world-leading image processing research into a world first in cloudbased healthcare. Cydar uses data, cloud computing and AI to improve patient outcomes in image-guided surgery.

CX 2019

JOTEC CryoLife Booth 440

RD Global Booth 238

www.cryolife.com www.jotec.com

www.invamed.net

CryoLife is a leader in the manufacturing and distribution of medical devices focused on aortic repair; devices include implantable tissues as well as mechanical heart valves, surgical adhesive, and a comprehensive portfolio of JOTEC surgical and endovascular stent grafts.

The combined company also offers customised grafts for the thoracoabdominal repair.

Lombard Medical Booth 432

Lombard Medical, Inc. is an Oxfordshire, UK-based medical device company focused on the minimally invasive treatment of abdominal aortic aneurysms (AAAs). The company has global regulatory approval for Aorfix, an endovascular stent graft that has been specifically designed to treat patients with the broadest range of AAA anatomies, including aortic neck angulation up to 90 degrees.

The company has also achieved CE mark for the Altura endograft system, an innovative ultra-low profile endovascular stent graft that offers a simple and predictable solution for the treatment of more standard AAA anatomies.

www.lombardmedical.com Merit Medical Booth 470

Merit Medical® offers an integrated portfolio of products designed to support your vascular surgery procedures, dialysis, peripheral vascular interventions, interventional radiology and cardiology.

Merit Medical® brings you innovative solutions for vascular challenges.

Discover our wide range and complete portfolio at our booth.

17

As a global leader in Medical Innovation Technologies, we work hard and with passion in order to bring people together toward a safer life. RD Global offers an integrated product portfolio designed to support Cardiovascular and Radiology procedures. Our mission is to contribute to heritage of humanity by achieving the best in multiple disciplines of medicine and biomedical engineering in order to serve optimal healthcare solutions.

Siemens Healthineers Booth 150

Siemens Healthineers enables healthcare providers worldwide to increase value by empowering them on their journey towards expanding precision medicine, transforming care delivery, improving patient experience and digitalising healthcare.

www.siemens-healthineers. com Straub Medical Booth 418

Straub Medical AG is a leading developer and manufacturer of endovascular systems and tools to treat both arterial and venous occlusive disease. Rotarex®S, Aspirex®S and Capturex® are the most prominent product families in our portfolio.

Our innovative minimally-invasive technologies target vascular occlusions with Swiss quality, effectiveness and precision. As of now, we contribute to improving the outcomes of endovascular interventions in more than 50 countries worldwide.

www.straubmedical.com

www.merit.com Philips Booth 444

At Philips, we look beyond technology to the experiences of patients, providers and caregivers across the health continuum, from healthy living to prevention, diagnosis, treatment and home care. We unlock insights leading to meaningful innovations from hospital to home. Our integrated solutions—packaged suites of systems, smart devices, software and services— combine broad and deep clinical expertise, technology and services, actionable data, consultative new business models and partnerships.

www.philips.com/igtdevices

www.cydarmedical.com

Charing Cross Special Edition

18

March 2019

CX 2019

CX 2019 Exhibitors Advanced Oxygen Therapy Inc Booth 138

EXHIBITORS 3D Systems Simbionix Booth 315

ANGIO Mentor™ is a multi-disciplinary endovascular training simulator, with an ever-expanding library of 32 interventions and 300+ cases. Stop by to instantly create your own training case using our revolutionary ANGIO Mentor iCase simulation editor. Request a demo at healthcare@3dsystems.com

www.3dsystems.com/healthcare Abbott Vascular Booth 232

At Abbott, we are committed to helping you live your best possible life through the power of health. For more than 125 years, we have brought new products and technologies to the world—in nutrition, diagnostics, medical devices and branded generic pharmaceuticals— that create more possibilities for more people at all stages of life. Today, 94,000 of us are working to help people to live not just longer, but better, in the more than 150 countries we serve.

www.abbott.com

ALN Implants Chirurgicaux Booth 122

ALN is one of the leaders in its field with its ALN optional vena cava filter.

This filter is well known in Europe for more than 25 years and is present for long in international markets including USA. Large Experience with Permanent filtration since 1991 Largest experience with Optional Filtration (More than 10,000 removals since 1999), the oldest one on the market!

The design of the filter has never been changed!

Filter with the most studies It is a real asset: permanent and /or temporary, prevention of thrombus migration, easy to implant, excellent corrosion resistance, with clinical experience for more than 25 years, CE mark and FDA approved and only one retrieval at 12 years.

www.aln2b.com AndraTec Booth TBC

AndraTec is a highly specialised innovative medical device company with the focus in unique medical devices such as XL PTA Balloons, New Venous Balloons, Unique Occluders to fill large lumina, Retrieval Devices, and Guide Wires as well as unique bifurcation stents and XL Covered and bare stents.

AndraTec connects with leading physicians around the world end believes strongly in the improvement with modern technology.

Product Lines are; AltoSa XL, AltoSaSFT, AltoSa-Premier, Exeter-Snare, Lokum-Guidewires, Optimus Stents, Pillar Bifurcation stents, Pillow occluder.

Advanced Oxygen Therapy Inc. (AOTI) offers a wide range of its patented Topical Wound Oxygen (TWO2) systems allowing this unique multimodality therapy to be delivered effortlessly across the continuum of care, all the way to the patient’s home.

Leading clinical trials have shown TWO2 to heal chronic DFU, VLU and PU at an unprecedented rate with far lower recurrence. TWO2 is also effective in healing post-surgical and burn wounds. Over 1,500,000 TWO2 treatments have be delivered to patients to date.

www.aotinc.net

Avenu Medical Booth 734

Avenu Medical, Inc. was founded to pursue unmet clinical needs in the ESRD and vascular access market. The company has developed the Ellipsys® Vascular Access System which is an innovative, ultrasound-guided, single catheter endoAVF® system used to percutaneously create an arteriovenous (AV) fistula for hemodialysis access.

Low power thermal energy is used to weld the walls of the vessels, creating a fused and permanent anastomosis without leaving any foreign material or implant (including sutures) in the resulting AV fistula.

www.avenumedical.com Balton SP. Z.O.O. Booth 304

Balton is a prominent manufacturer of innovative disposable medical equipment for anaesthesia, dialysis, surgery, gynaecology, urology, cardiology and radiology. Having 40 years of experience, the company specialises in manufacturing cardiovascular and endovascular devices, among which are coronary and peripheral stents and balloons as well as self-expanding stents.

www.balton.pl

BIBA MedTech Insights Booth 110

BIBA MedTech Insights is a leading provider of market analysis services.

We serve medical professionals and organisations in the medical device industry in Europe and North America.

Our research products include quarterly monitors, customised research and tailored services.

www.bibamedtech.com

www.andratec.com

Charing Cross Special Edition

BIOTRONIK Booth 402

BIOTRONIK is a global leader in cardio- and endovascular medical technology. Several million patients have been treated with BIOTRONIK coronary and peripheral vascular intervention products. BIOTRONIK Vascular Intervention has engineered many innovations, including Magmaris, the first clinically-proven Resorbable Magnesium Scaffold (RMS), Orsiro, the industry’s first hybrid drug-eluting stent and Pulsar, the world’s first 4F compatible stent for treating long lesions.

www.biotronik.com BTG Booth 212

BTG is a global healthcare company focused on Interventional Medicine.

Our innovative medical technology helps physicians treat their patients through minimally invasive procedures.

We have a growing portfolio of products that advance the treatment of cancer, vascular conditions and severe emphysema. BTG Vascular (EKOS™, BTG Crossing Devices, BTG Sentry) sets the standard for vascular therapies through evidence-based innovation, predictable and cost-effective procedures and strong safety profiles that improve patient outcomes.

www.btgplc.com Cardionovum Booth 716

Cardionovum is a leading company in innovative coronary and peripheral drug coating technologies improving clinical outcomes and quality of life.

LEGFLOW® DCB for peripheral artery disease treatment, APERTO® for hemodialysis shunt treatment, as well as RESTORE® for coronary artery disease treatment are the latest innovations with highest patient safety guarantee.

www.cardionovum.de Clinologix Booth 736

Clinlogix is a Global Clinical Research Organization working to improve human quality of life by supporting and accelerating innovation in the life science industry. Its full suite of clinical research services supports the regulatory and clinical development pathway of medical devices, biotechnologies and pharmaceuticals from bench to bedside. The company delivers this global expertise by way of its regional office locations in the USA, Germany, Colombia and Japan

www.clinologix.com Concept Medical Booth 401

Concept Medical is an India based research division of CMI founded in 2008, which is dedicated for research and development of drug delivering medical devices in various medicinal

applications including cardiovascular and peripheral medical devices.

Concept Medical believe in bringing innovations which inspires not only the industry but others to innovate and create something revolutionary, our products have been the leaders and not followers in the market.

Philosophy: Converting Concepts into reality.

www.conceptmedicals.com ECO Microwave Booth 208

Established in 2000, ECO is a leading manufacturer of medical instruments in China, which covers Microwave, High Frequency and Laser systems. With vision of “To Be No.1 in China and First-Class in the world”, and mission to help employees realize their self-worth and contribute to human health, ECO is trying every effort to deliver advanced technology and provide product solutions to healthcare industry at home and abroad.

www.ecomicrowave.com Edwards Lifesciences Booth 134

Edwards Lifesciences is dedicated to providing innovative solutions for people fighting advanced cardiovascular disease, the world’s leading cause of death and disability. Driven by a passion to help patients, the company and its 7000 employees partner with clinicians to develop innovative technologies that enable them to save and enhance lives.

www.edwards.com EVARplanning Booth 132

EVARplanning is a software company founded by Paolo Spada, Vascular Surgeon in Milan, Italy. Well known for its free web-app for the endograft configuration, EVARplanning has now expanded its team and expertise, to provide a comprehensive preoperative system, based on advanced algorithms and cutting-edge sharing technologies.

www.evarplanning.com F Care Systems Booth 116

F care systems was founded in 2001.

The company is a leading manufacturer of medical and aesthetic equipment.

Our focus lies on the treatment of various types of varicose veins and hemorrhoids based on the principle of thermocoagulation. Our innovations and new developments offer a wide range of solutions for practitioners and have a minimal impact on the patients daily life.

www.fcaresystems.com

20

March 2019

CX 2019

CX 2019 Exhibitors Laminate Medical Booth 409

EXHIBITORS Fist Assist Devices Booth 718

Fist Assist Devices, LLC is a company based in Silicon Valley, CA USA. We have developed a patented, external wearable (Fist Assist) designed for arm vein enhancement and vein dilation before and after AV fistula surgery for renal failure patients and venipuncture procedures. The company is completing the FACT trial at The University of Chicago and all regulatory requirements before sales launch in Europe and the USA.

www.fistassistdevices.com GE Healthcare Booth 311

GE Healthcare provides medical technologies and services to help solve the challenges facing healthcare providers around the world. From medical imaging, software, patient monitoring and diagnostics, to biopharmaceutical manufacturing technologies, GE Healthcare solutions are designed to help healthcare professionals deliver better, more efficient and more effective outcomes for more patients.

www.gehealthcare.com Huntleigh Booth 209

A proud member of the Arjo family, Huntleigh has been committed to supporting healthcare professionals in improving outcomes and enhancing patient wellbeing since 1979. We do this through our proven solutions for Vascular Assessment & Treatment and Fetal & Patient Monitoring. With innovation and customer satisfaction as our guiding principles, we strive for clinical excellence and improved performance, for life.

www.huntleigh-diagnostics. co.uk Intact Vascular Booth 408

Intact Vascular is committed to developing safe, efficacious and easy-to-use products for patients with vascular disease and the physicians who treat them. Founded in 2011, our core technology, the Tack Endovascular System® is a first-of-its-kind dissection repair device that is purpose-built and designed to provide precision treatment of peripheral arterial dissections following balloon angioplasty, in either above- or below-the-knee therapeutic interventions.

www.intactvascular.com

Laminate Medical Technologies is developing a new, external support device for AV fistulas, to be implanted during the fistula creation surgical procedure. The device aims to drive a change in the haemodialysis vascular access treatment paradigm and bring about a significant reduction in the annual fistula failure rate.

www.laminatemedical.com Legs Matter Booth 136

We are a coalition of healthcare organisations that have come together to make sure that anyone with a lower leg or foot problem understands their condition and receives the urgent care, attention and support they need. Stand up for Legs!

www.legsmatter.org

LifeTech Scientific Booth 523

LifeTech Scientific Corporation (Stock Code: 1302.HK) is the leading supplier of minimally invasive interventional medical devices to treat cardiovascular diseases. The company specialises in R&D, manufacture and sales, and its high-quality, innovative, proprietary products are extensively marketed in more than 90 countries by over 300 distributors.

www.lifetechmed.com LimFlow Booth 714

LimFlow is a private, venture-backed medical device company transforming the treatment of critical limb ischaemia with a novel technology solution to perform percutaneous deep vein arterialization.

www.limflow.com LSO Medical Booth 220

Founded in 2002, LSO Medical is a French company which designs, manufactures and sells Lasers. LSO Medical is expert in Endovenous Thermal Therapy with the laser Endotherme 1470nm and its Ringlight radial fibers. At CX 2019, come to discover the new patented SnakeBack technology to perfectly standardise endovenous energy delivery! In addition to its expertise in EVLT, LSO Medical proposes the unique Exotherme™ Laser for the superficial vascular lesions treatment.

www.lsomedical.com medi Booth 217

Global leaders in venous health care.

Visit the stand to see our wound care therapy chain.

Assess with the world’s fastest ABPI device—MESI ABPI MD—an accurate reading in one minute—no need for prior resting before testing!

Charing Cross Special Edition

Clean and debride with UCS premoistened debridement cloth – soft loop technology helps to catch wound debris and slough. Can be used both sides. Sterile and ready to use!

Heal venous leg ulcers with juxtalite the only adjustable Velcro device with measurable compression. Eight sizes and two lengths for all stages of venous disease.

www.mediuk.co.uk Micro Medical Booth 738

Micro Medical Solutions is an innovative, US-based medical device company committed to the advancement of the least invasive technology for the treatment of patients suffering from CLI. MMS’ lead product, MicroStent, is a uniquely designed self-expanding stent for the treatment of BTK peripheral artery disease. MMS’ mission is to improve patient quality of life and clinical outcomes, reduce amputation associated with CLI, and lessen the healthcare economic burden.

www.micromedicalsolutions.net Mölnlycke Booth 134

Mölnlycke is a world-leading medical solutions company. We are here to advance performance in healthcare across the world, and we aspire to equip everybody in healthcare with solutions to achieve the best outcomes.

www.molnlycke.co.uk optimed Booth 404

As a leading German medical device manufacturer optimed is dedicated to the development and production of innovative products for improved patient outcomes. Continuous investment in research and development of highquality portfolio solutions makes optimed a trusted partner for minimally invasive therapy experts. With focusing on vascular interventions our portfolio shows proven safety and efficacy in leading technologies e.g. self-expanding venous and arterial nitinol stents, PTA balloons and the CO2-Angioset..

www.opti-med.de Orbus Neich Booth 505

OrbusNeich® is a global pioneer in the provision of life-changing vascular solutions. Portfolio includes peripheral devices; JADE®, Sapphire II Pro PTA®, Scoreflex® PTA balloons & Teleport®/ Teleport® Control microcatheters together with coronary stents, balloons and microcatheters.

OrbusNeich is the exclusive distributor of the Stealth 360® Peripheral Orbital Atherectomy System from Cardiovascular Systems, Inc. outside of the USA and Japan.

www.orbusneich.com

Penumbra Booth 412

Penumbra, Inc., headquartered in Alameda, California, is a global healthcare company focused on innovative therapies. Penumbra designs, develops, manufactures and markets medical devices and has a broad portfolio of products that addresses challenging medical conditions and significant clinical needs. Penumbra sells its products to hospitals and clinics primarily through its direct sales organisation in the USA, most of Europe, Canada and Australia, and through distributors in select international markets.

www.penumbrainc.com Pie Medical Imaging Booth 538

Pie Medical Imaging (PMI) designs cardiovascular analysis software. PMI’s customers include leading research centres and core labs, as well as major equipment manufacturers, device vendors and local partners. PMI is well known for its 3mensio products for advanced CT imaging with dedicated workflows for planning of EVAR, TEVAR and f-EVAR procedures. With its CAAS product line PMI delivers also software solutions for X-ray, MRI and IVUS/OCT analysis.

www.piemedicalimaging.com Piur Imaging Booth 215

Piur Imaging is a medical device manufacturer that develops tomographic ultrasound solutions for the diagnostic of vascular diseases.

Our mission is to make vascular imaging more affordable and safer for the patient through the innovative tomographic ultrasound solution PIUR tUS. PIUR tUS extends regular ultrasound devices with a tomography function so physicians can produce three-dimensional diagnostic information without the side effects current 3D imaging technologies may introduce

www.piurimaging.com R&D Surgical Booth 720

R&D Surgical serve the surgical community with innovative products including: Portable next-generation LED surgical headlight weighing less than 30g Full range of custom surgical loupes offering unbeatable field of vision, and depth of focus, all while being light and comfortable.

Xenosys wireless HD surgical camera system

www.randdsurgical.com

22

March 2019

CX 2019

CX 2019 Exhibitors The University of Edinburgh Booth 135

EXHIBITORS Ra Medical Systems Booth 509

Ra Medical Systems, Inc. develops, manufactures, and markets excimer laser-based medical equipment. The DABRA Catheter and Laser System photochemically ablates arterial blockages. Ra Medical Systems transforms the lives of cardiovascular patients around the world by saving their limbs and lives.

www.ramed.com Regen Medical Booth 124

Part of the Joint Operations family, Regen Medical is a leading distributor in the fields of burns and woundcare.

Regen Medical prides itself on introducing new, innovate and groundbreaking products to the regenerative space within the UK. These include Epifix® from MiMedx®, a dehydrated Human Amnion/ Chorion Membrane (dHACM) Allograft.

www.regenmedical.com Scanlan International Booth 211

The Scanlan Family has been designing and manufacturing the highest quality surgical products since 1921. Quality is important because a surgical instrument is an extension of a surgeon’s hand.

When purchasing instruments, consider precision, balance, feel and durability then demand Scanlan. See our full-line of instrumentation at our booth.

www.scanlaninternational.com Shockwave Medical Booth 424

Shockwave Medical is a medical device company focused on developing and commercialising products intended to transform the way calcified cardiovascular disease is treated.

Shockwave Medical aims to establish a new standard of care for medical device treatment of atherosclerotic cardiovascular disease through its differentiated and proprietary local delivery of sonic pressure waves for the treatment of calcified plaque.

www.shockwavemedical.com Therenva Booth 533

Since 2007, Therenva is focused on improving endovascular treatments through efficient and user-friendly image guidance solutions. Our portfolio includes the leading case planning software EndoSize and the 3D intraoperative navigation system EndoNaut making image fusion technology available for any mobile C-arm in standard operating room.

Edinburgh Surgery Online delivers a range of part-time Masters degree programmes for surgeons providing structured learning for professional exams. Programmes are delivered entirely online by The University of Edinburgh in partnership with The Royal College of Surgeons of Edinburgh.

The ChM in Vascular & Endovascular Surgery supports preparation for FRCS and FEBVS exams. Through in-depth study students can improve their evidence-based knowledge and enhance their practice.

www.edinburghsurgeryonline. com Vascular News Booth 110

Vascular News is a trusted and editorially-independent newspaper for vascular and endovascular specialists.

It provides physicians with the latest news, conference coverage, comment and analysis by thought-leaders, and industry news in the vascular and endovascular world. Please visit booth 110 for a free subscription.

www.vascularnews.com Venous News Booth 110

Venous News is a trusted and editorially-independent newspaper for venous and phlebology specialists.

It provides physicians with the latest news, conference coverage, comment and analysis by thought-leaders, and industry news in the venous and phlebology world. Please visit booth 110 for a free subscription.

www.venousnews.com Venclose Booth 112

Venclose is a privately held, commercial-stage Silicon Valley medical technology company developing nextgeneration solutions for the treatment of venous reflux disease, also known as chronic venous insufficiency (CVI).

CVI is a progressive medical condition affecting more than 40 million adults in the USA alone. The VENCLOSE RF Ablation System offers physicians more versatility than earlier generation endovenous radiofrequency ablation technologies and is commercially available in the USA and Europe.

www.venclose.com

www.therenva.com

Charing Cross Special Edition

VentureMed Booth 732

VentureMed Group is an innovator in vessel preparation for the interventional treatment of PAD of the femoral popliteal and stenoses of arteriovenous fistula and grafts. The company’s FLEX System is specifically designed to dynamically produce longitudinal micro-incisions in plaque to create the ideal vessel environment to facilitate angioplasty.

www.flexvesselprep.com Veryan Medical Booth 438

Veryan has developed BioMimics 3D, a self-expanding, nitinol SFA/prox popliteal stent which imparts a natural, 3D curvature to the artery, to generate swirling flow, increase wall shear and reduce intimal hyperplasia. In the Mimics-RCT BioMimics 3D achieved significantly better performance than straight control stents. Veryan is now part of the Otsuka Medical Devices group.

www.veryanmed.com Vivasure Medical Booth 317

Vivasure Medical’s patented technology PerQseal® is a fully absorbable closure device for large-bore (up to 24F) arteriotomies. The device comprises an ultra-low profile, synthetic absorbable polymer implant and an easy-to-use ergonomically designed delivery system.

The intra-vascular patch seals the artery from the inside, without the need for sutures, collagen or metal clips. After deployment, the implant is rapidly endothelialised and fully absorbed, leaving nothing behind and restoring the vessel.

www.vivasuremedical.com Wisepress Booth 725

Wisepress.com, Europe’s leading conference bookseller, has a complete range of books and journals relevant to the themes of the meeting. Books can be purchased at the stand or, if you would rather not carry them, posted to you—Wisepress will deliver worldwide.

In addition to attending 200 conferences per year, Wisepress has a comprehensive medical and scientific bookshop online with great offers..

www.wisepres.com

Ziehm Imaging Booth 223

Founded in 1972, Ziehm Imaging has stood for the development, manufacturing and worldwide marketing of mobile X-ray-based imaging solutions for more than 45 years. Employing more than 500 people worldwide, the company is the recognized innovation leader in the mobile C-arm industry and a market leader in Germany and other European countries. The Nurembergbased manufacturer has received several awards for its ground-breaking technologies and achievements.

www.ziehm.com

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March 2019

Drug-eluting devices

US FDA continues to investigate paclitaxel devices in the leg A meta-analysis published in the Journal of the American Heart Association (JAHA) late last year by Konstantinos Katsanos (Patras, Greece) and colleagues, suggesting an increased risk of death at two and five years following the use of paclitaxel-coated balloons and stents in the femoropopliteal artery, has generated months of debate amongst the international interventionalist community. The conversation is still ongoing, with every key vascular conference of 2019 to date hosting discussion on the future of paclitaxelcoated and -eluting devices. Since then, prominent physicians have pointed out flaws in Katsanos et al’s methodology. Patientlevel data published after the JAHA meta-analysis by industry have revealed no increased mortality associated with the use of paclitaxel-releasing devices. Medtronic and Cook Medical have also announced corrections to their published data. Meanwhile, the continued investigation by the US Food and Drug Administration (FDA) indicates that the story is not yet over.

S

peaking from the floor of the Vascular Leaders Forum (VLF; 1–2 March, Washington, DC, USA), hosted by Vascular Interventional Advances (VIVA), FDA investigator Donna Buckley, who has “reviewed most of these devices and recommended them to be approved”, explained the regulatory body’s perspective: “Our first response to the meta-analysis was, I think, similar to everybody else’s: we were a little bit surprised. Nonetheless, it was compelling information that we took very seriously.”

The ongoing FDA evaluation is focusing primarily on US-based randomised controlled trials with data the regulatory body can validate.

The FDA’s preliminary evaluation confirmed the mortality signal reported

by Katsanos et al. Speaking at VLF, Buckley said the FDA’s own analysis of five US pre-market approval (PMA) trials has “converged to where we feel like it [the meta-analysis findings] is not a statistical glitch—but we still have all this incongruous information as well with all the statistical analysis that we have gone through.”

Also at VLF, Peter Schneider (Honolulu, USA) called the process that the FDA is undertaking to review the data “judicious, straightforward and spot on”.

Indeed, the FDA issued a letter to healthcare providers in January stating that it was evaluating the “recent information regarding the potential for increased long-term mortality” following paclitaxel-coated balloon or paclitaxel-eluting stent treatments in the femoropopliteal artery for patients with peripheral arterial disease (PAD). The agency said that whilst the data review was ongoing, the FDA recommends “continued surveillance” for patients treated with paclitaxel. The regulatory body stated in the letter that it believes

the “benefits continue to outweigh the risks” for approved devices within their indications.

extremity interventions.

At one year, all-cause patient death (28 randomised controlled trials with 4,432 patients) was similar between 17 paclitaxel-coated devices and control arms (2.3% vs. 2.3% crude risk of death). All-cause death at two years (12 randomised controlled trials with 2,316 patients) was significantly increased in case of paclitaxel vs. control (7.2% [101 deaths in 1,397 patients] vs. 3.8% [35 deaths in 919 patients] crude risk of death, number-needed-to-harm [NNH]: 29 patients [95% CI: 19–59]). Longterm risk of all-cause death up to five years (three randomised controlled trials with 863 patients) increased further in case of paclitaxel (14.7% [78 deaths out in 529 patients] vs. 8.1% [27 deaths in 334 patients] crude risk of death, NNH: 14 patients [95% CI: 9–32]).

Katsanos and colleagues wrote that meta-regression showed a significant relationship between exposure to paclitaxel (dose-time product) and absolute risk of death (0.4±0.1% excess risk of death per paclitaxel mg-year; p<0.001). “Trial sequential analysis excluded false-positive findings with 99% certainty (2-sided alpha, 1.0%),” they said.

These data led the authors to conclude that there is increased risk of death following application of

investigator Mårten Falkenberg (Gothenburg, Sweden) saying at the recent VLF: “We are at the moment struggling to make up our mind on how to proceed.”

Industry respond that their data do not support the potential association of increased mortality with paclitaxel use

Speaking to investors at the JP Morgan healthcare conference (7–10 January, San Francisco, USA), executives from Medtronic and Boston Scientific said their data do not show the safety risks cited in Katsanos et al’s analysis. According to Star Tribune, the companies stated that they are not backing away from drug-eluting devices used in blood vessels in the legs, despite the conclusions of the JAHA meta-analysis. Drug-coated balloons (DCBs) from both Medtronic and Boston Scientific (IN.PACT Admiral and Ranger, respectively) were used in the JAHA meta-analysis.

Since, several large industry players presented their own patient-level analysis at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), unanimously concluding that they could find no association between paclitaxel dose and mortality.

Vascular Leaders Forum panel

Katsanos and colleagues report an increased mortality signal with paclitaxel in the femoropopliteal arteries

In the original JAHA paper, published 6 December 2018, Katsanos et al conducted a systematic review and meta-analysis of 28 randomised controlled trials investigating paclitaxel-coated balloon angioplasty or paclitaxel-coated metal stents in the femoral and/or popliteal arteries. In all, 4,663 patients (89% intermittent claudication) were analysed. The primary safety measure was all-cause patient death, analysed at different time points. “Risk ratios and risk differences were pooled with a random effects model,” the authors wrote.

Previous randomised controlled trials have evidenced that paclitaxel-releasing balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularisation after lower

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[The FDA review process is] judicious, straightforward, and spot-on.” paclitaxel-coated balloons and stents in the femoropopliteal artery. “Further investigations are urgently warranted,” they wrote.

This finding prompted the cessation of patient enrolment of three randomised controlled trials within days of its release: SWEDEPAD 1, SWEDEPAD 2, and BASIL 3. At the date of publication of this newspaper, the status of the SWEDEPAD trials is still uncertain, with principal

An independent, third party, pooled analysis of all the IN.PACT Admiral DCB (Medtronic) clinical programmes, published in the Journal of the American College of Cardiology and including 1,980 patients, demonstrated that at five years, there is no statistically significant difference in all-cause mortality between the DCB and the control arm (9.3% vs. 11.2% respectively, p=0.399).

Ranger (Boston Scientific) SFA randomised trial three-year data from 105 patients showed no significant difference in all-cause mortality between DCB and control (13.8% vs.

10.7%, respectively), according to the presentation given at LINC with CEC-adjudicated cause of death.

Results from a Cook Medical press release also demonstrated the safety of their drug-eluting stent, the Zilver PTX. Patient-level data found no

March 2019 increased mortality at five years with Zilver PTX compared to non-coated stents and balloons (18.7% vs. 17.6% respectively, p=0.53).

A pooled analysis of patient-level data from Philips also demonstrates the “strong safety profile” of the company’s Stellarex DCB in abovethe-knee studies, according to a company statement at LINC. The independent, third party pooled analysis evidenced low mortality rates through three years after the treatment with no device-related deaths.

Five-year data from 1,189 patients in the LEVANT 2 trial within the Lutonix DCB (BD) programme showed no statistically significant difference in all-cause mortality between the DCB and the control group (14.2% vs. 10.6% respectively, p=0.22), as described at LINC. However, Medtronic and Cook Medical have since issued corrections to their published data regarding the safety of their devices, the IN.PACT Admiral DCB and the Zilver PTX drug-eluting stent, respectively.

Medtronic announced they have revised IN.PACT post-market study data due to a “programming error,” and Cook Medical note a mistake made during data publication: that two mortality figures were “inadvertently reversed”.

According to Medtronic, mortality data were inadvertently omitted from the summary tables included in the statistical analysis of their data presented at LINC. These deaths were, however, previously included and reported in Medtronic’s database, captured in the appropriate study exit forms and adjudicated by an independent clinical events committee, a press release issued by the company said. Immediately upon learning of this error, Medtronic notified the FDA and the study authors. The company added in the release that while a component of the recent patient-level metaanalysis will need to be updated, it has found the revised analysis still supports earlier conclusions.

Cook Medical announced that in a paper published in Circulation in 2016 assessing the clinical effectiveness of their Zilver PTX stent, the mortality figures for the Zilver PTX arm and the percutaneous transluminal angioplasty (PTA) arm were inadvertently swapped. Responding to this error, Circulation state: “When highresolution files were requested during production, an incorrect version of Figure 1 was mistakenly provided.

Subsequently, the published version of the flow chart in Figure 1 contained incorrect numbers. The authors now provide the corrected version of Figure 1.

“The following sentence from the ‘Safety’ section of the paper is incorrect: ‘The five-year all-cause mortality rate was 13.6% (10.2% for the primary DES group and 16.9% for the PTA group, p=0.03), and no deaths were adjudicated as procedure

Drug-eluting devices

We are at the moment struggling to make up our mind on how to proceed [with the SWEDEPAD 1 and 2 trials].” or device related.’ [...] The sentence should read: ‘The five-year all-cause mortality rate was 13.6% (16.9% for the primary DES group and 10.2% for the PTA group, p=0.03), and no deaths were adjudicated as procedure or device related.’”

Polling results

Polling from the 31st International

Symposium on Endovascular Therapy (ISET; 27–30 January, Hollywood, USA) and from the more recent VLF indicate that the majority of physicians will not change their use of paclitaxel devices following the Katsanos et al meta-analysis. At VLF, 60% (21 out of 35 physicians) of the polled audience said they would not be more conservative in recommending drug or

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device combinations for claudication following the discussion around the JAHA meta-analysis, and 86.5% (32 out of 37 responders) of those polled said they would not change their clinical practice as a result of the meta-analysis findings.

In addition, following a morning-long session at ISET, 79% of the audience responded to an anonymous poll to say that they do not believe the Katsanos et al findings are sufficient to change practice.

Sixty-nine percent of respondents said they would continue to use paclitaxel devices as they always have, with the remaining 31% saying they would use paclitaxel devices less.

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March 2019

Aortic aneurysm repair

European vascular community continues to dispute draft NICE AAA guidelines amidst publication delays At a session dedicated to the draft abdominal aortic aneurysm (AAA) guidelines put forward by the UK’s National Institute of Health and Care Excellence (NICE) at Controversies and Updates in Vascular Surgery (CACVS; 7–9 February, Paris, France), the controversy continued with several arguments against the proposed NICE recommendations in favour of open repair over endovascular aneurysm repair (EVAR).

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he draft document, first published in May 2018, has drawn a significant amount of comments in its consultation period from the UK vascular field. A final publication date, which has been repeatedly postponed since November 2018, remains “to be concluded” with no information currently available regarding potential amendments to the final recommendations.

The uncertainty of the situation was highlighted by Christopher Hammond (St James’s University Hospital, Leeds, UK)—a member of the clinical guidelines committee—who spoke at CACVS about the strictly defined and regulated decision-making process of the draft NICE guidelines. Answering an audience question from Michael Wyatt (Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK) on when the final guidelines may be expected, Hammond stated: “I am as much in the dark as you are. The internal machinations of the NICE process are opaque to me that, frankly, has been a source of quite a lot of anxiety to [the clinical guidelines committee].”

“My personal opinion,” Hammond said, “is that in some of those recommendations [published in May], we went too far. We have already made some changes to the draft recommendations—whether those recommendations remain as modified or whether we

modify them further, I do not know.”

Hammond noted that an extraordinary meeting for the committee was scheduled for the 28th of February, which he said at CACVS he hoped would be the last before the document is finalised, but cannot be certain there will not be more meetings required to “deliberate further”. Speaking to Vascular News in the days following this meeting, Hammond states that although the committee members are still unable to comment on the guidelines before their publication, he would give his assurance that “the committee and NICE take all stakeholder comments extremely seriously and we have considered them in detail. The stakeholder feedback and response exercise is not window dressing and is central to NICE’s concept of procedural equity and justice and has been very dilligently and carefully undertaken.”

A small warning: you need to know that something you do in your country affects others, on a very great scale.”

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Speaking at CACVS, Hammond concluded, “It is important that NICE treads a path between what is acceptable to the community of people treating patients, and what is supported by the evidence within the very clear context of how NICE makes decisions. I think the question we need to ask is whether the role of NICE is to show where we should be going, or accept where we are now and try to iterate towards that—and that is a very delicate balance.”

Arkadiusz Jawien (University of Nicolaus Copernicus, Bydgoszcz, Poland), co-moderating the session, stressed the importance of the guidelines not to take a step in the wrong direction, as Jawien noted that a number of other countries which may not have the funding for a national institution such as NICE, simply base their recommendations and government funded treatment policies on what is published in the UK. Thus, Jawien issued “a small warning: you need to know that something you do in your country affects others, on a very great scale.”

A Special Session at the Charing Cross Symposium (CX; 15–18 April, London, UK) is planned to shed light on the potential impact of the guidelines, in the UK and internationally, once published.

Christopher Hammond

March 2019

Drug-coated balloons

Six-month outcomes of AcoArt II adds to the evidence for drug-coated balloons in BTK arteries Further proof of a role for drug-coated balloons (DCB) in the treatment of below-the-knee (BTK) arterial lesions has been provided by a trial from China. The AcoArt II study compared the performance of Aco Tek’s Litos/Tulip—a magnesium stearatecoated balloon—to standard percutaneous transluminal angioplasty (PTA), and found equivalent safety and superior efficacy.

WEI GUO (CHINESE PLA General Hospital, Beijing, China), presenting at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany) on behalf of the investigators, said: “This is the first randomised trial in China to look at a drug-coated balloon below the knee, and demonstrated the safety and efficacy of this DCB from Aco Tek in treating BTK lesions. The positive results further improve the evidence of DCB for BTK [and] should inspire the further use of DCBs for BTK in clinical practice.”

The primary endpoint of the study was six-month angiographic primary patency, defined as freedom from target lesion occlusion, clinically driven target lesion revascularisation (CD-TLR), and major amputation above the ankle. The key secondary angiographic endpoint was late lumen loss at six months, and clinical secondary endpoints were CDTLR and ankle-brachial indices (ABI), both at six months. Complications were

defined as major adverse events such as death, CD-TLR, and major amputation at six months.

The study was conducted at 11 sites, and 120 patients were randomised 1:1 into DCB or PTA. Randomisation occurred at successful seal crossover, and was followed by pre-dilation and

criteria were total occlusion, life expectancy ≥1 year, and the presence of at least one run-off vessel. Guo clarified: “We excluded lesion lengths greater than 150mm in inflow arteries; that means in this study most of the patients had excellent inflow arteries.”

Patient and target lesion characteristics were similar in both arms: “For the demographic and risk factors, we could not find any difference between the two groups. Over 80% of [DCB] patients were Rutherford 4 and 5, and only 15% were Rutherford 6. About 50% of target vessels were the anterior tibial artery.” Average target lesion lengths were 177±86mm in the DCB arm, and 186±82mm in the PTA arm (p=0.56). “The chronic total occlusion (CTO) range was 75% in DCB and 78% in PTA, so in terms of target lesion characteristics, there is not any difference between the two groups.

And, we could not find any difference in the procedural outcomes.” Provisional stenting was 0% in the DCB arm versus

This is the first randomised trial in China to look at a drug-coated balloon below the knee [and] should inspire the further use of DCBs for BTK in clinical practice.” then treatment, with 61 patients in the DCB arm and 59 in the PTA arm.

Participants were aged 18–85 years, with Rutherford class 4–6 and a BTK target stenosis of >70%. Other inclusion

1.5% in the PTA group (p=0.32), and device success was 100% in both treatment arms.

At 180 days post-op, primary patency in the DCB group was 78.7% (37/48)

Lutonix DCB below the knee proves comparative to standard balloon angioplasty at six months

The safety and efficacy profile of the Lutonix drug coated balloon (DCB; BD) in difficult lesions in below-the-knee (BTK) arteries is comparable at six months to standard balloon angioplasty, with the benefits being amplified in more complex patients, an ongoing study reports.

CO-PRINCIPAL INVESTIGATOR OF the Lutonix Global BTK trial, Jihad Mustapha of the Advanced Cardiac and Vascular Amputation Centre in Grand Rapids, USA, presented six-month outcomes in difficult lesions at the Leipzig Interventional Course (LINC; 22– 25 January, Leipzig, Germany). Mustapha announced that “in terms of safety, the DCB and the percutaneous transluminal angioplasty (PTA) arms were almost the same. So, there is no safety signal here to worry about.”

Discussing the primary safety endpoint which was attained at one month, Mustapha noted “at 30 days it was good, but then we followed that through at six months and there was no change in terms of safety.”

Referring to a Kaplan-Meier analysis comparing efficacy of the treatments, a separation in favour of DCB was observable at 30 days, which then continued all the way to six months, “giving us for the first time an 85.3% DCB primary patency at 180 days, [a difference of] 14.6% DCB versus PTA [70.7% patency at 180 days].”

Rutherford category 5 patients, the DCB arm saw a 79.4% primary patency rate at 180 days, as compared to 61.6% for PTA in Rutherford 5 patients.

The prospective, multicentre, single-blinded,

randomised controlled trial aimed to demonstrate the superior efficacy and non-inferior safety of the Lutonix drug-coated balloon compared to standard PTA for treatment of stenosis or occlusion of BTK arteries. Participants were enrolled at 51 sites in eight countries between June 2013 and December 2017, and randomised 2:1 to Lutonix DCB (287) or standard PTA catheter (155).

Baseline characteristics were similar in both arms of the study, with “no difference in the demographics and risk factors between the DCB arm and the PTA arm,” Mustapha explained, with “no significant difference” in terms of co-morbidities. However, the DCB arm had 40% more TASC C and D lesions than the PTA group, and mean lesion length was longer.

Mustapha added that for the reference vessel, the average diameter was 2.5mm for the DCB arm and 2.6mm in the PTA arm, “and then run-off present through the foot—because you want it to cross the ankle—again, there was no difference between the two.”

Preliminary baseline angiography data for treated lesions showed that most of the treated target vessels had a single lesion (DCB 85.4%, 275/322; PTA 79.2%,

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vs. 28.3% (13/46) in the PTA arm (p<0.001). “The primary endpoint 180 days post-operatively demonstrates the superior performance of the DCB in treatment of the BTK arterial lesions; 78% [DCB] vs. 28% in PTA. The Kaplan-Meier curve of the primary endpoint at six months also are significantly different; 88% in DCB and 76% in PTA [p<0.001].”

Secondary angiographic endpoints showed that minimum lumen diameter at six months was 1.33mm for DCB subjects and 0.49mm for PTA (p<0.001), with late lumen loss of 0.35mm in the DCB group versus 1.08mm in PTA patients (p<0.001). CD-TLR was 4.9% (3/61) for participants in the DCB group compared to 20.3% (12/59) after PTA (p=0.006), and six-month ankle-brachial index showed a significant improvement following DCB (0.86 DCB vs. 0.77 PTA, p=0.04).

Data on 30-day safety shows, Guo added, “no difference between the two groups, and major adverse events at six months are also not any different.”

Furthermore, looking at mortality during follow-up, he explained: “Only one patient died in the DCB group, because of respiratory failure after pulmonary infarction; 12-month and 24-month [follow-up] is on-going, and we cannot find any difference.”

The researchers also reviewed the findings on accumulated deaths from the earlier AcoArt I SFA trial (n=200) and found no differences in mortality or morbidity between groups.

Guo indicated that although the findings from AcoArt II had been positive, follow-up would continue in order to determine longer-term outcomes.

145/183), and that the majority of interventions took place in the anterior tibial (AT) artery.

The primary safety endpoints were freedom from major adverse limb events and all-cause perioperative death at 30 days, as well as above-ankle amputation and major re-interventions, such as a new bypass graft, a jump/interposition graft revision, or thrombectomy/thrombolysis. The primary efficacy endpoint was a composite of limb salvage and primary patency at six months, which was defined as freedom from a composite of above-ankle amputation, target vessel occlusion, and clinically driven target lesion revascularisation (CD-TLR).

Investigators found that the primary safety endpoint at 30 days was 99.3% (283/285) in the DCB arm, and 99.4% (154/155) in the PTA arm (p<0.001). According to Mustapha, a “snapshot of all-cause mortality to date—so, up to three years,” demonstrated that “there is no difference between the two arms. There is no increase in mortality in the DCB arm versus the PTA arm [DCB 40/287 (13.9%), PTA 20/155 (12.9%)].”

The sub-analysis of patients classified as Rutherford 5—“by definition, more complex patients; longer lesions, more calcification, and actually more severe calcification”—showed that they in fact fared the best of all patients treated. “Looking at the safety of Rutherford 5 versus all DCB,” Mustapha reiterated, “we did not see any significant difference. It was the same at six months between all groups. Looking at the efficacy of Rutherford 5 class versus all drug-coated balloon, of all the patients in the study, Rutherford 5 patients benefitted the most, with an 18% efficacy [benefit] in the Rutherford 5 versus 15% efficacy [benefit] in all DCB.” Further clinical follow-up is planned for 12, 24, and 36 months.

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March 2019

Conference coverage

Three-year Japanese results show IN.PACT Admiral DCB offers “consistent and durable” treatment The IN.PACT Admiral drug-coated balloon (DCB; Medtronic) exhibits a consistent and durable treatment effect in “a more complex patient demographic than typically seen in other DCB pivotal trials”, Osamu Iida (Kansai Rosai Hospital, Hyogo, Japan) informed the audience at the Leipzig Interventional Course (22–25 January, Leipzig, Germany). These are the first reported outcomes from an independently-adjudicated, randomised, single-blind trial evaluating DCB use in Japanese patients through to three years, providing level I evidence in favour of the device’s use.

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he study investigators set out to assess the safety and efficacy of the IN.PACT Admiral DCB for the interventional treatment of de novo and non-stented restenotic lesions in the superficial femoral artery and the proximal popliteal artery as compared to treatment with standard percutaneous transluminal angioplasty (PTA).

The trial met both its primary effectiveness and primary safety endpoints at one year, and continued to demonstrate safety and efficacy at three years. The primary effectiveness endpoint was primary patency at 12 months, defined as freedom from clinically-driven target lesion revascularisation (TLR) and freedom from restenosis as determined

by duplex ultrasound-derived peak systolic velocity ratio (PSVR) less than or equal to 2.4.

Three-year primary patency by Kaplan-Meier estimate was significantly better in the DCB arm than the PTA arm: 68.9% compared to 46.9%. At one year, this difference was even more marked, with a primary patency in the DCB arm of 93.9%, compared to a primary patency of 46.9% in the PTA arm at the same time point.

The time to clinically-driven target lesion revascularisation was also significantly greater in the DCB arm, nearly four times longer in fact, at an average of 613.2±243.1 days (range: 235– 910 days), compared to just 168.2±65.4

days (range: 57–247 days) amongst the PTA cohort (p<0.001). In addition, although not statistically significant, the three-year freedom from clinically driven TLR was slightly better in the DCB arm, at 84.4% versus 81.3% in the PTA group.

The primary safety endpoint was freedom from device- and procedurerelated death through 30 days, and freedom from target limb major amputation and clinically-driven target vessel revascularisation within 12 months’ post-index procedure.

Iida told the LINC audience: “The 36-month major adverse event rate was very low in the DCB arm, just 20.9% [14 out of 67 patients], compared to 31% [9 out of 29 patients] in the PTA arm.”

The primary safety composite score was 83.6% for the DCB cohort, and 75.9% for the PTA cohort. All-cause death was low in both groups: 6% (four out of 67 patients) in the IN.PACT Admiral group, and 6.9% (two out of 29 patients) in the angioplasty group.

Iida also emphasised that these results in the IN.PACT Japan trial are consistent with those of the previous IN.PACT Global and IN.PACT SFA studies. The primary patency through to three years in the IN.PACT Admiral cohort of the Japan trial closely matches the 69.5% primary patency observed in the DCB arm of the IN.PACT SFA trial. Clinicallydriven target lesion revascularisation was 14.9% in the Japanese trial, compared with 15.2% in the IN.PACT SFA trial and 23.5% amongst the global clinical cohort.

A complex patient cohort

Iida described the patient cohort used in this trial as “a more complex patient demographic than typically seen in other DCB pivotal trials.” The average age in the DCB arm was 73.3±7.4, and the incidence of diabetes mellitus was high: 58.7% in the treatment group (40 out of 68 patients). In the PTA arm, the baseline characteristics were not statistically significantly different, with an average age of 74.2±6.1, and with 56.3% of the 32 patients being diabetic.

“This population is older, and has a higher proportion of diabetic patients, than is typically seen in other DCB clinical trials,” Iida said.

Lesion characteristics were also the same between the two arms of the study. The mean lesion length was 9.15±5.85cm in the 68 patients treated with the DCB, and 8.89±6.01cm in the 32 patients treated with angioplasty—“one of the longest [average lesion lengths] in any DCB trial”, according to Iida.

The difference in mean lesion length between the DCB and PTA arms was not statistically significant (p=0.838).

Unique to this trial, the study investigators used intravascular ultrasound (IVUS) to evaluate the ideal diameter for balloon selection. Iida explained that “IVUS is generally used by the Japanese physician as a part of daily practice.”

He added, “We observed a very low provisional stenting rate of 4.4% in the DCB arm, versus 3.1% in the PTA arm.”

Mortality from ruptured aneurysms decrease, but 43% occur in people not qualified for screening Even though the number of deaths due to ruptured aortic aneurysms (rAAA) has decreased in the USA by 68% in recent years, a significant number of deaths from ruptured aortic aneurysms occur in patients whose demographics exclude them from screening guidelines, according to a newly published study in the Journal of Vascular Surgery.

SPECIFICALLY, 34% OF deaths occurred in women and 9% occurred in men under age 65. Screening guidelines recommend screening men age 65 and older who have either smoked or a first degree relative with aortic aneurysm.

Ruptured aortic aneurysm has a very high mortality and is currently the 15th leading cause of death in US men over the age of 65. Over the past several decades, significant attention has been given to this disease in the form of risk factor modification, screening programmes and endovascular therapy for ruptures.

The mortality rate due to ruptured aortic aneurysm in the USA is not well-studied, as previous research

has focused on inpatient settings, operative mortality, specific communities or older data sets. The questions that remain include whether such improvements have had an impact on aneurysm mortality in the USA, and whether further improvements can be made to reduce this mortality.

Researchers, led by University of Chicago vascular surgeon Ross Milner, performed a retrospective review of the national death certificate data from the US National Vital Statistics System to study deaths due to ruptured aortic aneurysm between 1999 and 2016.

Of 104,458 deaths, the mean age was 77±11 years, 62% were male, and 92% were white. The overall age-adjusted incidence of fatal ruptures was 23 per one million; specifically, abdominal, 15.1 per million; thoracic, 3.1 per million and thoraco-abdominal, 0.4 per million.

Importantly, the annual incidence of rupture decreased by 68%, from 40 per million in 1999 to 13 per million in 2016. These trends were consistent across age groups, gender and race.

Other notable trends included a seasonal variation, with the highest rupture rates in winter, and a regional variation, with the lowest rates in the southern USA. “The reason for this significant decrease in mortality due to ruptured aortic aneurysm remains speculative,” Milner noted, “but is likely multifactorial, including risk factor modification, population screening, improvement

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This study highlights the significant strides that have been made to decrease mortality from aortic aneurysm in the USA over the past decade.” in regional centralisation, adequate emergency preparedness, and improvement in surgical care.”

He also noted the significant number of rupture deaths in patients not currently included in screening guidelines. Specifically, 43% of deaths occurred in either women (34%) or men under 65 years old (9%).

“Further studies are required to identify the efficacy and cost-effectiveness of population-based screening for aneurysm in women,” Milner said.

Undoubtedly this study highlights the significant strides that have been made to decrease mortality from aortic aneurysm in the USA over the past decade. This data furthers understanding as to the specific populations at higher risk for rupture and may suggest improvements in the criteria for screening, a statement from the Society for Vascular Surgery notes.

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March 2019

Advertorial

Sponsored by Lombard Medical

Altura Endograft System: A unique tool in the endovascular armamentarium Endovascular repair presents a safe and effective treatment method, but late failure of endovascular aneurysm repair (EVAR) and endoleak both remain a problem for vascular specialists. A recent paper in the Journal of Vascular Surgery1 has reported an independent association between late mortality and AAA sac diameter increases, irrespective of endoleak, and more than 50% of patients with sac expansion had no identifiable endoleak. Deery et al concluded that sac expansion of at least 5mm at one year warrants potential early intervention. Vascular News speaks to Dainis Krievins (Pauls Stradins Clinical University Hospital, Riga, Latvia), David Murray (Manchester University, Manchester, UK) and Paul Hayes (Cambridge University Hospitals) about the causes for EVAR failure, and how the Altura endograft from Lombard Medical can help vascular surgeons to navigate some of these challenges.

Why might late EVAR failure occur?

Hayes: Aneurysm sac expansion post EVAR usually represents some form of treatment failure. We are fairly good at diagnosing type I and II endoleaks, but a large proportion of patients with post-EVAR sac expansion do not have an identifiable endoleak.

For me, I think there are more cases of device integrity failure than we recognise. Over five years, an EVAR graft is subjected to around 200 million cardiac cycles and it would be a great surprise if there is no loss of fabric integrity in at least some of the devices.

We have treated cases in the past with no endoleak on a CT scan but an enlarging sac, that we have opened to explant and there are multiple small holes in the graft fabric, especially where sutures fix the fabric to the stent.

Murray: Late endograft failure can occur for a variety of different reasons related to aortic neck expansion or inadequate seal length and quality, iliac arteries length or dilation. or the aortic stent graft itself such as type III endoleak or limb dislocation.

Krievins: One reason for EVAR to fail is as a consequence of neck dilatation leading to endoleak or migration of the proximal end of the device. I believe the three most usual causes of neck dilatation include radial force from stent grafts, an underlying pathology of aneurysmal disease, and the presence of type II endoleaks which will pressurise the aneurysm and eventually, dilatation of the neck. Usually there is a component of all three causes when an EVAR fails.

Another reason for late EVAR failure is structural failure of the device, either by modular disconnection or by graft fabric damage; the classic type IIIa and IIIb endoleaks. Finally, a third reason for late EVAR failure is continued sac expansion without obvious endoleak— the so-called type V endoleak or “endotension”. As the cause for these failures is less specific, planning treatment can be more troublesome.

How does the Altura endograft meet these challenges?

Krievins: Altura is a dual lumen stent graft for its full length and therefore has no flow-divider. The endograft has recently been used to reline entire stent grafts and, where anatomy is

appropriate, reestablish a juxtarenal seal zone.

This means it can be possible to treat type I and type III endoleaks. When re-lining EVAR devices with other conventional Dainis Krievins EVAR implants, it is often difficult to fit a bifurcated device above the flow divider of the primary graft. The lack of a flow divider in Altura allows it to fit into short aortic bodies and maintain flow to both limbs. Other approaches might involve use of an aorto-uniiliac graft with femoral to femoral crossover, which is probably a less attractive solution.

Murray: I am very much of the view that the design of the Altura stent graft lends itself to deployment in healthy aortic neck and should always be deployed with the IFU. This will allow a healthy aortic seal of up to 15mmm, which can be off-set to renal arteries, maximising aortic coverage. We have also deployed the Altura to reline previous failed historic stents with type III endoleak at the flow divider. In these cases, assuming there is no aortic neck dilation or migration, the Altura is an easy relining fix, particularly in previous aortic stents with a relatively short main body.

Hayes: Whether it is being used to extend a migrated EVAR proximally, or reline a failing graft, Altura has a great advantage over other devices in that its two D-shaped main bodies allow a bifurcated repair to be performed inside a short EVAR main body. I do not think there is currently another CE-marked device that can do this routinely without resorting to a uni-iliac and crossover solution. The retrograde deployment of the limb segment of Altura allows highly accurate placement at the iliac bifurcation if clinicians are trying to repair a type IB leak in a fairly short common iliac artery.

How does Altura compare to other endovascular stent grafts in this setting, and what factors may contribute to a lasting relevance in the EVAR treatment space?

Hayes: I think there are a couple of Altura features that are important

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Can you tell us about a recent case of using Altura?

David Murray

Paul Hayes

Krievins: Last year I held a workshop for future Altura users. On the morning of the workshop, we admitted a 78-year-old male patient with abdominal/back pain and hypotension.

An emergent CT angiography scan confirmed the diagnosis of a ruptured abdominal aortic aneurysm, and we were able to use spare devices from our workshop to exclude this patient’s aneurysm under local anaesthesia.

Sizing with Altura was helpful in this instance as there are only three proximal and three distal diameters to select between. The limbs ‘trombone’ within the aortic implants so the implant was adjusted to length on the table. The patient was discharged four days later and is doing well.

Hayes: The last case we treated was a patient with short, calcified iliac vessels. The iliacs were both less than 3cm in length and the retrograde deployment of the limb stents allowed us to use all of the available length as we landed within a couple of millimetres of the iliac bifurcation. The braided stent used in the Altura is useful in calcified vessels, and also those with tight aortic bifurcations, to help maintain patency. We have not seen a single limb occlusion so far in our Altura cases. I have been contemplating the value of Altura for CERAB type cases but as yet we have not used it in this role, although I am sure before long someone will.

Murray: I am always struck by the simplicity of the 14F Altura stent system, the quick procedure time, low contrast and radiation dose per case.

However, the most striking clinical manifestation of this is the patients’ ability to recover and mobilise very early. We perform almost all Altura cases percutaneously now and the vast majority of cases are discharged at <24hrs. This has introduced the concept of day case EVAR, particularly for patients operated at the start of the list, for whom assuming local geography if favourable, are almost always ready to go later that evening if they wish.

in this regard. The first is the ability to reposition the proximal end of the device after initial deployment, enabling us to get a millimetre perfect placement each time. Secondly, the fact that the main body has been divided in two means that there has not needed to be any compromise on fabric thickness to achieve a low-profile solution. The fabric is the closest I have seen to our durable surgical grafts being used in an endovascular solution.

Krievins: Altura is currently the only available device that has two lumens for its entire length, and this is its primary advantage in this application.

The delivery systems are 14F, which can aid access and the flexibility of the graft is also good. Altura also has long proximal bare stents with active fixation to resist distal migration.

Last year we published data on the primary use of Altura in the Journal of Endovascular Therapy, updating the evidence for the endograft with encouraging four-year results presented at VEITHsymposium last November. We still need to see greater quantities of data, which the company is now collecting in its registry.

Murray: We now have about 30 patients in our experience in Manchester that have been followed out to three years post implant. We have not noted any elective type I endoleaks and the aortic necks have been stable in diameter.

Similarly, because of the bimodular system, we have not observed limb related dislocation. Furthermore, as the iliac deployment is retrograde allowing very References accurate common iliac 1. Deery SE et al. Aneurysm sac expansion coverage, we is independently associated with late mortality in patients treated with have observed endovascalr aneurysm repair. J Vasc Surg 2018 January; 67(1): 157-164. no type Ib endoleaks.

Altura Endograft System

March 2019

Conference coverage

Staged open repair for TAAA sees fewer complications and deaths Michael Jacobs (European Vascular Centre, Aachen-Maastricht, The Netherlands) led delegates attending the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany) through recent data which favours a staged open repair in thoracoabdominal aortic aneurysms (TAAA) over a single procedure, with reduced morbidity and mortality seen after a staged open repair process.

“THERE ARE ARGUMENTS for staging a procedure in addition to the collateral developments. There is a huge difference between a single cavity operation—it is much less traumatic if you only do the chest or the abdomen, instead of doing both cavities as there is reduced blood loss and need for transfusion, and, therefore, there are reduced inflammatory responses, which is crucial. There is also less renal failure. This all adds up to lower risks of spinal cord injury.”

The effects of extracorporeal circulation inflammatory provocation have been examined in many studies, as has its influence on systemic inflammation and the impact on serious sequelae and complications. “The greater the surgical trauma, the higher chance there is to develop these kinds of intensive care problems after the operation.”

A study from the European Vascular Centre, AachenMaastricht, Germany, will shortly be published in the European Journal of Vascular and Endovascular Surgery. Jacobs gave delegates a glimpse of the findings on the outcomes after staged versus unstaged open

repair of type II TAAA. Type II signified the most extensive operation—from the left subclavian down to the iliobifurcation.

A comparison of 76 open single procedures vs. 18 two-stage procedures, either hybrid (n=6) or open (n=12) TAAA, reveals “dramatic differences when it comes to mortality. If we look at the most important morbidities, they were not so different between the two groups. However, the paraplegia rates were significantly

The greater the surgical trauma, the higher chance there is to develop these kinds of intensive care problems after the operation.”

Lessons learned from underpowered results of the DEFINITIVE AR trial Physicians should be wary of spending time, effort, and money on studies that provide minimal scientific gains. said Aljoscha Rastan (Bern University Hospital, Bern, Switzerland) at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), reviewing the DEFINITIVE AR study of directional atherectomy and anti-restenotic therapy (DAART). Due to the study protocol, Rastan concluded the performance of the treatment remains “unclear”, and told LINC delegates to carefully review study protocols before undertaking new research, cautioning: “Do not waste your time, the time of your staff, or your research funds on studies that have limited or no scientific value.”

THE STUDY, PUBLISHED by Thomas Zeller and colleagues in Circulation: Cardiovascular Interventions (2017), was a prospective randomised multicentre study to assess the effect of treating lesions with directional atherectomy followed by a drug-coated balloon (DCB), versus treatment with DCB alone in patients with femoropopliteal artery disease. “This study is a good example,” Rastan noted, “As I am not sure whether we learned any lessons. The very low numbers of patients included in this trial is a major limitation of the results.” Zeller et al concluded that although the DAART treatment was “effective and safe, [...] the study was not powered to show significant differences between the two methods of revascularisation at one-year followup”, calling for an adequately powered randomised trial to investigate further.

Inclusion criteria of DEFINITIVE AR were Rutherford class 2–4, ≥70% stenosis of the superficial femoral artery (SFA) and/or the popliteal artery, and lesion length of 7–15cm. Exclusion criteria included in-stent restenosis, and multiple lesions in the target limb that required treatment. However, Rastan highlighted that patients with heavily calcified lesions were included but they were not randomised: “They were treated in a separate arm of the study, also with the DAART procedure.”

Following general and angiographic assessment, 48 subjects were randomised to DAART, and 54 to treatment with DCB alone, while a further 19 participants with severely calcified lesions were also treated with DAART. There were no significant differences between the groups’

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different between the one and two-stage procedures”.

Hospital mortality following unstaged open repair was 22.4% (17/76) vs. zero for both two-stage procedures, with one- and five-year survival rates of 74.7% and 53% for unstaged as compared with 90.9% survival at both one and five years after a two-stage open procedure, and 100% for both following a hybrid procedure.

The paraplegia rate for the single stage procedure was 10.5% (8/76) compared to 8.3% (1/12; p=1) for staged open repair, and zero for the staged hybrid procedure.

This supports findings from Etz et al (2010) looking at TAAA II single procedures versus staged descending and II-IV repair: “They also found that in the type II single procedures versus the staged there was a significant difference between the paraplegia rates [15% paraplegia versus none].”

Jacobs outlined his centre’s approach to the procedure, which involves “assessing the spinal cord perfusion, where the motor-evoke potentials within the hands and the legs are assessed. If we lose evoke potential in the legs, there is a problem in conduction and in the spinal cord. We have performed magnetic resonance studies, pre- and post-type II repairs, and have seen dramatic changes.”

He summarised: “In open repair [TAAA] type II, but also type III, we stage if technically feasible and start with the most threatening part first. You need large diameter grafts, and the interval is at least four weeks between the procedures. Of course, there is a potential danger when the patient is waiting for the second procedure that the aneurysm ruptures.”

patient characteristics. Although lesion characteristics were similar between groups for diameter stenosis, reference vessel diameter, occlusion rates, de novo lesions, and TASC classification, Rastan pointed to a significant difference in lesion length between DAART patients and patients treated with DCB alone, describing it as a “major limitation of this study”. For non-randomised participants with severe calcifications (n=19), lesion length was 118mm. Among randomised subjects, the DAART group (n=48) had a lesion length of 112mm, while DCBalone subjects (n=54) had a lesion length of 97mm (p=0.05). Furthermore, looking at procedural complications, including perforations following atherectomy and distal embolisations, Rastan commented: “We have to expect distal embolisations, major distal embolisations, even if we have a protection device in place like in this case—100% distal embolic protection device [for the non-randomised group] in place—and still we see some distal embolisations [5.3%, 1/19]. As for arterial perforations, we see that a few times after atherectomy; however, the risk of this is very low, and we can treat these perforations very easily with endovascular procedures.” There were no dissections of grade C/D or greater for the nonrandomised group treated with DAART; within the randomised arms, those treated with directional atherectomy plus DCB had a rate of 2.1% (1/48), with a rate of 18.5% (10/54, p=0.009) in those treated with DCB alone. High-grade dissections “were treated with prolonged dilatation and bailout stenting. The bailout stent rate in the DCB arm is very low [3.7%]; usually, I would expect a 7–8% bailout stenting rate”, commented Rastan.

At one year, the primary patency

Aljoscha Rastan

rate on angiography was 50% for the non-randomised subjects, 82.4% in those randomised to DAART, and 71.8% for those randomised to DCB only (p=0.41). On duplex ultrasound, the patency rate was 68.8%, 84.6%, and 81.3%, respectively (p=0.78). “There is no difference in the patency rate”, Rastan stated. “There is a trend towards better patency rates of the DAART group; however, we miss the edge of significance.”

Although the study was underpowered, the authors performed a sub-group analysis, pooling patients from both the randomised arms and the nonrandomised arms with long lesions (>10cm), for which Rastan noted “the trend was more obvious in favour for patients with the DAART procedure.

This was also the same for patients with severe calcification. But the cohorts are very small and what we see now is [...] probably just guesswork about what is the meaning of the truth behind these results.”

As a result, he concluded, the performance of DAART in femoropopliteal arteries in comparison to DCB treatment alone is “still unclear”.

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March 2019

Imaging

Assessing fibreoptic technology as an alternative to fluoroscopy

The use of Fiber Optic RealShape (FORS) technology for 3D navigation in endovascular repair is a feasible alternative to fluoroscopy. This conclusion was presented by Joost van Herwaarden, Department of Vascular Surgery at the University Medical Center in Utrecht, The Netherlands, at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

ACCORDING TO VAN Herwaarden, FORS-enabled angiographic devices are currently not commercially available, but there are three investigational devices for research—a hydrophilic guidewire, a Cobra catheter, and a Berenstein catheter (both Philips). These three devices were used to perform the clinical feasibility study, which looked at feasibility of using FORS technology in endovascular aortic and peripheral procedures.

FORS is the result of a collaboration between the medical centre and Philips; together they spent about eight years developing the alternative to X-rays.

The catheter and wires have optical glass fibres incorporated. By sending pulses of light through these fibres, the devices can be reconstructed and visualised in 3D and in real-time. In addition, white dots on the tips of the wires and catheters make it possible to determine the direction in which they are pointing. van Herwaarden explained that “more than 99% of cases [of endovascular procedures] are done by fluoroscopy. In my opinion, there are too many drawbacks of fluoroscopy.”

Among the drawbacks outlined by van Herwaarden are the lack of colour in imaging, the method of imaging in

2D rather than 3D which in certain circumstances can make “navigation more difficult than necessary”, and the harmfulness of X-rays to both patients and operators.

FORS investigators enrolled consecutive patients scheduled for standard or complex (fenestrated/ branched) endovascular aortic repair (EVAR), or for iliac or superficial femoral artery (SFA) percutaneous transluminal angioplasty, between July and December 2018. Of the 21 participants, 13 had EVAR, and eight had a peripheral endovascular intervention. They found that 60 of the 67 (91%) navigation tasks were completed successfully using a FORS-enabled guidewire and/or a FORSenabled catheter. Seven tasks were not completed successfully, according to van Herwaarden, “simply because we did not have the right shaped catheter available”.

Investigators rated the quality of the FORS image-based guidance as “better than standard guidance” in 16 cases (76%), and “at par with standard guidance” in five cases (24%).

Addressing the LINC audience, van Herwaarden shared some “remarkable moments” from challenging cases

to emphasise the benefits of the new technology over fluoroscopy. In one patient, moving to the aorta through a tortuous iliac artery was proving difficult.

Using the caudo-cranial rotation of the anatomy to move the image and create multiple unrestricted viewing angles allowed visualisation to determine whether the wire had turned back on itself, or had moved through a kink. As a result, “without X-ray, we managed to go quite quickly through this iliac artery.

This viewing angle that made navigation relatively simple would have been impossible with a C-arm.”

The second case he highlighted required cannulation of a contralateral limb within a deployed stent graft. The simultaneous use of two single shots in different angles made it possible to navigate without fluoroscopy. “We made two images in different angles, and you can use those images as a roadmap. Working like this we have two angles—bi-plane overlay—and that, in combination with 3D visualisation of the catheter and wire, makes is quite easy to get into this contralateral limb.”

Finally, a third case which presented a challenge navigating through stenotic

Fusion imaging allows instant repair of endoleaks and reduces radiation Fusion imaging during endovascular aneurysm repair (EVAR) reduces radiation compared to standard treatment of angiography, and allows reliable detection and correction of endograft-associated complications and endoleaks: this is the view of Dittmar Böckler (University Hospital Heidelberg, Heidelberg, Germany). He was speaking the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), outlining the choices of intraoperative imaging modality available for endoleak detection.

“E

ndoleaks are a major reason for death, and the leading reason and cause of revision of the EVAR in the long term,” Böckler cautioned. “It is important to detect endoleaks very early, on the table during EVAR, and to correct that immediately.

[Fusion imaging] reliably detects endograft associated complications. It has a high sensitivity to detect endoleaks during your EVAR procedure. You can really minimise reinterventions [and] the whole radiation dose can be reduced for a patient during a hospital stay.” Although angiography is the standard method of imaging for EVAR, Böckler introduced delegates to new tools that are now available to detect and correct endoleaks in the early stages of a procedure. One advantage they have over conventional treatment is the reduction in radiation levels, currently a “leading topic in endovascular treatment of arterial disease”, he said.

There are various means by which this can be achieved, including during the preset stage, or by introducing modifications such as decreasing the frame rate, or by a reduction in the set dose. Improved surgeon skills also play a part, as does

applying collimation, shorter acquisitions, avoiding magnification, or employing contrasted fluoroscopy or cone beam computed tomography (CT) during an aortic endovascular procedure.

Böckler further outlined the impact that applying these changes in his own centre has had on the dose for a standard renal EVAR procedure, with a reduction between 2012 and 2017 from 283.9 to 66.6Gycm2. “We implemented fusion imaging in the last eight years,” Böckler stated. “By using pre-operative CT angiography fusion with fluoroscopy on the table followed by registration, you can really reduce your radiation exposure to the patient and staff, and not really lose any quality of imaging, with good outcomes for your procedure. There is growing evidence for fusion really helping to have better outcomes and less interventions.”

A meta-analysis of seven studies on the impact of fusion imaging showed significant reduction in contrast and radiation in fenestrated EVAR (FEVAR), branched EVAR (BEVAR), thoracic EVAR (TEVAR), chimney technique EVAR (ChEVAR), and standard EVAR. “These were really convincing results,” Böckler

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said, “showing that fusion imaging is a part of daily practice and should be standard, at least in complex anatomies as well as for FEVAR and BEVAR.” Another technique highlighted in the session was contrast enhanced cone beam CT, which uses rotational angiography to automatically transfer information within seconds to a CT-like reconstruction.

Böckler described it as a “hot topic in the world of researchers, and in the literature”, with growing evidence in favour of its use. “There are very few papers out there—very low numbers so far—but increasing evidence shows that DynaCT (Siemens) really helps to detect endoleaks and to repair them in the same setting.”

Trials demonstrated that the reintervention rate was reduced from 31% to 7%, with 7% immediate reinterventions due the diagnosis of endoleaks or limb stenosis on intraoperative cone beam CT. Comparing Dyna CT (cone beam) with CT, he said: “Really there is no big difference—cone beam CT really can detect endoleaks, and you can correct them immediately. Sometimes [with CT] you miss them, and have to go back next day to correct them. Cone beam CT technology

vessels. “The patient had severe stenosis of the superficial femoral artery”, explained van Herwaarden. “What is important is that, because we have these distinctive colours of the catheter and [guide]wire, we can just use the normal regular black angiogram as an overlay which gives you much more detail. I think it is a big benefit. Furthermore, although it was a thin vessel, the wire and catheter went really smoothly through these diseased vessels.”

Reiterating that it may be some years before the technique becomes commercially available, however, he surmised that “endovascular procedures using FORS technology are feasible—we can navigate without fluoroscopy, we get clear 3D visualisation of wires and catheters, we can use multiple unrestricted viewing angles and bi-plane visualisation, and we can use a regular angiogram or any other X-ray image as a roadmap.”

In terms of what the future holds, van Herwaarden said: “FORS appears to be a very promising new technology that has huge potential to improve endovascular procedures, although expansion of the platform and further research to prove the benefits are needed.” is available and is a sensible and sensitive tool to detect endoleaks.” Böckler added that other events, such as intraluminal thrombus, can also be detected and immediately repaired.

Looking at how fusion imaging has altered workflow in the peri-operative assessment of EVAR, FEVAR, and BEVAR, he pointed out that “now, we go with fusion imaging to immediate evaluation on table, repairing if needed, and then we follow up with post-operative contrast enhanced ultrasound [CEUS].

We do Dyna CT whenever possible, and do immediate revision if we detect an endoleak or any other complication.”

Future options in fusion imaging, Böckler said, include 4D contrast enhanced cone beam CT (ceCBCT), which uses time resolutions imaging to provide different shading between late type I or type II endoleaks: “This is ongoing research, but it may help for the future in being really secure in defining the type of endoleak on table”. Additionally, colour-coded 2D DSA (syngo iFlow; Siemens) which supports endoleak categorisation is reportedly “also under investigation”.

Although, Böckler noted, the incidence of additional intraoperative corrections in the second stage is 7%, overall, fusion imaging is beneficial. “You reduce operating time, you reduce risk for the patient, and radiation. Cone beam CT can reduce case specific overall radiation per hospital stay […] because you minimise your angiography, and you skip your pre-discharge CT scan. And the reduced reintervention rate, due to on-table assessment, gives better outcomes for the future.”

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March 2019

Interview

A year in profiles The last year of Vascular News profile features have seen pioneering and influential leaders of the vascular and endovascular fields share some of their most important lessons and advice based on long, notable careers. This overview of their individual in-depth interviews is an annual look back at the insights and experiences they discussed.

Tilo Kölbel

C

oming from a family of medical professionals, Tilo Kölbel was destined to become one himself. He tells Vascular News about why in particular he chose to enter the vascular field, and comments on new vascular technology he is watching closely.

“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,” Kölbel says.

“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.”

With regard to new technology, he comments: “I follow closely developments such as the spidergraft for thoracoabdominal 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.”

Alison Halliday

A

s her term as the first female president of the European Society for Vascular Surgery (ESVS) came to an end in 2018, Alison Halliday reflected on what she achieved and the future of the society. “As the first woman to be elected president, other women in vascular surgery have, I hope, been encouraged to apply for office,” Halliday says.

“My aims on election were to increase diversity in ESVS and we have made significant moves (including the appointment of a diversity ‘councillor’) to improve this; at ESVS I also created the Global Village—where every country is given free exhibition space to showcase their vascular services and their culture, as well as providing a networking space for the duration of the meeting.

“Finally, I still plan to study the Minimum Standards for Vascular Services in Europe—with my colleagues, I hope we can then demonstrate to European states the areas in which their future services may be usefully

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improved.”

On encouraging women to become vascular surgeons, Halliday comments: “There are now many more women trainees in Vascular Surgery and some more Consultants. Mentorship has improved, but there is no doubt that women have to work hard to keep both the home and the job running smoothly.”

She continues: “Perhaps the biggest barrier women face is making the long-term choice to stay in surgery, even though their ability and patient commitment is not in doubt. One very positive factor is the “team” development, which is a better environment than the stand-alone consultant of the past—everyone appreciates good colleagues.”

Halliday told Vascular News, proudest moment of her career is “having my family at my graduation and my inaugural lecture as a professor, presenting the results of the first ACST trial and becoming president of the [ESVS]”.

March 2019

Gustavo Oderich

O

riginally from Porto Alegre in the south of Brazil, Gustavo Oderich speaks to Vascular News about his current research interests and the advice he would hope his mentees/fellows will always follow.

Oderich comments on how, at the Mayo Clinic, Minnesota, “we have built an advanced clinical research programme that is responsible for designing and conducting several prospective studies, many in conjunction with industry. We currently have a team that involves a research manager, two coordinators and two advanced post-doctoral clinical research fellows. We also offer hands-on three-month advanced training on fenestrated and branch endografting. Our team helps conduct over 25 device trials and two physician-sponsored device exemption protocols, which have enrolled nearly 300 patients in a prospective study.”

He continues to explain the “goal is to provide the highest possible quality of clinical data and level of evidence. […] Recently, we have presented at the Vascular Annual Meeting (VAM) a comparison of digital subtraction angiography, cone beam computed tomography (CT) and postoperative

Interview

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CT angiography. In that study, cone beam CT detected nearly all technical problems and decreased early reintervention compared to our historical results. We are currently investigating the use of cone beam CT as the only method of immediate surveillance imaging. We hope to present this second phase in the next Vascular Annual Meeting.”

Oderich shares that the “secret of a successful career in surgery is drive, opportunity and determination.

Without these three it is difficult or impossible to succeed at a higher level. Your training never ends and you need to adapt.” He advises that you should have “the patient in the focus of your attention and always aim to do the best for the patient. I assure you will have failures, but at least you will have the comfort of a peaceful mind.”

Speaking about interests outside of medicine and his passion for sailing, surfing and running, Oderich says, “my main interest is my family, Thanila and our two kids—Gabriel and Victoria. We are always together whenever we have any free time doing family activities. I love music and cinema and have an eclectic taste for the classic and the 1990s in general.”

Alberto Muñoz

A

lberto Muñoz discusses with Vascular News the landmark advances made in his 35 years as a surgeon, as well as his involvement in the World Federation of Vascular Societies (WFVS).

“It is amazing how it has changed since I started my surgical practice, from pulse palpation and angiography to duplex scanning, CTA, MRA, and digital subtraction angiography, and from open surgery to minimally invasive endovascular or hybrid interventions. The two most outstanding advances in vascular surgery during these 35 years have been non-invasive vascular diagnosis and endovascular interventions. Also, evidencebased medicine and the controlled randomised trial in Europe and the USA for carotid artery disease treatment, EVAR trials, BASIL trial and many others.”

As its president, Muñoz comments on why an organisation such as WFVS is important and a few of his achievements. “The WFVS was established by the major vascular societies of the world to provide a forum for the international exchange of educational, political, and scientific issues

related to the diagnosis, treatment, and prevention of vascular diseases,” Muñoz explains. “A Symposium of the World Federation is held annually at the same time and place as the congress of one of the member societies. This is important since the diagnosis and treatment of patients with vascular disease are in constant evolution. New technologies appear and we need to be aware of them and train ourselves in order to take good care of our patients. The idea is that relevant topics of vascular surgery be exchanged between the various World Vascular Societies in order to provide the best possible management in every corner of the world.”

He says, “I continue the work of my predecessors in organising the annual meeting of the WFVS, Latin-American Association for Vascular Surgery (ALCVA) and Uruguayan Society for Vascular and Endovascular Surgery (SUCIVE)”, adding “I hope the WFVS will continue to fulfil its mission of integrating vascular surgeons around the world and that the WFVS annual meetings generate more interest.

Also, that it continues to develop projects that benefit the world population in the prevention and management of vascular disease.”

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March 2019

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Vici stent meets primary endpoints in VIRTUS 12-month data New 12-month data from the VIRTUS trial demonstrate that patients who were treated with the Vici venous stent system (Boston Scientific) for iliac and femoral vein obstructions exhibited a high rate of patent, or open, target lesions. Primary safety and efficacy results from the trial were presented as a first-time data release at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany) by principal investigator Mahmood Razavi (St. Joseph Heart and Vascular Center, Orange, USA).

T

he VIRTUS trial evaluated the Vici stent in patients with clinically significant obstructions in the illiofemoral venous outflow tract resulting from post-thrombotic syndrome (PTS) or compressive diseases such as May-Thurner syndrome.

“The primary safety and efficacy endpoints were very successfully met, with very low p-values”, Razavi told the audience at LINC. The trial’s primary effectiveness endpoint saw a primary patency rate of 84% at 12 months, which was greater than the predefined performance goal (PGE) of 72.1% (p=<0.0001).

Nearly all the patients treated with the stent, and 98.8%, were free from major adverse events at 30 days post-procedure, thus surpassing the pre-defined safety performance goal (PGS) of 94%.

The VIRTUS IDE trial, submitted in June of 2018, is a prospective, multicentre, single-arm, non-randomised study that enrolled 170 patients with chronic disease; 75% (127) of whom were diagnosed as having postthrombotic lesions and the remaining 25% (43) were diagnosed with non-thrombotic lesions (i.e., MayThurner syndrome). Venography, Doppler ultrasound and intravascular ultrasound (IVUS) were performed pre- and post-stenting, as well as at 12-month follow-up.

“In treating patients with venous obstruction, the primary goal is to restore and maintain vessel patency to ensure the return of blood flow to the heart,” said Razavi. “In these results, the Vici stent demonstrated excellent performance outcomes in a difficult-to-treat patient population, which translates to improvement of long-term symptoms and enhanced quality of life in these patients.”

In terms of clinical severity, Razavi reported a Vascular Clinical Severity Score (VCSS) decrease of

Vici venous stent

4.4 points at 12 months, with a median VCSS of 10 in 146 patients falling to 5.6 in 132 patients followed up to 12 months. At baseline, 65.8% of patients presented in the category of most severe VCSS of 8 or more, which decreased to 33.3% at six months and further fell to 27.3% at one year.

Two adverse events (1.2%; n=169) were seen in the cohort at 30 days, both of which were described as “arterial or venous injury at the target vessel segment and/or target lesion location or at the access site requiring surgical or endovascular intervention”. There were no instances of device or procedure-related death, major bleeding at target or access site, acute deep vein thrombosis outside target vein segment, clinically significant pulmonary embolism or embolisation of the stent at 30 days.

“Physicians who select endovascular treatment options for their patients with venous disease are not only faced with challenging disease-states but must also account for the unique anatomical presentation of these deep veins that are subject to chronic obstruction and compression,” said Ian Meredith, executive vice president and global chief medical officer of Boston Scientific, in a company press release. “The results from the VIRTUS trial demonstrate the importance of having a therapeutic option that is specifically designed for venous application, thus helping patients avoid recurrent pain, swelling and other debilitating aspects of acute and chronic venous disease.”

The stent system was approved for use in Europe and other geographies that recognise CE mark in 2013. In the USA, the stent is an investigational device and is not available for sale. The device was developed by Veniti, a company which Boston Scientific acquired in 2018.

A need to clarify the role of compression in leg ulcer healing Speaking at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), Katja Mühlberg of the University of Leipzig, Germany, called for an improvement in the evidence base around the role of compression in healing venous leg ulcers (VLU).

Mühlberg outlined the need for more studies to determine the efficacy of different strategies on healing and recurrence, and their impact on patients and budgets.

SHE ARGUED: “THERE is an urgent need for education, and for adequately powered highquality randomised controlled trials comparing different diagnostic and treatment options, with reporting outcomes including time to ulcer healing, ulcer recurrence, adverse events, quality of life, and cost-effectiveness.”

Mühlberg outlined several shortcomings in the current understanding of compression therapy, including the optimum method of compression and its impact on larger ulcers and on long standing ulcers—as well as whether an exercise regimen adjuvant to compression therapy improves outcomes, and the role of debridement. Mühlberg also pointed to a lack of uniformity across countries in how compression strength is classified, likening it to “comparing apples and pears”.

To this point, the EVRA trial published in 2018 compared improvements in ulcer healing between compression therapy plus early intervention (within two weeks) and compression therapy alone plus deferred intervention (after six months). It was concluded that early intervention led to shorter times to ulcer healing, with higher rates of healing and a longer duration of an ulcer-free period.

“But,” Mühlberg asked, “are the effects the same on larger ulcer size and on long-standing ulcers? Larger and long-standing ulcers are negative prognostic markers for healing, and the ulcers which were included in this study were small ones and had a short duration of only three months. We do not know about long-term results because we have only one-year follow up.

And, which method is the best choice? We do not know, because all the endovenous methods were permitted in the study. The effect of conventional venous surgery was not studied.”

Although ambulation is known to improve venous healing, Mühlberg queried whether an “exercise regimen adjuvant to compression therapy increases ulcer healing too [compared Continued on page 40

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A need to clarify the role of compression in leg ulcer healing Continued from page 39

with compression alone]?” and pointed to a study that analysed the impact of progressive resistance exercise and physical activity: “The meta-analysis could show that the combination of seated heel raising with physical activity had the strongest association with venous leg healing, so we can say the evidence base is growing for incorporation of exercise into venous ulcer treatment.

“We know too, debridement is necessary, effective, and improves ulcer healing. What we do not know is, is there really good evidence, and how do different methods compare? We have surgical ones, mechanical methods, the biosurgical use of maggots, and so on.” However, Mühlberg pointed to a Cochrane review of 10 randomised controlled trials with 715 participants that were unable to perform a meta-analysis, “revealing a very limited evidence base for debridement”.

Research has also failed to determine the most effective method of treatment, as Mühlberg maintained there is no difference in outcomes on ulcer healing and time to healing in studies looking at compression stockings versus bandages, and no reliable data on ulcer recurrence is available. “We have at least moderate-quality evidence that supports compression over non-compression therapy, but without significant difference between the methods.

And, until now, we have low-quality evidence that supports the compression effect on ulcer

recurrence.”

A prospective randomised five-year follow-up study that compared compression class (CCL) 2 and CCL3 therapy showed a much lower ulcer recurrence for patients treated with CCL3 than CCL2.

However, a lack of clear recommendations about the intensity of Katja Mühlberg compression required makes interpretation of any results difficult, and, according to Mühlberg, could be “one reason for the low evidence of compression therapy in most of our trials”.

As compression class definitions vary internationally and across different healthcare systems, comparing research is complicated by the lack of standardisation. More than 50mmHg in the lower leg and 30–40mmHg in the thigh is needed in order to occlude a vein in the standing or sitting position, Mühlberg explained. However, the range between 30 and 50mmHg could be classified in Germany as either CCL 3 or 4, in France as CCL 4, and in Spain as CCL 2 or 3.

A lack of awareness about how to administer

The rise of CLaCS and aesthetic phlebology Kasuo Miyake Comment & Analysis Kasuo Miyake is a leader in Cryo-Laser and Cryo-Sclerotherapy (CLaCS) treatments for varicose veins. Based in Sāo Paulo, Brazil, Miyake heads the vein clinic founded by his late father, Hiroshi Miyake, a pioneer in the field of CLaCS and aesthetic phlebology. In this article, he writes about the developments seen since his father started his career, and outlines where we are today.

ONE OF THE studies by Dr Hiroshi Miyake, who passed away in 2018, was based on the surgical treatment of telangiectasias, especially when the telangiectasias are grouped together.

Hiroshi Miyake performed microphlebographies in the 1970s, and he found, having injected veins with contrast, that the grouped telangiectasias were connected to some deep veins.

Some were found to be connected to the saphenous veins. So, he began to perform phlebectomies with crochet hooks in order to disconnect the telangiectasias from these deep veins, which then facilitated the treatment of veins that had not responded to other treatments.

As time went by, new technologies

began to emerge. Augmented reality, which came about in 2005, quickly became a subject of study. The Clínica Miyake team was the first institution to study augmented reality and its application to varicose vein treatment— using the technology to look for feeder veins. They were the same feeder veins that Hiroshi Miyake studied in the 1970s. The only product that introduced augmented reality and its practical applications in the medical field was VeinViewer (Christie Medical Holdings).

The equipment was developed in order to better locate veins in the arm, and with no comparable devices available on the market, there were no competitors.

At Clínica Miyake, we studied augmented reality and its use in the

Charing Cross Special Edition

We physicians have a low knowledge about compression therapy, and only 31% of our venous leg ulcer patients receive any compression therapy at all.” compression therapy also contributes to the problem.

A German study that evaluated the knowledge and practical skills of healthcare professionals produced “very alarming numbers”, Mühlberg noted, leading to the question, “How many of our patients are correctly treated? We physicians have a low knowledge about compression therapy, and only 31% of our venous leg ulcer patients receive any compression therapy at all.”

One possible solution, she suggested, “could be telemedicine”, describing a system that is capable of reporting instantaneous changes in bandage pressure, moisture level and local temperature at the wound site. But in the meantime, she advised, information and understanding require further development.

treatment of those telangiectasias which strayed from its original purpose. Since we were able to see where the feeder veins were located, we were able to use the CLaCS technique in order to treat the feeder veins directly. We also used augmented reality in order to classify veins and to mark the location of the veins for surgical procedures.

At that time, we thought this was a revolutionary thing, but unfortunately, the vascular surgeon community was very sceptical towards it. Now, 14 years later, this technology is finally becoming more popular, even becoming a discussion topic at many conferences.

It is interesting to observe how the same thing happened with ultrasound. Due to a matter of low-definition ultrasound imaging and scepticism, it took a long time for ultrasound to be used in the field of aesthetic phlebology. Not to mention the cost, but nowadays for those who have their own clinic and have specialised in phlebology with aesthetic ends in mind, it is almost mandatory to have an ultrasound and augmented reality for diagnosis and treatment.

Therefore I think all of aesthetic phlebology will lean towards centralisation. The doctor will likely have all of the equipment in order to diagnose and treat, including an operating room, all in one clinic.

Gravitating towards “de-hospitalisation” will reduce dependency on a hospital structure for surgeries or treatment.

Another facet which is on the rise is photo-documentation. When discussing aesthetic treatments, the government or the healthcare insurance should not pay. Aesthetic phlebology is a private treatment and, being a private treatment,

the cost is much more elevated. It is an elective treatment and is therefore regarded as superfluous. Because of this, it is extremely important to perform photo-documentation. If a patient is not satisfied, he or she may return to complain, especially for a treatment with such a high cost. Similarly, if the patient thinks the treatment was not effective, it is important for the doctor to have proof of what the affected area looked like prior to treatment. It is for both the doctor and the patient: the doctor may know if the treatment method was effective and the patient can see the gradual improvements. Furthermore, if a patient’s case truly does not improve, then the doctor will know that he or she needs to alter the treatment plan.

In other news, as the founder and president of the International Meeting on Aesthetic Phlebology (IMAP), we are very excited about our 9th edition on May 3rd to 5th in Sāo Paulo, Brazil. The first IMAP was executed in 2011 with the objective of contributing to the development of Aesthetic Phlebology in the world. Since then, all eight editions have had renowned professionals from more than 30 countries.

At IMAP 2018, we received more than 350 doctors, and IMAP has established its place as a global reference in the advancement of venous treatments. We already have the esteemed Alun H Davies as our keynote speaker, along with an extensive list of international speakers and sponsors. IMAP’s official language is English, and we welcome all vascular surgeons/physicians.

Kasuo Miyake is a vascular surgeon and owner of Clínica Miyake in Sāo Paulo, Brazil.

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Adhesive closure of varicose veins With an expanding range of treatment options for superficial interventions, clinicians now have a choice of several strategies, technologies and devices to treat varicose veins. Tobias Hirsch (Vein Competency Centre, Halle, Germany) outlined the case for and against the use of endovenous glue in place of thermal ablation for varicose vein treatment at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

A

lthough thermal ablation is the standard treatment for varicose veins, as recommended by the American Venous Forum in 2011, and by the National Institute for Health and Care Excellence (NICE) in 2013, Hirsch pointed to “robust data and randomised controlled trials” showing a high occlusion rate with >93% after three years, “which is just as high as with open surgery”, and ≥85% after five years. “During the last 20 years, a wide range of devices has been developed to thermally treat varicose veins, so we have to ask ourselves—do we really need more devices?”

The heat, that induces vein shrinking, noted Hirsch, may result in side-effects: the use of needleinjected tumescent anaesthesia causing pain, and hyperpigmentation. There is also a risk of nerve injury and damage, especially when treating the small saphenous vein. “Damage to the sural nerve can cause numbness to the lower heel; hitting the sensory or motor or tibial nerve may result in paraesthesia or talipes calcaneus. The current data we have show paraesthesia in 5–10% of small saphenous veins treated, and a Korean group even identified paraesthesia in every fourth case.”

Reviewing current evidence, Hirsch assessed the advantages and pitfalls of endovenous glue, and outlined its benefits: “Adhesive closure means no heat, no tumescence. The active ingredient in several of these devices has been used in medicine since 1989.

We know that it is tissue-compatible in thousands of patients, and there is no indication of it being

carcinogenic.”

The procedure is very similar to thermal treatment options, Hirsch explained: “A guidewire is usually used, and once the machine is connected to the catheter the adhesive can be applied.

The catheter is withdrawn in 3cm increments, and nothing more than a plaster is needed to finish Tobias Hirsch the procedure.”

“The data we have show an excellent occlusion rate,” Hirsch noted, pointing to the VeClose study, a randomised controlled trial of endovenous cyanoacrylate closure which has shown that the endovenous glue technique is “not inferior to radiofrequency ablation (RFA); after three years, the results were even better [using glue].” The five-year results of the VeClose trial will be presented for the first time at the Charing Cross Symposium (CX; 15–18 April, London, UK).

Furthermore, an analysis of first-time users compared to trained operators showed complete occlusion in both groups (first-time users 19/19 [100%] vs. RFA 103/108 [95.4%]), with no difference between beginners and experienced doctors, suggesting the treatment is easy to learn. An additional advantage is that there is no need for additional devices, noted Hirsch.

Less invasive and more flexible developments for endovenous varicose vein therapy Less invasive therapeutic options are becoming more widely available for the endovenous treatment of varicose veins, creating the potential for greater flexibility and allowing larger numbers of patients to be treated. Anina Lukhaup, Angiologie Zentrum, Munich, Germany, provided a roundup of “promising new developments” in endovenous methods and therapies for varicose veins at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

“WE ARE ON our way to having even less invasive treatment options and therapeutic methods— minimally invasive, and even […] non-invasive therapeutic options. And, we can progress towards fewer thermal lesions; fewer thermal nerve lesions, and less tumescent anaesthesia.”

According to Lukhaup, although there is a variety of safe and effective options already available, there is room for improvement. “We want a minimal invasive treatment, suitable for all our patients’ [vessel anatomies], and ideally we want to have all the benefits of non-thermal treatment, but without inserting a substance which then remains for a long period in the body. We would like to have non-thermal tissue lesions, and maybe also avoid tumescent anaesthesia.”

A technology with the potential to be minimally invasive is high-intensity focused ultrasound. “This is already used for some medical issues, but has no certification yet for vein treatment. Research suggests it works well in varicose veins; animal studies on superficial occluded veins have yielded quite promising results,” said Lukhaup.

Furthermore, she suggested that the technology offers a solution for inguinal recurrences and perforated veins.

“Nowadays, a frequent option is to do a perforated ligation in this area, or to insert foam. It is all invasive [in an area] where there may be a wound infection and skin damage. This treatment would have the possibility to come from the outside with no invasiveness at all.”

Lukhaup also alluded to the Echopulse (Theraklion) technology that utilises ultrasound for real-time imaging. She pointed to its robotic treatment tool and ultrasound probe that delivers 3mgHz high-intensity focused ultrasound, saying “we still have to wait to see it works how in clinical practice, but I think it is a promising idea.”

Tools in the well-established field of radiofrequency ablation also continue to evolve. Lukhaup presented details of the Venclose (Venclose) system, which was launched at the end of 2018. “It is a more flexible radiofrequency ablation catheter and thinner than Benefit by Medtronic. It comes with a 6Fr sheath, and an additional aspect is that the heating tip is changeable between 2.5cm and 10cm.”

Charing Cross Special Edition

But although the procedure is simple to pick up, Hirsch acknowledged the treatment of junctions is “a little bit tricky. The manufacturer advises that there be a safety distance of 5cm from the tip of the catheter to the junction, but this is not the result we want. There is a bit of a learning curve to find the best placement for the catheter tip to produce a short stump which seems to be a precondition for a low recurrence rate.”

In addition, patients need to be made aware that the compound is an implant. “And, we have to think about toxicity and allergenic risk, especially as it takes the adhesive a long time to be resorbed. All trials show an excellent occlusion rate, but all trials also indicate a phlebitis-like reaction in up to 20% of cases.” He added that patients should also be warned that they may experience some pain one or two weeks after treatment, and that generalised skin affections are a possibility.

Addressing potential cutaneous side effects related to endovenous glue, Hirsch said, “acrylates are known to cause type IV allergic reactions, and this means contact eczema. The only way to treat contact eczema is to halt exposure.” However, Hirsch maintained that symptoms in connection with vein treatment such as hives and itching are suggestive of a histamine dependency and not type IV allergy, and this can be managed using steroids and antihistamines.

While maintaining that some “pitfalls” are possible and must be discussed with the patient pre-operatively, overall Hirsch concluded that “advantages make adhesive closure an effective add-on to thermal varicose treatment.”

This changeable tip has been advocated as a time-saving benefit, but Lukhaup disagreed.

“Radiofrequency ablation is already quite a fast treatment; in the end we save about one minute of procedure time so this does not make much of a difference.” For her, its advantage lies in its interchangeability: “If you have to treat two veins in one session […] it is quite useful that you can change the length of the heating tip catheter.”

There have also been further advances in the use of laser wavelength. “There has been a lot of research on lasers, and a lot of progress in laser treatments.

[One is] a longer wave laser, a 1940nm laser, a which has higher absorption rate, and therefore the energy remains more focused in the target area.”

Lukhaup noted that as a result of this, heat is also more focused, leading to a reduced temperature increase in surrounding tissues. She described the thermal laser treatment as “interesting”, particularly in regards to its possible role in reducing tumescence in surrounding tissue: “This laser might include an opportunity to use it without tumescence, or with less tumescent anaesthesia.

It has very good occlusion rates in clinical studies, and IMS Medical has launched its Simla 6 laser, available now to use, and to get more clinical results.”

She detailed a colleague’s use of a prototype, treating without tumescent anaesthesia: “I was quite surprised to see that it works; the patients feel a little bit of disturbance in some areas of the vessel, but they all got through the treatment without any anaesthesia.”

Techniques that are suitable for use in all vessel anatomies have not yet been developed, and there is still a need for compression; however, the new tools provide a welcome addition to long-standing methodology: “We have to see now how they work in clinical routine. The advantages are that it is getting less invasive and more flexible, and so we can have more patients treated with these methods.”

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NICE recommends UrgoStart wound dressings for diabetic and venous ulcers The UK’s National Institute for Health and Care Excellence (NICE) has published new guidance recommending UrgoStart wound dressings (Urgo Medical) for the treatment of diabetic foot ulcers and venous leg ulcers. Cost modelling, NICE reports, shows that using UrgoStart for these purposes is associated with a cost saving of £342 per patient after one year.

THE CONCLUSION OF the NICE medical technology guidance is that UrgoStart is associated with increased wound healing compared with noninteractive dressings and could result in fewer ulcer-related amputations. The committee recognised that the treatment

is also associated with significant cost savings for the UK National Health Service (NHS) and improved quality of life for patients.

Graham Bowen, clinical lead for Podiatry, Solent NHS Trust, Southampton, UK and chair of Foot in Diabetes

UK said “This is tremendous news.

Diabetes-related foot ulcers are extremely debilitating and can affect every aspect of the person’s life. UrgoStart can significantly reduce the healing time of foot ulcers, and will have a significant impact on thousands of patients living

with this condition. As we know, over 90% of all diabetes related amputations are preceded by a single foot ulcer so speeding up the healing process could help prevent many unnecessary amputations.

The NICE guidance shows that UrgoStart can have a major impact on clinical outcomes and reduces costs for the NHS which is good news for both patients and healthcare professionals.”

The NICE guidance committee acknowledged the robust clinical studies which “showed an increase in the rate of early wound healing with UrgoStart in patients with venous leg ulcers compared with standard treatment”.

UrgoStart (TLC-NOSF) is the only local treatment proven to reduce healing time.

UrgoStart is a lipido-colloid dressing (hydrocellular type) with soft-adherent TLC-NOSF Healing Matrix (NOSF impregnated in a TLC healing matrix).

UrgoStart (TLC-NOSF) is the only local treatment proven to reduce healing time. TLC-NOSF acts locally in the wound on the two key factors that impair wound healing. It inhibits excess matrix mettaloproteinases (MMPs), which in excess destroy extracellular matrix components; and promotes angiogenesis through migration and proliferation of endothelial cells, to deliver oxygen and nutrients to the wound.

The company states that NICE’s decision means that thousands more people with venous leg ulcers and diabetic foot ulcers could benefit from this unique wound treatment.

At any one time 115,000 people in the UK develop a diabetic foot ulcer, and 278,000 people are treated for venous leg ulcers every year—a condition which takes an average of 200 days to heal, making it a significant impact on quality of life and a cost-burden for public healthcare systems like the NHS. If half of the people with a venous leg ulcer were treated with the wound dressing, Urgo Medical estimates there would be an annual cost saving of £75 million to the NHS. Similarly, if half of the people with a diabetic foot ulcer received treatment with UrgoStart, the NHS could save £19.6 million per year.

Charing Cross Special Edition

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CASSINI trial results inconclusive on rivaroxaban effects in highrisk ambulatory cancer patients The CASSINI trial found that treatment with rivaroxaban did not significantly reduce the incidence of thromboembolism or death caused by thromboembolism in high-risk ambulatory patients with cancer during the 180-day study period. However, during the study’s intervention period, there was a significantly lower incidence of venous thromboembolism and death due to thromboembolism among patients treated with rivaroxaban, and there was a low incidence of major bleeding. The results of the trial were reported by Alok A Khorana (Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA) and colleagues in the New England Journal of Medicine.

IT IS KNOWN that cancer and cancer treatment put patients at risk of venous thromboembolism, but guidelines do not recommend routine thromboprophylaxis for patients with cancer even though it is possible that such treatment could improve their outcomes. The study investigators therefore sought to “assess the efficacy and safety of rivaroxaban thromboprophylaxis in patients with a solid tumour or lymphoma who had a Khorana score of two or higher and were initiating in a new systemic cancer regimen”.

The CASSINI trial was a double-blind, multicentre, randomised trial, which randomised high-risk ambulatory patients with cancer to receive either 10mg rivaroxaban or placebo daily for a period of up to 180 days.

The primary efficacy endpoint—a composite of deep vein thrombosis, pulmonary embolism or death from venous thromboembolism—was assessed for up to 180 days. The same endpoint was similarly assessed during the intervention period, which was the time from first receiving treatment or placebo to the last treatment plus two days. The primary safety endpoint was major bleeding.

Of 1,080 patients originally enrolled in the trial, 49 (4.5%) were found to have thrombosis during screening and 190 had other reasons to be excluded.

A total of 841 patients who were all assessed as having a higher risk of venous thromboembolism (Khorana score ≥2 at baseline) and an expected survival of more than six months were included in the

randomisation: 420 patients were assigned to the rivaroxaban group and 421 to the placebo group.

The mean intervention period of time when patients actually received treatment was 4.3 months, with 43.7% of patients in the rivaroxaban group and 50.2% of those in the placebo group stopping treatment before the end of the trial.

During the study period up to day 180, the primary endpoint occurred in 25 patients receiving rivaroxaban (6%) and 37 patients receiving placebo (8.8%; hazard ratio=0.66; 95% confidence interval [CI]=0.40–1.09; p=0.10).

During the intervention period, the primary endpoint occurred in 11 patients receiving rivaroxaban (2.6%) and 27 patients receiving placebo (6.4%; hazard ratio=0.40; 95% CI=0.20–0.80). Major bleeding occurred in eight patients receiving rivaroxaban (1.9%) and four patients receiving placebo (1%) (hazard ratio=1.96; 95% CI=0.59–6.49).

Khorana et al comment: “Although the primary endpoint occurred in a lower percentage of patients who had been randomly assigned to the rivaroxaban group in this analysis, the difference was not significant”. However, they note that “in a prespecified supportive analysis involving the same population but assessing the more conventional period of during the intervention, we found a difference of four percentage points in favour of rivaroxaban over placebo with regard to the primary composite endpoint of venous thromboembolism and venous thromboembolism-related death.”

We found a difference of four percentage points in favour of rivaroxaban over placebo [for] VTE and VTE-related death.”

Arterial and isolated distal thromboembolism, which are common in patients with cancer, were found in lower rates among the rivaroxaban-treated patients than in the patients receiving placebo. According to Khorana et al, this “could further increase the net benefit of prophylaxis for patients”.

A limitation of this study is the large percentage of patients who stopped the trial regimen prematurely, but this is not surprising in patients who mostly have advanced cancer.

The investigators conclude: “The results of the CASSINI trial provide important information regarding the baseline prevalence and incidence of thromboembolism among high-risk ambulatory patients with cancer”.

However, they were unable to confirm the benefits of treating these patients with rivaroxaban in their trial “because the between-group difference in the prespecified primary efficacy endpoint up to day 180 was not significant”.

COMPASS PAD findings change practice in high-risk patients Positive findings from the COMPASS PAD trial on the use of dual medical therapy with low-dose rivaroxaban and aspirin have already influenced the management of high-risk patients with peripheral arterial disease (PAD). Rupert Bauersachs (Klinikum Darmstadt, Darmstadt, Germany) recounted details at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany) of how the study findings have changed daily clinical practice.

“I

f we look at the whole spectrum of PAD patients that we are treating, we are mainly concerned with limb prognosis, but we must not forget the general prognosis of these patients with PAD is really poor; it is comparable to malignant disorders.

Rivaroxaban 2.5mg plus aspirin has been shown to be effective in all patients with PAD, but particularly those patients at high risk,” Bauersachs told the LINC audience.

A cohort of the main COMPASS trial consisted of >7,000 patients with symptomatic PAD or concomitant coronary artery disease (CAD) and PAD. The performance of low dose rivaroxaban (2.5mg twice daily) plus aspirin was compared with rivaroxaban 5mg, twice daily, and with a placebo group receiving aspirin alone. Rivaroxaban plus aspirin reduced major adverse cardiac events (MACE) by 28%, major adverse limb events (MALE) by 46%, and major amputation rates by 70%, with no significant increase in fatal or critical organ bleeding observed.

Bauersachs used three difficult cases with high-risk profiles similar to subsets within COMPASS PAD to demonstrate how he has applied these results to his own patients.

The first involved a 60-year-old male patient with symptomatic PAD, who had received repeated percutaneous transluminal angioplasties (PTA), suffered an acute myocardial infarction (AMI) at 48 years old, has a family history of heart disease, and has polyvascular disease (both CAD and PAD), and therefore, said Bauersachs: “He has a very high

cardiovascular risk, so he needs intensified prevention.”

Based on the evidence from COMPASS PAD that rivaroxaban 2.5mg twice daily plus aspirin significantly reduced the risk of MACE in patients with polyvascular disease, Bauersachs started the patient on low dose rivaroxaban: “In the combination of CAD and PAD, the cardiovascular risk for MACE—cardiovascular stroke, death, and AMI—is very high. And this is reduced by one-third with the addition of rivaroxaban 2.5mg [to aspirin]. The absolute risk reduction is almost 3%, while at the same time the risk for major bleeding is not different to those patients that only have CAD.” Bauersachs’ second case involved a male patient who previously had surgery for symptomatic PAD. This highrisk patient had carotid disease and diabetes and also required intensified CV protection. He was subsequently given rivaroxaban 2.5mg twice daily in addition to aspirin, as data from COMPASS PAD show that the risk of MACE in a subgroup of patients with CAD and diabetes is significantly reduced with the addition of low-dose rivaroxaban.

“Those patients with diabetes and on aspirin-only have a high MACE risk [7%],” Bauersachs explained, “which is significantly reduced with the addition of 2.5mg rivaroxaban [absolute relative risk reduction (ARR) 1.9%], while the bleeding risk is not increased in comparison to the patients that have no diabetes.”

The third case, Bauersachs described as “conservative”—a 61-year-old female with symptomatic PAD, as well as carotid disease and renal insufficiency.

She was a high-risk patient and intensified prevention

Charing Cross Special Edition

was necessary; he prescribed 2.5mg rivaroxaban as the study data showed the dual therapy significantly decreased the risk of MACE in patients with CAD or PAD and renal impairment.

“For patients with impaired renal function, their risk for MACE—cardiovascular death, stroke, and AMI—is greatly increased compared to those patients with normal renal function. Rivaroxaban with low dose reduced the risk by a 2% absolute, and 25% relative risk reduction [hazard ratio 0.75, 95% confidence interval 0.60–0.94], while in those patients with renal impairment, the risk of major bleeding was not increased compared to those patients with normal renal function.”

Putting the findings of COMPASS PAD into perspective, he pointed out: “We have to be aware that patients with PAD have a very high risk of both MACE and MALE events. Several subgroups of patients remain at a very high risk, despite anti-thrombotic treatment with aspirin, for example, those patients with cardiovascular disease—carotid artery, coronary artery disease—and PAD, with renal insufficiency, and diabetes. Rivaroxaban 2.5mg plus aspirin has been shown to be effective in all patients with PAD, but particularly those patients at high risk; there were significant reductions in relative risk and absolute risk.”

As a result, Bauersachs concluded: “Personally, I have started those high-risk patients with the COMPASS regimen—2.5mg rivaroxaban twice daily on top of aspirin. It is also important that we inform the patients on the need for, and on the risks and benefits of this additional dual pathway protection strategy.”

March 2019

Advertorial

47

Sponsored by Intact Vascular

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The Tack Endovascular System® developed by Intact Vascular, Inc., is purpose-built for post-percutaneous transluminal angioplasty (PTA) dissection repair. CE mark was declared in 2012 for the above-the-knee (ATK) system and in 2017 for the below-the-knee (BTK) system. The high-precision delivery system contains multiple pre-loaded Tack® implants that utilise a short 6mm length and open cell design to reduce the amount of metal in contact with the arterial wall. Tack implants self-size to the tapering anatomy of the lower extremity; ATK can be used in the superficial femoral artery (SFA) and proximal popliteal vessels with diameters 3.5–6mm and BTK is indicated for use in mid, distal and infrapopliteal arteries with diameters 1.5–4.5mm. The first-of-its-kind dissection repair device has been rigorously studied in over 800 patients.

Physician Michael Lichtenberg, head of the Interventional Angiology and German Venous Center at Klinikum Arnsberg in Arnsberg, Germany, performed the first commercial procedures with the Tack Endovascular System earlier this year. Lichtenberg says the “ability to space Tacks apart preserves future treatment options as the patients’ disease progresses. No bridges burned.”

The ability to space Tacks apart preserves future treatment options as the patients’ disease progresses.

No bridges burned.”

Case report 1 (SFA) A 69-year-old male patient with left calf claudication after 80 meters. Cardiovascular risk profile included diabetes and smoking (50 pack-years). No prior vascular interventions.

An 0.035” Cordis J-tip guidewire was advanced through a 100mm length high grade stenosis.

Reference vessel diameter was 6mm proximally and 5mm distally.

Standard angioplasty was performed with a threeminute inflation (6x100mm), followed by three-minute drug-coated balloon angioplasty (6x120mm).

Angiography revealed a long post-PTA dissection, grade C using NHLBI classification system (Figure 1).

Five Tacks were placed (Figure 2) along the tapering course of the vessel.

Final angiogram shows dissection resolution and apposition of dissection flaps against the artery wall (Figure 3).

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Case report 2 (BTK)

A 78-year-old male patient with an infected wound on second left toe and ischaemic rest pain (Rutherford clinical category 5) with a toebrachial index of 0.5 on the left. Risk factors include diabetes and chronic renal insufficiency.

Planned revascularisation of posterior tibial artery (Figure 4).

Small peroneal artery with insufficient collateralisation of the foot and forefoot.

Long segment occlusion of anterior tibial artery.

Antegrade recanalisation failed; successful retrograde puncture and wiring of distal posterior tibial artery with wire externalisation through a 5F sheath.

Three-minute antegrade balloon angioplasty with a 2.5x250mm balloon.

A persisting flow limiting dissection within the mid third of the artery (Figure 5) was treated with three Tacks (Figure 6) and resulted in unimpeded flow to the foot and forefoot via lateral and medial plantar arteries.

Not approved for sale in the United States. Tack Endovascular System is CE Mark authorized under EC directive 93/42/EEC. Tack Endovascular System® and Tack® are registered trademarks of Intact Vascular, Inc.

Charing Cross Special Edition

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March 2019

Advertorial

Sponsored by Veryan Medical

BioMimics 3D®: Improving long-term outcomes using nature’s own vascular protection, Swirling Flow® There has been much discussion on the safety aspects of drug-coated balloons (DCB) and drug-eluting stents (DES) recently. Various articles, published and in press, have argued for and against the safety of these devices citing early mortality fears and the presence of aneurysms in treated vessels.1

T

here will be more discussion on the subject as the vascular world moves towards consensus, but whatever the eventual outcome there is agreement that for the treatment of recoil and flow limiting dissection at the time of intervention, a stent is required2, 3 and furthermore the challenging issue of limiting restenosis when stenting is required now has a drug-free solution, Swirling Flow®, nature’s own vascular protection mechanism.

Using Swirling Flow® in the femoropopliteal artery

The distribution of atherosclerosis and the tendency of an artery to develop restenosis varies throughout the human arterial system; the femoropopliteal artery has both a high prevalence of atherosclerosis and a high tendency to develop restenosis.4,5 Part of the reason for the variable distribution of native arterial disease was explained in the 1969 Nature article which drew attention to the relationship between wall

shear stress (WSS) and a reduced tendency towards atherosclerosis.4 It is understood that normal arterial blood flow is laminar. In addition, the normal pattern of that laminar blood flow in the aorta and proximal branches is also spiral—referred to as Swirling Flow.5 WSS can be thought of as the velocity of blood against the internal wall of the vessel. Swirling Flow increases WSS when compared to non-swirling flow resulting in a reduced propensity to develop atherosclerosis when exposed to well recognised risk factors. Blood flow in the superficial femoral artery, where natural curvature is limited, particularly when straightened by a straight stent, is naturally less swirling and WSS is reduced (Figures 1a and 1b)—hence the high prevalence of both native disease and proliferative response to endovascular injury.

Animal studies have confirmed that areas of low WSS predict the development of neointimal hyperplasia (NIH) in grafts and stents.6 Treating the superficial femoral artery of patients with peripheral arterial

Figure 1(a) is a Computational Fluid Dynamics (CFD) model of swirling flow showing it becoming dampened in the iliac arteries, resulting in straight laminar flow in the SFA.

Figure 1(b) is a CFD model of high WSS in the iliac arteries (as a consequence of swirling flow) and low WSS in the SFA. The graph on the left shows a scale of WSS from low (pathogenic) to high (protective) reproduced from Malek AM, et al. JAMA. 1999;282:2035-2042

Charing Cross Special Edition

disease using straight nitinol stents has been shown to reduce WSS.7 Evaluation of coronary stents in humans showed that the pattern of in-stent restenosis is determined by the distribution of WSS.8, 9 These observations led to the development of the BioMimics 3D self-expanding nitinol stent with a helical centreline that is capable of inducing swirling flow (Figure 2). The ability of this stent to reduce restenosis was first tested in a porcine model where a straight stent was placed in one carotid artery and a helically-formed version of the same stent in the other, of the same animal. The study demonstrated that the helical centreline stent imparted non-planar curvature to the implanted segment and generated swirling flow; that the swirling flow significantly reduced the development of NIH (Figure 3); and that a correlation between the degree of curvature and the reduction in NIH was established.10 The BioMimics 3D stent was subsequently tested in the first randomised controlled trial (RCT) to directly

Figure 2. BioMimics 3D Stent.

Figure 3. Thirty-day histology of a straight nitinol stent (left) and the same stent with a 3D helical shape (right) in a porcine carotid model. Overall, in 10 animals studied, there was a 45% reduction in neointimal thickness (p<0.001).

March 2019

Advertorial

Figure 4. Kaplan-Meier survival estimate from loss of patency (Mimics-RCT Study).

compare two nitinol stents in the femoropopliteal segment.11 Mimics-RCT was a multicentre, core-lab controlled, prospective, randomised trial in which the BioMimics 3D stent was compared to a conventional straight stent control (LifeStent, CR Bard) in 76 patients with symptomatic occlusive disease of the superficial femoral and proximal popliteal arteries. Conventional radiographs and angiography confirmed that the BioMimics 3D stent imparts non-planar curvature to the diseased artery. Compared to the straight stent control, the BioMimics 3D stent had significantly better primary patency through two years (Figure 4). There was no change in clinically-driven target lesion revascularisation (CDTLR) in the BioMimics 3D arm between 12 and 24 months whereas there was a three-fold increase in CDTLR in the straight stent control arm over the same time period; a significant difference between the two stents (Figure 5).

Drug-coated balloons

Current drug-coated balloons use paclitaxel to address the biological mechanisms leading to restenosis. The drug is combined with an excipient to provide uniform dosage and rapid uptake into the vessel wall. Variations in the excipient, formulation and dosage of the paclitaxel results in the different behaviour of the individual DCBs. The pivotal trials showed improved performance over simple angioplasty, but these were regulatory studies in carefully selected patients with uncomplicated lesions and the importance of that in terms of generalisability of the value of DCBs deserves some attention.12-16 Severe calcification and an inability to completely pre-dilate the lesion were exclusions in these studies and effectively removed those lesions from any analysis. Furthermore, since only 12–26% of lesions were total occlusions, vessels in these populations with non-calcified, simple disease were unlikely to recoil after angioplasty resulting in a bailout stent rate of only 2.5–7%. When the same DCBs are used in patients more representative of routine clinical practice, and documented within the Global Registries, the lesion patency and CDTLR rates remain good, because these more clinically generalisable cohorts are in fact measuring the outcome of DCB plus stent.17, 18 These registry subjects were characterised by disease that is more complex than those recruited to the pivotal regulatory trials resulting in an average stent rate of 28–35.5%. Stent rate was related to both lesion length and the chronic total occlusion rate. In IN.PACT Global for instance, when the length of lesion exceeds 25cm, the stent rate was 53%, and in total occlusions the stent rate was 47%.19 The Kaplan-Meier survival estimates from the pivotal regulatory trials demonstrate that the improvement in patency and reduction in CDTLR over simple angioplasty occurs between six and 12 months, but after

49

Figure 5. Kaplan-Meier estimate of survival from clinically-driven target lesion revascularisation between 1 and 2 years (Mimics-RCT Study).

this time the Kaplan-Meier curves are parallel.19 This trend is also seen in the global registries.17, 18 It is clear, therefore, that there are limitations to the use of DCBs in the femoropopliteal segment: 1. A ‘DCB-only’ approach is not appropriate to clinical practice outside pivotal trials. Whilst the bailout stent rate was low in the pivotal trials the global registries demonstrate that a much higher use of stents is required to maintain high patency and low CDTLR rates.

2. Loss of patency is a combination of recoil, late negative remodelling and restenosis. DCBs alone clearly do not provide the scaffolding that a stent does, to overcome the recoil and remodelling.

Indeed, DCBs appear to have been tested in an environment that would avoid likely recoil; lesions were short and both calcified lesions and lesions that demonstrated recoil after the initial pre-dilatation were excluded in the pivotal trials.

3. The antiproliferative effects of the drug applied at the time of DCB angioplasty are necessarily time limited and yet contemporary data show that loss of patency due to restenosis occurs out to three to four years.20 Something other than the drug is required to affect these late events.

It would appear therefore that in common clinical practice a stent is required in a significant proportion of DCB-treated lesions. If a stent is used to support a DCB it would be sensible to use a device with good outcomes that would not only provide the scaffolding that DCB-only therapy lacks but could extend the period of low CDTLR past the initial 12 months when DCBs are effective. The BioMimics 3D stent was seen in a randomised controlled trial to have a better patency and a reduced CDTLR rate when compared to a straight nitinol stent. Furthermore, as there was no CDTLR between 12 and 24 months in the BioMimics 3D arm of the RCT, this suggests that the use of a proven DCB and BioMimics 3D might be the ideal combination.21

MIMICS Clinical Programme

The clinical validation of the Swirling Flow stent is continuing across a range of studies in the MIMICS Clinical Programme.

Following on from Mimics-RCT, MIMICS-2 is a prospective, multicentre, interventional study designed to evaluate the safety and effectiveness of BioMimics 3D in the treatment of 271 patients with symptomatic femoropopliteal disease. The study is being conducted under a US Food and Drug Administration (FDA) Investigational Device Exemption (IDE), with Japanese Pharmaceuticals and Medical Devices Agency (PMDA) concurrence under the “Harmonisation By Doing” initiative, and has already provided the necessary data to gain FDA premarket approval in October 2018. The

Mimics-RCT results at 12 months are reinforced by the larger MIMICS-2 Study in which the KaplanMeier curves for primary patency and CDTLR are similar to those for DES and DCB, suggesting that swirling flow may be the natural alternative to drug eluting technologies.22 Two-year data from MIMICS-2 will be presented by the study’s US principal investigator, Timothy Sullivan (Minneapolis, USA) at the Charing Cross Symposium (CX; 15–18 April, London, UK).

References 1. Katsanos K et al; Risk of Death Following Application of PaclitaxelCoated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018 Dec 18;7(24).

2. L aird JR, Katzen BT, Scheinert D et al. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther. 2012;19:1-9.

3. S chillinger M, Sabeti S, Loewe C et al. Balloon Angioplasty versus Implantation of Nitinol Stents in the Superficial Femoral Artery. N Engl J Med. 2006;354:1879-1888.

4. C aro CG, Fitz-Gerald JM, Schroter RC. Arterial wall shear and distribution of early atheroma in man. Nature. 1969;223:1159-1160.

5. C aro CG, Doorly DJ, Tarnawski M, Scott KT, Long Q, Dumoulin CL. Non-planar curvature and branching of arteries and non-planar flow.

Proc R Soc Lond. 1996;452:185-197.

6. L aDisa JF, Olson LE, Molthen RC et al. Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries. Am J Physiol Heart Circ Physiol. 2005;288:H2465-75.

7. S chlager O, Zehetmayer S, Seidinger D et al. Wall shear stress in the stented superficial femoral artery in peripheral arterial disease.

Atherosclerosis. 2014; 233: 76-82.

8. S anmartín M, Goicolea J, García C et al. Influence of shear stress on in-stent restenosis: in vivo study using 3D reconstruction and computational fluid dynamics. Rev Esp Cardiol. 2006;59:20-27.

9. W entzel JJ, Whelan DM, van der Giessen WJ et al. Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution. J Biomech. 2000;33:1287-1295.

10. D ata on file at Veryan Medical 11. Z eller T, Gaines PA, Ansel GM, Caro CG. Helical Centerline Stent Improves Patency: Two-Year Results From the Randomized Mimics Trial. Circ Cardiovasc Interv. 2016;9.

12. T epe G, Laird J, Schneider P et al. Drug-Coated Balloon versus Standard Percutaneous Transluminal Angioplasty for the Treatment of Superficial Femoral and/or Popliteal Peripheral Artery Disease: 12-Month Results from the IN.PACT SFA Randomized Trial.

Circulation. 2014.

13. L aird JR, Schneider PA, Tepe G et al. Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions: 24-Month Results of IN.PACT SFA. J Am Coll Cardiol. 2015;66:2329-2338.

14. S cheinert D, Schulte KL, Zeller T, Lammer J, Tepe G. Paclitaxelreleasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial. J Endovasc Ther. 2015;22:14-21.

15. S chroeder H, Meyer DR, Lux B, Ruecker F, Martorana M, Duda S. Two-year results of a low-dose drug-coated balloon for revascularization of the femoropopliteal artery: outcomes from the ILLUMENATE first-in-human study. Catheter Cardiovasc Interv.

2015;86:278-286.

16. R osenfield K, Jaff MR, White CJ et al. Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease. N Engl J Med. 2015;373:145-153.

17. D Scheinert. LINC 2016 presentation. Latest results from the Levant Global registry on challenging, real world lesion including long lesions, CTOs and ISR & lesions learned from Levant II 18. D Scheinert. VIVA 2016 presentation. Strengths and weaknesses of DCBs: Insights from the Global Registries.

19. L aird JR et al. Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions 24-Month Results of IN.PACT SFA. JACC. 2015 vol. 66, no. 21 2329–38.

20. I ida O, Uematsu M, Soga Y et al. Timing of the restenosis following nitinol stenting in the superficial femoral artery and the factors associated with early and late restenoses. Catheter Cardiovasc Interv.

2011;78:611-617.

21. S ullivan TM et al; Swirling Flow and Wall Shear: Evaluating the BioMimics 3D Helical Centerline Stent for the Femoropopliteal Segment. Int J Vasc Med. 2018 Feb 26;2018:9795174.

22. D ata on file at Veryan Medical.

BioMimics 3D and Swirling Flow are registered trademarks of Veryan Medical Ltd. The BioMimics 3D Vascular Stent System has FDA premarket approval (PMA) and CE Mark approval.

Not available for sale in Japan.

Veryan Medical is a member of the Otsuka Medical Devices group of companies. www.veryanmed.com

PAM 211 Issue 00

Charing Cross Special Edition

March 2019

51

New clinical practice guidelines for management of chronic kidney disease The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) provides evidence-based clinical practice guidelines for haemodialysis vascular access and related complications, and has done so since 1997. The latest guidelines, published in 2006, no longer reflect the most recent evidence for the management of vascular access, causing the haemodialysis and vascular access community to eagerly await the revised recommendations, which currently remain in the external review process and due in Spring 2019.

W

ith more than a decade between the last guidelines and the imminently anticipated ones, the time elapsed is reflected in numbers: the new guidelines will have over 160 statements, compared with the 130 statements of the 2006 guidelines. For the upcoming guidelines, approximately one third of these statements are based on a rigorous review process, and 2/3 predicated on expert opinion. In contrast, the previous guidelines— where the strength of the recommendation was given a letter grade, with A being backed by the strongest evidence—had <20% grade A statements, and the remainder grade B or expert opinion.

Charmaine Lok (University of Toronto, Toronto, Canada), chair of the KDOQI Guidelines for vascular access 2018, gave a talk at the Controversies and Updates in Vascular Surgery conference (CACVS; 7¬9 February, Paris, France) to provide a glimpse of the upcoming guidelines. When asked by an audience member if the 13 years between guidelines meant there was “a big risk of having an outdated practice in-between” the publications, Lok agreed, telling delegates: “Absolutely. That is why it took us so long to develop the guidelines, because there was such a significant amount of evidence that had to be reviewed. The benefit of having a long time between each is that it allowed time for studies to be conducted, so we could actually learn from them to help develop the next guidelines, but I agree with you.

“There has actually been a study on the ideal timeframe between guidelines: four years. We need to keep these guidelines ongoing. This was a complete renewal of the guidelines, so hopefully the next ones will truly be an update, to make them much more frequent, because the time lapses are far too great.”

Conceptual shifts

Lok told CACVS attendees that there had been several key conceptual shifts involved with this endeavour, to ensure the finished publication best mirrors the changes to the field in the intervening 13 years.

Expanding on one of these ideological changes at CACVS, Lok said: “Here is one of the biggest changes in concept: what we are trying to do is emphasise the end-stage kidney disease (ESKD) Life-Plan.

Everybody is well aware that chronic kidney disease has five stages, and we typically think about reaching stage V, which is ESKD, as the end. However, I really want you to re-think it. When a patient reaches stage V, that is the beginning of the patient’s ESKD life on dialysis or transplant. The beginning of their ESKD Life-Plan.”

Lok went on to explain that the end-stage kidney disease Life-Plan concept centred around the paradigm of attaining: “The right access, in the right patient, at the right time, for the right reasons”. This, Lok said, means thinking of and planning for the patient’s continued care across their entire ESKD life-time. She demonstrates this with an example of two patients, a teenager whose ideal treatment would be a preemptive transplant, and an obese comorbid adult man, who “may have a different trajectory.”

In addition to reconfiguring the approach to endstage kidney disease treatment to encompass the complete patient timeline, the new guidelines consider and encompass more than the focused “fistula first” concept that Lok describes as emphasised since the 2006 recommendations. Instead, Lok asked the attending physicians to focus on a four-step PLAN: Patient Life-plan Access Needs.

It is especially important to think cleverly about [vascular access] for younger patients, who have a whole life ahead of them.”

Patient Life-plan Access Needs

The first step of the P-L-A-N, Lok explained, involves considering the patient first, and what their ESKD Life-Plan looks like. Is the first ESKD modality choice haemodialysis or peritoneal dialysis? Or Transplant?

Assuming it is heamodialysis, the next step is to consider the patient’s access needs. Secondly, what is the access creation plan; for example, who will create the access, where (location) and when (timing).

Thirdly, the physicians are asked to come up with an access contingency plan, so they have a remedial plan for when the access becomes problematic; for example, before creating the fistula, to consider the plan of action if it fails to mature. Finally, Lok urged the CACVS audience to think about an access succession plan, before creating an access: it is not just about thinking fistula first, but considering the next access. This takes into account the patient’s longer-term plan. Lok said that it was “especially important to think

Promising first-time data indicate human stem cell trial is safe, prompting future efficacy study A first-in-human, phase I clinical trial using stem cells to prevent venous stenosis formation in arteriovenous (AV) fistulae yields promising results.

Sanjay Misra (Mayo Clinic, Rochester, USA) presented these results at the 31st annual International Symposium on Endovascular Therapy (ISET; 27–30 January 2019, Hollywood, USA), and won the award for best poster for the same research.

THIS WAS THE first time this research had been presented at a meeting, and generated much buzz about the potential of autologous adipose-derived mesenchymal stem cells (AMSCs) for increasing maturation and preventing venous stenosis formation in AV fistulae used for haemodialysis.

To contextualise the importance of this research, Misra says: “At one year, nearly 60% of AV fistulae will develop a malfunction, often due to venous stenosis formation, and nearly 40% fail to mature.

Pathologically, AV fistulae fail due to venous neointimal hyperplasia caused by an increase in pro-inflammatory gene expression, including monocyte chemoattractant protein-1 and tissue necrosis factor-1 alpha.”

Recognising that with the primary patency of surgical creation of AV fistulae being between 60–70% means there is a high failure rate of approximately 30%, Misra became interested in using stem cells derived from patients as their own therapy or drug.

Following preliminary research conducted in mice, the research group was granted an IND [Investigational New Drug application] from the US Food and Drug Administration (FDA) to pursue the study, which was a phase I safety trial. “Our primary concern was around safety. Would these cells be creating more infections? Will they be less irritating with respect to fevers? So we did a randomised trial comparing patients who received stem cells or no cells and followed them for one year,” Misra explains.

In the phase I, single-centre, prospective, blinded, randomised trial, the study investigators reported no adverse events related to stem cell delivery, and a success in terms of maturation rate with the stem cell cohort compared to the control arm. Crucially, the team at Rochester also reported no safety issues with respect to the cellular delivery.

One month after periadventitial delivery of the autologous AMSCs to the outflow vein of the AV fistula, the maturation rate for radial-cephalic fistulae was 100% in the stem cell arm, versus 66% in the control group. For brachial-cephalic fistulas, the maturation rate was 100% in both the stem cell and the control cohorts­—with four patients in each group.

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Continued on page 52

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New clinical practice guidelines for management of chronic kidney disease

Promising first-time data indicate human stem cell trial is safe, prompting future efficacy study

Continued from page 51

Continued from page 51

cleverly about this for younger patients, who have a whole life ahead of them.”

Changes to definitions

A further change outlined by Lok in her CACVS presentation, more pedantic than the over-arching conceptual changes described above, is the editing of several definitions. One such changed definition is “catheter dysfunction”. Previously, this had focused on blood pump speed, and was defined in 2006 to include the “failure to attain and maintain an extracorporeal blood flow of 300ml/ min or greater at a prepump arterial pressure more negative than 250mmHg.” The new guidelines will define catheter dysfunction thus: “Failure to maintain the prescribed extracorporeal blood flow required for adequate haemodialysis without lengthening the prescribed HD treatment.”

Lok explained: “In some situations as in Tassin, France or for patients receiving nocturnal haemodialysis, these patients undergo longer duration dialysis, at prescribed low blood pump speeds (<300 ml/min) and the patient’s

catheter is fine—you would not say it is malfunctioning. So with these guidelines, we looked at innovation in [the] dialysis [field], and how we might be able to keep definitions current.”

Permanent tunnelled catheter avoids occlusion in haemodialysis patients Endovascular insertion of a permanent catheter following dilatation of an occluded central vein in haemodialysis patients achieves acceptable rates of technical and long-term success. Investigators say the technique could be used as a bailout for patients who have no access to haemodialysis. Due to a lack of kidney donors, dialysis is the treatment of choice for patients with end-stage renal disease.

MID-TERM RESULTS of tunnelled catheter placement in haemodialysis patients with central venous stenosis or occlusion were outlined at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany)

by Hassan Lotfy, a vascular and endovascular consultant at Alexandria University, Egypt.

Non-tunnelled catheters are extensively used, but they increase the risks of central venous occlusion and can interfere with preparation and planning for the construction of an arteriovenous fistula for permanent vascular access. Occlusion occurs most commonly with subclavian catheters

(42–50%), but it is also associated with internal jugular vein catheters.

The main causes are believed to be catheter-induced trauma to the venous endothelium, leading to secondary

Nine patients were followed up to 12 months’ post-procedure. At this last follow-up, patients in the control group were receiving more interventions than those in the treatment arm: three patients in the control cohort (one brachial-cephalic and two radialcephalic) underwent five fistulograms with four percutaneous transluminal angioplasties of the cannulation zone, compared with one patient in the stem cell group. “So we are seeing an effect related to the cells, less frequency of interventions,” says Misra.

The Rochester-based team are continuing to enrol patients in this prospective, phase I trial, and a future study is being planned to help determine the efficacy of this therapy.

To date, 16 patients have been enrolled (11 men and five women). Patients have an average age of approximately 65 years and an average BMI of 37.99.

All of the 16 patients in the study were hypotensive, 10 had a history of diabetes mellitus, five were on haemodialysis, six had a history of coronary artery disease, and 11 had

At one year, nearly 60% of AVFs will develop a malfunction and nearly 40% fail to mature.”

inflammatory damage within the vessel wall, or increased flow and turbulence arising from the creation of an arteriovenous access, which initiates an inflammatory response and stimulates interstitial hyperplasia.

Lotfy explained: “Our method was to recanalise the [occluded] vein and insert a temporary catheter. All patients had computed tomographic venography (CTV) to confirm the Doppler ultrasound (DUS) finding.

All cases were operated on under local anaesthesia, with sedation if needed, and the access site was preferred to be as close as possible to the site of occlusion or stenosis. We used an ultrasound-guided [technique] through the patent distal part of the subclavian vein, basilic vein, or through the functioning arteriovenous fistula.”

The venogram identified and localised the closure site; to ensure stable access, the wire was then crossed over the lesion to the inferior vena cava, where it was exchanged for a stiffer one, and balloon dilatation was performed to create a small

channel into which the catheter could be introduced. A repeat venogram confirmed the presence of the channel within the occluded segment and the tunnelled catheter was then inserted, introduced either over the wire through the subclavian vein or via another percutaneous puncture.

Of the 30 participants in the study, 16 were male and 14 female, with a mean age of 53.2 years; 21 had central venous occlusion, and nine had central venous stenosis, described by Lotfy as “very critical [stenosis], more than 90%”. In 21 cases, the subclavian vein was affected, and in nine the innominate vein.

All cases were treated by angioplasty only, with no cases of stenting. “We do not use any stents for these cases because the aim is to reduce the catheter, not to maintain the reasons to have one,” said Lotfy.

“No procedural complications occurred. The technical success rate was 85%, with failure in 15% due to an inability to pass the wire. This failure was accounted for by total occlusion.

All patients with stenosis were successfully dilated.”

One-year follow-up to check the competency of subsequent dialysis sessions through the inserted catheter demonstrated that 100% of patients had an adequately functioning catheter, leading the researchers to conclude that dilatation of an occluded central vein followed by permanent catheter insertion can be achieved successfully using an endovascular method.

Non-tunnelled catheters are extensively used, but they increase the risks of central venous occlusion and can interfere with preparation and planning for the construction of an AVF for permanent vascular access. ”

Charing Cross Special Edition

dyslipidemia.

Misra indicated that a possible future direction of this work could be its use in conjunction with angioplasty for stenotic AV fistulae. He told delegates at ISET that there was interest from the cardiothoracic surgeons at Rochester in using this therapy in coronary artery bypass grafting (CABG), and concluded by remarking that “Obviously, we can start to think about using this in the lower extremity as well.”

He and his colleagues are in the process of filling an IDE for using this stem cell therapy with angioplasty and periadventitial catheters.

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Registry and IDE trial back Lutonix DCB in AV fistula

The safety of the Lutonix drug-coated balloon (DCB) in dysfunctional arteriovenous (AV) fistulae has been supported by findings from two trials reported at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany). Scott Trerotola of the Perelman School of Medicine, University of Pennsylvania (Philadelphia, USA) presented for the first time the 24-month safety results from the Lutonix AV Investigational Device Exemption (IDE) clinical trial. Complementing these findings, Panagiotis Kitrou, Patras University Hospital (Rio, Greece) outlined six-month data from the Lutonix AV global registry.

B

eginning his presentation, Trerotola informed delegates: “This is the only US Food and Drug Administration (FDA) approved DCB balloon for AV fistulae in the USA. Safety outcomes are non-inferior to angioplasty, mortality is non-inferior, and the mortality rate is lower than expected in the US population,” and added, “it is the only DCB with a multicentre randomised trial result at two years.”

Outcomes from the Lutonix AV global registry reinforced his findings, as Kitrou reported: “Target lesion primary patency at six months was 73.5% according to Kaplan-Meier analysis, and this reaches 75% at six months if you exclude the central veins. These results are consistent with the AV trial from Trerotola, as well as previously published data from retrospective analysis from our department.”

Lutonix AV IDE is a prospective multicentre trial at 23 clinical sites that randomised 285 subjects 1:1 to receive either the DCB (141) or percutaneous transluminal angioplasty (144). The objective was to assess the safety and effectiveness of the Lutonix 035 AV DCB percutaneous transluminal angioplasty catheter in the treatment of dysfunctional AV fistulae. The primary effectiveness endpoint was target lesion primary patency at six months, with a primary safety endpoint of freedom from any serious adverse event involving the AV access circuits through 30 days. Additional follow-up visits were at one, three, six, nine, 12, 18, and 24 months.

Patient characteristics were evenly matched between groups, “so any differences we cannot blame on demographics,” said Trerotola. Target lesion primary patency was achieved in 61.6% of patients in the Lutonix arm, and in 49.4% for those who underwent percutaneous transluminal angioplasty alone. According to Trerotola, the primary safety endpoint “was easily met”, and was 36.9% at 12 months in the Lutonix group and 28.7% in

controls (p= 0.0009). At 24 months, 20.6% in the Lutonix arm versus 16.5% in the control arm met this endpoint (p=0.0028). Yet, despite the p-values, Trerotola described the findings as “statistically indifferent, because this is a non-inferiority examination”.

Furthermore, there was no statistical difference between groups for mortality rates, with deaths at 24 months for

Inflation time was also crucial—the longer the inflation time, the better the results.”

Lutonix 23.4% (33) compared to 18.1% for subjects who received standard percutaneous transluminal angioplasty (26). However, one subject in the control group withdrew voluntarily from dialysis, and four in the Lutonix group.

“If you take out the ones that voluntarily withdrew, the difference now becomes 29 and 25, which is pretty much numerically indistinct,” Trerotola remarked.

According to Trerotola, the expected two-year mortality rate on dialysis is 33.4% in the USA on average.

Therefore, discussing the current findings, he suggested: “Perhaps because these [trial] patients come more frequently, or are getting better care, their mortality was actually substantially better in both groups than what is published by the US Renal Data System.”

The Lutonix AV global registry further supports the Lutonix DCB in AV fistula. The prospective, multicentre, single arm, real-world registry also investigates the clinical use and safety of the Lutonix DCB percutaneous transluminal angioplasty catheter. Specifically, it aims to examine the role of this DCB in the treatment of

Novel catheter delivering liquid paclitaxel safely and effectively prevents restenosis in below-theknee lesions The efficacy and safety of a novel catheter delivering liquid paclitaxel for the prevention of restenosis in below-the-knee lesions has been confirmed by study investigators across 17 sites in the USA. This is the conclusion of the COPPER BTK trial (Occlusion Perfusion Catheter for Optimal Delivery of Paclitaxel for the Prevention of Endovascular Restenosis—below-the-knee), presented by Pradeep Nair of the Cardiovascular Institute of the South Houma (Los Angeles, USA) at the 31st International Symposium on Endovascular Therapy (ISET; 27–30 January 2019, Hollywood, USA).

THE OCCLUSION PERFUSION catheter (Advanced Catheter Therapies) is a universal drug-delivery device.

According to an Editor’s note in Vascular Disease Management written by Nair in his capacity as New Technologies Section Editor for the

publication, this catheter “allows for delivery of antiproliferative drug[s] to a targeted treatment area, demonstrates exceptional medial layer drug uptake, and can be re-used for multiple treatment sites. Additionally, the outer occlusion balloons prevent downstream

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dysfunctional native and synthetic AV fistulae in the arm.

In what Kitrou described as “the biggest enrolment for a DCB so far”, 324 subjects have been registered in the study at 25 international sites.

While primary effectiveness and safety endpoints mirrored those in the Lutonix AV IDE study, followup via clinical assessment occurred at six months, and clinical or telephone assessments were carried out at three and 12 months.

Among participants, the mean age was 67 years, while 41.9% had diabetes, 73.4% suffered from hypertension, and 26.9% had dyslipidaemia. Kitrou explained: “Both fistulas and grafts were included in the study in a proportion of 3:1 [75% native fistula versus 25% synthetic graft]. In three out of four cases the access location was on the left arm.”

At six months, target lesion primary patency was 73.5%. Access circuit primary patency at six months was 70.9%, and freedom from primary safety events at 30 days was 96.1%.

Subgroup analysis of procedural variables determined that pre-dilatation in vessel preparation, and more than two minutes’ inflation time affected outcomes. “It will make a big difference if you properly prepare the vessels.

In cases that the fistula was not prepared there was a statistically significant difference in favour of preparation.

Inflation time was also crucial—the longer the inflation time, the better the results.”

Therefore—to conclude—Trerotola reported safety outcomes that were non-inferior to percutaneous transluminal angioplasty, which were reinforced by the Lutonix AV global registry. Moving forward with these findings, Trerotola said: “We have an ongoing study [...] which will enrol another 213 patients with this device.”

Additionally, Kitrou promised further details on these sub-analyses for the registry in the coming months.

washout of antiproliferative agent[s].

Ongoing trials will help establish its role in peripheral arterial disease intervention for both above- and below-the-knee applications.”

The prospective, non-randomised, open-label, multicentre study presented

by Nair at ISET aimed to evaluate the efficacy of the occlusion perfusion catheter after atherectomy and percutaneous transluminal angioplasty (PTA) in treating de novo and restenotic below-the-knee lesions, as determined by primary patency at six months. The safety profile of the device was also assessed, defined as freedom from major adverse events at one month. Major adverse events included target lesion revascularisation, major amputation, and target limb related death. A total of 35 patients enrolled in the study, with a mean lesion length of 119.1±80.4mm, and a diameter stenosis of 93.7±8.81%.

All patients were in Rutherford class 2–5.

At six months, primary patency was 88%, and the study investigators reported 96% freedom from clinicallydriven target lesion revascularisation.

There was no target lesion revascularisation, target limb related death, or major amputation in the target limb. The Rutherford classification also

improved on average over the course of the study: at baseline, the average Rutherford score was 3.6±0.8, and at six months, the average Rutherford score was 1.8±1.2.

These positive data drew Nair to summarise: “The delivery of liquid paclitaxel using the occlusion perfusion catheter under controlled pressure was technically achievable without procedural complications. The feasibility and initial efficacy of this device provide encouragement for this new technique, with the potential as an alternative approach for infrapopliteal revascularisation. In particular, the ability to treat very long or multi-vessel lesions with a single device could provide a more economical option.”

In addition, he added: “The safety profile in this small cohort study is particularly favourable, and focuses treatment at the target lesion with minimal drug loss that can occur with drug-coated balloons (DCBs).”

Nair acknowledges that longer term follow-up and larger clinical studies will be needed to support the initial findings of this technology with headto-head comparisons with DCB and balloon angioplasty (with and without atherectomy).

March 2019

Stents

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Zilver PTX drug-eluting stent 12-month outcomes on par with bypass surgery The performance of the Zilver PTX drug eluting stent (Cook Medical) in a recent trial was non-inferior to prosthetic bypass surgery in the treatment of femoropopliteal TASC C and D lesions, demonstrating similar patency rates and leading to shorter hospital stays and fewer complications. Marc Bosiers unveiled 12-month results and preliminary 24-month results from the ZILVERPASS randomised controlled trial (RCT) at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

“THIS WAS THE first randomised trial looking at bypass surgery above the knee versus an endovascular tool,” Bosiers said. “The Zilver PTX is at least non-inferior to classical bypass, with a shorter hospital stay and less 30-day complication rates. Looking at 12-month primary patency, which was our primary endpoint in this study, the Zilver PTX had a 74.5% [rate] vs. 72.5% in the bypass arm, so absolutely no difference.”

The ZILVERPASS RCT is a prospective multicentre study in four countries and 13 clinical centres, randomised 220 patients 1:1 to Zilver PTX (113) and surgical bypass (107). Inclusion criteria were all patients with Rutherford class 2–5, and lesion length ≥15cm. Exclusion criteria were previous surgery or endovascular procedure in the target vessel, any planned surgical intervention or procedure within 30 days of the study procedure, and any major amputation in the target or nontarget limb.

Bosiers explained: “The primary

endpoint in this trial was similar in both arms. We looked at absence of binary restenosis in the Zilver PTX arm and also the bypass arm, where we looked more especially at the proximal and distal anastomoses.”

In terms of patient demographics, Bosiers highlighted “slightly more patients” with critical limb ischaemia and/or hypertension in the bypass arm, as well as more obese patients with hypercholesterolaemia. “But, if we look at the lesion length we saw in both arms very long complex lesions, with an average lesion length of 25cm in both arms.” Among these, Bosiers noted, 94.5% were occluded.

Procedural characteristics were significantly different: “The procedural time in the vascular intervention was almost half of the time of the surgical intervention [59 minutes vs. 123 minutes, p<0.001], and also the hospital stay in the vascular arm was an average of 2.5 days, versus eight days if you did a bypass.”

Freedom from complication rate at 30 days was 95.6% for subjects treated with the drug-eluting stent versus 88.7% for those undergoing bypass surgery, a statistically significant difference (p=0.004). The most common complications arising from stent implantation were bleeding at puncture site and haematoma; infections and lymphoedema were most common following surgery.

The 12-month survival rate for bypass subjects was 96.1%, and in the Zilver PTX group it was 94.5%. “There was no difference between survival or deaths between the two arms, either in numbers or in reasons for death,” said Bosiers.

“If we look at the difference between claudicants and patients with critical limb ischaemia (CLI), because there were more patients with CLI in the bypass arm, also here there is no difference in terms of primary patency.” Primary patency rate for claudicants at 12-month follow-up was 75.8% for ZIlver PTX and

BELSTREAM sets out to BOLSTER three-year safety and efficacy data for the Lifestream covered stent

The BOLSTER trial has shown favourable three-year outcomes in the treatment of stenotic and occlusive lesions in the iliac arteries using CR Bard’s Lifestream expandable covered stent, with satisfactory patency rates and improved quality of life measures. Investigators have now set up BELSTREAM, a physician-initiated trial to study the stent’s performance in complex TASC C and D lesions.

T

he balloon-expandable vascular covered stent in the treatment of iliac artery occlusive disease (BOLSTER) trial reported 36-month data of the Lifestream stent at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany). Presenting the outcomes, John R Laird (Adventist Heart and Vascular Institute, St Helena, USA) told the conference: “The clinical outcomes were excellent; there was sustained clinical success at 36 months of 92.5%. We saw a primary patency of 92% at 12 months, dropping down to 77.2% at 36 months. One of the concerns with covered stents is that they become occluded and can be potentially more difficult to re-treat or recanalise, but we saw actually in the BOLSTER trial quite excellent secondary patency rates of 95.6% at 24 months, and 93.4% at 36 months.”

A prospective, multicentre, non-randomised singlearm trial, BOLSTER enrolled 155 participants at 17 investigational sites in the USA, Europe, and New Zealand. The trial was designed to investigate the safety and effectiveness of the balloon-expandable vascular covered stent for the treatment of stenosis and occlusions in the common and/or external iliac arteries.

According to Laird, “there was nothing particularly unusual about the baseline characteristics of these patients”, of which 69% were male, and 31% female.

In all, 197 lesions were treated in the 155 subjects, and 230 Lifestream covered stents were implanted, 26.6%

into the external iliac and 73.4% into the common iliac artery; 64% of lesions were moderately to severely calcified, but only 10.7% were totally occluded.

Freedom from target lesion revascularisation (TLR) on Kaplan Meier analysis was 94.7% at 12 months, and 83.9% at 36 months. Outlining a proportional analysis of the TLR rate, he said: “We do see from 12 to 24 months some drop off with regards to freedom from target lesion revascularisation, and a little bit of an additional drop off between 24 and 36 months.” The rate at one year was 5.4% (8/147) versus 14.2% (20/139) at two years, and 17.6% (23/131) at three years.

Cumulative improvement in clinical outcome was measured as an increase of ≥one in baseline Rutherford category value, with improvement maintained through 36 months. BOLSTER also demonstrated a clinical success rate of 92.5% at three years. And, patients’ quality of life, as assessed by the walking impairment questionnaire, improved from baseline to nine months by just over 32 points and was sustained through to three years.

“We saw similar clinical results with regard to the ankle brachial index, which increased from 0.7 to 0.95 at nine months, and that was again well-maintained out to 36 months. The Lifestream covered stent provided good clinical outcomes through three years for the treatment of stenotic and occlusive lesions in the iliac arteries, with satisfactory patency rates and really excellent overall clinical outcomes.”

74.4% for a bypass, and 70.7% versus 70.8%, respectively, in patients with critical limb ischaemia.

At 12 months, “freedom from target lesion revascularisation was also slightly better for the Zilver PTX at 80%, versus bypass at 76% [p=0.5379], and secondary patency was equal in both arms”, with the clinical endpoint of evolution in Rutherford classification showing “no difference—a sustained benefit and improvement of Rutherford classification”.

Bosiers also outlined preliminary data on two-year outcomes for 110 patients, describing a primary patency rate of 68.2% for Zilver PTX as “a sustained benefit”, vs. 63.7% for a bypass. Freedom from target level revascularisation at 24 months was 80.4% and 70.3% for Zilver PTX and bypass, respectively, and for “secondary patency, no difference”, with rates of 92.8% in the Zilver PTX arm and 88.1% in the bypass group. Follow-up has been extended to five years.

BELSTREAM seeks to prove stent efficacy in more complex lesions

Koen Deloose, head of Vascular Surgery at AZ Sint Blasius in Dendermonde, Belgium, further provided an update on BELSTREAM, a Belgian study which is currently enrolling to assess Lifestream in TASC C and D lesions. “Bare metal stents are working perfectly in simple TASC A and B lesions, but there is definitely room for improvement in the more complex TASC C and D lesions,” Deloose said at LINC. “Lifestream, with high flexibility and minimal foreshortening, seems to be an ideal tool for this task. The BELSTREAM trial has set out to prove this in a multicentre prospective way.”

Deloose described the lesions treated in BOLSTER as “very easy straightforward lesions. The majority were TASC A and B, almost 90%, and the mean lesion length was 3cm. In 10% of the cases occlusions were treated. That is the reason that we have set up a physician-initiated trial.”

BELSTREAM is a prospective, single-arm, nonrandomised multicentre study which aims to enrol 70 patients across seven Belgian centres. The study will assess the safety and efficacy of the covered stent for the treatment of stenoses and occlusions in complex TASC C and D lesions in iliac arteries.

The primary efficacy endpoint is primary patency at 12 months, and the primary safety endpoint is freedom from periprocedural serious adverse events (defined as procedure/device-related death or major adverse events at 30 days). Secondary endpoints include technical success, freedom from TLR or target vessel revascularisation, stent graft occlusion rate and amputation rate above the knee, as well as ankle brachial index (ABI). Inclusion criteria are Rutherford class 2–4, presence of stenosis of more than 50%, or occlusion. Extensions into the aorta or common femoral artery are excluded, but all other TASC C and D lesions are allowed.

“Enrolment is ongoing,” Deloose informed delegates, “41 patients are enrolled out of 70, and we expect the initial results next year during LINC.”

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March 2019

Conference coverage

ENGAGE registry aims to set a new standard for performance and management of EVAR Benchmarking of endovascular aneurysm repair (EVAR) performance must be established using contemporary devices, and the threshold for reintervention post-procedure should be lowered in certain high-risk individuals, according to an interpretation of the ENGAGE registry.

TWO PRESENTATIONS AT the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany) have recommended that the findings be used to bring about a change in the evidence base and in current practice. ENGAGE is a global post-market registry of participants consecutively enrolled between March 2009 and March 2011; 1,263 abdominal aortic aneurysm (AAA) patients were treated with the Endurant endograft (Medtronic) in 79 centres across 30 countries and six continents.

Follow-up period was 30 days, with annual visits through to 10 years.

Dittmar Böckler from the University of Heidelberg in Heidelberg, Germany, used the long-term results to dispute the use of a 2011 Circulation paper from Schanzer et al as a yardstick for predicting AAA sac enlargement after EVAR. “Sac diameter after EVAR is the main parameter to really prove long-term durability and results. Everybody knows [Schanzer et al] as one of the most cited papers—I would like to debunk that publication with data from ENGAGE.” Also speaking at LINC, Michel MPJ Reijnen (Rijnstate, Arnhem, The Netherlands) evaluated the clinical significance of type II endoleaks, and used the ENGAGE registry to demonstrate that the criteria for reintervention must be lowered for a subset of patients with an isolated type II endoleak who later present with a type I endoleak. “The subsequent development of type I endoleak results in a higher risk of aneurysm-related complications, including a very high rupture rate and very high need for second endovascular reinterventions. Identification of those patients that have a type II and later

develop a type I is the future challenge, and a lower threshold of reintervention is indicated in this subset.”

Type II endoleak subset sees better overall survival

Reijnen outlined a subanalysis of two groups in the registry. “We took those patients with an isolated type II endoleak and compared them to the subset that had no endoleak at all. And, in addition, we looked at another subset of those patients with a type II endoleak that later were diagnosed with a type Ia endoleak.”

Throughout five years of follow up, 197 (15.6%) patients were identified with an isolated type II endoleak. The other subset analysed 22 patients with a type II endoleak who later developed a type I. The mean time between diagnosis of type II and then type I was 32 months.

There were significantly more aneurysm enlargements among patients with an isolated type II endoleak, and significantly less sac regression, Reijnen noted. Freedom from secondary interventions was 79% in the type II endoleak group, as compared to 92% in the group with no endoleaks (p<0.0001).

“The difference is highly significant.

However, when we look at the real outcome measures, which are aneurysm related mortality and ruptures, there is no difference at all. You may debate whether this is because of reinterventions, or regardless of these interventions—that is something that we cannot conclude out of this database,” Reijnen explained.

Patients with type II endoleaks had a better overall survival compared to patients without any documented endoleaks, with freedom from all-cause mortality at five years of 77.2% vs.

67% (p=0.0101).

Within the second subanalysis, the incidence of aneurysm rupture for subjects with a type II and a subsequent type I endoleak was 18.2% (4/22) compared to 0.51% (1/197) in those with isolated type II endoleaks.

“Patients with a type II who later developed a type I experienced significantly lower freedom from AAA rupture,” Reijnen explained, “with 80.2% vs. 99.5% [p<0.001], and significantly lower freedom from AAA related mortality; 90.9% vs. 99.5% [p=0.002].

As can be expected, there were more ruptures in these patients, and more deaths because of ruptures in this subset.”

These patients also underwent significantly more second endovascular procedures—at five years, freedom from second procedures was 32.5% vs.

79.2% (p<0.0001). The frequency of reinterventions required in this small subset, Reijnen pointed out, increases the importance of early identification, and suggests that a lower specification for reintervening may be warranted in cases where a type I endoleak is suspected.

Improving long-term EVAR outcomes

Published in Circulation in 2011, Schanzer et al found a five-year postEVAR AAA sac enlargement rate of 41%, which Böckler described as “a really bad outcome after five years. Is that really the current benchmark these days? The devices available at that time were firstand second-generation devices—none of which are on the market anymore. Today, we have fourth- and fifth-generation devices. How much have EVAR results improved over the last five to 10 years,

Rivaroxaban and aspirin therapy for peripheral arterial disease improves patient outcomes Investigators from the COMPASS trial have advocated the use of dual therapy rivaroxaban and aspirin in the long-term treatment of high-risk patients with peripheral arterial disease (PAD). Sebastian Debus, of the University Medical Center Hamburg-Eppendorf in Germany, presented the latest evidence on rivaroxaban vascular dose in PAD at the Leipzig Interventional Course (LINC; 20–25 January, Leipzig, Germany), and said it significantly improved outcomes for these patients.

“T

he dual pathway inhibition of rivaroxaban vascular dose plus aspirin represents a major advance in the management of PAD, according to the COMPASS trial, and therefore, should now be considered for long-term treatment in high-risk patients with PAD,” Debus told delegates, adding the therapy is the only available treatment that significantly reduced the rate of major adverse limb events (MALE) and major adverse cardiovascular events (MACE). COMPASS showed that with rivaroxaban 2.5mg twice daily plus aspi-

rin, MACE rates were reduced by 28%, MALE rates by 46%, and major amputation rates by 70%. In addition, despite an expected increase in bleeding events, no significant increase was observed in fatal or critical organ bleeding.

Cardiovascular morbidity is the leading cause of mortality worldwide, and among cardiovascular patients those with PAD represent the cohort with by far the highest risk for cardiovascular mortality. Lifestyle changes and a healthy diet combined with medical therapies attempt to tackle the issue, and

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new anticoagulant and antithrombotic strategies are being developed.

However, according to Debus, new treatments have not been addressed by the current European Society of Cardiology (ESC) guidelines from 2017, with recommendations “mainly based on antithrombotic agents. Only in exclusive situations, like below-the-knee revascularisations, there was seen an indication for anticoagulants. Broadly,” he said “antithrombotic therapies are the main pillar of medical treatment in these patients.”

and are EVAR results more durable with new generation devices?”

Making a case for using ENGAGE as the standard, Böckler argued “the Schanzer paper had no consecutive enrolment, multiple first generation endografts were used, and only imaging data were assessed; clinical outcomes data were not collected. The real world all-comer registry ENGAGE has clinical data, used a single fourth generation device, and had a really independent clinical event committee [...] and more than 90% follow-up data after five years—a good base to judge. ENGAGE patients were treated both within IFU and outside IFU—that is real practice.”

Baseline anatomical characteristics were similar between both datasets.

Schanzer et al reported 41% AAA sac enlargement through five years compared to ENGAGE, which was 9.2% within IFU, and 18.6% out of IFU. “If you transfer [the ENGAGE] data, you see a significant improvement regarding freedom from AAA enlargement [ENGAGE inside IFU 83.6%, outside IFU 70.8%].” Only 61% had freedom from AAA enlargement inside IFU, with a rate of 56% outside IFU after 5 years. In addition, Böckler said, the 41% sac enlargement found in Schanzer et al may have been overestimated, as patients doing well would not have had an additional computed tomography (CT) and thus could have been missed.

“The often quoted Schanzer paper involves devices which are not on the market,” concluded Böckler. “The new benchmark should be the use of a contemporary device, if we discuss EVAR results these days.”

But, Debus conceded “bleeding rates continue to be an issue. Overall, bleeding rates [in COMPASS] were increased in the rivaroxaban groups; however, if we have a closer look to fatal bleedings and also intracranial bleedings, we can realise that there is no statistically significant difference between the rivaroxaban group and the placebo group with aspirin alone.”

In addition, although bleeding rates were increased, they remained low, and thrombotic and severe bleeding risk was reduced by 28% in the group taking rivaroxaban plus aspirin compared to placebo, providing, he said “an overall benefit for the patient with rivaroxaban 2.5mg twice daily daily plus aspirin versus aspirin alone in this large subgroup within the COMPASS trial. This means that for every 1,000 patients with PAD treated with rivaroxaban plus aspirin, 27 MACE or MALE events would be prevented, and one fatal and one critical organ bleeding event would be created over a 21-month observational period.”

March 2019

Conference coverage

DETOUR system demonstrates “excellent” safety and “promising” durability in large lesions at 12 months In a recent study, the DETOUR system for the treatment of extreme superficial femoral artery (SFA) lesions demonstrated “excellent” long-term safety and “promising” durability at 12 months. The results of the DETOUR I trial were presented by first author Sean Lyden of Cleveland Clinic (Cleveland, USA) at the 2019 Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

ACCORDING TO THE investigators, the DETOUR I trial represented the “largest prospective series evaluating the percutaneous treatment of SFA lesions” with an average lesion length of 39cm. The study yielded “excellent” long-term safety in patients with advanced disease and extremely long, complex lesions, with venous health maintained through 12 months. In addition, the DETOUR system, granted CE mark in February 2017, demonstrated “promising” durability at 12 months, which “compared favourably” to existing therapeutic durability, even in lesions long enough to be excluded from traditional peripheral trials.

Lyden and colleagues comment that 20 years into the “endo revolution”, patients with long-segment SFA disease have “limited” treatment options, and live with

“debilitating, lifestyle-limiting pain.”

The current failure rate at 12 months is 50%, they remark. Furthermore, existing endovascular devices are designed for shorter lesions, and thus deliver “suboptimal” results in long lesions.

The investigators describe the present study as a prospective, single-arm multicentre clinical evaluation of the DETOUR system and procedure for percutaneous bypass. Patients included in the study all had a de novo, chronic total occlusion (CTO), or in-stent restenosed (ISR) femoropopliteal lesion ≤10cm. In total, 77 patients, or 81 limbs, were enrolled. Follow up would be examined at 30 days, and subsequently three, six, 12, 18, 24, and 36 months.

Primary safety was defined as freedom from a major adverse event (MAE) at 30 days, and primary efficacy as primary

Sean Lyden

patency at six months (PSVR ≤2.5) with no target lesion revascularisation.

Lyden and colleagues detail lesion distribution by length: 97% were ≥25cm, 86.4% ≥30cm, 71.6% ≥35cm, and 33.1% ≥40cm. Of the patients with extreme lesions, defined as being ≥30cm, 88.1% were male, with an average age of 65.1±7.3. Of the 71 lesions in this group, lesion length was 38.7cm±3.8cm.

In the patients with extreme lesions, primary patency at 12 months was 76.1%, primary assisted patency 81.7% and secondary patency 94.4%. In terms of safety outcomes, freedom from death was 100% at 30 days, and 98.6% through

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12 months. Freedom from CD-TLR was 93% at 30 days and 77.5% at 12 months, freedom from acute limb ischaemia was 100% and 98.6%, respectively, and freedom from major amputation, 100% through both 30 days and 12 months.

In terms of functional improvement at 12 months, the authors note a “significant improvement” at 12 months based on the Rutherford Becker clinical classification, and a similar improvement at 18 months according to the ankle brachial index.

According to Lyden and colleagues, the DETOUR procedure has the “potential to fill a significant gap in the endovascular market”, describing it as an “endovascular solution that is complex-lesion neutral,” referring to CTO, Ca++, and ISR lesions and the 74% patency at 12 months compared to the average of 50%.

The investigators refer to the 18-month preliminary results from the DETOUR I trial from Ehrin Armstrong (Rocky Mountain Regional VA Medical Center, Denver, USA). Primary patency was 67.6%, primary assisted patency 78.9%, and secondary patency 94.4%.

At LINC, Lyden mentioned that the DETOUR II IDE trial is currently enrolling, and will serve to “build upon the growing body of clinical evidence.”

This will be a prospective, single-arm, multicentre clinical evaluation of the DETOUR system and procedure for percutaneous bypass. De novo, CTO, or ISR femoropopliteal lesions ≥15cm will be included.

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March 2019

Depression and peripheral arterial disease: A call to action Joel Ramirez S Marlene Grenon Comment & Analysis With “an indisputable association between depression and peripheral arterial disease (PAD)”—nearly a third of PAD patients experience comorbid depression or depressive symptoms— Joel Ramirez and S Marlene Grenon here call for vascular interventionalists to take a more active role in their patient’s mental health: increasing the awareness of the links between these two conditions, recognising the symptoms of depression, and referring patients to a mental health specialist where appropriate.

P

eripheral arterial disease (PAD) is a major global health problem, which has been increasing in incidence.1 PAD has been associated with an increased risk of limb amputation, adverse cardiovascular events, and mortality as well as impaired quality of life, which have collectively resulted in a high economic burden on society.2 Despite widespread campaigns to improve cardiovascular health, the prevalence of PAD is expected to increase with the aging world population. Given the large impact that PAD has, it is important that as vascular specialists we are able to adequately identify, prevent, and treat modifiable risk factors for PAD. Although not commonly recognised by interventionalists, the incidence of depression has been rising, particularly in young adults. Depression is a leading cause of disability worldwide,3 and has become a well-recognised risk factor for the development and progression of coronary artery disease (CAD). In fact, depression has been formally recognised by the American Heart Association (AHA) as a risk factor for CAD incidence and adverse outcomes, which has resulted in the creation of guidelines for depression screening in this patient population.4 Given the overlap between risk factors for CAD and PAD, investigators have recently begun to examine the association between depression and PAD. My colleagues and I have dedicated our recent research efforts to the problem of depression and PAD. Our understanding of the risk factors for the development and progression of PAD used to be narrower, as we primarily only considered traditional risk factors such as smoking, hypertension, hyperlipidemia, and diabetes among others. We now have a more comprehensive understanding of this disease and have recognised that mental

illness, specifically depression, may play a role in the development of PAD and adverse outcomes among PAD patients.

It has been reported that nearly a third of patients with PAD have comorbid depression or have experienced depressive symptoms.5 Among patients with PAD, depressive symptoms have been associated with worse claudication, decreased patency after peripheral revascularisation, and increased incidence of major amputation, adverse cardiac events, and mortality.6 From a pathophysiological perspective, our findings support mechanistic pathways linking depression to PAD. We have shown that worse depressive symptoms are correlated with higher levels of inflammation,7

Peripheral arterial disease associated with increased risk of limb loss.8 The scientific evidence supporting a relationship between depression and PAD is growing. To address this new burden of disease, we need to generate innovative solutions and engage leaders in vascular medicine and surgery. The first step in addressing the role of depression in PAD is increasing awareness of the relationships that have been reported.6 While outside the comfort zone of most interventionalists, understanding the role that depression plays in PAD could provide additional insight into opportunities to improve outcomes in this patient population. We have a responsibility to address the well-being of our patients, by enabling open dialogue about mental health and by ensuring that our patients are receiving proper screening and treatment for mental illness. Although most interventionalists are uncomfortable treating or managing mental illness, as the impact of depression on PAD becomes more clear, it is essential that we recognise the signs and symptoms of depression, and refer patients to mental health specialists or primary care physicians for appropriate diagnosis and treatment.

Our understanding of the pathophysiology that implicates depression with the development of atherosclerosis is largely based upon CAD animal models and patients with CAD. Although CAD has a similar pathophysiology to PAD, there are some differences, and research specific to PAD will be necessary to better understand the relationship between depression and PAD. Furthmore, our understanding of the clinical impact that depression has on PAD is currently limited to a few studies.6 We strongly encourage that investigators conduct basic science, translational, and clinical research examining the association between depression and PAD. For clinical and translational research studies, we recommend collecting data related to depression and/or eliciting a brief psychiatric history, documenting antidepressant medications or utilisation

Mental illness, specifically depression, may play a role in the development of PAD and adverse outcomes among patients with PAD.” which may mediate the development of PAD and adverse outcomes. Aside from its pro-inflammatory properties, we recently reviewed6 a tremendous body of evidence that suggests that depression can dysregulate the metabolic system, the hypothalamic-pituitary-axis, and the coagulation pathway, all of which are crucial to the proper functioning of the cardiovascular system. Although the relationship between depression and PAD is convincing, there are currently a paucity of reports examining how antidepressants or behavioral therapy alters the risk of PAD incidence or outcomes in this patient population. However, a recent study by Arya et al has observed that among patients with PAD and depression, the absence of antidepressant use was

of behavioral therapy, and screening for depression using validated questionnaires, such as the Patient Health Questionnaire-9 or Geriatric Depression Scale Short Form.

These variables can also be easily collected for secondary aims in other studies of patients with PAD. Additional research investigating the impact of depression on incidence, progression, and outcomes of PAD is necessary, in order to clarify the mechanisms linking these diseases.

As research examining the relationship between depression and PAD becomes more robust, we hope that screening and treatment guidelines will be created in order to influence everyday clinical practice.

Given that there are similar guidelines from the AHA for depression and CAD, this seems reasonable.4

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Furthermore, innovative digital health solutions that aim to approach the treatment of depression in ways that are more adapted to the needs of our population (e.g. telehealth and on-thego apps) are becoming more available.

Utilising these technologies may allow for improved identification and management of depression in PAD patients. We encourage vascular clinicians and investigators to engage with this rapidly evolving landscape of digital health innovation, where disruption may help improve care that PAD patients receive.

Recent evidence has demonstrated that an indisputable association exists between depression and PAD. Although our understanding of this relationship is still limited, we need to increase the awareness of the potential role that depression likely has among patients with PAD. This includes referring patients with PAD, or those who are at high risk of developing PAD, to mental health specialists or primary care physicians for screening, diagnosis, or treatment when appropriate.

Additionally, in order to further understand this relationship, more research focusing on depression and PAD must be done.

We urge investigators to further study this relationship and to collect information on mental health and specifically, depression, in study participants with PAD. Lastly, we call for vascular specialists to become more engaged in innovative digital health solutions that are becoming increasingly available for the treatment of chronic diseases and mental health.

Joel Ramirez is a senior medical student at the University of California, San Francisco School of Medicine, and a research fellow in the Department of Surgery, Division of Vascular and Endovascular Surgery, University of California, San Francisco, USA. S Marlene Grenon is a vascular surgeon in the Department of Surgery, Division of Vascular and Endovascular Surgery, University of California, San Francisco, USA, and at Evry Health, Dallas, USA. References: 1. F owkes FG, Rudan D, Rudan I, et al Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382: 1329-1340. 2013/08/07. DOI: 10.1016/S0140-6736(13)61249-0.

2. M orley RL, Sharma A, Horsch AD, et al Peripheral artery disease. BMJ 2018; 360: j5842. 2018/02/09. DOI: 10.1136/ bmj.j5842.

3. F errari AJ, Charlson FJ, Norman RE, et al Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010.

PLoS Med 2013; 10: e1001547. 2013/11/14. DOI: 10.1371/journal.pmed.1001547.

4. L ichtman JH, Bigger JT, Jr., Blumenthal JA, et al Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation 2008; 118: 1768-1775. 2008/10/01. DOI: 10.1161/ CIRCULATIONAHA.108.190769.

5. M cDermott MM, Greenland P, Guralnik JM, et al Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease. J Gen Intern Med 2003; 18: 461-467. 2003/06/26.

6. R amirez JL, Drudi LM and Grenon SM. Review of Biologic and Behavioral Risk Factors Linking Depression and Peripheral Artery Disease. Vasc Med 2018; In Press.

7. H ernandez NV, Ramirez JL, Khetani SA, et al Depression severity is associated with increased inflammation in veterans with peripheral artery disease.

Vasc Med 2018; 23: 445-453. 2018/07/24. DOI: 10.1177/1358863X18787640.

8. A rya S, Lee S, Zahner GJ, et al The association of comorbid depression with mortality and amputation in veterans with peripheral artery disease. J Vasc Surg 2018 2018/03/29. DOI: 10.1016/j.jvs.2017.10.092.

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March 2019

Innovation

BIBABriefings

More than 40% of physicians anticipate using fewer drug-coated balloons following Katsanos paper A BIBA MedTech survey indicates that 43% of physicians plan to use fewer drug-coated balloons for the management of peripheral arterial disease after a meta-analysis (by Katsanos et al) found that the application of paclitaxel-coated balloons and stents in the femoropopliteal artery was associated with an increased risk of death. A prior BIBA MedTech survey, conducted before the Katsanos paper was published, suggested that physicians believed that their use of drug-coated balloons would increase.

Source: BIBA MedTech Paclitaxel meta-analysis reaction survey January 2019.

I

n December 2018, Konstantinos Katsanos (Patras University Hospital, Rion, Greece) and colleagues caused shockwaves in the vascular community when they published a meta-analysis—in the Journal of the American Heart Association—that found that both paclitaxel-coated balloons and paclitaxel-eluting stents were associated with an increased risk of death at two years compared with control treatments (i.e. percutaneous transluminal angioplasty and/or bare metal stents) for the management of peripheral arterial disease. To try to understand how these findings might affect the use of paclitaxel devices (for peripheral interventions) in clinical practice, BIBA MedTech conducted a survey of physician subscribers of Vascular News and Interventional News. Of note, the survey was performed (in January 2019) prior to further data for paclitaxel being published. For details of these subsequent data, please see pages 22–25.

Of 101 respondents overall, 63% were vascular surgeons, 17% were interventional radiologists, 13% were endovascular surgeons, and 7% were categorised as “other” (including interventional cardiologists).

Furthermore, on average, respondents performed 72 procedures with drugcoated balloons as the primary treatment method (for a femoropopliteal lesion) and performed 17 procedures with drug-eluting stents as the primary treatment method. Just over half (51%) of respondents were from Europe (with 25% from the USA, 13% from Latin America, and 11% from other regions).

Unsurprisingly, given the reaction of the community to the paper, 98% of respondents had heard of the Katsanos meta-analysis.

Predicted use of paclitaxel devices

In the survey, respondents were asked if the main conclusion of the paper—that there was an increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs—were “in line with your own personal practice”. The majority (74%) said “no”. However, they indicated that they would use fewer paclitaxel devices (both balloons and stents) this year.

Of 93 respondents who used drugcoated balloons, about 43% said they anticipated performing fewer procedures using these devices this year, with 37% believing their use would remain the same and 20% thinking that they would perform more procedures (Figure 1).

Similarly, of the 71 respondents who currently use drug-eluting stents, nearly half (48%) predicted that they would perform fewer procedures with these devices this year, with 35% believing their use would be about the same and 17% think they would use more procedures (Figure 2).

These findings are in contrast to a BIBA MedTech survey that was performed prior to the publication of the Katsanos paper. This survey asked physicians working in the top five EU countries (France, Germany, Italy, Spain, and UK) about their management of peripheral lesions. To be included in the survey,

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Source: BIBA MedTech Paclitaxel meta-analysis reaction survey January 2019.

respondents had to perform a minimum of 30 superficial femoral artery procedures a year and a minimum of 10 below-the-knee procedures a year. Of the 149 respondents, 48% were vascular surgeons, 39% were interventional radiologists, and 13% were interventional cardiologists/angiologists.

For all types of lesions, respondents on average predicted that they would use drug-coated balloons in a greater proportion of procedures in the next 12 months than they had in the past 12 months. For example, with short (<15cm) lesions in the superficial femoral artery, respondents predicted that they would use drug-coated balloons as the primary treatment in 35% of procedures in the next 12 months vs. 27% of procedures performed in the past 12 months.

Similarly, they suggest that use of DES would increase.

Looking beyond the Katsanos paper The survey also asked respondents if they felt, following the Katsanos paper,

BIBA Briefings

whether “it is a priority to look beyond paclitaxel to other drugs” and the vast majority (80%) said they thought it was a priority. Furthermore, 64% saw the data as a “serious setback” for drug-elution in the periphery.

However, following patient-level data releases from industry in response to the meta-analysis, polling of delegates at 2019 conferences point in a different direction. At the recent Vascular Leaders Forum, 60% (21/35) of physicians said they would not be more conservative with their drug-device treatments and 86.5% (32/37) said they would not change their clinical practice as a result of the meta-analysis (see page 24).

The Charing Cross International Symposium (15–18 April, London, UK) will further explore the mortality risks of paclitaxel in a dedicated session (see page 6) and, throughout this year, BIBA MedTech will continue to survey those working in clinical practice about their attitudes to and usage of paclitaxel-coated and -eluting devices.

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America.

The platform also reviews data and news.

The aim of every report is to give an overview of the key information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions.

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

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March 2019

Conference coverage

Evidence reiterates a role for the Legflow DCB in complex femoropopliteal lesions The Legflow paclitaxel-coated balloon (Cardionovum) shows consistent efficacy and safety across different trials and in real-world patients, confirming its validity as an alternative treatment in complex and calcified femoropopliteal lesions.

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ata from two trials, REFLOW and LEGDEB, were presented at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany). Marc Bosiers of AZ Sint Blasius (Dendermonde, Belgium) outlined REFLOW’s sixmonth findings and some preliminary 12-month results, while Eugenio Stabile from the Universite Federico II (Naples, Italy) discussed the 12- and 24-month data from the LEGDEB registry.

REFLOW found a six-month survival rate of 98.3%, primary patency of 81%, and a freedom from target lesion revascularisation (TLR) of 90%, described

by Bosiers as “initially very good results, while the six-month Rutherford evolution was also positive and sustained.” He told delegates: “This new balloon is an effective alternative to treat ‘real-life’ long lesions; we need to wait for the final 12-month results for a more in depth analysis to give you more detailed information.”

Meanwhile, the LEGDEB registry achieved similar results in a study population containing high numbers of patients with critical limb ischaemia (CLI; 43%).

At one year, overall freedom from target lesion revascularisation was 83%, with the rate among claudicants at 87%, and subjects with CLI 78%. The rate of restenosis was 77.8%, in-stent restenosis 89.7%, and de novo lesions 82.9%.

Discussing of the LEGDEB findings, Stabile put the

data into context: “Despite the fact that [CLI] is 20 times higher than all the other registries, it is not affected in this more challenging population. The results in the long-term are really comparable. This is the kind of technology that can provide good immediate success, that can allow you to have at least four people out of five out of the cath lab at two years distant [from the procedure], and is not affected by the fact that you can treat a more complex population.”

According to Bosiers, the Legflow peripheral balloon catheter encompasses a design that ensures “an amorphous coating and almost no washout of the paclitaxel during delivery of the balloon, and good lipophilic wall penetration”. REFLOW looked at the efficacy of Legflow in long (>15–20cm) femoropopliteal lesions (TASC C and D) in 120 patients enrolled in Belgium and Germany. The primary endpoint was primary patency at 12 months. Participants were Rutherford class 2–5, with a de novo lesion in the femoropopliteal artery that was suitable for endovascular treatment, and the majority (70%) were claudicants.

Preliminary 12-month data on 90 patients reveal a survival rate of 94%, with primary patency of 70.5%.

According to Bosiers, this was “a good result” given the numbers of long calcified superficial femoral artery lesions. The clinical endpoint of freedom from target lesion revascularisation was 78.8%.

The LEGDEB registry is a prospective multicentre all-comers study of Legflow in femoropopliteal lesions, in which percutaneous transluminal angioplasties were performed according to local practice. The primary endpoint was freedom from restenosis at 12 and 24 months, with freedom from clinically-driven target lesion revascularisation being the secondary endpoint. In total, 140 patients were enrolled in Belgium, Italy, and from two centres in Bulgaria. Of these, 78% were male, 43% had CLI (Rutherford class ≥4), and the average Rutherford class across subjects was 3.5, with 57% claudicants.

In addition to the one-year findings of LEGDEB, Stabile presented preliminary two-year data on 70 patients.

Freedom from target lesion revascularisation was 83.3%, as it had been at one-year, and freedom from restenosis was 72.2% compared to 81% at one year. The sub-population had similar characteristics to the general LEGDEB registry, including a CLI rate of 31%. Describing the results as “pretty stable”, Stabile said: “Despite the fact that we have an increase in restenosis, this is not reflected in an increased need for clinically driven target lesion revascularisation.”

Further, he added: “The result is consistent with all kinds of lesions, and also with the kind of patients that we treat.

Critical limb ischaemia can increase systemic inflammation in the body and this can contribute to an accelerating and increasing risk of restenosis. [Here], the presence of CLI is not affecting the need for revascularisation. And you also have to consider that we have 47% of patients that were treated for a total occlusion.”

Stabile also reiterated that the clinical evidence for the technology was building, while robust evidence also supports its use in coronary arteries. “The data is getting more and more solid, and results are pretty much consistent. It is quite unique that we find three different studies with three different designs [LEGDEB, Rapid, and REFLOW], enrolled by many different physicians, and you end up with the same data on freedom from target lesion revascularisation at six months, and comparable results at 12 months.”

DEEPER trial demonstrates use of Spur stent in complex lesions Initial experience with the Temporary Spur stent delivery system (ReFlow Medical) suggests that the technology can safely and effectively treat complex lesions. Six-month data from the DEEPER trial—a non-randomised feasibility study of the Spur stent system for the treatment of lesions in the infrapopliteal artery—were released for the first time at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

PRESENTING THE FIRST-in-man results, Jihad Mustapha, associate professor of medicine at Michigan State University and chief executive officer at Advanced Cardiac and Vascular Amputation Prevention Centres in Grand Rapids, USA, said the results were “almost too good to be true”.

He described the clinical application as “phenomenal”, adding: “This is extremely promising technology.”

“Tibial arterial disease is mostly located in the arterial wall,” Mustapha explained. “It is not in the lumen. The obstacle that you have in front of you is to get the drug to where you need it to be—the medial adventitia. The Spur stent is designed to be a very elegant and soft type of device … a temporary selfexpanding framework stent that is placed in an open lumen, or a closed lumen—if it is closed, we will open it.”

The all-comers trial of Reflow Medical’s Temporary Spur stent system used a multiple progression clinical method: “The way we used the spur here is similar to the drug-coated balloon (DCB) approach. First, we do percutaneous transluminal angiography (PTA), followed with the spur stent deployment. The Spur stent is then further expanded with a balloon to allow even

This is extremely promising technology, [...] the primary endpoints, in terms of safety, it is too good to be true.” deeper penetration of the spurs into the arterial wall for two minutes, after which the balloon is deflated. The tracks that are made by the spur stent allow the drug to migrate into the media and some of the adventitia. Once completed, the Spur stent is then removed from the artery.”

The DEEPER trial was conducted in the Dominican Republic between October 2017 and May 2018, looking at all types of complex lesions. The primary efficacy endpoint was binary flow of treated lesion sites by continuous wave Doppler at six months. Primary safety endpoints were freedom from device- and procedurerelated death 30 days post-procedure, and freedom from target limb major amputation and clinically driven target lesion revascularisation (CD-TLR) at 12 months post-procedure.

The Spur stent was found to be effective in moderate and severe calcifications, and at preventing elastic recoil: “The

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phenomenally smooth transition of the area that was treated—I have never seen anything like that before. That tells me that the Spur stent is very effective in moderate and severe calcification. What was really impressive, and this is the first time ever I have seen this, is the elastic recoil elimination. We were able to advance the Spur stent through tortuosity and through long lesions. At 24 hours, we did not have any recoil and then, at one month, we actually had positive luminal gain. At three months, we had only 5% recoil.” A lumen reduction of 12% recorded at six months could be attributed to vessel healing, he surmised.

Investigators sought complex lesions for the study—most were TASC C (31.5%) and D (63.1%), with 5.3% classified as B lesions, and none as A; 95% of participants had diabetes and 35% chronic kidney disease. “We were able to find almost 96% TASC C and D to treat with

the Spur stent, and that was phenomenal, actually, because we wanted to put this to the test”, Mustapha explained. “Technical success for these complex lesions was 100% [in 45 systems]. We showed the device is very effective.”

Lesion length in chronic total occlusions (CTO) ranged from 20–130mm, with an average of 63mm; the longest length of spur-treated lesion was 270mm, with an average of 110mm, and the average number of spurs used was two.

Primary safety endpoints at six months were met, with no TLRs (0/6), no major amputations (0/6), and 0% all-cause mortality at 30 days (0/19).

Freedom from primary efficacy failure at six months was demonstrated as 86% patency (12/14) on angiography, and 80% patency (16/20) on ultrasound.

“This is extremely promising technology,” Mustapha said. “The primary endpoints, in terms of safety, it is too good to be true.”

Mustapha promised one-year data in May 2019, and further announced the start of a new trial—DEEPER OUS, a multicentre, non-randomised international (New Zealand, Switzerland, and Germany) study using the Spur system combined with various DCBs in 100 patients.

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March 2019

Drug-coated balloon

Paclitaxel balloon demonstrates good safety and efficacy profile in critical limb ischaemia The Ranger (Boston Scientific) paclitaxel-coated balloon catheter is safe in below-theknee (BTK) interventions and effectively inhibits restenosis, with good patency and clinical outcomes for patients with critical limb ischaemia, say researchers from the Ranger BTK study.

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ostantino Del Giudice, from the Vascular and Oncological Interventional Radiology Department directed by Marc Sapoval, Paris Descartes University, Paris, France released six-month data from the trial for the first time at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

“Ranger below-the-knee is safe in below-the-knee interventions. We had only one acute occlusion that was probably related to suboptimal periprocedural anticoagulation, and we can observe a significant inhibition of stenosis.”

The prospective, single-centre, all-comers, nonrandomised study aimed to prove the superior performance of the Ranger paclitaxel-coated balloon catheter for below-the-knee artery lesions when compared to non-coated balloons at six months postprocedure.

Between November 2016 and November 2017, consecutive patients were enrolled at Hôpital Européen George Pompidou. Enrolment occurred after successful intraluminal crossing of the guidewire, with 30 patients successfully treated. All had below-the-knee artery lesions of varying length, and were classified as Rutherford 4–6. Of these, 29 had a clinical follow-up

visit at six months. One patient died at three months, one had a major amputation due to a periprocedural acute occlusion, and a further eight withdrew angiographic consent, leaving 20 participants (67%) for angiographic follow-up at six months.

Baseline patient characteristics identified that 63.3% of subjects (19/30) had diabetes, 40% (12/30) had renal failure, and 97% were classified as Rutherford class 4 (70%, 21/30) or 5 (27%, 8/30). In addition, 63% of patients had lesions that were calcified to grade 3 or 4 under the Parker classification system.

The primary efficacy endpoint for the study was primary patency rate at six-month follow-up, with the primary safety endpoint a composite of all death and major amputation at six months. Secondary endpoints were late lumen loss, freedom from clinically-driven target lesion revascularisation in the amputation-free surviving patients, amputation-free survival, wound healing, and death, all at six months.

Investigators found that, at six months, the primary patency rate was 57.1%, with a late lumen loss of 0.99 (±0.66). Freedom from clinically-driven target lesion revascularisation was 93.3%, and there was a significant improvement in Rutherford score (p<0.0001) and anklebrachial indices (p<0.001). The primary safety endpoint

at six months was 6.6% (2/30), amputation rate was 3.3% (1/30), and wound healing was 56.7%. The death that occurred (3.3%, 1/30) was due to cancer. There was also a significant reduction in wound area (p<0.0002).

Del Giudice placed the findings in the context of other studies that looked at both coated and uncoated balloons.

“Considering existing results in the literature, we can see that we obtained the one improvement [among] uncoated balloon results, comparing with the previous studies of Schmidt and Iida.” Further comparing the Ranger BTK outcomes with other existing randomised studies of drug-coated balloons (DEBATE BTK, IN.PACT DEEP and BIOLUX III), Del Giudice noted the results were “more or less the same” in terms of patency and amputations, with the exception of IN.PACT DEEP which observed higher amputation rates (8.8% vs. 3.3% in both Ranger BTK and BIOLUX III).

Del Giudice concluded that the Ranger DCB is safe in below-the-knee interventions, demonstrating a “significant inhibition of stenosis”. He suggested that the sole incidence of acute occlusion in the study was “probably related to suboptimal periprocedural anticoagulation”, and emphasised the importance of good control. “It is important in this kind of long procedure periodically check the anticoagulation, because using drug coating ballon, we perform prolonged dilatation in small vessel and that could cause an acute thrombosis” However, he conceded the limitations of the study—“the small sample size and the high numbers of angiographic consent withdrawal, so there could be a bias. The majority of patients had good clinical results that refused to perform angiographic control, so we need more evidence with a larger randomised study.”

Follow-up will continue to one year.

COMPARE pilot study results show similar efficacy at two years for the Ranger and IN.PACT Admiral DCBs In a head-to-head comparison of the Ranger paclitaxel-coated percutaneous transluminal angioplasty (PTA) balloon catheter from Boston Scientific and the IN.PACT Admiral drug-eluting balloon from Medtronic in femoropopliteal interventions, a similar efficacy and primary patency was seen in both devices.

IN THIS PHYSICIAN-initiated study, the study investigators set out to compare the two different paclitaxelcoated balloons, each with a different coating and paclitaxel dose density, in the treatment of high grade stenotic or occluded lesions in the superficial femoropopliteal artery (SFA) and/or the proximal popliteal artery (PPA) in patients with peripheral arterial disease (PAD) with a Rutherford class between two and four. The Ranger balloon catheter was the investigational device, with a relatively low drug dose of 2µg/ mm2, and the IN.PACT drug-eluting balloon, with a paclitaxel dose of 3.5µg/ mm2, acted as the control.

Dierk Scheinert (Leipzig, Germany), the trial’s principal investigator, presented the results of the prospective, 15-site, randomised trial at the Leipzig Interventional Course meeting (22–25 January, Leipzig, Germany). “The study is being conducted in two phases,” Scheinert informed the LINC audience.

“There were initially 150 patients enrolled at 1:1 randomisation [in a pilot study], and then later on the study was expanded to a total cohort of 414 patients for testing of a formal noninferiority hypothesis.”

The trial demonstrated the “excellent

efficacy” of both devices, Scheinert said. Detailing the procedural outcomes of the first 150 patients enrolled in the pilot study, for which the 24-month data is available, Scheinert reports that the bailout stent placement, the “most important figure”, is “only” 22% and 25% in the IN.PACT and Ranger arms, respectively. This is, he says, “despite the relatively complex nature of the cohort.”

Of the first 150 patients treated in this trial, there were three deaths in two years. One death was in the IN.PACT Admiral group, and the remaining two were seen in the Ranger DCB cohort.

One death was from pancreatic cancer, one from cardiac decompensation, and one from enterococcal septicaemia.

Looking at the data from the full cohort of 414 patients to date, there have been seven deaths: three from the IN.PACT group, and four from the Ranger group.

This led Scheinert to the conclusion that all-cause mortality rates were “wellbalanced between the two devices with different dose density”, and says “there is no indication of any safety issue.”

Primary patency at two years between the two devices is very similar. Scheinert described how “there was an essentially identical [Kaplan-Meyer] curve between the two devices”. At 710 days, primary

Charing Cross Special Edition

patency was 0.77±0.05 in the IN.PACT DCB cohort, and 0.75±0.06 in the Ranger DCB cohort.

Patient characteristics

All patients enrolled in this study had symptomatic peripheral arterial disease with a Rutherford classification between two and four. Stenotic or occluded lesions of the SFA or the PPA were included, but no severe calcification was allowed. The lesion length was up to 30cm; Scheinert commented on this: “We stratified the randomisation process so that we could ensure that an equal percentage gets into both short lesion and long lesion cohorts.”

The baseline characteristics were equivalent in the Ranger DCB and IN.PACT DCB arms of the study. There was a fairly high incidence of diabetes mellitus amongst the patient cohort, with 34% of the Ranger group (25 patients) and 37% of the IN.PACT group (28 patients) being diabetic.

“I think it is fair to say that this is a relatively complex cohort”, Scheinert said when describing the lesion characteristics of the first 150 patients enrolled in the pilot study. The trial represented a complex, real-world lesion subset, with a mean target lesion length

All-cause mortality rates were wellbalanced between the two devices with different dose density.” of 117.4±100.4mm for the Ranger DCBtreated patients, and 122.3±91.2mm for the IN.PACT DCB-treated patients.

In total, around 40% of the lesions had chronic total occlusions (CTOs): 29 lesions in the Ranger subset (39.2%) and 34 lesions (44.7%) in the IN.PACT subset. In an additional complication, approximately 60% of the lesions across both groups had moderately severe or severe calcification as assessed by core lab.

Recruitment of the full study cohort—414 patients—has now been completed, and the results will be presented at LINC in 2020. The study is sponsored by the University of Leipzig, Germany, and funded through a research grant from Boston Scientific.

March 2019

Medical therapy

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Editors-in-chief of major cardiovascular journals claim medical misinformation puts “lives at stake” The editors-in-chief of major cardiovascular journals—of both US and European societies—have come together to “sound the alarm” about the dangers of medical misinformation that has been disseminated through the internet, social media, and other platforms. They claim that this misinformation is dangerous because it leads to patients’ refusing medication, such as statins, that have documented lifesaving benefits.

JOSEPH A HILL (Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, USA) and others write in Circulation and in several other international cardiovascular journals that medical misinformation “hyped through the internet, television, chat rooms, and social media” has caused many patients to think that the risks of statins are far worse than they actually are and, as a result, refuse to take the drugs.

“Most patients do not recognise that the benefits of statin use are invisible (‘I did not have a heart attack or stroke this past year’) whereas the small and typically reversible risks (e.g. muscle pain) are readily apparent,” they add.

The authors note that patients rejecting statins is just one example of the effects of medical misinformation, and that another is parents not letting their children be vaccinated following an infamous—and now widely discredited—paper that linked autism to the MMR vaccine.

Furthermore, Hill et al say that some celebrities, actors, activists, and

politicians promote false or misleading medical ideas and claim “not uncommonly” there are people acting with “purely venal motives”. According to Hill et al, “the strident alarms” by well-known people “speaking in absolute terms” exacerbate the problem of medical misinformation because their words resonate better with the general public than the “nuanced voices” of scientists. The authors state that scientists “appropriately couch their statements in statistical terms, which may come across to the public as equivocation”.

Hill et al, therefore, have written their editorial to “sound the alarms that human lives are at stake” and call on the media to “do a better job” at avoiding sharing medical misinformation. “It is unacceptable to posit false equivalents in these discussions [such as the risks and benefits of statins], often done to foster debate and controversy. It is easy to find a rogue voice but inappropriate to suggest that this voice carries the same weight as that emerging from

mainstream science,” they comment.

In particular, given misinformation tends to travels faster through social networks than does the truth, Hill et al write that the “purveyors of social media must be responsible for the content they disseminate” and it is no longer acceptable for these purveyors to “hide behind the cloak of the platform”.

They explain that, as editors-in-chief, they “reach out to thought-leading experts to evaluate the veracity of each report” they receive and “challenge

The internet and social media platforms are replete with false information, which does real harm to individuals globally.”

social media to do the same”—“to leverage the ready available of science-conversant expertise before disseminating content that may not be reliable”.

“Without exaggeration, significant harm, to society and individuals, derives from the wanton spread of medical misinformation. It is high time that this stops, and we lay at the feet of the purveyors of the internet and social media content the responsibility to fix this,” Hill et al conclude.

Hill told Vascular News: “The internet and social media platforms are replete with false information, which does real harm to individuals globally.

We charge the purveyors of these media to take the first steps in addressing this enormous problem, and we, in the academic medical community, stand ready to help.”

As well as being published in Circulation, the editorial was also published in the European Heart Journal, Journal of Electrocardiology, and the International Journal of Cardiology among others.

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March 2019

Market watch

Product News MedAlliance granted Breakthrough Device Designation from FDA for sirolimus DCB

MedAlliance SA has been granted Breakthrough Device Designation from the US Food and Drug Administration (FDA) for Selution, its sustained limus release (SLR) drug-coated balloon (DCB) catheter, for the treatment of coronary disease.

The FDA Breakthrough Device Program is intended to help patients receive more timely access to breakthrough technologies that have the potential to provide more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases or conditions. Under the programme, the FDA will provide MedAlliance with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.

“MedAlliance is honoured to have been selected for the FDA’s Breakthrough Device Program, which will allow US patients timely access to new technologies with the potential to provide safer and more effective treatment,” says Jeffrey B Jump, chairman and CEO of MedAlliance.

Selution’s technology involves unique micro-reservoirs made from biodegradable polymer intermixed with the anti-restenotic drug sirolimus. These micro-reservoirs provide controlled and sustained release of sirolimus. Extended release of sirolimus from stents has been demonstrated highly efficacious in both coronary and peripheral vasculatures.

MedAlliance’s proprietary CAT (Cellular Adhesive Technology) enables the microreservoirs to be coated onto balloons and adhered to the vessel lumen when delivered via an angioplasty balloon.

MedAlliance is the first and only company able to deliver sirolimus in a drug-coated balloon with an extended release profile similar to that of a drug-eluting stent (DES). Preclinical animal data shows therapeutic levels of sirolimus in tissue for greater than 60 days, and first-in-man clinical trial results in peripheral arteries demonstrate a late lumen loss of 0.19mm.

The FDA received the MedAlliance request to designate Selution as a Breakthrough Device in January 2019.

The proposed indications for use included “improving luminal diameter, after pre-dilatation, in treatment of coronary artery in-stent restenosis for stenotic lengths up to 36mm with reference vessel diameters of 2.25–4.5mm.” MedAlliance was recently informed by the FDA that “your combination product and proposed indication for use meet the criteria and have been granted designation as a Breakthrough Device”.

The goal of the Breakthrough Devices Program is to provide patients and healthcare providers with timely access

to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and de novo marketing authorisation, consistent with the agency’s mission to protect and promote public health.

The Breakthrough Devices Program offers manufacturers an opportunity to interact with the FDA’s experts through several different program options to efficiently address topics as they arise during the premarket review phase, which can help manufacturers receive feedback from the FDA and identify areas of agreement in a timely way. Manufacturers can also expect prioritised review of their submission.

Augmented reality surgical technology unveiled by Philips and Microsoft

At the MWC (25–26 February, Barcelona, Spain), formerly the Mobile World Congress, Philips unveiled a unique mixed reality concept developed in partnership with Microsoft for the operating room of the future. Based on Philips’ Azurion image-guided therapy platform and Microsoft’s HoloLens 2 holographic computing platform, the companies will showcase novel augmented reality applications for image-guided minimally invasive therapies. The technology allows wearers of the HoloLens 2 headset to access a virtual screen displaying data from the Azurion system, updated in real time, during procedures.

The Philips and Microsoft augmented reality concept, built for HoloLens 2, brings live imaging and other sources of vital data currently displayed on large 2D screens into a 3D holographic augmented reality environment that can be ergonomically, easily and intuitively controlled by the physician. The concept is being used to gather further clinical insights to support the development of future commercially-available augmented reality solutions for use in image-guided procedures.

“The transition from open surgery to image-guided procedures has driven a seismic shift in improving patient outcomes and reducing costs—not least by dramatically reducing the length of time a patient stays in a hospital after their procedure,” says Atul Gupta, chief medical officer for Image Guided Therapy at Philips and a practicing interventional and diagnostic radiologist.

“On our Azurion platform we seamlessly integrate a range of data sources in a way that is intuitive to understand and control. By collaborating with Microsoft and HoloLens 2 we can take it to the next level, immersing the physician in a tailored augmented reality environment.

This concept allows me to see the real world superimposed with the live data and 3D medical imagery needed to guide our precision therapy, and importantly

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also lets me control Azurion with voice recognition, eye tracking and advanced gestures. It is all about keeping our focus on the patient.”

“Mixed reality is giving people new ways to interact with the digital and physical world, bringing the benefits of the digital revolution to entirely new experiences across the globe,” comments Alex Kipman, technical fellow, AI and Mixed Reality at Microsoft. “I am thrilled to see companies in a broad range of industries achieve more using the products that we build with our partners and ecosystem. Mixed reality holds great potential in healthcare, and our collaboration with Philips shows how that potential is already beginning to be realised.”

Microsoft unveiled HoloLens 2 during the previous day of the conference.

HoloLens is a self-contained holographic computer that enables hands-free, headsup interaction with three-dimensional digital objects.

Since its global launch in February 2017, over half a million patients have been treated in more than 80 countries using the Azurion platform, which is powered by Philips’ proprietary ConnectOS and combines technical innovations in both software and hardware. ConnectOS allows the integration of advanced digital innovations on the Azurion platform.

growing area of image-guided minimally invasive surgery—continues to increase, as does the number of patients requiring treatment. In order to treat more patients at a lower cost, Philips say in a company statement, hospitals require a versatile fleet of C-arms with varying capabilities that easily adapt to the needs of different types of surgery and different operators. Philips claim that Zenition mobile C-arms are easy to move between operating rooms, simple to position around the patient and intuitive to operate.

“The Philips Zenition is a userfriendly system that is intuitive to use for both surgeons and nursing staff,” says Nikolaos Bonaros, associate professor of Cardiac Surgery at the Medical University of Innsbruck, Austria. “Its simplified workflow means that we can convert a room from a conventional operating room to a high-quality interventional room more quickly. At the same time the system provides high image quality at the level required for hybrid operating room procedures.”

Philips Zenition has a tablet-like user interface and this, coupled with the “Unify” workflow, mean that once an operator has learned to use one system on the platform, it is easy for them to operate them all, a press release states. The company also claim that the compact design of the device, as well

HoloLens 2 and Azurion

Philips launches Zenition mobile C-arm platform

Philips Zenition, a new mobile C-arm imaging platform from Philips, has launched in the USA, Germany, Austria and Switzerland. It is being introduced into these countries over the next six months, and is set to penetrate other markets in the second half of 2019.

Mobile C-arms are X-ray systems that are brought into the operating room to provide live image guidance during a wide range of surgeries, including orthopaedic, trauma and vascular procedures. According to a company press release, the Zenition mobile C-arm platform brings together innovations in image capture, image processing, ease-of-use and versatility pioneered on Philips’ earlier Azurion platform.

The scope and complexity of surgical interventions—especially in the rapidly

as its ability to capture images at the periphery of the image intensifier or flat detector, reduce the need for C-arm repositioning by 45%.

The Zenition C-arm systems incorporate the same image processing algorithms used on Philips’ Azurion platform. Additionally, the platform features Philips’ MetalSmart software, which automatically adjusts the contrast and brightness of images to aid image quality, purportedly useful when metal objects such as implants are present in the field of view.

Philips’ Zenition C-arms are CE marked and have received 510(k) clearance from the US Food and Drug Administration (FDA). They were showcased at the 2019 European Congress of Radiology (ECR) Exhibition (28 February–3 March, 2019, Vienna, Austria).

March 2019

Market watch

Product News BD receives FDA 510(k) clearance of WavelinQ 4F endoAVF system

BD has announced the 510(k) clearance from the US Food and Drug Administration (FDA) for the WavelinQ 4F endoAVF system earlier this month. The endoAVF system is the company’s most recent innovation in endovascular arteriovenous fistula (endoAVF) creation technology, which allows for the creation of an arteriovenous fistula in either the ulnar artery and ulnar vein or the radial artery and radial vein, expanding upon the current indication for the WavelinQ 6F system.

In the USA alone, there are more than 440,000 patients with end-stage renal disease (ESRD) who are surviving on haemodialysis. EndoAVF systems provide clinicians with a minimally invasive arteriovenous fistula (AVF) creation alternative to open surgery.

The WavelinQ 4F, with a slim profile, increases the anatomical AVF location options and enables additional venous wrist access points (ulnar vein or radial vein), providing increased procedural flexibility for physicians while reducing risk of scarring or arm disfigurement for patients compared to open surgical AV fistula creation.

“With BD WavelinQ 4F endoAVF system, I can provide my ESRD patients with two additional fistula location options compared to a surgical fistula,” said Paul Kreienberg, Albany Medical Center, Albany, USA. “These additional AV fistula sites and a minimally invasive procedure can increase the likelihood that patients will get a usable AV fistula.”

“People living with ESRD are an under-served patient population with very limited treatment options available to them,” said Steve Williamson, worldwide president of Peripheral Intervention at BD. “We are excited to add BD WavelinQ 4F endoAVF system to our portfolio of technologies that create, restore and/or maintain AV access for patients on haemodialysis. Endovascular specialists now have an additional tool that enables the flexibility needed to support AV fistula creation for their patients.”

CE mark approval for Nexus aortic arch stent graft expected in Q1 2019

Mario Lachat (University of Zürich, Zürich, Switzerland) presented mid-term results of an open-label, non-randomised single-arm investigational clinical study of the Nexus (EndoSpan) aortic arch stent graft system in 25 patients. Speaking at Controversies & Updates in Vascular Surgery (CACVS; 7–9 February, Paris, France), Lachat reported that the early data were “very encouraging”, and disclosed that the company expects CE approval for the device in the first quarter of 2019.

“Nexus is a relatively simple arch procedure,” Lachat said, noting that

“ease of implementation will allow for greater physician utility.” In 25 patients, successful access, deployment and procedural survival was attained in 100% of cases. Mean endoluminal repair time was 68 minutes, with a total mean procedural time of 186 minutes. At 30 days, two deaths were reported (8%; one ventricular fibrillation, one cardiac arrest) and two non-disabling strokes (8%).

One further death (4%; cardiovascular accident) was reported in follow-up beyond 30 days.

Highlighting the 100% immediate technical success rate, Lachat noted the study demonstrated the “excellent safety profile” of the device, with no aneurysmrelated deaths.

Lachat concluded that longer-term data are needed to further study performance of the Nexus aortic arch stent graft system.

Cook Medical receives US FDA approval for aortic dissection device

Cook Medical has announced its recent approval from the US Food and Drug Administration (FDA) for its Zenith endovascular aortic dissection system.

The system, consisting of a proximal stent-graft component and a distal bare stent component, provides physicians with a less invasive alternative to open surgery for repair of type B aortic dissection of the descending thoracic aorta. The device will be available for sale in the USA in the coming months, the company states in a press release.

“We are pleased to provide another minimally invasive option for aortic repair,” says Mark Breedlove, vice president of Cook Medical’s Vascular division. “The approval of this product gives us an opportunity to have a positive impact on the lives of patients with aortic dissections.”

“Cook Medical is committed to developing a variety of treatment options for aortic disease—from the arch to the iliacs, in order to help physicians fit a device to each patient’s unique disease state,” Breedlove says.

US FDA grants premarket approval to Manta vascular closure device

Teleflex has received premarket approval (PMA) from the US Food and Drug Administration (FDA) for the Manta vascular closure device. A press release reports that the device is the first commercially available biomechanical vascular closure device designed specifically for large bore femoral arterial access site closure. Manta is indicated for closure of femoral arterial access sites while reducing time to haemostasis following the use of 10–20F devices or sheaths (12–25F outer diameter) in endovascular catheterisation procedures.

The SAFE MANTA IDE clinical trial, the largest US prospective multicentre, single-arm trial of a purpose-designed

large bore femoral access site closure, demonstrated that the Manta device successfully achieves fast reliable biomechanical closure with rapid haemostasis, with all primary and secondary endpoints met. With its innovative design, the press release states, the Manta device has the potential to reduce bleeding complications and offset other procedural costs.

Zvonomir Krajcer (Texas Heart Institute, Houston, USA), the lead enroller and co-principal investigator of the SAFE MANTA IDE clinical trial, comments: “I am very encouraged by the results of the SAFE MANTA IDE clinical trial. The clinically proven major complication rate (as defined by the study protocol) of 5.3% and VARC-2 major vascular complications rate of 4.2% compare very favourably to suture mediated devices and the 24 second median time (65 second mean time) from deployment to haemostasis was impressive. We have been patiently waiting for this approval, are eager to use the Manta Device commercially and look forward to the efficiencies it can provide.”

Greg Walters, co-inventor of the Manta device and now vice president of access and closure in the Interventional business unit of Teleflex, states: “Our team has been working hard to obtain FDA premarket approval and were confident they would recognise the benefits that the Manta™ Device can provide to the patient. We have had great success with the device in Europe over the last two years with over 10,000 units sold, and are thrilled to bring this innovative solution to patients in the USA and further fulfil this significant and previously unmet clinical need in the structural heart and endovascular space.”

PreludeSYNC DISTAL compression device now available globally

The PreludeSYNC DISTAL compression device (Merit Medical) is now available in US, European, Middle Eastern, African, and Asia-Pacific markets. The device is the first product specifically designed to achieve haemostasis of the radial artery during procedures where access is gained via the distal radial artery.

Designed, according to a company press release, “with a comfortable band and a large window for site visibility”, the PreludeSYNC DISTAL compression device is applied over the arteriotomy, allowing the clinician to slowly inflate the balloon with air while simultaneously removing the sheath. It then maintains pressure at the site to allow the access wound to achieve patent haemostasis.

Merit is also answering demand for distal access training through its ThinkRadial course, which most recently took place on 9 February 2019. The course will feature a dedicated three-hour session specific to distal radial access, which will be streamed live online and available to interventional cardiologists and radiologists who want to learn the distal technique. Additional information about other ThinkRadial courses, including registration, may be found on the programme’s website.

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The live streaming event features Ferdinand Kiemeneij from Amsterdam, The Netherlands, widely considered the “father of transradial intervention”; Sandeep Nathan, an interventional cardiologist in Chicago, USA; and Darren Klass, an interventional radiologist based in Vancouver, Canada.

ICHOR Reperfusion System

ICHOR Reperfusion System receives FDA clearance

Euphrates Vascular, a company focused on the treatment of vascular occlusions, recently received 510(k) clearance for sale of its ICHOR Percutaneous Reperfusion System.

ICHOR is a Percutaneous Reperfusion System designed to treat organised thrombus and embolic events in the peripheral vasculature. ICHOR is a “one size fits all” system that replicates the standard of care of surgical embolectomy or thrombectomy in a minimally invasive manner: • Percutaneous approach reduces surgical complications • Mechanism of action minimises blood loss associated with aspiration • Mechanism of action does not require drug therapy which potentiates a reduction of common bleeding complications associated with lytics • Does not require general anaesthesia • Does not require the need for capital equipment (disposable only) • Easily adoptable by interventionalists • Incorporates a health economic element intended to make ICHOR a first line therapy for physicians, hospitals and office-based labs.

ICHOR will be the first marketable product for Euphrates Vascular with the Pulse NanoMED technology in the pipeline. The ICHOR and Pulse NanoMED systems were both designed to target vascular occlusions by eliminating the need for surgery or drug therapies and both attempt to treat further and deeper by overcoming today’s size limitations in material science.

“ICHOR will be an extraordinary tool in the clot management toolbox due to its ability to handle the organised clot many physicians struggle to treat. The Pulse NanoMED system may allow for us to change our approach in treating occlusions in areas such as the lower limb, the diabetic foot and perhaps in the neurovasculature, by simply being able to access the most tortuous anatomy and the smallest vasculature. The Pulse NanoMED system can enable us to go where no other devices have gone before,” said Troy Long, vascular interventional radiologist.

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March 2019

Market watch

Clinical News Lumee platform demonstrates successful oxygen monitoring in CLI patients

Profusa has announced promising clinical data from two studies evaluating the company’s Lumee Oxygen Platform, a tiny, injectable tissue-integrated biosensor and an intelligent data platform intended for continuous, real-time monitoring of tissue oxygen levels.

The data, presented at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), indicate that the Lumee platform measures tissue oxygen level changes in both healthy volunteers and patients with critical limb ischaemia (CLI).

The Lumee oxygen platform received CE mark in October 2016 for continuous monitoring of tissue oxygen.

The platform is CE marked for sale in the EU for monitoring tissue-oxygen perfusion as a general indication. In the USA, the Lumee oxygen platform is an Investigational Device limited by Federal Law to Investigational Use.

Measuring Changes in Tissue Oxygen

Peter Schneider, vascular surgeon and clinical researcher in limb salvage vascular procedures from Honolulu, USA presented the findings from a healthy volunteer feasibility study, which evaluated the performance of the Lumee oxygen platform in vivo to monitor changes in interstitial tissue oxygen compared to transcutaneous oximetry (tcpO2), demonstrating that the Lumee platform detected changes in tissue oxygen levels.

“Measurements of regional tissue oxygen serve as a proxy to monitor local perfusion and have the potential to guide crucial therapeutic decisions in multiple clinical disciplines for peripheral arterial disease (PAD), and wound management, that are now made on the basis of clinical judgement and experience alone without guidance,” says Schneider. “These findings presented at LINC show promise that the Lumee oxygen platform can become a valuable tool for clinicians when they need to assess perfusion.”

In the study, after the Lumee biosensor was injected in the forearm of seven healthy volunteers, vascular occlusion tests were performed on the arms of enrolled volunteers and simultaneous measurements of oxygen were recorded using both the Lumee platform and tcpO2, (a commonly used noninvasive technique that measures the oxygen level of tissue below the skin), with repeated tests occurring one to 10 weeks after biosensor injection. Results

Lumee Oxygen Platform

revealed that the Lumee platform and tcpO2 were highly correlated, with both technologies showing a statistically significant decrease in oxygen levels during occlusion (interruption of blood flow by pressure cuff) (p<0.001 for each device). Data also revealed that the Lumee platform detected faster rates of oxygen change during both the occlusion and recovery phases (p<0.001, Wilcoxon signed-rank test) and detected reactive hyperemia (increased blood flow) in a higher percentage of tests (38% versus 4% occlusion tests).

OMNIA Subset Analysis

Marianne Brodmann, interim head of the clinical division of angiology, department of internal medicine at Medical University in Graz, Austria presented findings from an interim analysis of the first 30 patients enrolled in the Oxygen Monitoring Near Ischemic Areas Study (OMNIA). The findings demonstrate that in patients with CLI, tissue oxygen level increases measured with the Lumee platform during revascularisation were positively correlated with changes compared to toe brachial index (TBI) and were significantly higher in patients who showed wound healing as compared to patients that did not.

“We are pleased to see that continuous monitoring of extravascular tissue oxygen using the Lumee oxygen platform showed a positive correlation to TBI, demonstrating that this technology could be useful to help guide clinical choices during CLI management,” said Brodmann. “These data also validate previous research that showed increases in oxygen during revascularisation may be a sensitive indicator of wound healing following the procedure.”

The OMNIA Study is an ongoing multicentre trial evaluating use cases of the Lumee oxygen platform. Preliminary analysis assesses the relationship between oxygen levels, traditional haemodynamics (blood flow) and wound healing in the affected limbs of patients with CLI before, during and one day after revascularisation using the Lumee platform, with follow-up visits around 30, 90, 180 and 365 days. Enrolled patients received four injected Lumee biosensors; three in the foot and one as a reference sensor in the arm.

Passeo-18 Lux DCB remains safe and effective at two years with “no signs” of paclitaxelrelated mortality

Two-year data on the Passeo-18 Lux drug-coated balloon (DCB; Biotronik) continue to validate its safety and effectiveness in intra-inguinal arteries.

Gunnar Tepe from the Klinikum Rosenheim in Germany presented 24-month results for the first time from the full cohort of the Passeo-18 Lux all-comers registry on behalf of the study group at the Leipzig Interventional

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Course (LINC; 22–25 January, Leipzig, Germany).

Tepe described the finding of 88.8% freedom from clinically-driven target lesion revascularisation (CD-TLR) as a “really good result in this challenging cohort”. The study also found 83.9% freedom from major adverse events, and 92.7% freedom from major target limb amputations with “a high number of patients which did not need to be amputated”. Despite a target lesion calcification rate of more than 76%, Tepe reported that only 15.7% of lesions treated required a stent.

Biolux P-III is a prospective, global, multicentre all-comers trial of almost 900 patients to further investigate the Passeo-18 Lux DCB efficacy and safety in infra-inguinal arteries. It is conducted across 47 sites in 16 countries in the EU, Australia, and Asia. The DCB has a special excipient and comes with a safety guard insertion device which helps the drug to remain on the balloon, and prevents its loss on the sheath. Tepe described the study as the only realworld registry in infra-inguinal arteries, and it is the world’s second largest allcomers DCB registry.

Outcomes were freedom from major adverse events at six months, and freedom from CD-TLR at 12 months.

Inclusion criteria were a lesion or lesions in the infra-inguinal arteries suitable for endovascular intervention treated with or scheduled to be treated with the DCB. Exclusion criteria were failure to successfully cross the target lesion with a guidewire. There were no patient or lesion characteristic limitations, and the use of additional devices was allowed.

“The special thing about the trial is that almost every patient could be enrolled, below-the-knee arteries as well as critical limb ischaemia (CLI) patients who may be excluded from other trials”, noted Tepe, with “42.1% CLI patients seen in the patient cohort and below-the-knee arteries were treated in almost 20% of the patients. In addition to that, [there were] high numbers of long lesions with C or D TASC classifications (32.6%), as well as a lot of patients with moderate to heavily calcified arteries (44.6%).”

Most patients were treated by predilatation (72.3%, 784/1085), and the technical success rate was 98.4% (1068/1085).

At 24 months, the full cohort demonstrated 88.8% freedom from CD-TLR, “a very high number of freedom from TLRs”. Tepe suggested the large proportion of CLI patients in the study contributed to the major limb amputations rate. The mortality rate was 11.9%, with no increase over time, and the long-term rate remained the same at 180 days.

“We have to also acknowledge that there were a lot of patients enrolled in this study who have a higher likelihood to die—CLI over 40%, diabetes almost 50%, and patients being enrolled with previous cancer rates at almost 12%.

This is not a prospective randomised trial comparing two percutaneous transluminal angioplasties (PTA) arms, so we cannot

really compare to a control group, but what we can do is to look into mortality data and to look at one versus two years.

There are not any major differences, nothing which strikes us and leads to the conclusion that this DCB is a risk or cause of mortality,” Tepe said.

The mortality rate among participants who are not CLI patients was lower: 2.9% (13/451) at 12 months and 5.5% (25/451) at 24 months. Other predictors of mortality were age, diabetes, and renal disease, and no significant differences in the distribution of cause of death between the first and second year were detected.

Feeding into the recent debate around

Passeo-18 Lux

paclitaxel use and late mortality, Tepe pointed out that dose of paclitaxel was not found to be a predictor of mortality in the Biolux P-III study. Although the low numbers within certain cohorts mean that dose dependency cannot be completely ruled out, Tepe observed “there are no signs that this drug-coated balloon is leading to mortality”, and concluded: “Biolux P-III [...] continues to confirm the safety and effectiveness of the Passeo-18 Lux DCB after 24 months.”

Tepe thus maintained that evaluated patient-level data showed no significant differences in the distribution of causes of death during the first year compared to the second year, and that no dose dependency of the mortality rate in the full cohort was observed.

Marianne Brodmann (Medical University of Graz, Austria) presented 24-month results from the largest CLI population enrolment in a real-world all-comer registry. Freedom from major target limb amputation was reported at 85.4%, and freedom from CD-TLR at 88.2%. The results also showed a crude mortality rate of 16.2% in the CLI subgroup.

Diabetes subgroup analysis reveals strong results in challenging population

Focusing on a complex population of patients with diabetes, Johannes B Dahm (MVZ Herz- und Gefäßzentrum HGZGöttingen, Krankenhaus Neu Bethlehem, Göttingen, Germany) presented the results of 460 diabetic subjects from the registry with 53.1% CLI and 23.4% BTK lesions. In this subgroup, Dahm reported 87.5% freedom from CD-TLR and 87.4% freedom of major target limb amputation at two years.

Biotronik is extending the followup of paclitaxel-coated balloon studies to include long-term five-year patient data retrospectively on randomised control trials (Biolux P-I and P-II) and prospectively in the currently running all-comers registry, Biolux P-III.

March 2019

Market watch

Clinical News Enrolment starts for efficacy study of human placental graft for diabetic foot ulcers

StimLabs has announced the first patient enrolment in the company’s clinical trial assessing the safety and efficacy of full-thickness human placental graft Revita as a wound covering for diabetic foot ulcers.

The multicentre randomised, controlled study will evaluate the efficacy of Revita in improving wound closure rates in DFUs as compared to current standards of wound care treatment. Revita is the first amniotic allograft to capture the complete, intact membrane in a shelf-stable format.

“We are thrilled to commence patient enrolment in this key diabetic foot ulcer study,” said John Daniel, founder and CEO of StimLabs. “As the first intact, shelf-stable placental membrane, Revita has set a new standard for amniotic tissue products, and the clinical outcomes we have seen across the country have been exceptional.

This study will build on the evidence we have collected to date, and validate the feedback we have received. We are also excited to leverage the power of Tissue Analytics for this study. This unique platform uses machine learning to more accurately evaluate wound characteristics, increasing the accuracy and integrity of our outcomes data.”

Diabetes is on the rise and affects approximately 30 million people in the USA. As many as 25% of patients with diabetes will develop a diabetic foot ulcer within their lifetime. Of that total, up to 24% of those individuals’ condition will lead to an amputation.

Amputated patients have around a 50% survival rate. In addition to these outcomes, diabetic foot ulcers are also a major financial burden on the healthcare system. Care for these patients costs public and private payers approximately US$9–13 billion annually, in addition to the costs associated with diabetes itself.

Study details

The study is a randomised, comparative, controlled trial that will evaluate the efficacy of Revita full thickness placental allograft in improving wound closure rates and mean closure time in diabetic foot ulcers as compared to current standards of wound care treatment. The trial will be conducted at primary institutions/centres in the USA. This trial focuses on patients who suffer from Type 1 or 2 Diabetes with diabetic foot ulcer(s) greater than 1cm2 and less than 25 cm2 for longer than four weeks prior to enrolment. The target enrolment is 40 patients, and patients will be randomised to either the treatment or control group. Additional study outcome measures include time to closure, number of patients with 50% ulcer volume decrease by day 28, and percent healed in the open label phase.

Revita

SIBERIA trial: Positive onemonth results for embolic prevention system

InspireMD has announced positive interim results from the SIBERIA trial, an investigator-initiated study of the CGuard embolic prevention system (EPS).

The data were presented at the Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany).

Andrey Karpenko and Pavel Ignatenko from the Siberian Federal Biomedical Research Center, Russia, presented the interim data from their first 50 patients in an independent, randomised clinical trial designed to ultimately include 100 consecutive patients with symptomatic and asymptomatic carotid artery disease. The patients are randomly assigned (1:1) into two treatment groups. Fifty patients will receive the CGuard EPS MicroNet mesh covered stent and the other 50 patients will receive a conventional carotid stent.

Primary endpoints were incidence and volume of new lesions in the brain after carotid stenting using diffusion weighted magnetic resonance imaging (DW-MRI) periprocedurally and at 30 days.

At the protocol-mandated interim analysis, after recruiting the first 50 patients in the study, the results at one month show that, despite having patients with higher risk factors in the CGuard group compared to the conventional carotid stent arm, the CGuard-treated patients had a significantly lower incidence of multiple lesions in the brain (16% vs. 44%), and a lower incidence of large cerebral lesions (24% vs. 40%).

Finally, major adverse clinical events after 30 days occurred in the conventional carotid stent arm but not in the CGuard EPS-treated patients (12% vs. 0%).

Karpenko commented, “We are excited that despite the higher-risk patient profile in the CGuard group, the interim results show a significant reduction of cerebral embolisation while patient outcomes suggest a clinically-relevant benefit of the CGuard EPS. This mandated interim analysis gives us confidence to continue enrolling patients in this trial and extending the data set in this potentially important advancement in the stroke prevention field.”

Atherectomy included in pivotal study of QT Vascular’s Chocolate Touch DCB The FDA has granted approval to

include the use of atherectomy for lesion preparation in its ongoing US pivotal study of the Chocolate Touch drugcoated balloon (DCB; QT Vascular) and the addition of subgroup analysis related to the use of atherectomy.

The Chocolate Touch device is the drug-coated version of the company’s Chocolate percutaneous transluminal angioplasty balloon, which was acquired

by Medtronic in January 2018 and is commercially available in the USA. The prospective, randomised Chocolate Touch pivotal study is being conducted in up to 50 centres in the USA, and selected centres in Europe and New Zealand. The study’s co-principal investigators are Mehdi Shishehbor (Cleveland, USA) and Thomas Zeller (Bad Krozingen, Germany).

In the company’s press release, Shishehbor comments: “The inclusion of atherectomy in the study is a unique element that expands the potential use of Chocolate Touch, both in hospitals and out-patient-based labs. The study will provide an important data set that is consistent with real-world practice, especially at [out-patient-based labs] where more and more patients are getting treated.”

The study is evaluating patients with disease in the superficial femoral and popliteal arteries in the legs. Patients are randomised 1:1 to the Lutonix DCB (BD). The study evaluates acute endpoints such as procedural successes and freedom from bail-out stenting, and long-term endpoints such as patency and target lesion revascularisation among others.

The Chocolate Touch DCB is not commercially available in the USA, and can only be used in the investigational device exemption clinical study. The device received CE mark in August 2015 and is available in the European Union and other countries.

Chocolate Touch DCB

Positive Valiant Captivia fiveyear outcomes anounced at STS

Medtronic has released new data supporting the long-term durability, safety, and efficacy of the Valiant Captivia thoracic stent graft system for the treatment of blunt thoracic aortic injury (BTAI). Himanshu J Patel of the University of Michigan Department of Cardiac Surgery, Ann Arbor, USA, presented the outcomes at The Society of Thoracic Surgeons Annual Meeting (STS; 26–29 January, San Diego, USA).

It was the first ever five-year industryissued dataset reported for patients with aortic transections undergoing thoracic

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endovascular aortic repair (TEVAR).

Blunt thoracic aortic injury is an emergency medical condition in which the aorta is damaged due to traumatic force to the chest, usually the result of elevated falls or other high-impact injuries such as motor vehicle accidents. It is the second leading cause of traumatic death after head injuries. The data presented by Patel came from the evaluation of the clinical performance of the Valiant thoracic stent graft with the Captivia delivery system for the endovascular treatment of blunt thoracic aortic injuries (RESCUE) trial, a long-term study of this high-risk cohort of patients.

“These data from the RESCUE trial demonstrate that TEVAR with Valiant Captivia continues to be a valuable, safe, and less invasive alternative to open surgery for patients facing lifethreatening aortic injury of blunt thoracic aortic injury, especially in the setting of critical multi-system injuries,” said Patel.

“This is the first five-year industry-issued dataset ever disseminated. The outcomes demonstrate Valiant Captivia to be a safe and durable therapy for high-risk blunt injury patients.”

The RESCUE study is a prospective, multicentre, non-randomised, descriptive study that evaluated a total of 50 patients with blunt injury to the descending thoracic aorta. Subjects enrolled had a mean injury severity score (ISS) of 38.4±14.4 and 70% (35/50) of blunt thoracic aortic trauma extent was grade III or higher, including one grade IV free rupture, indicative of this extremely high-risk patient cohort. The extent of arch repair required full (40%, 20/50) or partial (18%, 9/50) left subclavian artery coverage. Of the 31 patients available at five years, 90.3% (28/31) received clinical follow-up, while 67.7% (21/31) received imaging follow-up.

Data highlights at five-year follow up:

• Kaplan Meier freedom from all-cause mortality of 85.2% • No stroke or spinal cord ischaemia observed • 100% freedom from type 1 or 3 endoleaks • Kaplan-Meier freedom from secondary procedures of 90.6% • 00% freedom from retrograde type A dissections, conversions to open repair, or aortic perforations • 100% complete exclusion of the traumatic injury maintained • No instances of stent graft kinking, fracture, loss of patency, or migration “The Valiant Captivia five-year transection results demonstrate our commitment to life-saving treatments, and transparency in reporting long-term data to improve patient safety,” said John Farquhar, vice president and general manager of the Aortic business, which is part of the Aortic, Peripheral, and Venous division at Medtronic. “These data also support our continuing focus on providing safe and durable endovascular repair to patients who have traditionally been challenging to treat.”

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March 2019

Events

Calendar of events 12–13 March LINC Asia-Pacific Hong Kong

15–18 April Charing Cross Symposium London, UK

www.linc-around-the-world.com

www.cxsymposium.com

21–22 March Critical Limb Ischemia Course Padua, Italy

26–27 April 27th Annual Pennsylvania Hospital Vascular Symposium Philadelphia, USA

www.cli-courses.com

23–28 March SIR 2019: Society of Interventional Radiology Annual Scientific Meeting Austin, Texas www.sirmeeting.org

www.vascularmeeting.com

9–11 May

LIVE: Leading Innovative Vascular Education 2019 Larissa, Greece

www.conferre.gr/congress/live2019/

22–25 May 8th International Symposium on the Diabetic Foot The Hague, the Netherlands www.diabeticfoot.nl

23 May PNEC Simulation Summit for Vascular Trainees Seattle, USA www.pnec-seattle.org

23–24 May Critical Issues in Aortic Endografting Liverpool, UK www.critical-issues-congress.com

27–29 March SITE: International Symposium of Endovascular Therapeutics Barcelona, Spain

13–18 May

Paris Endovascular Aortic Course Le Plessis-Robinson, France

23–25 May Aortic Summit 2019 Lugano, Switzerland

www.sitesymposium.com

www.peacworkshop.com

www.aorticassociation.org

11–12 April 11th Congress of the Vascular Access Society Rotterdam, The Netherlands

17–18 May

24 May PNEC: Pacific Northwest Endovascular Conference Seattle, USA

www.vas2019.com

PALP: Program for Advanced Limb Preservation New York, USA

www.palpnyc.org

www.pnec-seattle.org

12–15 June SVS Vascular Annual Meetings National Harbor, Maryland, USA www.vascular.org

June 2015

n: Andrew Holde le stents Bioresorbab 13

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Issue 66

Michael Dake: device hed Arch branc 2

Janet Powe Profile

Page 24

E data r IMPROV One-yea nefit of EVAR be s suggest aneurysm ed ur pt in ru Page

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ia drugNew Eluv t shows eluting sten ary patency 94.4% prim months trial rate at nine IC clinical the MAJEST the Elu-

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nce of esults from ) the performa (Boston Scientific assessing ing stent a high via drug-elut lesions show rate

pliteal artery low reintervention ted in femoropo at the trial, presen rate and presented 2015, IMPROVE endovascular primary patency The data were controlled an April–1 May d at nine months.Symposium (28 randomised UK), show that nt of rupture data of the May, London, to Charing Cross in the treatme endovascular 12-month IC trial was that the from the CX 2015 (28 April–1 ed to open repair London, UK). of the MAJESTdrug-eluting stent revealed a trend towards Results compar time at data also The objective the Eluvia treating for the first cost-effective whenThe one-year repair, except y enabled more e whether nce when is sms. determin strateg over open le performa l popliteal artery than with y, if strategy l benefit the endovascular aortic aneury antly faster strateg showed acceptab and proxima compared no surviva abdominal that femoral and signific endovascular as conferred . It also showed in length superficial with l to home, life with strategy to 110mm nce goal, women from hospita nt quality of performa lesions up at nine benefitting be discharged -derived an excelle patency group to to a literature t of primary s also have es heard. patients the open repair for endpoin Patient 45.1% reinterven a primary open repair. the rupture, delegat with similar in Europe, analy(p=0.325) subgroup months.

57 patients mean age was they survive in each. A 2015 voting enrolled

The CX tion rates benefit for The trial at from Zealand. a stronger lesion length trial results to nth outcomes and New in women sis showed welve-mo e you the average Australia Do IMPROVE ular strategy patient data encourag years, and ular stratthe endovasc 12 months the individual of three ran69.3±9.3 more often? ülsbeck, The endovasc .1mm.

Müller-H perform EVAR versus men. open repair groups meta-analysis was 70.8±28 tor Stefan d the results and trials of ruptured investiga stays of 17 egy group Principal who presente a high AJAX domised controlled total hospital Germany, [ie. the Dutch and the IC included had average ly.

Flensburg, No – aneurysms added, “It respective that MAJEST ECAR trial and 26 days, mortality results, the lesions, and were at CX, said 22% trial, the French trial] also showed pubge of complex 64.9% of lesions E The 30-day percenta previously that ocUK IMPROV survival benefit t to note were total primary outcome, Medical Journal is importan and 46.2% a trend towards aneurysm repair extended British calcified lar no dify lished in the severely 77% of lesions femoral also found for endovascu was not statisticall . In addition of the superficial this (BMJ) in 2014, mortality between but in 78% l popclusions – poll (EVAR), portion 30-day Yes the proxima group and A CX audience ference in into the distal extended into nearly 80% significant. ular strategy 9% revealed that the endovasc group and subgroup artery, and results of the session primary a 94.4% artery”. the 12-month the open repair a strong benefit for d them liteal and a showed agreed that results E trial encourage analysis showed strategy in women at nine months, at the The trial the IMPROV often. ular rate with Eluvia the characterarisation 2 EVAR more the endovasc men. patency rate at baseline, on page to perform with Continued lesion revascul the fact that were similar Imperial College,data compared 3.6% target two groups in each latest Janet Powell, the the of istics presented ual patient te manthree-quarters London, UK, E (Immedia with almost aneurysms Pooled individ men. “The es from the IMPROV with with rupture: group being the patient data outcom the 12-month also very large trial that agement of presented this trial were in each group being lar repair) in from the Ron Balm Open vs. endovascu meta-analysis outcomes followprincipal average diameters outcomes from the she said. The and reported one-year of endovascular patient data over 8cm,” trials of strategy was mortality individual d controlled AJAX of ruptured ing either a one-year outcome were reinterven randomise or open repair . The s; the Dutch ted three outcomes repair first health-rela secondary aortic aneurysm ruptured aneurysm 2013), the discharge, benefit abdominal of Surgery tions, hospital costs, quality-adjustedte no survival trial (Annals trial (EJVES 2015) results demonstra lar strategy for rupECAR quality-of-life, tiveness.

French trial. cost-effec for the endovascuat one year. However, IMPROVE life-years and Powell noted that were and the UK for the all trials that tured aneurysm At CX 2015, answer the lar-first strategy “These were with a clinical designed to an endovascu ruptured aneurysms on patients In the trial was with a patient of performed aneurysm. what to do management discharge y room of ruptured question of mortality patients faster and it is suspicion to the emergencabdomidoes offer trial the 30-day ately who presents quality of life the AJAX of ruptured was approxim with better these factors with a diagnosis . “What we had tive. Both in both groups it was 22% and in also cost-effec patient and clinical an endonal aortic aneurysm for 25%, in ECAR a slightly was that using it was heard. are necessary which had anticipated aking, delegates in April in wherever IMPROVE, design, it was 35% decision-m vascular strategy, feasible, we could were published (EHJ). different study(BMJ 2014), but all These data of morphologically Heart Journal in each group operative mortality to lsbeck ate the benefit the European a pragmatic, multicenreduce 30-day open repair group Stefan Müller-Hü failed to demonstr setting. “The trial ranin the IMPROVE, from 47% in the emergent by the fact lar repair was and one Canada)a clinical EVAR UK endovascu (29 tre hampered 33% where so much patients with results were y,” she said. , 316 domised 613 repair performed on page 2 used extensivel “At one year, ruptured aneurysm stratthat open Continued diagnosis of lar-first Powell added: was 41.1% for VN App an endovascu was suitable patients to all-cause mortalitystrategy group and hing morphology ular egy (if aortic if not) and 297 to open @VN_publis the endovasc and open repair drew attention to also ews repair. Powell m/VascularN

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Charing Cross Special Edition

27–28 June BSET: British Society of Endovascular Therapy annual meeting Wotton-under-Edge, UK www.bset.co.uk

27–30 June 2019 Northeast National Conference Stamford, USA www.kent.edu/cpm/2019NNC

15–19 August ANZSVS Annual Scientific Meeting 2019 Adelaide, Australia www.anzsvs.org.au

23–27 August ESVS: European Society for Vascular Surgery annual meeting Hamburg, Germany www.esvs.org

31 October–3 November CEC: China Endovascular Course Beijing, China www.topcec.com

4–7 November VIVA: Vascular Interventional Advances Las Vegas, USA www.vivaphysicians.org

19–23 November VEITHsymposium New York, USA www.veithsymposium.org

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