Vascular News 84 – November 2019 US Edition

November 2019 | Issue 84 Ian Loftus:

Celia Riga:

Robotic technology

Page 22

Profile

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“Beware vulture capitalists”: Renowned inventor Thomas Fogarty outlines keys to success as medical device innovator and entrepreneur The pursuit of financial gain can often cloud the mission of innovation, Thomas Fogarty told a gathering at the inaugural International Society of Endovascular Specialists (ISEVS; 16–18 September, Houston, USA) Symposium in the keynote lecture.

“S

ometimes people want to make so much money, they lose sight of what they’re here for,” said Fogarty (Fogarty Institute for Innovation, Mountain View, USA) of his experiences as both an innovator and an investor. “We all like to make money, but if that’s all you’re focused on I don’t want to be around them.”

The remarks came in answer to a question posed by Alan Lumsden (Houston Methodist, Houston, USA) that sought to establish the most common mistakes young surgeon–innovators make when attempting to follow in the footsteps of people such as Fogarty. The worldrenowned cardiovascular surgeon and inventor answered by talking about his experience with a venture capitalist company, which he helped found.

He said: “Do you know what a venture capitalist is? Well, I was one of those once. In fact I co-founded a company. I think it was 18 months later that they kicked me out. Why? Venture capitalists are nothing but vultures. I call them vulture capitalists. That’s a very appropriate name … you can’t work with people who have the wrong motives.”

Fogarty pointed out another innovation hazard among emerging inventors: “If they’re very young, they think they know so much, and they’re so focused on being important by knowing so much,” he said.

Fogarty, whose inventions include the balloon catheter and the AneuRx stent graft, required little introduction owing to his stature in the cardiovascular surgery world. But Lumsden, chief of cardiovascular surgery at

Houston Methodist and host of the symposium, kicked off proceedings by telling the story of the Fogarty catheter’s genesis in the inventor’s passion for fishing, outlining how Fogarty came up with the idea and produced a prototype by tying the fingertip of a latex glove to a hollow tube with a piece of fishing line. “It moves clots unlike anything else,” said Lumsden.

Rod White (Long Beach Memorial Care Heart & Vascular Institute, Long Beach, USA) then introduced the lecture, setting a mirthful tone that was to run throughout. “If you look at this whole list of things [that Tom has achieved], he started off as a boxer—so that explains some of the stuff that’s going on.” More seriously, White also referred to an important lesson he learned while working with Fogarty: “Be the first one to know when a technology is not going to work.”

The address—entitled “What’s Innovation?”—saw Fogarty open by proclaiming: “Some of my best mentees are now my best mentors. A lot of guys are now

If you innovate, that technology can be used by other physicians.

You multiply what a surgeon does.”

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New patientlevel data “likely inadequate” to determine paclitaxel mortality signal A new meta-analysis from the VIVA/ NAMSA independent, patient-level data analysis shows a mortality risk that is slightly lower than the update revealed in June at the US Food and Drug Administration (FDA) device panel. While the investigators describe the analysis as “the most comprehensive […] of the available independent patient-level data to date”, they concede that—with less than 1,000 randomised controlled trial patients with long-term data—the result is “likely inadequate” to confirm either the presence, absence, or causality of a mortality signal.

AT THE RECENT Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2019; 24–28 September, San Francisco, USA), lead investigator Krishna Rocha-Singh (Prairie Heart Institute, Springfield, USA) reported a hazard ratio of 1.27 (95% confidence interval [CI] 1.03–1.58). The last update, presented at the FDA panel in June, was a hazard ratio of 1.38 (95% CI 1.06–1.8).

“This updated meta-analysis, which represents the most comprehensive analysis of available individual patient data to date, demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify any explanation,” Rocha-Singh told delegates at TCT. In December 2018, Katsanos et al described a Continued on page 4

Continued on page 4

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November 2019 | Issue 84

ISEVS 2019 keynote lecture

“Beware vulture capitalists”: renowned inventor Thomas Fogarty outlines keys to success as medical device innovator and entrepreneur Continued from page 1

teaching me that I was a mentor for.”

He continued: “If you innovate, that technology can be used by other physicians. That’s rewarding, because you multiply what a surgeon does. It’s a really interesting cycle that we go through, the process of learning. I’m still innovating and I do so in a private environment, a private hospital.”

Another question from the audience queried Fogarty on the importance of persistence in innovation, referring to his work on an atrial fibrillation intervention with nuclear devices that initially received little support, an innovation 14 years in the making. “Part of the problem was the concept was so outlandish, everybody said it wouldn’t work,” he said. “A lot of innovators have that same problem. The concept is so outlandish you can’t get anyone to invest in it. It is the biggest problem we have in raising money. Far out ideas are the most

valuable to human kind—our patients. But they cost a whole lot. It takes a long time.”

How might an inventor manage the risk that follows innovation, Fogarty was asked. “Well, follow the rules,” he answered. “That’s number one. Pay attention to the FDA. Because they will get you. Think of all the entities that could get you into trouble, and all of the regulations that you have to follow.”

What does Fogarty see for the future? “Innovation in the field of medicine is going to be even more critically important. Because there are many problems in many different areas. I think if we handle our innovations right, we’ll end up reducing cost.”

As the lecture was drawing to a close, Fogarty was asked how surgeons might balance promising ideas with maintaining patient care. He answered by referencing the importance of conducive environments. He circled back to his time at Stanford University.

“At Stanford, I was hired and re-fired two different times because I was interested in commercialisation,” he said. “Academia feels very often that those who relate to commercial entities are evil. Industry and the representatives of industry are often there only to contaminate the academic mission. That’s why they don’t like salespeople getting into hospitals. At Stanford, they were so adamant about salespeople… they used to give you pencils or pens that the dean required them to put in a large basket outside his office because they were contaminating by bribery with a pencil. That’s one reason I left Stanford the first time.”

L to R: Chris Zarins, Billy Cohn, Thomas Fogarty, Mike Silva, and Alan Lumsden

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New patient-level data “likely inadequate” to determine paclitaxel mortality signal Continued from page 1

hazard ratio of 1.93 in a meta-analysis published in the Journal of the American Heart Association (JAHA), which found an increased risk of death at two and five years following the use of paclitaxelcoated balloons and stents in the femoropopliteal artery. The paper was subsequently criticised for not using patient-level data.

The investigators of the present study describe that the Statistics Analysis Plan they used to assess the available data included the intent-to-treat approach as the primary analysis, incorporated all available follow-up time for patients and from all studies, and finally proportional hazard models and Kaplan-Meier estimates. Furthermore, multiple sensitivity analyses were performed, including as-treated, crossover, cause-specific mortality, and recovery of late missing data.

Rocha-Singh and colleagues included in the metaanalysis studies that only looked at devices approved in the USA for use in the femoropopliteal artery, that were only randomised controlled trials of paclitaxel versus a percutaneous transluminal angioplasty control, had a follow-up of at least two years, focused on overall effect as opposed to productspecific effect, and for which only individual patient-level data were available.

The study group report that, as of 10 May 2019, independent patient-level data were available for eight studies incorporating a total of 2,185 subjects, namely ILLUMENATE Pivotal, ILLUMENATE EU-RCT, IN.PACT SFA I/II, IN.PACT SFA Japan, Levant I, Levant II, Lutonix Japan, and Zilver PTX. In total, the enrolment period covered 2005–2015, a median follow-up of four years, 7,837.7 patientyears, 271 deaths, and 428 early patient exits.

They note that the primary model showed an increased mortality risk. Rocha-Singh and colleagues report 188/1,382 deaths in the control group out of the total number of subjects and 83/803 in the control group, with a hazard ratio of 1.38 (95% CI 1.06–1.8).

The new analysis, however, included recovery of long-term follow-up and vital status data as the investigators included the original JAHA analysis Continued on page 6

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November 2019 | Issue 84

Paclitaxel

New patient-level data “likely inadequate” to determine paclitaxel mortality signal Continued from page 4

from December 2018, the 2019 JAHA update, FDA original as treated data, FDA updated as-treated data, VIVA additional follow-up from May 2019, and also additional follow-up from August 2019.

In the latest analysis, the study group also used the following independent patient-level data dose– response analysis methods: paclitaxel dose based on total treatment received at index procedure, analyses adjusted for covariates via propensity matched scores given that the dose was not randomised, and a standardised dose that was created using log transformation, mean centring, scaling within studies, and attempts to control for differences between devices in excipient, coating, and range of doses.

The investigators note some limitations of the present study, including the fact that “substantial” missing data carries an unknown bias potential and uncertainty. However, they note that the recovery of missing data reduced the hazard ratio “incrementally”.

In summary, Roche-Singh and colleagues conclude: “The updated meta-analysis […] demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify an explanation.” They continue: “Consideration of ‘real-world evidence’, although hindered by issues of reliability, lack of followup, selection bias, and internal controls, may offer insights into paclitaxel device use and mortality.”

JACC: Cardiovascular Interventions publishes BD drugcoated balloon safety data A company-initiated, independent analysis of the Lutonix 035 drug-coated balloon (BD) femoropopliteal clinical programme has been published in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions. These data were simultaneously presented in a late-breaking session at Transcatheter Cardiovascular Therapeutics (TCT; 24–29 September, San Francisco, USA), the annual scientific symposium of the Cardiovascular Research Foundation.

THIS INDEPENDENT ANALYSIS evaluated Lutonix 035 DCB (n=1,093) and standard percutaneous transluminal angioplasty (PTA; n=250) safety outcomes using patient-level data and propensity-matching from three randomised controlled trials: LEVANT 1, LEVANT 2, and LEVANT Japan, as well as the Continued Access cohort of the LEVANT 2 trial, and confirmed that there was no statistically significant increase in mortality with the use of Lutonix 035 DCB. “While the FDA and Advisory Committee of Circulatory System Devices Panel in June identified a late mortality signal after treatment with paclitaxelcoated devices using a meta-analysis of randomised controlled trials at five years from multiple companies,

Lutonix (BD)

No evidence of increased mortality with paclitaxel-based devices in German claims database through 11 years A real-world safety analysis of paclitaxel-based devices in peripheral arteries, recently published in the European Heart Journal, showed no evidence for increased mortality over a period of 11 years. The authors remark: “Our analysis found the use of drug-eluting devices to be safe for endovascular therapy of the lower limbs.”

E

laborating on the findings, they comment: “Particularly with regard to long-term mortality, neither drug-coated balloons nor drugeluting stents were associated with increased risk compared to non-drugeluting devices.” Furthermore, they say, the analysis “exemplarily demonstrates the significance of health claims data for assessing urgent safety concerns without undue delay”.

In 9.2 million insurants of the German BARMER Health Insurance, Eva Freisinger (University Hospital Münster, Münster, Germany) and colleagues retrieved data on the application of paclitaxel-based drug-eluting stents (DES) and drug-coated balloons (DCB) from the time of their introduction on the market in 2007 until the present.

They then indexed all patients with first endovascular revascularisation

between 2007 and 2015, and followed them until 31 December 2017.

Freisinger and colleagues included each subsequently applied DES, DCB, baremetal stent, and uncoated balloon in a further analysis.

Multivariable Cox regression analysis considered potential non-linear timedependent hazard ratios of DES and DCB over a period of 11 years. The authors identified 64,771 patients who underwent 107,112 endovascular revascularisation procedures using 23,137 drug-eluting devices.

The investigators report that this analysis showed paclitaxel-based DES was not associated with increased longterm mortality for more than 11 years following application (all p>0.057).

DCB was associated with decreased long-term mortality for the first year post application (HR 0.92; p<0.001),

they recognised the benefits of these devices, including fewer reinterventions. They agreed that the magnitude of the signal should be interpreted with caution due to multiple limitations in the available data,” said Kenneth Ouriel, president and CEO, Syntactx, the clinical research firm that conducted the analysis, and former chairman of Surgery at the Cleveland Clinic.

He continued: “This large patient-level analysis found no statistically significant increase in mortality associated with Lutonix DCB treatment. Lutonix DCB remains a viable medical therapy for patients with peripheral arterial disease who demonstrate a high risk for restenosis and repeat femoropopliteal interventions.”

Further, a medical advisory committee comprised of an interventionalist and oncologist re-evaluated the cause of death in the LEVANT 1 and LEVANT 2 trials, including the LEVANT 2 Continued Access cohort. This independent review confirmed through adjudication that zero deaths were determined to be related to paclitaxel. Moreover, no clustering or pattern of death in any cardiovascular or non-cardiovascular categories was observed, which would have indicated a causal relationship between paclitaxel and death.

and indifferent correlation in the years thereafter (all p>0.202).

Addressing the significance of the study, the authors remark: “Our study debilitates current safety concerns resulting from previous findings,” referring to recent data which has indicated a two-fold increase in long-term mortality among patients treated with paclitaxel-based drug-eluting devices.

Though drug-eluting devices represent a well-established therapy being widely used for endovascular revascularisation for peripheral vessels, the authors note, these safety concerns affected international regulatory authorities to call for several alerts for further application of drug-eluting devices.

“Compared to the meta-analysis by Katsanos et al that resulted from smallsized selected cohorts of the underlying RCTs,” Freisinger and colleagues continue, “our data reflect the unselected real-world patient collective to which the

Our data reflect the unselected realworld patient collective to which the devices actually apply.”

Eva Freisinger

devices actually apply.”

Commenting on the patient cohort, they say it is “representative compared to other large epidemiological studies in terms of age, sex, cardiovascular risk burden, and LEAD [lower extremity artery disease] severity,” referring directly to studies by Olinic et al and Fowkes et al.

Though the authors stress that the present analysis covers a “large and comprehensive” database of unselected real-world patients, they admit that it is limited by the “general constraints” in the use of secondary healthcare data. Specifically, they note, real-world administrative data do not provide information on the underlying reason for DED treatment, representing a potential selection bias.

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November 2019 | Issue 84

Conference coverage

How to plan a functioning hybrid suite: 20 years of lessons learned Adrien Hertault Comment & Analysis In the age of increasingly complex endovascular procedures that require clinicians of various specialties, Adrien Hertault considers the complex task of how to plan a functioning hybrid suite.

T

he past two decades have been marked by the shift from traditional open repairs to endovascular procedures in vascular surgery. Initially performed with imageintensifier mobile C-arms rolled into the operating room when needed, the increasing complexity of endovascular procedures has led to the emergence of “hybrid” operating rooms. Creating a versatile environment to successfully answer those requirements is not an easy task, and is even more complex when clinicians from various specialties become users of the same operating room.

Hybrid rooms combine the image quality of a fixed imaging system, traditionally found in radiological suites, with the aseptic requirements of a standard operating room, and offer the opportunity for several medical specialties to define new standards of care. The current concept of a hybrid room also implies the building of an environment equipped with the latest imaging technologies and optimal dose reduction and radiation protection features.

When planning a hybrid suite, the first task is to gather and list precisely the needs of the various users who will

provide care in this multidisciplinary environment. Vascular surgeons, for example, perform procedures from the carotid to the pedal artery. Each of those procedures require different room settings, incorporating various positions for operators, the gantry, the monitors, lead protection, and so on. Arteriovenous fistula angioplasty or EVAR, for example, require very different settings. Right and left-handed practitioners might also have different needs. Therefore, it is essential to start by defining all the room settings that correspond to the daily practice of the hybrid room’s future users. The same process must be applied for each specialty using the room. As a result, it is often concluded that a truly versatile environment will require two sets of monitors. In order to complete a safe environment for patients’ care, it is also of paramount importance to involve the anesthesiology team in the design of these hybrid rooms.

The “open surgery” requirements must also be kept in mind. Surgical lights’ position and range must be carefully planned to cover the whole patient during hybrid procedures. Traditional radiological floating tables can easily be panned in every direction, and provide optimum conditions for endovascular cases. However, they lack the flexibility and modularity of classic surgical tables for open surgery. As a result, they offer different benefits, and one must consider which one will best answer its practice.

Once the clinical and technical specifications have been clearly

Protamine use found to significantly reduce re-operations for patients who undergo carotid endarterectomy in study involving large national registry Re-operations for bleeding are cut in half among patients who receive protamine during carotid endarterectomy. This was the main finding revealed by David Stone (DartmouthHitchcock Medical Center, Lebanon, New Hampshire, USA) at the annual meeting of the European Society for Vascular Surgery (ESVS; 24–27 September, Hamburg, Germany).

STONE AND HIS team of investigators discovered that protamine administration during the procedure “is an independent predictor of reduced bleeding complications reflected by a 50% reduction in reoperation for bleeding”. He told the audience during a scientific session. “It was not, however, associated with an increased incidence of thrombotic events. The consequences of re-operation for bleeding were not benign, but rather associated with substantially higher rates of MI [myocardial infarction], strokes and death.”

Stone identified a need for further research in protamine’s use during carotid endarterectomy, in the light of ongoing controversy surrounding the practice. “Protamine users will often cite diminished bleeding complications without an attendant increase in thrombotic events while other surgeons remain hesitant to use protamine, noting a perceived increased risk of thrombotic complications,” he said.

The latest research follows a 2010 study conducted

by Stone and a team of investigators which accessed a regional registry in New England, “demonstrating a 50% reduction in significant bleeding events at the time of endarterectomy with protamine use, without an increased risk of thrombotic complications”, he said.

Furthermore, the researchers believe this earlier work spurred an increase in protamine use across the USA. For the current study, the team widened their scope by using a large national registry to further examine the effect of protamine use during carotid endarterectomy across the country.

“Specifically, we sought to determine whether

[Protamine] should be adopted as a benchmark and guidelines for carotid surgery.” protamine had an impact on serious bleeding complications measured by re-operation for bleeding,” explained Stone. “We also sought to determine whether protamine changed the incidence of thrombotic events, specifically myocardial infarction, stroke, and death.”

The investigators identified all carotid endarterectomy procedures performed from 2012–2018, settling on a study cohort of nearly 73,000 operations.

identified, they must be discussed with suppliers. Each vendor will have its own solution to meet those requirements, while considering the structural limitations of the future hybrid room (size, shape, ceiling height, location, and so on). At this step, simulation of all possible settings, through various 3D modellings or virtual reality, is mandatory to ensure that the final design is fully functional. As the complexity of these rooms can be difficult to figure out, it is also a good option to obtain feedback from experienced hybrid room users having similar practices.

Last but not least, it is important to plan for the implementation and the future of the hybrid room when discussing with suppliers. Learning how to use this complex technology is not an easy task and, depending on the familiarity of each user with imaging and computer-assisted technologies, it can take several weeks to become autonomous. Therefore, several training sessions, adjusted to the level of each user, and the presence of industry trainers after the hybrid room has become operational should be incorporated into the initial contract. A maintenance contract should also be defined. Finally, hybrid rooms are rapidly evolving systems, so the possibility for future upgrades should also be considered.

Adrien Hertault is a vascular and endovascular surgeon at the Valenciennes General Hospital in Valenciennes, France.

Main outcome measures studied were bleeding requiring re-operation, MI, stroke, and death during hospitalisation, Stone said.

“Protamine administration was not randomised but determined by individual surgeon preference.”

The results showed variances in protamine use: David Stone approximately 70% of US surgeons either routine or rare users, with nearly one third using variably.

Similarly, use also differed by region, with some achieving over 90% utilisation while others remained under 50%.

“This variation in protamine use led to nearly a two-thirds to one-third cohort of endarterectomies in which protamine was or was not used, and thus created an excellent study population to address the questions posed in this analysis,” Stone said. “Our main finding is that re-operation for bleeding is reduced by 50% in patients who receive protamine (0.71% vs. 1.43%; p=0.0001).”

He added: “At the same time, we again found no significant difference in the incidence of major thrombotic complications, including MI, stroke and death, between protamine-treated and untreated patients.”

Whether or not protamine is administered, Stone said, the consequences of re-operating in the event of bleeding were significant. Such patients demonstrated higher risks of thrombotic events: seven-fold in the case of MI, eight-fold for stroke, and a 13-fold higher risk of death.

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November 2019 | Issue 84

Conference coverage

First-in-man application of TrackCath System yields promising results The TrackCath Catheter (Medyria) was found to be safe while not affecting the general condition of patients during endovascular repair of aortic aneurysms in a first-in-man clinical application. Furthermore, the system provides for a reduction in contrast dye and X-ray exposure during the identification and cannulation of the target vessel or side branch, Nikolaos Floros (University Hospital Dusseldorf, Dusseldorf, Germany) told a scientific prize session at the European Society for Vascular Surgery annual meeting (ESVS; 24–27 September, Hamburg, Germany).

FLOROS WAS PRESENTING the results of the ACCESS trial, carried out at four clinical sites in Germany to assess use of the TrackCath System.

“Complex endovascular aneurysm repair (EVAR) procedures such as fEVAR (fenestrated EVAR) or bEVAR (branched EVAR) expands the population of patients that can be treated endovascular,” he told the audience during his presentation. “But, as we also know, the cannulation and identification of aortic side branches of target vessels can be challenging, and that can be performed only with the use of X-ray and

contrast dye.”

As background, Floros referenced data showing that in each endovascular procedure X-ray exposure is high and contrast-induced. Acute kidney injury incidence can reach 20–25%, he said.

“A UK study of 950 EVARs with long-term followup found £12.2 million in extra treatment costs yearly and 5,100 extra bed days yearly for treatment of acute kidney injury,” Floros continued.

The TrackCath System—which uses a low-energy hot-wire anemometry principle to detect changes in blood flow, velocity and direction— “helps with the localisation of the side branches of target vessels and provides a technique for identifying side branches and targeting orifices without using X-ray and contrast dye,” he said.

The primary endpoints of the ACCESS trial were safety (all device-related serious adverse events) and performance (procedural success rate defined as successful TrackCath Catheter delivery of the distal end of the guidewire or of the 4Fr catheter to the selected

The TrackCath catheter was found to be safe while not affecting the general condition of patients.” targeted orifice), with secondary endpoints of blood flow velocity performance and the use of contrast dye and X-ray exposure.

Thirty-seven patients >18 years requiring endovascular intervention for a thoracoabdominal aortic aneurysm (TAAA) or an abdominal aortic aneurysm (AAA) were enrolled and assessed for safety.

Novel paclitaxel-nano-coated balloon achieves lower incidence of restenosis than PTA at two years Two-year results of EffPac—a randomised controlled trial to assess the safety and efficacy of a novel drug-coated balloon (DCB) with a nanotechnology coating—have been announced. The investigators, Ulf Teichgräber (University Hospital Jena, aGermany) and colleagues, report that use of the DCB, iVascular’s Luminor, resulted in a significantly lower incidence of binary restenosis compared to percutaneous transluminal angioplasty (PTA).

T

he new data, presented for the first time at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain), also showed a significant clinical and haemodynamic improvement from baseline, similar to the level of improvement achieved with plain balloon angioplasty, but with considerably fewer repeat revascularisations. The investigators found no difference to plain balloon angioplasty regarding safety.

The EffPac (Effectiveness of paclitaxel-coated Luminor balloon catheter versus uncoated balloon catheter in the arterio femoralis superficialis) trial was designed to assess the safety and efficacy of the Luminor paclitaxel drug-

Of these, 11 were roll-in patients, and the remaining 26 were also assessed for performance analysis.

The results demonstrated no serious adverse events in any of the patients across either phase, and a 98% success rate in terms of performance: 49 orifices out of 50 were successfully treated with the TrackCath system, Floros said. The single failure, he added, came in a patient with a tAAA type IV owing to “unsuccessful identification due to low signal, but there were no consequences for the patient”.

Meanwhile, contrast dye exposition was measured as having a median value of 1ml per orifice alongside an X-ray exposure of five minutes per orifice. The duration of target orifice identification was two minutes per orifice and one minute for cannulation. “Being one of the surgeons that performed these operations and used the catheter, I could state that the TrackCath System, always in combination with other tools such as 3D-image-reconstruction and fusion, can help us to reduce the contrast dye and X-ray exposure,” Floros concluded.

In reply to a question from the audience addressing whether fusion imaging had been deployed in the study and whether it use might further speed up identification and cannulation, Floros responded in the affirmative.

For some of the roll-in cases, “the learn phase,” he said, “I used the fusion image and it helped me to do the identification and cannulation more quickly”.

eluting balloon in inhibiting restenosis and in ensuring long-term patency. The investigators compared the DCB catheter to non-coated plain balloon angioplasty in stenotic or occlusive lesions of the femoropopoliteal artery.

Between September 2015 and December 2016, the investigators enrolled 171 subjects across 11 German study centres. Eighty-five of these patients were randomised to DCB angioplasty, with the remaining 86 assigned to the plain balloon angioplasty group. They note that before the 24-month mark, analysis was discontinued for 25 patients in the DCB group and 30 patients in the plain balloon angioplasty cohort.

The primary endpoint of the study was defined as late lumen loss at six months. The secondary endpoints at six,

12, and 24 months included primary patency, target lesion (TLR) and vessel (TVR) revascularisation, quality of life—assessed by the EQ-5D—change of Rutherford-Becker classification (RBC), ankle–brachial index (ABI), and major and minor amputation rates.

The authors comment that 12 months in to the study, the investigational DCB catheter proved “highly effective and safe in inhibiting restenosis”, and demonstrated a walking improvement in change of RBC compared to plain balloon angioplasty.

Twelve-month results of the safety and efficacy of the Luminor device had been released prior to the CIRSE 2019 presentation. The authors detail

The investigational DCB proved highly effective and safe in inhibiting restenosis.” that at six months, the late lumen loss was on average 0.92mm lower in the DCB group than in the plain balloon angioplasty group (95% confidence interval [CI] -1.36mm to -0.49mm, p<0.001). Significantly more patients showed a walking improvement after DCB treatment at six months (p=0.021).

TrackCath (Medyria)

Looking at the 24-month results, Teichgräber and colleagues reveal that primary patency (the rate of freedom from restenosis) was 90.2% (95% CI 80.4 to 95.2) in the DCB arm, compared to 94.7% (95% CI 86.4 to 98) at 12 months. The corresponding figures for the plain balloon angioplasty cohort were 62.7% (95% CI 50 to 73) and 71.3% (95% CI 59.4 to 80.3).

Freedom from TLR in the DCB group was 97.2% (95% CI 89.1 to 99.3) at 24 months, compared to 98.7% (95% CI 91.1 to 99.8) at 12 months. In the plain balloon angioplasty group, the figures were 78% (95% CI 66.5 to 86) and 81.6% (95% CI 71 to 88.7), respectively.

The investigators detail that in both groups patients were of similar age.

While the DCB cohort was 68±7.5 years old, on average, the plain balloon angioplasty group was 68.1±8.8 (p=0.979). There were slightly fewer male patients in the DCB group (60%) than in the plain balloon angioplasty group (69.8%; p=0.239), and also slightly fewer diabetic patients in the DCB group (36.5%), compared to 40.4% in the plain balloon angioplasty group (p=0.681). There were fewer current smokers in the plain balloon angioplasty group than among DCB patients (40.5% vs. 43%; p=0.856). There were just over double the number of patients with critical limb ischaemia in the DCB group (3.6%) than there were in the plain balloon angioplasty group (1.2%; p=0.929).

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November 2019 | Issue 84

Vascular trauma training

Vascular trauma training in Europe—current challenges and possible solutions Daniel Hinck Comment & Analysis Daniel Hinck discusses the current challenges facing vascular trauma training in Europe and how the German military tries to remedy them.

VASCULAR SURGERY, LIKE other specialisations, is shifting from open techniques to endovascular and minimally invasive techniques. This shift creates increased educational needs for vascular surgeons working in civil clinical settings and is reflected in the vascular residency training programme.

This also results in a considerable decrease in the opportunity to perform open surgical procedures.

Emergency treatment for acute vascular trauma often requires open vascular surgery and is, in many cases, the only option. Recent analysis of the Global Terrorism Database of the University of Maryland shows an increase in terrorist attacks leading to fatalities and severely injured casualties in Western Europe over past years. An evaluation of the terrorist assaults in Paris in November 2015, published this year,

shows that 10% of the wounded needed vascular surgery. Therefore present circumstances still require intensive training of low-volume, high-risk surgeries—those rarely practiced in daily clinical practice.

Physicians working in the military, in particular, hold a broad education in surgical techniques that is not being met by the current volume of open cases compared to endovascular cases.

In order to train appropriately qualified vascular residents and assure the best medical care for patients, the German military has considered instigating its own training curriculum. Some examples within the framework of damage control surgery include access to and control of bleeding of supra-aortic vessels, vascular shunting with arterial interponat, patch or bypass and liver suture. These should be handled reliably, and to reach that target

simulation models are used.

Examples of simulation training include trauma courses with human cadavers, anesthetised pigs, or artificial mannequins. The requirements of the simulation systems are demanding and one size does not fit all.

Corpses offer the advantage of accurate human anatomy, allowing better training in surgical access and exposure of injured vessels. Active bleeding is nearly impossible to demonstrate. In contrast, “live tissue training” with pigs is more realistic with regard to the biological quality and feel of the tissue, the perfusion of tissue and organs (leading to bleeding during the skin incision), and the pathophysiological reaction of the organism to the trauma, which corresponds to humans. Challenges for this program include its limited social acceptability and the ethical and legal guidelines attempting to lower the amount of experimental animals for teaching purposes.

To close the gap between live tissue training and training with human cadavers, combining human anatomy with realistic bleeding behaviour, extracorporal blood pumping systems have been tried on human cadavers.

Perfused cadavers make for more realistic trauma training and have remarkable potential for the future.

Technical surgery models also exist.

Depending of the level of training and the practised procedure, these can be

Present conditions require intensive training of lowvolume, high-risk surgeries.”

taken into consideration. Problems with these include unrealistic bleeding behaviour with no discernible difference between arterial and venous bleeding.

Furthermore, artificial blood has no clotting system and does not coagulate as expected in a real trauma patient. To date, no simulation model has been able to reproduce the complexity of the human organism for authentic surgical training.

For all technical capabilities, the financial aspect should not be underestimated. Technological progress and inventions have significant financial penalties. Purchase of a whole synthetic body model costs between €160,000– 200,000 without consumable supplies.

Hiring a practice model can cost between €20,000–50,000 per day.

As well as surgical skills, the surgeon needs the ability to communicate and interact as part of a team, possess an understanding of leadership and decisionmaking, and demonstrate a resistance to stress, as well as operate proactively, if treatment is to succeed. These are the bricks that guarantee an effective education.

Loss of trauma surgical expertise in the current training of specialists, and increasing sub-specialisation of the various specialties, presents a major challenge. Training with simulation systems could be one way to address these challenges.

To conlcude, cooperation between industry and the medical profession on the development of simulation mannequins should be pushed forward. This will result in the production of systems that meet the requirements of anatomy, bleeding behaviour and pathophysiological reactions found in the human body.

Daniel Hinck is head of the departments of General Surgery and Vascular Surgery at the Bundeswehr Hospital in Hamburg, Germany.

Disruption of the blood-spinal cord barrier predicts permanent paraplegia after endovascular TAAA repair In the largest prospective analysis of cerebrospinal fluid (CSF) in patients undergoing endovascular thoracoabdominal aneurysm repair (TAAA) to date, permanent paraplegia was found to be associated with shedding of bound ADVS-1 from the parenchymal cord into CSF and disruption of the blood-spinal cord barrier, which in turn leads to cord oedema and a leucocyte infiltration.

Jamie Kelly

he investigators conclude: “This characteristic CSF signature predicts irreversible paraplegia after TAAA repair and identifies ADVS-1 as a novel therapeutic target.” They elaborate: “ADVS-1 [an osmoreceptor essential in maintaining blood-spinal cord barrier integrity] inhibition after ischaemic stroke stabilises the blood/brain barrier, prevents cerebral oedema, and limits cytotoxic brain damage.”

First author Jamie Kelly (King’s College London, London, UK), recently won first prize for presenting these findings at the European Society of Vascular Surgery 33rd Annual Meeting (ESVS 2019; 24–27 September, Hamburg, Germany). Most compelling is the fact that the study group, led by Bijan Modarai, have modulated ADVS-1 in an in vivo model of spinal cord ischaemia (SCI), stabilising the blood-spinal cord barrier

associated with a significant infiltration of CD45+ leucocytes into the CSF (p<0.0001) and that levels of ADVS-1 were over seven-fold higher in CSF from permanently paraplegic patients compared with those that recovered (p=0.0008).

Furthermore, CSF ADVS-1 levels >15ng/ml predicted permanent paraplegia with a specificity of 100%, and permanent paraplegics were more likely to have pathological spinal cord swelling at T11 (1.9-fold greater cord volume), T12 (2.1-fold greater cord volume), and L1 (2.9-fold greater cord volume) on T-2 weighted MRI when compared with the other groups (p<0.05 at each level). Patient demographics, extent of aortic coverage and preoperative CSF content was comparable between patients with no SCI, those with reversible SCI, and those that remained paraplegic.

T

and reducing the severity of paraplegia.

Between October 2016 and August 2018, the study group prospectively recruited patients undergoing TAAA repair (open or endovascular using branched/fenestrated stent grafts) with a CSF drain in place. They collected CSF preoperatively and at 24-hour intervals until drain removal, performed detailed daily neurological examinations, and finally a neurologist—who was blinded to the study—made the diagnosis of SCI. The investigators detail that the content of CSF cells was characterised by flow cytometry and the CSF proteome was analysed by tandem-mass-tag labelled proteomics and principle component analysis. They used T2 weighted spinal cord MRI to measure cord volume by neuroradiologists blinded to patient outcomes.

The authors found that permanent paraplegia was

Bijan Modarai

16

November 2019 | Issue 84

ESVS 2019

Absence of long-term benefit of revascularisation in patients with intermittent claudication out to five years Five-year results of the IRONIC (Invasive Revascularisation Or No in Intermittent Claudication) trial show that a liberal strategy of revascularisation in patients with intermittent claudication did not translate to long-term health-related quality of life (HRQoL) benefits or to improved walking capacity at five years. These results are contrary to the outcomes at one- and two-year follow-up. Also at five-years, revascularisation was not a cost-effective option from a payer/healthcare perspective.

H

enrik Djerf presented these results on behalf of colleagues Mårten Falkenber, Lennart Jivegård, Mikael Svensson, and Joakim Nordanstig (Sahlgrenska University Hospital, Gothenburg, Sweden) at the 33rd Annual Meeting of the European Society of Vascular Surgery (ESVS 2019; 24–27 September, Hamburg, Germany).

During the session, Djerf concluded that future research should focus on a more precise targeting of intermittent claudication subgroups that might still benefit from revascularisation. Djerf and colleagues note that, despite little evidence of long-term benefit, revascularisation is an increasingly often offered as a treatment option to intermittent claudication patients.

The aim of the present study was to determine the long-term effectiveness and cost-effectiveness of revascularisation in addition to best medical treatment and exercise therapy, compared with a non-invasive treatment approach in patients with mild to severe claudication. The investigators targeted the two most widely used treatment strategies for claudication lower limb symptoms. Previously, intermediate results have been reported, and researchers can now reveal follow-up results out to five years.

In the trial, patients with mild to severe claudication due to iliac or femoropopliteal peripheral arterial disease were randomly assigned to either revascularisation (revascularisation, best medical therapy, and structured exercise therapy) or non-revascularisation (best medical therapy and structured exercise therapy). In the revascularisation group, the Trans-Atlantic Society Consensus (TASC) II recommendations were used to guide the choice of invasive technique (endovascular or open surgical revascularisation).

The primary outcome was HRQoL assessed with the Short Form 36 (SF-36) questionnaire, while supporting endpoints were change in disease-specific HRQoL (VascuQoL) and treadmill walking distances. Changes in HRQoL using the EuroQoL 5 dimension 3L and the “Dolan”-Tariff were used to assess quality-adjusted life years (QALYs). The data were then used to perform cost-effectiveness analyses from a payer/healthcare perspective.

Between 2010 and 2012, a total of 158 patients were randomised 1:1. With regard to the primary endpoint, no intergroup differences were observed for the different SF-36 sum- and domain-scores changes from baseline to five years, except for the SF-36 role emotional domain score which showed a greater improvement in the nonrevascularisation group (n=116, p=0.007).

No intergroup differences were observed in VascuQoL total and domain-scores changes (n=116). More patients had died in the revascularisation group (n=13 vs. n=7).

A revascularisation strategy resulted in almost twice the cost compared to a non-invasive treatment approach (€10,915 vs. €5,804), with no difference in the total

that “long-term follow-up data and health-economic assessments are warranted to further establish the role of revascularisation in intermittent claudication”.

Nordanstig and colleagues noted that there were certain limitations to the study. “Because our approach was to include the large group of claudicants in which the indication for revascularisation is not clear-cut,” they stated, “we have not specifically studied the effect of invasive treatment in selected subgroups,” suggesting that “in selected intermittent claudication subgroups, the effect of revascularisation could be different than in our unselected sample”. In addition, they remarked that they may have underestimated the effect of invasive treatment. “Fifty-two patients were excluded from participation because invasive treatment was considered mandatory by the responsible vascular surgeon,” they specify. Another limitation was that although the investigators believed their results may allow for general conclusions applicable to the majority of intermittent claudication patients, “they cannot readily be generalised to intermittent claudication patients with very mild or very severe symptoms”, as such patients were not part of the study sample.

In 2016, the British Journal of Surgery published twoyear results from the trial, which appeared similar to findings at one year. “A revascularisation strategy with unsupervised exercise improved health-related quality of life and intermittent claudication distance more than standard best medical therapy and unsupervised exercise programme in patients with lifestyle-limiting claudication,” Nordanstig and colleagues concluded.

Comment

Henrik Djerf

QALYs per patient between the revascularisation and the non-revascularisation group.

Revascularisation favoured at one and two years

The IRONIC study favoured revascularisation at one and two years. These positive findings, however, have not been maintained at long-term follow-up.

In 2014, one-year results of the IRONIC trial were published in Circulation. Joakim Nordanstig (Sahlgrenska Academy, Gothenburg University, Sweden) and colleagues had set out to test the hypothesis that an invasive treatment strategy versus noninvasive treatment improves HRQoL after one-year in unselected patients with intermittent claudication.

The investigators concluded that an invasive treatment strategy improves health-related quality of life and intermittent claudication distance after one year in patients with stable lifestyle-limiting claudication receiving current medical management, suggesting

Despite little evidence of long-term benefit, revascularisation is increasingly offered as a treatment option to intermittent claudication patients.”

Talking to Vascular News, Yan Gouëffic (Paris, France), comments on the five-year results: “In this single-centre, randomised clinical trial the investigators used as a primary endpoint EuroQoL 5 dimension (EQ-5D) 3L to assess quality of life. The EQ-5D is one of the most frequently used generic, preference-based instruments for measuring the health utilities of patients in economic evaluations and seems to be an appropriate measure for economic evaluation and health technology assessment in conditions where it has demonstrated evidence of responsiveness (Nalin Payakachat, Pharmacoeconomics 2015). However, these generic questionnaires are considered to be less sensitive to detect small but clinically important differences in treatment effects because they do not focus on specific effects of disease.

Regarding peripheral arterial disease, previous studies have demonstrated a better discriminative ability of disease-specific versus generic questionnaires to detect changes in quality of life in peripheral arterial disease patients (de vries, J Vasc Surg 2005; Sanne E Hoeks, J Vasc Surg 2009).”

He adds: “In the IRONIC trial, 70 patients received the allocated invasive treatment and 32 patients were treated by an infra inguinal angioplasty. According to the protocol, stent placement in the femoropopliteal segment was reserved for suboptimal angioplasty results (residual stenosis or flow-limiting dissection). Angioplasty as first line of femoropopliteal endovascular treatment is not an option anymore. Multiple studies have shown the superiority of stents or drug eluting therapy over angioplasty. Moreover, long-term data are now available in particularly for drug-eluting stents and confirm the sustained safety and clinical durability in comparison with standard angioplasty (Dake, Circulation 2016) Finally, he tells Vascular News: “The authors concluded that revascularisation was not a cost-effective option from a payer/healthcare perspective. Nowadays, medico economic assessment is a key point to assess medical. Usually the incremental cost effectiveness ratio that describes the extra cost per one additional unit of patient outcome is used as primary endpoint.

Furthermore, a societal perspective instead of a payer/ healthcare perspective should be considered since it includes the impact of an intervention on the welfare of the whole of society, not just on the individuals or organisations directly involved.

18

November 2019 | Issue 84

NICE guidelines

NICE guidelines on ruptured AAA will necessitate team training

At the first London Aorta meeting, a collaborative association between the London Aorta Masterclass and the London Aortic Symposium held 10–11 October in London, UK, Peter Holt (St. George’s Vascular Institute, London, UK) told delegates that “patients will be unnecessarily palliated” by the UK National Institute for Health and Care Excellence (NICE) guidelines for ruptured abdominal aortic aneurysms (AAA). He suggested that in order to deal with this, simulation and team training will become important.

A

s part of a session on emergency aortic surgery, chaired by Max Baghai (London, UK) and Mark Field (Liverpool, UK), Holt began his presentation by outlining the NICE guidelines for repairing ruptured aneurysms. He delineated that NICE recommends physicians consider the following: endovascular repair (EVAR) or open surgical repair for people with a ruptured infrarenal AAA, and open surgical repair for people with a ruptured complex AAA. The guidelines also suggest physicians do not offer complex EVAR to people with a ruptured AAA if open surgical repair is not suitable, except as part of a randomised controlled trial comparing complex EVAR with open surgical repair. In terms of anaesthesia and analgesia, the recommendations state that one should consider using local infiltrative anaesthesia alone for people having EVAR of a ruptured AAA. Looking closely at the guideline which advises physicians to consider EVAR or open surgical repair for people with ruptured AAA, Holt warned delegates: “Be aware that EVAR provides more benefit than open surgical repair for most people, especially for women and for men over the age of 70.” In addition, he noted that open surgical repair is likely to provide a better balance of benefits and harms in men <70 years old.

In terms of epidemiology, Holt pointed out that there are certain trends that should be considered before

Statins linked with reduced mortality in PAD patients, even when started late after diagnosis Statins are linked with reduced mortality in patients with peripheral arterial disease, even when started late after diagnosis, reports a study presented recently at the European Society of Cardiology 2019 Congress together with the World Cardiology Congress (ESC; 30 August–4 September).

Patients who stop taking the drug are at similar risk to those who never start. The research shows the importance of starting and adhering to lifelong medication, preferably at a high dose.

AROUND 200 MILLION people worldwide have peripheral arterial disease (PAD), a condition in which arteries in the legs are clogged. This

treating ruptured AAA. Using data from Lilja et al, published in the European Journal of Vascular and Endovascular Surgery, Holt noted that there is a trend towards older patients requiring treatment, comparing an average age of 72.8 in the period 1994–1999, to an average age of 75.3 in the period 2010–2014. Secondly, he reported that there is an increasing number of female patients undergoing ruptured AAA surgery, with 86.3% male patients between 1994 and 1999, compared to 79.6% between 2010 and 2014. Also noted was the

Delivery of the most clinically costeffective modality of treatment will be difficult.” increasing age of patients, with 19.1% of patients aged 80 years or over in the period 1994–1999 increasing to 33.3% in the period 2010–2014. Finally, he mentioned that there is a trend towards EVAR, comprising just 0.1% of surgeries for ruptured AAA 1994–1999, compared to 29.8% in 2010–2014.

Considering these figures, Holt stated: “It is very clear that EVAR is preferential for ruptured AAA, under local

restricts blood flow to the legs and raises the chances of stroke and heart attack.

Around 30% of patients have pain and cramping in their legs when they walk— referred to as intermittent claudication— while others have gangrene in the feet due to poor circulation.

Statins are recommended for all patients with PAD, together with smoking cessation, exercise, healthy diet, and weight loss. Statins diminish the risk of stroke and heart attack by reducing lowdensity lipoprotein (LDL) cholesterol, which causes atherosclerosis.

But adherence to statins is low: over the past five years, just 57% of patients in Europe took the medication as directed.

In 2016–2017, only one-third of patients on statins reached the LDL cholesterol target of below 1.8mmol/L (70mg/ dl).

This study examined whether adherence to statin therapy influenced survival in patients with symptomatic PAD. The study enrolled 691 patients admitted to hospital between 2010–2017 and followed-up for a median of 50 months.

At the beginning of the study, 73% of patients were on statins, increasing to 81% at the 50-month follow-up. The dose of drug also increased between the two time periods, which was paralleled by a significant drop in LDL cholesterol from 97 to 82mg/dL. Patients who stopped taking a statin had a similar mortality rate (33%) to those who never took the drug (34%).

Adhering to statins for 50 months was

anaesthetic where possible, especially for women, and especially is the patient is over 70 years old, and most are.”

“The problem is,” he continued, “we are advised to offer open surgical repair, unless there are anaesthetic or medical contraindications, not to offer EVAR to people with an unruptured infrarenal AAA if open surgical repair is suitable, and not to offer EVAR to people with an unruptured infrarenal AAA, if open surgical repair is unsuitable because of their anaesthetic and medical condition.”

Holt then referred to survey results to the question “If you were not routinely performing elective EVAR in your hospital, would you be able to deliver an emergency EVAR service for ruptured AAA as recommended?” Eighty-eight per cent of the respondents replied that they would not.

Considering the effects of these guidelines, Holt suggested that unruptured elective AAA will present as ruptured, including in NAAASP patients. He also posited that a lack of current practice will mean fewer patients are treated, referring to the fact that 24/7/365 service is not reliably delivered currently in many hospitals. In addition, only 27% of surgeries over the last three years have been EVAR, elective experience is being lost, and there being no consignment stock.

Finally, he put forward the outcome that treatable patients will be palliated, as most should have been treated electively.

Holt summarised that NICE will have an impact on the delivery of elective and ruptured AAA, that the number of aortic ruptures will increase, and that NAAASP will increase. In addition, he suggested that delivery of the most clinically cost effective modality of treatment (LA EVAR) will be difficult, and that patients will be unnecessarily palliated, leading to the conclusion that simulation and team training will become increasingly important in the future.

All PAD patients should take statins, preferably very potent statins, like rosuvastatin 40mg or atorvastatin 80mg.” linked with a 20% rate of death.

Taking high-dose statins throughout the study was linked with the lowest mortality rate (10%), while reducing the dosage during the study was related to the highest death rate (43%).

Study author Dr Jörn Dopheide of Bern University Hospital, Switzerland said: “The study shows that adherence to statins is essential for the best prognosis. We also show that it is never too late to start medication and benefit from it. On top of that, it is crucial not to reduce the dose because LDL cholesterol levels rise again, thus increasing the overall risk on top of the residual risk for further events.”

He concluded: “All PAD patients should take statins, preferably very potent statins, like rosuvastatin 40 mg or atorvastatin 80mg, or at the highest tolerable dose. In the rare case of statin intolerance, which was around 2% in our study, alternative lipid lowering therapies must be considered.”

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November 2019 | Issue 84

Stroke

Superior clinical outcomes for endovascular therapy candidates triaged directly to a comprehensive stroke centre For patients with emergent large vessel occlusion (ELVO or LVO) eligible for endovascular therapy, prehospital triage to a more distant comprehensive stroke centre (CSC) compared with a closer primary stroke centre (PSC) was associated with significantly shorter time to thrombectomy, better clinical outcomes and no delay to alteplase. Within a matched-pairs model, this association held true for the entire cohort, report Mahesh V Jayaraman, Ryan A McTaggart and colleagues (Warren Alpert Medical School of Brown University, Providence, USA.

P

ublished in the Journal of NeuroInterventional Surgery, Jayaraman et al write in their paper: “In a densely populated setting […], seven additional minutes of prehospital transport was associated with nearly an hour faster time to endovascular therapy, and a 16–26% absolute increase in functional independence.”

Between January 2016 and December 2017, a portion of the region (Rhode Island, Providence, USA) in which the study was conducted allowed field triage for patients who met severity criteria to a more distant CSC as opposed to the closest PSC. During these two years, 232 patients met inclusion criteria, and in turn, 144 were taken to the closest PSC and 88 to the more distant CSC. “The median additional transport time to the CSC was seven minutes,” write the authors. They also found that times from scene departure to alteplase and arterial puncture were faster in the direct group (50 vs. 62 minutes, 93 vs. 152 minutes, respectively; p<0.001).

Among patients who were independent before the stroke, the odds radio for less disability in the direct group was 1.47 (95% confidence interval [CI] 1.13–1.93, p=0.003), and 2.06 (95% CI 1.10–3.89, p=0.01) for the matched pairs. Moreover, the rate of symptomatic intracranial haemorrhage was 10/144 (7%) in the transfer group, and 1/88 (1%) in the direct group (p=0.06).

In light of the findings, McTaggart and colleagues believe, “these results will drive much needed change to regional stroke care delivery; better point-of entry protocols not only save lives but every minute reduction in time to endovascular therapy is estimated to save the healthcare system more than US$1,059.”

The study investigators provide additional background to the study. “Our region has a population of nearly 1.5 million people in Rhode Island and southeastern Massachusetts, and all 16 PSCs in our region use a standardised protocol to transfer patients to a single CSC where all endovascular therapy is performed,” they write.

Yet, with a portion of the region implementing a severitybased, field triage algorithm that directed emergency medical services to bypass closer PSCs to take patients directly to the CSC, the authors could compare the times to treatment and outcomes of patients.

The following criteria were used to identify eligible patients: a new, disabling neurological deficit (scoring

≥6 on the National Institutes of Health Stroke Scale [NIHSS]), initial non-contrast CT demonstrating lack of large completed infarction (scoring ≥6 on the Alberta Stroke Programme Early CT score [ASPECTS]), occlusion of the intracranial internal carotid or middle cerebral artery, the closest hospital from the scene was a PSC, as well as availability of 90-day clinical follow-up.

McTaggart and colleagues acknowledged that, in terms of demographic variables, there were higher rates of hyperlipidaemia in the transfer group (54% vs. 39%, p=0.02). Yet, the remainder of the demographics failed to elicit any significant differences between the two groups.

We need to critically re-evaluate why, where, and how we are accrediting stroke centres in the new mechanical thrombectomy era.”

Discussing the results further, the authors write that many may argue that the findings are not applicable to other regions. However, they referenced the STRATIS (Systematic evaluation of patients treated with neurothrombectomy devices for acute ischaemic stroke) registry, which includes 985 patients across 55 states in the USA, 65% of whom incurred a stroke within 25 miles of the hospital where endovascular was performed, and 40% within 10 miles. Thus, they surmised: “It is likely that there are many other regions that are similar to ours.”

Regardless, McTaggart and colleagues recognise that the optimal time parameters to determine triage to a more distant centre are unknown. According to the authors, a recent decision analysis has suggested that time to CSC, as well as time from onset, play a role in determining an optimal triage radius, and proposed that, Ryan McTaggart

VEITHsymposium and BLearning announce collaboration to launch VEITH TV VEITHsymposium and BLearning, the digital education division of BIBA Medical, are pleased to announce a collaboration on the creation and dissemination of digital education video content, which will be filmed at the 46th Annual VEITHsymposium in New York, USA (19–23 November 2019, New York City).

VEITHSYMPOSIUM IS A leading global conference covering all aspects of vascular medicine, vascular surgery

and endovascular intervention. BIBA Medical’s mission is to provide education, news, and insights to connect

for early presenting patients, the bypass threshold may increase up to 56 minutes. Further research to optimise the threshold for triage may be warranted, they write.

Nonetheless, based on this work and their recent research trying to optimise door-in, door-out times for LVO stroke at the regional PSCs (McTaggart et al, Stroke, 2018 49 [12]: 2969–2974), the Rhode Island Ambulance advisory board recently voted to eliminate the 30-minute threshold from the field triage protocol— all suspected LVO patients in Rhode Island are taken directly to the CSC (Level 1) stroke centre.

In relation to particular drawbacks of the study, McTaggart et al alluded to a lack of documented field severity score for all patients. “As a point of reference, during the study period, a total of 1,170 patients with a final diagnosis of acute ischaemic stroke were brought by the emergency medical services directly to the CSC, and, of these, 147 (12.6%) underwent thrombectomy,” write the authors. Therefore, they suggest that it is “beyond the scope of this work” to determine the accuracy of emergency medical services assessment and rates of over-or under-triage.

Furthermore, they acknowledged that the nonrandomised nature of their study somewhat limits its validity. Referring to the randomised controlled trial currently underway in Barcelona, RACECAT (Direct transfer to an endovascular centre compared to transfer to the closest stroke centre in acute stroke patients with suspected LVO), McTaggart and team write that a similar trial in the USA may be “logistically difficult”, given the “fragmented nature of the healthcare system”.

In turn, they explain that their matched-pairs design with mixed modelling of pre-stroke and 90-day score, and matching according to time to CSC and NIHSS score, provides a strong alternative to randomisation for the observational data.

While concluding that the results should be interpreted with caution, in regions where the distribution and workflow metrics of stroke centres are not similar, McTaggart and colleagues write, “Prehospital triage may be the last remaining, yet modifiable, bottleneck within an otherwise optimised stroke system of care.”

“The most important link in the stroke chain of survival in Rhode Island is, by far, the ability of our emergency medical service professionals to leverage their ability to make important field triage decisions for stroke patients just as they do for trauma patients,” McTaggart tells Vascular News.

He adds: “Emergency medical service professionals need to be focused on doing what is right for patients, rather than navigating the geopolitics of stroke; we need to critically reevaluate why, where, and how we are accrediting stroke centres in the new mechanical thrombectomy era.”

the global community of physicians, healthcare providers, and medical manufacturing industry. BLearning is the company’s video production capability that seeks to develop and deliver highquality digital education content.

As part of this specific cooperation project, the VEITHsymposium leadership will work closely with BLearning to create and realise the filming, production and release of digital education videos that will be filmed in a dedicated studio during this year’s conference.

“Interesting video highlights and late-breaking information will be filmed by our expert faculty during

the meeting, edited professionally and released in a timely fashion to provide vital educational material to keep the vascular community clinically up-todate,” said Frank J Veith, chairman of VEITHsymposium.

“It is a privilege for BLearning to collaborate with VEITHsymposium.

The creation of a dedicated studio will ensure that many of the key highlights of the outstanding education presented at VEITHsymposium can be shared with the global vascular community in a new, watchable format,” said Stephen Greenhalgh, business development director, BIBA Medical.

22

November 2019 | Issue 84

New technologies

The current status of new technologies and robotics in vascular surgery Celia Riga Comment & Analysis Celia Riga discusses the rise of new technologies in vascular surgery.

THE ROYAL COLLEGE of Surgeons recently published the Commission on the Future of Surgery identifying which technologies will make the greatest impact in years to come. Technologies such as robotics, artificial intelligence, and wearables feature heavily and are all in use today. This leaves us, the clinical teams, with three options: become innovators, early adopters or consumers.

Each option comes with different merits and responsibilities.

Health technology assessment (HTA) to evaluate safety, feasibility and efficiency constitutes an essential prerequisite for all novel technologies.

For robotic catheter technology utilising

the Magellan co-axial catheter platform (Hansen Medical/Auris), the HTA process at Imperial College London over the last decade is a good example of translational bench-to-bedside research, involving proof of concept, a rigorous pre-clinical evaluation programme, first-in-man, subsequent collaboration with industry for FDA approval and CE marking, in-house engineering input through the Hamlyn Centre for Robotic Surgery and a graduated clinical evaluation programme. We have treated 116 patients at Imperial College Healthcare NHS Trust, with 150 intervention targets and excellent technical success through a range of

interventions. The most important message from this series and our early clinical experience is that 16% of these cases had previously failed with manual approaches and 42% of the total cohort were selected due to adverse anatomy. We, as well as others, have demonstrated safety and feasibility for robotic endovascular technology, yet the greatest benefit is seen in the more complex endovascular tasks. When compared with manual manipulation there appears to be less unnecessary movements and contact with the vessel wall, shorter path-lengths from access to target and reduced variability in performance even in the hands of highly experienced operators.

Radiation exposure for operators is significantly reduced as the workstation is located away from the X-ray source.

The stability of the robotic sheath obviates the need for axillary access.

Even when manual input is required, robotic sheath stability facilitates the necessary exchanges reducing radiation further. Learning curves are short: for experienced operators, performance is enhanced. Current commercial robotic catheter systems do not have integrated localisation capabilities. They do, however, provide the ideal platform for integrating sensing and intelligent imaging technologies in a move towards X-ray-free intervention, and that is our current focus at Imperial’s Hamlyn centre supported by an EPSRC multimillion-pound investment.

Patients seem to embrace novel

Frailty an important independent risk factor in vascular surgery patients but there is no evidence to deny intervention based on frailty score alone A systematic review and meta-analysis has found that frailty is an independent risk factor in vascular surgery patients but there is no evidence to deny intervention in any patient based on frailty score alone. This was the main conclusion delivered by John Houghton (University of Leicester, Leicester, UK) in a scientific prize session at the European Society for Vascular Surgery annual meeting (ESVS; 24-27 September, Hamburg, Germany).

I

n the study, Houghton et al sought to investigate the methods used to assess frailty and sarcopenia in vascular surgery patients, and associations with patient factors, such as lifestyle, demographics, and comorbidities, as well as with outcomes.

“Frailty is complex and multifactorial. It is a distinct health state, which is defined as an increased vulnerability to poor recovery from a stressor,” Houghton told the session. “Frail patients are at increased risk of poor outcomes such a loss of independence and death from even a minor stressor.

Sarcopenia is defined as a progressive loss of skeletal muscle strength coupled with a reduction in quantity or quality of skeletal muscle. And it has been extensively reported in the surgical literature as a surrogate for frailty but predominantly using CT [computed tomography] alone to define sarcopenia.”

The research team deployed a standard systematic review methodology, searching multiple databases with independent reviewers screening articles and extracting data. They deliberately took a broad view, Houghton said, including all vascular surgery pathologies, and patients both undergoing and not undergoing a

procedure, in the meta-analysis “only if they reported patient factors and/or outcomes for frail and non-frail vascular surgery patients separately”.

Some 53 studies were included in the systematic review, with 29 of them having used the frailty assessment. “The majority of the frailty tools used have not been well validated in the general population of older adults,” Houghton explained. “Only nine studies used a well-validated tool such as the Clinical Frailty Scale. Twenty-five studies reported sarcopenia, the vast majority of which used CT alone. None of these measures have been well validated in the general population of older adults.

“We included 18 studies in the meta-analysis, representing data from nearly 63,000 patients. We assessed risk of bias using the Robins-E tool. Two-thirds of studies were at a serious risk of bias.”

In terms of association of age with frailty, the researchers performed a subgroup analysis, grouping studies by the way that they assessed frailty: “Either a well-validated tool, an unvalidated tool, or by sarcopenia alone,” said Houghton, with “all subgroups [showing] an association with age frailty, and in the pooled analysis

technologies yet adoption is slow.

Barriers to adoption include culture, implementation and training challenges, and predominantly cost. Lack of high-level evidence also hinders more widespread use. Generation of highlevel evidence, however, requires time but the dynamic nature of medical robotics is not compatible with level-1 or randomised trials to generate level-1 evidence and inform on long-term efficacy. Another important constraint is when the primary diffusion driver moves from R&D to marketing as it restricts continuing enhancement of novel technologies based on clinical feedback, once they have reached the market.

The medical robotics market is expected to reach US$22.billion by 2027 and the NHS has already seeded £50 million towards a robotic framework.

Robotic catheter technology is somewhat limited to procedural stage yet it is safe and feasible and particularly valuable for complex tasks such as FEVAR, manipulation in the arch, and complex embolisations. There is great potential for radiation reduction for patients and staff. In an era where there is a pressing need to improve the durability and cost-effectiveness of endovascular intervention, robotics will play a key role through endosuturing, sensing, image guidance, materials, manufacturing and surveillance strategies.

Celia Riga is a consultant vascular surgeon and senior lecturer at Imperial College London, UK.

frail patients were on average four years older than nonfrail vascular surgery patients.”

Other patient factors associated with frailty that were identified included lower body mass index, female sex, and respiratory disease. The research team also discovered an inverse association with smoking, said Houghton, likely “because these patients were younger, with predominantly smoking-related vascular surgery disease and therefore less frail.”

Also of note, Houghton added: “There is no association with a number of comorbidities that have been shown to be associated with frailty in a general population of older adults. And this is likely to be because the burden of comorbidity in vascular surgery patients is much higher.”

We included 18 studies in the metaanalysis, representing data from nearly 63,000 patients.”

In terms of association with outcome, the researchers found that frailty was independently associated with postoperative complications, 30-day mortality, and long-term mortality. “Interestingly though, sarcopenia alone was not associated with any outcome in any of the individual meta-analyses that we performed,” said Houghton.

Houghton identified several limitations to the team’s work, including what he called the “significant heterogeneity” of studies included in the review and meta-analysis, as well as the “generally relatively poor” quality of the studies included, which he said came with a high risk of bias.

Issue 84 | November 2019

New guidelines

Updated venous thromboembolism guideline for cancer patients unveiled

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

P

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

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

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

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

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

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

The updated guideline addresses six clinical questions:

Should hospitalised patients with cancer receive anticoagulation for VTE prophylaxis?

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

Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?

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

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

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

In response to the first clinical question,

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

Falanga is in accordance, adding, “The

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

Anna Falanga

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

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

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

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

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

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

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

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

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

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

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November 2019 | Issue 84

Latest research

Fractional flow reserve testing can identify peripheral vascular surgery patients with unsuspected silent coronary ischaemia Preoperative evaluation of patients undergoing peripheral vascular surgery using coronary computed tomography-derived fractional flow reserve (FFRCT) testing can identify patients with unsuspected silent coronary ischaemia, a study has found.

PRESENTING THE FINDINGS at the 33rd Annual Meeting of the European Society for Vascular Surgery (ESVS 2019; 24–27 September, Hamburg, Germany), the study’s lead author Dainis Krievins (Pauls Stradins Clinical University Hospital, Riga, Latvia) said that FFRCT can help to guide a multidisciplinary team approach to reduce postoperative death or myocardial infarction (MI) in peripheral vascular surgery (PVS) patients. The study’s authors suggest that there is a need for prospective controlled studies to further define the role of coronary FFRCT in the evaluation and treatment of peripheral vascular surgery patients.

FFRCT is a noninvasive cardiac diagnostic test, which can identify silent ischaemia in stable chest pain patients.

Its value in preoperative evaluation of

peripheral vascular surgery patients, for which there is a high prevalence of silent coronary ischaemia, is unknown.

Presenting the findings of the study, Krievins said that the objective was to determine whether preoperative diagnosis of silent coronary ischaemia using FFRCT could modify patient management and reduce postoperation adverse cardiac events in patients with no cardiac symptoms needing lowerextremity revascularisation.

Krievins and colleagues conducted a prospective study in 135 patients with no cardiac history, who were admitted for lower elective peripheral vascular surgery. Patients had standard preoperative cardiac evaluation, and in addition underwent coronary computed tomography angiogram (CTA) and FFRCT analysis. Study patients were

compared to a matched control group of 135 similar patients with no cardiac history who underwent similar vascular surgery during the 18 months prior to starting the prospective study and had standard preoperative cardiac evaluation.

There were no significant differences between the two groups with respect to patient comorbidities, or type of surgery performed, Krievins said.

Silent coronary ischaemia was present in 68% of study patients, with 53% having multivessel ischaemia. PVS was performed in all control patients and 130 study patients. No postoperative deaths occurred in the study patients, whereas five occurred in the control patients, all caused by MI. Major adverse cardiac events at 30 days in the study patients were one out of 135 (0.7%) vs. seven of 135 (5.2%) in the control patients (p=0.06). Elective coronary angiography was performed in 75 study patients with left main, severe, or multivessel ischaemia within one to three months postoperation, with coronary revascularisation in 54 (47 stents and seven coronary artery bypass grafts).

Cumulative events during the 12-month follow-up showed that, compared with control patients, study patients had a significant reduction in major adverse cardiac events (2.2% vs. 8.1%; p=0.03), cardiac death (0% vs. 5.9%; p=0.01), and MI (2.2% vs. 8.1%; p=0.03).

“The level and extent of coronary ischaemia was surprising because none of the patients had symptoms of coronary artery disease. In the control

Thirty-day mortality after thoracic endovascular aneurysm repair found to be significantly higher in women than men for intact degenerative thoracic aortic aneurysms Thirty-day mortality after thoracic endovascular aneurysm repair (TEVAR) for the management of intact degenerative thoracic aortic aneurysms appears to be much higher in women than men in a new study published in the October issue of the European Journal of Vascular and Endovascular Surgery. However, the research team, led by Janet Powell (Imperial College London, London, UK), uncovered no concrete reasons for the difference that they identified, although the greater use of iliac conduits in women needs further investigation.

A

dditionally, Powell and colleagues also found that for open repair there is a lack of contemporary evidence due to insufficient recent data.

Their paper, entitled “Sex specific differences in the management of descending thoracic aortic aneurysms: systematic review with meta-analysis”, specifically set out to assess how men and women differed in terms of 30-day mortality, length of hospital stay and adverse neurological events following repair by means of either TEVAR or open surgery.

The authors referred to two recent systematic reviews that had indicated women have much higher perioperative mortality than men following both lower limb re-vascularisation and intact abdominal aortic aneurysm repair. “Many surgeons attribute these sex specific differences to the smaller and perhaps more calcified arteries in women, with the more challenging aortic morphology being an additional reason for AAA

[abdominal aortic aneurysm] repair. The thoracic aorta is the largest-diameter artery in the body and therefore the sex specific differences in mortality following thoracic aortic intervention may be less pronounced.”

Some 4,246 studies were screened for inclusion, from which 90 were identified for possible inclusion in the analysis. Seven of them made the cut under the defined inclusion and exclusion criteria.

The results showed that for TEVAR, seven studies were identified, including 2,758 women and 4,674 men, the authors noted: “Of these studies, six were eligible

The greater use of iliac conduits in women needs further investigation.”

group no ischaemic changes were found on the ECG. This influenced patient management in the study group. Indicated vascular surgery was performed in 130 patients with cardiac anaesthesia and close monitoring.

Vascular surgery was postponed in five patients, one patient underwent coronary revascularisation and four patients underwent medical treatment.

In the control group, peripheral vascular surgery was performed in all cases receiving standard medical care,” Krievins said.

Postoperative coronary angiography was performed in 75 patients with silent coronary ischaemia with coronary revascularisation in 54 patients. The authors noted reduced cardiac deaths and MIs and improved one-year survival in those with FFRCT testing compared to the surgery with no cardiac symptoms receiving standard pre- and post-care.

“In conclusion, preoperative evaluation of patients undergoing peripheral vascular surgery using FFRCT can identify patients with unsuspected silent coronary ischaemia and this can help guide a multidisciplinary team approach to reduce postop cardiac complications and improve survival compared to standard patient care. Favourable results of staging peripheral and coronary revascularisation in the study suggests the need for prospective controlled studies to further define the role of coronary CT-FFRCT in the evaluation and treatment of peripheral vascular surgery patients,” Krievins concluded.

for the primary outcome of 30-day mortality, including 1,756 women and 2,619 men. There were 94/1756 deaths in women and 82/2,619 deaths in men, yielding a pooled 30-day mortality of 5% (95% confidence interval [CI]: 3-7) in women and 3% (95% CI: 2-4) in men (OR: 1.75; 95% CI: 1.29-2.38). Length of hospital stay was longer in women, with a standardised mean difference of 0.3 days (95% CI: 0.14-0.47; six studies): metaregression analysis did not identify the slightly older age of women as significant factor in either of these differences. Stroke rate was not different between the sexes. For open repair only a single study, with national coverage, was identified: this study reported similar 30day mortality in men and women.”

The meta-analysis confirmed that there are sexspecific differences in short-term outcomes following TEVAR, the researchers wrote – “with an almost 1.8 times higher 30-day mortality and a longer hospital stay in women than in men”. As for open repair, they point out that changes in clinical practice result in scant data and uncertainty around whether sex-specific differences.

Limitations of the review, the authors concede, included a paucity of separate outcome data for men and women from medium- to large-sized studies and no standardized reporting of outcome events, particularly with regards to neurological events. In addition, some of the analyses were dominated by the large Vascular Quality Initiative study from the USA. They concluded: “For descending TAAs [thoracic aortic aneurysms], operative mortality and LoHS [length of hospital stay] for TEVAR are higher in women than men. These differences are not attributable to either age or neurological events and the reasons for the sex differences require further investigation. There are too few recent data to comment on sex specific differences relating to open repair and, with the increasing preference for TEVAR, there may never be sufficient data.”

Issue 84 | November 2019

Market insights

Source: BIBA MedTech Aortic Segmentation Monitor

Medtronic receives US FDA Breakthrough Device Designation for complex EVAR device The US Food and Drug Administration (FDA) has granted Breakthrough Device Designation to Medtronic for its novel Valiant thoracoabdominal aneurysm (TAAA) stent graft. A press release reports that the device is designed to offer an off-theshelf solution for complex endovascular aneurysm repair (EVAR) procedures, adding that the Valiant TAAA has a “size matrix to enable broad patient applicability for one of vascular surgery’s most difficult pathologies”.

ACCORDING TO THE press release, the aim of FDA Breakthrough Device Designation programme is 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”. Specifically, with the programme, the FDA will provide Medtronic with priority review and interactive communication regarding device development and clinical trial protocols through to commercialisation decisions. Murray Shames (Division of Vascular and Endovascular Surgery, University of South Florida College of Medicine, Tampa, USA), an investigator for Valiant TAAA, comments: “Breakthrough designation from the FDA means that we will be able to deliver this much needed treatment to patients sooner than expected. With an open surgery mortality rate of 25%, it is critical that we deliver for this unmet patient need. Physicians and industry must continue to innovate and provide hope for those with challenging disease states.”

The press release reports that, at present, the Valiant TAAA is

being evaluated in five physiciansponsored investigation device exemption (IDE) trials for the management of thoracoabdominal aneurysms. Furthermore, the Valiant system was developed in collaboration with Patrick Kelly (Sanford Health Commercialization, Sioux Falls, USA)—a vascular surgeon and inventor who specialises in complex vascular disease. John Farquhar, vice president and general manager of the Aortic business, which is part of the Cardiac and Vascular Group at Medtronic, says: “In addition to a high mortality rate for open surgical repair, physicians do not have good options when it comes to treatment for failed endografts. The FDA’s breakthrough designation for Valiant TAAA and our collaboration with leading physicians is an example of our willingness to take a courageous approach and challenge the limitations of current treatment options. This is about going further, together to improve patient outcomes.”

Complex open surgery is the standard of care for thoracoabdominal aneurysms but, according to the press release, it is associated with high morbidity and mortality. Furthermore, 40%

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Source: BIBA MedTech Aortic Segmentation Monitor

of patients are not considered candidates for surgical treatment.

Of note, the BIBA MedTech Aortic Segmentation Monitor shows that the endovascular approach was the most common method for treating complex aneurysms—e.g. thoracoabdominal aneurysms or juxtarenal aneurysms—in Western Europe in Q2: 60.1% vs. 39.9% for open surgery.

The Monitor also indicates that EVAR with a custom-made device(s) is typically the predominant endovascular approach for such complex aneurysms while EVAR with an off-the-shelf device (similar to the Valiant TAAA) tends to be the least used approach. Figure 1 shows the breakdown of complex aortic procedures by aortic segment and procedure type. Medtronic had the second highest share (20.2%) of the Q2 complex EVAR market but, with its Zenith range, Cook Medical was the market leader (47.9%).

Expanding the Valiant TEVAR range

As well as expanding its complex EVAR range, Medtronic also plans to add to its range of device for thoracic endovascular aortic (TEVAR) procedures. The Valiant Navion Left Subclavian Artery (LSA) stent graft received FDA Breakthrough Device Designation in May this year and, the press release explains, its aim is “to allow for more timely delivery of treatment options for patients in left subclavian artery coverage during TEVAR”.

BIBA Briefings

The Valiant Navion LSA is based on the investigational Valiant Mona LSA device and the Valiant Navion stent (which received FDA approval last year). Like Valiant Navion, the Valiant Navion LSA has a lowprofile design but also has a branch cuff that is intended to replicate the natural anatomy of the LSA to maximise seal and patency.

“By leveraging our low-profile, Valiant Navion platform, we hope Valiant Navion LSA will expand endovascular treatment options to those in need. It is a matter of putting patients first and delivering innovation where it matters most,” comments Farquhar.

Data from the Valiant EVO global clinical trial, which was published in the Journal of Vascular Surgery earlier this year, show that only 2.3% of patients who received a Valiant Navion device for the management of descending thoracic aneurysms had a major device effect at 30 days. Furthermore, the rate of endoleaks was 2.5% (one type Ia and one type II).

The Aortic Segmentation Monitor shows that 31.8% of non-valvular aortic procedures (21,213 overall) performed in Q2 were for the thoracic aorta. Furthermore, of these thoracic procedures, 37% were with an endovascular approach vs. 4% for a hybrid procedure vs. 59% for open procedures. In contrast to the complex EVAR market, Medtronic was the leader of the thoracic endovascular market (36%). see Figure 2.

BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments.

For editorial enquiries, please contact Dawn Powell: dawn@bibamedical.com For sales enquiries (including BIBA MedTech Insights), please contact Merveille Anderson: merveille@bibamedical.com

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November 2019 | Issue 84

Interview

Profile

Ian Loftus

Ian Loftus talks to Vascular News about various aspects of his professional life, from a surgical placement which inspired his career path through to professorship at St George’s Hospital in London, UK. The current president of the Vascular Society of Great Britain and Ireland, Loftus talks us through what to expect at this year’s upcoming annual meeting, as well as giving his perspective on the biggest challenges currently facing vascular surgery.

What led you to become a vascular surgeon?

I went to medical school with the ambition of following a career in primary care. But during my third year, on my first placement to a surgical team, I assisted in an appendicectomy with a very charismatic registrar. I immediately knew I wanted to be a surgeon.

My father died when I was 16 years old from complications after a carotid endarterectomy. During my second year at medical school my elder brother also died, as a consequence of a medical error. While initially making me question my future in medicine, ultimately these two events are what drove me to do what I do now. My ambition has always been to work to the very highest standards, providing the very best outcomes for vascular patients under my care, but also nationally, in an environment of complete transparency and integrity.

Who have been your professional mentors, and what lessons did you learn from them?

During my early training professor Peter Bell was the most influential mentor, but the whole team in Leicester, UK (Ross Naylor, Nick London, and Mark McCarthy in particular) supported me wholeheartedly. They gave me a huge amount of hands on training, backed up by supporting me with a programme of research. Peter Bell, the Professor of Surgery in Leicester, took me under his wing as a medical student and convinced me that I had the ability to succeed, especially when I doubted I would make it to the end of medical school.

He gave me much needed confidence and was very much a father figure for me in the early years. From nearly failing my early pre-clinical years, I graduated with distinction and won the Leicester University prize for clinical excellence. As well as being an incredibly gifted surgeon and academic, professor Bell was also a great team player and family man. He treated everyone in the hospital the same, from the theatre porter to the chief executive.

In my years as a junior Consultant, Matt Thompson was my invaluable mentor. He is a truly great aortic surgeon, which combined with an enviable breadth of knowledge and balanced clinical opinion, is very rare in our speciality. He is the person who has shaped my career more than any. I will be indebted to him for the rest of my career, and beyond.

In the last year, which new paper presentation has caught your attention?

The paper on the long-term outcomes from the OVER trial, published in May 2019 (Lederle et al, New England Journal of Medicine 2019: 380; 2126-35).

The publication from the EVAR trials in the UK have demonstrated less favourable outcomes for patients who underwent endovascular repair out to 15 years. This and other long-term trial data have been very influential in the conclusions of the draft NICE guidelines in England. However, the paper from the OVER trial was quite different, demonstrating an equivalent long-term survival but with trends towards better overall survival in the endovascular group and higher aneurysm related mortality in the open surgery group.

What have you achieved as president of the VSGBI?

On a positive note, I am very proud of a Quality Improvement Programme for patients with lower limb ischaemia. The Audit and Quality Improvement Committee of the Vascular Society under the auspices of Jonathon Boyle has produced an ambitious care pathway and timelines for the management of patients, especially for critical ischaemia, which is now the focus of a national Quality Improvement Programme.

We are appointing two research fellows to assess the impact on outcomes across the country, jointly funded by the Circulation Foundation and the Royal College of Surgeons of England.

However, much of my period as President has been consumed with dealing with the controversies surrounding the draft NICE guidelines for the management of patients with aortic aneurysms, put out for a period of consultation in 2018. Until this is resolved to a satisfactory conclusion, it will be difficult to feel I have achieved enough. I, and the current Council of the Society, feel it is vital to the future of vascular services in the UK to have a more balanced approach to aortic aneurysm repair than the guidelines in their draft form would allow, incorporating patient choice and a personalised approach to treatment.

Vascular specialists […] should be able to perform all vascular interventions as long as they can demonstrate appropriate training, outcomes and governance arrangements.”

What do you look forward to at the upcoming VSGBI annual meeting?

The theme of the meeting is “A safe and sustainable vascular service for the future”. We have a tremendous programme of high quality speakers. In the light of the controversies surrounding the long term aneurysm trial publications and the draft NICE guidelines, I am particularly looking forward to the Kinmonth lecture from Jan Blankenstein, entitled “The Current Status of EVAR- 2 decades of daydreams and nightmares”.

We also have lectures from the guidelines director from NICE (Paul Chrisp) and the national lead for the “Getting it Right First Time” programme, professor Tim Briggs.

Of course, I hope that the NICE aneurysm guidelines will come to a satisfactory conclusion by then. It would be good to be able to address the members of our Society with an agreed and workable solution to what has been a very challenging issue for all concerned.

In your opinion, what are the biggest challenges currently facing vascular surgery?

Demonstrating that what we do is clinically- and costeffective in the long term. As practice has shifted more to the endovascular approach, so we rely on technology to match our ambition. We have seen problems with the adoption and late failure of some of these technologies, and the draft NICE guidelines have challenged the cost effectiveness of endovascular aneurysm repair more broadly. Other therapies may suffer the same fate.

We have to strive to demonstrate that what we do is always in the best interests of the patient, but also be conscious of the financial restraints of a tax-based healthcare system in the UK. We must also overcome the inter-disciplinary frictions and anxieties that surround the endovascular work.

Vascular specialists from whichever discipline, who are trained appropriately, should be able to perform all

Issue 84 | November 2019

Interview

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Fact File

Current appointments (selected)

2019: President, Vascular Society of Great Britain and Ireland 2019: Chair, National Vascular Registry Committee 2019: Board member, National Joint Vascular Programme 2009–present: Director, South West London and East Surrey Aneurysm Screening Programme, UK 2005–present: Consultant vascular surgeon and professor of Vascular Surgery, St George’s Hospital NHS Trust and St George’s University of London, UK

Previous appointments (selected)

2015: President, British Society of Endovascular Therapy 2013: Chair, Audit and Quality Improvement Committee of the Vascular Society of Great Britain and Ireland 1999–2004: Lecturer in Surgery/Honorary specialist registrar, Leicester University and Leicester Hospitals, UK 1996–1998: Research fellow, Department of Surgery, Leicester University, UK Education 1986–1992: Leicester University Medical School, UK

Recent publications (selected)

vascular interventions as long as they can demonstrate appropriate training, outcomes, and governance arrangements. To do so, they must be able to work in appropriately resourced and supported multi-disciplinary teams.

Could you tell us about one of your most memorable cases?

Probably the first ruptured aneurysm I treated with an endovascular approach stands out among many memorable cases during my career. I had become accustomed to patients languishing on intensive therapy units for days after open repair of a ruptured aneurysm, often returning to theatre for abdominal compartment syndrome or other complications, and taking many months to return to normal activity and daily function.

Many years ago we convinced our hospital to install a hybrid theatre, fully stocked with everything required for an endovascular practice. I clearly remember my first patient who I treated under local anaesthetic with a stent graft for a ruptured infrarenal aneurysm, who later that

day was sat up in bed having a cup of tea, chatting to his family. He was discharged a few days later and remains well with annual ultrasound surveillance to this day.

This has become our unit standard practice and is the only clinical scenario where an endovascular approach is recommended within the draft NICE guidelines. I do not believe this could be achieved without an elective practice. I feel strongly that this would be a big step backwards for the profession.

How do you like to spend your time outside of work?

I have discovered cycling rather late in life but now take every opportunity to jump into lycra and hit the country lanes around that surround London. This year I completed an event for the Circulation Foundation charity called “The Ride 100” in just over five hours, a 100-mile circuit starting and finishing in central London. I am grateful for the support of my friends and colleagues in raising nearly £2000 for research into vascular disease.

Boufi M, Patterson BO, Grima MJ, et al.

Systematic review of reintervention after thoracic endovascular repair for chronic type B dissection. Ann Thorac Surg. 2017 Apr 20.

Budtz-Lilly J, Venermo M, Debus S, et al.

Assessment of international outcomes of intact abdominal aortic aneurysm repair over 9 years. Eur J Vasc Endovasc Surg. 2017 Apr 13. pii: S1,078–5884(17)30159–4.

Stenson KM, De Bruin JL, Holt PJ, et al.

Extended use of endovascular aneurysm sealing: Chimneys for juxtarenal aneurysms.

Semin Vasc Surg. 2016 Sep;29(3):120–125.

Karthikesalingam A, Vidal-Diez A, Holt PJ, et al. Thresholds for abdominal aortic aneurysm repair in England and the United States. N Engl J Med. 2016 Nov 24;375(21):2051–2059.

Paraskevas KI, Loftus IM. Safety of carotid revascularization within 48 hours of symptomatic presentation. J Cardiovasc Surg (Torino). 2017 Apr;58(2):139–142.

Issue 84 | November 2019

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EVAR patients may experience significant long-term decrease in renal function

A recent analysis, with some of the longest follow-up to date, suggests that patients undergoing endovascular aneurysm repair (EVAR) may experience a significant longterm decrease in renal function. The authors, Edmund R Charles and colleagues at the Leicester Vascular Institute for Health Research (NIHR) Leicester Biomedical Centre (Leicester, UK) argue, “This needs to be taken into account when offering EVAR in younger patients,” and suggest that renal follow-up and preservation should be optimised in this patient group.

O

ver the short-term, EVAR is associated with superior outcomes compared with open repair; however, the progression of renal function after EVAR remains unknown because of the use of inconsistent reporting measures. This study aimed to define long-term renal decline following elective EVAR using estimated glomerular filtration rate (eGFR).

The investigators note that the present analysis, which appeared in the September 2019 issue of the European Journal of Vascular and Endovascular Surgery, contains the longest reporting of renal outcomes following elective EVAR in the literature to date using precise validated hard renal measures (eGFR).

In the study, patients were followed up over a median of nine years (range five–17 years). Their mean eGFR dropped from a preoperative value of 67ml/min/1.73m2 (standard deviation [SD]: 9.4) to 52ml/min/1.732 (SD 7.7), which amounts to a yearly loss of 1.7 units. Six patients (2%) required renal replacement therapy (RRT) during late follow-up. Patients requiring RRT and those with an eGFR loss exceeding 20% at latest follow-up

compared with baseline were more likely to die during late follow-up (odds ratio 2.4 and 3.3 respectively, p<0.001).

Charles and colleagues detail that the prospectively maintained in house database was used to identify consecutive patients having elective EVAR who had been followed-up for more than five years. Overall, 275 patients (23 females, 8%; mean age, 75 years) who were not previously on RRT were included (January 2000–July 2010). Preoperative, postoperative, and most recent eGFR values were evaluated using the chronic kidney disease epidemiology collaboration equation.

The primary outcome was change in eGFR at latest follow-up.

The investigators note a few limitations of the study. Firstly, although the analysis is based on a prospectively maintained institutional database, it is not a prospective cohort study, and outcomes were reported retrospectively. Furthermore, comparative analyses were limited, given that an appropriate matched group of patients have open abdominal aortic aneurysm

This conclusion is important for decision making when selecting patients suitable for EVAR, especially younger patients.”

Kidney model

(AAA) repair and no AAA could not be identified.

Finally, a significant number of patients from the original cohort were either lost to follow-up or died before completing their five-year follow-up, hence only 275 patients were included in the final analysis.

Charles and colleagues summarise: “It appears that patients undergoing EVAR exhibit a significant loss of eGFR over the long term and this is associated with poor survival”. They suggest that this conclusion is important for decision making when selecting patients suitable for EVAR, especially younger patients, and also for guiding follow-up in this high-risk patient group. “Renal function preservation should become part of regular follow-up in this setting, especially in male patients with established cardiovascular disease,” they comment.

Standardised vascular access protocol improves patient safety and reduces costs of peripheral IV catheter insertions Implementation of a standardised set of best practices for inserting peripheral intravenous catheters (PIVC) resulted in significant clinical and economic benefits, according to a newly published study from Hartford Hospital (Hartford, USA) and PICC Excellence. These benefits include higher PIVC insertion success, longer dwell times with fewer complications, greater patient satisfaction and significantly reduced costs associated with IV therapy.

INVESTIGATORS REPORTED AN 89% success rate of completing therapy with one PIVC per patient and a projected cost savings of US$2.9 million per year as a result of using the set of practices, known as the PIV5Rights Bundle. Results of the study were published in the Fall 2019 issue of the Journal of the Association for Vascular Access (JAVA).

The goal of the prospective multimodal comparator design study was to determine if a hospital could increase catheter dwell times and decrease adverse outcomes by using evidence-based best practices, including PIVC insertions performed by a dedicated vascular access specialty team (VAST) compared to current practice of a generalist clinician.

“Placing PIVCs is both a science and an art, and it needs to be in the hands of clinicians who have a thorough understanding of all aspects of vascular access and how they can affect patient safety,” said lead study author Lee Steere, Unit Leader of IV Therapy Services at Hartford Hospital. “This expertise is crucial to ensuring that the catheter is inserted correctly the first time and lasts until the end of treatment as often as possible.”

The PIVC specialist model was validated by the clinical and economic benefits observed in the study, Steere said. As a result of the study success and financial savings, Hartford Hospital nearly tripled the size of its VAST employees between 2015 and 2019.

In the USA, PIVC failure rates average 53%, with one of every two catheters failing to make it to treatment’s end. The PIV5Rights Bundle used in the study was designed to address the most common reasons for PIVC failure (infiltration, phlebitis, occlusion, infection and accidental dislodgement), in order to help hospitals achieve the goal of one PIVC per patient per hospital visit.

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The dialysis access mindset: A leadership model to fit the times Nicholas Inston Therese Wykoff Comment & Analysis In this article, Nicholas Inston and Therese Wykoff propose a novel approach to the “complex” process of dialysis access delivery.

Using concepts borrowed from business and commercial settings allows a model for what they have termed the “dialysis access mindset”.

G

uidelines have currently changed from the traditional, dogmatic, rule-based approach to a much more individualised “Patient life plan”-centered pathway. The lack of high-quality evidence, rapidly emerging technologies, and the application to a heterogenous patient group have resulted in most recommendations being expert opinion. As such, the role of individuals within the dialysis access team requires a different approach from many other areas of clinical care.

The current commercial landscape for organizations can be described as VUCA, an acronym for volatile, uncertain, complex, and ambiguous.1 This concept is well-suited to describe the nature of the current dialysis access landscape. End stage renal disease (ESRD) is a growing disease area with increasing disease burden, as well as complexity. Improved survival in the existing dialysis access cohort results in patients’ vascular needs becoming increasingly challenging. Innovations in the field are being introduced at a faster rate than both evidence and training can be delivered. The specialties delivering dialysis access (transplant surgery, interventional radiology, interventional nephrology, vascular surgery) are equipped with different training backgrounds, experience, and expertise. This variation leads to diverse perspectives for optimal solutions and how to get to those solutions for the same problem in the same patient.

Global disparity exists regarding factors such as patient characteristics, available resources, cultural attitudes for renal replacement therapy (RRT), and international variation in availability and approval for interventional devices and pharmaceutical agents. This VUCA environment can be overwhelming and leave individual members of the dialysis access team feeling ill-equipped to successfully lead.

The leader of the dialysis access team must be able to assess and select the best option, often under time pressures.

This requires deep knowledge and experience, but also an open mindset to

new ideas and willingness to adapt with the changing environment. Successful navigation through this VUCA environment requires a certain set of attitudes by the dialysis access team.

A proposed model of a “Dialysis access mindset” includes three main components: 1. Growth mindset, 2.

Future outlook, and 3. Patient centricity.

1. Growth mindset

The growth mindset is simple idea with profound ramifications described by Stanford University psychologist Carol Dweck from her research on motivation and achievement.2 She identifies two

mindsets that are indicators of success; those with a fixed mindset, who believe that their traits are static—these people tend to stick to what they know, resist new ideas, and are very sensitive (i.e.: not receptive) to feedback, and those with a growth mindset who believe that they have unlimited potential to learn and grow. They are not afraid to try new things and even to fail; they embrace new challenges and are very open to new ideas. They welcome feedback and continuously want to improve. In dialysis access, an openness to diversity of thought is more likely to lead collectively to innovation and the creation of real actionable solutions. Embracing a growth mindset means learning to detach from a place that feels stable, certain and comfortable, and welcoming feedback and insight. Whilst your mindset comes from within yourself, it can grow and be adapted through gaining new information

via interactions with colleagues involved in the many levels of dialysis access. Traditionally, this has been achieved through conferences, societies and journals. New advancements in technology invite the growth mindset via online forums, providing digital training and exchange of ideas and perspectives with colleagues across different specialties and in different geographic regions. Kidney Academy, a non-profit entity dedicated to the global dialysis access community, is currently building an online platform to deliver accredited training and education, as well as offering a forum for collaboration and idea sharing for this community.

2. Future outlook—“Begin with the end in mind”

The recent shift in thinking strategically in kidney care can be seen in the new Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for vascular access from the National Kidney Foundation.3 Rather than one-size-fits-all, the mindset has shifted to the End Stage Kidney Disease life plan.4 Because patients often undergo a series of procedures to maintain access, this plan should be defined early for each individual patient so that viable options will remain later in life. This is similar in principle to the concept of “Begin with the end in mind” described in Steven Covey’s book The 7 Habits of Highly Effective People and is a principle used in leadership training across many industries and businesses.5 When this paradigm is applied to dialysis access, the physician is asked to serve

as a specialist, rather than a technician, embracing a more comprehensive approach to dialysis access and renal care.6 The big picture strategy of a specialist requires understanding the patient’s priorities, foresight, planning, consideration of several treatment options, and continuous evaluation.

When a physician ‘begins with the end in mind’, challenges are met as learning opportunities, different questions emerge, and possibilities expand because solutions are evaluated in a co-creative fashion.

3. Patient centricity

Meet your new boss: the patient. With more complexity comes a greater need to engage a multidisciplinary team to create solutions. In the center of this team is the patient. Despite the changing external environment, some things stand the test of time. The dialysis mission

statement is one of those things. The overarching mission within any dialysis access algorithm is to do what is best or appropriate for the informed patient every time. The recently published KDOQI guidelines agree with keeping the patient at centre focus, recognising the complexity and individuality of patients on dialysis access.

By nature, many clinicians dislike the application of business psychology and personal improvement to clinical care. They often, through training and personality, favour harder science and defined endpoints. However, the science, along with patient care, is rapidly changing and clinicians must adapt. Dialysis access care requires a more open mindset than many areas of medicine due to the nature of the disease.

Numerous interventions are typically required for an individual patient over many years. Certain interventions have insufficient evidence, and clinicians may lack experience in a particular intervention. Expectations from referring physicians may be high whilst outcomes are often poor. The consequences of one action may have repercussions many years down the line. The change from previous dogmatic approaches in dialysis access algorithms to the current more holistic approaches in the new KDOQI guidelines is to be welcomed if we wish to improve the quality of care for patients requiring RRT. Focus on qualitative factors (e.g. what’s important for the patient) rather than quantitative targets (e.g. % fistulas vs catheters) is long overdue.

Continuous improvement in dialysis access care requires collaboration, teamwork, and shared knowledge, with the patient as the central focus of decision-making, and a lifetime perspective to guide appropriate interventions at specific times. To do this all clinicians should be open to improving not only their clinical skillset, but also themselves and their own mindset.

References 1. Giles, S. (2018) The New Science of Radical Innovation: The Six Competencies Leaders Need to Win in a Complex World. Dallas, BenBella Books, Inc. 2. Dweck CS, Yeager DS. Mindsets: A View From Two Eras. Perspect Psychol Sci. 2019;14(3):481-96.

3. https://www.kidney.org/sites/default/files/kdoqi_ vasc-access-review2019_v2.pdf 4. Lok CE, Davidson I. Optimal choice of dialysis access for chronic kidney disease patients: developing a life plan for dialysis access. Semin Nephrol. 2012; 32: 530-537.

5. COVEY SR. The 7 habits of highly effective people: restoring the character ethic. : New York, Free Press.; 2004.

6. Field M, Tullett K, Khawaja A, Jones R, Inston NG. Quality improvement in vascular access: The role of patient-reported outcome measures. J Vasc Access.

2019:1129729819845624.

7. Davidson I, Gallieni M, Sacena R, Dolmatch B. A patient centered decision making dialysis access algorithm. J Vasc Access. 2007: 8: 59-68.

Nicholas Inston is a consultant renal transplant vascular surgeon at the University Hospitals Birmingham in Birmingham, UK. Therese Wykoff is the programme director of the Kidney Academy, a nonprofit organisation serving the global dialysis access community.

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No increased short- to midterm mortality among dialysis access patients treated with paclitaxelcoated balloon A systematic review and meta-analysis, recently published in the Journal of Endovascular Therapy, found no difference in short- to midterm mortality among patients who underwent dialysis access treatment using a drug-coated balloon compared with percutaneous transluminal angioplasty with an uncoated balloon. “With proven benefit and no evidence of harm,” say the authors, they recommend “ongoing use of [paclitaxelcoated balloons] for the failing dialysis access”.

“T

o our knowledge, there has been no systematic review and meta-analysis specifically investigating mortality following paclitaxel-coated device use in the treatment of the dysfunctional dialysis access circuit,” comment the study investigators, including first author Krystal Dinh (Westmead Hospital, Westmead, Australia) and lead author Roman Varcoe (Prince of Wales Private Hospital, Randwick, Australia).The aim of this study, therefore, was to perform a systematic review and meta-analysis of eight randomised controlled trials to investigate the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty with an uncoated balloon.

At the pooled mean follow-up of 13.5 months, allcause mortality—the primary outcome—was similar in the paclitaxel-coated balloon and percutaneous transluminal angioplasty groups, at 13.8% and 11.2%, respectively (RR 1.26, 95% confidence interval [CI] 0.85–0.89, p=0.25).

In addition, subgroup analysis confirmed that there were no statistically significant differences in mortality at six, 12, and 24 months after treatment. Six-month follow-up data was available in all eight studies included in the meta-analysis and showed results of 5.2% vs. 4.8%, respectively (RR 1.24, 95% CI 0.62–2.47, p=0.55); at 12-months, for which there were six studies’ worth of data, the results were 6.3% vs. 6% (RR 1.06, 95% CI 0.43–2.63, p=0.9); and 24-month follow-up data, available across three studies, revealed figures of 19% vs. 13.5% (RR 1.38, 95% CI 0.9–2.12, p=0.14).

Dinh and colleagues remark that the present analysis was performed to assess the single endpoint of mortality “in direct response” to the meta-analysis published by Katsanos et al in December 2018,

which identified higher mortality rates in patients with peripheral arterial disease (PAD) who underwent endovascular treatment of the femoropopliteal arteries with paclitaxel-coated balloons and stents compared to a similar group where no paclitaxel was used.

“In contrast to those findings, our study found no association for patients undergoing treatment for the failing [dialysis access],” the authors state. They recognise that although the meta-analysis by Katsanos and colleagues did not include patients undergoing treatment for dialysis access stenosis, the US Food and Drug Administration (FDA) warning letter that followed in March 2019 did not distinguish between paclitaxel-coated devices used for the treatment of PAD and dialysis access failure.

In response to this, Dinh and colleagues postulate: “The potential issues of patient safety and medicolegal liability are likely to result in reduced use of paclitaxelcoated devices, a technology shown to reduce reintervention rates”.

They emphasise the fact that paclitaxel-coated balloons are “proven to avoid restenosis and reintervention,” and, “in the absence of a safety signal,” recommend ongoing use while further study is undertaken.

The investigators note a few limitations of the present study. Firstly, the number of studies and participants analysed in the meta-analysis was smaller than that of Katsanos et al. In addition, the duration of follow-up in the included studies was short, with only three extending to the 24-month follow-up, and none extended to the four to five years reported in the Katsanos et al study, which render Dinh and colleagues “unable to make any inferences about long-term mortality outcomes”. Finally, like the Katsanos et al study, the present analysis was a summary-level metaanalysis that was unable to collect patient level data

and specific causes of death. The authors believe that “additional insights would certainly be gained if we had access to cause and time of death results”.

They recognise that while it is unclear whether the drug paclitaxel was responsible for the increased death rates observed by Katsanos et al, it is “very likely” that any increased risk would be difficult to detect, and less relevant due to the significant risk of life that is known to result from increased repeat interventions and venous catheters in this high-risk population.

The authors conclude: “It is important that we interpret the paclitaxel safety signal alongside a complete understanding of the evidence for patient benefit that may be gained through the use of paclitaxel-coated balloon angioplasty in [dialysis access]”.

The present analysis was performed to assess the single endpoint of mortality in direct response to the metaanalysis published by Katsanos et al.”

“Some light at the end of the tunnel”: Meta-analysis welcomed by vascular access community

Commenting on the present study, Robert Jones (Queen Elizabeth Hospital, Birmingham, UK) and Kate Steiner (Lister Hospital, Stevenage, UK) tell Vascular News: “The recently published meta-analysis by Dinh et al addressing the use of paclitaxel balloons in AV [arteriovenous] access intervention is welcomed and clearly demonstrates a lack of associated mortality signal at two years, thereby providing some light at the end of the tunnel in the ongoing paclitaxel controversy.”

They continue: “The concerns around late mortality with paclitaxel products used in peripheral vascular disease, raised in the previously published meta-analysis by Katsanos et al, has had a massive impact and potential negative effect on AV access patients. These two patient groups are very different and loss of a fistula or graft in a dialysis patient with subsequent reliance on dialysis catheters has a wellestablished association to increased mortality.

“As well as providing some reassurance around mortality, the trials included in the current metaanalysis by Dinh et al highlight and remind us of the improved patency and lower re-intervention rate with paclitaxel balloons used to treat dysfunctional fistulas and grafts compared to plain balloons and the benefit this conveys to this patient group.”

“The reflex reaction to the Katsanos paper,

The […] metaanalysis is welcomed and clearly demonstrated a lack of associated mortality signal at two years.”

L to R: Roman Varcoe, Robert Jones, and Kate Steiner

particularly in the UK, has led to a blanket cull on the use of paclitaxel balloons in a number of centres across the country treating a large AV access population.

The Katsanos paper did not mention AV access and furthermore subsequent national guidelines failed to specifically address this application or provide any guidance in this regard.”

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e-PTFE-covered stent demonstrates better target lesion primary patency compared to angioplasty The results of AVeNEW, the first level-one clinical study dedicated solely to the use of a covered stent designed to treat stenosis in the arteriovenous (AV) fistula access circuit, show that the Covera vascular covered stent (Bard) demonstrates “significantly better” target lesion primary patency compared to percutaneous transluminal angioplasty (PTA) at six months, with the difference sustained in the 12-month data. Access circuit patency was also maintained at 12 months.

L

ead investigator Bart Dolmatch (The Palo Alto Medical Foundation, Mountain View, USA) recently presented this “first look” at the 12-month results of the AVeNEW study at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).

Dolmatch and colleagues describe AVeNEW as a prospective, international, multicentre, randomised controlled clinical trial, designed to assess the Covera stent compared to angioplasty for the treatment of stenotic lesions in the venous outflow of upper extremity AV access circuits in patients dialysing with

an autogenous fistula.

The Covera stent, which received US Food and Drug Administration (FDA) approval in July 2018, is described on the FDA website as “an expandable, flexible, metal [nitinol] tube covered with a material called expanded polytetrafluoroethylene [ePTFE].”

Dolmatch and colleagues comment that AVeNEW is “the first level-one clinical trial dedicated solely to the use of a covered stent graft designed to treat stenosis in the AV fistula access circuit,” and they conclude that the covered stent group demonstrated “significantly better” target lesion primary patency compared to the PTA group at six months, with the difference sustained at 12 months. Access circuit primary patency was numerically different at six months, and “statistically better” for the stent graft group at 12 months.

The investigators enrolled 280 patients with stenosis ≥50% in the venous outflow of the AV access circuit, and with clinical or haemodynamic evidence of fistula dysfunction, at 20 centres across the USA, Europe, Australia, and New Zealand.

They detail that patients received either PTA alone or PTA followed by covered stent placement. The primary endpoints were six-month target lesion primary patency and 30-day safety.

Secondary outcomes included target lesion primary patency at 12 months, and access circuit primary patency at six and 12 months.

The proportion of patients free from a primary safety event with the covered stent (95%) was non-inferior to PTA (96.4%) at 30 days (p=0.002, significant for non-inferiority).

Target lesion primary patency was significantly better for the covered stent group (78.7%) versus the PTA group

Covera stent (Bard)

(47.9%) at six months (Kaplan-Meier analysis) and remained statistically significant at 12 months (57.5% vs.

21.2%, respectively; p<0.001). Access circuit primary patency at six months numerically favoured the covered stent (50.7%) group compared to the PTA group (43.8%) while at 12 months the difference was statistically significant (28.9% vs. 17.7%, respectively; p=0.016).

The investigators summarise that the covered stent conferred more than a 30% improvement in patency at the target lesion compared to PTA at both six and 12 months. Furthermore, the covered stent group had statistically superior access circuit patency at 12 months. “Clinical follow-up is ongoing,” they comment, “and will continue out to three years”.

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Highlights of i-VAS 2019

“A yearly hub for innovation in vascular access”: i-VAS 2019 and beyond Following the 2019 International Vascular Access Symposium (i-VAS 2019; 13 September, Paris, France), current president Alexandros Mallios talks to Vascular News about his highlights of this year’s meeting, what we can look forward to next year, and what makes i-VAS stand out in the field of vascular access.

1. Can you provide a brief history of the i-VAS meeting?

I did my Vascular Surgery fellowship in Tulsa, USA, between 2012 and 2014. When I went there, I was already fully trained as a Vascular Surgeon in Europe and already fairly experienced in Vascular Access surgery. I realised that between the USA and Europe there are significant differences in the way things are being done and none was superior than the other they were just different and complementary. I discovered the Proximal Radial Artery Fistula and other interesting techniques with the pioneer of “Fistula First” William C Jennings (goes by Tip), who then became my mentor and friend and I realised that although in the beginning I thought I knew everything, there was still plenty of stuff to learn. As Tip says very wisely and with a perfect southern accent: “People don’t know what they don’t know”. I was a very good example of that (laughing would go here if it was to be reproduced as a live interview).

When I came back I decided to do a meeting that will bring the two worlds (America and Europe) together for an intense meeting, focused in Vascular Access and innovation, with live cases and debates where industry has the opportunity to expose all the new material that is being developed, presented by the people with the widest experience world-wide. I asked Pierre Bourquelot and William Jennings to be my co-directors and then the rest is history.

3. What makes i-VAS stand out in the field of vascular access?

I-VAS was created with a vision to be a yearly hub for innovation in vascular access. There are really not so many international meetings focused in vascular access and even less in new innovative technologies. If you go to all the big meetings like CX, Veith, CACVS, CIRSE, there is always a vascular access session, but it is always in the periphery. People go there to listen other more sexy stuff. If I had to choose between a

4. What are your highlights of the i-VAS 2019 meeting?

I believe the two lives of the pAVF technologies would be the one that I would choose, although many other presentations were amazing. For the first time we had a live case for both Ellipsys and Wavelinq. Our case was uneventful as usual but we did it locally and we have done already so many in many conferences, including CiDA last year where BD had a great video case presented by Erik Peden. Panos Kitrou from Patras, Greece did a very good job this year and we all know how challenging it can be to do a live case especially for a new device and for the first time in the world ever.

We had Tobias Steinke who has big experience with Wavelinq and while Panos was doing his case Tobias explained lots of tips and tricks and potential pitfalls for the device: that was really very cool and helpful.

We had some connection problems but this is just an opportunity for improvement next year.

5. What can we expect from the next meeting?

2. Now in its second year, how has i-VAS developed since the inaugural meeting?

Being kind of a “new kid on the bloc”, as far as organising meetings is concerned, there is a big challenge in organising a meeting that is yearly in a sense, that you want to have all the big names and the interesting stuff presented but in the same time trying to avoid repeating yourself.

This year we had more people presenting that were not available last year, including Tobias Steinke and Charmaine Lok, colleagues that are definitely top notch in the field of vascular access, people who know their stuff and when they present the audience is captivated.

We also had Bob Lee from the FDA and Pr. Amabile representing the equivalent authority in France, who explained what the processes are for new devices to get approved and used in both continents.

We also had more partners from the industry presenting lots of interesting new technologies and data, like the Hero graft, the inside out surfacer and the VasQ external support, while I shouldn’t forget to mention that we supported the humanitarian actions with a presentation from BOL regarding the work that is being done in countries of the third world where experts go as volunteers to do vascular access surgery under very difficult conditions, I was blessed to participate to quite a few in Jamaica and Guatemala where we did adults and children respectively.

products are the same. Universities and governments cannot follow any more and support this expensive modern medicine in a world where resources are more and more scarce and budgets more and more tight.

Everyone has biases for whatever reasons, it can be because of his financial interests or his own personal bad experience with a product, or just because he thinks that what he does is always the best—a very common place for surgeons. For me things are simple; when you go up on the podium, you put up your disclosures, which are public data anyway most of the time, you put up your slides and your arguments and the audience will judge if you are a colleague worthy of respect or an industry puppet.

That is s what i-VAS is all about—everything on the table.

We needed a dedicated forum where people will join from all continents.” presentation by Stephan Haulon on branched stent grafts for the aortic arch or percutaneous fistulae by Mallios et al, I would probably go to listen to Stephan!

So, we really need a dedicated forum where people will join from all continents, Paris is very central (and beautiful) and this helps a lot.

Also, we are not hesitant to acknowledge the central role of industry in pushing technology forward. I believe there is a level of hypocrisy when people are pointing fingers around when someone is a consultant or shareholder for a company, as if it means that he is not independent anymore when he expresses his scientific opinion. Conferences cannot happen without the money from the industry, while research and new

Lots of new things are coming... We will change the venue in order to have more space for attendees and booths, more space for workshops also, better acoustics and better overall conditions in the room that were in good for the first two years but need to get better as we move forward. We will also add half day more, in order to have a dedicated time for hands-on workshops only for all industry partners, and also allow more time for presentations and discussions as I think that this year the programme was too dense and as a result we finished too late. People may have better things to do on a Friday night in Paris.

We will also add on site translation with personal headsets—given that lots of our attendees are French speaking this might improve the understanding and exchange of opinions. I am also working in partnership with other meetings and colleagues—we will try to keep everyone excited... stay tuned.

6. In the digital age, why is it important to continue to attend meetings such as this?

I am pretty much a “high tech junkie” myself, but I can tell you that conferences will always remain relevant because humans will always need the personal contact that cannot be replaced by the internet and digital technology. Sure, you can watch and study a technique over the internet and see an expert doing a case on YouTube, there is nothing wrong with that; we should all do it, as it is great and very efficient training, but meeting the actual person live, asking him questions, networking with your colleagues and industry, shaking hands and even having a glass of wine together at the end of an intense day of scientific brainstorming are all part of a healthy social life that we need to maintain and cannot be replaced by technology.

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A thumbnail sketch of haemodialysis access: Past, present, and future in the USA Bart Dolmatch Comment & Analysis Bart Dolmatch gives an overview of the history of haemodialysis access in the USA, and balances the pros and cons of current access options. He outlines his hopes for the increasing role he believes interventional radiologists should play in the management of end-stage renal disease patients, and how innovation is helping physicians achieve better clinical results.

WHILE THE INCIDENCE of endstage renal disease (ESRD) in the USA has reached a plateau over the past few years, prevalence continues to climb due to lower mortality rates.1 ESRD is treated with renal replacement, but it is costly and places a growing financial burden upon Medicare participants. Medicarepaid claims for ESRD, including renal replacement, represented over 7% of all Medicare payments and exceeded US$35 billion in 2015–2016.2 Renal replacement can be performed with a kidney transplantation, peritoneal dialysis, or haemodialysis. For many people, transplantation may be the best option, but due to the ongoing shortage of donor organs, fewer than 3% of people with ESRD received a preemptive transplant. Peritoneal dialysis, conveniently performed at home by most people, accounted for only 9.7% of all renal replacement. Haemodialysis accounted for renal replacement for nearly 90% of the ESRD population in the USA.1 Haemodialysis is simply the process of cycling a person’s blood through a filtration system, removing toxins while balancing fluids and electrolytes, and returning the blood back to the patient’s circulatory system. Efficient cycling of

blood requires a way to both remove and replace blood, typically through one of three methods: a dual lumen catheter; an arteriovenous graft (AVG); or an arteriovenous fistula (AVF). An AVG is a surgically inter-posed conduit between an artery and vein that is accessed for haemodialysis. An AVF is the direct connection of an artery to vein, where the venous side of the circuit serves as the access site. Both an AVG and AVF are accessed for haemodialysis using two-needle cannulation—one for cycling blood to the dialyser, the other to return blood to the patient.

All three types of vascular access have pros and cons. Catheters are convenient but have the highest morbidity rates compared to AVGs and AVFs.3,4 AVGs have a high rate of usability, but up to 75% failed in their first year.5 Once an AVF is ready for repeated successful haemodialysis, it is often an excellent long-term vascular access solution with better durability than an AVG. However up to 60% of AVFs were not ready for use within four to five months after surgery, and many were abandoned before any attempt to salvage.6 While there are problems with all forms of haemodialysis access, the

AVF remains the preferred modality and accounts for about two-thirds of haemodialysis access in the USA.5 For more than 50 years, creation of an AVF was the purview of surgeons. However, in 2018, two catheter-based systems were cleared for percutaneous AVF creation by the US Food and Drug Administration (FDA)—BD’s WavelinQ and Avenu Medical’s Ellipsys. The hope is that percutaneous AVFs, created without pre-operative delay, will have high rates of early unassisted usability and remain functional. So far, data are encouraging.6,7 AVGs and AVFs often develop stenoses that reduce dialysis efficiency and can lead to thrombosis. Percutaneous transluminal angioplasty (PTA) has been used for decades, though with varying durability. We have learned that bare metal stents do not improve durability over successful PTA.8,9,10 However, covered stents from BD, such as the Flair, Fluency and Covera, as well as

The hope is that percutaneous AVFs, created without preoperative delay, will have high rates of early unassisted usability and remain functional.

So far, data are encouraging.”

Gore and Associate’s Viabahn, reduce restenosis rates. These covered stents have demonstrated superior outcomes in prospective clinical trials when compared to PTA.11–15 In addition, BD’s Lutonix drug-coated balloon also confers improved outcomes compared to PTA.16 The past few years have seen great strides in creating and maintaining haemodialysis access. We now have new ways to achieve better results, with the hope that through ongoing innovation

IN.PACT AV access trial meets primary safety and effectiveness endpoints Medtronic has announced the first-ever results from the IN.PACT AV access clinical study comparing the investigational IN.PACT AV drug-coated balloon (DCB) to percutaneous transluminal angioplasty (PTA) in patients with de novo or non-stented restenotic arteriovenous (AV) fistulae lesions. The study met primary safety and effectiveness endpoints.

Th

e IN.PACT AV Access study is a randomised controlled trial (RCT), which has enrolled 330 subjects at 29 sites in the USA, Japan, and New Zealand. The primary effectiveness endpoint was defined as freedom from clinically-driven target lesion revascularisation (CDTLR) or access circuit thrombosis measured through six months post-procedure and the primary safety endpoint

was defined as the serious adverse event rate involving the AV access circuit through 30 days post-procedure.

Additional endpoints include but are not limited to: access circuit primary patency, cumulative target lesion revascularisations, and number of interventions required to maintain target lesion patency.

The study enrolled a challenging patient population who had been undergoing dialysis for an average

and comparative prospective clinical research, we can improve the lives of patients with ESRD. Bart Dolmatch is an interventional radiologist at The Palo Alto Medical Foundation and El Camino Hospital, Palo Alto, USA. References 1. 2018, United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 1, https://www.usrds. org/2018/view/v2_01.aspx, Accessed 15 August, 2019 2. 2018, United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 9: Healthcare Expenditures for Persons with ESRD, https://www.usrds. org/2018/view/v2_09.aspx, Accessed 15 August, 2019 3. CE Lok and R Foley, Vascular Access Morbidity and Mortality: Trends of the Last Decade, Clinical Journal of the American Society of Nephrology (CJASN), 2013; 8 (7):1,213–1,219 4. G Ocak, et al, Haemodialysis catheters increase mortality as compared to arteriovenous accesses especially in elderly patients, Nephrology Dialysis Transplantation, 2011; 26(8):2,611–2,617 5. 2018 United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 3: Vascular Access. https://www.usrds.org/2018/view/ v2_03.aspx, Accessed 15 August, 2019 6. C Lok et al, Endovascular Proximal Forearm Arteriovenous Fistula for Hemodialysis Access: Results of the Prospective, Multicenter Novel Endovascular Access Trial (NEAT), American Journal of Kidney Disease, 2017; 70(4):486–497 7. JE Hull, WC Jennings, RI Cooper, et al, The Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access, Journal of Vascular and Interventional Radiology, 2018; 29(2):149–158 8. SF Quinn, ES Schuman, TA Demlow, et al, Percutaneous transluminal angioplasty versus endovascular stent placement in the treatment of venous stenoses in patients undergoing hemodialysis: intermediate results. Journal of Vascular and Interventional Radiology, 1995;6(6):851–855 9. GA Beathard, Gianturco self-expanding stent in the treatment of stenosis in dialysis access grafts, Kidney International, 1993;43(4):872–877 10. EK Hoffer, S Sultan, MM Herskowitz, ID Daniels, SJA Sclafani, Prospective randomized trial of a metallic intravascular stent in hemodialysis graft maintenance. Journal of Vascular and Interventional Radiology, 1997;8(6):965–973 11. ZJ Haskal, S Trerotola, B Dolmatch, E Schuman, et al, Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts, 2010, New England Journal of Medicine, 2010;362:494–503 1. Haskal ZJ, Saad TF, Hoggard JG, Cooper RI, et al, Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: TwoYear Results of the RENOVA Study, Journal of Vascular and Interventional Radiology, 2016 Aug;27(8):1,105– 1,114 1. A Falk, ID Maya, AS Yevzlin, and RESCUE Investigators, A Prospective, Randomized Study of an Expanded Polytetrafluoroethylene Stent Graft versus Balloon Angioplasty for In-Stent Restenosis in Arteriovenous Grafts and Fistulae: Two-Year Results of the RESCUE Study, Journal of Vascular and Interventional Radiology, 2016; 27(10):1,465–1,476 12. T Vesely, W DaVanzo, T Behrend, et al, Balloon angioplasty versus Viabahn stent graft for treatment of failing or thrombosed prosthetic hemodialysis grafts. Journal of Vascular and Interventional Radiology, 2016 Nov;64(5):1,400–1,410 13. Covera Vascular Covered Stent Instructions for Use, Bard Peripheral Vascular, B05872 Rev.3/05-18. https://www.accessdata.fda.gov/cdrh_docs/pdf17/ P170042D.pdf, Accessed August 15, 2019 14. SO Trerotola, J Lawson, P Roy-Chaudhury, and TF Saad; for the Lutonix AV Clinical Trial Investigators, Drug-Coated Balloon Angioplasty in Failing AV Fistulas: A Randomized Controlled Trial, Clinical Journal of the American Society of Nephrology (CJASN), 2018; 13(8):1,215–1,224

of 4.3 years. Overall, the IN.PACT AV DCB group demonstrated clinical benefit compared to the PTA control group. Key data highlights include: Per Kaplan-Meier estimates, the primary patency rate of the target lesion at 180 days was 86.1% in the IN.PACT AV DCB group compared to 68.9% in the PTA control group (p<0.001).

Per Kaplan-Meier estimates, the primary patency rate of the target lesion at 210 days was 81.4% in the IN.PACT AV DCB group compared to 59.0% in the PTA control group (p<0.001).

Patients in the IN.PACT AV DCB group required 56% fewer reinterventions to maintain target lesion patency through 210 days compared to those in the PTA control group.

A low rate of access circuit-related serious adverse events, with 4.2% in the IN.PACT AV DCB study group compared to 4.4% in the PTA control group through 30 days.

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November 2019 | Issue 84

Chronic total occlusions

The retrograde approach to CTOs: What, who, when, where, why, and how Lorenzo Patrone Comment & Analysis Lorenzo Patrone talks to Vascular News about retrograde access to lower limb arterial chronic total occlusions (CTOs).

What

The retrograde approach to lower limb arterial chronic total occlusions was originally described more than thirty years ago but is still sometimes considered taboo.

Who?

I strongly believe that every operator should master the retrograde approach to lower limb arterial CTOs. I routinely run workshops on advanced lower limb recanalisations at my institution, which are open to motivated vascular surgeons and interventional radiologists. The retrograde approach is one of my main focuses during the course, offering the possibility to learn tips and tricks from my recorded and live cases.

When?

The retrograde approach to CTOs should be used sooner rather than later during the procedure in order to increase the recanalisation success rate, thus avoiding having to reschedule the patient for another endovascular procedure/bypass.

I personally use the retrograde approach in 30–40% of my cases, when I struggle more than five to 10 minutes in re-entering into the distal true lumen or when I perforate the vessel during the recanalisation attempt from the antegrade access. The recanalisation success rate using this approach is extremely high.

Furthermore, it allows you to preserve the distal landing zone of the occluded artery with the potential subintimal dissection just limited to the occluded arterial segment.

Where?

The distal superficial femoral artery, proximal anterior tibial artery, dorsalis pedis artery and posterior tibial artery are the preferable choices but any artery can potentially be punctured in a retrograde fashion.

Why?

The retrograde access has almost always been described as a bailout solution after failed standard antegrade approach. The recently published C-TOP classification

has shown how the on-table morphology of the plaque can already predict if patients could benefit from a retrograde approach. This could then be used as the first approach to treating the CTO (a higher rate of successful intraluminal recanalisation from the retrograde approach is described by Fanelli et al when compared to the antegrade one), or to increase the chances of final success by reconnecting with the antegrade wire in the middle of the occluded artery.

The retrograde access is almost always used to exteriorise the wire from the antegrade access. In very rare cases it can be used as the main or even only access from where to introduce balloons or stent.

How?

Retrograde access can be obtained by ultrasound or fluoroscopic guidance, depending on the skill set of the operator and the location/anatomy of the chosen artery. The distal SFA, dorsalis pedis artery and distal posterior tibial artery are usually easily accessible under ultrasound. This approach presents the advantages of better accuracy, real time visualisation of the needle (particularly important in case of patient under local anaesthesia), and avoids radiation exposure to the operator.

The fluoroscopic guidance is, on the other hand, easier to manage for any operator and preferable for retrograde access through a peroneal or proximal anterior tibial artery puncture. Proficient use of fluoroscopic filters can minimise the radiation exposure to the operator.

In this method the needle needs to be advanced at 45 degrees to the skin while keeping it completely in line with the artery to minimise the chance of missing the artery.

The very vast majority of retrograde accesses do not require the insertion of a sheath, and an 0.018’’ wire and a compatible catheter are usually sufficient to cross the occlusion. The actual outer diameter of the sheath is always 2Fr bigger than the indicated size, so by going sheath-less one avoids greater trauma to the punctured vessel.

Angioplasty alone at the level of the retrograde access site is enough to obtain haemostasis in the majority of cases.

Ten tips and tricks

1. The bigger the vessel, the easier the puncture. I think that the distal SFA is probably the most suitable target for someone who wants to start practising in retrograde punctures. If the operator feels comfortable with ultrasound, a good trick could be to scan the patient’s distal thigh by ultrasound before starting the operation and mark on the skin at the level of a possible entry point (remember, however, that if the same distal SFA will be punctured under fluoroscopic guidance the access site will significantly change, being more medial). To have a sterile window already prepared before starting with the recanalisation reduces the effort in getting the access at a later stage.

2. When puncturing under fluoroscopic

suggest you to keep at least 7–8cm between your puncture site and the distal occluded vessel, in order to achieve sufficient stability once the wire needs to be inserted and the recanalisation starts.

7. Always avoid surgical exposure of the vessels at the level of the ankle, especially in critical limb ischemia patients. The ultrasound approach for these vessels is usually relatively easy and the percutaneous access avoids possible difficult wound healing in already arterially compromised patients.

8. There are different ways to externalise the wire advanced from the retrograde access. One is to try to pass it into a catheter advanced from the antegrade access (6F for the above-knee vessels and 4F for the below-knee ones); the other one is to use a snare, inserted from the antegrade access, to grab it.

In my practice, I now approach all the long SFA occlusions with an initial

Figure 1 a) Distal SFA puncture b) Distal AT puncture c) Proximal AT puncture d) US guided access at the level of the distal PT

guidance, try to zoom in on your potential retrograde access site to increase your accuracy.

3. The needle which I routinely use is the 21Gx7cm one which is part of any micropuncture kit. I then use a 21Gx15cm Chiba needle when the body habitus of the patient suggests to me that the distance to the distal superficial femoral artery, proximal anterior tibial artery, or peroneal artery is longer than in the majority of patients.

4. Always use a 0.018”x300cm long wire, which has to be passed through the needle as soon as the puncture is made because you will benefit from all its length once the wire is through the antegrade and the retrograde access.

5. There is never the need to position the patient prone for a distal SFA/popliteal access. A moderate extrarotation of the knee permits to reach the distal SFA and the proximal popliteal artery in the vast majority of the cases under ultrasound or fluoroscopic guidance. If needed, the tibioperoneal trunk and the distal popliteal artery can be punctured under fluoroscopic guidance through the interossea membrane.

6. Always remember that, when puncturing a deep vessel as the distal superficial femoral artery, the proximal anterior tibial artery, or the peroneal artery under fluoroscopic guidance, you will hit the vessel roughly 4–5cm above your skin entrance. I therefore

over the hill common femoral artery access in order to facilitate grabbing a wire inserted through a retrograde approach by withdrawing my sheath/ catheter to the level of the external iliac artery.

9. Another important trick, useful for patients who need to be punctured distally under fluoroscopic guidance and are not under general or spinal, is to avoid the local anaesthesia before the retrograde puncture. It will be easier and quicker to puncture the distal vessel without getting movement artefacts due to the stinging of the local anaesthesia which can then be easily provided once the retrograde access is secured by the insertion of the wire.

10. Finally, when puncturing distal vessels under fluoroscopic guidance, remember to use one hand to advance the needle and the other one to simultaneously hold the foot. In case the patient moves between the angiogram and the puncture, you can always align the vessel to your reference image again with small controlled movements of the foot.

Lorenzo Patrone is a vascular and interventional radiology consultant at the West London Vascular and Interventional Centre (Northwick Park Hospital, London, UK).

All references for this article are online at www.vascularnews.com.

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November 2019 | Issue 84

Carotid endarterectomy

Flow cytometry-ADP test can predict occurrence of microembolic signals during carotid endarterectomy The flow cytometry-ADP test developed by researchers at UMC Utrecht can predict the occurrence of micro-embolic signals during carotid endarterectomy (CEA), Aarent Brand (UMC Utrecht, Utrecht, The Netherlands) said during a scientific prize session at the annual meeting of the European Society for Vascular Surgery (ESVS; 24-27 September, Hamburg, Germany). By way of contrast, the VerifyNow system cannot, Brand and his team found after conducting research into platelet activation measurements.

THE RESEARCHERS HAD set out to investigate the predictive value of platelet activity measurement on the incidence of micro-embolic signals while a CEA procedure is taking place.

“What we did is record perioperative microembolic signals bilaterally with transcranial Doppler imaging,” Brand explained.

The study involved 197 patients undergoing CEA. To measure platelet reactivity, the team used the VerifyNow P2Y12-assay (also used to measure bleeding risk) and the flow cytometry-based assay, measuring the response to ADP and the thrombin receptor-activating peptide (TRAP).

The study’s primary endpoint was unilateral microembolic signals, with the secondary outcome major adverse cardiovascular events (MACE).

Explaining his centre’s flow cytometry-based assay, Brand explained: “It is done with whole blood. It is not a point of care test in the same way but it is a fairly quick procedure. You have whole blood, you add an agonist, in this case either ADP or protease-activated receptor agonist. Then we fixate the platelets after activation and we measure them using forward and sideward scatter analysis. We used median fluorescence

intensity to see how much activation is happening.”

The results of the study demonstrated that 49 out of 197 patients showed microembolic signals.

“In previous studies,” said Brand, “they found that having over 20 solid microemboli during the procedure puts you at high risk for ischaemic brain lesions. So in our population we can see that that is only eight patients out of almost 200.”

The researchers found that flow cytometry did correlate with the number of microembolic signals, Brand continued. “This was the case for both ADP-

The study’s primary endpoint was unilateral microembolic signals, with the secondary outcome major adverse cardiovascular events.”

activated platelet measurements and TRAP-activated platelet measurements. VerifyNow did not correlate with this at all.”

Investigating further, Brand went on, the team found that the frequency of these microembolic signals was correlated with the flow cytometry ADP measurement (p=0.021).

“We found that the VerifyNow still did not correlate with the microembolic frequency,” he said. “We found that the TRAP, which is a second messenger, did not correlate with the frequency either.

“In practice, a lot of physicians use HTPR (high on-treatment platelet reactivity) states of patients, still having active platelets despite anti-platelet therapy, as a means of figuring out which patients are at high risk.

So it does correlate with showing microembolic signals and could be predictive.”

Brand added: “Being at high risk did correlate with our flow cytometry measurement. And again, the VerifyNow and TRAP did not show any correlation.

Also, as a secondary outcome we used MACE and we saw that, again, the flow cytometry results did correlate with MACE and the other tests did not.”

Further investigation is required, Brand said, while flow cytometry is more laborious, taking longer and not a point-of-care test. “We still do not know the optimal time for testing. Is it directly after receiving antiplatelet therapy, is it just before the surgery?” Those are questions Brand and his team, Suzanne Korporaal, Rolf Urbanus, and Gest Jan de Borst are currently probing at UMC Utrecht circulatory health research.

He concluded: “The flow cytometry-ADP test can predict the occurrence of micro-embolic signals. The VerifyNow cannot. It may be possible to single out patients at risk of ischaemic lesions in the future using flow cytometry-based assay.”

Blood vessel damage, not nerve damage, may be cause for side effects of traumatic brain injury The effects of a traumatic brain injury are clear—problems with memory, headaches, and emotions­—but what is unclear is the underlying pathological causes for those symptoms. According to new research led by researchers at the National Institutes of Neurological Disorders and Stroke (NINDS), those underlying pathological causes may actually involve more extensive blood vessel damage than previously known. These findings could help target better treatment of these common injuries.

T

he study, “Traumatic microbleeds and vascular injury,” was published in October 2019 in the journal Brain, and was a collaborative effort between the Uniformed Services University of the Health Sciences (USU), the National Institutes of Health (NIH), the University of Maryland, and the Cold Spring Harbor Laboratory.

Traumatic brain injury sustained in sports or on the battlefield can have fatal or lasting effects, but until now it has been unclear how these symptoms develop pathologically. Therefore, the researchers sought to better understand the pathological mechanisms that cause these symptoms by examining the brains of hundreds of patients very soon after injury using high-resolution imaging

techniques. They looked, specifically, at traumatic microbleeds—where trauma left a physical imprint on the brain that appeared as dark lesions on MRI scans, according to Lawrence Latour, the study’s lead author and a researcher at NINDS. Of the study’s 439 patients with acute traumatic brain injury (less than 48 hours after injury), about 30% had evidence of traumatic microbleeds (blood vessel injury). The traumatic microbleeds were also identified in 27% of mild, 47% of moderate, and 58% of severe traumatic brain injury patients. They also found that traumatic microbleeds were seen in more than 25% of patients with mild traumatic brain injury, suggesting that traumatic microbleeds are not

exclusive to patients with moderate or severe traumatic brain injury. Overall, blood vessel damage was much more widespread than we expected in patients with traumatic brain injury.

“These findings are also significant because the presence of traumatic microbleeds was an independent predictor of outcome,” according to Regina Armstrong, director of Translational Research in USU’s Center for Neuroscience and Regenerative Medicine (CNRM) who also collaborated on the study. The researchers also found patients who had traumatic microbleeds were more than twice as likely to have a disability as a result of their traumatic brain injury upon follow-up at 30 and 90 days post

injury.

“This study is important to the general public, and especially the military, to help detect TBI and provide treatments to those at risk of prolonged symptoms,” Armstrong said. “Future studies are needed to explore therapies targeting the effects of traumatic microbleeds in acute traumatic brain injury, including traumatic brain injuries that result from high-impact blast exposures.”

The study was supported by USU’s CNRM, the NINDS, and the Intramural Research Programs at the NIH Clinical Center.

The Uniformed Services University of the Health Sciences (USU) is the USA’s only Federal health sciences university.

USU educates, trains and prepares uniformed services health professionals, officers and leaders to directly support the Military Health System, the National Security and National Defense Strategies of the USA and the readiness of the country’s armed forces.

The Center for Neuroscience and Regenerative Medicine (CNRM) is a joint federal military traumatic brain injury (TBI) research program between the Uniformed Services University of the Health Sciences (USU) and the National Institutes of Health (NIH). CNRM performs a range of research with an emphasis on interventional clinical trials, focused on building a substantial evidence base that will influence and enhance clinical practice in the diagnosis and treatment of traumatic brain injury in service members.

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November 2019 | Issue 84

Latest research

Overview of 20 RCTs finds carotid artery stenting results in higher rates of 30-day death or stroke than carotid endarterectomy Carotid artery stenting (CAS) confers higher rates of 30-day death or stroke than carotid endarterectomy (CEA), an overview of primary and secondary analyses from 20 randomised controlled trials (RCTs) comparing the two procedures has found. Furthermore, in a paper published in the European Journal of Vascular and Endovascular Surgery, lead author Andrew Batchelder (The Leicester Vascular Institute, Leicester, UK) et al also reported that, after 30 days, the rate of late ipsilateral stroke was virtually identical for both CEA and CAS. THE RESEARCHERS CARRIED out a systematic review and meta-analysis of data from 20 RCTs, involving 126 publications in 36 medical or surgical journals between 1998 and 2019.

The project comprised three sections. The first was a meta-analysis of 30-day outcomes including: death, stroke, death/stroke, disabling stroke, death/disabling stroke, myocardial infarction (MI), death/stroke/MI, and cranial nerve injury. These were then meta-analysed for (i) CEA vs. CAS in all asymptomatic patients, (ii) CEA vs. CAS in all symptomatic patients, (iii) CEA vs.

CAS in asymptomatic patients where RCTs recruited more than 500 patients (excluding carotid angioplasty) and (iv) CEA vs. CAS in symptomatic patients where RCTs recruited more than 500 patients (also excluding carotid angioplasty). The second section provided an overview of clinically useful secondary analyses, while the third section dealt with meta-analyses for the prevalence of late stroke after CEA and CAS. “Even for those interested in the management of carotid disease, it remains a daunting task to

keep abreast of the literature,” the authors wrote.

Compared with CEA, the 30-day rate of death or stroke was significantly higher after CAS in seven trials involving 3,467 asymptomatic patients (OR: 1.64; 95% CI: 1.02-2.64) and in 10 RCTs involving 5,797 symptomatic patients (OR: 1.71; 95% CI: 1.38–2.11).

“Excluding procedural risks, late ipsilateral stroke was about 4% at nine years for both CEA and CAS, i.e., CAS was durable,” the authors noted. Given the durability of CAS in the RCTs, the authors stressed the importance of reducing 30-day risks after CAS,

Reducing procedural death/stroke after CAS may be achieved through better case selection.”

New 3D technology can repair aneurysms previously deemed inoperable Surgeries to repair complex thoracoabdominal aortic aneurysms are difficult and sometimes fraught with complications. Up to 25% of patients who undergo the vascular procedure experience subsequent renal problems caused by contrast dyes needed to pinpoint the locations of major vessels originating near or from the life-threatening arterial bulges.

S

urgeons at UC San Diego Health, the academic health system of the University of California, San Diego in San Diego, USA, are using a new imaging technology that harnesses artificial intelligence and machine learning to reduce the need for contrast agents, the patient’s time in surgery and the potential for post-operative kidney complications. UC San Diego Health is among the first healthcare systems in the USA to offer the technology.

The aorta is the primary artery carrying blood from the heart to the rest of the body. Aortic aneurysms occur when the walls of the artery weaken and lose their elasticity, resulting in a balloon-like bulge. The damaged tissue may eventually rupture without warning—with fatal consequences.

In traditional endovascular repair of aortic aneurysms, surgeons use contrast dyes to reveal the size and scope of the aneurysm, then X-rays are used to guide a stent graft—a plastic- or fabric-coated metal tube—to the weakened section of arterial wall to prevent it from tearing.

The new technology, called Dynamic Morphology Correction and developed

by UK-based Cydar Medical, allows surgeons to work faster with more precision and with minimal contrast dye.

Instead, surgeons rely upon dynamic 3D image overlays of the human body, built using computerised prediction models based on the patient’s preoperative X-ray and anatomy. The models allow surgeons to minimise iodine contrast and its risk to kidneys, lower radiation exposure during surgery

in order for CAS to deliver comparable early and late outcomes compared with CEA. The authors concluded that reducing procedural death/stroke after CAS may be achieved through better case selection.

Examples included preferentially performing CEA in symptomatic patients aged 70 years and over, especially in interventions undertaken within 14 days of symptom onset and in situations where the stroke risk after CAS is predicted to be higher; including segmental or remote plaques, plaque length >13mm, where two or more stents might be needed and in the presence of a heavy burden of brain white matter lesions.

New (post-operative) white matter lesions were more common after CAS (52% vs. 17%), and were associated with higher rates of late stroke and/or transient ischaemic attack (23% vs. 9%), but there was no evidence in the RCTs that new white matter lesions predisposed towards late cognitive impairment.

Restenoses were more common after CAS (10%) but this did not translate into an increased risk of late ipsilateral stroke. Restenoses (70–99%) after CEA were, however, associated with an increase in late ipsilateral stroke (OR: 3.87; 95% CI: 1.96-7.67; p<0.001).

Concluding this systematic review and meta-analysis, the research team identified several key issues to be resolved in the future: (i) will newer stent technologies and improved cerebral protection enable CAS to be performed within 14 days after symptom onset with risks similar to CEA (ii) what is the optimal annual volume of CAS procedures to maintain competency? (iii) how can the delivery of risk factor control and best medical treatment be improved? Finally (iv) the authors questioned whether there was a role for CEA/CAS in preventing or reversing cognitive decline?

In summary, the authors determined that the 20 RCTs provided important primary and secondary data that have been—and will continue to be—used to influence national and international guidelines of practice.

and measurably reduce time on the operating table.

“It allows me to fix aneurysms that were very difficult to fix before, and I can do it knowing that I’m reducing my radiation and contrast volume to my patients,” said Mahmoud Malas, MD, chief of Vascular and Endovascular Surgery at UC San Diego Health.

Aortic aneurysms occur primarily in men over the age of 60 when arteries have become more twisted and the use of stiff stents and wires is more challenging.

“This is a disease of the elderly,” Malas said. “In the past, we would sometimes have to say, ‘We’re sorry, but we just can’t help.’ This technology has opened up a new way for us to treat people we couldn’t previously.”

Cydar’s technology builds a 3D model of a patient’s aneurysm and surrounding vessels using a pre-operative CT scan.

This is significantly more accuracte than before, and I get into the major vessel with my catheter within a minute and without any contrast.”

On the day of surgery, surgeons take a real-time image of the patient’s body with two bone landmarks within the CT scan. The data are fused with the pre-operative image to form a 3D reconstruction of the image which the surgeon can use in the operating room as a guide to the aneurysm and its treatment, while preserving major aortic branches that feed the kidneys, bowels and liver.

“In the past, we would use a significant amount of contrast to just localise the visceral vessels, which could damage the kidneys,” Malas said.

“This is significantly more accurate than before, and I get into the major vessel with my catheter within a minute and without any contrast. We used to spend eight to 10 hours on these procedures.

Now we can do them in half the time.”

Mahmoud Malas

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November 2019 | Issue 84

Market watch

Clinical News New Cook Medical paclitaxel data presented at CIRSE 2019 confirm safety of Zilver PTX

New data on the use of Zilver PTX, Cook Medical’s paclitaxel-coated stent for peripheral arterial disease (PAD), confirm the safety of the device. These data was presented at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).

Michael Dake, senior vice president of health sciences at the University of Arizona, Tucson, president-elect of the Society of Interventional Radiology Executive Council, and global principal investigator, presented new 5-year data on Zilver PTX that Cook Medical gathered from the randomised controlled trial (RCT) performed to obtain US Food and Drug Administration (FDA) approval.

Cook Medical is the only organisation that has publicly provided longterm, patient-level data on the use of paclitaxel-coated devices for PAD. In addition to previously released information, the presentation included new data that had not been previously published.

This new data includes information from patients who had not previously completed the study, such as those who had been lost to follow up, giving a more complete view of how paclitaxelcoated devices affect patients.

The data confirms no significant difference in all-cause mortality for the Zilver PTX drug-eluting stent compared to traditional angioplasty or a bare metal stent (BMS). The findings further show that treatment with Zilver PTX and paclitaxel dose were not predictors of mortality. However, age and other serious conditions common in PAD patients were associated with mortality.

The findings that Dake presented have been published online in CardioVascular and Interventional Radiology (CVIR), a peer-reviewed journal, in a paper entitled “Paclitaxel-coated Zilver PTX drug-eluting stent treatment does not result in increased long-term allcause mortality compared to uncoated devices”.

“Our clinical program evaluates the Zilver PTX technology across a broad, real-world patient population— including patients at high risk for restenosis and reintervention. Zilver PTX offers proven long-term benefits that help patients get back to living,” said Mark Breedlove, vice president of Cook Medical’s Vascular division.

The patient-level data used for the RCT analysis, as well as Dr Dake’s presentation and other Zilver PTX information, is available at https:// www.cookmedical.com/peripheralintervention/paclitaxel/.

Intact Vascular announces positive one-year data from TOBA III clinical trial

Intact Vascular has announced the positive one-year results of its Tack Optimised Balloon Angioplasty (TOBA) III clinical trial, successfully achieving both primary and secondary endpoints. Marianne Brodmann, head of the Clinical Division of Angiology, Medical University of Graz, Austria, and principal investigator of the TOBA III trial, presented the data during the high impact clinical research session of the 31st Transcatheter Cardiovascular Therapeutics (TCT) meeting (25–29 September, San Francisco, USA), the annual scientific symposium of the Cardiovascular Research Foundation.

This multi-centre, single-arm, prospective study was conducted in Europe and investigated the combination of the Tack endovascular system with Medtronic’s IN.PACT Admiral drug-coated balloon as a treatment in

post-angioplasty dissections. I believe this new therapeutic paradigm will change the standard of care for abovethe-knee interventions.”

The observational data from the long lesion subset (>150 and ≤250mm) was analysed separately. Results from these 32 patients notably demonstrated 98.8% complete dissection resolution and 89.3% K-M vessel patency, with 96.8% K-M freedom from clinically-driven reintervention at 12-months and a 0% bailout stent rate.

Bluegrass Vascular announce publication of positive clinical results

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

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

Marianne Brodmann presenting TOBA III data at TCT 2019

the superficial femoral (SFA) and/or proximal popliteal (PPA) arteries. The study enrolled 201 patients, including 169 patients with arterial lesions ≤150mm in length and a subset of 32 patients with long arterial lesions (>150 and ≤250mm). All patients suffered from peripheral arterial disease (PAD) and underwent balloon angioplasty, consequently experiencing at least one dissection requiring repair.

Results from the 169 patient standard lesion cohort (≤150mm) impressively demonstrated 97.7% complete dissection resolution, 95% K-M vessel patency and 97.5% K–M freedom from clinicallydriven reintervention at 12-months.

This was accomplished with a 0.6% bailout stent rate. These results add to the body of clinical evidence supporting the use of the Tack system for post-PTA dissection repair and further demonstrate the long-term effectiveness of the technology, an Intact Vascular press release states.

“I am extremely pleased with the clinically compelling results of the TOBA III study,” comments Marianne Brodmann. “The Tack system provides a safe and effective solution for treating

fluoroscopy was 13.3 and 3.7 minutes, respectively.

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

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

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

The company recently filed a de novo request for the Surfacer ystem with

the US Food and Drug Administration (FDA) based on the positive clinical results of the company’s SAVE-US pivotal trial. The company anticipates that FDA will grant the request and the Surfacer system will be commercially available in the USA in 2020.

Terumo Aortic announces completion of enrolment of RelayPro US pivotal study

Terumo Aortic has announced the completion of enrolment of the RelayPro pivotal study in the USA. RelayPro is a low profile, next generation thoracic stent graft device designed to expand the treatment of thoracic endovascular aortic repair to patients with smaller access vessels.

RelayPro, having obtained CE Mark in 2018, utilises the same stent design, material and dual sheath technology as Terumo Aortic’s RelayPlus device, with the additional benefit of a 3 to 4 Fr reduction in outer profile.

The study is a prospective, multicentre, non-blinded, nonrandomised study of the RelayPro thoracic stent graft in patients with thoracic aortic aneurysms and penetrating atherosclerotic ulcers.

The primary endpoint for safety is a composite of major adverse events while the primary endpoint for effectiveness is a composite of technical and clinical success.

One-hundred and ten patients have been enrolled in the study across sites in both the United States and Japan.

Wilson Szeto (Cardiothoracic surgeon, University Medical Centre of Pennsylvania) Co-Principal Investigator, commented, “RelayPro’s ability to land accurately combined with its low profile will allow me to successfully treat complex anatomy with precision.”

This trial marks the first time both Bare Stent and Non-Bare Stent (NBS) configurations of RelayPro have been used in the USA. Venkatesh Ramaiah (Vascular Surgeon, HonorHealth Medical Group, Arizona) co-principal Investigator, stated, “One of the key benefits of RelayPro is being able to choose from a range of proximal configurations allowing me to tailor my device selection to meet the individual needs of each patient.”

The completion of enrolment is an important milestone for Terumo Aortic as it progresses towards the approval of RelayPro in the USA and Japan.

RelayPro (Terumo Aortic)

Issue 84 | November 2019

Market watch

Product News Insera announces first two stroke patients treated with its cyclical aspiration system

Insera Therapeutics has announced that the first two ischaemic stroke patients have been treated with its flagship cyclic aspiration system, CLEAR. The company received CE mark approval for its flagship product, the CLEAR Aspiration System, in March 2019.

“We used the CLEAR aspiration system to remove blood clots from two stroke patients, one from the anterior circulation and the other from the posterior circulation. I am extremely pleased with the device and believe the cyclical nature of the aspiration offers unique safety and efficacy advantages over existing devices,” said Vladimir Kalousek, interventional neuroradiologist at the Sisters of Charity Hospital, Zagreb, Croatia.

The CLEAR Aspiration System is a digital vacuum aspiration system that allows operators to employ uniform suction or cyclical suction patterns. The pump can be optionally operated via an iPad app, which also collects system of care chronology such as time metrics in the stroke chain of survival, as well as key angiosuite metrics such as expand Thrombolysis in Cerebral Infarction (eTICI) outcomes.

“Cyclical aspiration was used as primary therapy for the first patient resulting in first pass eTICI 3 outcome (complete vessel re-opening) within six minutes. The first patient had a blood clot resulting in a large vessel occlusion in the M1 segment of the middle cerebral artery and had a witnessed stroke onset in the early time window. The second patient had a blood clot in the posterior circulation in the basilar artery with extremely tortuous vessels and had an unknown time of stroke onset as she woke up with stroke symptoms. Cyclical aspiration was used successfully in conjunction with stent retriever technology for removing the entirety of the clot,” added Kalousek.

“Our aspiration technology offers the ability to vary the vacuum suction pressures and intervals within the safe vacuum suction range up to -98.2kPa (-29inHg) with the explicit goal of increasing first-pass recanalisation, reducing vessel vasospasm and resulting clot fragmentation compared to static aspiration (namely uniform suction pressure),” said Vikram Janardhan, chief executive officer of Insera Therapeutics.

LimFlow stent

LimFlow receives FDA approval for US study of minimally-invasive technology designed to prevent amputations in CLTI patients

LimFlow has announced that the US Food and Drug Administration (FDA) has approved its investigational device exemption (IDE) for the PROMISE II pivotal study of the LimFlow Percutaneous Deep Vein Arterialisation (pDVA) System.

PROMISE II is a multicentre, prospective, single-arm study to be conducted in the USA and Japan. Using an adaptive statistical design, the study plans to enrol 60 to 120 “no option” chronic limb-threatening ischaemia (CLTI) patients. Endpoints include amputation-free survival at six months, limb salvage and wound healing, and subjects will be followed out to three years. The “no option” patients who are candidates for the PROMISE II study are no longer eligible for conventional endovascular or surgical therapy for CLTI, as determined by an independent physician committee.

The approval to initiate the pivotal trial follows the completion of sixmonth follow-up of the US early feasibility study—PROMISE I—that successfully enrolled 32 patients at seven centres. Interim outcomes from the first 10 patients treated in the PROMISE I study showed nine patients surviving and amputation-free at one year, with seven of these patients experiencing complete wound healing.

These results were presented in May at the New Cardiovascular Horizons Conference by Steve Henao, of the New Mexico Heart Institute. The complete results of PROMISE I will be presented during the Late Breaking Trials Session at the VIVA conference in Las Vegas, USA (4–7 November).

“For these late-stage CLTI patients, success can be defined in two ways: wound healing and amputation-free survival. This exciting new therapy has the potential to restore blood flow to the ischaemic foot, which may help patients heal their wounds and keep their feet. I am very encouraged by the early experiences in the USA, and outcomes from this pivotal trial may offer hope to the many Americans who might otherwise face major amputations,” said Daniel Clair, PROMISE II principal investigator and chair of the department of surgery at the University of South Carolina (USC) and Palmetto HealthUSC Medical Group.

“Major amputations have a devastating effect on the lives of patients and their families, and each one is a personal tragedy. CLTI is a public health crisis and far too many limb amputations are performed in the world today, costing the healthcare system many billions of dollars,” said LimFlow CEO Dan Rose. “As part of the FDA

Breakthrough Devices program, LimFlow is excited to commence its US pivotal trial on the heels of the successful experience from the US feasibility study. This is a tremendous milestone that furthers our mission of empowering vascular specialists to offer new hope to their CLTI patients who may be only days away from losing a limb.”

CLTI is the most severe form of PAD and often occurs in patients suffering from coronary artery disease, diabetes, obesity, high cholesterol and high blood pressure, many of which are growing health problems. Patients with CLTI often experience profound, chronic pain and develop festering wounds or infections that lead to major limb amputation, an event closely associated with increased mortality and reduced quality of life. To relieve the symptoms of CLTI, patients today are treated primarily with angioplasty or open bypass surgery. In many late-stage patients, however, neither option is feasible due to extensive disease in the target arteries or other anatomical constraints.

Orchestra BioMed announce FDA breakthrough device designation for Virtue sirolimus-eluting balloon

Virtue (Orchestra BioMed)

Orchestra BioMed, in partnership with Terumo Corporation, today announced that the company has secured breakthrough device designation by the US Food and Drug Administration (FDA) for its Virtue sirolimus-eluting balloon (SEB) in the treatment of belowthe-knee (BTK) peripheral arterial disease.

According to a press release, Virtue SEB is a novel, first-in-class drug/device combination product that delivers a sustained-release sirolimus formulation directly to the artery during balloon angioplasty, without the need for a coating.

“Virtue SEB’s unique design enables delivery of sustained-release sirolimus during angioplasty without the need for coating or permanent implant. This highly differentiated design makes this product the ideal candidate for Breakthrough Device Designation in BTK peripheral artery disease,” says James P Zidar, clinical professor of medicine, UNC Health Systems, physician-in-chief, Heart & Vascular Corporate.

He continues: “Currently, there is a significant unmet need in the BTK stenosis treatment landscape. The presence of underlying comorbidities renders many patients unsuitable for bypass surgery. Angioplasty with plain balloons, which has been the default

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endovascular therapy for years, has a low success rate. Adding a proven anti-restenotic agent like sirolimus has the potential to enhance this treatment approach and drive better patient outcomes.”

“Our team is grateful that the FDA has recognised the potential value Virtue SEB can provide patients and physicians by granting this second Breakthrough Device Designation for an important arterial therapeutic indication,” said Darren R Sherman, president, chief operating officer and co-founder of Orchestra BioMed. “This designation will be critical as we continue to work with Terumo to accelerate Virtue SEB’s global clinical and regulatory program in both coronary and peripheral indications. In BTK disease, treatment with Virtue SEB has the potential to improve long-term outcomes and reduce periprocedural complications which can extend hospital stay and increase cost of treatment.”

FDA clears Artis icono family of angiography systems from Siemens Healthineers

The US Food and Drug Administration (FDA) has cleared the Artis icono, a family of angiography systems from Siemens Healthineers that permit a range of minimally invasive procedures to be performed in a single interventional suite.

The Artis icono biplane system is engineered for optimal utilisation in neuroradiology and abdominal imaging, while the Artis icono floor is a floor-mounted, single-plane system for vascular, interventional cardiology, surgical, and oncology procedures. Both systems in the Artis icono family expand the reach of precision medicine.

At its core, the Artis icono platform delivers the new OPTIQ image chain, which fundamentally redesigns image processing for 2D imaging. OPTIQ increases image quality across a wide range of C-arm angles and patient weights, regulating acquisition parameters to automatically achieve optimal image contrast at patient radiation doses that conform to the As Low As Reasonably Achievable (ALARA) guiding principal for radiation safety. The platform also improves the Siemens Healthineers roadmap function, which creates subtracted angiography images for easier navigation of the patient’s vascular system during subsequent fluoroscopy, allowing dose reduction during the fluoro mode.

Additionally, the Artis icono platform significantly enhances ease of use through Case Flows, which provide personalised workflow plans to optimise

Artis Icono (Siemens Healthineers)

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November 2019 | Issue 84

Market watch

Product News

Revolution (Rex Medical)

imaging parameters and system positions, in addition to displaying layouts for the entire procedure. Case Flows adapt to user needs, providing flexibility when executing certain sequences. Users can therefore standardise procedures across multiple Artis icono labs for improved outcomes and more consistent documentation.

Rex Medical receives 510k clearance for Revolution Peripheral Atherectomy System

Rex Medical recently announced that it has received 510k clearance from the US Food and Drug Administration (FDA) for the Revolution Peripheral Atherectomy System.

Regulatory clearance was based on data provided by the REVEAL investigational device exemption (IDE) clinical trial. The results of this pivotal trial demonstrated the safety and effectiveness of the Revolution Peripheral Atherectomy System for lower extremity peripheral arterial revascularisation in 121 subjects with femoropopliteal/tibial occlusive disease.

The trial met prespecified primary and secondary safety and effectiveness endpoints.

The Revolution device is indicated for atherectomy of the peripheral vasculature and to break apart and remove thrombus from the peripheral arteries in patients with occlusive atherosclerotic disease.

According to a press release, the Rex Medical Revolution Peripheral Atherectomy System is an innovative and ergonomically designed low profile rotational atherectomy system (140,000 RPM) with continuous mechanical aspiration for below-the-knee (BTK) and above-the-knee (ATK) applications, including multiple plaque morphologies ranging from thrombus and soft plaque to severely calcified lesions and chronic total occlusions (CTOs). This device is operated by a 72-watt power supply, similar in size to a laptop computer charger, and requires no capital equipment and minimal setup time prior

to use.

Jeffrey G Carr, Tyler Cardiac and Endovascular Center, served as the study’s principal investigator and stated, “The recent clearance of Revolution technology will assist the interventional community in the effective reduction of calcification and vessel preparation in multiple lesion morphologies prior to adjunctive therapy, utilising percutaneous transluminal angioplasty (PTA), drug-coated balloons, and stenting. Continuous mechanical aspiration to reduce the potential for distal embolisation is a distinct advantage associated with this technology. Intraprocedural embolisation continues to be a key concern for many atherectomy procedures.”

Piur Imaging launches wireless tomographic ultrasound system

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

Infinity (Piur Imaging)

It consists of a small video box that connects to the video output of third-party ultrasound scanners, and a patented sensor-based tracking unit that attaches to any linear probe. Both units connect wirelessly to a standard laptop to transmit real-time 2D ultrasound images and information about transducer movement. An AI-based reconstruction algorithm turns this information into ultrasound volumes that can be analysed, stored, and shared, similar to CT or MR scans.

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

Non-vascular applications include thyroid and nerve imaging.

The device can be ordered on a subscription-base for a few hundred euros a month and is available in Europe as of now.

Beacon Tip catheters available in Europe again

Beacon Tip catheters (Cook Medical) are once again available to physicians in Europe. As of September 2019, the catheters are available in the UK, Ireland, Norway, Sweden, Finland, Denmark, Germany, Poland, the Netherlands, Luxembourg, Belgium, France, Switzerland, Austria, Hungary, Spain, and Italy. Cook is continuing to work on releasing the products to customers in the rest of Europe, the Middle East and Africa in the near future.

“Patient safety is always a priority for us, and we are proud of the changes we have made. Improved packaging allows for physicians to once again have access to catheters, designed for torqueability, visibility and pushability, to improve procedural outcomes”, said Mike Williams, global director of Cook Medical’s Vascular programmes. Beacon Tip catheters are used for diagnostic angiographic procedures and feature a visible distal tip designed to improve visualisation when using fluoroscopic guidance.

In 2016, Cook Medical issued a voluntary global recall of all Beacon Tip catheters following concerns that the tips were fracturing due to environmental factors. As patient safety is always a priority, engineers at Cook began intensive testing to find a solution. The products now come with specialised foil packaging to help protect the catheters from the environmental effects that contributed to the recall.

Cook invested resources into innovating the product packaging and meeting regulatory standards from multiple governing bodies. The catheters were reintroduced in the USA and Canada in 2018 and are now approved for physician use in many countries in Europe.

MagicTouch AVF sirolimuscoated balloon granted breakthrough device designation for use in dialysis access

Concept Medical has been granted breakthrough device designation from the US Food and Drug Administration (FDA) for MagicTouch AVF, its sirolimus drug-coated balloon (DCB) catheter, for the treatment of stenotic lesions of arteriovenous fistulae or arteriovenous graft in haemodialysis treatment of renal failure.

The FDA received a request from Concept Medical to designate MagicTouch AVF as a breakthrough device in July 2019. The proposed indications for the breakthrough

device designation for the MagicTouch sirolimus-coated balloon catheter is indicated for use in percutaneous transluminal angioplasty (PTA), after appropriate vessel preparation for treatment of stenotic lesions of dysfunctional native arteriovenous dialysis fistula or graft with 4–12 mm diameter and up to 100mm in length.”

On 28 August, Concept Medical was 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 world’s first pilot study to investigate the safety and efficacy of Magic Touch percutaneous transluminal angioplasty (PTA) sirolimus balloon, in vascular access interventions, was started in Singapore in 2018. Led by principal investigator, Tan Chieh Suai, a multi-disciplinary team of doctors consisting of interventional nephrologists, vascular surgeons and interventional radiologists, is conducting the study entitled “Sirolimus coated angioplasty balloon in the salvage of thrombosed arteriovenous graft” in Singapore General Hospital.

In response to the breakthrough designation for Magic Touch AVF, adjunct assistant professor Tan Chieh Suai, senior consultant and director for the Interventional Nephrology Program in the Department of Renal Medicine in Singapore General Hospital and DukeNUS Medical School, said, “The award of the breakthrough device designation for the use of sirolimus-coated balloons in dialysis access is fantastic news for patients on haemodialysis, as there is an urgent need for effective and durable treatment for narrowing (stenosis) within the dialysis circuit.”

Tjun Yip Tang, associate professor and consultant vascular and endovascular surgeon, Singapore General Hospital, Singapore has highly appreciated the success of Concept Medical and said, “We are still in the early stage in the clinical study of drug-coated balloons for haemodialysis access patients. The paclitaxelbased technology study results have certainly been encouraging, but more research is required to determine if other devices may prove to be more effective or uniquely beneficial for specific anatomical or clinical subtype presentations.”

The breakthrough device designation granted to Magic Touch AVF offers Concept Medical an opportunity to interact with the FDA’s experts.

Under the programme, the FDA will provide Concept Medical with priority review and interactive communication regarding device development and clinical trial protocols through to commercialisation decisions.

Luminor DCB now reimbursed in France

It was recently announced that luminor 18 and luminor 35 DCBs (iVascular), are now listed on the French LPPR list for de novo lesions of the femoropopliteal arteries.

Issue 84 | November 2019

Market watch

Product News Luminor is a paclitaxel-coated balloon specifically designed for dilatation of stenosis located in the iliac, femoral, iliofemoral, popliteal, infrapopliteal and renal arteries, as well as for the treatment of obstructive lesions of arteriovenous fistulas, whether original or artificial.

Eric Ducasse (CHU Bordeaux, Vascular Surgery Unit, France) has been one of the first Luminor user in France: “Luminor is the first paclitaxel DCB reimbursed in France since the Katsanos’s publication. It underlines that French authorities do trust its last generation coating technology, which is unique and has demonstrated efficacy, and above all, safety. I am confident that French use and data analysis will confirm it shortly.”

The latest EFFPAC trial 2-year outcomes with Luminor, have shown outstanding results in terms of primary patency (90.2%) and freedom from TLR (97.2%) in the superficial femoral artery and popliteal artery for TASC A and B lesions. This trial is also showing no increased risk of death detected at two-years, (one death in the DCB group versus two deaths in the POBA group), evidencing a relative risk (RR) of 0.48. Ulf Teichgräber (University of Jena, Germany) and Koen Deloose (AZ

St Blasius, Dendermonde, Belgium), discussed the latest data during the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).

According to a press release, he unique iVascular proprietary coating nanotechnology, TransferTech, differentiates Luminor DCB. It uses the paclitaxel in a microcrystalline molecular structure, that is spread on the balloon together with the excipient, by ultrasound spray pulse.

In addition, the balloon surface is covered with multiple and independent nanodrops layers, providing a flexible coating that adapts to the balloon movement and ensure paclitaxel to be released in the target lesion without particle loss in the blood flow.

TORUS SFA stent graft pivotal study granted unconditional IDE approval

PQ Bypass recently announced it has received full approval of its investigational device exemption (IDE) trial of the company’s TORUS stent graft, a novel stent graft platform designed for the treatment of peripheral artery disease (PAD) in the superficial

femoral artery (SFA).

By acquiring early US Food and Drug Administration (FDA) feedback through the pre-submission process, the TORUS-2 study (The PQ Bypass pivOtal IDE intra-aRterial stent graft study for occlUsive and re-Stenotic fem-pop revascularisation) is the company’s second IDE approved in less than two years and is the first pivotal IDE for an SFA stent graft since Viabahn received initial PMA approval in 2005.

The TORUS-2 IDE approval comes close on the heels of the approval for the DETOUR-2 trial. Having been exposed to the TORUS stent graft in the context of the DETOUR procedure, increasing demand is being vocalised to get this same stent graft studied for its

Torus stent graft (PQ Bypass)

safety and efficacy within the SFA as an intra-arterial stent graft.

“We have developed a robust technology, which is currently being studied in our DETOUR-2 percutaneous bypass IDE,” said Heather Simonsen, senior vice president and general manager of PQ Bypass. “Now we are expanding our focus to also address SFA

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lesions earlier in the disease process to target a market that currently has only one entry.”

PAD, left under- or untreated, can deteriorate the body’s vascular system to the point of rest pain, amputation, and even death. Current therapies, such as balloon angioplasty, atherectomy, and bare metal stents, frequently do not provide satisfactory long-term patency and will often require cyclical re-treatment. Stent grafts, unlike bare metal stents, aid in halting the progression of PAD, rather than solely treating the symptoms and allowing the disease to advance.

“This is an incredible win, on the part of every member of the PQ Bypass family,” continues Rich Ferrari, CEO and chairman of the board. “It really speaks to the quality of the work we have done as a company, both internally and in our clinical trials, as well as the TORUS stent graft itself. All of us at PQ are excited about running two pivotal IDE studies that are aiming to provide treatment for such a large and underserved population.”

The company will begin enrolling in the prospective, single-arm, global multicentre study in Q4 of 2019. The study has been approved to enrol up to 188 subjects at up to 40 sites. The TORUS stent graft received CE mark as a part of the DETOUR procedure in 2017.

The TORUS stent graft is limited by federal law to investigational use only and is not available for sale in the USA.

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November 2019 | Issue 84

Market watch

Industry News

Laser technology

AngioDynamics acquires Eximo Medical and its 355nm laser atherectomy technology

According to a press release, AngioDynamics has acquired Eximo Medical and its proprietary 355nm wavelength laser-technology platform for US$46 million in upfront consideration with up to US$20 million of contingent consideration related to certain technical and revenue milestones. The transaction is being funded exclusively through the use of cash on hand.

This transaction expands AngioDynamics’ existing Vascular Interventions and Therapies (VIT) product portfolio by adding Eximo’s proprietary laser technology, which has received 510(k) clearance for use in the treatment of peripheral artery disease (PAD). The Eximo technology complements AngioDynamics’ leading thrombus management and venous insufficiency technologies.

“The acquisition of Eximo brings a remarkable, foundational technology to our portfolio that will change the way caregivers deliver treatment to patients with PAD,” said Jim Clemmer, president and chief executive officer of AngioDynamics. “The market is ripe for disruption, and the level of precision, safety, and efficiency offered to physicians by this laser technology creates a substantially differentiated alternative to legacy atherectomy devices.”

Physicians provide atherectomy treatment to over 200,000 Americans annually, and Eximo’s laser technology represents a technological breakthrough among medical devices used in atherectomy procedures to treat PAD today. In acquiring Eximo and its laser technology, AngioDynamics enters a growing US$500+ million market with an innovative medical solution that offers greater versatility, a wider range of treatments, and strong clinical data to support its efficacy.

Differentiated from other legacy medical devices, Eximo’s laser technology is the only system capable of delivering short, high-powered pulsedlaser energy in 355nm wavelength without compromising the integrity of

its fibre optic cables during atherectomy procedures. The technology addresses the risk of perforation through tissue selectivity, addresses the risk of embolisation to the patient through the availability of aspiration and is indicated to provide treatment for InStent Restenosis (ISR), which is the gradual re-narrowing of the artery after a blockage has been previously treated with a stent.

Additionally, Eximo’s laser technology advances patient treatment options and care by treating a variety of PAD lesion types both above- and below-the-knee. The technology is a safe, fast, and effective system that clinical studies have shown to be effective in treating lesions ranging from soft plaque to severely calcified.

“We are very happy to join AngioDynamics”, said Yoel Zabar, chief executive officer of Eximo Medica. “We believe that AngioDynamics’ existing resources and commercial acumen will enable a large number of patients to benefit from Eximo’s laser technology, and we look forward to extending its utility into other indications within vascular and elsewhere. We would also like to thank the number of physicians that have already partnered with us during our journey, and we look forward to continuing our work together as we expand our physician base.”

Pulsar stent (Biotronik)

Proximo Medical named commercialisation partner for Biotronik’s PVI portfolio in select US markets According to a press release, Proximo Medical has been announced as the commercial partner for Biotronik’s peripheral vascular intervention (PVI) platform in select US markets.

Proximo Medical is a fractional commercial organisation for startup medical device technologies and established medical device companies looking to expand adoption on select products in the US market.

Biotronik’s PVI portfolio is designed for the treatment of peripheral artery disease and includes the Pulsar stent, which is the only 4-French (4F) selfexpanding stent approved in the USA.

Additional products include the Astron stent system, Passeo PTA balloon catheters and Fortress introducer sheaths.

“By partnering Biotronik’s solutions and innovations with Proximo, we accelerate our ability to help physicians deliver improved outcomes to patients,” states Ryan Walters, president, Biotronik. “At Biotronik, our focus is always on innovation that improves patient lives. We know millions of Americans suffer from peripheral artery disease and this partnership will help ensure this patient population has access to safe and effective treatment options.”

“I was an investigator in the trial of the Biotronik Pulsar stent,” states Craig Walker, president and medical director, Cardiovascular Institute of the South; clinical professor of Medicine, Tulane University and Louisiana State University Medical Schools; and chairman, New Cardiovascular Horizons. “I was impressed that this stent, which has a 4F delivery system, was easy to deploy accurately and had good clinical patency. I think this will be very helpful particularly in cases where standard 5F or 6F sheaths may be occlusive.”

CryoLife enters into strategic distribution agreement with Endospan

According to a press release, Cryolife has entered into strategic distribution and credit facility agreements with Endospan. Under the terms of the agreement, CryoLife will have exclusive European distribution rights to Nexus, the first off-the-shelf endovascular stent graft system approved for the repair of both aneurysms and dissections in the aortic arch.

CryoLife will pay a total upfront payment of US$10 million. Additionally, CryoLife will provide up to US$15 million in debt financing to Endospan subject to progress on the US clinical development program for the Nexus Stent Graft System.

Minimally invasive techniques are standard-of-care for treating descending aortic disease and heart disease, but highly invasive, highmortality open surgery is still being used in the difficult-to-treat aortic arch anatomy. The Nexus Stent Graft System is uniquely engineered to address this significant area of unmet and

Nexus stent graft system

underserved clinical need. The European market for the treatment of aortic arch disease including aneurysms and dissections is approximately US$150 million annually.

Nicolas Doll, Sana Cardiac Surgery, Stuttgart, Germany, commented, “NEXUS is a highly differentiated stent graft system that allows physicians to repair aneurysms and dissections in the aortic arch through an endovascular approach. NEXUS is especially important for elderly patients who are not suited for open surgery, and for patients with a prior Type A dissection that was repaired in an open surgical approach.”

Omar Ishrak to step down as Medtronic CEO next year

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

The Board of Directors has unanimously appointed Geoff Martha, currently executive vice president (EVP) of the company’s Restorative Therapies Group (RTG), to assume the newly created role of Medtronic president and become a member of the Medtronic Board of Directors, effective 1 November 2019. He will also succeed Ishrak as Medtronic CEO, effective 27 April 2020. As president, according to the press release, Martha will lead Medtronic’s operating groups and regions. Brett Wall, president of Medtronic’s Brain Therapies division, was appointed EVP and group president of RTG, succeeding Martha, effective 1 November 2019.

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

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

Ishrak comments: “We have announced leadership changes that meet both the Board’s objective of executing a thoughtful leadership transition, as well as my personal desire to begin transitioning my duties as CEO to a new leader coinciding with the start of our next fiscal year. This plan and its timing enable Geoff and I to partner on achieving Medtronic’s key financial performance goals as well as delivering on our critical pipeline milestones, including several important product launches. Leading Medtronic as CEO is an honour and a privilege, and I know that Geoff is the right leader to take Medtronic to the

Issue 84 | November 2019

Market watch

Product Industry News

Omar Ishrak

next level of its growth and evolution.

Geoff is a results-oriented, dynamic, and innovative business leader who is passionately committed to our mission, the advancement of our growth strategy and the development and diversity of our people. I am confident he has the right track record, commitment, vision and judgment to lead our company.”

Scott Donnelly, Medtronic’s lead director, and chairman, president and CEO of Textron, says: “As Omar approaches the company’s mandatory executive officer retirement of 65 years of age next year, we have ensured Medtronic has the right leadership at

the right time to advance its mission and deliver shareholder return through a seamless transition. The Board is extremely grateful to Omar for his outstanding leadership—as the company’s annual revenues have doubled and its market capitalisation has increased by more than US$100 billion during his tenure. We are confident Omar’s contributions to Medtronic will continue as executive chairman. The Board’s succession planning process prioritises developing leaders from within the company, and we are pleased that we could advance Geoff and Brett for these roles. During his time at Medtronic, Geoff has demonstrated his unique ability to lead, innovate and drive results, and the Board has full confidence in him and his ability to take Medtronic into its next chapter of growth.”

Admedus sells CardioCel and VacsuCel to focus on TAVI

Admedus has sold the distribution rights to its CardioCel and VascuCel product range for A$36.2 million to US-based LeMaitre Vascular. A press release from Admedus announces that it will focus on advancing its transcatheter aortic valve implantation (TAVI) programme and other potential products.

LeMaitre is a global provider of implants and devices for the treatment of peripheral vascular diseases. CardioCel and VascuCel are regenerative bioscaffold platform technologies used for cardiovascular procedures and repairs. Surgeons use CardioCel products to treat congenital heart defects, vessel and cardiovascular repairs, and peripheral vascular reconstruction. Admedus points out that CardioCel product range is the only one to have achieved 10 years without calcification or degradation in man, a significant benefit to patients otherwise forced to undergo recurrent operations. VascuCel is used as a patch in great vessel repair, peripheral vascular reconstruction, and suture line buttressing.

The deal consists of an A$22.8 million upfront payment, plus two instalments of A$1m each after 12 and 36 months.

Subject to the achievement of certain milestones, there will also be earnout payments of up to A$11.4 million, for a total of A$36.2 million (at the current US$0.67/A$1 rate).

The statement from Admedus also outlines that it retains manufacturing rights for up to three years and will continue manufacturing CardioCel and VascuCel at its facility in Western Australia for LeMaitre. The manufacturing agreement ensures Admedus a 20% margin over cost.

Admedus also retains sole-control on all intellectual property for the underlying ADAPT technology platform/process,

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including its breakthrough TAVI device and single-piece 3D aortic valve.

Wayne Paterson, Admedus’ chief executive officer, said: “This transaction is a transformational milestone for Admedus, realising the value from its CardioCel and VascuCel products.

Importantly, the deal firmly positions the Company for its next growth phase anchored by its groundbreaking TAVI programme. This is what management set-out to achieve for shareholders two years ago. The partnership strategy was possible only after we built a credible product profile over the past two years.

LeMaitre’s sales infrastructure and scale will propel the clinical credibility and brand profile Admedus has already established for CardioCel and VascuCel. We anticipate LeMaitre’s channel will successfully expand the adoption of these products,” He adds: “Admedus plans its firstin-human studies for its single-piece 3D aortic valve in 2020. Based on Admedus’ current laboratory and animal study findings—combined with the highly differentiated anti-calcification properties of all products generated using the ADAPT technology—there is potential for single-piece 3D aortic valve and TAVI devices to be a breakthrough for patients.”

Deborah Heart and Lung Center announces affiliation with Cleveland Clinic Heart and Vascular Institute Deborah Heart and Lung Center is

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November 2019 | Issue 84

Events

Calendar of events 4–7 November VIVA 2019 Las Vegas, USA

4–6 December 9th Munich Vascular Course Munich, Germany

www.vivaphysicians.org

www.mac-conference.com

23–25 January CACVS: Controversies and Updates in Vascular Surgery Paris, France www.cacvs.org

17–18 November EVTM: Endovascular Trauma Management Symposium Denver, USA

5 December Vascular Anomalies Special Interest Group London, UK

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19–23 November VEITHsymposium New York, USA

5–7 December Verve Symposium Sydney, Australia

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www.vervesymposium.com

21–23 February American Society of Diagnostic and Interventional Nephrology: ASDIN Las Vegas, USA

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

12–14 December 44th Annual Northwestern University Vascular Symposium Chicago, USA

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www.cme.northwestern.edu/conferences

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13–14 December CIV World Paris, France

25–26 March LINC Asia-Pacific Hong Kong

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

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22–24 March EVC: European Vascular Course Maastricht, The Netherlands

27 March SITE: International Symposium of Endovascular Therapeutics Barcelona, Spain www.sitesymposium.com

September

idelines scular gu g Global va limb-threatenin ic on chron Redefining a ia: ischaem ease critical dis

Limbof Chronic work Management es on the years of collaborative s and r Guidelin surgeon of four of having Global Vascula the product chronic limb- r The goal tion of the year sees the world. for patients with for Vascula The publica Ischaemia this ys s around the Society publication. The Threateningr experts and societie treatment pathwacement from r es’ of Vascula the guidelin by vasculato agree on the optimal ed in an announ fruition in European Journal describ come to the providers ischaemia was (JVS). journals: which has r Surgery societies’ threatening a “quixotic quest”, two of the the Journal of Vascula as Surgery was published in and (EJVES) document scular Surgery and Endova evaluation the definition, focuses on global patient he document ent of a large with mortality, and managem a disease associated particular and life. With population quality of practice, creating n, and impaired amputatio evidence-based as well as research, on guiding emphasis ks for treatment evidence or ed framewor standardis areas of low-levelperception of the insight into the overall providing stages of severity. and changing for spectrum and unmet needs, include a wider Conte from the Society disease to were Michael from the European from Kohl Co-editors Philippe Bradbury Vascular Surgery, Surgery and Andrew Nearly 60 Vascular Societies. ts Society for of Vascular Participan Federation on the project. specialties that the World worked all d authors additional and represente . continents n of spanned six tening ischaemia limb-threa to the publicatio treat chronic Vascular News prior Vascular Guidelines to Speaking “the Global for Vascular , Conte said and the guidelines effort from the Society Vascular Surgery all are a combined Society for who have European Societies, the Surgery, of Vascular the past.” In the effort Federation in the World nt guidelines guidelines, Conte independe ive joint produced that we set of collaborat important project we are to create a most very first and limb ischaemia—which said, “the .” was advanced tening ischaemia undertook chronic limb-threa now calling is in a name? used definition to CLTI: What From CLIterminology from the widely limb(CLI) to chronic of a key shift The shift in ischaemia limb of critical (CLTI) is indication this patient g ischaemia g and treating threatenin around lising, identifyin the terminology in conceptua changed . “We have population

T

2019 | Issue

83

en: Alan Lumsd

Profile

Page 26

Page 29

nted” “Unprecede t developmen ic of NICE aort guideline aneurysm

Institute N of the National guideline VERSIO THE DRAFT Care Excellence (NICE) on in and for consultati for Health when released that patients with ndation created a furore, be offered its recomme should only 2018, with d aneurysm able to undergo an unrupture if they were fit and providers open surgery, . Many surgeons, service guideline draft the procedure ers have called the n has been and stakehold and its publicatio “unimplementable” since then.

Board,” deferred the NICE repeatedly of the now sits with UK), president “The guideline (London, and Ireland says Ian Loftus for Great Britain nted. “There Vascular Societycalls this step unprecede re-wording who sides and (VSGBI), ise on both ,” he tells Vascular the must be comprom workable guidance closely with to make this that NICE is working .

News, noting progress the guideline onal Interventi ers to Society of stakehold in discussion the British VSGBI and together been of (BSIR) have cated the concerns of Radiology and communi a letter to members NICE In with g community. has been challengin set the vascular writes: “It is no date VSGBI, Loftus and at present there with NICE, for all concernedWe remain in touch help to find a n. to our for publicatio reiterated our desire Conte interests of Michael about the fact that [...] and have is in the best “to recognise solution that did raise our concerns and tening workable Conte said, “We limb-threa s NICE The He adds: constitute this problem,” s, with both scenarios. patients.” practice, what of the guideline in different it.” in current suggests that to change the wording may be different limb ischaemia were unable ischaemia below which of critical BSIR, but perfusion concept of is okay. value previous threshold which everyoneexpanding there is some and above the is critical, 4 diabetes and on page everyone is that with Continued realised we What

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21–24 April Charing Cross Symposium London, UK www.cxsymposium.com

17–20 June SVS Vascular Annual Meeting Toronto, Canada www.vascular.org