Interventional News Issue 80—November 2020

November 2020 | Issue 80

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Bart Dolmatch: AVeNEW study results

Profile: Adam Hatzidakis Trailblazing IR in Greece page 24

Catalysed by COVID-19, societies say hybrid conferences are here to stay

“2020 has changed so much. But the need for IO education remains the same.” Cued to music and set against a backdrop of footage from previous conferences, lone individuals on laptops, and graphics of the now instantly-recognisable SARS-CoV-19 virus, this is the text that appears on the promotional video for the Symposium on Clinical Interventional Oncology (CIO), which took place virtually for the first time ever this year, with sessions livestreamed on each Tuesday in October 2020. “Undeterred by setbacks,” it continues, “this is your year to learn differently. Meet differently. See IO… differently.” At the time of writing, CIO 2020 is the most recent conference in the interventional radiology (IR) space to deliver education and networking opportunities online. As interventional radiologists look ahead to 2021, Interventional News speaks with thought leaders from IR societies across the world to capture their reflections on how the COVID-19 pandemic is impacting medical education.

➜

➜

2 METRES

POSITIVES OF IN-PERSON MEETINGS

POSITIVES OF VIRTUAL MEETINGS

THE HYBRID

“I

do not think the pandemic is the end of the inperson meeting, rather the beginning of offering meetings accessible to all,” Erica Holland (USA), interim executive director of the Society of Interventional Radiology (SIR), says. “SIR’s meetings, especially the annual scientific meeting, always feel like a family reunion, and we are looking forward to reuniting with our IR family as soon as it is safe to do so.”

Originally slated to be an in-person meeting in Seattle, USA, on 28 March–2 April 2020, the SIR annual scientific meeting was amongst the first events to be cancelled due to the COVID-19 pandemic. Constantino Peña (Miami Cardiac & Vascular Institute, Miami, USA), SIR 2020 programme chair, tells this newspaper this was “a disappointment”: “The annual meeting committee had spent so many months planning the programme, the awards ceremonies, and the networking events, and was excited to share them with our peers. We knew many of the researchers were eager to share their science with their colleagues and hear the feedback that is so important to expanding their work.

“But we were confident at the time that we made the

right decision and that has been proven by how the spring unfolded. As a medical society, we knew we needed to lead by example during this public health emergency and ensure we were protecting our patients, colleagues, families, and communities by not creating a potential to spread the virus further. Interventional radiologists are data-driven, and the data we were presented at the time was unmistakable.

There was community spread in the Seattle area, then the

There are wonderful, unexpected benefits of virtual learning experiences, and there are also cherished, deeply missed aspects of in-person learning experiences.”

Continued on page 4

Early stage curative

Advanced stage

downstaging tumour

Radioembolization

GEST 2020: Y-90 in all HCC stages page 30

Portal vein embolization with NBCA promotes greter liver growth than PVA, BestFLR trial finds In a comparison of the regenerative capacity of portal vein embolization (PVE) before major hepatectomies with two different embolic materials, N-butyl-cyanoacrylate (NBCA) was shown to be superior to polyvinylalcohol (PVA) particles plus coils.

Speaking during the virtual European Conference of Interventional Oncology (ECIO; 4 November 2020, online), José Hugo Luz (Curry Cabral Hospital and Nova Medical School, Lisbon, Portugal) presented the results of the randomised, controlled BestFLR (Best future live remnants) trial.

LIVER REGENERATION STRATEGIES, such as PVE, are crucial in enabling patients to undergo major hepatectomies, Luz informed delegates. Contextualising the BestFLR trial, he went on to explain that PVE has gained acceptance as the standard of care for inducing liver growth in the last few decades. However, the optimal embolic material for PVE has not yet been established. “There are some suggestions in the literature that NBCA glue (Glubran, GEM) with Lipiodol (Guerbet) might generate more liver hypertrophy,” he said.

The BestFLR investigators therefore set out to determine which embolic material, NBCA-Lipiodol or PVA plus coils, produces the highest healthy liver growth during PVE. In order to be enrolled in the study, the future liver remnant (FLR)—the volume of healthy liver that will remain with the patient after surgery—had to be 25% or less of the total liver volume in healthy liver patients, 35% or less in colorectal patients, and 40 to 45% or less in patients with cirrhosis or cholestatic liver disease.

The 60 patients enrolled in the trial were randomly assigned to receive PVE with either NBCA-Lipiodol or PVA plus coils (30 in each group). Baseline characteristics, such as age, sex, comorbidities, weight, height, and presence of cirrhosis, were equivalent amongst the two cohorts. The most common tumour types included in the study were colorectal metastases (45%) an cholangiocarcinoma Continued on page 6

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November 2020 | Issue 80

Virtual conferences

Catalysed by COVID-19, societies say hybrid conferences are here to stay Continued from page 1

epicentre of America’s outbreak. There was a call from local officials, the Centers for Disease Control and Prevention [CDC] and the World Health Organisation [WHO] to limit social interactions and avoid large groups to stop the spread.

There was the information from our members telling us their institutions were limiting travel to flatten the curve and ready to respond to the inevitable outbreaks in their hometowns.

The team came together, and absorbed and analysed data quickly to make a correct and timely decision.”

The emergence of a post-pandemic hybrid model

The annual meeting of the Chinese College of Interventionalists (CCI), initially scheduled for April 2020, was postponed due to the pandemic. Whilst SIR 2020 took place as a fully virtual event 13–14 June, CCI 2020 was rescheduled for 27–30 August as a hybrid virtual/ in-person meeting in Nanjing, China.

“Although this new meeting mode brings a unique attendee experience for CCI meetings, it also presents a big challenge in terms of planning, in order to ensure audience satisfaction,” Gao-Jun Teng, CCI president, says, thinking back to the months of preparation that went into the 2020 event. Seven host venues were used in total; a “main” venue in Nanjing, and six “branch venues” across the country, which CCI say “were to let more IR professionals easily get involved”. In total, there were over 16,000 registered participants, who were able to access 153 scientific and workshop sessions, 796 lectures, and 76 live demonstrations of IR procedures.

“I am proud to conclude CCI 2020 a big success,” Teng told virtual and in-person attendees of the meeting’s closing ceremony, “and [declare] it a ‘sweet marriage’ between the virtual and physical meeting settings. Except for the completely online English-speaking sessions, almost all lectures were delivered in physical meeting rooms in Nanjing and the other six cities, while most audiences could just stay at home. This has no doubt brought attendees great convenience to participate with minimum travel and cost. Most importantly, it also broke territorial boundaries to allow more attendees to engage in and more citizens to appreciate this fairly new but strongly developing, medical specialty.” Indeed, following the strength of the hybrid model’s success at CCI 2020, the college is continuing with this format in 2021.

These boons of increased attendance and accessibility facilitated by the virtual meeting have been echoed by other IR societies. President of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Afshin Gangi (University Hospital of Strasbourg,

Strasbourg, France) weighs in: “While I do believe that the virtual model brought a lot to the table in terms of accessibility, I strongly believe that the major congresses will go back to an in-person format after the pandemic.

This, however, will not mean in-person only. We at CIRSE plan to also further develop a strong virtual component of our physical congresses; a hybrid model if you will.

Medical education in general will of course require both in-person courses and congresses, as well as online learning opportunities. I believe for IR in particular, it is vital for professionals to be able to physically come together to meet, discuss important data, and interact with the latest technology. Virtual-only will not be the future.”

Speaking on behalf of SIR, Holland muses: “One of the interesting benefits of being all virtual is the fact that it has allowed us to expand access to our offerings to our members. We often hear that attendance at the annual scientific meeting is staggered in practices to ensure coverage at the home institutions, meaning some interventional radiologists attending may not be able to stay for the whole meeting, if they are able to attend at all. That is not generally an issue for virtual meetings as you can log on when you are available and absorb the discussion and even watch it on demand later on, depending on the meeting.

“Post-pandemic, I think you will see a pent-up demand for meeting again in person. Networking and community are a huge part of SIR’s meetings and part of the value of an in-person meeting are the sidebar conversations that happen after a presentation or when you bump into colleagues on your way to plenary session or expo hall. Those are impossible to replicate in the virtual space.

“At the same time, not everyone will be ready or able to attend our events in person, so we may see a hybrid model emerge that live streams what is happening on site for those who cannot be there in person.

We may see a hybrid model emerge that live streams what is happening on site for those who cannot be there in person.”

“In addition, some of the virtual networking opportunities SIR created to fill the gaps while meeting sizes are still restricted, like our new virtual angio club series, are specifically designed to stay in the long term. Many of our members work in areas that do not have local angio clubs where they can regularly meet with their peers, learn, and exchange ideas. While SIR’s virtual club was born out of the necessity presented by the pandemic,

News in brief

The latest stories from the interventional world

n SAVER REGISTRY: “The SAVER registry reinforces the safety and effectiveness profile for the Stellarex drug-coated balloon (DCB; Philips) in a realworld patient population,” Konstantinos Stavroulakis (St Konstantinos Franziskus Hospital–Vascular Stavroulakis Surgery, Munich, Germany) told the live, online audience during the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).

For more on this story go to page 10. n CROSSFIRE TRIAL: Irreversible electroporation (IRE) significantly induces a window of reduced immune suppression two weeks post treatment, allowing the activation of effector T cells that seem to be correlated with improved survival, according to preliminary flow cytometry results of the CROSSFIRE trial presented during the 2020 CIRSE meeting.

For more on this story go to page 32. n HOW ABLATOIN IS TRANSFORMING CANCER CARE: Raul Uppot (Boston, USA) speaks to Interventional News about the evolution of liver ablation, from the first procedure in November 1986—where the hepatic tumour was injected with alcohol—to the potential of this treatment modality to offer systemic, curative cancer care, possibly even without inserting a single needle.

For more on this story go to page 37.

Raul Uppot

Continued on page 6

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November 2020 | Issue 80

IR around the world

Catalysed by COVID-19, societies say hybrid conferences are here to stay Continued from page 4

it uncovered an important, longstanding need in our community, and we are excited to have this series continue in the long term to support interventional radiologists in their practice no matter where they are.”

When asked if she believed the future of medical conferences would follow a virtual, live, or hybrid model, Jena Eberly Stack, executive director of Society of Interventional Oncology (SIO), commented: “This is the million-dollar question! While I do not have a crystal ball, I can say that there are wonderful, unexpected benefits of virtual learning experiences, and there are also cherished, deeply missed aspects of in-person learning experiences. I am sure we will see a mix of both once we are able to safely meet in person again, offering tailored opportunities based on the type of information and education being shared.”

Spring IR conferences confirm they will be online-only events

Unlike the annual scientific meetings originally scheduled in the springtime, CIRSE had several months to anticipate the possibility of hosting a virtual meeting, something Gangi says was “essential […] to ensure everything went smoothly online”. Commenting on the event, held 12–15 September 2020, he adds: “We received overwhelmingly positive feedback from our stakeholders regarding the high calibre of educational content, interactive learning, and networking opportunities, and first-rate organisation. While of course we missed the opportunity of physically meeting together as in previous years, the CIRSE 2020 Summit was able to ensure an equally high level of educational content with our top-notch faculty streaming in from around the world, giving over 1,000 presentations, and also provide ample networking opportunities through the interactive presentation formats and chat functions available at every level of the platform.”

In total, there were 18,000 active users on the CIRSE 2020 Summit platform, the society claim, with almost

Portal vein embolization with NBCA promotes greter liver growth than PVA, BestFLR trial finds Continued from page 1

(35%).

Detailing the embolization technique used by the triallists, Luz recounted: “We injected PVA particles of increasing size until [we reached] flow stasis, followed by proximal coils (6–12mm in diameter) to achieve complete venous occlusion”. For NBCA-Lipiodol glue, they injected a solution of different concentrations depending on the approach used: when injecting from the contralateral side, a 1:3 dilution was used, and when obtaining ipsilateral access to the liver, they used a 1:5 dilution through a microcatheter.

The primary outcome of the BestFLR

5,000 attendees from 115 different countries logging in and creating more than 20,000 chat messages over the course of the four live event days. While Gangi says these figures paint a positive picture of intra-conference communication, he adds this caveat: “I think the quality of interaction and collective creativity that is achievable online is not the same as we usually have at a physical congress. I therefore strongly hope that we will be able to meet again in-person at the CIRSE annual congress in 2021 in Lisbon, Portugal.” At the time of publication, this meeting is scheduled for 25–29 September 2021.

When questioned on his event expectations for 2021, Gangi said: “We are in the same spot as everyone else at the moment: waiting for a vaccine and hoping the situation will improve. While we hope and plan for in-person meetings, we are prepared to host the meetings in any format we can, and that might be online or in a hybrid format. One thing is certain—all CIRSE events in 2021, including the European Congress on Interventional Oncology (ECIO), the European Conference on Embolotherapy (ET), and the CIRSE annual scientific meeting will take place.”

Gearing up for SIO 2021, which will be held virtually 5–8 February 2021, Stack reflect on the 12 months’ experience the society has had to prepare for a potential online meeting (the society’s annual scientific meeting was one of the few IR congresses able to take place in person this year, 31 January–3 February 2020, New Orleans, USA). “The world certainly looks different today than it did a year ago, and our preparations for SIO 2021 reflect this shift in our landscape,” she says.

“We have held and observed several virtual events over the last seven months, and the learnings from those activities have provided feedback we are incorporating into our planning process for SIO 2021. Providing timely programming, valuable avenues to skill-build, and quality networking opportunities remain our commitment to our attendees, and we are achieving this through thoughtful programme development. SIO 2021 will be an interactive experience—not just a series of webinars—designed to mimic the best parts of an inperson event and capitalise on the unique opportunities a virtual event has to offer.”

SIR 2021 will also be held online. Peña assures readers that this “will be a completely different experience from any previous SIR meeting, including

trial was liver regeneration at 14 and 28 days after PVE, assessed by computed tomography (CT) volumetry. The specific endpoints measured were FLR degree of hypertrophy, FLR absolute hypertrophy, and kinetic growth rate (KGR). Secondary outcomes included the occurrence of post-hepatectomy liver failure, intraoperative incidents, blood loss, transfusions, surgery duration and hospital stay, PVE contrast volume used, fluoroscopy and total procedure time, as well as the rate of minor and major complications after PVE. All patients gave voluntary informed consent to participate in the trial, which is registered in a World Health Organisation (WHO) registry network.

Triallists encourage earlier assessment of patients for hepatectomy in light of positive results at 14 days post-embolization with NBCA-Lipiodol

After 14 and 28 days, all volumetric parameters were superior for PVE with NBCA-Lipiodol compared to PVE with PVA plus coils. PVE with NBCA-

the SIR 2020 virtual offering”. He elaborates: “Given the uncertainty of the landscape, the unique nature of our specialty, and the need for members to stay safe and healthy to deliver patient care, we decided to postpone the in-person portion of our programming now so that we have adequate time to plan for and deliver an all virtual format that provides the same cutting-edge, highquality programming that our members expect from the annual scientific meeting.

“Unlike SIR 2020’s virtual offering, which was deployed as a standard webinar platform, for 2021 we will replicate the feel of an in-person event as closely as possible through an interactive platform complete with meeting rooms, plenary sessions, an interactive expo hall, and on-demand offerings. We are also exploring

Delegates attending CCI 2020 in person

ways to deliver the important networking opportunities, committee meetings, and our awards ceremonies honouring those who have greatly contributed to the advance of the specialty. […] We are confident that SIR members will find this online learning experience a notto-be-missed event.”

Indeed, Holland believes the switch to all virtual education this year, which she says “is spurring SIR to move forward with a total reimagining” of their educational offerings, was actually already a part of the society’s strategic plan. “The pandemic has been a catalyst for us to take things down to the brass tacks and rebuild it anew in a way that is as agile as IR,” she surmises. The consensus amongst the international IR community is that conferences with at least a virtual component are here to stay.

Lipiodol yielded a greater absolute liver hypertrophy: 46.4% at 14 days versus 29.6% at 14 days post-embolization with PVA plus coils (p<0.001), and 57% at 28 days compared with 36.7% at 28 days for the PVE with coils group (p<0.001).

“An interesting finding that we had in this study is that many patients were ready for liver surgery after just 14 days,” Luz said. In the NBCA-Lipiodol

Many patients were ready for liver surgery after just 14 days. These data encourage us to assess patients earlier.” cohort, 87% of patients had a sufficient FLR ratio for surgery after 14 days. This was higher than amongst the PVA plus coils cohort, where 55% of patients were eligible for surgery after the same time period (p=0.008).

“These data encourage us to assess patients earlier,” Luz told the ECIO audience, “14 days after PVE if we are using NBCA-Lipiodol, which we are now following these trial results. This shorter waiting period enables patietnts to undergo curative hepatectomy, and might decrease tumour progression, which is the main cause of precluding liver surgery.”

Addressing patient outcomes, he shared that 24 patients (80%) in the NBCA-Lipiodol group underwent a successful hepatectomy after PVE, compared to 23 (76%) in the PVA plus coils group (p=0.32). Three patients in the NBCA-Lipiodol cohort (12%) and seven patients in the PVA plus coils cohort (27%) had clinically-relevant liver failure (p=0.27).

Fluoroscopy and total PVE time were also significantly lower for NBCALipiodol versus PVA plus coils (16 minutes vs. 25 minutes, p<0.001, and 60 minutes vs. 80 minutes, p=0.0023, respectively).

At the time of writing, the results of the BestFLR trial are under submission for publication.

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November 2020 | Issue 80

TCT highlights

Starting to close the door on the paclitaxel controversy: TCT latebreaking trials Findings from a series of late-breaking trials in the endovascular field were presented recently at TCT Connect (14–18 October, virtual), the 32nd annual scientific symposium of the Cardiovascular Research Foundation (CRF). Sahil A Parikh (Columbia University Medical Center, New York, USA) and Frank Veith (New York University Medical Center, New York, USA) moderated the session, with Marc Bonaca (University of Colorado, Aurora, USA) and Robert A Lookstein (Mount Sinai Health System, New York, USA) on the panel.

F

irst on the virtual podium was Connie N Hess (University of Colorado, Aurora, USA), who presented results of a large subgroup analysis of the VOYAGER PAD randomised clinical trial. This showed neither a mortality risk nor benefit associated with the use of paclitaxel drug-coated devices in the treatment of peripheral arterial disease (PAD). The study also found that the benefit of rivaroxaban use in reducing ischaemic limb and cardiovascular outcomes was consistent regardless of if a drug-coated device was used.

This analysis examined the long-term safety of drugcoated devices and evaluated whether rivaroxaban 2.5mg twice daily plus low dose aspirin versus low dose aspirin alone on the primary efficacy endpoint was consistent with versus without drug-coated device (DCD) use.

During the qualifying endovascular lower extremity revascularisation, a DCD was used for 31% (n=1,358) of patients. Patients receiving a DCD more frequently had prior endovascular lower extremity revascularisation, a higher baseline use of dual antiplatelet therapy and statins, and were more often treated for claudication than non-DCD patients.

In the unweighted analysis, lower associated mortality was observed among patients receiving DCD versus non-DCD (2.9 vs. 3.9 per 100 patient-years; 3.5year Kaplan-Meier cumulative incidence of 10.2% vs.13.8%). After weighting, there was no association between DCD use and mortality (3.5-year cumulative incidence 12.1% vs. 12.6%, HR 0.95, 95% CI 0.83– 1.09, p=0.49). The benefit of rivaroxaban 2.5mg twice daily with aspirin compared to aspirin alone in reducing ischaemic limb and cardiovascular outcomes was also consistent regardless of whether a DCD was used.

IN.PACT 0.014 DCB may offer a clinical benefit in patients with CLI

Antonio Micari (University of Messina, Messina, Italy) presented first-ever results from Medtronic’s IN.PACT BTK study, a feasibility study assessing the safety and effectiveness of the company’s IN.PACT 0.014 drugcoated balloon (DCB) in critical limb ischaemia (CLI) patients with chronic total occlusion in the infrapopliteal arteries. The IN.PACT BTK study is a prospective, multicentre, 1:1, randomised feasibility study assessing the safety and effectiveness of the IN.PACT 0.014 DCB, a 3.5 μg/mm2 dose paclitaxel-coated balloon, versus conventional percutaneous transluminal angioplasty (PTA) for the treatment of chronic total occlusions in the infrapopliteal arteries. The study enrolled 50 patients at nine sites in Europe.

At nine months, patients in the DCB group experienced a reduction in sub-segmental late lumen loss compared to those in the PTA control group (0.59±0.94mm vs. 1.26±0.81mm, respectively, p=0.017), a 53% lower late lumen loss than the PTA control group. Using the classic late lumen loss method, patients in the DCB group experienced lower late lumen loss compared to those in the PTA control group at nine months (0.89±0.77mm versus 1.31±0.72mm respectively, p=0.07 ), a 32% lower late lumen loss than the PTA control group.

Historically, there has not been a DCB technology that has demonstrated effectiveness in this vessel bed. According to a Medtronic press release, the data

presented at TCT demonstrate that IN.PACT 0.014 may offer a clinical benefit in patients with CLI.

ILLUMENATE Global: Four-year results support durable long-term outcomes with Stellarex DCB

Andrew Holden (Auckland City Hospital, Auckland, New Zealand) reported on late safety and efficacy outcomes for the low-dose Stellarex DCB (Philips) in de novo and restenotic femoropopliteal lesions.

He revealed that four-year data from the trial show favourable safety and efficacy outcomes consistent with the ILLUMENATE randomised controlled trials, and also demonstrate similar efficacy in prespecified cohorts including different gender groups and diabetics.

ILLUMENATE Global is a prospective, single-arm, multicentre study conducted in the EU. The patient population included those with Rutherford Clinical Classification of 2–4 indicated for treatment of the superficial femoral artery (SFA) and/or popliteal artery for de novo or restenotic lesions. Follow-up office visits were at one, six, 12, 24, and 36-months post-procedure

We are barely scratching the surface on drug-based delivery in the below the knee circulation.” and included clinical, haemodynamic, and functional outcomes.

At four years, the rate of major target limb amputation was 0.8% and that of all-cause mortality was 8.1%.

Clinically-driven target lesion revascularisation through four years was 75.6% at day 1,460 and the subgroup analysis revealed no difference in prespecified cohorts.

“The ILLUMENATE Global study supports durable long-term outcomes with the Stellarex DCB and is applicable to a complex population,” Holden said.

Bullfrog device shows promise in TANGO registry

Ehrin J Armstrong (UCHealth Heart and Vascular Center, Aurora, USA) presented results of the TANGO registry. This Phase 2 study aimed to assess the sixmonth efficacy and safety of the Bullfrog micro-infusion device (Mercator MedSystems) adventitial deposition of two escalating doses of temsirolimus in reducing angiographic neointimal hyperplasia and target lesion failure after revascularisation of below-the-knee arteries.

This prospective, multicentre, dose-escalation, comparative, double-blinded study enrolled 61 patients undergoing endovascular revascularisation of ≥1 angiographically significant BTK lesions. Treatment was applied after completion of artery revascularisation, and divided into control (saline; 0.25–0.5mL/cm of lesion length), low-dose temsirolimus (0.1mg/mL; 0.025– 0.05mg/cm of lesion length), or high-dose temsirolimus (0.4mg/mL; 0.1–0.2mg/cm of lesion length) groups in a dual-blinded, randomised fashion.

Primary and secondary efficacy endpoints were transverse-view vessel area loss percentage (TVAL%) of the target lesion and clinically relevant target lesion failure (CR-TLF) at six months, respectively.

The primary safety endpoint was freedom from a major adverse limb event or perioperative death (MALE+POD) at 30 days.

Armstrong reported that superior primary efficacy of the treatment arm was apparent in the per protocol (PP) and PP-TASC B–D (excluding 15 patients with TASC A lesions) subgroups, and that TVAL% reductions of 13.9% and 22.3% were seen in the PP and PP-TASC B–D subgroups at six months, respectively.

In addition, freedom from CR-TLF rates were substantially higher in those patients treated with temsirolimus, and differences between treatment and control for freedom from CR-TLF at six months were 27.1% and 39.2% in the PP and PP TASC B–D subgroups, respectively. Freedom from composite of 30day MALE+POD was 100% in all groups.

“Findings suggest that adventitial deposition of temsirolimus using the Bullfrog micro-infusion device improves six-month vessel patency when applied to BTK arteries after successful endovascular revascularisation,” Armstrong concluded.

FLASH registry: Acute haemodynamic improvement with percutaneous mechanical thrombectomy in a realworld pulmonary embolism population

Catalin Toma (University of Pittsburgh, Pittsburgh, USA) presented results from the FLASH registry.

FLASH is a 500-patient prospective, multicentre registry study designed to evaluate real-world outcomes after treatment of patients with intermediate and high risk PE with FlowTriever (Inari Medical).

Toma reported that mortality through 48 hours was 0% and that just three patients out of 320 (1.3%) experienced major adverse events—all of which were major bleeds.

Ablation of accessory renals might reduce blood pressure

Yu Sato (CVPath Institute, Gaithersburg, USA) spoke on the anatomy of the human accessory renal artery periarterial renal sympathetic nerve for renal denervation.

Sato began by detailing that accessory renal arteries have been reported in about 30% of patients. Some renal denervation clinical trials have excluded patients with accessory renal arteries, while others have included such patients but excluded those with accessory renal arteries less than 3/4mm in diameter. Moreover, some studies have suggested that renal denervation for accessory renal arteries may have an additional advantage of blood pressure reduction. The aim of this study was to evaluate the anatomic distribution of peri-arterial nerves in human accessory renal arteries.

Sato concluded that accessory renal arteries have twothirds the number of nerves as compared to dominant renal arteries, and that the number of nerves around the accessory renal arteries is dependent on renal artery size.

“Our results suggest that ablation of peri-arterial nerves in accessory renal arteries should result in an additional blood pressure reduction,” he remarked, adding that future renal denervation clinical trials should consider including ablation of peri-arterial nerves in accessory renal arteries.

Closing the door on the paclitaxel controversy

“I think we are really starting to close the door on the paclitaxel controversy,” Lookstein commented at the end of the session. “There is clearly a lot more work that needs to be done for paclitaxel below the knee and it is encouraging to see that there is going to be work on that. We are barely scratching the surface on drug-based delivery in the below the knee circulation, so there is a lot more work to do.”

Issue 80 | November 2020

IN.PACT Admiral DCB shows “significant advantage” over uncoated devices in fempop artery treatment analysis The IN.PACT Admiral drug-coated balloon (DCB; Medtronic) demonstrated a significant advantage in overall survival, amputation-free survival, and target-lesion revascularisation after femoropopliteal artery treatment through four-year follow-up when compared to uncoated balloons, a single-institution, retrospective review that tackled a head-to-head comparison between two discrete paclitaxel-coated devices found.

FURTHERMORE, THE LUTONIX balloon, angioplasty DCB (BD) showed a less clear advantage as a standalone in major outcomes compared to uncoated procedure and balloons. Meanwhile, between paclitaxel bare-metal stent balloons, the IN.PACT Admiral was found placement were more to be advantageous over Lutonix only in common. the arena of amputation-free survival.

The results The findings were delivered in a showed a four-year talk entitled “Clinical outcomes differ Alexander King survival rate of after femoropopliteal artery treatment 64.1% among those between individual paclitaxel-coated given the IN.PACT Admiral device, balloons”, presented by Alexander H 60.6% in patients treated with the Lutonix King (University Hospitals Cleveland DCB, and 51% in those who received an Medical Center, Cleveland, USA) during uncoated device. Rates of freedom from the Midwestern Vascular Surgical Society major amputation were 93.2% for the (MVSS) annual meeting (9–12 September, IN.PACT Admiral, 88.9% for the Lutonix, virtual), which selected the study as the and 85.8% for the uncoated group. winner of the Emerick Szilagyi Award for “Again, the IN.PACT Admiral showed clinical research. superiority over a non-coated balloon With three paclitaxel-coated balloons but there was not a significant difference currently approved for use by the US between the two DCBs,” noted King.

Food and Drug Administration (FDA), “Amputation-free survival showed King and colleagues at UH Cleveland differences across all balloon types,” set out to compare outcomes between the he continued. “IN.PACT showed rates two: “Available DCBs employ different of amputation-free survival of 64.3%, paclitaxel composition, dose, and Lutonix 57.5%, and non-coated 46.6%. excipient,” he explained. “DCBs decrease All three were significantly different from restenosis compared to uncoated balloons, each other on Kaplan Meier analysis.” but have not been compared to each In terms of freedom from target-lesion other. Our aim was to compare outcomes revascularisation, IN.PACT was found in patients treated with two discrete to have an advantage over non-coated DCBs”—further noting there has been no balloons. However, no differences prior head-to-head comparisons between between the two paclitaxel-coated paclitaxel-coated devices. balloons were observed. Four-year rates Some 1,419 patients who had were 75.4% for the IN.PACT Admiral, undergone femoropopliteal artery 72.3% for the Lutonix, and 71.5% for percutaneous revascularisation from non-coated devices.

2010–2019 were analysed to determine how use of the two devices impacts on Possible effects of adjunctive survival, amputation rates, and need for therapies “cannot be ruled reintervention. out” King detailed the investigation’s Study design limitations. “This study was limited by The patients were placed in one of three the retrospective, nonrandomisation of groups: 41.6% were treated with an the design,” he said. “Additionally, the uncoated balloon, with 58.4% receiving choice of balloon was left up to physician a DCB. Of the latter, 60.6% were discretion and may therefore be subject assigned the IN.PACT Admiral and to inherent biases. Paclitaxel was often 39.4% the Lutonix. Primary outcomes used in conjunction with other therapies. included all-cause mortality, freedom The possible effects of those adjunctive from major amputation, amputationtherapies cannot be ruled out.” free survival, and freedom from targetKing added that despite the noted lesion revascularisation, which were limitations, the research team was compared using Kaplan Meier analysis. able to conclude that individual DCBs Multivariable logistic progression was may not yield equivalent outcomes, also deployed. but that “through four-year follow-up, Furthermore, adjunctive stenting was the IN.PACT Admiral showed a clear used in 26% of patients, atherectomy in advantage over uncoated balloons, while 17%, and a combination of both in 3.6%, Lutonix had a less clear advantage.

King explained. In the paclitaxel group, Further studies are certainly needed atherectomy was more common, while to determine the ideal paclitaxel among those who received an uncoated composition, dose, and excipient.”

Drug-coated balloons

9

November 2020 | Issue 80

10 Peripheral interventions

First@CIRSE

Win for paclitaxel as SAVER registry “reinforces the safety profile” of Stellarex DCB “The SAVER registry reinforces the safety and effectiveness profile for the Stellarex drug-coated balloon (DCB; Philips) in a real-world patient population,” Konstantinos Stavroulakis (St Franziskus Hospital–Vascular Surgery, Munich, Germany) told the live, online audience during the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).

“THESE REAL-WORLD REGISTRY DATA provide important outcome information for healthcare providers for the debate on the safety of drug-eluting technology,” he opined. The Stellarex DCB is a low-dose (2µg/mm2) paclitaxel device, with proven effective drug tissue transfer and residency. Compared to competitors, it has limited drug loss, “a very important feature”, in Stavroulakis’ words.

SAVER stands for the Stellarex Vascular e-Registry, a multicentre, European registry with external monitoring and clinical event committee adjudication. Patients are followed up through to three years, and experience a 12-month visit. The aim of the SAVER registry is to assess the safety and efficacy of Stellarex DCB use in

Stefan Müller-Hülsbeck (L) and Konstantinos Stavroulakis during CIRSE 2020

the superficial femoral, popliteal, and/or infra-popliteal arteries in a broad, real-world patient population. The registry is split into two patient cohorts: claudicants, and chronic limb-threatening ischaemia (CLTI) patients.

In the claudicant group—Rutherford category 2–3— the primary safety endpoints were freedom from 30-day device- and procedure-related death, and freedom from 12-month target limb major amputation and clinicallydriven target lesion revascularisation (CD-TLR). The efficacy endpoint for claudicants was freedom from 12-month CD-TLR. In the CLTI group—Rutherford category 4–5—the primary safety endpoints were freedom from composite major adverse limb events and perioperative death through 30 days. The efficacy endpoint was freedom from six-month CD-TLR. An interim analysis of the first 1,000 claudicant patients revealed a procedural success rate of 97.9%, and a lesion success rate of 98.5%. “Bailout stenting was required in 24% of the patients, showing that we can treat the majority of these PAD [peripheral arterial disease] patients effectively, with no additional permanent scaffold,” Stavroulakis said.

There was a 0% periprocedural mortality, and “just” 0.6% significant distal embolization. Target vessel thrombosis was seen in 0.2% of the patient cohort, and emergent surgical revascularisation in 0.1%.

The majority of patients (87.4%; 892 of 1,021) reached the primary safety endpoint, with freedom

New prediction model for target lesion revascularisation grants “new level of security” to paclitaxel devices in the peripheral arteries “Please feel free to utilise this in your practice,” Michael Dake (University of Arizona Health Sciences, Tucson, USA) urged on the first day of the Cardiovascular and Interventional Radiological Society of Europe 2020 Symposium (CIRSE; 12–15 September, virtual). Speaking during a FIRST@CIRSE session, he presented a new, interactive, web-based tool built to predict patients’ freedom from target lesion revascularisation (TLR) following treatment with the Zilver PTX (Cook Medical) drug-eluting stent (DES).

DAKE AND COLLEAGUES USED patient and lesion factors from five global clinical studies from Cook Medical to develop a prediction model for freedom from target lesion revascularisation (TLR) following

use of the Zilver PTX DES. These clinical studies examined both premarket and post-market outcomes with the Zilver PTX stent in patients with femoropopliteal disease. In total, they collated data from 2,374 patients, and

from device- and procedure-related death through 30 days post-procedure, and freedom from target limb major amputation and CD-TLR through 12 months post-procedure. Giving additional outcomes at one-year, Stavroulakis told the CIRSE audience that all-cause death was 3.2%, and the amputation rate was 2.7%, with the major amputation rate 0.8%—“acceptable” outcomes in this real-world population.

Regarding the efficacy endpoint, 87.7% of patients had freedom from CD-TLR at 12-months postprocedure, a “robust” finding. Kaplan-Meier evaluation demonstrated 98.7% freedom from CD-TLR at 30 days, 95% at 180 days, and 88.6% at 365 days.

Recounting the additional secondary outcomes, Stavroulakis told registrants that the majority of patients (87.6%) improved by at least one Rutherford class; 8.9% had no change in Rutherford category, and 3.5% worsened from baseline. There was a significant improvement in walking capacity at 12 months, as measured via the six-minute walk test: at baseline, the mean distance a patient could walk during the test was 52±24.4m; by 12 months, this had risen to 169±123.7m.

Quality of life scores and the ankle-brachial index also improved from baseline to 12 months.

These results led Stavroulakis to conclude that there was a low rate of procedural complications when the Stellarex DCB was used in claudicants, and the device had a high safety profile.

included 15 risk factors in their creation of the model.

“It is noteworthy that over 50% of the patients included in the model had over five-year follow-up. In fact, this is the first prediction model to estimate the impact of patient and lesion characteristics on freedom from TLR through five years for patients with PAD [peripheral arterial disease],” Dake enthused. “Based on unique patient profiles, the model provides expected patient outcomes following treatment with the Zilver PTX DES, and may assist in defining algorithms for patients as the value of population management is increasingly recognised.”

Turning to the freedom from TLR results, Dake informed the CIRSE audience that 94% of the complete dataset (2,227 cases, with a median follow-up time of two years) was used to generate the model. Freedom from TLR was 90.5% at one-year, and 75.2% at five years.

Describing the model more closely,

Stefan Müller-Hülsbeck and Michael Dake during CIRSE 2020

Dake next related the 15 risk factors that were considered when the tool was under construction: sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, dexamethasone, popliteal involvement, total occlusion, calcification, prior interventions, and the number of patient runoff vessels. “Most all of these have been in the past implicated as being high risk for TLR in studies performed over the last two decades,” Dake disclosed.

Issue 80 | November 2020

Peripheral interventions 11

“No signal of increased risk of long-term mortality” with paclitaxel-coated Luminor DCB, EffPac trial finds

multiple comorbidities, which were hardly associated with the application of paclitaxel.” Patients in the plain balloon angioplasty cohort died of heart failure, sepsis, cholangiocarcinoma, respiratory failure, and suicide.

“A correlation between paclitaxel and cause of death is [therefore] quite unlikely,” Teichgräber concluded.

The total number of adverse events per patient was higher in the DCB group than in the plain balloon angioplasty group, though this difference was not statistically significant (3.2±2.8 vs. 2.9±2.6; p=0.59). The proportion of patients who experienced any adverse event was slightly higher in the plain angioplasty arm of the study, but again, this difference was not statistically significant (88.5% vs. 86.5%, respectively; p=0.81). “So there is no real difference in adverse events between both groups,” Teichgräber summarised. Except for serious malignancies, there were no significant between-group differences in the incidence of adverse event types.

Summing up, Teichgräber said: “I believe that such an ad hoc analysis on discontinued patients in randomised controlled trials gives us a full picture on all-cause mortality for our follow-up patients.

“As we do not have a class effect between different DCB products, with our ad hoc analysis we can only give information on Luminor balloons, and their coating technology. Therefore, it is important that other trials, with other DCB products, go the same way as we did with EffPac, and assess what happened to their lack-of-follow-up patients, and [see] if they could show equivalent results of all-cause mortality in their full cohort.”

An ad hoc, two-year analysis of the EffPac study found no signal of increased risk of long-term mortality, nor any adverse events, within two years of drug-coated balloon (DCB) angioplasty using a Luminor-35 device (iVascular). This was the conclusion presented by Ulf Teichgräber (University Hospital Jena, Jena, Germany) at the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual).

TEICHGRÄBER IS THE PRINCIPAL investigator of the EffPac trial, a prospective, randomised controlled trial initiated by the federal authorities in Germany, and conducted at eleven study sites, that compares the paclitaxel-coated Luminor balloon with plain balloon angioplasty in the femoropopliteal artery segment of patients with peripheral arterial disease (PAD).

The primary efficacy endpoint of this study was late lumen loss at six months; secondary endpoints included primary patency, freedom from target lesion revascularisation (TLR), Rutherford category, anklebrachial index, and quality of life score. All-cause mortality and target limb amputation were assessed as the primary safety endpoints.

Just published in Radiology, Teichgräber described how the investigators conducted an ad hoc, two-year review of mortality and morbidity following DCB angioplasty in EffPac patients. Two-year follow-up of the EffPac trial was in fact completed in February 2019, but another study cast its shadow over the results.

Konstantinos Katsanos (Patras, Greece) et al published a meta-analysis in the Journal of the American Heart Association (JAHA) in late 2018 that found an increased association between late mortality risk and paclitaxel use in the femoropopliteal arteries. “Numerous public debates about the safety of paclitaxel-coated balloons were triggered”, Teichgräber recalled.

This led the Federal Institute for Drug and Medical Devices in Germany (BfArM) to request a formal hearing on mortality of all ongoing studies concerning

He continued: “Risk factors common in PAD patients collectively contributed to overall prognosis. As expected, chronic limb-threatening ischaemia (CLTI), lesion length, and total occlusion have a significant impact on TLR. Other factors, such as diabetes and calcification, do not have a significant impact on TLR.” He then talked through three example patient profiles to illustrate how listening physicians could use this predictive model in their own practices. The risk factors any given patient may have are fed into the model, which then churns out

The model provides expected patient outcomes following treatment with the Zilver PTX DES.”

paclitaxel use in the peripheral arteries.

While the EffPac trial could not confirm a correlation between paclitaxel application and all-cause mortality—there was one death in the DCB arm, out of a total of 82 patients, and seven out of 85 in the plain angioplasty arm—a lot of patients were lost to follow-up.

In total, the EffPac trial randomised 171 patients into two arms: those treated with the Luminor DCB (85 patients), and those who received plain angioplasty (86 patients). At 24 months, 60 patients were left in the DCB group, and 56 in the plain angioplasty group, due to a lack of follow-up in nearly one third of randomised patients. This represented a discontinuation of 25 Ulf Teichgräber patients in the DCB arm, and 30 patients in the plain angioplasty arm.

Under entreaty from the BfArM, Teichgräber set out to find those EffPac participants lost to follow-up in order to gain further information on two-year mortality rates with paclitaxel devices.

“Paclitaxel showed a very low [mortality] risk ratio of only 0.15 compared to other trials, meaning there is no correlation of all-cause mortality associated with Luminor balloons,” Teichgräber said. “Another interesting aspect [to look at] is cause of death. The only case of death in the DCB group was due to

There is no correlation of allcause mortality associated with Luminor balloons.”

an estimation of the risk that patient has of maintaining freedom from TLR out to five years, with a standard error given, when treated with the Zilver PTX. These results also translate into a freedom from TLR Kaplan-Meier curve. The physician can then make an informed treatment decision based on individual risk factors.

and that there was an increased number of prior interventions in both the singlearm study and the Japan post-market study, as both these trials included instent restenosis. “Patients with in-stent restenosis were not allowed to enter the other trials,” he explained.

The baseline data

Praising Dake for these results, moderator Stefan Müller-Hülsbeck (Diako Hospital, Flensburg, Germany) commented: “I think you have shown once again that paclitaxel is probably safe, and we meet a new level of security when using these kinds of devices, especially when using this kind of predictability model.” He then asked Dake if the model is already in use, and if so, if he was using it for his patients during his daily practice.

“This is actually the first debut of this model and this website,” Dake responded. “The manuscript will be published in Cardiovascular and Interventional Radiology (CVIR).” He

Teasing apart the larger dataset to examine trends in baseline patient demographics, Dake said: “Looking a bit closer at some of these individual patient demographics, and how they are distributed within the various trials included in the analysis, you can see some differences. Of note, in the Japan post-market study, [there is] a very high frequency of renal disease, and a higher frequency of CLTI. In terms of diabetes, there was a high frequency in all studies, approaching 50%.”

Appraising the baseline lesion characteristics, Dake informed viewers that 42% of patients had total occlusions,

“This is the first step”

encouraged CIRSE attendees to visit the site themselves and “really get a sense of getting comfortable with how individual risk factors can affect TLR going out through five years”.

Referring to his presentation as the launch of this predictive model, Dake closed the discussion by postulating: “Maybe other device manufacturers will look at this as a model and adopt predictive models as a way to counsel patients and their families in the clinic regarding their individual risk factors, modification of those risk factors, and how we can predict what results might be with different devices. I think this is the first step. I think this is an outcropping of what we have seen as a result of the Katsanos paper [Konstantinos Katsanos (Patras, Greece) et al published a paper in late 2018 that suggested the existence of an increased mortality risk with paclitaxel devices used in the peripheral arteries]. The next level now is [to evaluate the] efficacy in terms of using paclitaxel in individual patients.”

November 2020 | Issue 80

12 CIRSE 2020

First@CIRSE

24-month AVeNEW study results: Covered stent angioplasty “statistically superior” to angioplasty alone in ESRD patients Against the backdrop of increasing endstage renal disease (ESRD) prevalence in the USA, Bart Dolmatch (Palo Alto Medical Foundation, Portola Valley, USA) presented the 24-month results of the prospective, randomised controlled AVeNEW study at the Cardiovascular and Interventional Radiological Society of Europe 2020 Symposium (CIRSE; 12–15 September, virtual).

THIS IS THE FIRST LEVEL ONE TRIAL dedicated solely to assess the safety and efficacy of the Covera (BD) covered stent designed to treat stenosis in the arteriovenous fistula (AVF) access circuit, Dolmatch claimed. The two-year results showed statistically superior target lesion primary patency and AVF circuit primary patency with the use of the covered stent compared with angioplasty alone.

Renal replacement is expensive, online attendees of the FIRST@CIRSE session heard, and largely achieved with haemodialysis using an AVF. However, Dolmatch explained how AVF stenosis interferes with efficient haemodialysis, leading physicians to try and find a

treatment modality that reduces its occurrence.

“Angioplasty has been our go-to for many years,” he said. “We know that the durability after angioplasty is OK, but the question is, can we improve upon angioplasty durability when treating fistula stenosis?”

Enter the AVeNEW study, a prospective, multicentre, multinational clinical trial of 280 patients with stenotic AVFs and clinical AVF dysfunction. Patients were randomised 1:1 to either the percutaneous transluminal angioplasty (PTA) group, or the angioplasty with the Covera stent group.

The study met both its primary safety and efficacy endpoints: freedom from a primary safety event out to 30 days, and target lesion primary patency at six months, respectively. There was no significant difference in freedom from a primary safety event out to 30 days between the covered stent cohort and the angioplasty alone cohort (95% and 96.4%, respectively; p=0.002). Target lesion primary patency at six months was “superb” and “statistically superior” in the covered stent group compared to angioplasty (78.7% and 47.9%, respectively; p<0.001).

A 12-month exploratory subgroup analysis of target lesion primary patency revealed that, regardless of certain lesion characteristics, there was “a preferential, better outcome using the covered stent compared to angioplasty alone. A Kaplan-Meier plot showed that the freedom from loss of target lesion primary patency was superior shortly after implantation of the covered stent compared to angioplasty, and remained statistically better at all time points, with more than a 30% better patency at 24 months.

Secondary outcomes were also better for the covered stent cohort, Dolmatch related. The index of patency function and mean access circuit reinterventions were both superior in the covered stent group, while secondary patency was the same in both groups (91.4%). “Interestingly, all-cause death was lower in the covered stent group than the angioplasty group,” Dolmatch continued. “I am not sure if this is statistically significant, we have not done that analysis yet, but it is a curious finding.”

Looking specifically at freedom from loss of access

Calls in Germany for reimbursement as analysis shows drug-eluting technology is cost-effective Stefan Müller-Hülsbeck (Ev Luth Diakonissenanstalt zu Flensburg, Flensburg, Germany) presented attendees of the online meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual) with an update from the IMPERIAL head-to-head randomised trial comparing the Eluvia drug-eluting stent (DES; Boston Scientific) with the Zilver PTX DES (Cook Medical) for the treatment of femoropopliteal artery lesions.

“T

hrough 24 months, there was a significantly lower clinically-driven target lesion revascularisation (CD-TLR) rate for the Eluvia DES than for the Zilver PTX [12.7% vs. 20.1%; p=0.0495],” Müller-Hülsbeck told registrants. An “excellent” primary patency rate was sustained with the Eluvia DES (83% from Kaplan-Meier estimates), and both study devices showed a low mortality rate at 24 months: 7.1% for Eluvia, and 8.3% for Zilver PTX.

In addition, Müller-Hülsbeck reported a significant improvement in mobility and pain/discomfort dimensions of health-related quality of life, sustained over 24 months in both treatment arms.

Cost-effectiveness analysis of the US Medicare system and the German health insurance system showed cost savings; on average, US$1,300 per patient was saved when patients were treated with the Eluvia device in the USA. “This shows, once again, that when we choose Eluvia, we might achieve a high value

Fabrizio Fanelli (L) and Bart Dolmatch during CIRSE 2020

circuit primary patency, he commented: “Access circuit patency for an AVF drops off regardless of which group you are in, and yet, at 24 months, there is a statistically superior outcome of circuit patency for the covered stent group compared to the angioplasty group [p=0.02].”

Angioplasty has been our go-to for many years, but the question is, can we improve upon angioplasty durability when treating fistula stenosis?”

Read more Renal News stories from page 17

when treating our patients with this kind slightly better data, but this is just a of drug-eluting technology, due to the hope. Once again, I think that with both higher TLR rates we might achieve.” technologies, we have options to treat Moderator Fabrizio Fanelli (Careggi our patients adequately, to provide them University Hospital, Florence, Italy) with drug-eluting technology.” queried if Müller-Hülsbeck believed Fanelli next asked if Müller-Hülsbeck the “pretty important gap between the thought this could “push the use of drugELUVIA DES and the Zilver PTX” eluting stents” in the future. would grow in the future, or would “I think yes,” Müller-Hülsbeck become more similar. replied, “especially in the USA. In “That is hard to answer! Probably the Germany, I do not know exactly, results from [using] both stents could because the difference there is slightly differ, but I think there is also a high lower, but it is my hope—as we want probability that the curves in terms of to avoid patients coming back for early target lesion revascularisation might target lesion revascularisation—that come closer, so we have to see what will this kind of technology becomes more happen in five years,” Müller-Hülsbeck accepted by insurance companies for responded. “The reimbursement. five-year data I am mentioning Michael [Dake] that because, at the presented [see moment, especially page 8] with the in Germany, we Zilver PTX are do not receive any really outstanding. reimbursement My personal hope if we use drugfor the patient is eluting technology, that, with Eluvia, either the Zilver we might achieve PTX or the Eluvia Stefan Müller-Hülsbeck (L) and Fabrizio Fanelli at CIRSE 2020 equal or even stent.”

Issue 80 | November 2020

Peripheral arterial disease 13

Patients with multiple revascularisations derive “particularly robust benefit” from rivaroxaban Symptomatic peripheral arterial disease (PAD) patients undergoing recurrent lower extremity revascularisation have higher rates of ischaemic events, particularly acute limb ischaemia, than those patients who are undergoing their first peripheral revascularisation. This is the conclusion presented by Marc Bonaca (University of Colorado, Aurora, USA) at the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual). Bonaca and colleagues conducted a subgroup analysis from the VOYAGER PAD trial, which examined the efficacy and safety of rivaroxaban in patients with PAD undergoing recurrent lower extremity revascularisation.

“WE KNOW FROM TRIALS OF patients with PAD that a history of a prior peripheral revascularisation is associated with a very high risk of acute limb ischaemia, even long-term, years after the intervention was done,” Bonaca told online attendees. “More recent data from the landmark COMPASS trial show that, in patients with chronic PAD, those who had a prior history of revascularisation are at major heightened risk of major adverse limb events.”

VOYAGER PAD is a trial of 6,564 patients with symptomatic lower extremity PAD undergoing peripheral revascularisation. Patients were randomised 1:1 in a double-blind fashion to either the rivaroxaban group, where they received 2.5mg of the drug twice daily, or a placebo group. The primary efficacy endpoint was a five-point composite of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic stroke, or cardiovascular death. The primary safety endpoint was thrombolysis in myocardial infarction major bleeding.

In an assessment of the primary efficacy endpoint, the rivaroxaban group performed better than the placebo group, with fewer incidences of the five major complications included in the composite measurement. “In spite of best medical therapy in this population [the placebo group], the event rate was nearly 20%, which was extremely high,” Bonaca said. A Kaplan-Meier curve plotting cumulative incidence of the composite measurement of major adverse events against time since randomisation revealed that, at three-years posttreatment initiation, the event rate was 19.9% in the placebo arm, and 17.3% in the rivaroxaban arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.76–0.96; p=0.009).

“Rivaroxaban risk-benefit was apparent early, and continued over time,” Bonaca commented, “with an absolute risk reduction of 2.6% at three years, and a number needed to treat of just 39.”

Against this backdrop of successful

rivaroxaban use in the main VOYAGER PAD trial, Bonaca et al conducted a subanalysis investigating symptomatic PAD patients undergoing recurrent lower extremity revascularisation versus those undergoing their first revascularisation.

They hypothesised that repeat revascularisation patients would have a higher rate of acute limb ischaemia, and would derive “even greater benefits with a rivaroxaban plus aspirin strategy versus aspirin alone”.

The presence of known prior revascularisation was reported by investigators at baseline, and was defined as any history of endovascular, hybrid, or surgical lower extremity revascularisation. The primary outcome was the same composite as in the VOYAGER PAD study.

From a comorbidity perspective,

The benefit of rivaroxaban appears even greater in those who had a prior history of revascularisation.” the prior revascularisation group had a higher risk profile, Bonaca shared, with more hypertension, diabetes, and hyperlipidaemia. PAD characteristics were similar between the two cohorts, with the prior revascularisation group having a slightly lower risk: “They were more likely to be treated with an endovascular revascularisation, they had less frequently presented with acute limb ischaemia versus claudication, and the [average] ankle-brachial index was a bit higher. […] It is worth noting that they were very well-treated.”

In the placebo cohort, the cumulative event rate for those with no prior lower extremity revascularisation was 17.7%—

Figure 1 (above): Fabrizio Fanelli (L) and Marc Bonaca Figure 2: Cumulative incidence of a composite event rate comprising acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic stroke, or cardiovascular death in the placebo and rivaroxaban cohorts. LER is lower extremity revascularisation.

“very high,” Bonaca pointed out, “even in this very well-treated population.”

Nevertheless, those patients who had had a prior revascularisation had a higher cumulative event rate of 23.8%, representing a 6.1% increase in risk.

“When we look at the efficacy of rivaroxaban, stratified in these two groups [prior revascularisation and no prior revascularisation], we see the benefit is there for both groups,” Bonaca explained.

In the rivaroxaban cohort, those with no prior revascularisation had a cumulative event rate of 16.9%, while those who had undergone an earlier revascularisation had a cumulative event rate of 18.1%. The impact of prior revascularisation was therefore less in the rivaroxaban cohort than in the placebo cohort.

Comparing the placebo and rivaroxaban cohorts (Figure 2), Bonaca told delegates: “The benefit of rivaroxaban appears even greater in those who had a prior history of revascularisation, with a HR of 0.73, and a trend towards heterogeneity, meaning there may be an even greater benefit in this high-risk group.”

Wondering what could be driving this difference, Bonaca and colleagues looked at the limb outcomes of acute limb ischaemia and vascular amputation in patients treated with rivaroxaban with and without prior lower extremity revascularisation. In placebo patients with no prior revascularisation, rates

of acute limb ischaemia and vascular amputation were lower at three-years post-randomisation than they were in the group of patients who had had previous revascularisation: 6% versus 10.8%, and 3.4% versus 4.5%, respectively.

As Bonaca put it: “Patients in the prior revascularisation group have a very high risk of acute limb ischaemia, almost 11%, and that is driving this risk profile, and that benefit for acute limb ischaemia [with rivaroxaban] is even greater in patients with a prior history of revascularisation. This does look like our hypothesis—that repeat revascularisation patients are at higher risk and would derive a greater benefit of rivaroxaban—was met in this analysis.

“Rivaroxaban plus aspirin versus aspirin alone reduces irreversible harm events, so the heart, limb, and brain in patients that are undergoing revascularisation, but in this subgroup with prior revascularisation, there is a particularly robust benefit, and really notably in acute limb ischaemia. The current analysis demonstrates that within this population, those with multiple revascularisations are at higher risk than those who have undergone a first revascularisation only, and may derive particularly robust benefit from rivaroxaban plus aspirin versus aspirin alone. These observations further demonstrate the heterogeneity of risk in the PAD population, and may assist in clinical risk stratification and therapeutic decision-making.”

November 2020 | Issue 80

14 Venous interventions

Deep vein arterialisation should be considered in “no option” CLTI patients, two-year LimFlow data show Midterm results from a study of the largest population of patients with no-option chronic limb-threatening ischaemia (CLTI) treated with percutaneous deep vein arterialisation (pDVA) using the LimFlow device show that, in this complex group of patients, this treatment method is feasible, with a high technical success rate and amputationfree survival at six through to 24 months, coupled with effective wound healing. In selected patients with no-option CLTI, percutaneous deep vein arterialisation could be a recommended treatment to prevent amputation and heal wounds, Costantino Del Giudice (Université de Paris, Paris, France) told delegates attending the online 2020 meeting of the Cardiovascular and Radiological Society of Europe (CIRSE; 12–15 September, virtual).

T

hese results from the ALPS (Midterm outcomes of percutaneous deep venous arterialisation with a dedicated system for patients with no-option chronic limb-threatening ischemia) multicentre study were published in the Journal of Endovascular Therapy in August this year, in addition to being presented at the CIRSE congress. The ALPS registry is the largest study to date of no-option CLTI patients treated with the LimFlow system reporting mid- and long-term results, and is a multicentre, retrospective study conducted at centres in Alkmaar, The Netherlands; Leipzig, Germany; Paris, France; and Singapore encompassing 32 endstage—or “no-option”—CLTI patients.

The investigators set out to evaluate the midterm results of patients suffering from no-option CLTI treated with a dedicated system (the LimFlow system) for percutaneous deep venous arterialisation. Thirty-two consecutive CLTI patients were treated with this method using the Limflow device at four centres between 11 July 2014 and 11 June 2018 and retrospectively analysed. Of all patients, 21 (66%) had diabetes, eight (25%) were on immunosuppression, four (16%) had dialysis-dependent renal failure, nine (28%) had Rutherford category six ischaemia, and 25 (78%) were deemed at high risk of amputation. The primary outcome was amputation-free survival (AFS) at six months. Secondary outcomes were wound healing, limb salvage, and survival at six, 12, and 24 months.

Technical success was achieved in 31 patients (96.9%). The median follow-up was 34 months (range 16–63). At six, 12, and 24 months, estimates were 83.9%, 71%, and 67.2% for AFS, 86.8%, 79.8%, and 79.8% for limb salvage, and 36.6%, 68.2%, and 72.7% for complete wound healing, respectively. Median time to complete wound healing was 4.9 months (range 0.5–15). The deep vein arterialisation circuit occluded during follow-up in 21 patients; the median time to occlusion was 2.6 months. Reintervention for occlusion was performed in 17 patients: 16 because of unhealed wounds and one for a newly developed ulcer.

Deep vein arterialisation offers hope for “no option” patients “No option” patients are those where no possible endovascular or surgical procedure will help, due to either the absence of a target vessel or thanks to unsuccessful prior interventions. These patients frequently have calcified vessels, diabetes mellitus, dialysis, and/or long-term corticoid therapy. The risk of amputation and persistent wound is 58% when these patients are treated with conservative therapy, and the risk of death at one-year follow-up is 20%.

Deep vein arterialisation aims to improve the blood flow to the foot. “We direct nutritional improvement by reversal of flow through venules,” Del Giudice told the CIRSE audience, describing how deep vein arterialisation works. “This stimulates arteriogenesis, and recruits hibernating collaterals.”

entry in the distal lateral or medial plantar vein from a subintimal channel in the plantar artery can be intentionally pursued as a bailout tactic; the guidewire tip is pointed opposite to the arterial wall calcifications.

Yet another method is the venous arterialisation simplified technique (VAST). This utilises a low-profile balloon catheter and a snare to facilitate arteriovenous fistula creation during venous arterialisation.

An arteriovenous fistula could also be created using a low-profile balloon catheter and an outback catheter. Del Giudice described a case where he and his team treated a patient using this method: “Without any target vessel in the distal leg,” he said, “we performed subintimal ligation towards the posterior tibial artery, and then we used the outback [catheter] to advance the balloon into the posterior tibial vein, and create the [arteriovenous] fistula, advancing the guidewire. Finally, we performed a valvotomy with a low-profile balloon, and stented the vein from the ankle to the arteriovenous fistula.”

Showing a table comparing the outcomes at six months from these different techniques, Del Giudice

LimFlow percutaneous deep vein arterialisation system

Not all patients are candidates for this procedure. We need salvageable tissue to obtain some results.”

The most important step, he shared, is patient selection. “Patients have to have a good heart function, a good life expectancy, foot arteries not treatable by an endovascular or surgical approach, a Rutherford class 5–6, a Wound, Ischaemia, and Foot Infection (Wifi) score of 3, and no infection,” Del Giudice listed.

According to the speaker, the Limflow technique is the most commonly used method.

The LimFlow technique: How it works

Del Giudice talked CIRSE registrants through a case demonstrating the use of the Limflow technique.

This first involved performing arteriography and venography scans to aid target vessel selection. Next, the interventionalists advanced the venous and arterial catheters to the target vessel, where the artery and vein were closest, and created an arteriovenous fistula, bridging the two vessels. Then, they advanced the guidewire along the vessel, using it to push the balloon through the arteriovenous fistula to create a passage.

Blood flow is diverted from the blocked artery into the vein to salvage the lower leg.

Del Giudice shared an alternative technique whereby

was positive: “There is good primary patency, ranging from 40–90% at six months, and good wound healing outcomes, ranging from 40–100%. Major amputations ranged from 0–33.3% at six-month follow-up.”

Earlier trials: The PROMISE I study

The PROMISE I study was an early feasibility study launched in mid-2017 to establish the clinical safety of the Limflow technique. It aimed to provide enough data for the investigators to move on to a pivotal trial, to identify and address any operator challenges, and to determine patient characteristics and therapeutic parameters that impact performance. Enrolment was completed in 2019, and the triallists have since reported a 97% technical success rate in the 32 patients treated in the USA as part of this study. Overall survival was 96%, freedom from amputation was 77%, and amputation-free survival was 74%.

“The importance of this study was that it allowed us to understand that not all patients are candidates for this procedure. We need salvageable tissue to obtain some results,” Del Giudice said. “Moreover, the results [show that] this is quite different from an arterial canalisation.

Deep vein arterialisation requires four to six weeks for tissue granulation to start. Oedema can occur in the treated limb after deep vein arterialisation, but typically resolves within three to four weeks. We need to preserve native arterial perfusion and mange pedal loop outflow during the maturation process. It is also important to monitor changes in foot tissue colour. In terms of wound care, multidisciplinary collaboration is required, and patients may need some minor amputation management [and] debridement.”

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Issue 80 | November 2020

Flow reduction and stenosis are major AV access complications during early months of the pandemic In a multicentre cross-sectional study, Jia Shi (Huazhong University of Science and Technology, Wuhan, China) and colleagues assessed the management of vascular access in haemodialysis patients during the early months of the COVID-19 pandemic. They found that catheter flow reduction and stenosis of arteriovenous access were the major vascular access complications. In addition, most of the vascular access sites established were catheters, and many of the vascular access complications remained untreated.

SHI AND COLLEAGUES WRITE in the Journal of Vascular Access (JVA) that the management of vascular access during the COVID-19 pandemic is “currently unknown”. In order to address this, the investigators collected vascular access data from haemodialysis patients treated at 44 hospitals in Hubei province in China from 22 January to 10 March 2020 and estimated the management of vascular access during the outbreak of the pandemic.

“To the best of our knowledge,” they write, “this study is the first crosssectional study to estimate the vascular access data of haemodialysis patients in Hubei”. It is also the first to document the indirect effect of the COVID-19 pandemic on the management of vascular access in Hubei.

The authors detail that of the 9,231 haemodialysis patients included in the study, 5,387 patients (58.4%) were male and 2,959 patients (32.1%) were older than 65 years.

Writing in JVA, Shi et al report that arteriovenous fistula (AVF) was the most predominant type of vascular access, accounting for 76.5%. In addition, they observed that 496 patients (5.4%) developed vascular access complications and that catheter flow reduction was the most common vascular access complication. Among those with arteriovenous access, they found that stenosis was the predominant complication.

Furthermore, the authors relay that 280 vascular access sites were placed in patients newly diagnosed with uraemia, of whom 260 (92.8%) underwent catheter insertion, which consisted of 132 catheters, seven percutaneous transluminal angioplasties, six arteriovenous repairs, and four AVFs. Shi and colleagues state that occlusion of the arteriovenous access

had the highest rescue rate (92.7%), while many other vascular access complications remained untreated. The number of patients diagnosed with confirmed and suspected COVID-19 were 69 and 142, respectively.

Finally, they report that a total of 146 patients died, of whom 29 patients (19.9%) died due to vascular access complications.

Type of vascular access in haemodialysis “is of utmost importance”

“The type of vascular access in haemodialysis patients is of utmost importance, as it is associated with numerous complications,” Shi et al stress in the discussion of their findings.

They detail that the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines and other guideline committees recommend AVF as the first choice of vascular access type for haemodialysis.

“According to the KDQOI clinical practice guidelines,” Shi and colleagues write, “the target for functional AVF in prevalent haemodialysis patients is ≥65%, and catheter use should be less than 10%”. However, they detail that vascular access use varies greatly across countries. They reference the 2013 Dialysis Outcomes and Practice Patterns Study (DOPPS) study, which showed that the rate of AVF use varies across the world, with 49% use in Canada and 92% use in Russia, while central venous catheter use was 45% in Canada and 6% in Russia. In China, AVF use was 87% and CVC use was 10%. “In the present study, the rate of AVF use was 76.5%, which was lower than that reported in the Chinese DOPPS data (87%),” they state.

Shi et al put forward a number of possible reasons why this rate

was lower in the present study, one being that the reduced number of non-emergency services during the pandemic may have resulted in a reduced amount of AVF surgery, evidenced by the 395 catheters placed, and only 24 AVF surgeries conducted during the pandemic.

They mention another possible reason as being that the number of participants in the present study was far greater than that in the DOPPS (9,132 vs. 1,123).

Finally, they detail that the rate of central venous catheter use in secondary hospitals was higher than that in tertiary hospitals, “as the selection of the vascular access type is affected by many factors, including patients’ demographic factors, patients’ adherence to vascular access care, variation in operation ability among vascular access doctors, and cooperation between healthcare professionals and patients,” they explain, going on to acknowledge: “Further research is needed to determine the cause of the observations”.

Conclusions limited by study design and short research time, authors concede

The authors acknowledge that selection bias may affect their results due to the cross-sectional design of the study.

For example, they recognise that selection bias may affect their results and conclusions due to the crosssectional design of the study. They also

note that, as a result of the relatively short research time, the prevalence of vascular access complications may not be representative of patients at other times. Moreover, they concede that they do not have vascular access data for the same population before the COVID-19 pandemic, and therefore state that they cannot compare the establishment and treatment of vascular access complications observed in this study with previous data.

Shi and colleagues conclude that this indicated that catheter flow reduction and AVF/arteriovenous graft stenosis were the major causes of vascular access complications. In addition, most of the vascular access established during the COVID-19 outbreak were non-tunnel catheters, and vascular access occlusion received the highest percentage of rescue procedure during the pandemic.

This study is the first cross-sectional study to estimate the vascular access data of haemodialysis patients in Hubei.”

SAVE registry findings back safety of Surfacer system The Surfacer Inside-Out access catheter system device (Bluegrass Vascular) is safe and effective for patients with thoracic central venous obstruction requiring central venous access. That is conclusion of the prospective, multicentre SAVE (Surfacer system to facilitate access in venous occlusions) registry, published recently in the Journal of Vascular and Interventional Radiology (JVIR).

GÜRKAN SENGÖLGE (MEDICAL UNIVERSITY OF VIENNA, VIENNA, Austria), co-author on the paper details: “We gained access with Surfacer technology in over 98% of the cases.”.

“The publication of the results of the SAVE registry expands and strengthens the clinical evidence confirming the role the Surfacer system has in helping to establish central venous access in patients with venous obstructions,” states Maurizio Gallieni (University of Milan, Milan, Italy), who was a co-lead author.

The Surfacer system has received US Food and Drug Administration (FDA) de novo device clearance in the USA and is CE marked in Europe.

November 2020 | Issue 80

Study finds 3mm arteriotomy may be routinely utilised for brachiocephalic fistula creation In a recently-published study, Jeremy Crane (Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK) and colleagues conclude that a 3mm-long arteriotomy may be routinely utilised for brachiocephalic fistula creation in an attempt to limit the incidence of steal syndrome, while maintaining clinical patency outcomes.

“THE ARTERIOVENOUS FISTULA [AVF] IS the modality of choice for long-term haemodialysis access,” the Journal of Vascular Access (JVA) paper begins. The authors cite lower rates of access-related infection and improved patient and access survival when compared to other modalities such as arteriovenous grafts or longstanding tunnelled central venous catheters as the reasons behind this.

However, AVF formation is “not to be taken lightly,” Crane and colleagues warn, noting dialysis access-associated steal syndrome (DASS) as an “important” and “potentially limb threatening” complication.

They explain that the hallmarks of steal syndrome are symptoms and signs of peripheral vascular insufficiency within the limb distal to the AVF, which are often detected through a thorough clinical history and examination.

They go on to describe the feasibility of routinely fashioning a brachiocephalic fistula utilising a 3mmlong arteriotomy in an attempt to reduce the incidence

of symptomatic steal syndrome, while maintaining clinical patency outcomes.

Crane and colleagues describe the study as a retrospective analysis of prospectively collected clinical data from a single surgeon.

They detail that they included all patients who underwent brachiocephalic fistula formation using a routine 3mmlong arteriotomy within Hammersmith Hospital between January 2017 and March 2018 in the study. Primary outcomes included primary failure, failure of maturation, secondary patency, and steal syndrome.

Writing in JVA, Crane et al relay that 68 brachiocephalic AVFs were fashioned utilising a 3mm arteriotomy during the study period, adding that the mean age was 60.5 years with 59% having a history of diabetes mellitus. The mean follow-up was 368 days, the authors write.

The authors report that primary failure occured in 10 (14.7%) of patients, and that cannulation was achieved in 67.3% of remaining fistulae within three months, rising to 87.3% by six months.

Older age and diabetes mellitus identified as risk factors for poor patency rates following vascular access construction Different risk factors affect patency between vascular access construction and the first percutaneous transluminal angioplasty, Mahoko Yoshida (Hiroshima University Hospital, Hiroshima, Japan) and colleagues conclude in the Journal of Vascular Access (JVA). Their results indicate that a poor patency rate is commonly associated with advanced age, and diabetes mellitus.

“THESE FINDINGS SUGGEST that older patients and those with diabetes mellitus are more likely to experience vascular access problems after both vascular access construction and percutaneous transluminal angioplasty [PTA], and that different risk factors should be taken into account when managing patients undergoing haemodialysis after vascular access construction and PTA,” the study authors write. “Understanding the risk factors that contribute to vascular access problems may lead to better surveillance and focused care in high-risk patients,

resulting in more effective management of vascular access.”

Dialysis: “A global health concern”

The number of patients undergoing dialysis worldwide has been increasing each year, the study authors write, and is considered a global health concern.

The majority of dialysis patients receive haemodialysis, and are known to suffer from various complications, including cardiovascular disease and infections.

The most frequent issue relates to problems with vascular access: stenosis,

In terms of primary patency, Crane and colleagues note that this was 76% and 69% at six and 12 months, respectively.

Secondary patency at the same time points was 91% and 94%, respectively. Finally, the authors detail that dialysis access steal syndrome was clinically apparent in three (4.4%) patients, with all cases being managed conservatively.

The authors recognise that steal syndrome is multifactorial in origin and not purely related to anastomosis calibre.

In addition, “follow-up among the patients included in the study is limited,” Crane and colleagues write, adding that late presentations of DASS due to ongoing arterial and venous remodelling and subsequent increase in fistula flow may subsequently occur.

A randomised trial with clear documentation of venous and arterial diameter along with postoperative duplex ultrasound and haemodialysis access flow assessment would be useful, they suggest.

A randomised trial with clear documentation of venous and arterial diameter along with postoperative duplex ultrasound and haemodialysis access flow assessment would be useful.”

thrombosis, aneurysm, and infection.

“In fact,” Yoshida et al say, “the medical expenses for vascular accessrelated complications is estimated at JPY 10,953,310,000/year”. The investigators therefore surmise that “recognition of risk factors for vascular access failure is needed not only to improve the quality of life of patients undergoing haemodialysis, but also to reduce medical expenditure”.

They conducted a multicentre, prospective, observational study of 611 patients who had started haemodialysis between 1 April 2012 and 31 March 2018, and investigated the primary and secondary patency rates after construction of a radiocephalic arteriovenous fistula (AVF) and arteriovenous graft (AVG). Primary patency was defined as the period from vascular access construction to PTA or surgical revision within 24 months; secondary patency was defined as the period from vascular access construction to the date of vascular access abandonment. The study also examined the patency rate following PTA—defined as the period from the first PTA to the next PTA or surgical revision within 12 months—as well as the clinical factors that contributed to the development of restenosis.

All patients were followed-up until

December 2018.

Post-PTA patency unaffected by vascular access form in older patients

The study results reveal that radiocephalic AVF exhibited better 24-month primary and secondary patency rates than AVG in patients who started haemodialysis: 54.5% and 91.6% versus 25.1% and 70.3%. The authors note that these 24-month primary and secondary patency rates after vascular

The majority of dialysis patients receive haemodialysis, and are known to suffer from various complications, including cardiovascular disease and infections.”

Continued on page 20

November 2020 | Issue 80

Older age and diabetes mellitus identified as risk factors for poor patency rates following vascular access construction Continued from page 18

access construction are higher than those reported in the literature by researchers investigating patients outside of Japan. They postulate that the higher patency rates seen in Japanese patients could be due to the fact that they undergo haemodialysis with lower blood flow, which they suggest may enable the vascular access to be used for longer periods.

While the patency rates after vascular access construction between the two vascular access forms (radiocephalic AVF and AVG) was not significantly different in the multivariate analysis, they did show a significant difference in the log-rank test. “With respect to the post-PTA patency rate, although radiocephalic AVF appeared to result in a better patency rate than that of AVG, the difference was not statistically significant in either the log-rank test or Cox proportional hazard model,” Yoshida and colleagues discuss. “A previous study reported that AVF exhibited a better patency rate after both vascular access construction and PTA than AVG. Notably, another study showed that the patency rate of AVF did not differ from that of AVG in advanced-age patients undergoing haemodialysis, especially those aged >65 years. In the present study, the

median age of the patients was 70 years, suggesting that rather than the vascular access form, the background of the patients may be more strongly associated with the patency rate.”

Risk factors for vascular access complications

A Cox proportional hazard model demonstrated that ageing, female sex, diabetes mellitus, low serum albumin, and use of an erythropoietinstimulating agent were associated with poor primary patency after vascular access construction in this study. Of these identified risk factors, ageing, diabetes mellitus, and low serum albumin may be indicative of a patient’s poor general condition, the study authors muse, while female sex has reportedly been associated with smaller vascular diameter, which can increase the number of vascular access problems.

“Taken together these results indicate that vascular access patency might be improved if modifiable risk factors identified in the present study are well controlled,” Yoshida et al write.

Furthermore, ageing, diabetes mellitus, polycystic kidney disease, initiation of haemodialysis with the use of a temporary catheter, and a

shorter period from vascular access construction to use were associated with poor patency after the first PTA. These results led the study investigators to conclude that patients need to start haemodialysis “urgently”.

“These findings suggest that with the exception of ageing and diabetes mellitus, different risk factors contribute to the incidence of vascular access problems after surgical construction of vascular access and restenosis after PTA,” the authors conclude.

“Our data showed that stenosis accounted for 92% of vascular access problems. […] These findings suggest that the presence or absence of

Understanding the risk factors that contribute to vascular access problems may lead to better surveillance and focused care in high-risk patients.” procedure-induced stimulation may cause differences in the risk factors that influence the patency rates after vascular access construction and that after PTA.”

Risk factors for poor patency rates after vascular access construction Different risk factors affect patency

Ellipsys system offers greater patient eligibility and reduced time to dialysis, study finds Two devices for creating minimally invasive dialysis access—the Ellipsys vascular access system (Avenu Medical) and the WavelinQ 4F system (BD)—demonstrated high rates of technical success and low rates of complications in a new study.

IN ADDITION, BOTH TECHNOLOGIES enabled patients to start dialysis sooner compared to surgery, offering significant quality-of-life benefits. The results were published in the Journal of Vascular and Interventional Radiology.

For patients with end-stage renal disease (ESRD) who require haemodialysis, the preferred type of vascular access is an arteriovenous fistula (AVF)—a permanent connection between a vein and artery in the arm. Until recently, the only way to create an AVF was through a surgical procedure that subjects patients to discomfort, longer recovery times, and delayed dialysis.

Both the Ellipsys and WavelinQ devices offer a nonsurgical alternative by using a minimally invasive approach to create a percutaneous arteriovenous fistula (pAVF). The new single-centre

between vascular access construction and the first PTA, Mahoko Yoshida (Hiroshima University Hospital, Hiroshima, Japan) and colleagues conclude in JVA. Their results indicate that a poor patency rate is commonly associated with advanced age, diabetes mellitus, female sex, low serum albumin, and the use of an erythropoietin-stimulating agent.

“These findings suggest that older patients and those with diabetes mellitus are more likely to experience vascular access problems after both vascular access construction and PTA, and that different risk factors should be taken into account when managing patients

study, led by vascular surgeon Robert Shahverdyan (Vascular Access Center, Hamburg, Germany), compared the outcomes for 100 patients who underwent pAVF procedures (65 Ellipsys and 35 WavelinQ) from December 2017 to December 2019.

The Ellipsys system had a technical success rate of 100%, and only 27.7% of patients required secondary interventions following fistula creation.

The WavelinQ system demonstrated similar outcomes, with a technical success rate of 97% and 26.5% of patients requiring secondary interventions.

Overall, 79.5% of Ellipsys patients and 58% of WavelinQ patients were able to successfully begin dialysis with their fistula. At 12 months, 82% of Ellipsys fistulas were still functional, compared to 60% of WavelinQ fistulas.

“For every patient, my goal is to create the best

undergoing haemodialysis after vascular access construction and PTA,” the study authors write.

“Understanding the risk factors that contribute to vascular access problems may lead to better surveillance and focused care in high-risk patients, resulting in more effective management of vascular access.”

possible dialysis access with the fewest possible interventions,” said Shahverdyan.

“Our data show that with careful planning, both systems can safely and quickly create percutaneous fistulas with a high rate of success, though the Ellipsys system appears to create more durable access that is also easier to repair if that becomes necessary.”

Compared to surgical fistulas, both devices reduced the time to dialysis (cannulation). The mean time to cannulation for WavelinQ was 90 days, compared to 60 days with Ellipsys. In fact, 75% of Ellipsys fistulas were ready for cannulation at just four weeks, with a small number of patients ready for early cannulation within a few days of fistula creation, Shahverdyan notes.

“This study confirms other newly published data showing how much faster we can start using the Ellipsys percutaneous fistula for dialysis—a finding that has significant patient safety benefits,” said interventional radiologist Jeffrey Hull (Richmond Vascular Center, Richmond, USA).

“The sooner a patient can start dialysis with their fistula, the sooner we can get them off such riskier dialysis access methods as central venous catheters, which are associated with much higher rates of infection and other complications.”

Issue 80 | November 2020

Medtronic to acquire Avenu Medical Medtronic recently announced the planned acquisition of Avenu Medical, a medical device company focused on the endovascular creation of arteriovenous fistulas (AVFs) for patients with end-stage renal disease (ESRD) undergoing dialysis.

Terms of the transaction were not disclosed.

A PRESS RELEASE EXPLAINS THAT AVENU Medical’s Ellipsys vascular access system is a single-catheter, ultrasound-guided device that inserts a catheter percutaneously into the arm to create a durable AVF. The procedure can be performed in the hospital outpatient centre, ambulatory surgery center (ASC), or physician’s office.

“AVFs are like lifelines to patients undergoing dialysis. Until recently, the only option to create a fistula was through invasive surgery, which is associated with high failure rates,” said Jeffrey Hull (Richmond Vascular Center, Richmond, USA), cofounder of Avenu Medical. “The Ellipsys system has shown durable outcomes out to two years and has the ability to shorten procedure times and potentially

reduce costs. Unlike open surgery, sutures are not required after the procedure and the patient leaves with just an adhesive bandage.”

The Ellipsys vascular access system bears the CE mark for distribution in the European Union and is cleared by the US Food and Drug Administration. It is indicated in both geographies for the creation of a proximal radial artery to perforating vein anastomosis for percutaneous creation of an AVF. “Medtronic’s acquisition of Avenu aligns directly with our vision of bringing less invasive,

of Medicine,” said Mark Pacyna, vice president and general manager of the Peripheral Vascular business at Medtronic. “Now with the acquisition of Avenu Medical, we can support procedures across the vascular access care continuum, while continuing to provide innovative endovascular therapies that will ultimately reach even more patients with ESRD around the world.”

At time of publication, the acquisition is expected to close by November 2020, subject to the satisfaction of certain closing conditions. The acquisition of Avenu Medical is the sixth in a series of tuck in acquisitions that Medtronic has made in 2020.

The transaction is expected to be immaterial to Medtronic's adjusted earnings per share in the first two years before turning accretive in fiscal year 2023. In addition, this transaction is expected to meet Medtronic's long-term financial metrics for acquisitions.

endovascular solutions to patients requiring durable vascular access,” said Mark Ritchart, president and chief executive officer of Avenu Medical.

“With Medtronic’s extensive market presence, clinical leadership, and market development expertise, coupled with Avenu’s customer-focused team and innovative technology, we are confident that together, we can drive awareness and adoption of this technology globally.”

“Within the last year, we have seen significant momentum with the launch of the IN.PACT AV drug-coated balloon (DCB) in the USA and primary endpoint results of the IN.PACT AV Access study being published in The New England Journal

AVFs are like lifelines to patients undergoing dialysis. Until recently, the only option to create a fistula was through invasive surgery, which is associated with high failure rates.”

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November 2020 | Issue 80

Dialysis access needs to be a priority in the COVID-19 era Panagiotis Kitrou Nicholas Inston Comment & Analysis Panagiotis M Kitrou and Nicholas Inston discuss the impact of the COVID-19 pandemic on vascular access services. Despite the disruption caused, they believe the pandemic should be viewed as a catalyst for change. It is time to “redesign and restructure” vascular access programmes, they tell Interventional News.

T

he COVID-19 pandemic has resulted in major disruption in the delivery of clinical services on a scale previously unseen. In many countries, rationing of facilities and severely restricted or zero access to operating theatres has been imposed.

It has been estimated that 28.4 million surgical procedures have been cancelled globally, with the highest cancellation rates in benign disease.1 The crisis has affected different countries and even different regions of countries variably. In Asia, 47% of healthcare practices suspended elective vascular surgery completely and 23% scaled down activity.2 In the UK, it has been estimated that to clear the backlog of cancelled surgery at 20% extra activity will require 11 months, even if further surgeries are not factored in.

To manage constrained services, many societies issued prioritisation to allow rationing based on clinical risk, mainly based on estimated urgency and need for treatment. These have been classified as 1a. emergency <24 hours; 1b. urgent (up to 72 hours); 2. up to one month; 3. up to three months; and 4. over three months by the Royal Colleges in the UK,3 and by the Society for Vascular Surgery (SVS) as 1. postpone; 2a. consider postponing; 2b. postpone if possible; and 3. do not postpone.4

Provision of vascular access for dialysis “less than ideal” before pandemic The impact of COVID-19 on dialysis access is not yet known, but it is predicted that the rates of definitive access have been severely affected.

Prior to the pandemic, the provision of vascular access for dialysis was already identified as being less than ideal. In the

USA, 80% of patients initiate dialyses on a central venous catheter (CVC)5 and international rates of definitive access are highly variable.6 Despite this, benefits of definitive vascular access and avoidance of CVCs are clearly demonstrated, particularly in the less comorbid patients.7,8 The problems encountered during the first peak of the pandemic are likely to have resulted in many patients starting dialysis on a CVC. This is multifactorial.

Patients with chronic kidney disease (CKD) stages 4 and 5 require access in preparation for dialysis. These vulnerable patients have been advised to follow enforced shielding practices. As such, they neither fall into a high priority

is not yet possible to assess whether COVID-19 infection had adverse outcomes. Anecdotally, claims have been made for prothrombotic tendencies, particularly in those severely affected, but data on fistula loss secondary to infection are not yet clear. Dysfunctional access may have been afforded higher priority and performing maintenance procedures may have avoided CVC insertions. It is unclear whether patients presented later during the pandemic due to shielding risks, or hospitals operated policies of inserting a CVC to reduce lengthy salvage procedures.

The consequences arising from increased CVC placement and reduced fistula creation and salvage will result in multiple issues. Repeated hospitalisation, bloodstream infections, catheter dysfunction, central venous stenosis, and occlusion are all a product of increased catheter use and as a consequence healthcare costs will increase.9 This significant economic and healthcare burden will not only start to show now, but as renal failure is a chronic disease will have significant effect on health economics in the long term. In addition, CVCs have a negative impact on the quality of life and longevity of haemodialysis patients and constitutes a major deviation from best practice guidelines and a serious setback in the standard of care previously delivered.10

“Robust plans” needed for second wave

Whilst some countries are unfortunately currently dealing with the first wave, others are now experiencing a second wave. The needs of CKD and dialysis patients require robust plans to optimise safe creation, maintenance, and salvage of definitive vascular access and avoidance of the use of CVCs.

To manage dialysis access appropriately during peaks of COVID-19 will require better identification of those in need.” group for surgery nor are advised to attend hospital appointments in person.

Assessment for vascular access generally requires ultrasound mapping and this may have been avoided to elude virus exposure. Pre-emptive living donor transplantation, which may have eliminated the need for vascular access, may have been suspended.

In patients infected with COVID-19, the requirement for renal replacement therapy was high, particularly in those requiring intensive care. The impact of multiple vascular access attempts on these patients and long-term effects on renal function remain to be seen, but may add a further healthcare need.

For patients with existing access data,

These strategies may require local modifications. Ideally cold (green) sites should be used, although dialysis patients’ inability to isolate due to thrice weekly treatment may prohibit pure “clean” pathways. Risk assessments may need specific “renal pathways” to be developed rather than apply standard surgical risk stratification.

Where surgical services are overwhelmed or resources compromised, other strategies should be considered, particularly endovascular approaches to maintenance, salvage, and even creation using percutaneous devices.

This may increase the availability of additional operators, (e.g. interventional nephrologists and interventional

radiologists) where staff redeployment or sickness is a problem, and also allow procedures to be performed in alternative facilities, avoiding hot sites and potentially freeing up theatres.

In order to prepare for further waves of COVID-19, the provision of the best dialysis access, including peritoneal dialysis, will require close working with the wider multidisciplinary team involved in assessment, creation, cannulation, surveillance, maintenance, and salvage of definitive access.

An opportunity for change

To manage dialysis access appropriately during peaks of COVID-19 will require better identification of those in need, with more timely assessment and creation of access. Early identification of problematic access through skilled clinical examination, timely and appropriate referral for diagnostics, and treatment using optimal technologies by those with expertise should be available. Follow-up and surveillance should be based around dialysis sessions and training of dialysis centre staff to cannulate, examine, and identify problems with liaison and accessibility to expertise made easily available.

The challenges of dialysis access may have been exacerbated by the pandemic, but all these requirements were present before. This is an opportunity for vascular access programmes to redesign and restructure, not only to deal with the pandemic, but to build better programmes suited to the needs of the large global population of renal patients.

Panagiotis M Kitrou is an interventional radiologist at Patras University Hospital, Patras, Greece.

Nicholas Inston is a consultant transplant and vascular access surgeon at the University Hospital Birmingham NHS Trust, Birmingham, UK. References 1. CovidSurg C, Nepogodiev D, Bhangu A. Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans. Br J Surg 2020.

2. Ng JJ, Ho P, Dharmaraj RB, et al. The global impact of COVID-19 on vascular surgical services. J Vasc Surg 2020; 71(6):2182–3 e1.

3. RCS. Clinical guide to surgical prioritisation during the coronoavirus pandemic.

4. SVS. Vascular conditions by category, with Teir Class 2020 [Available from: https://vascular.org/sites/default/ files/Vascular%20surgery%20triage%20by%20 Tier%20Class%203.24.20.pdf].

5. USRDS. USRDS 2019 Report 2019 [https://www. usrds.org/2019/view/USRDS_2019_ES_final.pdf].

6. Pisoni RL ZL, Port FK, Robinson BM. Trends in US vascular access use, patient preferences, and related practices: an update from the US DOPPS Practice Monitor with international comparisons. Am J Kidney Dis 2015; 65(6):905–915. Am J Kidney Dis 2015; 65:905–15.

7. Ravani P, Quinn R, Oliver M, et al. Examining the association between hemodialysis access type and mortality: the role of access complications. Clin J Am Soc Nephrol 2017; 12(6):955–64.

8. Quinn RR, Oliver MJ, Devoe D, et al. The effect of predialysis fistula attempt on risk of all-cause and access-related death. J Am Soc Nephrol 2017; 28(2):613–20.

9. Vassalotti JA, Jennings WC, Beathard GA, et al.

Fistula first breakthrough initiative: targeting catheter last in fistula first. Semin Dial 2012; 25(3):303–10.

10. Lok CE HT, Lee T, et al. KDOQI vascular access guideline work group. KDOQI clinical practice guideline for vascular access: 2019 update. Am J Kidney Dis 2020; 75(4).

October 2020 | Issue 80

24 Interview

Profile

Adam Hatzidakis

The first person to perform a transjugular intrahepatic portosystemic shunt procedure (TIPS) in Greece, Adam Hatzidakis discusses his career-long love affair with the hepatobiliary-pancreatic system, and describes the delights and difficulties of being a trailblazer in the interventional radiology (IR) space. Speaking seven months after the SARS-CoV-2 virus first caused multiple governments to impose national lockdowns and resulted in widespread international travel bans, Hatzidakis also hopes that the shift to digital conferences is here to stay, at least in part, “so that more colleagues may benefit from the international educational opportunities on offer”.

What initially attracted you to interventional radiology (IR)?

I was initially attracted to radiology because I loved imaging and trying to find the “pathological hidden in the physiological”. Then I discovered IR, where I had the possibility to “clean” the physiological from the pathological.

Have you had important mentors for you throughout your career?

Yes, several. To start, my first professor, Nicholas Gourtsoyiannis, in Heraklion, Crete. He taught us the importance of becoming clinical radiologists, and how to have a presence on the international stage. Together with my tutor and friend Spyros Karampekios, we performed the first IR procedures in Heraklion, back in 1993.

Next, my IR teacher, Panos Galis, at the AirForce Hospital in Athens, Greece. He was a Greek pioneer in vascular IR, and I learned many tricks from his experience.

Another three titans of IR who have been personally important: Plinio Rossi from Rome, Italy; Rolf Guenther from Aachen, Germany; and Andreas “Andy” Adam from London, UK. Besides great IR teaching, in London I learned how to manage, in Aachen how to organise, and in Rome how to improvise. All of these experiences were of great value.

Why are you specifically drawn to the hepato-biliary-pancreatic system? What do we still have to learn about treatment in this system?

In the era of magnetic resonance cholangiopancreatography (MRCP), endoscopists have fewer possibilities to practice so many endoscopic retrograde cholangiopancreatographies (ERCPs), with the result that new doctors are less well trained. So, radiologists usually have more to do. Biliary IR is delicate work, offering you a lot of challenging cases.

Performing malignant cases is good training for tough benign cases.

In 1996, you performed the first transjugular intrahepatic portosystemic shunt procedure (TIPS) in Greece. How did this come about?

That was my passport to the future. The case went well, although the patient was not able to survive for a long time. Performing this case helped to create a lot of respect for my work and IR more generally, but the expectations others have from you can become a very heavy burden. I learned that I had to constantly perform at a high level, and try to be involved in novel procedures, so that everybody could benefit from this. I think one can feel that they have to fulfil the obligation to continue working at a high scientific level in order to show the younger generation of interventional radiologists their way to the top.

In 1998, you were one of the first

interventional radiologists in Greece to perform percutaneous liver tumour ablation. What are the most exciting aspects of working at the vanguard?

This is the reason why I like working in university hospitals. Patients and other medical specialties can trust you more easily when it comes to new methods and techniques. Of course, you have to perform the procedures well and safely, with nice results to keep a good and trustworthy name. Sometimes this is not enough, because other specialties do not want to move to new methods and lose control of their patients, or stop performing what is common practice to them in favour of IR methods. The same happened in the old days with oncologists who did not want to stop chemotherapy protocols and send patients to radiofrequency ablation (RFA) in order to calculate total survival rates. The same thing still happens now with other IR techniques such as vertebroplasty, varicocele and fibroid embolization, and I am afraid it will also happen with prostatic artery embolization.

I am confident that the role of IR departments will come out of this crisis more powerful than before, because we provide minimally invasive solutions without the need for intensive care unit beds.”

Could you describe a particularly memorable case?

Yes, definitely the first TIPS procedure done in Greece.

I was still a final year radiology resident and I was asked to try to perform it. There were five university professors outside the angiography suite, and I needed five hours to complete the case. I would, of course, never have managed it without their trust and the good help of two senior radiologists who were my teachers and the backbone of our department.

As deputy chair of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) programme committee 2019–2021, and upcoming chair of the same committee, what are your goals for scientific education over the next two years?

Providing medical education has become difficult due to travel restrictions. But this problem has convinced international medical societies to transition to a digital

education format. Our last CIRSE Summit (12–15 September, virtual) is such an example. The set-up we managed to create in such a short time and the transformation of the programme from a live event to a digital one was a big challenge.

I am confident that this shift to online learning has come to stay. The future will be full of hybrid congresses with both live and distant participation. I hope during the next two years that we will be able to go back to face-to-face events, as these are very important for communication between doctors and industry, but also maintain some remote-learning capabilities, so that more colleagues may benefit from the international educational opportunities on offer.

How has the COVID-19 pandemic impacted IR this year, and do you foresee a lasting change to the discipline?

Issue 80 | October 2020

Interview 25 It was a hard time for everybody. Our university hospital in Thessaloniki closed for almost every other activity. We were asked to perform only emergency cases. But due to the fact that the surgical departments also decreased their activities, we managed to keep a decreased but adequate number of cases to continue our clinical work. I am confident that the role of IR departments will come out of this crisis more powerful than before, because we provide minimally invasive solutions without need for intensive care unit (ICU) beds.

On a personal level, what are the central preoccupations when treating patients during a global pandemic?

Be aware of COVID-19-positive patients, treat them carefully, and keep your staff safe.

In your opinion, what is the most interesting research coming out of Greece in the IR space right now?

Greek interventional radiologists try hard to maintain a high level of medical service, and to convince patients and other physicians about the possibilities our treatments can offer. Research has always been a tough task in our country, usually due to a lack of financial resources. Nevertheless, there are centres of excellence like in Patras, where a lot of research work is conducted in the peripheral vascular disease space and in arteriovenous fistula creation. Athens also has a couple of centres working on interventional oncology therapies in the thorax, abdomen, and musculoskeletal systems. We in Thessaloniki are trying to create a centre of excellence for primary and secondary liver tumours, in good cooperation with a local transplant centre. I am pretty confident that this cooperation will be fruitful in the future.

What are the main challenges when treating cancer patients via IR techniques? How and why is interdisciplinary collaboration important?

Hepatocellular carcinoma (HCC) patients are quite complex. Experienced hepatologists, together with surgical oncology and transplant colleagues, are needed to decide how to treat every case. The cooperation of hospital tumour boards demonstrates the importance of being a clinical radiologist; being treated as an equal is the best reward for your work.

What are your hobbies and interests outside of medicine?

I love travelling and learning about other cultures. I am a big fan of various sports, especially soccer, basketball, and tennis, which I also played myself. I enjoy good company with my beautiful family and many good friends, which I am blessed to have.

Interventional Radiological Society of Europe (CIRSE)

Current Appointments

Professor of Radiology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Head of Interventional Radiology, Department of Radiology, AHEPA University of Thessaloniki, Thessaloniki, Greece Chair, Department of Radiotherapy, AHEPA University of Thessaloniki, Thessaloniki, Greece Deputy chair, programme committee, Cardiovascular and

Society positions (selected) Secretary, Hellenic College of Radiology Member, executive committee, Greek Society of Interventional Radiology (GSIR)

Medical education and appointments

Chief, Department of Radiation Oncology, AHEPA University Hospital of Thessaloniki, Thessaloniki, Greece

Head, Interventional Radiology Unit, AHEPA University Hospital of Thessaloniki, Thessaloniki, Greece Professor, Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece Head, Department of Conventional Radiology and CT, Institute of Medical Imaging, University Hospital of Heraklion, Heraklion, Greece

November 2020 | Issue 80

26 CX Aortic Vienna

CX AORTIC VIENNA

Timing of intervention is critical for type B dissection, CX Aortic Vienna audience believe CX Aortic Vienna (8–11 September, online) shone the spotlight on thoracic aortic dissections, with discussion of both type A and B using endovascular and open approaches. Polling revealed that 94% of viewers believe timing of intervention is key for type B dissection, and discussion emphasised the benefits of staged procedures.

J

oseph Bavaria (Hospital of the University of Pennsylvania, Philadelphia, USA) began with a presentation in which he advocated moving toward “a definitive aortic solution” in acute type A dissections—describing what he sees as a new paradigm for the open zone 2/1 arch with sequential delayed branch arch thoracic endovascular aortic repair (TEVAR). Bavaria presented outcomes from various Debakey type 1 dissection cases, describing these as “catastrophic”, and arguing in favour of a change in approach in order to improve outcomes. The key concept in doing so, he suggested, is a strategy involving zone 2 arch replacement with sequential branched TEVAR. He said: “The future based on our data, our increased sophistication, and the availability of new technology is that in patients with less than 10‒15 years of life expectancy, usually >65, we use the classic hemiarch operations. A patient with an arch tear or distal malperfusion is suitable for an on-table frozen elephant trunk procedure. In patients who are younger than 65-years-old and stable, we perform a Zone 2 arch with possible sequential arch branch TEVAR, usually in a few weeks.”

Robin Heijmen (Antonius Hospital, Nieuwegein, The Netherlands) then discussed the value of transapical access for thoracic aortic procedures. Heijmen opened noting that the true value of TEVAR is its less-invasive approach, adding that the transfemoral route is preferred in most cases. However, where there is severe iliofemoral pathology this may not be possible, he said, adding that in these instances transapical access can be an alternative. Transapical access involves approaching through the “apex” of the left ventricle. “In recent years in more than 15 patients we have used transapical TEVAR safely and effectively and do appreciate its value in treating thoracic aortic pathology in case of an inadequate peripheral access,” Heijmen commented.

Following on from Heijmen, Germano Melissano (Vita-Salute San Raffaele University, Milan, Italy) detailed a new technical approach for type B dissection—the STABILISE concept—combining proximal descending aortic endografting with distal bare metal stenting. This technique results in a completely remodelled aorta throughout its whole length, according to Melissano. He also detailed the aims of the STABILISE Registry which is seeking to

Medical management “effective” for the treatment of Grade II blunt thoracic aortic injuries Ali Azizzadeh (Cedars-Sinai Medical Center, Los Angeles,

gather data on the use of the technique in 200 patients for a follow-up period of two years. The registry has been included in the top 10 candidates of aortic disease trials found on clinical trials.gov, in a study published in the Journal of Internal Medicine.

According to Kevin Mani (Uppsala University, Uppsala, Sweden) chronic type B aortic dissection can be successfully treated with TEVAR, however re-interventions are not uncommon, he told the CX Aortic Vienna audience, with the success of TEVAR dependent on the extension of the disease. In his presentation, covering the role of endovascular treatment in chronic type B aortic dissections, Mani reminded the audience that the endovascular toolbox includes both false lumen occlusion devices as well as

When it is possible, open surgical repair still represents the treatment of choice for chronic type B aortic dissection.” thoracoabdominal fenestrated repair. “TEVAR is not a one-off treatment in chronic type B aortic dissections and you have to prepare for future battles,” he said.

“Move sooner”, was the message from William Jordan (Emory University School of Medicine, Atlanta, USA) who offered the international CX Aortic Vienna audience his insights into the early treatment of type B aortic dissections. He noted that acute type B aortic dissection is a high risk condition, with a high rate of mortality, particularly for patients undergoing open repair and added that increasingly, treatment of type B aortic dissection has moved towards TEVAR in recent years. He then presented data on early versus late repair, using either TEVAR or open approaches— highlighting an improved 10-year survival in patients who underwent early repairs, specifically with TEVAR. Jordan concluded that endovascular therapy provides less invasive treatment for complex aortic pathology, and that early intervention is associated with better long-term survival.

USA) took to the virtual podium during CX Aortic Vienna (8–11 September, online) to discuss the medical management of blunt thoracic aortic injury, as viewed through the lens of the Aortic Trauma Foundation global registry. He believes the most recent data support revision of the current Society for Vascular Surgery (SVS) clinical practice guidelines.

THE CURRENT SVS CLINICAL practice guidelines recommend medical therapy for Grade I traumatic aortic

Clockwise from top left, Roger Greenhalgh, Stephan Haulon, Juerg Schmidli, Enrico Rinaldi, William Jordan and Kevin Mani

Clockwise from top left, Roger Greenhalgh, Stephan Haulon, Juerg Schmidli, Germano Melissano, Robin Heijmen and Joseph Bavaria

Polling results suggest a consensus that timing of intervention in type B dissections is a key consideration

Closing the session, Enrico Rinaldi (San Raffaele Scientific Institute, Milan, Italy) offered participants a series of technical tips for the open repair of chronic type B dissection. He noted that European guidelines recommend open repair for patients with aneurysmal or symptomatic chronic type B dissection with a low surgical risk. “When it is possible, open surgical repair still represents the treatment of choice for chronic type B aortic dissection,” Rinaldi said. His presentation highlighted the need for identification and management of the true and false lumen, proper graft selection based upon patient characteristics, challenges in intercostal artery reattachment, and management of the ascending aorta.

injury, and TEVAR or open repair for Grade II–IV. In 2016, the Aortic Trauma Foundation launched an international, multicentre, prospective blunt traumatic aortic injury registry. To date, 794 patients have been enrolled at 37 centres.

Azizzadeh et al set out to determine the outcomes of medical management for blunt traumatic aortic injury, and analysed a subset of patients in the Aortic Trauma Foundation’s global registry who had this treatment type listed as their definitive therapy. It included 432 patients treated from 2016–2020; 57% had medical management initially, and 26% had medical management planned

as definitive therapy. In this latter group, 59.6% had Grade I injuries, 23.7% had Grade II, and 16.7% had Grade III–IV. Twelve of the 114 patients (10.5%) required intervention after failed medical management. The majority (83.3%) of these patients had Grade III injury. Eleven of the 12 patients (92%) underwent TEVAR, and one underwent open repair.

While the overall in-hospital mortality was 7.9% (nine of 114 patients), the aortic-related mortality was zero, leading Azizzadeh et al to conclude that medical management “appears to be safe and effective, with a low overall intervention rate and no aortic-related deaths”.

November 2020 | Issue 80

28 Fertility and UAE

Fertility after uterine artery embolization: Still an unsolved issue, CIRSE delegates heard Fertility in patients who have had uterine artery embolization (UAE) is still a “hot topic,” Jean-Pierre Pelage (University Hospital and Medical Center, Caen, France) told delegates attending the online meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12– 15 September, virtual). “We have confusing data in the literature—we know fertility after UAE is possible, and that UAE is a valuable alternative to hysterectomy and multiple myomectomy in symptomatic patients, but the role of embolization in the specific subset of women trying to get pregnant remains controversial.”

WHILE SOME STUDIES HAVE DEMONSTRATED a 100% pregnancy rate following UAE, Pelage warned his audience that every patient is different, as is every procedure; there may be technical differences in how an embolization is conducted at different centres. There are some reports in the literature of complications specifically associated with fertility after UAE. In the EMMY trial, the level of follicle-stimulating hormone (FSH)—used as a measure of ovarian impact, with higher values typically seen in patients with a diminished ovarian reserve—was seen to increase after embolization.

However, this trend was more strongly observed in women over 45 years of age.

Complications from UAE include non-target embolization, mainly due to uterine-to-ovarian artery

anastomoses, and extensive myometrial and endometrial ischaemic damage, largely due to an aggressive embolization technique. The latter complication can result in hysterectomy, which Pelage said “is obviously a disaster for women trying to get pregnant.”

“There are some studies reporting very low pregnancy rates, including our initial experience: in 66 women offered embolization as a last resort treatment, there is virtually 0% pregnancy,” Pelage commented.

“All these studies are confusing,” he said, “including the only randomised controlled trial dedicated to fertility [from Michal Mara (Charles University, Prague, Czech Republic) et al, published in 2008]. The pregnancy Jean-Pierre Pelage presenting during the 2020 meeting of the Cardiovasular and Interventional Radiological Society of Europe

rate was lower after embolization, and the final term pregnancy rate was also very low.”

However, he did give the CIRSE audience some good news as well: “We know that you can expect spectacular volume reduction both of fibroids and of the uterus, which is good news for pregnancy. Embolization is a good alternative to myomectomy, which is the reference treatment for pregnancy-seeking women.”

In addition, Pelage’s group reported encouraging hormonal function following UAE, with no side effects of embolization on the ovarian reserve. Some studies have reported high rates of pregnancy: 61% (14 of 23 women) in a paper from Kavous Firouznia (Tehran University of Medical Sciences, Tehran, Iran) and colleagues published in 2009, which also reported no

UAE preserves fertility in patients with uterine arteriovenous malformations, single centre study shows Uterine artery embolization (UAE) preserved fertility in “at least 75% of patients with acquired uterine arteriovenous malformations,” according to a recent single centre study presented at the virtual 2020 Global Embolization and Cancer Symposium Technologies (GEST) meeting (4–6 September, online) by Dmitry Akinfiev (National Medical Research Center for Obstetrics, Gynecology and Perinatology, Kulakov, Russia).

“I

n our work, the clinical effectiveness of UAE in acquired uterine arteriovenous malformations is 86.2%,” he shared.

Akinfiev and his team conducted a retrospective, single centre study involving 29 patients, with a mean age of 29.1 years—“rather low”, in the presenter’s words, with the oldest patient included in the study being 43 years old. “All [patients included in the study] were fertile,” Akinfiev informed delegates. The study investigators performed 34 UAE procedures, and the mean patient follow-up was 2.5 years (range: one to six years).

Uterine arteriovenous malformations are rare, the GEST audience were told.

“Speaking of risk factors for acquired uterine arteriovenous malformations,” Akinfiev said, “in 80% of cases, the malformation was associated with curettage [19 patients had curettage following a miscarriage; four patients had a normal pregnancy and underwent curettage; one patient had a diagnostic curettage and no pregnancy]. Also, we had one patient with arteriovenous malformation after vacuum aspiration [following a normal pregnancy].” A further two patients developed uterine arteriovenous malformations due to

significant complications post-procedurally; and 59.5% (44 of 74 women) in a paper from João Pisco (St Louis Hospital, Lisbon, Portugal) et al, published in 2011.

Detailing his own institution’s recent experience, Pelage told registrants: “[We had a] 56% pregnancy rate in better-selected women, so younger than in our first cohort.” The 16 women included in this more recent study had an average age of 35 years, and nine of the group were actively trying to conceive. One-year postembolization, five of the women were pregnant.

Citing the results of the FEMME trial, published in the New England Journal of Medicine (NEJM) in July 2020, Pelage highlighted the team’s fertility results: “They reported a significant number of pregnancies after embolization, even higher than in the surgery [myomectomy] group. Since it was not the primary objective, I well understand that you cannot draw definitive conclusions based on this paper.”

Pelage summarised: “Pregnancy results are very variable, ranging from 14–61% from one study to another. The same [is true] for the miscarriage rate, obviously with miscarriage being more common in older women. From the existing literature, there seems to be an interest on the hormonal function [elevated FSH levels is more frequent after UAE], there seems to be a higher rate of pregnancy after myomectomy compared to embolization, and the rate of miscarriage seems to be higher after embolization. But again, most cases are not treated in a randomised trial, and treated women are older or have more fertility-confounding factors when treated with embolization.”

These summations led him to conclude that, “Despite the encouraging results of recent publications, we should still consider embolization with caution in pregnancyseeking women. In our centre, we always discuss as a group with the referring gynaecologist to decide whether we should offer embolization or myomectomy, and we know that prospective randomised trials are very difficult to conduct in this group of women.”

gestational trophoblastic disease, and two patients acquired malformations for unknown reasons.

The team used irregular uterine bleeding as the primary indication for embolization. Eight patients (27%) needed a blood transfusion prior to UAE, and 10 procedures of 34 (29%) were emergency UAEs. All patients underwent ultrasound and computed tomography (CT)angiography before and after the procedure. “Those were our main diagnostic instruments,” Akinfiev divulged. “Importantly, we performed CT-angio from the diaphragm to the bottom of [the] pelvis.”

Akinfiev told the GEST attendees that 10 of the 34 procedures were expanded by embolizing additional arteries: branches of the internal iliacs, ovarian arteries, and superior mesenteric artery branches. Twenty-seven (80%) of the procedures were performed via the radial approach, and embolizations were performed with gelfoam and non-spherical polyvinyl acetate (PVA) particles under 500µm. “I prefer to use gelfoam in cubes,” Akinfiev disclosed.

The evaluation parameters for the study were the elimination of abnormal uterine bleeding, and the absence or significant reduction of arteriovenous shunting on CT-angio.

Of the 29 patients, 25 (86%) experienced clinical success after one

procedure. Of the four who underwent a second procedure, the clinical success rate was 75%, with one patient having to have a third embolization. This third UAE was a clinical success.

There was a significant correlation between the clinical findings and the diagnostic findings, as presented on CT-angio. Of the 34 procedures, 27 were both clinically successful, and diagnostic imaging revealed a reduction or absence of arteriovenous shunting following UAE. In two cases, the interventionalists reported a clinical success, but diagnostic imaging showed the presence of arteriovenous shunting post-procedurally. All five clinical failures showed arteriovenous shunting on CT-angio. “There were no patients with CT-angio success and clinical failure,” Akinfiev said.

Next, he turned to reproductive outcomes. Of the 29 patients included in the study, 12 (41%) desired pregnancy, and 17 (59%) did not. In the desiring pregnancy subgroup, nine (75%) women did become pregnant, and all nine have since given birth, “a rather encouraging result,” according to Akinfiev.

“We had only one patient with a comorbidity during pregnancy,” he continued, “a patient with placental presentation. Our obstetricians had to perform a caesarean section in the 35th week of gestation due to threatening bleeding.”

November 2020 | Issue 80

30 Y-90 radioembolization

Radioembolization with Y-90 now “a versatile treatment option” for HCC patients of all stages Robert Lewandowski Comment & Analysis As presented at the Global Embolization Oncology Symposium Technologies (GEST) 2020 meeting (4–6 September, virtual), Robert Lewandowski discusses the evolution of radioembolization with Yttrium-90 (Y-90) over the past decade. Initially a lobar therapy, Y-90 can today be performed via a segmental delivery of microspheres to hepatocellular carcinoma (HCC) patients at earlier stages in their disease, and multiple tumours can be targeted in a sameday session. Furthermore, Lewandowski recounts how threshold dosimetry is now allowing for curative-intent therapy, and explains that the most recent data suggest this personalised dosimetry approach can be applied to a more advanced HCC population.

T

he historical role of radioembolization with Y-90 for patients with HCC is in the salvage setting; it has been employed to treat patients considered poor candidates for trans-arterial chemoembolization (TACE) or those that failed TACE. In contradistinction to the selective approach of TACE, radioembolization has been performed in a lobar (or sequential lobar) fashion. Despite these differences in patient selection and technique, evidence has supported the application of radioembolization over TACE in intermediate staged HCC patients because of improved quality of life metrics and longer time to progression. The median overall survival (OS) for patients with intermediate-stage HCC treated with Y-90 is 25 months.

A serendipitous observation following uni-lobar radioembolization was the development of an atrophy-hypertrophy complex; the treated hepatic lobe and targeted tumour decrease in size, with resultant hypertrophy in the contralateral lobe. For patients who would be candidates for surgical resection but present with an inadequate future liver remnant (FLR), radiation lobectomy was developed as a new paradigm to facilitate hepatic resection. With standard dosimetry, FLR hypertrophy is a timedependent process with approximately 10% hypertrophy from baseline at one-month post Y-90, and 45% by nine-months post Y-90. More recently, modified radiation lobectomy techniques have been developed to increase the rate of hypertrophy and to deliver more effective cancer therapy.

Early stage curative

The application of radioembolization is evolving from its lobar therapy origins; radioembolization is increasingly utilised in a segmental fashion to treat earlier stage disease. The results of the PREMIERE trial, a prospective, randomised trial for patients with unresectable tumours not amenable to ablation, revealed significantly improved outcomes for segmental radioembolization versus segmental TACE (time-to-progression >26 months vs. 6.8 months, respectively). These results have been corroborated by other US sites, including the University of Washington in Seattle, Mount Sinai Hospital, New York, and the Mayo Clinic, Jacksonville. The true potential of segmental radioembolization, however, is in its ablative potential.

Radiology-pathology correlative studies have revealed that complete pathologic necrosis at explant is best obtained when the volumes of perfusion are targeted with glass microsphere dosimetry >190 Gray. A recent multicentre analysis has reset this threshold dose for segmental radioembolization. In this analysis, all tumours treated with a segmental radiation dose >400 Gray achieved complete pathologic necrosis at explant.

High tumour response rates on imaging, long time to tumour progression, and meaningful complete pathologic response rates have made radiation segmentectomy a versatile therapy, allowing for downstaging to liver transplant, bridging

Advanced stage

downstaging tumour

Radioembolization Radioembolization with Y-90 has evolved over the past 10 years, morphing from a lobar therapy for patients with HCC advanced beyond being amenable to TACE into a versatile treatment option for patients across the Barcelona Clinic Liver Cancer staging paradigm.”

to liver transplant, or as a potentially definitive curative-intent therapy for early stage HCC. Median overall survival outcomes for Child-Pugh A patients with solitary HCC <5cm appear consistent with those for other curative therapies (i.e., ablation, surgical resection, liver transplant): 6.7 years from date of Y-90.

The evolution of radioembolization from a lobar therapy to a segmental therapy includes technical modifications beyond threshold dosimetry to achieve complete pathologic necrosis.

Many of these techniques have been developed for TACE over the past several decades. The first concept is that of same-day radioembolization: the planning angiogram, macro-aggregated albumin (MAA) administration to determine lung shunt fraction (LSF), and Y-90 administration can be performed in a single session. This is particularly appealing for patients with early stage disease amenable to radiation segmentectomy. Sameday radioembolization might further be streamlined by eliminating the requirement for the MAA administration in patients with limited disease burden.

Recent data support this concept by confirming low LSF for those HCC patients within Milan criteria. The second concept is that of performing radioembolization to extra-hepatic tumour perfusing branches. There is no established optimal embolic device to treat tumours via parasitised extra-hepatic arteries; there are now published reports describing the delivery of Y-90 via the inferior phrenic arteries, the adrenal artery, and the cystic artery. The final concept is that of segmental administration of Y-90 to multi-focal disease. With segmental radioembolization, multi-focal disease can be targeted in a single session through separate selective arterial catheterisations and dose vial administrations.

In conclusion, radioembolization with Y-90 has evolved over the past 10 years, morphing from a lobar therapy for patients with HCC advanced beyond being amenable to TACE into a versatile treatment option for patients across the Barcelona Clinic Liver Cancer staging paradigm. This evolution has allowed for radioembolization to be performed in a similar fashion to TACE: segmental/ selective delivery of Y-90 microspheres to HCC patients at earlier stages in their disease, targeting multiple tumours as well as extra-hepatic tumour-perfusing branches, often in a same-day session.

Most importantly, threshold dosimetry is now allowing for curative-intent therapy, supported by explant data. This concept of threshold, or personalised, dosimetry has more recently been expanded and applied to the advanced HCC population (DOSISPHERE-01 TRIAL), accepted for publication in the Lancet Gastroenterology & Hepatology.

Robert J Lewandowski is a professor of Radiology, Medicine, and Surgery, and the director of Interventional Oncology at the Northwestern University Feinberg School of Medicine, Chicago, USA.

November 2020 | Issue 80

32 Irreversible electroporation

CROSSFIRE trial: IRE induces a more immunepermissive environment in pancreatic cancer patients, correlated with improved survival Irreversible electroporation (IRE) significantly induces a window of reduced immune suppression two weeks post treatment, allowing the activation of effector T cells that seem to be correlated with improved survival, according to preliminary flow cytometry results of the CROSSFIRE trial. Speaking during the 2020 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual), Bart Geboers (Amsterdam UMC, Amsterdam, The Netherlands) described how his team investigated the immune modulatory effects of IRE and MR-guided stereotactic ablative body radiotherapy (SABR) in patients with locally advanced pancreatic cancer.

P

ancreatic cancer is one of the most aggressive cancers, Geboers informed the CIRSE audience, with a five-year overall survival of less than 10%. Thirty percent of all patients present with locally advanced disease, and are not amenable for surgical resection. The median overall survival for patients with locally advanced pancreatic cancer is approximately 12–14 months. “The problem with pancreatic cancer is that it is barely immunogenic, and the tumour cells can escape the immune system,” Geboers explained. “This might explain the disease’s aggressiveness.”

Describing the pathophysiology of the cancer, he said the low immunogenicity is “probably two-fold”: the cancer suppresses the tumour microenvironment, and is associated with a lack of spontaneous apoptosis.

In terms of suppressing its microenvironment, the tumour releases suppressive cytokines that induce activation and proliferation of specific T cell subsets that are immunosuppressive—regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). In turn, these reduce the activation and proliferation of effector T cells, including Helper T cells (CD4) and cytotoxic T cells (CD8), thereby providing the tumour with a “T cell tolerance”.

The second problem is the rarity of spontaneous tumour cell apoptosis. This means no epitopes are released that can be taken up by dendritic cells and used by the immune system to develop an adaptive response in the lymph nodes. Overcoming tumour-induced immune suppression is therefore difficult.

Tumour microenvironment temporarily shifts to become more immunopermissive two weeks after IRE

In order to assess the immune response, Geboers and colleagues took a venous blood sample from each patient before IRE or SABR, two weeks after treatment (to evaluate the immediate response), and three months

The problem with pancreatic cancer is that it is barely immunogenic, and the tumour cells can escape the immune system. This might explain the disease’s aggressiveness.”

activities). Two weeks after IRE, there was a significant upregulation of PD1 on the CD4 T cells. All the other checkpoints remained low. None of the checkpoints were significantly upregulated in the SABR group at any time point following ablation. “When looking at the activation status of the CD4 and CD8 T cells, we found that Ki67, which is a marker for T cell activation, was significantly upregulated at two weeks after SABR, in both CD4 and CD8 T cells, but was only significantly upregulated on the CD8 T cells two weeks after IRE ablation,” Geboers shared.

A linear regression model demonstrated that an increase in programmed cell death protein 1 (PD1), on both CD4 and CD8 T cells two weeks after IRE, was significantly associated with improved overall survival.

No significant correlation was seen between PD1 upregulation and overall survival in the SABR group.

“We found a significant downregulation of regulatory T cells two weeks after IRE that was simultaneous with a PD1 upregulation on CD4 T cells,” Geboers summarised. “The fact that the expression of the other checkpoints remained low argues against T cell exhaustion, but rather indicates that we are looking at a real effector T cell activation that might be amenable for PD1 blockade with checkpoint inhibitory drugs.”

The CIRSE audience were left with this promising take-home message: transient PD1 T cell upregulation combined with simultaneous regulatory T cell decrease after IRE is consistent with previously described systemic immune stimulatory effects of IRE, and supports combination with pharmacologic PD1 checkpoint inhibition.

“These findings warrant further studies, for which we designed the PANFIRE III trial,” Geboers told delegates.

This will be a Phase I trial in which 18 patients with oligometastatic pancreatic cancer will be included. The study has three arms: the first six patients will be treated with Nivolumab (a PD1 blockade; this is the control); the second six patients will be treated with IRE ablation of the primary tumour followed by Nivolumab; the final six patients will be treated with TLR-9 ligand intratumoural injection, followed by incomplete IRE ablation of the primary tumour and Nivolumab.

Altering the immune balance of the tumour microenvironment

Geboers and colleagues hypothesised that ablation can alter the immune balance, changing the microenvironment from an immunosuppressive one to a more immunopermissive one. “We know that ablation results in a reduction in the tumour mass, and so a reduction in suppressive cytokines. This will lead to a reduction in T cell tolerance, and allow the development of effector T cells,” he explained. In addition, ablation induces apoptosis and necrosis, meaning there will be a release of immunogenic epitopes that can be taken up by antigen-presenting cells. Furthermore, “IRE has the advancement of being vessel-sparing,” Geboers said, so antigen-presenting cells can transport epitopic antibodies to lymph nodes, where an adaptive immune response can occur.

To test this thinking, the investigators conducted an immunological side study of the CROSSFIRE trial, where pancreatic cancer patients were prospectively enrolled between January 2016 and February 2020.

Patients with locally-advanced pancreatic cancer were pre-treated with FOLFIRINOX, before being randomised between IRE or SABR.

Bart Geboers presenting at CIRSE 2020

post-treatment (to evaluate the durable immune response). Flow cytometry analysis was used to detect the type, frequency, and activation status of circulating immune cells.

A T cell analysis of 36 patients (19 treated with IRE, 17 with SABR) revealed that, two weeks after IRE, there was a significant downregulation of the regulatory T cells in the peripheral blood flow, as predicted by Geboers and colleagues. This downregulation returned to baseline three months after IRE. There was a trend for down regulation of the regulatory T cells three months after SABR, though this was not significant.

The investigators next looked at checkpoint expression of CD4 and CD8 T cells (the effector or helper T cells that were suppressed by the tumour’s

Ablation results in a reduction in the tumour mass, and so a reduction in suppressive cytokines. This will lead to a reduction in T cell tolerance, and allow the development of effector T cells [stimulating an immune response].”

Issue 80 | November 2020

Immuno-oncology and IR 33

Combination of immunooncology and liver-directed therapy: Where do we stand?

Brad Wood Comment & Analysis Ushering in “the era of IO”, Brad Wood calls for interventional oncologists to learn the language of immuno-oncology—“the other IO”—in order to improve care for cancer patients. Discussing the “speculative but huge potential impact” of combining interventional radiology (IR) approaches with an understanding of immunooncology, Wood informs readers that this is not merely an exciting opportunity to increase the scope of interventional oncologists’ work, but a necessary step in ensuring the discipline stays at the vanguard of oncologic treatment.

IT HAS BEEN KNOWN FOR decades that local-regional therapies like ablation and embolization can stimulate a tumour-specific systemic immune response, or even, on some occasions, tumour regression remote from the treated area. What is not known is who, what, where, when, and how to make it happen more often. Enter the era of IO, which to most people means immuno-oncology, and not interventional oncology. Bridging the gap (between IO and the other IO) requires learning the language and themes of cancer immunology. Interventional radiology (IR) has several hammers to pull out of our big IO toolbox. However, we need to determine whether to freeze, fry, shake, shock, zap, or choke a tumour— that is, whether to use cryoablation, radiofrequency ablation (RFA), microwave ablation (MWA), irreversible electroporation (IRE), high-intensity focused ultrasound (HIFU), histotripsy, transarterial chemoembolization [TACE], or Yttrium-90 (Y-90) radioembolization.

We also need to determine which histology to treat, at what stage, alongside what IO drug, and in what sequence. Where in the cancer immunity cycle do the IO tools immuno-modulate?

How do we balance pro-immune versus pro-metastatic pathways? The window of opportunity remains open for answering the many questions in a rational way.

Checkpoint inhibition takes the brakes off our natural immune response to tumours. Although revolutionary and Nobel prize-worthy, checkpoint inhibitors usually fail as monotherapy, are costly, and are not without side effects. Enter IR/IO. Local IO therapies alongside checkpoint inhibition can convert an “immune-cold” tumour into an “immunehot” tumour, potentially turning local into systemic. Immunomodulatory mechanisms boil down to enhancement of: 1) antigen release and presentation, 2) antigen-presenting cell (APC) maturation, 3) T cell priming proliferation and

EMBO DEB-TACE Y90

study.1,2 This showed disease stabilisation in the bulk of patients with advanced and heavily pre-treated HCC via this combination approach, often with intentional subtotal treatment of the target tumours. This study also has strong blood and tissue evidence for an immune mechanism when looking at responders versus non-responders.

For cholangiocarcinoma, a similar approach with subtotal ablation can be taken.3 Human tissue and survival data convince more medical oncologists at a multidisciplinary tumour board meeting than curing mice in 1,000 lab studies. In this setting, the local or regional therapy is meant to boost the immune system, deposit antigens, promote APC and T cell maturation, broaden the T cell receptor response, and tip the balance of immuneregulation away from immune tolerance and towards tumour-specific T cell activation. More recently, Bevacizumab plus Atezolizumab was approved by the US Food and Drug Administration (FDA) for locally-advanced HCC,4 and ongoing clinical trials will hopefully address whether and when local ablation or

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Although revolutionary and Nobel prize-worthy, checkpoint inhibitors usually fail as monotherapy, are costly, and are not without side effects.

Enter IR/IO.” trafficking, and, 4) reduction of immune tolerance and immune resistance. The molecular tumour micro-environment and the dynamic immune compartments (blood vessels, lymph nodes, target tumours, and remote tumours) also merit consideration.

Initial clinical experience with checkpoint inhibition drugs plus ablation or embolization for advanced hepatocellular carcinoma (HCC) was first reported over five years ago in a National Institute of Health (NIH)

embolization add value. The therapeutic options are evolving fast, so IR needs to organise a clinical trial infrastructure so we can ask hypothesis-driven questions in a standardised fashion. Team science wins.

Emerging data support aggressive local-regional therapies when immunotherapy fails locally in established tumours (versus new widespread metastases). Specifically, when stratified by patterns of failure, local therapy has been shown to be

particularly effective after failed checkpoint inhibition, supporting an aggressive re-treatment approach, when progression is confined to established tumours (rather than new breakthrough metastases).5 Like ablation, drug-eluting bead TACE (DEB-TACE) and Y-90 radioembolization reduce regulatory T cells (good) and expand T cell responses in HCC. Doxorubicin potentiates immunogenic cell death and enhances cross-priming, but ischaemia cascades turn on damage/pathogen-associated molecular patterns (DAMPS/PAMPS), HIF1a, and cell stress pathways. IRE may leave vessel highways intact for APC and T cell trafficking, which may explain why IRE (shock) may be better for immunomodulation than RFA (heat) or cryoablation (freeze) for T cell activation. Histotripsy may be better than heat when combined with checkpoint inhibition.6 Both IRE and cryoablation release more proteins than heat. Yet RFA heat may have a favourable impact upon immunosuppressive T-regs than cryoablation. Cryoablation may have the most inflammation and cell stress signals. Any ablation might recruit more good macrophages than bad, when the margin interacts with the tumour (thus leaving tumour behind). Yet, colorectal metastases may explode when partially treated and exposed to the hypoxia of partial treatment.

Clearly, we need to biopsy more after IO therapies. We need to learn more about the tools to measure immune effects (such as immunohistochemistry, flow cytometry, and sequencing). It is a great time to have a coffee with an expert from another discipline!

So when you freeze, fry, shake, shock, zap, or choke the tumour—treat the patient, not the picture. Do not be a technical robot and just treat geometric spots in the liver. Think before ablating.

Create the proper tumour microenvironment via timing, sequence, and delivery of rational IO plus IO immunomodulation. This is a one-time opportunity, with speculative but huge potential impact. New immuno-oncology trials with checkpoint inhibitor drug combinations have exploded in the past two years.7 Where is IR? We need to be at the table and not on the menu.

Brad Wood is an interventional oncologist at the National Institutes of Health (NIH) Center for Interventional Oncology, Bethesda, USA. References: 1. Presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, 2015 Duffy AG et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma.

Journal of Hepatology. 2017 Mar;66(3):545–551.

2. Changqing Xie et al. Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer. Hepatology. 2019 May;69(5):2048–2060.

3. Richard Finn et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. New England Journal of Medicine. 2020 May; 382:1894–1905.

4. Nicholas Klemen et al. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Journal of Immunotherapy of Cancer. 2019 July;7:196.

5. Eranki A, et al: High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy. Clinical Cancer Research 2020 Mar 1;26(5):1152-1161.

6. Greten TF, et al: Combined locoregionalimmunotherapy for liver cancer. Journal of Hepatology 2019 May;70(5):999-1007.

Issue 80 | November 2020

Interventional oncology 35

Cancer treatment beyond systemic chemotherapy: Local intra-tumoural injections demonstrate abscopal effect Preclinical and clinical studies show that local, intra-tumoural injection of immunomodulatory agents can result in the shrinking of tumours distant from the site of inoculation. Furthermore, when chemotherapy drugs are used as the immunomodulator, it may circumnavigate the need for systemic chemotherapy delivery. These are the conclusions presented by Thierry de Baere (Institut Gustave Roussy Université ParisSaclay, Villejuif, France) at the 2020 Symposium on Clinical Interventional Oncology (CIO; every Tuesday in October, online). “Because this is a new field, there are a lot of open questions,” he said. “What is the best target, how should I access the target, is it safe, is it the correct organ, how should I deliver [the drugs], what dose, which regimen, can I monitor the delivery of the drugs?”

“T

his is a very new, exciting field, and there is a space for interventional radiologists,” he told viewers. Showing a graph depicting the number of new intratumoural immunotherapy trials conducted each year since 1992, de Baere demonstrated the rapid growth of research in this space: from a low of one trial in 1992, to a high of 40 trials in 2016.

When injecting immunostimulatory agents into the tumour, interventionalists hope to achieve local priming, de Baere explained. “We want to trigger a tumour-specific immune response, but we also hope that this [local] response will result in distant effects,” he continued. The idea underpinning human intra-tumoural injections in cancer care is that these “distant effects”— known as abscopal effects—will confer systematic antitumour immunity at non-injected tumour sites.

Many different compounds can be used as immunostimulatory agents, and can be used at different stages of tumour immunity. De Baere expanded: “We use products that will release tumour antigens—could be peptides, could be viruses. We want to activate antigen presentation, we want to stimulate cytotoxic cells on site, and we want to deplete or block regulatory T cells [Tregs].”

After detailing the procedural details of intra-tumoural injection, which involve many technical decisions, de Baere stated: “Of course we should be part of this journey, because I think nobody can deliver better local treatment than interventional radiologists.”

A systemic response from a local treatment

Lipiodol offers an effective therapeutic option for melanoma patients suffering postoperative complications from radical lymphadenectomy Lymphatic fistulae and/or lymphoceles in the groin following radical lymphadenectomy are frequent, and therapeutic options are needed to avoid severe restrictions for oncologic patients waiting for adjuvant medical therapies. This is the key message Florian Offensperger (General and Interventional Radiology, Stuttgart Clinics, Stuttgart, Germany) wants audience members to take home from the 2020 virtual Global Embolization and Cancer Symposium Technologies (GEST) meeting (4–6 September, online).

“IT IS IMPORTANT TO SAY THAT there are treatment options,” he told attendees of the live event on Friday 4 September, “because we often have excellent patients who have been told that there is no other option but to wait.”

Stuttgart Clinics, where Offensperger works, is one of the largest surgical centres in Germany.

Discussing postoperative lymphatic complications following radical inguinal lymphadenectomy in patients with malignant melanoma, Offensperger says: “Where wood is chopped, splinters must fall”. However, his talk offers hope for how best to deal with these splinters—a complication need not spell disaster for a patient.

The basic lymphatic intervention performed at the Stuttgart Clinics for

patients with postoperative complications from radical inguinal lymphadenectomy is pedal Lipiodol lymphangiography combined with second-line interventions.

“In our opinion,” Offensperger says, this is “the best treatment for these patients”.

He informs the GEST audience that the technical success rate of conventional lymphangiography is 75–100%, and the cure rate of postoperative lymphatic leakage for pedal conventional lymphangiography is 51–70% (time to cure, two to 29 days). “Conventional lymphangiography is safe, feasible, and effective in the management of postoperative lymphatic leakage,” he concludes, showing a pre-recorded video of the procedure to illustrate how it works to his audience. “Personally, I really like this intervention, because it is a delicate

De Baere and other interested interventionalists hoping for confirmation of abscopal effects from local intratumoural injection are eagerly awaiting the results of ILLUMINATE 301, a randomised, phase III study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy. Tilsotolimod is a toll-like receptor agonist with potent immunostimulating activity, as described in the literature.

In a presentation given by Adi Diab (The University of Texas MD Anderson Cancer Center, Houston, USA) at the European Society of Molecular Oncology (ESMO) annual meeting back in October 2018, the intra-tumoural injection of tilsotolimod combined with ipilimumab resulted in a decrease in the size of an off-target melanoma tumour—one that was not injected with any drugs. Committing this finding to the collective medical memory, Diab and colleagues describe in Annals of Oncology how, in the phase I/II ILLUMINATE 301 study, intratumoural tilsotolimod with ipilimumab was “well-tolerated, demonstrating durable responses (including complete response >21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in responders, and an abscopal effect”. At the time of writing, phase III results from ILLUMINATE 301 are anticipated in the first fiscal quarter of 2021.

Offering a personal example, de Baere showed the CIO audience a case performed at his own institution.

The patient had a single injection of ipilimumab into a liver metastasis, as well as systemic treatment with nivolumab. “You can see we had an overall response from all of the tumours, despite [the fact that] only one tumour was injected.

task requiring many interventional techniques,” he shared.

In the present study, Offensperger and colleagues conducted a prospective analysis of their institutional digital databases for melanoma patients. They compared patients who had been treated with lymphatic angiography alone with those who had been treated with lymphatic angiography combined with sclerotherapy.

Between October 2014 and June 2019, 13 patients met the inclusion criteria: nine in the lymphatic angiography alone group, and four in the combined lymphatic angiography and sclerotherapy group. Mean patient age was 66.4 years (range: 46.8–83.4 years), and the interval between radical inguinal lymphadenectomy and lymphatic angiography was 17.8 days (range: seven to 34). The technical success rate for lymphatic angiography was 93%. The amount of Lipiodol used to perform the procedure was 15.4ml (range: 6–22ml), and in the combined group sclerotherapy was applied after an interval of 10 days

Personally, I really like this intervention, because it is a delicate task requiring many interventional techniques.”

(range: zero to 23). Sclerotherapy was performed either with 3–5ml ethanol, or with a glue/ Lipiodol 1:5 mixture (6–8ml) under fluoroscopy or computed tomography (CT) guidance.

The clinical success rate was higher in patients treated with lymphatic angiography and sclerotherapy, 100% compared with 78%. However, the interval between intervention and cure was slightly shorter in the cohort treated with lymphatic angiography alone: 23 days (range: four to seven) versus 29 days (range: 24–33). While there were no minor procedure-related complications in the group of patients treated with lymphatic angiography alone, there was one in the combined cohort (representing 25% of the patients treated in this arm of the study), a local infection cured by antibiotic treatment. There were no major procedure-related complications in the study.

These results led Offensperger to conclude that “Lymphatic angiography, with or without sclerotherapy, is an essential tool to cure therapy-refractory lymphatic fistulae after radical inguinal lymphadenectomy in patients with malignant melanoma.

“Lymphatic angiography in combination with sclerotherapy seems to result in higher clinical success rates,” he continued, “but also in higher complication rates when compared with lymphatic angiography alone.” However, he stressed that he wanted to leave GEST attendees with the understanding that lymphatic angiography in combination with sclerotherapy is a safe and effective option.

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Issue 80 | November 2020

Hepatic ablation 37

“A whole new world for IR”: How ablation is transforming cancer care Speaking during a livestreamed session dedicated to state-of-theart liver therapy hosted by the Symposium on Clinical Interventional Oncology (CIO) in October, Raul Uppot (Massachusetts General Hospital, Boston, USA) discussed the evolution of liver ablation, from the first procedure in November 1986—where the hepatic tumour was injected with alcohol—to the potential of this treatment modality to offer systemic, curative cancer care, possibly even without inserting a single needle. Here, he shares his thoughts on the past, present, and future of ablation with Interventional News.

if you were able to surgically debulk disease in the liver for certain cancers (such as colorectal cancer), then you could improve survival. The same data is now being applied to IR, where, if you can debulk as much of the tumour in the liver, then you can potentially improve overall survival.

What is the evidence for ablation in the treatment of liver metastases?

I think the biggest trial out there that we are excited about is the COLLISION trial—this is a trial that will compare the treatment of colorectal cancer metastases with ablation versus surgery. The trial started in 2017, is expected to recruit 600 or so patients, and has a planned end date of 2022. The strength of this trial is that it is a multicentre, randomised controlled trial that will try to answer the question: is ablation as good or better than surgical resection, the current gold standard?

Given our historical data on

were really just to provide a good option for locally controlling liver tumours. I do not think that the first time an ablation was done, there was ever any belief that we would treat widespread, systemic disease with a single probe. So it is very exciting now to learn that certain tools we now have, such as irreversible electroporation (IRE) and cryoablation, can potentially incite systemic effects.

There are now a lot of trials going on exploring the combination of immunotherapy drugs and ablation.

I think where ablation fits into this whole paradigm is that, by destroying the tumour, you are able to release antigens; the release of these antigens, combined with immunotherapy drugs, could potentially affect overall systemic disease. I personally have had a few patients where treating a single tumour in the adrenal glands or the kidneys has ultimately resulted in a decrease in size of metastatic tumours in other parts of the body. This was accidental—we call it an abscopal effect. I think this has happened enough times that people have realised there is a way to study this, there is a way to learn how this could potentially be occurring, and control it, and use immunotherapy drugs to help it, so it is exciting, because I think for the first time it is a whole new world for IR. The ability to put a needle into one lesion, treat that, yet somehow affect systemic tumour control everywhere else, and improve overall survival in the patient.

What is the key message you would like your IR colleagues to take home from your CIO presentation on liver ablation?

What are the benefits of ablation of the liver, and are there any downsides?

The beauty of ablation is that, in a very minimally invasive way, you can treat tumours. In the past, when we were just doing biopsies, it was amazing to us that you could put a needle directly into the target to sample it for diagnostic purposes. Since the late 1980s, we have moved towards being able to treat tumours in a similarly minimally invasive fashion. The ability to use CT or ultrasound to put a small needle into something, to completely treat a tumour that previously would have required surgery, pull the needle out, put a band aid on, and send the patient home—that is what is unique about ablation.

Ablation allows you to treat tumours in a minimally invasively fashion, and we now have the data to show that the ability to do that has long-term impacts on our patients. As with any procedure that we do, there are risks, the same you would have with any procedure: bleeding, infection, injury to adjacent organs.

How has the use of hepatic ablation changed over time?

The first hepatic ablation involved the insertion of a small needle into a tumour that was then injected with alcohol.

People realised that alcohol could destroy tissue, so thought ‘Why not kill tumours by injecting alcohol into them?’ Since then, we have developed more advanced equipment that can burn or freeze tumours.

The applications have evolved as well. We initially treated primary hepatocellular tumours, and, over many studies, we have shown that [ablation] is very successful at local control and improving overall survival in patients.

But we have also evolved into other tumours, such as treating metastatic disease. I think an exciting part of interventional radiology (IR) now is the ability to treat metastatic disease: colorectal cancer, pancreatic cancer, breast cancer metastases to the liver.

Management of all of these tumours are based on a background knowledge from the surgical literature. For example,

It is exciting that, using a small probe, you can insert it into the liver and impact care.” ablation, especially for the treatment of hepatocellular cancer, we know that we can treat tumours with a good margin, so the expectation is that, in much the same way as surgery has improved survival in terms of debulking metastases disease to the liver, ablation could probably do the same thing, but with lower costs, less hospitalisation time, and with an equivalent survival to surgically treated patients.

What does the future of ablation look like?

When ablation first started, our goals

What I want people to know is that liver ablation started off as a small trial: can we kill a tumour with a small needle?

Over the past 30 years, we have shown that that is possible. It is exciting that, using a small probe, you can insert it into the liver and impact care: completely treat large tumours, multiple tumours, and yet the patient goes home as an outpatient with just a band-aid. The ability to do great oncological care and work with a small needle is exciting about ablation.

The other thing I am very excited about is that, over time, there has been a constant evolution in the technology [for ablation]. We started off with alcohol, but we evolved to radiofrequency ablation (RFA), cryoablation, microwave ablation, and IRE. There is a constant evolution in these technologies: we are constantly moving towards smaller and lighter probes that are more efficient in what they can destroy. There are new technologies on the horizon, such as histotripsy, that allow one to treat a tumour without inserting a needle. The ability to use ultrasound waves to kill tumour [cells] is what is coming down the pipeline. It is very exciting, the notion that a person could come in with a large liver tumour and one could treat it in a very minimally invasive fashion and, ultimately, improve the patient’s survival.

Issue 80 | November 2020

Neurovascular interventions 39

New devices for endovascular thrombectomy discussed at CIRSE In a session of the 2020 Cardiovascular and Radiological Society of Europe (CIRSE) meeting (12–15 September, virtual) focused on the hottest news in the endovascular thrombectomy space, Antonin Krajina (University Hospital, Hradec Králové, Czech Republic) shared new devices available for the procedure, and enthused about their potential in stroke management.

F

irst describing his, hypothetical, ideal device for endovascular thrombectomy, Krajina said that it should be “easy to use and have fast access to the clot”. Stent retrievers are assessed by their ability to integrate the clot and to keep hold of it during retrieval; radiopacity of the stent retriever therefore plays an important role, Krajina stated. Additionally, he explained how there is a significant association between first-pass complete reperfusion and favourable clinical outcome, with two to three times higher odds for a favourable clinical outcome compared with complete reperfusion after multiple passes.

Indeed, his key take-home message was that clot integration is a function of delivery technique, duration of device implantation, and clot mechanics. His talk therefore detailed how device design influences these aspects of performance. In addition, he urged his listeners to “use all tricks in the attempt to remove the clot at the first pass” (including aspiration via balloon guide), and detailed how the COMPASS trial results provide Level 1 data that an aspiration thrombectomy as first-pass approach is non-inferior to a stent-retriever as a first-line approach for the treatment of selected patients with acute large vessel ischaemic stroke.

clot burden, and in middle cerebral artery occlusions.

Higher rates of favourable outcome at discharge and 90 days were observed for the short stent retriever group (p<0.001). This led them to conclude, as Krajina related to the CIRSE audience, that stent retriever length “should be adjusted to clot burden score and vessel occlusion site.” Krajina clarified: “Stents for short occlusion are appropriate if they are 20mm long; for longer occlusions, we need longer stent retrievers.”

“What position of the stent-retriever in relation to the occlusion/ embolus is the most effective?” Krajina asked his viewers rhetorically. “If it [the stent-retriever] is too –proximal and/or only partially engaged into the clot, it is less probable that we can remove the whole clot,” he explained. “If the clot is more proximal to the stent-

The importance of device design

Comparing the Solitaire X device (Medtronic), the CatchView stent retriever (Balt), and the Embotrap III device (Cerenovus), Krajina showcased how each had platinum markers on the proximal and distal ends, explaining that these acted as radiopacity markers.

Turning to the capacity to integrate the clot, he next discussed the relative benefits of using a short (20mm) or a long (30mm) stent retriever: “A longer [stent retriever] may increase the capacity to catch the clot,” he said. This was proven by Gaurav Girdhar (Medtronic, Irvine, USA) et al in their January 2020 publication in Interventional Neurology, which concluded that stent length had a significant effect on first pass success rate (p<0.05). The authors wrote: “Longer stent retrievers may be safe and effective in improving first pass success for fibrin-rich clots in vitro and in vivo models of large vessel occlusion”. However, Krajina added that a longer stent retriever means higher friction, which in turn increases the probability of the device getting stuck and then elongating, resulting in a loss of apposition to the arterial wall. The embolisation risk of the clot is also higher with longer devices, he explained, as longer dwell times affect the likelihood of distal embolization.

“Stent retrieval length should be adjusted to clot extent,” Krajina said, citing a June 2020 paper published in Cerebrovascular Diseases from Hanna Styczen (University Hospital Essen, Essen, Germany) and colleagues. Styczen et al hypothesised that increased stent retriever length may improve the rate of complete angiographic reperfusion and decrease the respective number of attempts, resulting in a better clinical outcome. They conducted a retrospective analysis of 394 patients with large vessel occlusion in the anterior and posterior circulation treated with stent retriever mechanical thrombectomy, sorting patients by propensity matching into two groups: those treated with a short (20mm) device, and those treated with a long (30mm) device. They found that, in the anterior circulation, short stent retrievers had a significantly higher rate of first-pass reperfusion in cases with low

Use all tricks in the attempt to remove the clot at the first pass.” retriever, the probability that we remove it during firstpass is higher. To verify the relationship of the clot and the stent-retriever position, we perform an angiogram after stent-retriever deployment.”

Next, Krajina discussed how to decide what diameter stent-retriever device to use to increase the probability of successfully removing the clot at first pass, 4mm or 6mm. “If you look at a diameter of the M1 segment in males, it is about 2.5mm, and the diameter of the internal carotid artery is around 3mm,” he informed delegates.

Writing in the Journal of Neurointerventional Surgery in 2018, Mark Davison (Rush University Medical Center, Chicago, USA) and colleagues said: “Compared with males, females consistently fare worse following mechanical thrombectomy for large vessel ischaemic strokes. Understanding why this gender disparity occurs may guide improvements in future treatment strategies.”

In their study, they aimed to determine whether gender differences in cerebral arterial diameter correlated with clinical outcomes following stroke thrombectomy.

They therefore performed an observational study of 92 consecutive acute ischaemic stroke patients (42 women)

undergoing mechanical thrombectomy between June 2013 and August 2016 at a single, urban tertiary care medical centre. Catheter angiographic images were used to manually measure proximal segment arterial diameters in a standardised fashion, and medical record review was used to obtain relevant independent and dependent variables. Internal carotid artery terminus diameters for men and women were 3.08mm and 2.81mm, respectively (p=0.01). M1 segment middle cerebral artery diameters for men and women were 2.47mm and 2.18mm, respectively (p<0.0001). Nearly half (48%) the patients in the upper middle cerebral artery calibre tercile attained a favourable mRS 90day value compared with 35% in each of the lower and middle terciles (p=0.51). Larger middle cerebral artery diameters correlated with favourable discharge disposition (p=0.21).

This led Davison et al to conclude: “These results provide limited evidence that males have larger cerebral arterial diameters than females and that larger arterial diameters may improve the odds for favourable clinical outcomes. If future studies validate these findings, arterial diameter may become a relevant variable in the design of improved thrombectomy strategies.”

However, Krajina went on to say that “More and more studies are proving that stent-retrievers with larger diameters do not appear to provide clear benefits”.

A 2017 paper published in the American Journal of Neuroradiology reported how, in their investigation of the effects of different diameters of Solitaire retrievers on clinical outcomes, Dong Yang (Jinling Hospital, Second Military Medical University, Nanjing, China) et al found “no evidence of a differential effect of intra-arterial therapy based on the size of the stentretrievers”. Though they also found that, in patients with atherosclerotic disease, favourable reperfusion was associated with deployment of a small stent.

Demonstrating new designs for stent retrievers that he believes are improving interventionalists’ ability to successfully perform endovascular thrombectomy, Krajina introduced the NeVa stent retriever from Vesalio, which has clot pockets oriented at 90 degrees to each other that increase the first-pass effect. The Embotrap III device (Cerenovus) has an inner channel to stabilise the clot during retrieval, and an outer cage to engage and integrate the clot. With this latest re-design, the distal mesh of the Embotrap III device is also denser than previous iterations.

Access and delivery catheters and guidewires

“Besides stent-retrievers, we also need delivery catheters and guidewires,” Krajina said. In his view, the most important aspects to consider for these devices are navigability, pushability, kink resistance, and whether or not they can be assembled as a coaxial set.

A survey of Society of Neurointerventional Surgery (SNIS) neurointerventionalists that received 78 responses (approximately 10% of SNIS membership), published in the Journal of Neurointerventional Surgery, indicated an increase in aggressiveness in pursuing thrombectomy based on selection criteria.

Nearly 40% of respondents (39.7%) reported using catheter aspiration thrombectomy as a frontline therapy.

A further 28.2% opted for stent-retriever mechanical thrombectomy, and another 28.2% said they adopted a combined approach, utilising stent-retrievers with aspiration.

“Interventional neuroradiologists love to combine access catheters to create coaxial double, triple systems,” Krajina told CIRSE registrants, “sometimes in difficult or tortuous anatomy, referred to as a ‘tower of power’, to have enough support for intracranial catheters.”

To create such a set, the length and diameter of the catheter used is important, the CIRSE audience heard: “Ideally one should use the shortest length necessary to do the job.”

Issue 80 | November 2020

Market watch 41

Clinical News

Edward Choke and colleagues at Sengkang General Hospital, Singapore

Enrolment initiated in world’s first RCT with sirolimuscoated balloon for belowthe-knee PAD treatment

Concept Medical has announced the enrolment of the first patient in the FUTURE BTK (Randomised controlled trial of first sirolimus coated balloon versus standard balloon angioplasty in the treatment of below-the-knee artery disease) trial. The index patient was successfully enrolled on 26 August 2020 in Singapore.

FUTURE BTK is a randomised, double-blind, placebo-controlled, multicentere trial. It is aimed at determining the effectiveness of MagicTouch PTA sirolimus-coated balloon versus standard balloon angioplasty for the treatment of below the knee arterial disease in chronic limbthreatening ischaemia (CLTI) patients.

Edward Choke (Sengkang General Hospital, Singapore), principal investigator of FUTURE-BTK comments: “CLTI is a condition which puts patients at an increased risk of limb amputation and death. Its burden is likely to grow in the coming years given the rising trends in key risk factors such as age and diabetes. Effective revascularisation is the cornerstone of treatment, but this is often hampered by high rates of restenosis and reintervention after conventional balloon angioplasty”.

He adds: “The novel MagicTouch PTA sirolimus-coated balloon has emerged as one of the most promising transcatheter technologies in preventing restenosis for below-the-knee lesions.

The earlier data on the efficacy of MagicTouch PTA from small studies are encouraging but these need to be confirmed or refuted. I look forward to the FUTURE BTK randomised controlled trial, which will test whether the MagicTouch PTA sirolimus-coated balloon can improve the patency of below-the-knee arteries in CLTI patients, and this will hopefully bring us closer to our goal of reducing leg amputations”.

The trial will enrol 210 patients with Rutherford class 4 to 6 CLTI. These

patients will be randomised in 2:1 fashion to receive either MagicTouch PTA or standard balloon angioplasty.

Primary outcome will be primary patency at six months, defined as duplex peak systolic velocity ratio (PSVR) of 2.4 or less.

The trial is designed to follow a blinding protocol in order to minimise bias. Patients, care providers, investigators, and outcome assessors, including vascular technologists performing the duplex ultrasound, will be blinded to the treatment allocations.

The patients will be followed up for two years.

PQ Bypass completes enrolment in DETOUR II pivotal study

PQ Bypass has announced enrolment of the final subject in the company’s DETOUR II investigational device exemption (IDE) clinical trial. This milestone occurs only a month after the Detour system entered the US Food and Drug Administration (FDA)’s breakthrough device programme.

DETOUR II is led by national coprincipal investigators Sean Lyden (Cleveland Clinic, Cleveland, USA) and Jihad Mustapha (Advanced Cardiac and Vascular Centers, Grand Rapids, USA).

Both receive compensation for their duties in this role.

“The speed with which we were able to enroll DETOUR2 in 2020 speaks to the large patient population that exists with long-segment femoropopliteal disease that has sub-optimal endovascular options,” says Lyden.

“If percutaneous fem-pop bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR1 study, it could be a game changer for the way we treat complex, long-segment SFA [superficial femoral artery] disease today,” continues Mustapha.

DETOUR II is a prospective, multicentre trial evaluating the Detour system for percutaneous femoralpopliteal bypass in patients with extremely long, complex lesions in the SFA. The study enrolled 202 patients in 36 sites in the USA and Europe, and is assessing freedom from major adverse events (MAE) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness is primary patency at 12 months.

Ra Medical Systems announces 10 subjects have been enrolled in its DABRA trial

Ra Medical Systems has announced enrolment of the tenth subject in its pivotal clinical trial to evaluate the safety and effectiveness of the Dabra excimer laser system as an atherectomy device for the treatment of peripheral arterial disease (PAD).

“Patient screening and enrolment have recently increased with five clinical sites now cleared to enrol subjects as we pursue an atherectomy indication for Dabra,” said Will McGuire, Ra Medical Systems CEO. “Earlier this year enrolment in this trial had stalled due to the COVID-19 pandemic, which also impacted our ability to activate new clinical sites. We are pleased that nine subjects have been enrolled in the past two months at our clinical study sites, all of which are operating via applicable COVID-19 protocols.”

The open-label pivotal atherectomy clinical trial can enrol up to 100 patients with symptoms of PAD (Rutherford Class 2–5) at up to 10 sites. Outcome measures include safety, acute technical success, and clinical success. The trial’s primary efficacy endpoint is the mean reduction in percent diameter stenosis in each patient’s primary lesion as measured by angiography immediately following treatment with Dabra, before any adjunctive treatment.

The trial’s safety and clinical success endpoints are major adverse events at 30 days and incidence of primary target lesion revascularisation at six months.

Dabra received US Food and Drug Administration (FDA) 510(k) clearance in May 2017 for use in ablating a channel in occlusive peripheral vascular disease.

Dabra excimer laser system

Sirtex Medical completes enrollment of landmark US RESiN registry

Sirtex Medical reports that enrollment in the US RESiN registry has reached a milestone of 1,650 patients and 12.8 months of follow-up, allowing for a satisfactory number of patients enrolled for meaningful data analysis.

Under the leadership and direction of the trial’s executive committee, the registry will close enrollment at the 45 centres and will move to a new phase of data review and evaluation, publication, and presentation. The US RESiN registry, a database of patients eligible for treatment with SIR-Spheres Y-90 resin microspheres (Sirtex), started enrollment in 2015 and represents one of the largest prospective, multicentre, observational studies conducted in the field of interventional oncology.

The registry should provide robust real-world evidence to characterise the effectiveness, safety, and clinical impact of SIR-Spheres Y-90 resin microspheres,

a Sirtex press release states. To date, the RESiN registry has yielded several publications, including oral and poster presentations at international medical oncology and interventional radiology congresses, as well as a recent submission of, “Incidence and risk factors for sustained hepatic function toxicity six months after Y-90 radioembolization: Interim analysis of the radiation-emitting SIR-spheres in non-resectable liver tumour (RESIN) registry.”

Sirtex and Vanderbilt will focus efforts to expand the number of publications arising from this data base and topic areas of interest, such as an assessment of different pre-treatment planning dosimetry methods, orphan tumour outcomes, and specific cohorts of interest.

First two patients enrolled in PRISTINE study with Selution SLR

MedAlliance has announced enrolment of the first two patients in the PRISTINE registry with Selution sustained limus release (SLR) 018 drug-eluting balloon (DEB) for the treatment of patients with below-the-knee disease. This is the first DEB accepted by the US Food and Drug Administration (FDA) for its breakthrough programme.

The PRISTINE registry is a follow up to the encouraging results seen in the PRESTIGE clinical trial (belowthe-knee, chronic limb threatening ischaemia [CLTI]) at six months.

PRISTINE is a prospective registry to investigate the safety and efficacy of treatment with Selution SLR sirolimus drug-coated balloon in TASC C and D athero-occlusive infrainguinal disease in patients with CLTI from Singapore.

The objective of the registry is to evaluate over 12 months safety and performance outcomes in 75 patients, with Selution SLR DEB in the treatment of infrainguinal occlusive lesions (TASC C and D) in patients with CLTI at Singapore General Hospital.

The clinical primary safety endpoint of the registry is freedom from major adverse events through 30 days and the performance primary endpoint is freedom from clinically-driven target lesion revascularisation (CD-TLR) within six months. The secondary endpoints are primary patency at six and 12 months follow-up, freedom from CD-TLR at 12 months, clinical success at follow-up in Rutherford score by one class or more, wound healing at six months, and freedom from major target limb amputation within six and 12 months post index procedure.

“We are excited about the commencement of this large singlecentre prospective study focusing on patients with chronic limb threatening ischemia receiving the novel sirolimus drug-eluting balloon”, says Chong Tze Tec (Singapore General Hospital, Singapore). “We believe this registry will give us detailed insight into the efficacy and safety of this new balloon technology which will benefit this challenging group of patients.”

Issue 80 | November 2020

Market watch 43

Industry News

CDC recognises and codifies critical limb-threatening ischaemia in ICD-10-CM

A coalition organised by the CLI Global Society has announced its proposal to distinctly recognise “critical limb ischaemia” (CLI) and “chronic limbthreatening ischaemia” (CLTI) in the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) was approved by the Centers for Disease Control and Prevention (CDC) and went into effect on 1 October 2020.

The ICD-10-CM is a worldwide standard reference set of disease codes used to report medical services provided to patients. The announcement marks a major step forward in tracking patient treatments and outcomes for CLI and CLTI, which affect millions of patients globally.

The CLI Global Society worked in close partnership with the vascular specialist community to develop the proposal. Coalition members include: Robert Lookstein, CLI Global Society (CLIGS) Barry T Katzen, (CLIGS) Sean Roddy, Society for Vascular Surgery (SVS) Mitchell Weinberg, Society for Vascular Medicine (SVM) Bulent Arslan, Society of Interventional Radiology (SIR) Mehdi Shishehbohr, Society for Cardiac Angiography and Intervention (SCAI) The goal of this initiative is to support coding professionals, educators, compliance staff, and physicians to identify and accurately report CLI and CLTI in clinical documentation, electronic medical records, and medical billing in order to track and monitor patient treatments and outcomes in the future.

“This effort is a first step in building awareness of the complexity associated with caring for patients who suffer from CLI within public and commercial payers and the broader healthcare community,” says Barry Katzen, board chair of the CLI Global Society. “These dedicated codes, now newly identified for CLI, are critical in our goal to improve quality of life by preventing amputations and death due to CLI.” Robert Lookstein, chair of the Vascular Societies Workgroup and CLI Global Society board member, acknowledges the collective effort of his colleagues, “who came together to

prioritise the need for a well-defined and accessible method to identify, report, and track CLI for the benefit of patients who suffer from this disease.

“We also look forward to continued partnership as we launch initiatives to educate our membership, our hospitals, and healthcare provider staff regarding these changes,” Lookstein explains.

“They have the potential to positively impact the care we provide to these extremely vulnerable patients across the United States and around the world.”

CLI and CLTI are advanced forms of peripheral arterial disease (PAD), a common circulation problem that occurs when arteries that carry blood throughout the body become narrowed or blocked, restricting blood flow to legs and feet. Those who smoke, have diabetes or chronic kidney disease, or suffer from high blood pressure or high cholesterol are susceptible to CLI and its complications. Left untreated, CLI can lead to tissue loss, gangrene, amputations, and eventually death.

“The statistics are grim,” says Jihad Mustapha, founding board member of the CLI Global Society. “We know 60% of patients who receive an amputation due to PAD or CLI die within two years—this is higher than the five-year mortality rate for patients with breast, colon, and prostate cancer.

“In order to fight this deadly disease, we need to have accurate data. This seemingly small change to medical coding will allow us to save countless limbs—and lives.”

Authors from 750 German universities to publish in CVIR Endovascular free of charge

As of August 2020, corresponding authors from more than 750 German universities and research institutions are able to publish in Cardiovascular and Interventional Radiology (CVIR) Endovascular free of charge thanks to a deal Springer Nature has signed with these German research institutions.

An explanatory statement on the Springer Nature website reads: “If you

Springer Nature website

are a corresponding author affiliated with a German university or research institution, you are entitled to publish open access in our journals with fees covered by the German DEAL agreement.

“More than 900 German institutions are eligible to participate in the agreement between Springer Nature and Projekt DEAL, meaning that

corresponding authors affiliated with these institutions are eligible to publish their articles open access without being invoiced by Springer Nature. The agreement includes more than 2,000 hybrid journals across the Springer Nature portfolio (from January 2020) and more than 500 fully OA journals (from August 2020).”

First patient enrolled in FUTURE SFA study of MagicTouch sirolimuscoated balloon

Concept Medical has announced the enrolment of the first patient in the FUTURE SFA (Randomised controlled trial of first sirolimus coated balloon versus standard balloon angioplasty in the Treatment of superficial femoral Philips launches QuickClear artery and popliteal artery disease) study. mechanical thrombectomy The index patient was successfully system for blood clot enrolled on 12 September in Singapore. removal in latest portfolio FUTURE SFA is a randomised, expansion double blind, placebo-controlled, Royal Philips has announced the multicentre trial to determine the launch of the QuickClear mechanical effectiveness of the MagicTouch thrombectomy system. The singlePTA sirolimus drug-coated balloon use system delivers an all-in-one (DCB) versus standard percutaneous aspiration pump and catheter to transluminal angioplasty for the remove blood clots from the vessels treatment of superficial femoral and of the peripheral arterial and venous popliteal arterial disease. systems and has received US Food and Sirolimus-coated balloons are Drug Administration (FDA) 510(k) considered to be the next new clearance. generation of DCBs and the novel The system’s design aims to MagicTouch PTA sirolimus-coated simplify the use of the device balloon (SCB), has emerged and improve procedure times as one of the most promising without the need for capital transcatheter technologies equipment or accessories. in preventing restenosis for Chris Landon, senior vice diseased arteries. president and general The principal investigator QuickClear manager of image-guided of FUTURE SFA is Edward therapy devices at Philips, Choke (Sengkang General claims that “by taking away Hospital, Singapore), who the high initial capital expenditure costs comments: “I am inspired by the associated with traditional mechanical bold, imaginative, and futuristic thrombectomy systems, QuickClear concepts presented by the Nanolute can help bring cost-effective solutions technology of the MagicTouch PTA to both the hospital and outpatient care sirolimus-coated balloon. In contrast settings.” to other contemporary technologies, The small footprint of the sterile MagicTouch PTA offers a solution device allows it to be placed easily which optimises both the deliverability on the table next to the patient. The and the absorption of sirolimus into the company claims that the system can vessel wall.” easily work at maximum aspiration He adds: “Initial experience with the power within seconds and that the XTOSI first in man study suggested consistency of the aspiration power that MagicTouch PTA can provide an during the procedure supports faster effective way of revascularisation for procedure times.

PAD patients, by keeping the vessels Furthermore, the system’s range of open longer and reducing the need catheters includes a large 10F aspiration of repeated angioplasty procedures. catheter which, according to the I look forward to the FUTURE SFA company’s own in-house data, provides randomised controlled trial, which will 59% more aspiration volume than 8F test whether the Magic Touch PTA aspiration catheters. sirolimus-coated balloon can improve Bryan Fisher (The Surgical Clinic, the patencies of femoral and popliteal Nashville, USA) says that the arteries in PAD patients. We hope to “QuickClear is a simple and easy to use establish whether SCB will emerge as mechanical thrombectomy system.” He the new standard of care which will adds that it “is significantly smaller than impact the way we treat PAD.” other systems without compromising The trial will enrol 153 patients with aspiration power.”

Rutherford class 3 to 6 PAD. These The QuickClear mechanical subjects will be randomised in 2:1 thrombectomy system is the latest fashion to receive either Magic Touch expansion of the company’s portfolio PTA or standard balloon angioplasty. after acquiring Intact Vascular.

Primary outcome will be primary Philips’ peripheral vascular patency at six months, defined as portfolio already includes advanced duplex peak systolic velocity ratio interventional imaging systems for (PSVR) of 2.4 or less. precision guidance; intravascular The trial is designed to follow a ultrasound (IVUS) catheters to assess rigorous blinding protocol in order to the location of the disease and lesion minimise bias. Patients, care providers, morphology and guide and confirm investigators and outcome assessors, the treatment; peripheral atherectomy including vascular technologists devices to remove blockages; and performing the duplex ultrasound, will peripheral therapy devices, such as be blinded to the treatment allocations.

Philips’ Stellarex drug-coated balloon, The patients will be followed up for to treat lesions. two years.

Issue 80 | November 2020

Market watch 45

Teleflex announces expanded indications for the Arrow EZ-IO intraosseous vascular access system

Product News Biotronik’s Passeo-35 Xeo PTA balloon catheter is now available in Europe

Biotronik has announced European market release of the Passeo 35 Xeo percutaneous transluminal angioplasty (PTA) balloon catheter. A company press release states that, compared to other available PTA balloons, the device offers physicians improved crossability, excellent trackability, and pushability in a wide range of sizes.

“The new Passeo-35 Xeo balloon handled impressively well, crossing easily even in an occlusive lesion,” comments Gerd Grözinger (University Hospital Tübingen, Tübingen, Germany), after performing the firstin-human procedure with the balloon.

“The deflation time was also very fast compared to other balloons, which can save valuable procedure time.”

To aid in challenging lesion crossing, the Passeo-35 Xeo catheter offers a low entry profile, smooth tip taper, and up to 19.5% more pushability compared to competitors, facilitating improved catheter navigation in the peripheral vasculature. Catering to a full range of lesion sizes, the device is available in balloon diameters from 3–12mm and lengths of up to 250mm, with usable catheter lengths of 90, 130 and 170cm.

Additionally, the Passeo-35 Xeo catheter is fully 5F compatible for balloon sizes up to 7mm in diameter and 250mm in length.

The Passeo-35 Xeo balloon is indicated to dilate stenosis in the iliac, femoral, popliteal and infrapopliteal arteries, and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulae. It is also recommended for post-dilatation of balloon-expandable and self-expanding stents in the peripheral vasculature.

Passeo-35 Xeo is the platform for Biotronik’s recently released Dynetic-35 balloon-expandable cobalt chromium stent system.

CMS grants additional reimbursement for the Eluvia drug-eluting vascular stent system

Boston Scientific announced that the US Centers for Medicare and Medicaid Services (CMS) granted a new technology add-on payment (NTAP) for the Eluvia drug-eluting vascular stent system as part of the 2021 inpatient prospective payment system (IPPS).

The NTAP designation, awarded to new medical devices determined to substantially improve the diagnosis or treatment of Medicare beneficiaries, will be effective on 1 October 1 2020 and will provide eligible hospitals with incremental reimbursement for the Eluvia stent system for up to three years.

The Medicare criteria for an NTAP designation is based on newness of the device, cost, and a substantial clinical

improvement.

The Eluvia stent system was developed for the treatment of peripheral arterial disease (PAD). The Eluvia stent reopens the blocked artery and restores blood flow, while also utilising a drug-polymer combination to offer a sustained, low-dose release of drug to prevent tissue regrowth within the stented artery.

“The CMS determination is a very positive development for patients with PAD and supports what we have confirmed through our clinical trials— the Eluvia stent offers clinically superior outcomes compared to other peripheral drug-coated technology available to clinicians and their patients,” said Jeff Mirviss, executive vice president and president, Peripheral Interventions, Boston Scientific.

Teleflex has announced it has received 510(k) clearance from the US Food and Drug Administration to expand the indications for use of the Arrow EZ-IO intraosseous vascular access system. This device can be used when intravenous access is difficult or impossible to obtain in emergent, urgent, or medically necessary cases.

The Arrow EZ-IO system is now available with the expanded indication stating use of the device may be extended for up to 48 hours when alternate intravenous access is not available or reliably established in adults, and in paediatric patients 12 years and older.

“Vascular access is one of the most basic, yet critical, components of patient care,” said Michelle Fox, corporate vice president and chief medical officer, Teleflex. “The ability to use the EZ-IO system for a longer dwell time provides clinicians the option to utilise intraosseous (IO) access for the entire duration of therapy in patients with difficult vascular access where therapy is required for up to 48 hours.”

Gore enhances Gore Viabahn endoprosthesis portfolio with lower profile delivery

Eluvia drug-eluting stent

“The decision is particularly important given the level of consideration and evaluation related to the role of paclitaxel in the peripheral vasculature, and we believe this designation reflects the unique attributes of the Eluvia stent, which are clearly differentiated and improve the quality of life for the millions of people suffering from symptoms of PAD.” The NTAP designation will support access to the Eluvia stent for Medicare beneficiaries in the hospital inpatient setting, making it possible for eligible hospitals to receive NTAP payment in addition to the standard Medicare severity diagnosis related group (MSDRG) payment.

The US Food and Drug Administration (FDA) approval of the Eluvia stent system in September 2018 was based on findings from the IMPERIAL trial, which exhibited the highest 24-month primary patency reported to date for the treatment of femoropopliteal disease in a US pivotal trial with a drug-coated balloon or drugeluting stent. Trial data confirmed a statistically significant lower clinicallydriven target lesion revascularisation (TLR) rate of 12.7% for patients treated with the Eluvia stent, in contrast to 20.1% observed within the Zilver PTX drug-eluting peripheral stent cohort (p=0.0495), thus reducing the need for repeat procedures at 24 months.

Gore has announced the US launch of the lower profile, large diameter Gore Viabahn endoprosthesis.

Gore previously received approval from the US Food and Drug Administration (FDA) for the enhanced Gore Viabahn endoprosthesis.

“With broad clinical indications for use and numerous product improvements, the Viabahn device continues to be a dependable choice that demonstrates positive results in patients with complex vascular disease,” comments Amit J Dwivedi, (University of Louisville, Louisville, USA), who has implanted the lower profile device in complex arterial anatomy.

“Older patients with co-morbidities such as hypertension, diabetes, and obesity may benefit from a less invasive endoluminal approach versus surgical bypass. These latest enhancements, including a lower profile, provide physicians with additional options for treating these patients.”

This innovative Viabahn device design reduces the delivery profile for larger 9–13mm diameter stent grafts by up to 3Fr, enabling delivery through smaller sheaths.

Smaller introducer sheaths have resulted in a lower risk of vascular access complications in select patient populations, a Gore press release states. Additionally, new radiopaque markers on the distal and proximal ends enhance visualisation under fluoroscopy, facilitating positioning and device delivery, as well as precise and predictable placement.

“In addition to the radiopaque markers that facilitate positioning and

deployment, the new lower profile enables use of a smaller sheath, potentially reducing the risk of damage at the access site,” says Yevgeniy (Eugene) Rits (Wayne State University; Detroit Medical Center; Harper University Hospital, Detroit, USA).

“Combined with the trackability and flexibility I have always trusted with Viabahn devices, this new lower profile offering will become very instrumental in my dialysis access practice.”

Viabahn endoprosthesis

Currently, the Viabahn device is indicated for use in superficial femoral artery (SFA) lesions, iliac lesions, in-stent restenosis of SFA lesions, and in stenosis or thrombotic occlusion at the venous anastomosis of synthetic arteriovenous access grafts for haemodialysis.

Philips launches latest version of its Azurion imaging platform

Royal Philips has announced the next-generation of its Azurion imageguided therapy platform, designed to improve the quality and efficiency of interventional procedures.

The platform now integrates control of imaging, physiology, haemodynamic and informatics applications, as well as intuitive control of the gantry, at the tableside, allowing clinicians to control all compatible applications from a touch screen while performing procedures. This can eliminate the need for clinicians to leave the sterile field and step into an adjacent control room, as well as supporting faster and better informed decision making, a company press release states.

Philips is also introducing a new 3D imaging solution called Smart-CT, where users are guided through image acquisition and can review and interact with the acquired CT-like 3D images on the tableside touch screen module using 3D visualisation and measurement tools. These tools have been designed to support procedures in a range of clinical domains, including neurology, oncology, and cardiovascular procedures.

Boston Scientific receives FDA approval for the Ranger DCB

Boston Scientific announced it has received US Food and Drug Administration (FDA) approval of the Ranger drug-coated balloon (DCB), developed for the treatment of patients with peripheral arterial disease (PAD) in the superficial femoral artery (SFA) and proximal popliteal artery (PPA).

According to a press release, the Ranger DCB was designed with a low therapeutic drug dose and proprietary

November 2020 | Issue 80

46 Market watch

Product News coating which efficiently transfers the drug into the tissue, resulting in high primary patency rates and low systemic drug exposure for patients.

“This approval allows us to bring more treatment options with exceptional outcomes and proven safety to US physicians and their patients who are facing this challenging disease,” said Jeff Mirviss, president, Peripheral Interventions, Boston Scientific.

“Adding the Ranger DCB to our drugeluting portfolio, which also includes our Eluvia drug-eluting vascular stent system, reinforces our commitment to providing differentiated technology with strong clinical evidence that supports data-driven treatment decisions for millions of patients suffering from PAD worldwide.”

The FDA approval is based on results from the RANGER II SFA pivotal trial, which evaluated the safety and effectiveness of the Ranger DCB versus standard percutaneous transluminal angioplasty (PTA) for the treatment of patients with PAD in the SFA and PPA. In the randomised controlled trial, both primary endpoints were met: The primary safety endpoint of

12-month freedom from major adverse events (MAE) was 94.1% for those treated with the Ranger DCB vs. 83.5% for standard PTA (Pnoninferiority <0.0001).

Additionally, patients who received therapy with the Ranger DCB had a significantly lower target lesion revascularisation rate—a component of MAE—of 5.5% in contrast to 16.5% observed with standard PTA (p=0.0011), substantially reducing a patient’s need for repeat procedures.

The primary efficacy endpoint of 12-month binary primary patency—a measure of the target vessel remaining unobstructed—was 82.9% for the

Ranger drug-coated balloon

Ranger DCB and 66.3% for standard PTA (p=0.0017). Primary patency by Kaplan-Meier estimate was 89.8% for the Ranger DCB and 74% for PTA at 12 months (p=0.0005).

“The Ranger DCB eases deliverability for a wide range of lesion complexities via a low profile platform that is compatible with smaller diameter guidewires and has shown consistent results in multiple randomised controlled trials,” said Ravish Sachar, physician-in-chief for Heart and Vascular services at UNC Rex Hospital (Raleigh, USA) and principal investigator of the RANGER II SFA trial. “For physicians seeking to limit systemic drug loss without compromising outcomes, data demonstrate the Ranger DCB is a safe and effective treatment option.”

The Ranger DCB also demonstrated nearly 90% primary patency in the investigator-sponsored COMPARE trial—the first head-to-head prospective, randomised controlled trial to compare two different DCBs. In the trial, the Ranger DCB demonstrated a similar primary patency rate of 88.4% to that of the 89.4% observed with IN.PACT Admiral drug-coated balloon (Medtronic) by Kaplan-Meier estimate (p=0.81), with a significantly lower drug dose density (2µg/mm2 paclitaxel vs.

3.5µg/mm2 paclitaxel, respectively).

Medtronic Abre stent receives US FDA approval to treat venous outflow obstruction

Medtronic has received US Food and Drug Administration (FDA) approval for use of the Abre venous self-expanding stent system in the iliofemoral veins in patients with symptomatic iliofemoral venous outflow obstruction.

The FDA approval is based on 12-month results from the ABRE clinical study, presented at the 2020 Charing Cross Symposium, which assessed the safety and efficacy of the investigational Abre stent in 200 patients with iliofemoral venous outflow obstruction across the spectrum of deep venous obstruction including those with post thrombotic syndrome, nonthrombotic iliac vein lesions (NIVL), and those who presented with an acute deep vein thrombosis (aDVT).

The study also included a challenging patient population: 44% (88/200) required stents that extended below the inguinal ligament into the common femoral vein (CFV). The study met its primary safety endpoint with a 2% (4/200) rate of major adverse events within 30 days. The study also met its 12-month primary effectiveness endpoint with an overall primary patency rate of 88% (162/184). No stent fractures and no stent migrations were reported in the study.

Calendar of events Please be advised that the events listed opposite, because of COVID-19, are subject to change. Please check the relevant website for further details as the event may be cancelled, postponed, or become a virtual event.

Mar

November 2020– February 2021 The CIRSE webinars: Interventional Oncology 2.0 Virtual

25–29 January 2021 Leipzig Interventional Course (LINC) Leipzig, Germany

20–24 March 2021 Society of Interventional Radiology (SIR) 2020 Virtual

9–11 May 2021 International Symposium on Endovascular Therapy (ISET) Hollywood, USA

www.leipzig-interventional-course.

www.sirmeeting.org

www.iset.org

www.ecio.org

com

1–3 December British Society of Interventional Radiology (BSIR) Annual Meeting 2020 Virtual

5–8 February 2021 Society of Interventional Oncology (SIO) Annual Meeting Virtual

19–22 April 2021 Charing Cross (CX) Vascular and Endovascular Controversies Digital Edition Virtual

16–19 June 2021 European Conference on Embolotherapy (ET) Nice, France

www.bsir.org/meetings

www.sio-central.org

www.cirse.org/events

www.cxsymposium.org

Issue

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to continues elUS FDA paclitax investigatevices in the leg coated de

(JAHA) Association suggesting an Heart the Americ ) and colleagues, el-coated Journal of , Greece the use of paclitax ed in the debate g os (Patras months of still ongoing, nalysis publishntinos Katsan five years followin is A meta-a generated year by Konsta at two and artery, has The conversationon the future of late last ed risk of death popliteal nity. pointed t commu hosting discussion in the femoro an increas ans have the and stents tional interventionalis to date ent physici after balloons nce of 2019 then, promin published ted with the the interna amongst key vascular conferedevices. Since patient-level data y associa ced with every ology, and no increased mortalit also announUS ed and -eluting have method l d el-coat al’s the Medica reveale os et paclitax ation by and Cook in Katsan by industry have out flaws medtronic the continued investig over. nalysis devices. hile, is not yet JAHA meta-a el-releasing data. Meanw s that the story ed paclitax of use (FDA) indicate to their publish correctionsDrug Administration Food and

Leaders

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Profile

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acle: Alex Barn IR Paediatric

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Artificial intelligence will cause shift” “paradigm e in IR practic

ed for increas are calling n computer Clinicians and betwee engineers collaboration biomedical ists as machine scientists, oncolog more to play a interventional radiology is posited learning role in interventionalg the initial prominent ures, from informinselection (IR) proced through to patiente. In a diagnosis, cedural guidanc Journal The gy and intrapro published in tional Radiolo recent primer Wang and r and Interven

Katsan mortal of Vascula Letzen, Clinton School of popliteal Leaders Forum an increased the Vascular (JVIR), Brian , all of the Yale outline the in the femoro hosted the floor of r 2018, paclitaxel USA, n DC, USA), FDA peaking from Julius Chapiro 6 Decembe e learning New Haven, (VIVA), March, Washingto arteries JAHA paper, publishedc review and metaAdvances (VLF; 1–2 Medicine, of tions of machinwhere Interventional has “reviewed most ing In the original conducted a systemati a future

by Vascular clinical applica , who trials investigat the al visualise -coated Katsanos et randomised controlled Donna Buckley, ded them to be approved” (AI) enables , for IRs, and or paclitaxel first 28 investigator intelligence In angioplasty and recommen perspective: “Our analysis of ne to become artificial to these devices body’s e of -coated balloon popliteal arteries. of the discipli the regulatory ysis was, I think, similar ss, paclitaxel in the femoral and/or nt claudication) were elevation ’s words, “the epitom explained Nonethele metal stents the meta-anal a little bit surprised. all-cause (89% intermitte in Chapiro response to medicine”. were measure was very seriously.” all, 4,663 patients else’s: we personalised points. “Risk n that we took primarily primary safety their everybody time The informatio g different analysed.

AGUES outline learning with a random analysed at it was compellinFDA evaluation is focusingwith data the g machine AND COLLE patient death, differences were pooled trials integratin LETZEN The ongoing ent, AI can risk d controlled in IR: “By wrote. preliminary ratios and randomise evidenced vision of AI , treatment, and managem the authors on US-based can validate. The FDA’s reported by trials have model,” highest-quality the tly effects body ed controlled signal significan into diagnosis s to provide that meets regulatory the mortality said the FDA’s physician Previous randomis balloons and stents lesion confirmed efficient manner Whereas empower -coated and target at VLF, Buckley (PMA) trials evaluation care in an that paclitaxel of vessel restenosis al. Speaking t approval tal clinical practice. personalised ysis interventions.

Katsanos et rates pre-marke modern incremen the US of on meta-anal extremity ed five of reduce it [the after lower the demands traditionally focused (28 randomis all own analysis to where we feel like for a new has d between revascularisationall-cause patient death t we still have , AI allows medicine was similar research, has “converge a statistical glitch—bu rapidly analysed vs. all the statistical At one year, not 4,432 patients) hypothesis-based‘big data’ can be have arms (2.3% n as well with findings] is trials with and control where us informatio years controlled that may otherwise paradigm -coated devices death at two this incongruo have gone through.” new insights was , USA) called 17 paclitaxel of death). All-cause ve trials.” we uncovering 2,316 patients) risk of prospecti the data analysis that Peter Schneider (Honolulu of trials with 2.3% crude g to review the Society vs. control required decades Also at VLF, ed controlled is undertakin meeting of year features deaths case of paclitaxel (12 randomis that the FDA and spot on”.

[SIR] this The annual increased in patients] vs. 3.8% [35 the process providers Radiology ional rward significantly straight-fo Interventional learning in intervent summit a letter to healthcare deaths in 1,397of death, number-needed-to“judicious, IR FDA issued evaluating the “recent (7.2% [101 its first machine and the BOLD-A crude risk Indeed, the 19–59]). Long-termed April, New that it was session, (24 increased long-term - in 919 patients] patients [95% CI: stating for NYU oncology 29 (three randomis in January paclitaxel the potential Stanford and and ethical in balloon or harm [NNH]: death up to five years n regarding regulatory initiated by informatio increased further paclitaxel-coated pliteal artery for will tackle risk of all-cause with 863 patients) for AI research. on page 4 following York, USA) in 529 patients] mortality” trials in the femoropo(PAD). The agency g to data use Continued deaths out [78 death, controlled pertainin treatments of (14.7% issues crude risk eluting stent arterial disease FDA case of paclitaxel in 334 patients] peripheral ongoing, the treated deaths patients with the data review was vs. 8.1% [27 ce” for patients [95% CI: 9–32]).that meta-regression 2 that said that whilst d surveillan in the letter on page NNH: 14 patientscolleagues wrote ds “continue body stated for Continued recommen Katsanos and . The regulatory to outweigh the risks” with paclitaxel continue the “benefits indications. it believes within their approved devices

Panellists

S

at the Vascular

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