November 2020 | Issue 80 www.interventionalnews.com 12 Profile: GEST 2020: Adam Hatzidakis Y-90 in Featured in Bart Dolmatch: Early stage Advanced stage this issue: AVeNEW Trailblazing IR in curative downstaging tumour all HCC study results Greece stages page 24 page 30 Radioembolization Catalysed by COVID-19, Portal vein embolization with societies say hybrid NBCA promotes greter liver growth conferences are here to stay than PVA, BestFLR “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 trial finds 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), In a comparison of the regenerative which took place virtually for the first time ever this year, with sessions livestreamed on each capacity of portal vein embolization Tuesday in October 2020. “Undeterred by setbacks,” it continues, “this is your year to learn (PVE) before major hepatectomies differently. Meet differently. See IO… differently.” At the time of writing, CIO 2020 is the most with two different embolic materials, recent conference in the interventional radiology (IR) space to deliver education and networking N-butyl-cyanoacrylate (NBCA) was opportunities online. As interventional radiologists look ahead to 2021, Interventional News shown to be superior to polyvinyl- speaks with thought leaders from IR societies across the world to capture their reflections on alcohol (PVA) particles plus coils. how the COVID-19 pandemic is impacting medical education. 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 2 METRES 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, POSITIVES OF POSITIVES OF the optimal embolic material for PVE has not yet been established. “There are some IN-PERSON MEETINGS VIRTUAL MEETINGS THE HYBRID suggestions in the literature that NBCA glue (Glubran, GEM) with Lipiodol (Guerbet) might generate more liver hypertrophy,” he said. do not think the pandemic is the end of the in- right decision and that has been proven by how the spring The BestFLR investigators therefore set person meeting, rather the beginning of offering unfolded. As a medical society, we knew we needed to lead out to determine which embolic material, “Imeetings accessible to all,” Erica Holland (USA), by example during this public health emergency and ensure NBCA-Lipiodol or PVA plus coils, produces interim executive director of the Society of Interventional we were protecting our patients, colleagues, families, and the highest healthy liver growth during PVE. Radiology (SIR), says. “SIR’s meetings, especially the communities by not creating a potential to spread the virus In order to be enrolled in the study, the future annual scientific meeting, always feel like a family reunion, further. Interventional radiologists are data-driven, and liver remnant (FLR)—the volume of healthy and we are looking forward to reuniting with our IR family the data we were presented at the time was unmistakable. liver that will remain with the patient after as soon as it is safe to do so.” There was community spread in the Seattle area, then the surgery—had to be 25% or less of the total Originally slated to be an in-person meeting in Seattle, liver volume in healthy liver patients, 35% or USA, on 28 March–2 April 2020, the SIR annual scientific less in colorectal patients, and 40 to 45% or meeting was amongst the first events to be cancelled There are wonderful, less in patients with cirrhosis or cholestatic due to the COVID-19 pandemic. Constantino Peña unexpected benefits liver disease. (Miami Cardiac & Vascular Institute, Miami, USA), SIR The 60 patients enrolled in the trial were 2020 programme chair, tells this newspaper this was “a of virtual learning randomly assigned to receive PVE with either disappointment”: “The annual meeting committee had experiences, and there NBCA-Lipiodol or PVA plus coils (30 in spent so many months planning the programme, the each group). Baseline characteristics, such as awards ceremonies, and the networking events, and was are also cherished, deeply age, sex, comorbidities, weight, height, and excited to share them with our peers. We knew many of missed aspects of in-person presence of cirrhosis, were equivalent amongst the researchers were eager to share their science with their the two cohorts. The most common tumour colleagues and hear the feedback that is so important to learning experiences.” types included in the study were colorectal expanding their work. metastases (45%) an cholangiocarcinoma “But we were confident at the time that we made the Continued on page 4 Continued on page 6

4 Virtual conferences November 2020 | Issue80 Catalysed by COVID-19, Strasbourg, France) weighs in: “While I do believe that the virtual model brought a lot to the table in terms of The latest stories societies say hybrid accessibility, I strongly believe that the major congresses News from the will go back to an in-person format after the pandemic. in brief interventional world conferences are here to stay This, however, will not mean in-person only. We at CIRSE plan to also further develop a strong virtual component Continued from page 1 of our physical congresses; a hybrid model if you will. epicentre of America’s outbreak. There was a call from local Medical education in general will of course require both officials, the Centers for Disease Control and Prevention in-person courses and congresses, as well as online learning [CDC] and the World Health Organisation [WHO] to limit opportunities. I believe for IR in particular, it is vital for n SAVER REGISTRY: social interactions and avoid large groups to stop the spread. professionals to be able to physically come together to “The SAVER registry There was the information from our members telling us their meet, discuss important data, and interact with the latest reinforces the safety and institutions were limiting travel to flatten the curve and ready technology. Virtual-only will not be the future.” effectiveness profile for the Stellarex drug-coated balloon to respond to the inevitable outbreaks in their hometowns. Speaking on behalf of SIR, Holland muses: “One of (DCB; Philips) in a real- The team came together, and absorbed and analysed data the interesting benefits of being all virtual is the fact world patient population,” quickly to make a correct and timely decision.” that it has allowed us to expand access to our offerings Konstantinos Stavroulakis (St to our members. We often hear that attendance at the Franziskus Hospital–Vascular Konstantinos The emergence of a post-pandemic hybrid annual scientific meeting is staggered in practices to Surgery, Munich, Germany) Stavroulakis model ensure coverage at the home institutions, meaning some told the live, online audience The annual meeting of the Chinese College of interventional radiologists attending may not be able to stay during the 2020 meeting of the Cardiovascular Interventionalists (CCI), initially scheduled for April 2020, for the whole meeting, if they are able to attend at all. That and Interventional Radiological Society of Europe was postponed due to the pandemic. Whilst SIR 2020 took is not generally an issue for virtual meetings as you can log (CIRSE; 12–15 September, virtual). place as a fully virtual event 13–14 June, CCI 2020 was on when you are available and absorb the discussion and For more on this story go to page 10. rescheduled for 27–30 August as a hybrid virtual/ in-person even watch it on demand later on, depending on the meeting. meeting in Nanjing, China. “Post-pandemic, I think you will see a pent-up demand n CROSSFIRE TRIAL: “Although this new meeting mode brings a unique for meeting again in person. Networking and community Irreversible attendee experience for CCI meetings, it also presents a big are a huge part of SIR’s meetings and part of the value of an electroporation (IRE) significantly induces challenge in terms of planning, in order to ensure audience in-person meeting are the sidebar conversations that happen a window of reduced satisfaction,” Gao-Jun Teng, CCI president, says, thinking after a presentation or when you bump into colleagues immune suppression back to the months of preparation that went into the 2020 on your way to plenary session or expo hall. Those are two weeks post event. Seven host venues were used in total; a “main” venue impossible to replicate in the virtual space. treatment, allowing in Nanjing, and six “branch venues” across the country, “At the same time, not everyone will be ready or able to the activation of which CCI say “were to let more IR professionals easily attend our events in person, so we may see a hybrid model effector T cells get involved”. In total, there were over 16,000 registered emerge that live streams what is happening on site for those that seem to be participants, who were able to access 153 scientific and who cannot be there in person. correlated with improved survival, according workshop sessions, 796 lectures, and 76 live demonstrations to preliminary flow cytometry results of the of IR procedures. CROSSFIRE trial presented during the 2020 CIRSE meeting. “I am proud to conclude CCI 2020 a big success,” Teng We may see a hybrid told virtual and in-person attendees of the meeting’s closing model emerge that live For more on this story go to page 32. ceremony, “and [declare] it a ‘sweet marriage’ between n the virtual and physical meeting settings. Except for the streams what is happening HOW ABLATOIN IS TRANSFORMING completely online English-speaking sessions, almost all CANCER CARE: on site for those who cannot Raul Uppot (Boston, USA) speaks to Interventional lectures were delivered in physical meeting rooms in News about the evolution of liver ablation, from Nanjing and the other six cities, while most audiences could be there in person.” the first procedure in November 1986—where just stay at home. This has no doubt brought attendees the hepatic tumour was injected with alcohol—to great convenience to participate with minimum travel and the potential of this treatment modality to offer cost. Most importantly, it also broke territorial boundaries “In addition, some of the virtual networking systemic, curative cancer care, possibly to allow more attendees to engage in and more citizens to opportunities SIR created to fill the gaps while even without inserting a single needle. appreciate this fairly new but strongly developing, medical meeting sizes are still restricted, like our new For more on this story specialty.” Indeed, following the strength of the hybrid virtual angio club series, are specifically go to page 37. model’s success at CCI 2020, the college is continuing with designed to stay in the long term. Many of this format in 2021. our members work in areas that do not have These boons of increased attendance and accessibility local angio clubs where they can regularly facilitated by the virtual meeting have been echoed by meet with their peers, learn, and exchange other IR societies. President of the Cardiovascular and ideas. While SIR’s virtual club was born out Raul Uppot Interventional Radiological Society of Europe (CIRSE), of the necessity presented by the pandemic, Afshin Gangi (University Hospital of Strasbourg, Continued on page 6

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6 IR around the world November 2020 | Issue80

5,000 attendees from 115 different countries logging in the SIR 2020 virtual offering”. He elaborates: “Given Catalysed by COVID-19, and creating more than 20,000 chat messages over the the uncertainty of the landscape, the unique nature of societies say hybrid course of the four live event days. While Gangi says our specialty, and the need for members to stay safe and these figures paint a positive picture of intra-conference healthy to deliver patient care, we decided to postpone conferences are here to stay communication, he adds this caveat: “I think the quality the in-person portion of our programming now so that of interaction and collective creativity that is achievable we have adequate time to plan for and deliver an all Continued from page 4 online is not the same as we usually have at a physical virtual format that provides the same cutting-edge, high- it uncovered an important, longstanding need in our congress. I therefore strongly hope that we will be able quality programming that our members expect from the community, and we are excited to have this series to meet again in-person at the CIRSE annual congress annual scientific meeting. continue in the long term to support interventional in 2021 in Lisbon, Portugal.” At the time of publication, “Unlike SIR 2020’s virtual offering, which was radiologists in their practice no matter where they are.” this meeting is scheduled for 25–29 September 2021. deployed as a standard webinar platform, for 2021 we When asked if she believed the future of medical When questioned on his event expectations for 2021, will replicate the feel of an in-person event as closely as conferences would follow a virtual, live, or hybrid Gangi said: “We are in the same spot as everyone possible through an interactive platform complete with model, Jena Eberly Stack, executive director of Society else at the moment: waiting for a vaccine and hoping meeting rooms, plenary sessions, an interactive expo of Interventional Oncology (SIO), commented: “This is the situation will improve. While we hope and plan hall, and on-demand offerings. We are also exploring the million-dollar question! While I do not have a crystal for in-person meetings, we are prepared to host the ball, I can say that there are wonderful, unexpected meetings in any format we can, and that might be benefits of virtual learning experiences, and there are online or in a hybrid format. One thing is certain—all also cherished, deeply missed aspects of in-person CIRSE events in 2021, including the European Congress learning experiences. I am sure we will see a mix of on Interventional Oncology (ECIO), the European both once we are able to safely meet in person again, Conference on Embolotherapy (ET), and the CIRSE offering tailored opportunities based on the type of annual scientific meeting will take place.” information and education being shared.” Gearing up for SIO 2021, which will be held virtually 5–8 February 2021, Stack reflect on the 12 months’ Spring IR conferences confirm they will experience the society has had to prepare for a potential be online-only events online meeting (the society’s annual scientific meeting Unlike the annual scientific meetings originally was one of the few IR congresses able to take place in scheduled in the springtime, CIRSE had several months person this year, 31 January–3 February 2020, New to anticipate the possibility of hosting a virtual meeting, Orleans, USA). “The world certainly looks different Delegates attending CCI 2020 in person something Gangi says was “essential […] to ensure today than it did a year ago, and our preparations for everything went smoothly online”. Commenting on SIO 2021 reflect this shift in our landscape,” she says. ways to deliver the important networking opportunities, the event, held 12–15 September 2020, he adds: “We “We have held and observed several virtual events committee meetings, and our awards ceremonies received overwhelmingly positive feedback from our over the last seven months, and the learnings from those honouring those who have greatly contributed to the stakeholders regarding the high calibre of educational activities have provided feedback we are incorporating advance of the specialty. […] We are confident that SIR content, interactive learning, and networking into our planning process for SIO 2021. Providing members will find this online learning experience a not- opportunities, and first-rate organisation. While of timely programming, valuable avenues to skill-build, to-be-missed event.” course we missed the opportunity of physically meeting and quality networking opportunities remain our Indeed, Holland believes the switch to all virtual together as in previous years, the CIRSE 2020 Summit commitment to our attendees, and we are achieving this education this year, which she says “is spurring SIR was able to ensure an equally high level of educational through thoughtful programme development. SIO 2021 to move forward with a total reimagining” of their content with our top-notch faculty streaming in from will be an interactive experience—not just a series of educational offerings, was actually already a part of around the world, giving over 1,000 presentations, and webinars—designed to mimic the best parts of an in- the society’s strategic plan. “The pandemic has been also provide ample networking opportunities through person event and capitalise on the unique opportunities a a catalyst for us to take things down to the brass tacks the interactive presentation formats and chat functions virtual event has to offer.” and rebuild it anew in a way that is as agile as IR,” she available at every level of the platform.” SIR 2021 will also be held online. Peña assures surmises. The consensus amongst the international IR In total, there were 18,000 active users on the CIRSE readers that this “will be a completely different community is that conferences with at least a virtual 2020 Summit platform, the society claim, with almost experience from any previous SIR meeting, including component are here to stay.

trial was liver regeneration at 14 and 28 Lipiodol yielded a greater absolute liver “These data encourage us to assess Portal vein days after PVE, assessed by computed hypertrophy: 46.4% at 14 days versus patients earlier,” Luz told the ECIO tomography (CT) volumetry. The 29.6% at 14 days post-embolization with audience, “14 days after PVE if we are embolization with specific endpoints measured were FLR PVA plus coils (p<0.001), and 57% at 28 using NBCA-Lipiodol, which we are NBCA promotes degree of hypertrophy, FLR absolute days compared with 36.7% at 28 days now following these trial results. This hypertrophy, and kinetic growth rate for the PVE with coils group (p<0.001). shorter waiting period enables patietnts greter liver (KGR). Secondary outcomes included “An interesting finding that we had to undergo curative hepatectomy, and the occurrence of post-hepatectomy liver in this study is that many patients were might decrease tumour progression, growth than PVA, failure, intraoperative incidents, blood ready for liver surgery after just 14 which is the main cause of precluding loss, transfusions, surgery duration and days,” Luz said. In the NBCA-Lipiodol liver surgery.” BestFLR trial finds hospital stay, PVE contrast volume Addressing patient outcomes, he used, fluoroscopy and total procedure Many patients shared that 24 patients (80%) in the Continued from page 1 time, as well as the rate of minor and NBCA-Lipiodol group underwent a (35%). major complications after PVE. All were ready for successful hepatectomy after PVE, Detailing the embolization technique patients gave voluntary informed compared to 23 (76%) in the PVA plus used by the triallists, Luz recounted: consent to participate in the trial, liver surgery after coils group (p=0.32). Three patients in “We injected PVA particles of increasing which is registered in a World Health just 14 days. These the NBCA-Lipiodol cohort (12%) and size until [we reached] flow stasis, Organisation (WHO) registry network. seven patients in the PVA plus coils followed by proximal coils (6–12mm in data encourage us cohort (27%) had clinically-relevant diameter) to achieve complete venous Triallists encourage earlier to assess patients liver failure (p=0.27). occlusion”. For NBCA-Lipiodol glue, assessment of patients Fluoroscopy and total PVE time were they injected a solution of different for hepatectomy in light of earlier.” also significantly lower for NBCA- concentrations depending on the positive results at 14 days Lipiodol versus PVA plus coils (16 approach used: when injecting from the post-embolization with cohort, 87% of patients had a sufficient minutes vs. 25 minutes, p<0.001, and contralateral side, a 1:3 dilution was NBCA-Lipiodol FLR ratio for surgery after 14 days. This 60 minutes vs. 80 minutes, p=0.0023, used, and when obtaining ipsilateral After 14 and 28 days, all volumetric was higher than amongst the PVA plus respectively). access to the liver, they used a 1:5 parameters were superior for PVE with coils cohort, where 55% of patients were At the time of writing, the results of dilution through a microcatheter. NBCA-Lipiodol compared to PVE eligible for surgery after the same time the BestFLR trial are under submission The primary outcome of the BestFLR with PVA plus coils. PVE with NBCA- period (p=0.008). for publication.

8 TCT highlights November 2020 | Issue80

Primary and secondary efficacy endpoints were Starting to close the door on the transverse-view vessel area loss percentage (TVAL%) of the target lesion and clinically relevant target paclitaxel controversy: TCT late- lesion failure (CR-TLF) at six months, respectively. The primary safety endpoint was freedom from a breaking trials major adverse limb event or perioperative death (MALE+POD) at 30 days. Findings from a series of late-breaking trials in the endovascular field were presented Armstrong reported that superior primary efficacy of recently at TCT Connect (14–18 October, virtual), the 32nd annual scientific symposium the treatment arm was apparent in the per protocol (PP) of the Cardiovascular Research Foundation (CRF). Sahil A Parikh (Columbia University and PP-TASC B–D (excluding 15 patients with TASC Medical Center, New York, USA) and Frank Veith (New York University Medical Center, New A lesions) subgroups, and that TVAL% reductions of York, USA) moderated the session, with Marc Bonaca (University of Colorado, Aurora, USA) 13.9% and 22.3% were seen in the PP and PP-TASC and Robert A Lookstein (Mount Sinai Health System, New York, USA) on the panel. B–D subgroups at six months, respectively. In addition, freedom from CR-TLF rates were irst on the virtual podium was Connie N Hess presented at TCT demonstrate that IN.PACT 0.014 may substantially higher in those patients treated with (University of Colorado, Aurora, USA), who offer a clinical benefit in patients with CLI. temsirolimus, and differences between treatment Fpresented results of a large subgroup analysis and control for freedom from CR-TLF at six months of the VOYAGER PAD randomised clinical trial. This ILLUMENATE Global: Four-year results were 27.1% and 39.2% in the PP and PP TASC B–D showed neither a mortality risk nor benefit associated support durable long-term outcomes subgroups, respectively. Freedom from composite of 30- with the use of paclitaxel drug-coated devices in the with Stellarex DCB day MALE+POD was 100% in all groups. treatment of peripheral arterial disease (PAD). The study Andrew Holden (Auckland City Hospital, Auckland, “Findings suggest that adventitial deposition of also found that the benefit of rivaroxaban use in reducing New Zealand) reported on late safety and efficacy temsirolimus using the Bullfrog micro-infusion ischaemic limb and cardiovascular outcomes was outcomes for the low-dose Stellarex DCB (Philips) in de device improves six-month vessel patency when consistent regardless of if a drug-coated device was used. novo and restenotic femoropopliteal lesions. applied to BTK arteries after successful endovascular This analysis examined the long-term safety of drug- He revealed that four-year data from the trial show revascularisation,” Armstrong concluded. coated devices and evaluated whether rivaroxaban 2.5mg favourable safety and efficacy outcomes consistent with twice daily plus low dose aspirin versus low dose aspirin the ILLUMENATE randomised controlled trials, and FLASH registry: Acute haemodynamic alone on the primary efficacy endpoint was consistent also demonstrate similar efficacy in prespecified cohorts improvement with percutaneous with versus without drug-coated device (DCD) use. including different gender groups and diabetics. mechanical thrombectomy in a real- During the qualifying endovascular lower extremity ILLUMENATE Global is a prospective, single-arm, world pulmonary embolism population revascularisation, a DCD was used for 31% (n=1,358) of multicentre study conducted in the EU. The patient Catalin Toma (University of Pittsburgh, Pittsburgh, patients. Patients receiving a DCD more frequently had population included those with Rutherford Clinical USA) presented results from the FLASH registry. prior endovascular lower extremity revascularisation, Classification of 2–4 indicated for treatment of the FLASH is a 500-patient prospective, multicentre registry a higher baseline use of dual antiplatelet therapy and superficial femoral artery (SFA) and/or popliteal artery study designed to evaluate real-world outcomes after statins, and were more often treated for claudication than for de novo or restenotic lesions. Follow-up office visits treatment of patients with intermediate and high risk PE non-DCD patients. were at one, six, 12, 24, and 36-months post-procedure with FlowTriever (Inari Medical). In the unweighted analysis, lower associated mortality Toma reported that mortality through 48 hours was observed among patients receiving DCD versus was 0% and that just three patients out of 320 (1.3%) non-DCD (2.9 vs. 3.9 per 100 patient-years; 3.5- We are barely experienced major adverse events—all of which were year Kaplan-Meier cumulative incidence of 10.2% scratching the major bleeds. vs.13.8%). After weighting, there was no association between DCD use and mortality (3.5-year cumulative surface on drug-based Ablation of accessory renals might incidence 12.1% vs. 12.6%, HR 0.95, 95% CI 0.83– delivery in the below the reduce blood pressure 1.09, p=0.49). The benefit of rivaroxaban 2.5mg twice Yu Sato (CVPath Institute, Gaithersburg, USA) spoke on daily with aspirin compared to aspirin alone in reducing knee circulation.” the anatomy of the human accessory renal artery peri- ischaemic limb and cardiovascular outcomes was also arterial renal sympathetic nerve for renal denervation. consistent regardless of whether a DCD was used. Sato began by detailing that accessory renal arteries and included clinical, haemodynamic, and functional have been reported in about 30% of patients. Some renal IN.PACT 0.014 DCB may offer a clinical outcomes. denervation clinical trials have excluded patients with benefit in patients with CLI At four years, the rate of major target limb amputation accessory renal arteries, while others have included such Antonio Micari (University of Messina, Messina, Italy) was 0.8% and that of all-cause mortality was 8.1%. patients but excluded those with accessory renal arteries presented first-ever results from Medtronic’s IN.PACT Clinically-driven target lesion revascularisation through less than 3/4mm in diameter. Moreover, some studies BTK study, a feasibility study assessing the safety and four years was 75.6% at day 1,460 and the subgroup have suggested that renal denervation for accessory effectiveness of the company’s IN.PACT 0.014 drug- analysis revealed no difference in prespecified cohorts. renal arteries may have an additional advantage of blood coated balloon (DCB) in critical limb ischaemia (CLI) “The ILLUMENATE Global study supports durable pressure reduction. The aim of this study was to evaluate patients with chronic total occlusion in the infrapopliteal long-term outcomes with the Stellarex DCB and is the anatomic distribution of peri-arterial nerves in arteries. The IN.PACT BTK study is a prospective, applicable to a complex population,” Holden said. human accessory renal arteries. multicentre, 1:1, randomised feasibility study assessing Sato concluded that accessory renal arteries have two- the safety and effectiveness of the IN.PACT 0.014 DCB, Bullfrog device shows promise in thirds the number of nerves as compared to dominant a 3.5 μg/mm2 dose paclitaxel-coated balloon, versus TANGO registry renal arteries, and that the number of nerves around the conventional percutaneous transluminal angioplasty Ehrin J Armstrong (UCHealth Heart and Vascular accessory renal arteries is dependent on renal artery size. (PTA) for the treatment of chronic total occlusions in the Center, Aurora, USA) presented results of the TANGO “Our results suggest that ablation of peri-arterial nerves infrapopliteal arteries. The study enrolled 50 patients at registry. This Phase 2 study aimed to assess the six- in accessory renal arteries should result in an additional nine sites in Europe. month efficacy and safety of the Bullfrog micro-infusion blood pressure reduction,” he remarked, adding that At nine months, patients in the DCB group device (Mercator MedSystems) adventitial deposition future renal denervation clinical trials should consider experienced a reduction in sub-segmental late lumen of two escalating doses of temsirolimus in reducing including ablation of peri-arterial nerves in accessory loss compared to those in the PTA control group angiographic neointimal hyperplasia and target lesion renal arteries. (0.59±0.94mm vs. 1.26±0.81mm, respectively, failure after revascularisation of below-the-knee arteries. p=0.017), a 53% lower late lumen loss than the PTA This prospective, multicentre, dose-escalation, Closing the door on the paclitaxel control group. Using the classic late lumen loss method, comparative, double-blinded study enrolled 61 patients controversy patients in the DCB group experienced lower late undergoing endovascular revascularisation of ≥1 “I think we are really starting to close the door on the lumen loss compared to those in the PTA control group angiographically significant BTK lesions. Treatment was paclitaxel controversy,” Lookstein commented at the at nine months (0.89±0.77mm versus 1.31±0.72mm applied after completion of artery revascularisation, and end of the session. “There is clearly a lot more work respectively, p=0.07 ), a 32% lower late lumen loss than divided into control (saline; 0.25–0.5mL/cm of lesion that needs to be done for paclitaxel below the knee and the PTA control group. length), low-dose temsirolimus (0.1mg/mL; 0.025– it is encouraging to see that there is going to be work on Historically, there has not been a DCB technology 0.05mg/cm of lesion length), or high-dose temsirolimus that. We are barely scratching the surface on drug-based that has demonstrated effectiveness in this vessel (0.4mg/mL; 0.1–0.2mg/cm of lesion length) groups in a delivery in the below the knee circulation, so there is a bed. According to a Medtronic press release, the data dual-blinded, randomised fashion. lot more work to do.” Issue80 | November 2020 Drug-coated balloons 9 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, amputation- therapies cannot be ruled out.” free survival, and freedom from target- King 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.” 10 Peripheral interventions November 2020 | Issue80 First@CIRSE

Win for paclitaxel as SAVER registry “reinforces the safety profile”

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

DCB the superficial femoral, popliteal, and/or infra-popliteal from device- and procedure-related death through 30 arteries in a broad, real-world patient population. The days post-procedure, and freedom from target limb “The SAVER registry reinforces the registry is split into two patient cohorts: claudicants, and major amputation and CD-TLR through 12 months safety and effectiveness profile for chronic limb-threatening ischaemia (CLTI) patients. post-procedure. Giving additional outcomes at one-year, the Stellarex drug-coated balloon In the claudicant group—Rutherford category 2–3— Stavroulakis told the CIRSE audience that all-cause (DCB; Philips) in a real-world patient the primary safety endpoints were freedom from 30-day death was 3.2%, and the amputation rate was 2.7%, population,” Konstantinos Stavroulakis device- and procedure-related death, and freedom from with the major amputation rate 0.8%—“acceptable” (St Franziskus Hospital–Vascular Surgery, 12-month target limb major amputation and clinically- outcomes in this real-world population. Munich, Germany) told the live, online driven target lesion revascularisation (CD-TLR). The Regarding the efficacy endpoint, 87.7% of patients audience during the 2020 meeting of efficacy endpoint for claudicants was freedom from had freedom from CD-TLR at 12-months post- the Cardiovascular and Interventional 12-month CD-TLR. In the CLTI group—Rutherford procedure, a “robust” finding. Kaplan-Meier evaluation Radiological Society of Europe (CIRSE; category 4–5—the primary safety endpoints were demonstrated 98.7% freedom from CD-TLR at 30 days, 12–15 September, virtual). freedom from composite major adverse limb events 95% at 180 days, and 88.6% at 365 days. and perioperative death through 30 days. The efficacy Recounting the additional secondary outcomes, “THESE REAL-WORLD REGISTRY DATA endpoint was freedom from six-month CD-TLR. Stavroulakis told registrants that the majority of provide important outcome information for healthcare An interim analysis of the first 1,000 claudicant patients (87.6%) improved by at least one Rutherford providers for the debate on the safety of drug-eluting patients revealed a procedural success rate of 97.9%, class; 8.9% had no change in Rutherford category, and technology,” he opined. The Stellarex DCB is a and a lesion success rate of 98.5%. “Bailout stenting 3.5% worsened from baseline. There was a significant low-dose (2µg/mm2) paclitaxel device, with proven was required in 24% of the patients, showing that improvement in walking capacity at 12 months, as effective drug tissue transfer and residency. Compared we can treat the majority of these PAD [peripheral measured via the six-minute walk test: at baseline, the to competitors, it has limited drug loss, “a very arterial disease] patients effectively, with no additional mean distance a patient could walk during the test was important feature”, in Stavroulakis’ words. permanent scaffold,” Stavroulakis said. 52±24.4m; by 12 months, this had risen to 169±123.7m. SAVER stands for the Stellarex Vascular e-Registry, a There was a 0% periprocedural mortality, and “just” Quality of life scores and the ankle-brachial index also multicentre, European registry with external monitoring 0.6% significant distal embolization. Target vessel improved from baseline to 12 months. and clinical event committee adjudication. Patients are thrombosis was seen in 0.2% of the patient cohort, and These results led Stavroulakis to conclude that there followed up through to three years, and experience a emergent surgical revascularisation in 0.1%. was a low rate of procedural complications when the 12-month visit. The aim of the SAVER registry is to The majority of patients (87.4%; 892 of 1,021) Stellarex DCB was used in claudicants, and the device assess the safety and efficacy of Stellarex DCB use in reached the primary safety endpoint, with freedom had a high safety profile.

included 15 risk factors in their creation New prediction model for of the model. “It is noteworthy that over 50% target lesion revascularisation of the patients included in the model had over five-year follow-up. In fact, grants “new level of security” this is the first prediction model to estimate the impact of patient and lesion to paclitaxel devices in the characteristics on freedom from TLR through five years for patients with PAD [peripheral arterial disease],” Dake peripheral arteries enthused. “Based on unique patient Stefan Müller-Hülsbeck and Michael “Please feel free to utilise this in your practice,” Michael Dake profiles, the model provides expected Dake during CIRSE 2020 (University of Arizona Health Sciences, Tucson, USA) urged on patient outcomes following treatment the first day of the Cardiovascular and Interventional Radiological with the Zilver PTX DES, and may assist Dake next related the 15 risk factors Society of Europe 2020 Symposium (CIRSE; 12–15 September, in defining algorithms for patients as that were considered when the tool was virtual). Speaking during a FIRST@CIRSE session, he presented a the value of population management is under construction: sex, age, diabetes, new, interactive, web-based tool built to predict patients’ freedom increasingly recognised.” hypertension, hypercholesterolemia, from target lesion revascularisation (TLR) following treatment with Turning to the freedom from TLR renal disease, smoking status, the Zilver PTX (Cook Medical) drug-eluting stent (DES). results, Dake informed the CIRSE Rutherford classification, lesion length, audience that 94% of the complete dexamethasone, popliteal involvement, DAKE AND COLLEAGUES USED use of the Zilver PTX DES. These dataset (2,227 cases, with a median total occlusion, calcification, prior patient and lesion factors from five clinical studies examined both pre- follow-up time of two years) was used to interventions, and the number of patient global clinical studies from Cook market and post-market outcomes with generate the model. Freedom from TLR runoff vessels. “Most all of these have Medical to develop a prediction the Zilver PTX stent in patients with was 90.5% at one-year, and 75.2% at five been in the past implicated as being high model for freedom from target lesion femoropopliteal disease. In total, they years. risk for TLR in studies performed over revascularisation (TLR) following collated data from 2,374 patients, and Describing the model more closely, the last two decades,” Dake disclosed. Issue80 | November 2020 Peripheral interventions 11

multiple comorbidities, which were hardly associated “No signal of increased risk of long-term with the application of paclitaxel.” Patients in the plain balloon angioplasty cohort died of heart failure, sepsis, mortality” with paclitaxel-coated Luminor cholangiocarcinoma, respiratory failure, and suicide. “A correlation between paclitaxel and cause of death is DCB, EffPac trial finds [therefore] quite unlikely,” Teichgräber concluded. The total number of adverse events per patient An ad hoc, two-year analysis of the EffPac study found no signal of increased risk of was higher in the DCB group than in the plain long-term mortality, nor any adverse events, within two years of drug-coated balloon balloon angioplasty group, though this difference (DCB) angioplasty using a Luminor-35 device (iVascular). This was the conclusion was not statistically significant (3.2±2.8 vs. 2.9±2.6; presented by Ulf Teichgräber (University Hospital Jena, Jena, Germany) at the 2020 p=0.59). The proportion of patients who experienced meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; any adverse event was slightly higher in the plain 12–15 September, virtual). angioplasty arm of the study, but again, this difference was not statistically significant (88.5% vs. 86.5%, TEICHGRÄBER IS THE PRINCIPAL paclitaxel use in the peripheral arteries. respectively; p=0.81). “So there is no real difference investigator of the EffPac trial, a prospective, While the EffPac trial could not confirm a in adverse events between both groups,” Teichgräber randomised controlled trial initiated by the federal correlation between paclitaxel application and all-cause summarised. Except for serious malignancies, there authorities in Germany, and conducted at eleven mortality—there was one death in the DCB arm, out of were no significant between-group differences in the study sites, that compares the paclitaxel-coated a total of 82 patients, and seven out of 85 in the plain incidence of adverse event types. Luminor balloon with plain balloon angioplasty in angioplasty arm—a lot of patients Summing up, Teichgräber said: the femoropopliteal artery segment of patients with were lost to follow-up. “I believe that such an ad hoc peripheral arterial disease (PAD). In total, the EffPac trial analysis on discontinued patients in The primary efficacy endpoint of this study was randomised 171 patients into randomised controlled trials gives us late lumen loss at six months; secondary endpoints two arms: those treated with the a full picture on all-cause mortality included primary patency, freedom from target lesion Luminor DCB (85 patients), for our follow-up patients. revascularisation (TLR), Rutherford category, ankle- and those who received plain “As we do not have a class brachial index, and quality of life score. All-cause angioplasty (86 patients). At 24 effect between different DCB mortality and target limb amputation were assessed as months, 60 patients were left in products, with our ad hoc analysis the primary safety endpoints. the DCB group, and 56 in the we can only give information on Just published in Radiology, Teichgräber described plain angioplasty group, due to Luminor balloons, and their coating how the investigators conducted an ad hoc, two-year a lack of follow-up in nearly one technology. Therefore, it is important review of mortality and morbidity following DCB third of randomised patients. This that other trials, with other DCB angioplasty in EffPac patients. Two-year follow-up represented a discontinuation of 25 Ulf Teichgräber products, go the same way as we of the EffPac trial was in fact completed in February patients in the DCB arm, and 30 did with EffPac, and assess what 2019, but another study cast its shadow over the results. patients in the plain angioplasty arm. happened to their lack-of-follow-up patients, and Konstantinos Katsanos (Patras, Greece) et al published Under entreaty from the BfArM, Teichgräber set out [see] if they could show equivalent results of all-cause a meta-analysis in the Journal of the American Heart to find those EffPac participants lost to follow-up in mortality in their full cohort.” Association (JAHA) in late 2018 that found an increased order to gain further information on two-year mortality association between late mortality risk and paclitaxel rates with paclitaxel devices. There is no use in the femoropopliteal arteries. “Numerous public “Paclitaxel showed a very low [mortality] risk ratio debates about the safety of paclitaxel-coated balloons of only 0.15 compared to other trials, meaning there correlation of all- were triggered”, Teichgräber recalled. is no correlation of all-cause mortality associated This led the Federal Institute for Drug and Medical with Luminor balloons,” Teichgräber said. “Another cause mortality associated Devices in Germany (BfArM) to request a formal interesting aspect [to look at] is cause of death. The with Luminor balloons.” hearing on mortality of all ongoing studies concerning only case of death in the DCB group was due to

He continued: “Risk factors common an estimation of the risk that patient has and that there was an increased number encouraged CIRSE attendees to visit the in PAD patients collectively contributed of maintaining freedom from TLR out to of prior interventions in both the single- site themselves and “really get a sense of to overall prognosis. As expected, five years, with a standard error given, arm study and the Japan post-market getting comfortable with how individual chronic limb-threatening ischaemia when treated with the Zilver PTX. These study, as both these trials included in- risk factors can affect TLR going out (CLTI), lesion length, and total occlusion results also translate into a freedom from stent restenosis. “Patients with in-stent through five years”. have a significant impact on TLR. TLR Kaplan-Meier curve. The physician restenosis were not allowed to enter the Referring to his presentation as the Other factors, such as diabetes and can then make an informed treatment other trials,” he explained. launch of this predictive model, Dake calcification, do not have a significant decision based on individual risk factors. closed the discussion by postulating: impact on TLR.” “This is the first step” “Maybe other device manufacturers He then talked through three example The baseline data Praising Dake for these results, will look at this as a model and adopt patient profiles to illustrate how listening Teasing apart the larger dataset to moderator Stefan Müller-Hülsbeck predictive models as a way to counsel physicians could use this predictive examine trends in baseline patient (Diako Hospital, Flensburg, Germany) patients and their families in the clinic model in their own practices. The risk demographics, Dake said: “Looking a commented: “I think you have shown regarding their individual risk factors, factors any given patient may have are bit closer at some of these individual once again that paclitaxel is probably modification of those risk factors, and fed into the model, which then churns out patient demographics, and how they safe, and we meet a new level of security how we can predict what results might be are distributed within the various trials when using these kinds of devices, with different devices. I think this is the The model included in the analysis, you can see especially when using this kind of first step. I think this is an outcropping some differences. Of note, in the Japan predictability model.” He then asked of what we have seen as a result of the provides post-market study, [there is] a very high Dake if the model is already in use, and Katsanos paper [Konstantinos Katsanos expected patient frequency of renal disease, and a higher if so, if he was using it for his patients (Patras, Greece) et al published a paper frequency of CLTI. In terms of diabetes, during his daily practice. in late 2018 that suggested the existence outcomes following there was a high frequency in all studies, “This is actually the first debut of of an increased mortality risk with approaching 50%.” this model and this website,” Dake paclitaxel devices used in the peripheral treatment with the Appraising the baseline lesion responded. “The manuscript will be arteries]. The next level now is [to Zilver PTX DES.” characteristics, Dake informed viewers published in Cardiovascular and evaluate the] efficacy in terms of using that 42% of patients had total occlusions, Interventional Radiology (CVIR).” He paclitaxel in individual patients.” 12 CIRSE 2020 November 2020 | Issue80 First@CIRSE

treatment modality that reduces its occurrence. “Angioplasty has been our go-to for many years,” 24-month he said. “We know that the durability after angioplasty is OK, but the question is, can we improve upon AVeNEW study angioplasty durability when treating fistula stenosis?” Enter the AVeNEW study, a prospective, multicentre, results: Covered multinational clinical trial of 280 patients with stenotic AVFs and clinical AVF dysfunction. Patients were stent angioplasty randomised 1:1 to either the percutaneous transluminal angioplasty (PTA) group, or the angioplasty with the “statistically Covera stent group. The study met both its primary safety and efficacy endpoints: freedom from a primary safety event Fabrizio Fanelli (L) and Bart Dolmatch during superior” to out to 30 days, and target lesion primary patency at CIRSE 2020 six months, respectively. There was no significant angioplasty alone in difference in freedom from a primary safety event out circuit primary patency, he commented: “Access circuit to 30 days between the covered stent cohort and the patency for an AVF drops off regardless of which ESRD patients angioplasty alone cohort (95% and 96.4%, respectively; group you are in, and yet, at 24 months, there is a p=0.002). Target lesion primary patency at six months statistically superior outcome of circuit patency for the Against the backdrop of increasing end- was “superb” and “statistically superior” in the covered covered stent group compared to the angioplasty group stage renal disease (ESRD) prevalence in stent group compared to angioplasty (78.7% and [p=0.02].” the USA, Bart Dolmatch (Palo Alto Medical 47.9%, respectively; p<0.001). Foundation, Portola Valley, USA) presented A 12-month exploratory subgroup analysis of target the 24-month results of the prospective, lesion primary patency revealed that, regardless of Angioplasty has randomised controlled AVeNEW study certain lesion characteristics, there was “a preferential, been our go-to at the Cardiovascular and Interventional better outcome using the covered stent compared Radiological Society of Europe 2020 to angioplasty alone. A Kaplan-Meier plot showed for many years, but Symposium (CIRSE; 12–15 September, that the freedom from loss of target lesion primary the question is, can we virtual). patency was superior shortly after implantation of the covered stent compared to angioplasty, and remained improve upon angioplasty THIS IS THE FIRST LEVEL ONE TRIAL statistically better at all time points, with more than a durability when treating dedicated solely to assess the safety and efficacy of the 30% better patency at 24 months. Covera (BD) covered stent designed to treat stenosis Secondary outcomes were also better for the covered fistula stenosis?” in the arteriovenous fistula (AVF) access circuit, stent cohort, Dolmatch related. The index of patency Dolmatch claimed. The two-year results showed function and mean access circuit reinterventions statistically superior target lesion primary patency were both superior in the covered stent group, while and AVF circuit primary patency with the use of the secondary patency was the same in both groups covered stent compared with angioplasty alone. (91.4%). “Interestingly, all-cause death was lower Renal replacement is expensive, online attendees of in the covered stent group than the angioplasty the FIRST@CIRSE session heard, and largely achieved group,” Dolmatch continued. “I am not sure if this is Read more Renal News with haemodialysis using an AVF. However, Dolmatch statistically significant, we have not done that analysis stories from page 17 explained how AVF stenosis interferes with efficient yet, but it is a curious finding.” haemodialysis, leading physicians to try and find a Looking specifically at freedom from loss of access

Calls in Germany for 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 reimbursement as analysis higher TLR rates we might achieve.” technologies, we have options to treat Moderator Fabrizio Fanelli (Careggi our patients adequately, to provide them shows drug-eluting technology University Hospital, Florence, Italy) with drug-eluting technology.” queried if Müller-Hülsbeck believed Fanelli next asked if Müller-Hülsbeck is cost-effective the “pretty important gap between the thought this could “push the use of drug- ELUVIA DES and the Zilver PTX” eluting stents” in the future. Stefan Müller-Hülsbeck (Ev Luth Diakonissenanstalt zu Flensburg, would grow in the future, or would “I think yes,” Müller-Hülsbeck Flensburg, Germany) presented attendees of the online meeting become more similar. replied, “especially in the USA. In of the Cardiovascular and Interventional Radiological Society of “That is hard to answer! Probably the Germany, I do not know exactly, Europe (CIRSE; 12–15 September, virtual) with an update from the results from [using] both stents could because the difference there is slightly IMPERIAL head-to-head randomised trial comparing the Eluvia differ, but I think there is also a high lower, but it is my hope—as we want drug-eluting stent (DES; Boston Scientific) with the Zilver PTX DES probability that the curves in terms of to avoid patients coming back for early (Cook Medical) for the treatment of femoropopliteal artery lesions. target lesion revascularisation might target lesion revascularisation—that come closer, so we have to see what will this kind of technology becomes more hrough 24 months, there In addition, Müller-Hülsbeck reported happen in five years,” Müller-Hülsbeck accepted by insurance companies for was a significantly lower a significant improvement in mobility responded. “The reimbursement. “Tclinically-driven target and pain/discomfort dimensions of five-year data I am mentioning lesion revascularisation (CD-TLR) rate health-related quality of life, sustained Michael [Dake] that because, at the for the Eluvia DES than for the Zilver over 24 months in both treatment arms. presented [see moment, especially PTX [12.7% vs. 20.1%; p=0.0495],” Cost-effectiveness analysis of the US page 8] with the in Germany, we Müller-Hülsbeck told registrants. An Medicare system and the German health Zilver PTX are do not receive any “excellent” primary patency rate was insurance system showed cost savings; really outstanding. reimbursement sustained with the Eluvia DES (83% on average, US$1,300 per patient was My personal hope if we use drug- from Kaplan-Meier estimates), and both saved when patients were treated with for the patient is eluting technology, study devices showed a low mortality the Eluvia device in the USA. “This that, with Eluvia, either the Zilver rate at 24 months: 7.1% for Eluvia, and shows, once again, that when we choose we might achieve Stefan Müller-Hülsbeck (L) and Fabrizio PTX or the Eluvia 8.3% for Zilver PTX. Eluvia, we might achieve a high value equal or even Fanelli at CIRSE 2020 stent.” Issue80 | 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 rivaroxaban use in the main VOYAGER patients with PAD that a history of a PAD trial, Bonaca et al conducted a prior peripheral revascularisation is subanalysis investigating symptomatic associated with a very high risk of acute PAD patients undergoing recurrent lower limb ischaemia, even long-term, years extremity revascularisation versus those after the intervention was done,” Bonaca undergoing their first revascularisation. told online attendees. “More recent They hypothesised that repeat data from the landmark COMPASS revascularisation patients would have trial show that, in patients with chronic a higher rate of acute limb ischaemia, Figure 1 (above): Fabrizio Fanelli (L) and Marc Bonaca PAD, those who had a prior history of and would derive “even greater benefits Figure 2: Cumulative incidence of a composite event rate comprising acute limb revascularisation are at major heightened with a rivaroxaban plus aspirin strategy ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic risk of major adverse limb events.” versus aspirin alone”. stroke, or cardiovascular death in the placebo and rivaroxaban cohorts. LER is lower VOYAGER PAD is a trial of 6,564 The presence of known prior extremity revascularisation. patients with symptomatic lower revascularisation was reported by extremity PAD undergoing peripheral investigators at baseline, and was “very high,” Bonaca pointed out, “even of acute limb ischaemia and vascular revascularisation. Patients were defined as any history of endovascular, in this very well-treated population.” amputation were lower at three-years randomised 1:1 in a double-blind fashion hybrid, or surgical lower extremity Nevertheless, those patients who had post-randomisation than they were in the to either the rivaroxaban group, where revascularisation. The primary outcome had a prior revascularisation had a group of patients who had had previous they received 2.5mg of the drug twice was the same composite as in the higher cumulative event rate of 23.8%, revascularisation: 6% versus 10.8%, and daily, or a placebo group. The primary VOYAGER PAD study. representing a 6.1% increase in risk. 3.4% versus 4.5%, respectively. efficacy endpoint was a five-point From a comorbidity perspective, “When we look at the efficacy of As Bonaca put it: “Patients in the composite of acute limb ischaemia, rivaroxaban, stratified in these two prior revascularisation group have a major amputation of vascular aetiology, groups [prior revascularisation and very high risk of acute limb ischaemia, myocardial infarction, ischaemic stroke, The benefit of no prior revascularisation], we see the almost 11%, and that is driving this or cardiovascular death. The primary benefit is there for both groups,” Bonaca risk profile, and that benefit for acute safety endpoint was thrombolysis in rivaroxaban explained. limb ischaemia [with rivaroxaban] is myocardial infarction major bleeding. appears even In the rivaroxaban cohort, those even greater in patients with a prior In an assessment of the primary with no prior revascularisation had a history of revascularisation. This does efficacy endpoint, the rivaroxaban group greater in those cumulative event rate of 16.9%, while look like our hypothesis—that repeat performed better than the placebo group, who had a those who had undergone an earlier revascularisation patients are at higher with fewer incidences of the five major revascularisation had a cumulative risk and would derive a greater benefit of complications included in the composite prior history of event rate of 18.1%. The impact of prior rivaroxaban—was met in this analysis. measurement. “In spite of best medical revascularisation.” revascularisation was therefore less “Rivaroxaban plus aspirin versus therapy in this population [the placebo in the rivaroxaban cohort than in the aspirin alone reduces irreversible group], the event rate was nearly 20%, placebo cohort. harm events, so the heart, limb, and which was extremely high,” Bonaca the prior revascularisation group had Comparing the placebo and brain in patients that are undergoing said. A Kaplan-Meier curve plotting a higher risk profile, Bonaca shared, rivaroxaban cohorts (Figure 2), revascularisation, but in this subgroup cumulative incidence of the composite with more hypertension, diabetes, and Bonaca told delegates: “The benefit with prior revascularisation, there is a measurement of major adverse events hyperlipidaemia. PAD characteristics of rivaroxaban appears even greater particularly robust benefit, and really against time since randomisation were similar between the two cohorts, in those who had a prior history of notably in acute limb ischaemia. The revealed that, at three-years post- with the prior revascularisation group revascularisation, with a HR of 0.73, and current analysis demonstrates that treatment initiation, the event rate was having a slightly lower risk: “They a trend towards heterogeneity, meaning within this population, those with 19.9% in the placebo arm, and 17.3% in were more likely to be treated with an there may be an even greater benefit in multiple revascularisations are at higher the rivaroxaban arm (hazard ratio [HR], endovascular revascularisation, they had this high-risk group.” risk than those who have undergone a 0.85; 95% confidence interval [CI], less frequently presented with acute limb Wondering what could be driving first revascularisation only, and may 0.76–0.96; p=0.009). ischaemia versus claudication, and the this difference, Bonaca and colleagues derive particularly robust benefit from “Rivaroxaban risk-benefit was [average] ankle-brachial index was a bit looked at the limb outcomes of acute rivaroxaban plus aspirin versus aspirin apparent early, and continued over time,” higher. […] It is worth noting that they limb ischaemia and vascular amputation alone. These observations further Bonaca commented, “with an absolute were very well-treated.” in patients treated with rivaroxaban demonstrate the heterogeneity of risk in risk reduction of 2.6% at three years, and In the placebo cohort, the cumulative with and without prior lower extremity the PAD population, and may assist in a number needed to treat of just 39.” event rate for those with no prior lower revascularisation. In placebo patients clinical risk stratification and therapeutic Against this backdrop of successful extremity revascularisation was 17.7%— with no prior revascularisation, rates decision-making.” 14 Venous interventions November 2020 | Issue80 CONTROVERSIES CHALLENGES CONSENSUS entry in the distal lateral or medial plantar vein from a subintimal channel in the plantar artery can be Deep vein arterialisation should intentionally pursued as a bailout tactic; the guidewire tip is pointed opposite to the arterial wall calcifications. be considered in “no option” Yet another method is the venous arterialisation simplified technique (VAST). This utilises a low-profile balloon catheter and a snare to facilitate arteriovenous CLTI patients, two-year LimFlow fistula creation during venous arterialisation. An arteriovenous fistula could also be created using a data show low-profile balloon catheter and an outback catheter. Del Giudice described a case where he and his team treated Midterm results from a study of the largest population of patients with no-option chronic a patient using this method: “Without any target vessel limb-threatening ischaemia (CLTI) treated with percutaneous deep vein arterialisation in the distal leg,” he said, “we performed subintimal (pDVA) using the LimFlow device show that, in this complex group of patients, this ligation towards the posterior tibial artery, and then we treatment method is feasible, with a high technical success rate and amputation- used the outback [catheter] to advance the balloon into free survival at six through to 24 months, coupled with effective wound healing. In the posterior tibial vein, and create the [arteriovenous] selected patients with no-option CLTI, percutaneous deep vein arterialisation could be a fistula, advancing the guidewire. Finally, we performed recommended treatment to prevent amputation and heal wounds, Costantino Del Giudice a valvotomy with a low-profile balloon, and stented the (Université de Paris, Paris, France) told delegates attending the online 2020 meeting of the vein from the ankle to the arteriovenous fistula.” Cardiovascular and Radiological Society of Europe (CIRSE; 12–15 September, virtual). Showing a table comparing the outcomes at six months from these different techniques, Del Giudice hese results from the ALPS (Midterm outcomes of percutaneous deep venous arterialisation with Ta dedicated system for patients with no-option Vascular & Endovascular 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 Controversies Update 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 end- stage—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 19–22 APRIL 2021 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, LimFlow percutaneous MONDAY-THURSDAY eight (25%) were on immunosuppression, four (16%) deep vein arterialisation had dialysis-dependent renal failure, nine (28%) had system Rutherford category six ischaemia, and 25 (78%) Peripheral Venous & Acute Vascular Aortic were deemed at high risk of amputation. The primary Arterial Lymphatic Stroke Access Controversies outcome was amputation-free survival (AFS) at six was positive: “There is good primary patency, ranging Controversies Controversies Controversies Controversies Controversies months. Secondary outcomes were wound healing, limb Not all patients from 40–90% at six months, and good wound healing salvage, and survival at six, 12, and 24 months. are candidates for outcomes, ranging from 40–100%. Major amputations Technical success was achieved in 31 patients ranged from 0–33.3% at six-month follow-up.” (96.9%). The median follow-up was 34 months (range this procedure. We need 16–63). At six, 12, and 24 months, estimates were salvageable tissue to Earlier trials: The PROMISE I study 83.9%, 71%, and 67.2% for AFS, 86.8%, 79.8%, and The PROMISE I study was an early feasibility study 79.8% for limb salvage, and 36.6%, 68.2%, and 72.7% obtain some results.” launched in mid-2017 to establish the clinical safety DIGITAL EDITION for complete wound healing, respectively. Median time of the Limflow technique. It aimed to provide enough to complete wound healing was 4.9 months (range data for the investigators to move on to a pivotal trial, 0.5–15). The deep vein arterialisation circuit occluded The most important step, he shared, is patient to identify and address any operator challenges, and WWW.CXSYMPOSIUM.COM during follow-up in 21 patients; the median time to selection. “Patients have to have a good heart function, to determine patient characteristics and therapeutic occlusion was 2.6 months. Reintervention for occlusion a good life expectancy, foot arteries not treatable by an parameters that impact performance. Enrolment was was performed in 17 patients: 16 because of unhealed endovascular or surgical approach, a Rutherford class completed in 2019, and the triallists have since reported wounds and one for a newly developed ulcer. 5–6, a Wound, Ischaemia, and Foot Infection (Wifi) a 97% technical success rate in the 32 patients treated in score of 3, and no infection,” Del Giudice listed. the USA as part of this study. Overall survival was 96%, Deep vein arterialisation offers hope for According to the speaker, the Limflow technique is freedom from amputation was 77%, and amputation-free CX 2021 will be streamed live “no option” patients the most commonly used method. survival was 74%. “No option” patients are those where no possible “The importance of this study was that it allowed us daily with audience participation, endovascular or surgical procedure will help, due The LimFlow technique: How it works to understand that not all patients are candidates for this to either the absence of a target vessel or thanks Del Giudice talked CIRSE registrants through a case procedure. We need salvageable tissue to obtain some discussion and polling to unsuccessful prior interventions. These patients demonstrating the use of the Limflow technique. results,” Del Giudice said. “Moreover, the results [show frequently have calcified vessels, diabetes mellitus, This first involved performing arteriography and that] this is quite different from an arterial canalisation. dialysis, and/or long-term corticoid therapy. The risk venography scans to aid target vessel selection. Next, Deep vein arterialisation requires four to six weeks for of amputation and persistent wound is 58% when these the interventionalists advanced the venous and arterial tissue granulation to start. Oedema can occur in the patients are treated with conservative therapy, and the catheters to the target vessel, where the artery and treated limb after deep vein arterialisation, but typically risk of death at one-year follow-up is 20%. vein were closest, and created an arteriovenous fistula, resolves within three to four weeks. We need to preserve Deep vein arterialisation aims to improve the blood bridging the two vessels. Then, they advanced the native arterial perfusion and mange pedal loop outflow flow to the foot. “We direct nutritional improvement guidewire along the vessel, using it to push the balloon during the maturation process. It is also important to by reversal of flow through venules,” Del Giudice through the arteriovenous fistula to create a passage. monitor changes in foot tissue colour. In terms of wound told the CIRSE audience, describing how deep vein Blood flow is diverted from the blocked artery into the care, multidisciplinary collaboration is required, and arterialisation works. “This stimulates arteriogenesis, vein to salvage the lower leg. patients may need some minor amputation management and recruits hibernating collaterals.” Del Giudice shared an alternative technique whereby [and] debridement.” EDUCATION INNOVATION EVIDENCE CONTROVERSIES CHALLENGES CONSENSUS

Vascular & Endovascular Controversies Update

19–22 APRIL 2021 MONDAY-THURSDAY

Peripheral Venous & Acute Vascular Aortic Arterial Lymphatic Stroke Access Controversies Controversies Controversies Controversies Controversies Controversies DIGITAL EDITION WWW.CXSYMPOSIUM.COM

CX 2021 will be streamed live daily with audience participation, discussion and polling

EDUCATION INNOVATION EVIDENCE

Issue80 | November 2020

was lower in the present study, one note that, as a result of the relatively Flow reduction and stenosis being that the reduced number of short research time, the prevalence of non-emergency services during the vascular access complications may not pandemic may have resulted in a be representative of patients at other are major AV access reduced amount of AVF surgery, times. Moreover, they concede that they evidenced by the 395 catheters placed, do not have vascular access data for the complications during early and only 24 AVF surgeries conducted same population before the COVID-19 during the pandemic. pandemic, and therefore state that they months of the pandemic They mention another possible reason cannot compare the establishment In a multicentre cross-sectional study, Jia Shi (Huazhong as being that the number of participants and treatment of vascular access University of Science and Technology, Wuhan, China) and in the present study was far greater than complications observed in this study colleagues assessed the management of vascular access in that in the DOPPS (9,132 vs. 1,123). with previous data. haemodialysis patients during the early months of the COVID-19 Finally, they detail that the rate of Shi and colleagues conclude that this pandemic. They found that catheter flow reduction and stenosis central venous catheter use in secondary indicated that catheter flow reduction of arteriovenous access were the major vascular access hospitals was higher than that in tertiary and AVF/arteriovenous graft stenosis complications. In addition, most of the vascular access sites hospitals, “as the selection of the were the major causes of vascular established were catheters, and many of the vascular access vascular access type is affected by many access complications. In addition, complications remained untreated. factors, including patients’ demographic most of the vascular access established factors, patients’ adherence to vascular during the COVID-19 outbreak were SHI AND COLLEAGUES WRITE had the highest rescue rate (92.7%), access care, variation in operation non-tunnel catheters, and vascular in the Journal of Vascular Access while many other vascular access ability among vascular access doctors, access occlusion received the highest (JVA) that the management of vascular complications remained untreated. The and cooperation between healthcare percentage of rescue procedure during access during the COVID-19 pandemic number of patients diagnosed with professionals and patients,” they the pandemic. is “currently unknown”. In order to confirmed and suspected COVID-19 explain, going on to acknowledge: address this, the investigators collected were 69 and 142, respectively. “Further research is needed to determine vascular access data from haemodialysis Finally, they report that a total of the cause of the observations”. This study patients treated at 44 hospitals in Hubei 146 patients died, of whom 29 patients province in China from 22 January (19.9%) died due to vascular access Conclusions limited by is the first to 10 March 2020 and estimated the complications. study design and short cross-sectional management of vascular access during research time, authors the outbreak of the pandemic. Type of vascular access in concede study to estimate “To the best of our knowledge,” they haemodialysis “is of utmost The authors acknowledge that selection the vascular write, “this study is the first cross- importance” bias may affect their results due to the sectional study to estimate the vascular “The type of vascular access in cross-sectional design of the study. access data of access data of haemodialysis patients in haemodialysis patients is of utmost For example, they recognise that Hubei”. It is also the first to document importance, as it is associated with selection bias may affect their results haemodialysis the indirect effect of the COVID-19 numerous complications,” Shi et al and conclusions due to the cross- patients in Hubei.” pandemic on the management of stress in the discussion of their findings. sectional design of the study. They also vascular access in Hubei. They detail that the Kidney Disease The authors detail that of the 9,231 Outcomes Quality Initiative (KDOQI) haemodialysis patients included in the guidelines and other guideline study, 5,387 patients (58.4%) were male committees recommend AVF as the SAVE registry findings back and 2,959 patients (32.1%) were older first choice of vascular access type for than 65 years. haemodialysis. safety of Surfacer system Writing in JVA, Shi et al report that “According to the KDQOI clinical arteriovenous fistula (AVF) was the practice guidelines,” Shi and colleagues The Surfacer Inside-Out access catheter system device most predominant type of vascular write, “the target for functional AVF (Bluegrass Vascular) is safe and effective for patients with access, accounting for 76.5%. In in prevalent haemodialysis patients thoracic central venous obstruction requiring central venous addition, they observed that 496 is ≥65%, and catheter use should be access. That is conclusion of the prospective, multicentre patients (5.4%) developed vascular less than 10%”. However, they detail SAVE (Surfacer system to facilitate access in venous access complications and that catheter that vascular access use varies greatly occlusions) registry, published recently in the Journal of flow reduction was the most common across countries. They reference the Vascular and Interventional Radiology (JVIR). vascular access complication. Among 2013 Dialysis Outcomes and Practice those with arteriovenous access, they Patterns Study (DOPPS) study, which GÜRKAN SENGÖLGE (MEDICAL UNIVERSITY OF VIENNA, VIENNA, found that stenosis was the predominant showed that the rate of AVF use varies Austria), co-author on the paper details: “We gained access with complication. across the world, with 49% use in Surfacer technology in over 98% of the cases.”. Furthermore, the authors relay that Canada and 92% use in Russia, while “The publication of the results of the SAVE registry expands 280 vascular access sites were placed in central venous catheter use was 45% and strengthens the clinical evidence confirming the role patients newly diagnosed with uraemia, in Canada and 6% in Russia. In China, the Surfacer system has in helping to establish central of whom 260 (92.8%) underwent AVF use was 87% and CVC use was venous access in patients with venous obstructions,” states catheter insertion, which consisted 10%. “In the present study, the rate Maurizio Gallieni (University of Milan, Milan, Italy), who was of 132 catheters, seven percutaneous of AVF use was 76.5%, which was a co-lead author. transluminal angioplasties, six lower than that reported in the Chinese The Surfacer system has received US Food arteriovenous repairs, and four AVFs. DOPPS data (87%),” they state. and Drug Administration (FDA) de novo device Shi and colleagues state that Shi et al put forward a number clearance in the USA and is CE marked in Europe. occlusion of the arteriovenous access of possible reasons why this rate November 2020 | Issue80

In terms of primary patency, Crane and colleagues Study finds 3mm arteriotomy note that this was 76% and 69% at six and 12 months, respectively. Secondary patency at the same time points was may be routinely utilised for 91% and 94%, respectively. Finally, the authors detail that dialysis access steal syndrome was clinically brachiocephalic fistula creation apparent in three (4.4%) patients, with all cases being managed conservatively. In a recently-published study, Jeremy Crane (Imperial College Healthcare NHS Trust, The authors recognise that steal syndrome is Hammersmith Hospital, London, UK) and colleagues conclude that a 3mm-long multifactorial in origin and not purely related to arteriotomy may be routinely utilised for brachiocephalic fistula creation in an attempt to anastomosis calibre. limit the incidence of steal syndrome, while maintaining clinical patency outcomes. In addition, “follow-up among the patients included in the study is limited,” Crane and colleagues “THE ARTERIOVENOUS FISTULA [AVF] IS of symptomatic steal syndrome, while maintaining write, adding that late presentations of DASS due the modality of choice for long-term haemodialysis clinical patency outcomes. to ongoing arterial and venous remodelling and access,” the Journal of Vascular Access (JVA) paper Crane and colleagues describe the study as a subsequent increase in fistula flow may subsequently begins. The authors cite lower rates of retrospective analysis of prospectively collected occur. access-related infection and improved clinical data from a single surgeon. A randomised trial with clear documentation of patient and access survival when They detail that they included all venous and arterial diameter along with postoperative compared to other modalities such as patients who underwent brachiocephalic duplex ultrasound and haemodialysis access flow arteriovenous grafts or longstanding fistula formation using a routine 3mm- assessment would be useful, they suggest. tunnelled central venous catheters long arteriotomy within Hammersmith as the reasons behind this. Hospital between January 2017 and However, AVF formation is March 2018 in the study. Primary A randomised “not to be taken lightly,” Crane outcomes included primary failure, trial with clear and colleagues warn, noting failure of maturation, secondary patency, dialysis access-associated steal and steal syndrome. documentation of venous syndrome (DASS) as an “important” and Writing in JVA, Crane et al relay that 68 and arterial diameter “potentially limb threatening” complication. brachiocephalic AVFs were fashioned utilising They explain that the hallmarks of steal syndrome a 3mm arteriotomy during the study period, adding along with postoperative are symptoms and signs of peripheral vascular that the mean age was 60.5 years with 59% having a duplex ultrasound and insufficiency within the limb distal to the AVF, which history of diabetes mellitus. The mean follow-up was are often detected through a thorough clinical history 368 days, the authors write. haemodialysis access and examination. The authors report that primary failure occured They go on to describe the feasibility of routinely in 10 (14.7%) of patients, and that cannulation was flow assessment would fashioning a brachiocephalic fistula utilising a 3mm- achieved in 67.3% of remaining fistulae within three be useful.” long arteriotomy in an attempt to reduce the incidence months, rising to 87.3% by six months.

thrombosis, aneurysm, and infection. December 2018. Older age and diabetes “In fact,” Yoshida et al say, “the medical expenses for vascular access- Post-PTA patency mellitus identified as risk related complications is estimated unaffected by vascular at JPY 10,953,310,000/year”. The access form in older investigators therefore surmise that patients factors for poor patency rates “recognition of risk factors for vascular The study results reveal that access failure is needed not only to radiocephalic AVF exhibited better following vascular access improve the quality of life of patients 24-month primary and secondary undergoing haemodialysis, but also to patency rates than AVG in patients who construction reduce medical expenditure”. started haemodialysis: 54.5% and 91.6% They conducted a multicentre, versus 25.1% and 70.3%. The authors Different risk factors affect patency between vascular access prospective, observational study of 611 note that these 24-month primary and construction and the first percutaneous transluminal angioplasty, patients who had started haemodialysis secondary patency rates after vascular Mahoko Yoshida (Hiroshima University Hospital, Hiroshima, between 1 April 2012 and 31 March Japan) and colleagues conclude in the Journal of Vascular 2018, and investigated the primary Access (JVA). Their results indicate that a poor patency rate is and secondary patency rates after The majority commonly associated with advanced age, and diabetes mellitus. construction of a radiocephalic of dialysis arteriovenous fistula (AVF) and “THESE FINDINGS SUGGEST resulting in more effective management arteriovenous graft (AVG). Primary patients receive that older patients and those with of vascular access.” patency was defined as the period haemodialysis, diabetes mellitus are more likely to from vascular access construction to experience vascular access problems Dialysis: “A global PTA or surgical revision within 24 and are known to after both vascular access construction health concern” months; secondary patency was defined suffer from various and percutaneous transluminal The number of patients undergoing as the period from vascular access angioplasty [PTA], and that different dialysis worldwide has been increasing construction to the date of vascular complications, risk factors should be taken into account each year, the study authors write, and access abandonment. The study also including when managing patients undergoing is considered a global health concern. examined the patency rate following haemodialysis after vascular access The majority of dialysis patients receive PTA—defined as the period from the cardiovascular construction and PTA,” the study haemodialysis, and are known to suffer first PTA to the next PTA or surgical disease and authors write. “Understanding the risk from various complications, including revision within 12 months—as well factors that contribute to vascular access cardiovascular disease and infections. as the clinical factors that contributed infections.” problems may lead to better surveillance The most frequent issue relates to to the development of restenosis. and focused care in high-risk patients, problems with vascular access: stenosis, All patients were followed-up until Continued on page 20

November 2020 | Issue80

shorter period from vascular access between vascular access construction Older age and diabetes mellitus construction to use were associated and the first PTA, Mahoko Yoshida with poor patency after the first PTA. (Hiroshima University Hospital, identified as risk factors for poor These results led the study investigators Hiroshima, Japan) and colleagues patency rates following vascular to conclude that patients need to start conclude in JVA. Their results haemodialysis “urgently”. indicate that a poor patency rate is access construction “These findings suggest that with commonly associated with advanced the exception of ageing and diabetes age, diabetes mellitus, female sex, Continued from page 18 mellitus, different risk factors contribute low serum albumin, and the use of an access construction are higher than median age of the patients was 70 to the incidence of vascular access erythropoietin-stimulating agent. those reported in the literature by years, suggesting that rather than the problems after surgical construction “These findings suggest that older researchers investigating patients vascular access form, the background of vascular access and restenosis after patients and those with diabetes mellitus outside of Japan. They postulate that the of the patients may be more strongly PTA,” the authors conclude. are more likely to experience vascular higher patency rates seen in Japanese associated with the patency rate.” “Our data showed that stenosis access problems after both vascular patients could be due to the fact that accounted for 92% of vascular access access construction and PTA, and that they undergo haemodialysis with lower Risk factors for vascular problems. […] These findings suggest different risk factors should be taken blood flow, which they suggest may access complications that the presence or absence of into account when managing patients enable the vascular access to be used A Cox proportional hazard model for longer periods. demonstrated that ageing, female While the patency rates after vascular sex, diabetes mellitus, low serum Understanding access construction between the two albumin, and use of an erythropoietin- vascular access forms (radiocephalic stimulating agent were associated the risk factors AVF and AVG) was not significantly with poor primary patency after that contribute to different in the multivariate analysis, vascular access construction in this they did show a significant difference study. Of these identified risk factors, vascular access in the log-rank test. “With respect to ageing, diabetes mellitus, and low problems may lead the post-PTA patency rate, although serum albumin may be indicative of a radiocephalic AVF appeared to result in patient’s poor general condition, the to better surveillance a better patency rate than that of AVG, study authors muse, while female sex and focused care in the difference was not statistically has reportedly been associated with significant in either the log-rank test smaller vascular diameter, which can high-risk patients.” or Cox proportional hazard model,” increase the number of vascular access Yoshida and colleagues discuss. “A problems. procedure-induced stimulation may previous study reported that AVF “Taken together these results indicate cause differences in the risk factors undergoing haemodialysis after vascular exhibited a better patency rate after that vascular access patency might be that influence the patency rates after access construction and PTA,” the study both vascular access construction improved if modifiable risk factors vascular access construction and that authors write. and PTA than AVG. Notably, another identified in the present study are well after PTA.” “Understanding the risk factors that study showed that the patency rate of controlled,” Yoshida et al write. contribute to vascular access problems AVF did not differ from that of AVG Furthermore, ageing, diabetes Risk factors for poor may lead to better surveillance and in advanced-age patients undergoing mellitus, polycystic kidney disease, patency rates after vascular focused care in high-risk patients, haemodialysis, especially those aged initiation of haemodialysis with the access construction resulting in more effective management >65 years. In the present study, the use of a temporary catheter, and a Different risk factors affect patency of vascular access.”

Ellipsys system offers greater patient possible dialysis access with the fewest possible interventions,” said Shahverdyan. eligibility and reduced time to dialysis, “Our data show that with careful planning, both systems can safely and quickly create percutaneous study finds fistulas with a high rate of success, though the Ellipsys system appears to create more durable Two devices for creating minimally invasive dialysis access—the Ellipsys vascular access that is also easier to repair if that becomes access system (Avenu Medical) and the WavelinQ 4F system (BD)—demonstrated necessary.” high rates of technical success and low rates of complications in a new study. Compared to surgical fistulas, both devices reduced the time to dialysis (cannulation). The mean IN ADDITION, BOTH TECHNOLOGIES study, led by vascular surgeon Robert Shahverdyan time to cannulation for WavelinQ was 90 days, enabled patients to start dialysis sooner compared (Vascular Access Center, Hamburg, Germany), compared to 60 days with Ellipsys. In fact, 75% to surgery, offering significant quality-of-life compared the outcomes for 100 patients who of Ellipsys fistulas were ready for cannulation at just benefits. The results were published in the Journal of underwent pAVF procedures (65 Ellipsys and 35 four weeks, with a small number of patients ready Vascular and Interventional Radiology. WavelinQ) from December 2017 to December 2019. for early cannulation within a few days of fistula For patients with end-stage renal disease (ESRD) The Ellipsys system had a technical success creation, Shahverdyan notes. who require haemodialysis, the preferred type of rate of 100%, and only 27.7% of patients required “This study confirms other newly published vascular access is an arteriovenous fistula (AVF)—a secondary interventions following fistula creation. data showing how much faster we can start using permanent connection between a vein and artery in The WavelinQ system demonstrated similar the Ellipsys percutaneous fistula for dialysis—a the arm. Until recently, the only way to create an outcomes, with a technical success rate of 97% and finding that has significant patient safety benefits,” AVF was through a surgical procedure that subjects 26.5% of patients requiring secondary interventions. said interventional radiologist Jeffrey Hull patients to discomfort, longer recovery times, and Overall, 79.5% of Ellipsys patients and 58% of (Richmond Vascular Center, Richmond, USA). delayed dialysis. WavelinQ patients were able to successfully begin “The sooner a patient can start dialysis with their Both the Ellipsys and WavelinQ devices offer dialysis with their fistula. At 12 months, 82% fistula, the sooner we can get them off such riskier a nonsurgical alternative by using a minimally of Ellipsys fistulas were still functional, compared to dialysis access methods as central venous catheters, invasive approach to create a percutaneous 60% of WavelinQ fistulas. which are associated with much higher rates of arteriovenous fistula (pAVF). The new single-centre “For every patient, my goal is to create the best infection and other complications.” Issue80 | November 2020

reduce costs. Unlike open surgery, sutures are not of Medicine,” said Mark Pacyna, vice president Medtronic to required after the procedure and the patient leaves and general manager of the Peripheral Vascular with just an adhesive bandage.” business at Medtronic. “Now with the acquisition The Ellipsys vascular access system bears the CE of Avenu Medical, we can support procedures across acquire Avenu mark for distribution in the European Union and is the vascular access care continuum, while continuing cleared by the US Food and Drug Administration. It to provide innovative endovascular therapies that is indicated in both geographies for the creation of a will ultimately reach even more patients with ESRD Medical proximal radial artery to perforating vein anastomosis around the world.” for percutaneous creation of an AVF. At time of publication, the acquisition is expected Medtronic recently announced the “Medtronic’s acquisition of Avenu aligns to close by November 2020, subject to the satisfaction planned acquisition of Avenu Medical, directly with our vision of bringing less invasive, of certain closing conditions. The acquisition of a medical device company focused Avenu Medical is the sixth in a series of tuck in on the endovascular creation of acquisitions that Medtronic has made in 2020. arteriovenous fistulas (AVFs) for The transaction is expected to be immaterial patients with end-stage renal to Medtronic's adjusted earnings per share in disease (ESRD) undergoing dialysis. the first two years before turning accretive in Terms of the transaction were fiscal year 2023. In addition, this transaction not disclosed. is expected to meet Medtronic's long-term financial metrics for acquisitions. A PRESS RELEASE EXPLAINS THAT AVENU Medical’s Ellipsys vascular access system is a endovascular solutions to patients requiring durable single-catheter, ultrasound-guided device that inserts vascular access,” said Mark Ritchart, president AVFs are like a catheter percutaneously into the arm to create a and chief executive officer of Avenu Medical. durable AVF. The procedure can be performed in the “With Medtronic’s extensive market presence, clinical lifelines to patients hospital outpatient centre, ambulatory surgery center leadership, and market development expertise, undergoing dialysis. Until (ASC), or physician’s office. coupled with Avenu’s customer-focused team “AVFs are like lifelines to patients undergoing and innovative technology, we are confident that recently, the only option dialysis. Until recently, the only option to create together, we can drive awareness and adoption of this to create a fistula was a fistula was through invasive surgery, which is technology globally.” associated with high failure rates,” said Jeffrey Hull “Within the last year, we have seen significant through invasive surgery, (Richmond Vascular Center, Richmond, USA), co- momentum with the launch of the IN.PACT AV founder of Avenu Medical. “The Ellipsys system has drug-coated balloon (DCB) in the USA and primary which is associated with shown durable outcomes out to two years and has endpoint results of the IN.PACT AV Access study high failure rates.” the ability to shorten procedure times and potentially being published in The New England Journal

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is not yet possible to assess whether radiologists) where staff redeployment COVID-19 infection had adverse or sickness is a problem, and also Dialysis access outcomes. Anecdotally, claims have allow procedures to be performed in been made for prothrombotic tendencies, alternative facilities, avoiding hot sites particularly in those severely affected, and potentially freeing up theatres. but data on fistula loss secondary to In order to prepare for further waves needs to be a priority infection are not yet clear. Dysfunctional of COVID-19, the provision of the best access may have been afforded higher dialysis access, including peritoneal priority and performing maintenance dialysis, will require close working in the COVID-19 era procedures may have avoided CVC with the wider multidisciplinary team insertions. It is unclear whether patients involved in assessment, creation, presented later during the pandemic due cannulation, surveillance, maintenance, to shielding risks, or hospitals operated and salvage of definitive access. policies of inserting a CVC to reduce lengthy salvage procedures. An opportunity for change Panagiotis Kitrou The consequences arising from To manage dialysis access appropriately increased CVC placement and reduced during peaks of COVID-19 will require Nicholas Inston fistula creation and salvage will result in better identification of those in need, multiple issues. Repeated hospitalisation, with more timely assessment and bloodstream infections, catheter creation of access. Early identification Comment & Analysis dysfunction, central venous stenosis, and of problematic access through skilled occlusion are all a product of increased clinical examination, timely and Panagiotis M Kitrou and Nicholas Inston discuss the impact of catheter use and as a consequence appropriate referral for diagnostics, and the COVID-19 pandemic on vascular access services. Despite the healthcare costs will increase.9 This treatment using optimal technologies disruption caused, they believe the pandemic should be viewed significant economic and healthcare by those with expertise should be as a catalyst for change. It is time to “redesign and restructure” burden will not only start to show available. Follow-up and surveillance vascular access programmes, they tell Interventional News. now, but as renal failure is a chronic should be based around dialysis sessions disease will have significant effect on and training of dialysis centre staff he COVID-19 pandemic has USA, 80% of patients initiate dialyses health economics in the long term. In to cannulate, examine, and identify resulted in major disruption in on a central venous catheter (CVC)5 and addition, CVCs have a negative impact problems with liaison and accessibility the delivery of clinical services international rates of definitive access on the quality of life and longevity of to expertise made easily available. T 6 on a scale previously unseen. In many are highly variable. haemodialysis patients and constitutes The challenges of dialysis access may countries, rationing of facilities and Despite this, benefits of definitive a major deviation from best practice have been exacerbated by the pandemic, severely restricted or zero access to vascular access and avoidance of CVCs guidelines and a serious setback in the but all these requirements were present operating theatres has been imposed. are clearly demonstrated, particularly in standard of care previously delivered.10 before. This is an opportunity for It has been estimated that 28.4 million the less comorbid patients.7,8 vascular access programmes to redesign surgical procedures have been cancelled The problems encountered during the “Robust plans” needed for and restructure, not only to deal with globally, with the highest cancellation first peak of the pandemic are likely to second wave the pandemic, but to build better rates in benign disease.1 The crisis have resulted in many patients starting Whilst some countries are unfortunately programmes suited to the needs of the has affected different countries and dialysis on a CVC. This is multifactorial. currently dealing with the first wave, large global population of renal patients. even different regions of countries Patients with chronic kidney disease others are now experiencing a second variably. In Asia, 47% of healthcare (CKD) stages 4 and 5 require access wave. The needs of CKD and dialysis Panagiotis M Kitrou is an practices suspended elective vascular in preparation for dialysis. These patients require robust plans to optimise interventional radiologist at Patras surgery completely and 23% scaled vulnerable patients have been advised to safe creation, maintenance, and salvage University Hospital, Patras, Greece. down activity.2 In the UK, it has been follow enforced shielding practices. As of definitive vascular access and Nicholas Inston is a consultant estimated that to clear the backlog of such, they neither fall into a high priority avoidance of the use of CVCs. transplant and vascular access surgeon cancelled surgery at 20% extra activity at the University Hospital Birmingham will require 11 months, even if further NHS Trust, Birmingham, UK. surgeries are not factored in. To manage dialysis access To manage constrained services, References appropriately during peaks 1. CovidSurg C, Nepogodiev D, Bhangu A. Elective many societies issued prioritisation to surgery cancellations due to the COVID-19 pandemic: allow rationing based on clinical risk, global predictive modelling to inform surgical recovery of COVID-19 will require better plans. Br J Surg 2020. mainly based on estimated urgency and 2. Ng JJ, Ho P, Dharmaraj RB, et al. The global impact of identification of those in need.” COVID-19 on vascular surgical services. J Vasc Surg need for treatment. These have been 2020; 71(6):2182–3 e1. classified as 1a. emergency <24 hours; 3. RCS. Clinical guide to surgical prioritisation during the coronoavirus pandemic. 1b. urgent (up to 72 hours); 2. up to one group for surgery nor are advised to These strategies may require local 4. SVS. Vascular conditions by category, with Teir Class month; 3. up to three months; and 4. attend hospital appointments in person. modifications. Ideally cold (green) 2020 [Available from: https://vascular.org/sites/default/ files/Vascular%20surgery%20triage%20by%20 over three months by the Royal Colleges Assessment for vascular access generally sites should be used, although dialysis Tier%20Class%203.24.20.pdf]. in the UK,3 and by the Society for requires ultrasound mapping and this patients’ inability to isolate due to thrice 5. USRDS. USRDS 2019 Report 2019 [https://www. usrds.org/2019/view/USRDS_2019_ES_final.pdf]. Vascular Surgery (SVS) as 1. postpone; may have been avoided to elude virus weekly treatment may prohibit pure 6. Pisoni RL ZL, Port FK, Robinson BM. Trends in US vascular access use, patient preferences, and related 2a. consider postponing; 2b. postpone if exposure. Pre-emptive living donor “clean” pathways. Risk assessments practices: an update from the US DOPPS Practice possible; and 3. do not postpone.4 transplantation, which may have may need specific “renal pathways” to Monitor with international comparisons. Am J Kidney Dis 2015; 65(6):905–915. Am J Kidney Dis 2015; eliminated the need for vascular access, be developed rather than apply standard 65:905–15. Provision of vascular access may have been suspended. surgical risk stratification. 7. Ravani P, Quinn R, Oliver M, et al. Examining the association between hemodialysis access type and for dialysis “less than ideal” In patients infected with COVID-19, Where surgical services are mortality: the role of access complications. Clin J Am before pandemic the requirement for renal replacement overwhelmed or resources compromised, Soc Nephrol 2017; 12(6):955–64. 8. Quinn RR, Oliver MJ, Devoe D, et al. The effect of The impact of COVID-19 on dialysis therapy was high, particularly in those other strategies should be considered, predialysis fistula attempt on risk of all-cause and access-related death. J Am Soc Nephrol 2017; access is not yet known, but it is requiring intensive care. The impact of particularly endovascular approaches 28(2):613–20. predicted that the rates of definitive multiple vascular access attempts on to maintenance, salvage, and even 9. Vassalotti JA, Jennings WC, Beathard GA, et al. Fistula first breakthrough initiative: targeting catheter access have been severely affected. these patients and long-term effects on creation using percutaneous devices. last in fistula first. Semin Dial 2012; 25(3):303–10. Prior to the pandemic, the provision of renal function remain to be seen, but This may increase the availability of 10. Lok CE HT, Lee T, et al. KDOQI vascular access guideline work group. KDOQI clinical practice vascular access for dialysis was already may add a further healthcare need. additional operators, (e.g. interventional guideline for vascular access: 2019 update. Am J identified as being less than ideal. In the For patients with existing access data, nephrologists and interventional Kidney Dis 2020; 75(4).

24 Interview October 2020 | Issue80

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 hepato- biliary-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 radiologists in Greece interventional radiology (IR)? to perform percutaneous liver tumour I was initially attracted to radiology because I loved ablation. What are the most exciting imaging and trying to find the “pathological hidden in aspects of working at the vanguard? the physiological”. Then I discovered IR, where I had This is the reason why I like working in university the possibility to “clean” the physiological from the hospitals. Patients and other medical specialties can pathological. trust you more easily when it comes to new methods and techniques. Of course, you have to perform the Have you had important mentors for you procedures well and safely, with nice results to keep throughout your career? a good and trustworthy name. Sometimes this is not Yes, several. To start, my first professor, Nicholas enough, because other specialties do not want to move Gourtsoyiannis, in Heraklion, Crete. He taught us the to new methods and lose control of their patients, or stop importance of becoming clinical radiologists, and how to performing what is common practice to them in favour have a presence on the international stage. Together with of IR methods. The same happened in the old days with my tutor and friend Spyros Karampekios, we performed oncologists who did not want to stop chemotherapy the first IR procedures in Heraklion, back in 1993. protocols and send patients to radiofrequency ablation Next, my IR teacher, Panos Galis, at the AirForce (RFA) in order to calculate total survival rates. The same Hospital in Athens, Greece. He was a Greek pioneer thing still happens now with other IR techniques such in vascular IR, and I learned many tricks from his as vertebroplasty, varicocele and fibroid embolization, experience. and I am afraid it will also happen with prostatic artery Another three titans of IR who have been personally embolization. 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 am confident I learned how to manage, in Aachen how to organise, that the role of IR and in Rome how to improvise. All of these experiences were of great value. departments will come out of this crisis more Why are you specifically drawn to the hepato-biliary-pancreatic system? What powerful than before, do we still have to learn about treatment because we provide in this system? In the era of magnetic resonance minimally invasive cholangiopancreatography (MRCP), endoscopists have fewer possibilities to practice so many endoscopic solutions without the retrograde cholangiopancreatographies (ERCPs), with need for intensive care the result that new doctors are less well trained. So, radiologists usually have more to do. Biliary IR is unit beds.” delicate work, offering you a lot of challenging cases. Performing malignant cases is good training for tough Could you describe a particularly benign cases. memorable case? Yes, definitely the first TIPS procedure done in Greece. education format. Our last CIRSE Summit (12–15 In 1996, you performed the first I was still a final year radiology resident and I was September, virtual) is such an example. The set-up transjugular intrahepatic portosystemic asked to try to perform it. There were five university we managed to create in such a short time and the shunt procedure (TIPS) in Greece. How professors outside the angiography suite, and I needed transformation of the programme from a live event to a did this come about? five hours to complete the case. I would, of course, digital one was a big challenge. That was my passport to the future. The case went never have managed it without their trust and the good I am confident that this shift to online learning well, although the patient was not able to survive for help of two senior radiologists who were my teachers has come to stay. The future will be full of hybrid a long time. Performing this case helped to create a and the backbone of our department. congresses with both live and distant participation. I lot of respect for my work and IR more generally, but hope during the next two years that we will be able to go the expectations others have from you can become a As deputy chair of the Cardiovascular back to face-to-face events, as these are very important very heavy burden. I learned that I had to constantly and Interventional Radiological for communication between doctors and industry, but perform at a high level, and try to be involved in novel Society of Europe (CIRSE) programme also maintain some remote-learning capabilities, so procedures, so that everybody could benefit from this. I committee 2019–2021, and upcoming that more colleagues may benefit from the international think one can feel that they have to fulfil the obligation chair of the same committee, what are educational opportunities on offer. to continue working at a high scientific level in order your goals for scientific education over to show the younger generation of interventional the next two years? How has the COVID-19 pandemic radiologists their way to the top. Providing medical education has become difficult due impacted IR this year, and do you to travel restrictions. But this problem has convinced foresee a lasting change to the In 1998, you were one of the first international medical societies to transition to a digital discipline? Issue80 | 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 „ Head, Interventional Radiology of Europe (CIRSE) Unit, AHEPA University Hospital of Thessaloniki, Thessaloniki, Current Appointments Society positions (selected) Greece „ Professor of Radiology, Faculty of „ Secretary, Hellenic College of „ Professor, Radiology, Medicine, Aristotle University of Radiology Aristotle University of Thessaloniki, Thessaloniki, Greece „ Member, executive committee, Thessaloniki, Thessaloniki, „ Head of Interventional Radiology, Greek Society of Interventional Greece Department of Radiology, AHEPA Radiology (GSIR) „ Head, Department of University of Thessaloniki, Conventional Radiology and Thessaloniki, Greece Medical education and CT, Institute of Medical „ Chair, Department of Radiotherapy, appointments Imaging, University AHEPA University of Thessaloniki, „ Chief, Department of Radiation Hospital of Thessaloniki, Greece Oncology, AHEPA University Heraklion, „ Deputy chair, programme Hospital of Thessaloniki, Heraklion, committee, Cardiovascular and Thessaloniki, Greece Greece 26 CX Aortic Vienna November 2020 | Issue80

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.

oseph Bavaria (Hospital of the University of gather data on the use of the technique in 200 patients Clockwise from top left, Roger Greenhalgh, Pennsylvania, Philadelphia, USA) began with for a follow-up period of two years. The registry has Stephan Haulon, Juerg Schmidli, Enrico Rinaldi, Ja presentation in which he advocated moving been included in the top 10 candidates of aortic disease William Jordan and Kevin Mani toward “a definitive aortic solution” in acute type trials found on clinical trials.gov, in a study published A dissections—describing what he sees as a new in the Journal of Internal Medicine. paradigm for the open zone 2/1 arch with sequential According to Kevin Mani (Uppsala University, delayed branch arch thoracic endovascular aortic Uppsala, Sweden) chronic type B aortic dissection repair (TEVAR). Bavaria presented outcomes from can be successfully treated with TEVAR, however various Debakey type 1 dissection cases, describing re-interventions are not uncommon, he told the CX these as “catastrophic”, and arguing in favour of a Aortic Vienna audience, with the success of TEVAR change in approach in order to improve outcomes. The dependent on the extension of the disease. In his key concept in doing so, he suggested, is a strategy presentation, covering the role of endovascular involving zone 2 arch replacement with sequential treatment in chronic type B aortic dissections, Mani branched TEVAR. reminded the audience that the endovascular toolbox He said: “The future based on our data, our increased includes both false lumen occlusion devices as well as sophistication, and the availability of new technology Clockwise from top left, Roger Greenhalgh, Stephan Haulon, Juerg Schmidli, Germano is that in patients with less than 10‒15 years of life Melissano, Robin Heijmen and Joseph Bavaria expectancy, usually >65, we use the classic hemi- When it is possible, arch operations. A patient with an arch tear or distal open surgical malperfusion is suitable for an on-table frozen elephant trunk procedure. In patients who are younger than repair still represents 65-years-old and stable, we perform a Zone 2 arch with the treatment of choice possible sequential arch branch TEVAR, usually in a few weeks.” for chronic type B aortic Robin Heijmen (Antonius Hospital, Nieuwegein, The Netherlands) then discussed the value of transapical dissection.” access for thoracic aortic procedures. Heijmen opened noting that the true value of TEVAR is its less-invasive thoracoabdominal fenestrated repair. “TEVAR is not a approach, adding that the transfemoral route is one-off treatment in chronic type B aortic dissections preferred in most cases. However, where there is severe and you have to prepare for future battles,” he said. iliofemoral pathology this may not be possible, he said, “Move sooner”, was the message from William Polling results suggest a consensus that timing of intervention in type B dissections is a key adding that in these instances transapical access can be Jordan (Emory University School of Medicine, Atlanta, consideration an alternative. Transapical access involves approaching USA) who offered the international CX Aortic Vienna through the “apex” of the left ventricle. “In recent audience his insights into the early treatment of type Closing the session, Enrico Rinaldi (San Raffaele years in more than 15 patients we have used transapical B aortic dissections. He noted that acute type B aortic Scientific Institute, Milan, Italy) offered participants a TEVAR safely and effectively and do appreciate its dissection is a high risk condition, with a high rate of series of technical tips for the open repair of chronic value in treating thoracic aortic pathology in case of an mortality, particularly for patients undergoing open type B dissection. He noted that European guidelines inadequate peripheral access,” Heijmen commented. repair and added that increasingly, treatment of type recommend open repair for patients with aneurysmal Following on from Heijmen, Germano Melissano B aortic dissection has moved towards TEVAR in or symptomatic chronic type B dissection with a low (Vita-Salute San Raffaele University, Milan, Italy) recent years. He then presented data on early versus surgical risk. “When it is possible, open surgical repair detailed a new technical approach for type B late repair, using either TEVAR or open approaches— still represents the treatment of choice for chronic type dissection—the STABILISE concept—combining highlighting an improved 10-year survival in patients B aortic dissection,” Rinaldi said. His presentation proximal descending aortic endografting with distal who underwent early repairs, specifically with TEVAR. highlighted the need for identification and management bare metal stenting. This technique results in a Jordan concluded that endovascular therapy provides of the true and false lumen, proper graft selection completely remodelled aorta throughout its whole less invasive treatment for complex aortic pathology, based upon patient characteristics, challenges in length, according to Melissano. He also detailed the and that early intervention is associated with better intercostal artery reattachment, and management of the aims of the STABILISE Registry which is seeking to long-term survival. ascending aorta.

Medical USA) took to the virtual podium injury, and TEVAR or open repair for as definitive therapy. In this latter group, during CX Aortic Vienna (8–11 Grade II–IV. In 2016, the Aortic Trauma 59.6% had Grade I injuries, 23.7% had management September, online) to discuss Foundation launched an international, Grade II, and 16.7% had Grade III–IV. the medical management of multicentre, prospective blunt traumatic Twelve of the 114 patients (10.5%) “effective” for blunt thoracic aortic injury, as aortic injury registry. To date, 794 required intervention after failed medical viewed through the lens of the patients have been enrolled at 37 centres. management. The majority (83.3%) of the treatment of Aortic Trauma Foundation global Azizzadeh et al set out to determine these patients had Grade III injury. Eleven registry. He believes the most the outcomes of medical management of the 12 patients (92%) underwent Grade II blunt recent data support revision of for blunt traumatic aortic injury, and TEVAR, and one underwent open repair. the current Society for Vascular analysed a subset of patients in the Aortic While the overall in-hospital mortality thoracic aortic Surgery (SVS) clinical practice Trauma Foundation’s global registry was 7.9% (nine of 114 patients), the guidelines. who had this treatment type listed as aortic-related mortality was zero, leading injuries their definitive therapy. It included 432 Azizzadeh et al to conclude that medical THE CURRENT SVS CLINICAL patients treated from 2016–2020; 57% management “appears to be safe and Ali Azizzadeh (Cedars-Sinai practice guidelines recommend medical had medical management initially, and effective, with a low overall intervention Medical Center, Los Angeles, therapy for Grade I traumatic aortic 26% had medical management planned rate and no aortic-related deaths”.

28 Fertility and UAE November 2020 | Issue80

anastomoses, and extensive myometrial and endometrial significant complications post-procedurally; and 59.5% Fertility after uterine ischaemic damage, largely due to an aggressive (44 of 74 women) in a paper from João Pisco (St Louis embolization technique. The latter complication can Hospital, Lisbon, Portugal) et al, published in 2011. artery embolization: result in hysterectomy, which Pelage said “is obviously a Detailing his own institution’s recent experience, Still an unsolved issue, disaster for women trying to get pregnant.” Pelage told registrants: “[We had a] 56% pregnancy rate “There are some studies reporting very low pregnancy in better-selected women, so younger than in our first CIRSE delegates heard rates, including our initial experience: in 66 women cohort.” The 16 women included in this more recent offered embolization as a last resort treatment, there is study had an average age of 35 years, and nine of the Fertility in patients who have had uterine virtually 0% pregnancy,” Pelage commented. group were actively trying to conceive. One-year post- artery embolization (UAE) is still a “hot “All these studies are confusing,” he said, “including embolization, five of the women were pregnant. topic,” Jean-Pierre Pelage (University the only randomised controlled trial dedicated to fertility Citing the results of the FEMME trial, published in Hospital and Medical Center, Caen, France) [from Michal Mara (Charles University, Prague, Czech the New England Journal of Medicine (NEJM) in July told delegates attending the online meeting Republic) et al, published in 2008]. The pregnancy 2020, Pelage highlighted the team’s fertility results: of the Cardiovascular and Interventional “They reported a significant number of pregnancies Radiological Society of Europe (CIRSE; 12– after embolization, even higher than in the surgery 15 September, virtual). “We have confusing Jean-Pierre [myomectomy] group. Since it was not the primary data in the literature—we know fertility after Pelage presenting objective, I well understand that you cannot draw UAE is possible, and that UAE is a valuable during the 2020 definitive conclusions based on this paper.” meeting of the alternative to hysterectomy and multiple Cardiovasular Pelage summarised: “Pregnancy results are very myomectomy in symptomatic patients, and Interventional variable, ranging from 14–61% from one study to but the role of embolization in the specific Radiological another. The same [is true] for the miscarriage rate, subset of women trying to get pregnant Society of Europe obviously with miscarriage being more common in older remains controversial.” women. From the existing literature, there seems to be an interest on the hormonal function [elevated FSH WHILE SOME STUDIES HAVE DEMONSTRATED rate was lower after embolization, and the final term levels is more frequent after UAE], there seems to be a a 100% pregnancy rate following UAE, Pelage warned pregnancy rate was also very low.” higher rate of pregnancy after myomectomy compared his audience that every patient is different, as is every However, he did give the CIRSE audience some good to embolization, and the rate of miscarriage seems to procedure; there may be technical differences in how news as well: “We know that you can expect spectacular be higher after embolization. But again, most cases are an embolization is conducted at different centres. There volume reduction both of fibroids and of the uterus, not treated in a randomised trial, and treated women are are some reports in the literature of complications which is good news for pregnancy. Embolization is a older or have more fertility-confounding factors when specifically associated with fertility after UAE. In the good alternative to myomectomy, which is the reference treated with embolization.” EMMY trial, the level of follicle-stimulating hormone treatment for pregnancy-seeking women.” These summations led him to conclude that, “Despite (FSH)—used as a measure of ovarian impact, with In addition, Pelage’s group reported encouraging the encouraging results of recent publications, we should higher values typically seen in patients with a diminished hormonal function following UAE, with no side effects still consider embolization with caution in pregnancy- ovarian reserve—was seen to increase after embolization. of embolization on the ovarian reserve. Some studies seeking women. In our centre, we always discuss as a However, this trend was more strongly observed in have reported high rates of pregnancy: 61% (14 of 23 group with the referring gynaecologist to decide whether women over 45 years of age. women) in a paper from Kavous Firouznia (Tehran we should offer embolization or myomectomy, and we Complications from UAE include non-target University of Medical Sciences, Tehran, Iran) and know that prospective randomised trials are very difficult embolization, mainly due to uterine-to-ovarian artery colleagues published in 2009, which also reported no to conduct in this group of women.”

gestational trophoblastic disease, and procedure. Of the four who underwent UAE preserves fertility two patients acquired malformations for a second procedure, the clinical success unknown reasons. rate was 75%, with one patient having The team used irregular uterine to have a third embolization. This third in patients with bleeding as the primary indication for UAE was a clinical success. embolization. Eight patients (27%) There was a significant correlation uterine arteriovenous needed a blood transfusion prior to between the clinical findings and the UAE, and 10 procedures of 34 (29%) diagnostic findings, as presented on malformations, single centre were emergency UAEs. CT-angio. Of the 34 procedures, 27 All patients underwent ultrasound were both clinically successful, and study shows and computed tomography (CT)- diagnostic imaging revealed a reduction angiography before and after the or absence of arteriovenous shunting Uterine artery embolization (UAE) preserved fertility in “at procedure. “Those were our main following UAE. In two cases, the least 75% of patients with acquired uterine arteriovenous diagnostic instruments,” Akinfiev interventionalists reported a clinical malformations,” according to a recent single centre study divulged. “Importantly, we performed success, but diagnostic imaging showed presented at the virtual 2020 Global Embolization and Cancer CT-angio from the diaphragm to the the presence of arteriovenous shunting Symposium Technologies (GEST) meeting (4–6 September, bottom of [the] pelvis.” post-procedurally. All five clinical online) by Dmitry Akinfiev (National Medical Research Center for Akinfiev told the GEST attendees failures showed arteriovenous shunting Obstetrics, Gynecology and Perinatology, Kulakov, Russia). that 10 of the 34 procedures were on CT-angio. “There were no patients expanded by embolizing additional with CT-angio success and clinical n our work, the clinical Uterine arteriovenous malformations arteries: branches of the internal iliacs, failure,” Akinfiev said. effectiveness of UAE in are rare, the GEST audience were told. ovarian arteries, and superior mesenteric Next, he turned to reproductive “Iacquired uterine arteriovenous “Speaking of risk factors for acquired artery branches. Twenty-seven (80%) outcomes. Of the 29 patients included in malformations is 86.2%,” he shared. uterine arteriovenous malformations,” of the procedures were performed via the study, 12 (41%) desired pregnancy, Akinfiev and his team conducted Akinfiev said, “in 80% of cases, the the radial approach, and embolizations and 17 (59%) did not. In the desiring a retrospective, single centre study malformation was associated with were performed with gelfoam and pregnancy subgroup, nine (75%) women involving 29 patients, with a mean curettage [19 patients had curettage non-spherical polyvinyl acetate (PVA) did become pregnant, and all nine have age of 29.1 years—“rather low”, in following a miscarriage; four patients particles under 500µm. “I prefer to use since given birth, “a rather encouraging the presenter’s words, with the oldest had a normal pregnancy and underwent gelfoam in cubes,” Akinfiev disclosed. result,” according to Akinfiev. patient included in the study being 43 curettage; one patient had a diagnostic The evaluation parameters for the “We had only one patient with a years old. “All [patients included in the curettage and no pregnancy]. Also, study were the elimination of abnormal comorbidity during pregnancy,” he study] were fertile,” Akinfiev informed we had one patient with arteriovenous uterine bleeding, and the absence or continued, “a patient with placental delegates. The study investigators malformation after vacuum aspiration significant reduction of arteriovenous presentation. Our obstetricians had to performed 34 UAE procedures, and the [following a normal pregnancy].” A shunting on CT-angio. perform a caesarean section in the 35th mean patient follow-up was 2.5 years further two patients developed uterine Of the 29 patients, 25 (86%) week of gestation due to threatening (range: one to six years). arteriovenous malformations due to experienced clinical success after one bleeding.”

30 Y-90 radioembolization November 2020 | Issue80

The application of radioembolization to liver transplant, or as a potentially Radioembolization with is evolving from its lobar therapy definitive curative-intent therapy for origins; radioembolization is increasingly early stage HCC. Median overall survival utilised in a segmental fashion to treat outcomes for Child-Pugh A patients with Y-90 now “a versatile earlier stage disease. The results of solitary HCC <5cm appear consistent the PREMIERE trial, a prospective, with those for other curative therapies treatment option” randomised trial for patients with (i.e., ablation, surgical resection, liver unresectable tumours not amenable transplant): 6.7 years from date of Y-90. to ablation, revealed significantly The evolution of radioembolization for HCC patients improved outcomes for segmental from a lobar therapy to a segmental radioembolization versus segmental therapy includes technical modifications TACE (time-to-progression >26 months beyond threshold dosimetry to of all stages vs. 6.8 months, respectively). These achieve complete pathologic necrosis. results have been corroborated by other Many of these techniques have been US sites, including the University of developed for TACE over the past Washington in Seattle, Mount Sinai several decades. The first concept is Hospital, New York, and the Mayo that of same-day radioembolization: the Clinic, Jacksonville. The true potential planning angiogram, macro-aggregated of segmental radioembolization, albumin (MAA) administration to Robert Lewandowski however, is in its ablative potential. determine lung shunt fraction (LSF), Radiology-pathology correlative studies and Y-90 administration can be have revealed that complete pathologic performed in a single session. This necrosis at explant is best obtained when is particularly appealing for patients Comment & Analysis the volumes of perfusion are targeted with early stage disease amenable with glass microsphere dosimetry >190 to radiation segmentectomy. Same- As presented at the Global Embolization Oncology Symposium Gray. A recent multicentre analysis has day radioembolization might further Technologies (GEST) 2020 meeting (4–6 September, virtual), Robert reset this threshold dose for segmental be streamlined by eliminating the Lewandowski discusses the evolution of radioembolization with radioembolization. In this analysis, requirement for the MAA administration Yttrium-90 (Y-90) over the past decade. Initially a lobar therapy, Y-90 all tumours treated with a segmental in patients with limited disease burden. can today be performed via a segmental delivery of microspheres radiation dose >400 Gray achieved Recent data support this concept by to hepatocellular carcinoma (HCC) patients at earlier stages in complete pathologic necrosis at explant. confirming low LSF for those HCC their disease, and multiple tumours can be targeted in a same- High tumour response rates on imaging, patients within Milan criteria. The day session. Furthermore, Lewandowski recounts how threshold long time to tumour progression, and second concept is that of performing dosimetry is now allowing for curative-intent therapy, and explains meaningful complete pathologic response radioembolization to extra-hepatic that the most recent data suggest this personalised dosimetry rates have made radiation segmentectomy tumour perfusing branches. There approach can be applied to a more advanced HCC population. a versatile therapy, allowing for is no established optimal embolic downstaging to liver transplant, bridging device to treat tumours via parasitised he historical role of extra-hepatic arteries; there are now radioembolization with Y-90 published reports describing the Tfor patients with HCC is in the delivery of Y-90 via the inferior phrenic salvage setting; it has been employed to arteries, the adrenal artery, and the treat patients considered poor candidates cystic artery. The final concept is that for trans-arterial chemoembolization of segmental administration of Y-90 (TACE) or those that failed TACE. In to multi-focal disease. With segmental contradistinction to the selective approach radioembolization, multi-focal disease of TACE, radioembolization has been can be targeted in a single session through performed in a lobar (or sequential separate selective arterial catheterisations lobar) fashion. Despite these differences and dose vial administrations. in patient selection and technique, Early stage Advanced stage In conclusion, radioembolization evidence has supported the application with Y-90 has evolved over the past 10 of radioembolization over TACE in curative downstaging tumour years, morphing from a lobar therapy intermediate staged HCC patients because for patients with HCC advanced beyond of improved quality of life metrics and being amenable to TACE into a versatile longer time to progression. The median treatment option for patients across the overall survival (OS) for patients with Barcelona Clinic Liver Cancer staging intermediate-stage HCC treated with Y-90 paradigm. This evolution has allowed is 25 months. for radioembolization to be performed A serendipitous observation following in a similar fashion to TACE: segmental/ uni-lobar radioembolization was the selective delivery of Y-90 microspheres development of an atrophy-hypertrophy Radioembolization to HCC patients at earlier stages in their complex; the treated hepatic lobe and disease, targeting multiple tumours as targeted tumour decrease in size, with well as extra-hepatic tumour-perfusing resultant hypertrophy in the contralateral branches, often in a same-day session. lobe. For patients who would be Most importantly, threshold dosimetry is candidates for surgical resection but now allowing for curative-intent therapy, present with an inadequate future liver Radioembolization with Y-90 has supported by explant data. This concept remnant (FLR), radiation lobectomy of threshold, or personalised, dosimetry was developed as a new paradigm to evolved over the past 10 years, has more recently been expanded facilitate hepatic resection. With standard morphing from a lobar therapy for and applied to the advanced HCC dosimetry, FLR hypertrophy is a time- population (DOSISPHERE-01 TRIAL), dependent process with approximately patients with HCC advanced beyond accepted for publication in the Lancet 10% hypertrophy from baseline at being amenable to TACE into a versatile Gastroenterology & Hepatology. one-month post Y-90, and 45% by nine-months post Y-90. More recently, treatment option for patients across Robert J Lewandowski is a professor of modified radiation lobectomy techniques Radiology, Medicine, and Surgery, and have been developed to increase the the Barcelona Clinic Liver Cancer the director of Interventional Oncology rate of hypertrophy and to deliver more staging paradigm.” at the Northwestern University Feinberg effective cancer therapy. School of Medicine, Chicago, USA.

32 Irreversible electroporation November 2020 | Issue80

activities). Two weeks after IRE, there was a significant CROSSFIRE trial: 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 IRE induces a more immune- 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 permissive environment in significantly upregulated at two weeks after SABR, in both CD4 and CD8 T cells, but was only significantly pancreatic cancer patients, upregulated on the CD8 T cells two weeks after IRE ablation,” Geboers shared. A linear regression model demonstrated that an correlated with improved survival increase in programmed cell death protein 1 (PD1), on both CD4 and CD8 T cells two weeks after IRE, was Irreversible electroporation (IRE) significantly induces a window of reduced immune significantly associated with improved overall survival. suppression two weeks post treatment, allowing the activation of effector T cells that No significant correlation was seen between PD1 seem to be correlated with improved survival, according to preliminary flow cytometry upregulation and overall survival in the SABR group. results of the CROSSFIRE trial. Speaking during the 2020 meeting of the Cardiovascular “We found a significant downregulation of regulatory and Interventional Radiological Society of Europe (CIRSE; 12–15 September, virtual), T cells two weeks after IRE that was simultaneous Bart Geboers (Amsterdam UMC, Amsterdam, The Netherlands) described how his team with a PD1 upregulation on CD4 T cells,” Geboers investigated the immune modulatory effects of IRE and MR-guided stereotactic ablative summarised. “The fact that the expression of the body radiotherapy (SABR) in patients with locally advanced pancreatic cancer. other checkpoints remained low argues against T cell exhaustion, but rather indicates that we are looking at a ancreatic cancer is one of the most aggressive Tumour microenvironment real effector T cell activation that might be amenable for cancers, Geboers informed the CIRSE audience, temporarily shifts to become more PD1 blockade with checkpoint inhibitory drugs.” Pwith a five-year overall survival of less than immunopermissive two weeks after IRE The CIRSE audience were left with this promising 10%. Thirty percent of all patients present with locally In order to assess the immune response, Geboers and take-home message: transient PD1 T cell upregulation advanced disease, and are not amenable for surgical colleagues took a venous blood sample from each combined with simultaneous regulatory T cell decrease resection. The median overall survival for patients with patient before IRE or SABR, two weeks after treatment after IRE is consistent with previously described locally advanced pancreatic cancer is approximately (to evaluate the immediate response), and three months systemic immune stimulatory effects of IRE, and 12–14 months. “The problem with pancreatic cancer is supports combination with pharmacologic PD1 that it is barely immunogenic, and the tumour cells can checkpoint inhibition. escape the immune system,” Geboers explained. “This The problem “These findings warrant further studies, for which might explain the disease’s aggressiveness.” we designed the PANFIRE III trial,” Geboers told Describing the pathophysiology of the cancer, he said with pancreatic delegates. the low immunogenicity is “probably two-fold”: the cancer is that it is barely This will be a Phase I trial in which 18 patients with cancer suppresses the tumour microenvironment, and is oligometastatic pancreatic cancer will be included. The associated with a lack of spontaneous apoptosis. immunogenic, and the study has three arms: the first six patients will be treated In terms of suppressing its microenvironment, the tumour cells can escape with Nivolumab (a PD1 blockade; this is the control); tumour releases suppressive cytokines that induce the second six patients will be treated with IRE ablation activation and proliferation of specific T cell subsets the immune system. This of the primary tumour followed by Nivolumab; the final that are immunosuppressive—regulatory T cells (Tregs) six patients will be treated with TLR-9 ligand intra- and myeloid-derived suppressor cells (MDSC). In turn, might explain the disease’s tumoural injection, followed by incomplete IRE ablation these reduce the activation and proliferation of effector aggressiveness.” of the primary tumour T cells, including Helper T cells (CD4) and cytotoxic T and Nivolumab. 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.

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 Bart Geboers presenting at CIRSE 2020 reduction in T cell tolerance, and allow the development Ablation results in of effector T cells,” he explained. In addition, ablation post-treatment (to evaluate the durable immune induces apoptosis and necrosis, meaning there will be response). Flow cytometry analysis was used to detect a reduction in the a release of immunogenic epitopes that can be taken up the type, frequency, and activation status of circulating tumour mass, and so a by antigen-presenting cells. Furthermore, “IRE has the immune cells. advancement of being vessel-sparing,” Geboers said, so A T cell analysis of 36 patients (19 treated with IRE, reduction in suppressive antigen-presenting cells can transport epitopic antibodies 17 with SABR) revealed that, two weeks after IRE, cytokines. This will lead to lymph nodes, where an adaptive immune response there was a significant downregulation of the regulatory can occur. T cells in the peripheral blood flow, as predicted by to a reduction in T cell To test this thinking, the investigators conducted an Geboers and colleagues. This downregulation returned tolerance, and allow the immunological side study of the CROSSFIRE trial, to baseline three months after IRE. There was a trend where pancreatic cancer patients were prospectively for down regulation of the regulatory T cells three development of effector enrolled between January 2016 and February 2020. months after SABR, though this was not significant. Patients with locally-advanced pancreatic cancer The investigators next looked at checkpoint T cells [stimulating an were pre-treated with FOLFIRINOX, before being expression of CD4 and CD8 T cells (the effector or immune response].” randomised between IRE or SABR. helper T cells that were suppressed by the tumour’s Issue80 | November 2020 Immuno-oncology and IR 33

study.1,2 This showed disease stabilisation particularly effective after failed Combination of immuno- in the bulk of patients with advanced checkpoint inhibition, supporting an and heavily pre-treated HCC via this aggressive re-treatment approach, when oncology and liver-directed combination approach, often with progression is confined to established intentional subtotal treatment of the tumours (rather than new breakthrough therapy: Where do we stand? target tumours. This study also has metastases).5 Like ablation, drug-eluting strong blood and tissue evidence for bead TACE (DEB-TACE) and Y-90 an immune mechanism when looking radioembolization reduce regulatory T at responders versus non-responders. cells (good) and expand T cell responses For cholangiocarcinoma, a similar in HCC. Doxorubicin potentiates approach with subtotal ablation can be immunogenic cell death and enhances taken.3 Human tissue and survival data cross-priming, but ischaemia cascades Brad Wood convince more medical oncologists at a turn on damage/pathogen-associated multidisciplinary tumour board meeting molecular patterns (DAMPS/PAMPS), than curing mice in 1,000 lab studies. In HIF1a, and cell stress pathways. IRE this setting, the local or regional therapy may leave vessel highways intact for Comment & Analysis is meant to boost the immune system, APC and T cell trafficking, which deposit antigens, promote APC and T cell may explain why IRE (shock) may be Ushering in “the era of IO”, Brad Wood calls for interventional maturation, broaden the T cell receptor better for immunomodulation than RFA oncologists to learn the language of immuno-oncology—“the other response, and tip the balance of immune- (heat) or cryoablation (freeze) for T cell IO”—in order to improve care for cancer patients. Discussing the regulation away from immune tolerance activation. Histotripsy may be better than “speculative but huge potential impact” of combining interventional and towards tumour-specific T cell heat when combined with checkpoint radiology (IR) approaches with an understanding of immuno- activation. More recently, Bevacizumab inhibition.6 Both IRE and cryoablation oncology, Wood informs readers that this is not merely an exciting plus Atezolizumab was approved by the release more proteins than heat. Yet opportunity to increase the scope of interventional oncologists’ US Food and Drug Administration (FDA) RFA heat may have a favourable impact work, but a necessary step in ensuring the discipline stays at the for locally-advanced HCC,4 and ongoing upon immunosuppressive T-regs than vanguard of oncologic treatment. clinical trials will hopefully address cryoablation. Cryoablation may have whether and when local ablation or the most inflammation and cell stress IT HAS BEEN KNOWN FOR signals. Any ablation might recruit more decades that local-regional therapies good macrophages than bad, when the like ablation and embolization can margin interacts with the tumour (thus stimulate a tumour-specific systemic leaving tumour behind). Yet, colorectal immune response, or even, on some metastases may explode when partially occasions, tumour regression remote RFA, MWA, Laser, HIFU treated and exposed to the hypoxia of from the treated area. What is not known partial treatment. is who, what, where, when, and how to EMBO Clearly, we need to biopsy more after make it happen more often. Enter the DEB-TACE IO therapies. We need to learn more era of IO, which to most people means HOT about the tools to measure immune immuno-oncology, and not interventional Y90 effects (such as immunohistochemistry, oncology. Bridging the gap (between Cryo-thermal flow cytometry, and sequencing). It is a IO and the other IO) requires learning ablation great time to have a coffee with an expert the language and themes of cancer HIFU from another discipline! immunology. Interventional radiology So when you freeze, fry, shake, (IR) has several hammers to pull out of ELECTRO- shock, zap, or choke the tumour—treat our big IO toolbox. However, we need the patient, not the picture. Do not be a to determine whether to freeze, fry, MECHANCIAL technical robot and just treat geometric shake, shock, zap, or choke a tumour— COLD spots in the liver. Think before ablating. that is, whether to use cryoablation, IRE, Cavitation, Create the proper tumour micro- radiofrequency ablation (RFA), Cryoablation Boiling Histrotripsy environment via timing, sequence, microwave ablation (MWA), irreversible and delivery of rational IO plus IO electroporation (IRE), high-intensity US Nano-cups immunomodulation. This is a one-time focused ultrasound (HIFU), histotripsy, opportunity, with speculative but huge transarterial chemoembolization [TACE], potential impact. New immuno-oncology or Yttrium-90 (Y-90) radioembolization. trials with checkpoint inhibitor drug We also need to determine which combinations have exploded in the past histology to treat, at what stage, two years.7 Where is IR? We need to be at alongside what IO drug, and in what Although revolutionary and Nobel the table and not on the menu. sequence. Where in the cancer immunity prize-worthy, checkpoint inhibitors cycle do the IO tools immuno-modulate? Brad Wood is an interventional How do we balance pro-immune versus usually fail as monotherapy, are costly, oncologist at the National Institutes of pro-metastatic pathways? The window of and are not without side effects. Health (NIH) Center for Interventional opportunity remains open for answering Oncology, Bethesda, USA. the many questions in a rational way. Enter IR/IO.” References: Checkpoint inhibition takes the brakes 1. Presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, 2015 off our natural immune response to Duffy AG et al. Tremelimumab in combination with ablation tumours. Although revolutionary and trafficking, and, 4) reduction of immune embolization add value. The therapeutic in patients with advanced hepatocellular carcinoma. Journal of Hepatology. 2017 Mar;66(3):545–551. Nobel prize-worthy, checkpoint inhibitors tolerance and immune resistance. The options are evolving fast, so IR needs to 2. Changqing Xie et al. Tremelimumab in combination with usually fail as monotherapy, are costly, molecular tumour micro-environment organise a clinical trial infrastructure so microwave ablation in patients with refractory biliary tract cancer. Hepatology. 2019 May;69(5):2048–2060. and are not without side effects. Enter and the dynamic immune compartments we can ask hypothesis-driven questions 3. Richard Finn et al. Atezolizumab plus Bevacizumab IR/IO. Local IO therapies alongside (blood vessels, lymph nodes, target in unresectable hepatocellular carcinoma. New England in a standardised fashion. Team science Journal of Medicine. 2020 May; 382:1894–1905. checkpoint inhibition can convert an tumours, and remote tumours) also merit wins. 4. Nicholas Klemen et al. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable “immune-cold” tumour into an “immune- consideration. Emerging data support aggressive progression-free survival after local therapy for metastatic hot” tumour, potentially turning local Initial clinical experience with local-regional therapies when melanoma. Journal of Immunotherapy of Cancer. 2019 July;7:196. into systemic. Immunomodulatory checkpoint inhibition drugs plus immunotherapy fails locally in 5. Eranki A, et al: High-Intensity Focused Ultrasound mechanisms boil down to enhancement ablation or embolization for advanced established tumours (versus new (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy. Clinical of: 1) antigen release and presentation, 2) hepatocellular carcinoma (HCC) was widespread metastases). Specifically, Cancer Research 2020 Mar 1;26(5):1152-1161. antigen-presenting cell (APC) maturation, first reported over five years ago in 6. Greten TF, et al: Combined locoregional- when stratified by patterns of failure, immunotherapy for liver cancer. Journal of Hepatology 3) T cell priming proliferation and a National Institute of Health (NIH) local therapy has been shown to be 2019 May;70(5):999-1007.

Issue80 | November 2020 Interventional oncology 35

De Baere and other interested interventionalists hoping for confirmation of abscopal effects from local intra- Cancer treatment beyond systemic tumoural injection are eagerly awaiting the results of ILLUMINATE 301, a randomised, phase III study of chemotherapy: Local intra-tumoural tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced injections demonstrate abscopal effect melanoma following progression on or after anti-PD-1 therapy. Tilsotolimod is a toll-like receptor agonist with Preclinical and clinical studies show that local, intra-tumoural injection of potent immunostimulating activity, as described in the immunomodulatory agents can result in the shrinking of tumours distant from the site of literature. inoculation. Furthermore, when chemotherapy drugs are used as the immunomodulator, In a presentation given by Adi Diab (The University it may circumnavigate the need for systemic chemotherapy delivery. These are the of Texas MD Anderson Cancer Center, Houston, conclusions presented by Thierry de Baere (Institut Gustave Roussy Université Paris- USA) at the European Society of Molecular Oncology Saclay, Villejuif, France) at the 2020 Symposium on Clinical Interventional Oncology (CIO; (ESMO) annual meeting back in October 2018, the every Tuesday in October, online). “Because this is a new field, there are a lot of open intra-tumoural injection of tilsotolimod combined questions,” he said. “What is the best target, how should I access the target, is it safe, with ipilimumab resulted in a decrease in the size of is it the correct organ, how should I deliver [the drugs], what dose, which regimen, can I an off-target melanoma tumour—one that was not monitor the delivery of the drugs?” injected with any drugs. Committing this finding to the collective medical memory, Diab and colleagues his is a very new, exciting field, and there Many different compounds can be used as describe in Annals of Oncology how, in the phase I/II is a space for interventional radiologists,” immunostimulatory agents, and can be used at different ILLUMINATE 301 study, intratumoural tilsotolimod “The told viewers. Showing a graph depicting stages of tumour immunity. De Baere expanded: “We with ipilimumab was “well-tolerated, demonstrating the number of new intratumoural immunotherapy trials use products that will release tumour antigens—could be durable responses (including complete response >21 conducted each year since 1992, de Baere demonstrated peptides, could be viruses. We want to activate antigen months), dendritic cell activation, type I interferon the rapid growth of research in this space: from a low of presentation, we want to stimulate cytotoxic cells on response, CD8+ T-cell proliferation in responders, and one trial in 1992, to a high of 40 trials in 2016. site, and we want to deplete or block regulatory T cells an abscopal effect”. At the time of writing, phase III When injecting immunostimulatory agents into [Tregs].” results from ILLUMINATE 301 are anticipated in the the tumour, interventionalists hope to achieve local After detailing the procedural details of intra-tumoural first fiscal quarter of 2021. priming, de Baere explained. “We want to trigger a injection, which involve many technical decisions, Offering a personal example, de Baere showed the tumour-specific immune response, but we also hope that de Baere stated: “Of course we should be part of this CIO audience a case performed at his own institution. this [local] response will result in distant effects,” he journey, because I think nobody can deliver better local The patient had a single injection of ipilimumab into continued. The idea underpinning human intra-tumoural treatment than interventional radiologists.” a liver metastasis, as well as systemic treatment with injections in cancer care is that these “distant effects”— nivolumab. “You can see we had an overall response known as abscopal effects—will confer systematic anti- A systemic response from a local from all of the tumours, despite [the fact that] only one tumour immunity at non-injected tumour sites. treatment tumour was injected.

task requiring many interventional (range: zero to 23). Sclerotherapy was Lipiodol offers an effective techniques,” he shared. performed either with 3–5ml ethanol, In the present study, Offensperger or with a glue/ Lipiodol 1:5 mixture therapeutic option for and colleagues conducted a prospective (6–8ml) under fluoroscopy or computed analysis of their institutional digital tomography (CT) guidance. melanoma patients suffering databases for melanoma patients. They The clinical success rate was higher compared patients who had been treated in patients treated with lymphatic with lymphatic angiography alone angiography and sclerotherapy, 100% postoperative complications with those who had been treated with compared with 78%. However, the lymphatic angiography combined with interval between intervention and cure from radical lymphadenectomy sclerotherapy. was slightly shorter in the cohort treated Between October 2014 and June 2019, with lymphatic angiography alone: 23 Lymphatic fistulae and/or lymphoceles in the groin following 13 patients met the inclusion criteria: days (range: four to seven) versus 29 radical lymphadenectomy are frequent, and therapeutic options are nine in the lymphatic angiography days (range: 24–33). While there were no needed to avoid severe restrictions for oncologic patients waiting alone group, and four in the combined minor procedure-related complications for adjuvant medical therapies. This is the key message Florian lymphatic angiography and sclerotherapy in the group of patients treated with Offensperger (General and Interventional Radiology, Stuttgart group. Mean patient age was 66.4 lymphatic angiography alone, there was Clinics, Stuttgart, Germany) wants audience members to take home years (range: 46.8–83.4 years), and one in the combined cohort (representing from the 2020 virtual Global Embolization and Cancer Symposium the interval between radical inguinal 25% of the patients treated in this arm Technologies (GEST) meeting (4–6 September, online). lymphadenectomy and lymphatic of the study), a local infection cured by angiography was 17.8 days (range: seven antibiotic treatment. There were no major “IT IS IMPORTANT TO SAY THAT patients with postoperative complications to 34). The technical success rate for procedure-related complications in the there are treatment options,” he told from radical inguinal lymphadenectomy lymphatic angiography was 93%. The study. attendees of the live event on Friday is pedal Lipiodol lymphangiography amount of Lipiodol used to perform the These results led Offensperger to 4 September, “because we often have combined with second-line interventions. procedure was 15.4ml (range: 6–22ml), conclude that “Lymphatic angiography, excellent patients who have been told that “In our opinion,” Offensperger says, this and in the combined group sclerotherapy with or without sclerotherapy, is an there is no other option but to wait.” is “the best treatment for these patients”. was applied after an interval of 10 days essential tool to cure therapy-refractory Stuttgart Clinics, where He informs the GEST audience that lymphatic fistulae after radical inguinal Offensperger works, is one of the the technical success rate of conventional Personally, lymphadenectomy in patients with largest surgical centres in Germany. lymphangiography is 75–100%, and malignant melanoma. Discussing postoperative lymphatic the cure rate of postoperative lymphatic I really like “Lymphatic angiography in complications following radical inguinal leakage for pedal conventional this intervention, combination with sclerotherapy seems lymphadenectomy in patients with lymphangiography is 51–70% (time to to result in higher clinical success malignant melanoma, Offensperger says: cure, two to 29 days). “Conventional because it is a rates,” he continued, “but also in higher “Where wood is chopped, splinters must lymphangiography is safe, feasible, complication rates when compared with fall”. However, his talk offers hope for and effective in the management of delicate task lymphatic angiography alone.” However, how best to deal with these splinters—a postoperative lymphatic leakage,” he requiring many he stressed that he wanted to leave GEST complication need not spell disaster for concludes, showing a pre-recorded video attendees with the understanding that a patient. of the procedure to illustrate how it works interventional lymphatic angiography in combination The basic lymphatic intervention to his audience. “Personally, I really like techniques.” with sclerotherapy is a safe and effective performed at the Stuttgart Clinics for this intervention, because it is a delicate option.

THE MOST TRUSTED DIALYSIS ACCESS TOOLS

Every day you take on the challenge of managing dialysis access patients. We understand and proudly offer the most comprehensive portfolio of innovative devices – devices that are not just proven to work, but also chosen most often to help patients like yours.

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Please consult product labels and instructions for use for indications, contraindications, hazards, warnings and precautions. © 2019 BD. BD, the BD logo, Bard, Conquest, Covera, GlidePath, Lutonix, and WavelinQ are trademarks of Becton, Dickinson and Company or its affiliates.Illustrations by Mike Austin. All rights reserved. BD Switzerland Sarl | Terre-Bonne Park - A4 Route de Crassier 17 1262 Eysins - Switzerland. Bard Peripheral Vascular, Inc. | www.bardpv.com | 1 800 321 4254 | 1625 W. 3rd Street Tempe, AZ 85281 0820/6047 Issue80 | November 2020 Hepatic ablation 37

if you were able to surgically debulk were really just to provide a good option disease in the liver for certain cancers for locally controlling liver tumours. I do “A whole new (such as colorectal cancer), then you not think that the first time an ablation could improve survival. The same data was done, there was ever any belief that is now being applied to IR, where, if you we would treat widespread, systemic world for IR”: can debulk as much of the tumour in the disease with a single probe. So it is liver, then you can potentially improve very exciting now to learn that certain overall survival. tools we now have, such as irreversible How ablation is electroporation (IRE) and cryoablation, What is the evidence for can potentially incite systemic effects. ablation in the treatment of There are now a lot of trials going transforming liver metastases? on exploring the combination of I think the biggest trial out there that we immunotherapy drugs and ablation. are excited about is the COLLISION I think where ablation fits into this cancer care trial—this is a trial that will compare the whole paradigm is that, by destroying treatment of colorectal cancer metastases the tumour, you are able to release Speaking during a livestreamed session dedicated to state-of-the- with ablation versus surgery. The trial antigens; the release of these antigens, art liver therapy hosted by the Symposium on Clinical Interventional started in 2017, is expected to recruit 600 combined with immunotherapy drugs, THE MOST TRUSTED Oncology (CIO) in October, Raul Uppot (Massachusetts General or so patients, and has a planned end date could potentially affect overall systemic Hospital, Boston, USA) discussed the evolution of liver ablation, of 2022. The strength of this trial is that disease. I personally have had a few from the first procedure in November 1986—where the hepatic it is a multicentre, randomised controlled patients where treating a single tumour tumour was injected with alcohol—to the potential of this treatment trial that will try to answer the question: in the adrenal glands or the kidneys has DIALYSIS ACCESS TOOLS modality to offer systemic, curative cancer care, possibly even is ablation as good or better than surgical ultimately resulted in a decrease in size without inserting a single needle. Here, he shares his thoughts on resection, the current gold standard? of metastatic tumours in other parts of the past, present, and future of ablation with Interventional News. Given our historical data on the body. This was accidental—we call it an abscopal effect. I think this has happened enough times that people have Every day you take on the challenge of managing dialysis realised there is a way to study this, there is a way to learn how this could access patients. We understand and proudly offer the most potentially be occurring, and control it, comprehensive portfolio of innovative devices – devices and use immunotherapy drugs to help it, so it is exciting, because I think for that are not just proven to work, but also chosen most often the first time it is a whole new world for IR. The ability to put a needle into one to help patients like yours. 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 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 What are the benefits of How has the use of hepatic treat large tumours, multiple tumours, ablation of the liver, and are ablation changed over time? It is exciting and yet the patient goes home as an there any downsides? The first hepatic ablation involved the outpatient with just a band-aid. The The beauty of ablation is that, in a very insertion of a small needle into a tumour that, using ability to do great oncological care and minimally invasive way, you can treat that was then injected with alcohol. a small probe, work with a small needle is exciting tumours. In the past, when we were People realised that alcohol could destroy about ablation. just doing biopsies, it was amazing to tissue, so thought ‘Why not kill tumours you can insert it The other thing I am very excited us that you could put a needle directly by injecting alcohol into them?’ Since into the liver and about is that, over time, there has been a into the target to sample it for diagnostic then, we have developed more advanced constant evolution in the technology [for purposes. Since the late 1980s, we equipment that can burn or freeze impact care.” ablation]. We started off with alcohol, * On the U.S. Market have moved towards being able to tumours. but we evolved to radiofrequency treat tumours in a similarly minimally The applications have evolved as ablation (RFA), cryoablation, microwave invasive fashion. The ability to use CT well. We initially treated primary ablation, especially for the treatment of ablation, and IRE. There is a constant or ultrasound to put a small needle into hepatocellular tumours, and, over many hepatocellular cancer, we know that we evolution in these technologies: we are something, to completely treat a tumour studies, we have shown that [ablation] can treat tumours with a good margin, so constantly moving towards smaller and that previously would have required is very successful at local control and the expectation is that, in much the same lighter probes that are more efficient surgery, pull the needle out, put a band improving overall survival in patients. way as surgery has improved survival in in what they can destroy. There are aid on, and send the patient home—that But we have also evolved into other terms of debulking metastases disease new technologies on the horizon, such is what is unique about ablation. tumours, such as treating metastatic to the liver, ablation could probably do as histotripsy, that allow one to treat a Ablation allows you to treat tumours in disease. I think an exciting part of the same thing, but with lower costs, tumour without inserting a needle. The a minimally invasively fashion, and we interventional radiology (IR) now is less hospitalisation time, and with an ability to use ultrasound waves to kill now have the data to show that the ability the ability to treat metastatic disease: equivalent survival to surgically treated tumour [cells] is what is coming down to do that has long-term impacts on our colorectal cancer, pancreatic cancer, patients. the pipeline. It is very exciting, the patients. As with any procedure that we breast cancer metastases to the liver. notion that a person could come in with a do, there are risks, the same you would Management of all of these tumours are What does the future of large liver tumour and one could treat it have with any procedure: bleeding, based on a background knowledge from ablation look like? in a very minimally invasive fashion and, Please consult product labels and instructions for use for indications, contraindications, hazards, warnings and precautions. infection, injury to adjacent organs. the surgical literature. For example, When ablation first started, our goals ultimately, improve the patient’s survival. © 2019 BD. BD, the BD logo, Bard, Conquest, Covera, GlidePath, Lutonix, and WavelinQ are trademarks of Becton, Dickinson and Company or its affiliates.Illustrations by Mike Austin. All rights reserved. BD Switzerland Sarl | Terre-Bonne Park - A4 Route de Crassier 17 1262 Eysins - Switzerland. Bard Peripheral Vascular, Inc. | www.bardpv.com | 1 800 321 4254 | 1625 W. 3rd Street Tempe, AZ 85281 0820/6047

Issue80 | November 2020 Neurovascular interventions 39

undergoing mechanical thrombectomy between June 2013 and August 2016 at a single, urban tertiary care New devices for endovascular medical centre. Catheter angiographic images were used to manually measure proximal segment arterial thrombectomy discussed at CIRSE diameters in a standardised fashion, and medical record review was used to obtain relevant independent and In a session of the 2020 Cardiovascular and Radiological Society of Europe (CIRSE) dependent variables. Internal carotid artery terminus meeting (12–15 September, virtual) focused on the hottest news in the endovascular diameters for men and women were 3.08mm and thrombectomy space, Antonin Krajina (University Hospital, Hradec Králové, Czech 2.81mm, respectively (p=0.01). M1 segment middle Republic) shared new devices available for the procedure, and enthused about their cerebral artery diameters for men and women were potential in stroke management. 2.47mm and 2.18mm, respectively (p<0.0001). Nearly half (48%) the patients in the upper middle cerebral irst describing his, hypothetical, ideal device for clot burden, and in middle cerebral artery occlusions. artery calibre tercile attained a favourable mRS 90- endovascular thrombectomy, Krajina said that Higher rates of favourable outcome at discharge and day value compared with 35% in each of the lower Fit should be “easy to use and have fast access to 90 days were observed for the short stent retriever and middle terciles (p=0.51). Larger middle cerebral the clot”. Stent retrievers are assessed by their ability to group (p<0.001). This led them to conclude, as Krajina artery diameters correlated with favourable discharge integrate the clot and to keep hold of it during retrieval; related to the CIRSE audience, that stent retriever length disposition (p=0.21). radiopacity of the stent retriever therefore plays an “should be adjusted to clot burden score and vessel This led Davison et al to conclude: “These results important role, Krajina stated. Additionally, he explained occlusion site.” Krajina clarified: “Stents for short provide limited evidence that males have larger cerebral how there is a significant association between first-pass occlusion are appropriate if they are 20mm long; for arterial diameters than females and that larger arterial complete reperfusion and favourable clinical outcome, longer occlusions, we need longer stent retrievers.” diameters may improve the odds for favourable clinical with two to three times higher odds for a favourable “What position of the stent-retriever in relation to the outcomes. If future studies validate these findings, clinical outcome compared with complete reperfusion occlusion/ embolus is the most effective?” Krajina asked arterial diameter may become a relevant variable in the after multiple passes. his viewers rhetorically. “If it [the stent-retriever] is too design of improved thrombectomy strategies.” Indeed, his key take-home message was that clot –proximal and/or only partially engaged into the clot, it However, Krajina went on to say that “More and integration is a function of delivery technique, duration is less probable that we can remove the whole clot,” he more studies are proving that stent-retrievers with larger of device implantation, and clot mechanics. His talk explained. “If the clot is more proximal to the stent- diameters do not appear to provide clear benefits”. therefore detailed how device design influences these A 2017 paper published in the American Journal of aspects of performance. In addition, he urged his Neuroradiology reported how, in their investigation of listeners to “use all tricks in the attempt to remove the the effects of different diameters of Solitaire retrievers clot at the first pass” (including aspiration via balloon on clinical outcomes, Dong Yang (Jinling Hospital, guide), and detailed how the COMPASS trial results Second Military Medical University, Nanjing, China) provide Level 1 data that an aspiration thrombectomy et al found “no evidence of a differential effect of as first-pass approach is non-inferior to a stent-retriever intra-arterial therapy based on the size of the stent- as a first-line approach for the treatment of selected retrievers”. Though they also found that, in patients patients with acute large vessel ischaemic stroke. with atherosclerotic disease, favourable reperfusion was associated with deployment of a small stent. The importance of device design Demonstrating new designs for stent retrievers that Comparing the Solitaire X device (Medtronic), the he believes are improving interventionalists’ ability CatchView stent retriever (Balt), and the Embotrap to successfully perform endovascular thrombectomy, III device (Cerenovus), Krajina showcased how each Krajina introduced the NeVa stent retriever from had platinum markers on the proximal and distal ends, Vesalio, which has clot pockets oriented at 90 degrees explaining that these acted as radiopacity markers. to each other that increase the first-pass effect. The Turning to the capacity to integrate the clot, he next Embotrap III device (Cerenovus) has an inner channel discussed the relative benefits of using a short (20mm) to stabilise the clot during retrieval, and an outer cage to or a long (30mm) stent retriever: “A longer [stent engage and integrate the clot. With this latest re-design, retriever] may increase the capacity to catch the clot,” the distal mesh of the Embotrap III device is also denser he said. This was proven by Gaurav Girdhar (Medtronic, than previous iterations. Irvine, USA) et al in their January 2020 publication in Interventional Neurology, which concluded that stent Use all tricks in the Access and delivery catheters and length had a significant effect on first pass success rate attempt to remove guidewires (p<0.05). The authors wrote: “Longer stent retrievers “Besides stent-retrievers, we also need delivery catheters may be safe and effective in improving first pass success the clot at the first pass.” and guidewires,” Krajina said. In his view, the most for fibrin-rich clotsin vitro and in vivo models of large important aspects to consider for these devices are vessel occlusion”. However, Krajina added that a longer navigability, pushability, kink resistance, and whether or stent retriever means higher friction, which in turn retriever, the probability that we remove it during first- not they can be assembled as a coaxial set. increases the probability of the device getting stuck pass is higher. To verify the relationship of the clot and A survey of Society of Neurointerventional Surgery and then elongating, resulting in a loss of apposition the stent-retriever position, we perform an angiogram (SNIS) neurointerventionalists that received 78 to the arterial wall. The embolisation risk of the clot is after stent-retriever deployment.” responses (approximately 10% of SNIS membership), also higher with longer devices, he explained, as longer Next, Krajina discussed how to decide what diameter published in the Journal of Neurointerventional dwell times affect the likelihood of distal embolization. stent-retriever device to use to increase the probability Surgery, indicated an increase in aggressiveness in “Stent retrieval length should be adjusted to clot of successfully removing the clot at first pass, 4mm or pursuing thrombectomy based on selection criteria. extent,” Krajina said, citing a June 2020 paper published 6mm. “If you look at a diameter of the M1 segment Nearly 40% of respondents (39.7%) reported using in Cerebrovascular Diseases from Hanna Styczen in males, it is about 2.5mm, and the diameter of the catheter aspiration thrombectomy as a frontline therapy. (University Hospital Essen, Essen, Germany) and internal carotid artery is around 3mm,” he informed A further 28.2% opted for stent-retriever mechanical colleagues. Styczen et al hypothesised that increased delegates. thrombectomy, and another 28.2% said they adopted stent retriever length may improve the rate of complete Writing in the Journal of Neurointerventional Surgery a combined approach, utilising stent-retrievers with angiographic reperfusion and decrease the respective in 2018, Mark Davison (Rush University Medical aspiration. number of attempts, resulting in a better clinical Center, Chicago, USA) and colleagues said: “Compared “Interventional neuroradiologists love to combine outcome. They conducted a retrospective analysis with males, females consistently fare worse following access catheters to create coaxial double, triple of 394 patients with large vessel occlusion in the mechanical thrombectomy for large vessel ischaemic systems,” Krajina told CIRSE registrants, “sometimes anterior and posterior circulation treated with stent strokes. Understanding why this gender disparity occurs in difficult or tortuous anatomy, referred to as a ‘tower retriever mechanical thrombectomy, sorting patients may guide improvements in future treatment strategies.” of power’, to have enough support for intracranial by propensity matching into two groups: those treated In their study, they aimed to determine whether gender catheters.” with a short (20mm) device, and those treated with a differences in cerebral arterial diameter correlated with To create such a set, the length and diameter of the long (30mm) device. They found that, in the anterior clinical outcomes following stroke thrombectomy. catheter used is important, the CIRSE audience heard: circulation, short stent retrievers had a significantly They therefore performed an observational study of 92 “Ideally one should use the shortest length necessary to higher rate of first-pass reperfusion in cases with low consecutive acute ischaemic stroke patients (42 women) do the job.”

Issue80 | November 2020 Market watch 41

“Patient screening and enrolment a Sirtex press release states. To date, have recently increased with five clinical the RESiN registry has yielded several sites now cleared to enrol subjects as publications, including oral and we pursue an atherectomy indication poster presentations at international Clinical News for Dabra,” said Will McGuire, Ra medical oncology and interventional Medical Systems CEO. “Earlier this radiology congresses, as well as a patients will be randomised in 2:1 year enrolment in this trial had stalled recent submission of, “Incidence fashion to receive either MagicTouch due to the COVID-19 pandemic, which and risk factors for sustained hepatic PTA or standard balloon angioplasty. also impacted our ability to activate new function toxicity six months after Y-90 Primary outcome will be primary clinical sites. We are pleased that nine radioembolization: Interim analysis of patency at six months, defined as duplex subjects have been enrolled in the past the radiation-emitting SIR-spheres in peak systolic velocity ratio (PSVR) of two months at our clinical study sites, non-resectable liver tumour (RESIN) 2.4 or less. all of which are operating via applicable registry.” The trial is designed to follow a COVID-19 protocols.” Sirtex and Vanderbilt will focus blinding protocol in order to minimise The open-label pivotal atherectomy efforts to expand the number of bias. Patients, care providers, clinical trial can enrol up to 100 patients publications arising from this data base investigators, and outcome assessors, with symptoms of PAD (Rutherford and topic areas of interest, such as an including vascular technologists Class 2–5) at up to 10 sites. Outcome assessment of different pre-treatment performing the duplex ultrasound, will measures include safety, acute technical planning dosimetry methods, orphan be blinded to the treatment allocations. success, and clinical success. The trial’s tumour outcomes, and specific cohorts The patients will be followed up for two primary efficacy endpoint is the mean of interest. Edward Choke and colleagues at years. reduction in percent diameter stenosis Sengkang General Hospital, Singapore in each patient’s primary lesion as First two patients enrolled PQ Bypass completes measured by angiography immediately in PRISTINE study with Enrolment initiated in world’s enrolment in DETOUR II following treatment with Dabra, before Selution SLR first RCT with sirolimus- pivotal study any adjunctive treatment. MedAlliance has announced enrolment coated balloon for below- PQ Bypass has announced enrolment The trial’s safety and clinical success of the first two patients in the PRISTINE the-knee PAD treatment of the final subject in the company’s endpoints are major adverse events at registry with Selution sustained limus Concept Medical has announced the DETOUR II investigational device 30 days and incidence of primary target release (SLR) 018 drug-eluting balloon enrolment of the first patient in the exemption (IDE) clinical trial. This lesion revascularisation at six months. (DEB) for the treatment of patients FUTURE BTK (Randomised controlled milestone occurs only a month after Dabra received US Food and Drug with below-the-knee disease. This is trial of first sirolimus coated balloon the Detour system entered the US Food Administration (FDA) 510(k) clearance the first DEB accepted by the US Food versus standard balloon angioplasty in and Drug Administration (FDA)’s in May 2017 for use in ablating a and Drug Administration (FDA) for its the treatment of below-the-knee artery breakthrough device programme. channel in occlusive peripheral vascular breakthrough programme. disease) trial. The index patient was DETOUR II is led by national co- disease. The PRISTINE registry is a follow successfully enrolled on 26 August 2020 principal investigators Sean Lyden up to the encouraging results seen in in Singapore. (Cleveland Clinic, Cleveland, USA) and the PRESTIGE clinical trial (below- FUTURE BTK is a randomised, Jihad Mustapha (Advanced Cardiac and the-knee, chronic limb threatening double-blind, placebo-controlled, Vascular Centers, Grand Rapids, USA). ischaemia [CLTI]) at six months. multicentere trial. It is aimed at Both receive compensation for their PRISTINE is a prospective registry determining the effectiveness of duties in this role. to investigate the safety and efficacy of MagicTouch PTA sirolimus-coated “The speed with which we were able treatment with Selution SLR sirolimus balloon versus standard balloon to enroll DETOUR2 in 2020 speaks to drug-coated balloon in TASC C and D angioplasty for the treatment of below the large patient population that exists athero-occlusive infrainguinal disease in the knee arterial disease in chronic limb- with long-segment femoropopliteal patients with CLTI from Singapore. threatening ischaemia (CLTI) patients. disease that has sub-optimal The objective of the registry is to Edward Choke (Sengkang General endovascular options,” says Lyden. evaluate over 12 months safety and Hospital, Singapore), principal “If percutaneous fem-pop bypass performance outcomes in 75 patients, investigator of FUTURE-BTK is shown to be safe and effective, with Selution SLR DEB in the treatment comments: “CLTI is a condition which similar to the outcomes demonstrated of infrainguinal occlusive lesions (TASC puts patients at an increased risk of in DETOUR1 study, it could be a game C and D) in patients with CLTI at limb amputation and death. Its burden changer for the way we treat complex, Dabra excimer laser system Singapore General Hospital. is likely to grow in the coming years long-segment SFA [superficial femoral The clinical primary safety endpoint given the rising trends in key risk factors artery] disease today,” continues Sirtex Medical completes of the registry is freedom from major such as age and diabetes. Effective Mustapha. enrollment of landmark US adverse events through 30 days and revascularisation is the cornerstone of DETOUR II is a prospective, RESiN registry the performance primary endpoint is treatment, but this is often hampered multicentre trial evaluating the Detour Sirtex Medical reports that enrollment freedom from clinically-driven target by high rates of restenosis and system for percutaneous femoral- in the US RESiN registry has reached lesion revascularisation (CD-TLR) reintervention after conventional balloon popliteal bypass in patients with a milestone of 1,650 patients and 12.8 within six months. The secondary angioplasty”. extremely long, complex lesions in the months of follow-up, allowing for a endpoints are primary patency at six He adds: “The novel MagicTouch SFA. The study enrolled 202 patients in satisfactory number of patients enrolled and 12 months follow-up, freedom from PTA sirolimus-coated balloon has 36 sites in the USA and Europe, and is for meaningful data analysis. CD-TLR at 12 months, clinical success emerged as one of the most promising assessing freedom from major adverse Under the leadership and direction at follow-up in Rutherford score by transcatheter technologies in preventing events (MAE) within 30 days of the of the trial’s executive committee, the one class or more, wound healing at restenosis for below-the-knee lesions. index procedure as the primary safety registry will close enrollment at the six months, and freedom from major The earlier data on the efficacy of endpoint. The primary effectiveness is 45 centres and will move to a new target limb amputation within six and 12 MagicTouch PTA from small studies primary patency at 12 months. phase of data review and evaluation, months post index procedure. are encouraging but these need to be publication, and presentation. The US “We are excited about the confirmed or refuted. I look forward Ra Medical Systems RESiN registry, a database of patients commencement of this large single- to the FUTURE BTK randomised announces 10 subjects eligible for treatment with SIR-Spheres centre prospective study focusing on controlled trial, which will test whether have been enrolled in its Y-90 resin microspheres (Sirtex), started patients with chronic limb threatening the MagicTouch PTA sirolimus-coated DABRA trial enrollment in 2015 and represents one ischemia receiving the novel sirolimus balloon can improve the patency Ra Medical Systems has announced of the largest prospective, multicentre, drug-eluting balloon”, says Chong of below-the-knee arteries in CLTI enrolment of the tenth subject in its observational studies conducted in the Tze Tec (Singapore General Hospital, patients, and this will hopefully bring pivotal clinical trial to evaluate the field of interventional oncology. Singapore). “We believe this registry us closer to our goal of reducing leg safety and effectiveness of the Dabra The registry should provide robust will give us detailed insight into the amputations”. excimer laser system as an atherectomy real-world evidence to characterise the efficacy and safety of this new balloon The trial will enrol 210 patients with device for the treatment of peripheral effectiveness, safety, and clinical impact technology which will benefit this Rutherford class 4 to 6 CLTI. These arterial disease (PAD). of SIR-Spheres Y-90 resin microspheres, challenging group of patients.”

Issue80 | November 2020 Market watch 43

corresponding authors affiliated with First patient enrolled in these institutions are eligible to publish FUTURE SFA study of their articles open access without being MagicTouch sirolimus- invoiced by Springer Nature. The coated balloon Industry News agreement includes more than 2,000 Concept Medical has announced the hybrid journals across the Springer enrolment of the first patient in the prioritise the need for a well-defined Nature portfolio (from January 2020) FUTURE SFA (Randomised controlled and accessible method to identify, and more than 500 fully OA journals trial of first sirolimus coated balloon report, and track CLI for the benefit of (from August 2020).” versus standard balloon angioplasty in patients who suffer from this disease. the Treatment of superficial femoral “We also look forward to continued Philips launches QuickClear artery and popliteal artery disease) study. partnership as we launch initiatives to mechanical thrombectomy The index patient was successfully educate our membership, our hospitals, system for blood clot enrolled on 12 September in Singapore. and healthcare provider staff regarding removal in latest portfolio FUTURE SFA is a randomised, these changes,” Lookstein explains. expansion double blind, placebo-controlled, “They have the potential to positively Royal Philips has announced the multicentre trial to determine the CDC recognises and codifies impact the care we provide to these launch of the QuickClear mechanical effectiveness of the MagicTouch critical limb-threatening extremely vulnerable patients across the thrombectomy system. The single- PTA sirolimus drug-coated balloon ischaemia in ICD-10-CM United States and around the world.” use system delivers an all-in-one (DCB) versus standard percutaneous A coalition organised by the CLI Global CLI and CLTI are advanced forms aspiration pump and catheter to transluminal angioplasty for the Society has announced its proposal of peripheral arterial disease (PAD), remove blood clots from the vessels treatment of superficial femoral and to distinctly recognise “critical limb a common circulation problem that of the peripheral arterial and venous popliteal arterial disease. ischaemia” (CLI) and “chronic limb- occurs when arteries that carry blood systems and has received US Food and Sirolimus-coated balloons are threatening ischaemia” (CLTI) in the throughout the body become narrowed Drug Administration (FDA) 510(k) considered to be the next new International Classification of Diseases, or blocked, restricting blood flow to clearance. generation of DCBs and the novel Tenth Revision, Clinical Modification legs and feet. Those who smoke, have The system’s design aims to MagicTouch PTA sirolimus-coated (ICD-10-CM) was approved by the diabetes or chronic kidney disease, simplify the use of the device balloon (SCB), has emerged Centers for Disease Control and or suffer from high blood pressure or and improve procedure times as one of the most promising Prevention (CDC) and went into effect high cholesterol are susceptible to CLI without the need for capital transcatheter technologies on 1 October 2020. and its complications. Left untreated, equipment or accessories. in preventing restenosis for The ICD-10-CM is a worldwide CLI can lead to tissue loss, gangrene, Chris Landon, senior vice diseased arteries. standard reference set of disease codes amputations, and eventually death. president and general The principal investigator used to report medical services provided “The statistics are grim,” says Jihad manager of image-guided QuickClear of FUTURE SFA is Edward to patients. The announcement marks a Mustapha, founding board member of therapy devices at Philips, Choke (Sengkang General major step forward in tracking patient the CLI Global Society. “We know 60% claims that “by taking away Hospital, Singapore), who treatments and outcomes for CLI and of patients who receive an amputation the high initial capital expenditure costs comments: “I am inspired by the CLTI, which affect millions of patients due to PAD or CLI die within two associated with traditional mechanical bold, imaginative, and futuristic globally. years—this is higher than the five-year thrombectomy systems, QuickClear concepts presented by the Nanolute The CLI Global Society worked in mortality rate for patients with breast, can help bring cost-effective solutions technology of the MagicTouch PTA close partnership with the vascular colon, and prostate cancer. to both the hospital and outpatient care sirolimus-coated balloon. In contrast specialist community to develop the “In order to fight this deadly disease, settings.” to other contemporary technologies, proposal. Coalition members include: we need to have accurate data. This The small footprint of the sterile MagicTouch PTA offers a solution „ Robert Lookstein, CLI Global seemingly small change to medical device allows it to be placed easily which optimises both the deliverability Society (CLIGS) coding will allow us to save countless on the table next to the patient. The and the absorption of sirolimus into the „ Barry T Katzen, (CLIGS) limbs—and lives.” company claims that the system can vessel wall.” „ Sean Roddy, Society for Vascular easily work at maximum aspiration He adds: “Initial experience with the Surgery (SVS) Authors from 750 German power within seconds and that the XTOSI first in man study suggested „ Mitchell Weinberg, Society for universities to publish in consistency of the aspiration power that MagicTouch PTA can provide an Vascular Medicine (SVM) CVIR Endovascular free during the procedure supports faster effective way of revascularisation for „ Bulent Arslan, Society of of charge procedure times. PAD patients, by keeping the vessels Interventional Radiology (SIR) As of August 2020, corresponding Furthermore, the system’s range of open longer and reducing the need „ Mehdi Shishehbohr, Society authors from more than 750 German catheters includes a large 10F aspiration of repeated angioplasty procedures. for Cardiac Angiography and universities and research institutions catheter which, according to the I look forward to the FUTURE SFA Intervention (SCAI) are able to publish in Cardiovascular company’s own in-house data, provides randomised controlled trial, which will The goal of this initiative is to support and Interventional Radiology (CVIR) 59% more aspiration volume than 8F test whether the Magic Touch PTA coding professionals, educators, Endovascular free of charge thanks to aspiration catheters. sirolimus-coated balloon can improve compliance staff, and physicians to a deal Springer Nature has signed with Bryan Fisher (The Surgical Clinic, the patencies of femoral and popliteal identify and accurately report CLI these German research institutions. Nashville, USA) says that the arteries in PAD patients. We hope to and CLTI in clinical documentation, An explanatory statement on the “QuickClear is a simple and easy to use establish whether SCB will emerge as electronic medical records, and medical Springer Nature website reads: “If you mechanical thrombectomy system.” He the new standard of care which will billing in order to track and monitor adds that it “is significantly smaller than impact the way we treat PAD.” patient treatments and outcomes in the other systems without compromising The trial will enrol 153 patients with future. aspiration power.” Rutherford class 3 to 6 PAD. These “This effort is a first step in building The QuickClear mechanical subjects will be randomised in 2:1 awareness of the complexity associated thrombectomy system is the latest fashion to receive either Magic Touch with caring for patients who suffer expansion of the company’s portfolio PTA or standard balloon angioplasty. from CLI within public and commercial after acquiring Intact Vascular. Primary outcome will be primary payers and the broader healthcare Springer Nature website Philips’ peripheral vascular patency at six months, defined as community,” says Barry Katzen, board portfolio already includes advanced duplex peak systolic velocity ratio chair of the CLI Global Society. “These are a corresponding author affiliated interventional imaging systems for (PSVR) of 2.4 or less. dedicated codes, now newly identified with a German university or research precision guidance; intravascular The trial is designed to follow a for CLI, are critical in our goal to institution, you are entitled to publish ultrasound (IVUS) catheters to assess rigorous blinding protocol in order to improve quality of life by preventing open access in our journals with the location of the disease and lesion minimise bias. Patients, care providers, amputations and death due to CLI.” fees covered by the German DEAL morphology and guide and confirm investigators and outcome assessors, Robert Lookstein, chair of the agreement. the treatment; peripheral atherectomy including vascular technologists Vascular Societies Workgroup and “More than 900 German institutions devices to remove blockages; and performing the duplex ultrasound, will CLI Global Society board member, are eligible to participate in the peripheral therapy devices, such as be blinded to the treatment allocations. acknowledges the collective effort of agreement between Springer Nature Philips’ Stellarex drug-coated balloon, The patients will be followed up for his colleagues, “who came together to and Projekt DEAL, meaning that to treat lesions. two years.

Issue80 | November 2020 Market watch 45

Teleflex announces deployment, the new lower profile expanded indications for the enables use of a smaller sheath, Arrow EZ-IO intraosseous potentially reducing the risk of damage vascular access system at the access site,” says Yevgeniy Product News Teleflex has announced it has received (Eugene) Rits (Wayne State University; 510(k) clearance from the US Food Detroit Medical Center; Harper Biotronik’s Passeo-35 Xeo improvement. and Drug Administration to expand University Hospital, Detroit, USA). PTA balloon catheter is now The Eluvia stent system was the indications for use of the Arrow “Combined with the trackability and available in Europe developed for the treatment of peripheral EZ-IO intraosseous vascular access flexibility I have always trusted with Biotronik has announced European arterial disease (PAD). The Eluvia system. This device can be used when Viabahn devices, this new lower profile market release of the Passeo 35 Xeo stent reopens the blocked artery and intravenous access is difficult or offering will become very instrumental percutaneous transluminal angioplasty restores blood flow, while also utilising impossible to obtain in emergent, urgent, in my dialysis access practice.” (PTA) balloon catheter. A company a drug-polymer combination to offer or medically necessary cases. press release states that, compared to a sustained, low-dose release of drug The Arrow EZ-IO system is now other available PTA balloons, the device to prevent tissue regrowth within the available with the expanded indication offers physicians improved crossability, stented artery. stating use of the device may be excellent trackability, and pushability in “The CMS determination is a very extended for up to 48 hours when a wide range of sizes. positive development for patients alternate intravenous access is not “The new Passeo-35 Xeo balloon with PAD and supports what we have available or reliably established in handled impressively well, crossing confirmed through our clinical trials— adults, and in paediatric patients 12 easily even in an occlusive lesion,” the Eluvia stent offers clinically superior years and older. comments Gerd Grözinger (University outcomes compared to other peripheral “Vascular access is one of the most Viabahn endoprosthesis Hospital Tübingen, Tübingen, drug-coated technology available to basic, yet critical, components of patient Germany), after performing the first- clinicians and their patients,” said Jeff care,” said Michelle Fox, corporate Currently, the Viabahn device is in-human procedure with the balloon. Mirviss, executive vice president and vice president and chief medical indicated for use in superficial femoral “The deflation time was also very fast president, Peripheral Interventions, officer, Teleflex. “The ability to use the artery (SFA) lesions, iliac lesions, compared to other balloons, which can Boston Scientific. EZ-IO system for a longer dwell time in-stent restenosis of SFA lesions, and save valuable procedure time.” provides clinicians the option to utilise in stenosis or thrombotic occlusion at To aid in challenging lesion crossing, intraosseous (IO) access for the entire the venous anastomosis of synthetic the Passeo-35 Xeo catheter offers a low duration of therapy in patients with arteriovenous access grafts for entry profile, smooth tip taper, and up difficult vascular access where therapy haemodialysis. to 19.5% more pushability compared is required for up to 48 hours.” to competitors, facilitating improved Philips launches latest catheter navigation in the peripheral Gore enhances Gore version of its Azurion vasculature. Catering to a full range of Viabahn endoprosthesis imaging platform lesion sizes, the device is available in portfolio with lower profile Royal Philips has announced the balloon diameters from 3–12mm and delivery next-generation of its Azurion image- lengths of up to 250mm, with usable Gore has announced the US launch of guided therapy platform, designed to catheter lengths of 90, 130 and 170cm. the lower profile, large diameter Gore improve the quality and efficiency of Additionally, the Passeo-35 Xeo catheter Viabahn endoprosthesis. interventional procedures. is fully 5F compatible for balloon sizes Gore previously received approval The platform now integrates control up to 7mm in diameter and 250mm in Eluvia drug-eluting stent from the US Food and Drug of imaging, physiology, haemodynamic length. Administration (FDA) for the enhanced and informatics applications, as well The Passeo-35 Xeo balloon is “The decision is particularly Gore Viabahn endoprosthesis. as intuitive control of the gantry, at indicated to dilate stenosis in the iliac, important given the level of “With broad clinical indications the tableside, allowing clinicians to femoral, popliteal and infrapopliteal consideration and evaluation related to for use and numerous product control all compatible applications arteries, and for the treatment of the role of paclitaxel in the peripheral improvements, the Viabahn device from a touch screen while performing obstructive lesions of native or synthetic vasculature, and we believe this continues to be a dependable choice procedures. This can eliminate the need arteriovenous dialysis fistulae. It is also designation reflects the unique attributes that demonstrates positive results in for clinicians to leave the sterile field recommended for post-dilatation of of the Eluvia stent, which are clearly patients with complex vascular disease,” and step into an adjacent control room, balloon-expandable and self-expanding differentiated and improve the quality of comments Amit J Dwivedi, (University as well as supporting faster and better stents in the peripheral vasculature. life for the millions of people suffering of Louisville, Louisville, USA), who informed decision making, a company Passeo-35 Xeo is the platform for from symptoms of PAD.” has implanted the lower profile device in press release states. Biotronik’s recently released Dynetic-35 The NTAP designation will support complex arterial anatomy. Philips is also introducing a new balloon-expandable cobalt chromium access to the Eluvia stent for Medicare “Older patients with co-morbidities 3D imaging solution called Smart-CT, stent system. beneficiaries in the hospital inpatient such as hypertension, diabetes, and where users are guided through image setting, making it possible for eligible obesity may benefit from a less invasive acquisition and can review and interact CMS grants additional hospitals to receive NTAP payment endoluminal approach versus surgical with the acquired CT-like 3D images reimbursement for the Eluvia in addition to the standard Medicare bypass. These latest enhancements, on the tableside touch screen module drug-eluting vascular stent severity diagnosis related group (MS- including a lower profile, provide using 3D visualisation and measurement system DRG) payment. physicians with additional options for tools. These tools have been designed to Boston Scientific announced that the The US Food and Drug treating these patients.” support procedures in a range of clinical US Centers for Medicare and Medicaid Administration (FDA) approval of This innovative Viabahn device domains, including neurology, oncology, Services (CMS) granted a new the Eluvia stent system in September design reduces the delivery profile for and cardiovascular procedures. technology add-on payment (NTAP) for 2018 was based on findings from the larger 9–13mm diameter stent grafts the Eluvia drug-eluting vascular stent IMPERIAL trial, which exhibited the by up to 3Fr, enabling delivery through Boston Scientific receives system as part of the 2021 inpatient highest 24-month primary patency smaller sheaths. FDA approval for the Ranger prospective payment system (IPPS). reported to date for the treatment of Smaller introducer sheaths have DCB The NTAP designation, awarded to femoropopliteal disease in a US pivotal resulted in a lower risk of vascular Boston Scientific announced it new medical devices determined to trial with a drug-coated balloon or drug- access complications in select patient has received US Food and Drug substantially improve the diagnosis or eluting stent. Trial data confirmed a populations, a Gore press release Administration (FDA) approval of the treatment of Medicare beneficiaries, statistically significant lower clinically- states. Additionally, new radiopaque Ranger drug-coated balloon (DCB), will be effective on 1 October 1 2020 driven target lesion revascularisation markers on the distal and proximal developed for the treatment of patients and will provide eligible hospitals with (TLR) rate of 12.7% for patients treated ends enhance visualisation under with peripheral arterial disease (PAD) in incremental reimbursement for the with the Eluvia stent, in contrast to fluoroscopy, facilitating positioning and the superficial femoral artery (SFA) and Eluvia stent system for up to three years. 20.1% observed within the Zilver PTX device delivery, as well as precise and proximal popliteal artery (PPA). The Medicare criteria for an NTAP drug-eluting peripheral stent cohort predictable placement. According to a press release, the designation is based on newness of the (p=0.0495), thus reducing the need for “In addition to the radiopaque Ranger DCB was designed with a low device, cost, and a substantial clinical repeat procedures at 24 months. markers that facilitate positioning and therapeutic drug dose and proprietary 46 Market watch November 2020 | Issue80

Ranger DCB and 66.3% for standard Medtronic Abre stent PTA (p=0.0017). Primary patency by receives US FDA approval Kaplan-Meier estimate was 89.8% for to treat venous outflow the Ranger DCB and 74% for PTA at obstruction Product News 12 months (p=0.0005). Medtronic has received US Food and „ “The Ranger DCB eases Drug Administration (FDA) approval for coating which efficiently transfers the 12-month freedom from major deliverability for a wide range of use of the Abre venous self-expanding drug into the tissue, resulting in high adverse events (MAE) was 94.1% for lesion complexities via a low profile stent system in the iliofemoral veins in primary patency rates and low systemic those treated with the Ranger DCB platform that is compatible with patients with symptomatic iliofemoral drug exposure for patients. vs. 83.5% for standard PTA (Pnon- smaller diameter guidewires and has venous outflow obstruction. “This approval allows us to bring inferiority <0.0001). shown consistent results in multiple The FDA approval is based on more treatment options with exceptional „ Additionally, patients who received randomised controlled trials,” said 12-month results from the ABRE outcomes and proven safety to US therapy with the Ranger DCB had Ravish Sachar, physician-in-chief clinical study, presented at the 2020 physicians and their patients who are a significantly lower target lesion for Heart and Vascular services Charing Cross Symposium, which facing this challenging disease,” said revascularisation rate—a component at UNC Rex Hospital (Raleigh, assessed the safety and efficacy of Jeff Mirviss, president, Peripheral of MAE—of 5.5% in contrast to USA) and principal investigator the investigational Abre stent in 200 Interventions, Boston Scientific. 16.5% observed with standard PTA of the RANGER II SFA trial. “For patients with iliofemoral venous outflow “Adding the Ranger DCB to our drug- (p=0.0011), substantially reducing a physicians seeking to limit systemic obstruction across the spectrum of deep eluting portfolio, which also includes patient’s need for repeat procedures. drug loss without compromising venous obstruction including those our Eluvia drug-eluting vascular stent „ The primary efficacy endpoint of outcomes, data demonstrate the with post thrombotic syndrome, non- system, reinforces our commitment to 12-month binary primary patency—a Ranger DCB is a safe and effective thrombotic iliac vein lesions (NIVL), providing differentiated technology with measure of the target vessel remaining treatment option.” and those who presented with an acute strong clinical evidence that supports unobstructed—was 82.9% for the The Ranger DCB also demonstrated deep vein thrombosis (aDVT). data-driven treatment decisions for nearly 90% primary patency in the The study also included a challenging millions of patients suffering from PAD investigator-sponsored COMPARE patient population: 44% (88/200) worldwide.” trial—the first head-to-head prospective, required stents that extended below The FDA approval is based on results randomised controlled trial to compare the inguinal ligament into the common from the RANGER II SFA pivotal two different DCBs. In the trial, the femoral vein (CFV). The study met trial, which evaluated the safety and Ranger DCB demonstrated a similar its primary safety endpoint with a 2% effectiveness of the Ranger DCB versus primary patency rate of 88.4% to (4/200) rate of major adverse events standard percutaneous transluminal that of the 89.4% observed with within 30 days. The study also met angioplasty (PTA) for the treatment of IN.PACT Admiral drug-coated balloon its 12-month primary effectiveness patients with PAD in the SFA and PPA. (Medtronic) by Kaplan-Meier estimate endpoint with an overall primary In the randomised controlled trial, both (p=0.81), with a significantly lower drug patency rate of 88% (162/184). No stent primary endpoints were met: dose density (2µg/mm2 paclitaxel vs. fractures and no stent migrations were „ The primary safety endpoint of Ranger drug-coated balloon 3.5µg/mm2 paclitaxel, respectively). reported in the study.

Calendar of events

November 2020– 25–29 January 2021 20–24 March 2021 9–11 May 2021 February 2021 Leipzig Interventional Course Society of Interventional International Symposium on Please be advised The CIRSE webinars: (LINC) Radiology (SIR) 2020 Endovascular Therapy (ISET) that the events listed Interventional Oncology 2.0 Leipzig, Germany Virtual Hollywood, USA opposite, because of COVID-19, are subject Virtual www.leipzig-interventional-course. www.sirmeeting.org www.iset.org to change. Please www.ecio.org com check the relevant website for further 19–22 April 2021 16–19 June 2021 details as the event 1–3 December 5–8 February 2021 Charing Cross (CX) European Conference on may be cancelled, British Society of Society of Interventional Vascular and Endovascular Embolotherapy (ET) postponed, or become a virtual event. Interventional Radiology Oncology (SIO) Annual Controversies Digital Edition Nice, France (BSIR) Annual Meeting 2020 Meeting Virtual www.cirse.org/events Virtual Virtual www.cxsymposium.org www.bsir.org/meetings www.sio-central.org

Mar Issue 19 73

Laura Findeiss: Profile Page 30 Interventional News is a trusted, independent source US FDA continues to Alex Barnacle: Paediatric IR investigate paclitaxel- Page 32 coated devices in the leg A meta-analysis published in the Journal of the American Heart Association (JAHA) late last year by Konstantinos Katsanos (Patras, Greece) and colleagues, suggesting Artificial of news and opinion in the interventional world. an increased risk of death at two and five years following the use of paclitaxel-coated balloons and stents in the femoropopliteal artery, has generated months of debate intelligence amongst the international interventionalist community. The conversation is still ongoing, with every key vascular conference of 2019 to date hosting discussion on the future of paclitaxel-coated and -eluting devices. Since then, prominent physicians have pointed will cause out flaws in Katsanos et al’s methodology, and patient-level data published after the JAHA meta-analysis by industry have revealed no increased mortality associated with the use of paclitaxel-releasing devices. medtronic and Cook Medical have also announced “paradigm shift” corrections to their published data. Meanwhile, the continued investigation by the US Food and Drug Administration (FDA) indicates that the story is not yet over. in IR practice

Clinicians are calling for increased collaboration between computer scientists, biomedical engineers and interventional oncologists as machine learning is posited to play a more prominent role in interventional radiology (IR) procedures, from informing the initial diagnosis, through to patient selection and intraprocedural guidance. In a Sign up for a free print subscription* recent primer published in The Journal Katsanos and colleagues’ report Panellists at the Vascular Leaders Forum of Vascular and Interventional Radiology an increased mortality signal with (JVIR), Brian Letzen, Clinton Wang and peaking from the floor of the Vascular Leaders Forum paclitaxel in the femoropopliteal Julius Chapiro, all of the Yale School of (VLF; 1–2 March, Washington DC, USA), hosted arteries Medicine, New Haven, USA, outline the by Vascular Interventional Advances (VIVA), FDA In the original JAHA paper, published 6 December 2018, clinical applications of machine learning S Katsanos et al conducted a systematic review and meta- for IRs, and visualise a future where investigator Donna Buckley, who has “reviewed most of analysis of 28 randomised controlled trials investigating these devices and recommended them to be approved”, artificial intelligence (AI) enables the paclitaxel-coated balloon angioplasty or paclitaxel-coated explained the regulatory body’s perspective: “Our first elevation of the discipline to become, metal stents in the femoral and/or popliteal arteries. In response to the meta-analysis was, I think, similar to in Chapiro’s words, “the epitome of all, 4,663 patients (89% intermittent claudication) were personalised medicine”. and e-newsletter subscription** everybody else’s: we were a little bit surprised. Nonetheless, analysed. The primary safety measure was all-cause outline their it was compelling information that we took very seriously.” patient death, analysed at different time points. “Risk The ongoing FDA evaluation is focusing primarily LETZEN AND COLLEAGUES ratios and risk differences were pooled with a random on US-based randomised controlled trials with data the vision of AI in IR: “By integrating machine learning effects model,” the authors wrote. into diagnosis, treatment, and management, AI can regulatory body can validate. The FDA’s preliminary Previous randomised controlled trials have evidenced evaluation confirmed the mortality signal reported by empower physicians to provide the highest-quality that paclitaxel-coated balloons and stents significantly Katsanos et al. Speaking at VLF, Buckley said the FDA’s personalised care in an efficient manner that meets reduce the rates of vessel restenosis and target lesion own analysis of five US pre-market approval (PMA) trials the demands of modern clinical practice. Whereas revascularisation after lower extremity interventions. medicine has traditionally focused on incremental has “converged to where we feel like it [the meta-analysis At one year, all-cause patient death (28 randomised findings] is not a statistical glitch—but we still have all hypothesis-based research, AI allows for a new controlled trials with 4,432 patients) was similar between this incongruous information as well with all the statistical paradigm where ‘big data’ can be rapidly analysed, 17 paclitaxel-coated devices and control arms (2.3% vs. analysis that we have gone through.” uncovering new insights that may otherwise have 2.3% crude risk of death). All-cause death at two years Also at VLF, Peter Schneider (Honolulu, USA) called required decades of prospective trials.” (12 randomised controlled trials with 2,316 patients) was the process that the FDA is undertaking to review the data The annual meeting of the Society of significantly increased in case of paclitaxel vs. control “judicious, straight-forward and spot on”. Interventional Radiology [SIR] this year features (7.2% [101 deaths in 1,397 patients] vs. 3.8% [35 deaths Indeed, the FDA issued a letter to healthcare providers its first machine learning in interventional in 919 patients] crude risk of death, number-needed-to- in January stating that it was evaluating the “recent oncology session, and the BOLD-AIR summit harm [NNH]: 29 patients [95% CI: 19–59]). Long-term information regarding the potential for increased long-term initiated by Stanford and NYU (24 April, New risk of all-cause death up to five years (three randomised mortality” following paclitaxel-coated balloon or paclitaxel- York, USA) will tackle regulatory and ethical controlled trials with 863 patients) increased further in Continued on page 4 eluting stent treatments in the femoropopliteal artery for issues pertaining to data use for AI research. case of paclitaxel (14.7% [78 deaths out in 529 patients] patients with peripheral arterial disease (PAD). The agency vs. 8.1% [27 deaths in 334 patients] crude risk of death, said that whilst the data review was ongoing, the FDA NNH: 14 patients [95% CI: 9–32]). Continued on page 2 recommends “continued surveillance” for patients treated Katsanos and colleagues wrote that meta-regression with paclitaxel. The regulatory body stated in the letter that it believes the “benefits continue to outweigh the risks” for www.interventionalnews.com approved devices within their indications.

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