Vascular News 90 – July 2021 US Edition by BIBA Publishing

July 2021 | Issue 90

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Peter Schneider New tools for CLTI

FORS: First use of new technology in the USA page 14

Vascular community rallies to reduce “devastating” lowerextremity amputations

“To stop, and indeed reverse, the increasing trend of amputation, actionable policies that will reduce the incidence of chronic limb-threatening ischaemia [CLTI] and enhance delivery of optimal care are needed”, a recent policy statement by the American Heart Association (AHA) begins. The Association has set a target to reduce non-traumatic lower-extremity amputations by 20% by 2030.

ark A Creager, director of the Heart and a “great unmet need worldwide” for quicker diagnosis Vascular Center at Dartmouth Hitchcock and treatment, he remarked. Medical Center (Lebanon, USA) and Writing in the April edition of Circulation, Creager colleagues, on behalf of the AHA Advocacy and colleagues propose a series of actions, focused on Coordinating Committee, describe non-traumatic lowerexpanding availability and accessibility, improving extremity amputation as a “devastating complication” public awareness of PAD, and the greater use of of peripheral arterial disease (PAD), noting a significant effective PAD management strategies. They also suggest impact on patients and society. ways in which regulatory and institutional policies can They recognise that, while amputation is an help to facilitate the AHA’s recommended changes. “important and potentially sole treatment option” for certain patients, it “often is preventable”, Healthcare disparities necessitate even among patients with advanced PAD. focus on “availability and The AHA believes there is “considerable accessibility” of care opportunity” to improve the care of patients with The authors cite poverty, racial disparities, and PAD and thereby reduce the risk of CLTI, foot geographic limitations as factors that can increase ulceration, and limb amputation. a person’s risk of amputation and therefore must be Creager and colleagues write that a number of considered in any policy recommendations. The AHA evidence-based diagnostic and therapeutic Creager and colleagues note a “complex” has set a target to reduce approaches can reduce amputation risk. association between poverty and prognosis non-traumatic lowerHowever, their implementation and adherence with PAD. They write that, among patients extremity amputations by are “suboptimal” for a variety of reasons. with severe PAD, such as CLTI, those with BY 2030 dual eligibility for Medicare and Medicaid had These include the underdiagnosis of PAD, lack of knowledge among patients and healthcare higher mortality and amputation risk compared professionals regarding PAD management, with those eligible only for Medicare, which is inadequate access to vascular or foot care specialists, “likely to reflect that people with dual eligibility have a and medical cost. high risk factor profile”. “Racial disparities in the USA are dramatic”, the authors Data highlight “concerning” trends in add. They note that, among Medicare beneficiaries with amputation levels diabetes and PAD, four-fold differences in amputation risk While several reports have shown a general decrease in are recognised between Black Americans and other racial amputations, Creager et al detail, recent data from the or ethnic groups. National Inpatient Sample paint a different picture. The Regarding geographical disparities, Creager and authors highlight “concerning” trends noted by Linda S colleagues relay that the Mountain region in the USA Geiss (Centers for Disease Control and Prevention, Atlanta, observed 5,550 amputations per 100,000 patients with USA) et al in a 2019 Diabetes Care report regarding PAD, compared to 8,400 in the East South Central region. patients with diabetes. Creager and colleagues identify a “Improving access to care through insurance expansions “recent resurgence” of amputation rates among this patient and increasing the availability and accessibility to group in Geiss and colleagues’ data: after a 43% decline interventions that reduce the risk of amputation would be between 2000 and 2009, the amputation rate increased by necessary components to affect amputation rates among 50% from 2009 to 2015. high-risk populations”, the authors propose. While the data mentioned in the AHA statement focus largely on the USA, recent dialogue at the Charing Increasing awareness of PAD is “critical” Cross (CX) 2021 Digital Edition (19–22 April, online) Another of the actions the AHA recommend is improving highlighted the global nature of the problem. In a public awareness of PAD. The authors stress that this is a roundtable discussion with the CLI Global Society, Barry “critical” element, as a current lack of awareness among Katzen (Miami Cardiac and Vascular Institute, Miami, clinicians and patients is hindering the diagnosis and USA) noted that, “in many parts of the world, the most management of the condition. common vascular procedure is an amputation”. There is Continued on page 4

20%

Profile: Ali AbuRahma page 20

Large study shows continued and quickening decline in AAA mortality According to a new, populationbased analysis, abdominal aortic aneurysm (AAA) mortality has continued to decline, and “at a faster rate than ever” in the second decade of the 21st century. Authors C Y Maximilian Png (Massachusetts General Hospital, Boston, USA), Edward Choke (Sengkang General Hospital, Singapore), and colleagues attribute this continued and accelerating decline to multiple factors, highlighting in particular the impact of sustained reductions in smoking and hypertension. THE AUTHORS DESCRIBE THEIR work, published as an Editor’s Choice Paper in the June edition of the European Journal of Vascular and Endovascular Surgery (EJVES), as the largest population-based analysis of AAA mortality to date, incorporating data from 17 countries across four continents. Despite the evidence showing a strong general trend, Png, Choke, et al do acknowledge and detail heterogeneity among countries included in the study and notable geographical limitations. It is known that the early 21st century witnessed a decrease in mortality from AAA, the authors begin, noting an association with “variations in the prevalence of cardiovascular risk factors”. The aim of this study was to investigate whether this trend had continued into the second decade of the century by looking at data from 2001 through 2015. The researchers first extracted the International Classification of Disease codes for AAAs, thoracoabdominal aortic aneurysms, and aortic aneurysms of unspecified site (both ruptured and without rupture) from the World Health Organisation (WHO) mortality database. In addition, they collected data on risk factors from the Institute of Health Metrics and Evaluation and WHO InfoBase, as well as data on population from the World Development Indicators database. In order to be included in the analysis, countries had to have <30% of mortality data missing and at least 10 annual AAA-related deaths, the authors communicate. Out of the 17 countries included in total, 11 were European, and two each were Australasian, Continued on page 6

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July 2021 | Issue 90

Lower-extremity amputation

Vascular community rallies to reduce “devastating” lower-extremity amputations Continued from page 1

Creager and colleagues state that primary care physicians with low awareness of PAD will be less likely to use guideline-directed medical therapy, noting recent studies showing that smoking cessation therapy was offered to only a minority of patients with PAD and that only a limited number of patients with diabetes were receiving foot care. The authors relay that some PAD awareness initiatives have been created to address the issue of awareness, including Stay in Circulation, PAD Awareness Month, and Legs for Leg. In addition, they reveal that the AHA, in conjunction with key stakeholder organisations, will soon unveil the first National PAD Action Plan—a “comprehensive road map for a coordinated, enduring approach to vascular health”.

Hospitals “should incorporate” evidencebased PAD management strategies

Greater use of effective PAD management strategies can mitigate the risk of lower-extremity amputations, Creager et al communicate. In the policy statement, they list a series of diagnostic and therapeutic approaches, which they suggest all health management organisations and hospitals “should incorporate” as quality measures. Among the strategies listed are wider use of the anklebrachial index (ABI) to diagnose PAD, smoking cessation, regular foot care in patients with diabetes, statins—for which there is a “body of evidence” indicating an association with risk reduction of major limb events— multidisciplinary wound care, timely referral to vascular specialists, and revascularisation. Speakers and panellists at CX 2021 echoed the importance of a multidisciplinary team and proper imaging. Emphasising also the benefit of early and accurate diagnosis, Michael Edmonds (King’s College London and King’s College Hospital NHS Foundation Trust, London, UK) stressed: “Time is tissue”.

“It is time to take action”: Implementation crucial to achieving 2030 target

In order to meet the AHA’s goal of a 20% reduction in amputations by 2030, the authors propose the following policies: ●A doption of quality and performance measures to promote optimal medical management of patients with PAD (statins, smoking cessation, and glucose control) ● Coverage for annual foot monitoring of patients with diabetes ● Robust US Food and Drug Administration regulation of all tobacco products

●A vailability of comprehensive tobacco cessation therapy with no copay ● Integration of clinical decision support to diagnose and manage PAD in electronic health records ● Consistent reimbursement for the ABI test across all states ●A ffordable, accessible, and equitable medical care for all patients with PAD ● Professional education on PAD diagnosis and management ● Dedicated funding opportunities to support PAD research A wide range of stakeholders would be involved in implementing these initiatives, the authors note, specifying that researchers, healthcare professionals, healthcare systems, policymakers, patients and caregivers, and the general public can all contribute to reduce non-traumatic lower-extremity amputations. “It is time to take action”, the authors conclude. “We urge that policymakers ranging from regulatory bodies to health systems and individual institutions refer to this policy statement and implement its recommendations to achieve the goal of reducing the rate of non-traumatic lowerextremity amputations by 20% by 2030.”

There is considerable opportunity to improve the care of patients with PAD.” Words become actions: ARC Act reintroduced in the USA

In May, members of the PAD Task Force—including the Association of Black Cardiologists, CardioVascular Coalition, CLI Global Society, Preventative Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology—commended reintroduction of the Amputation Reduction and Compassion (ARC) Act (HR 2631), legislation intended to reduce unnecessary amputations due to PAD. The bill provides coverage of PAD screening for at-risk beneficiaries under the Medicare and Medicaid programmes without the imposition of costsharing requirements. Jeffrey Carr (Tyler Cardiac and Endovascular Center, Tyler, USA), co-founder of the Outpatient Endovascular and Interventional Society (OEIS) and a member of the CardioVascular Coalition, comments on the significance of the bill: “With the introduction of the ARC Act, and in recognition of National Minority Health Month, we have the opportunity to expand coverage for simple, non-invasive screening tests that will empower patients to take steps to manage their PAD before amputation becomes necessary.”

News in brief

The latest stories from the vascular world

n NEW TOOLS FOR CLTI: “I am going to give you reasons to be excited about your critical limb practice,” Peter Schneider (San Francisco, USA) told delegates attending the International Symposium on Endovascular Therapy 2021 (ISET; 9–11 May, Miami, USA), in a talk focusing on innovative tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI). “I think critical limb ischaemia has come to the forefront of our practices and of community awareness, and finally now the tools are starting to show that,” he opined.

For more on this story go to page 8. n HIGH-FLOW FISTULAS IN AV ACCESS: Discussions at this year’s Charing Cross (CX) 2021 Digital Edition (19–22 April, online) indicated that high-flow arteriovenous fistulas (AVFs) remain one of the more divisive topics in the field of vascular access. This was most apparent in the outcome of a debate on whether reducing flow in asymptomatic high-flow fistula patients is necessary, with audience polling revealing an exact 50/50 split across CX attendees.

For more on this story go to page 24. n VENOUS THROMBOEMBOLISM: Joseph Caprini (Chicago, USA), who has dedicated his career to the understanding of venous thromboembolism (VTE), traces the development of thrombosis research. He outlines important milestones, addresses key unanswered questions, and considers the latest findings regarding COVID-19 and VTE.

For more on this story go to page 30.

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July 2021 | Issue 90

AAA mortality

Large study shows continued and quickening decline in AAA mortality Continued from page 1

North American, and Asian. Writing in EJVES, Png, Choke, and colleagues report that male AAA mortality decreased in 13 countries (population weighted average, -2.84%), while female AAA mortality decreased in 11 countries (population weighted average, -1.64%). Looking at the specifics, they detail that the USA (-5.24%), the UK (-4.53%), and The Netherlands (-4.27%) had the largest annual decreases. Of note, the researchers highlight that four countries—Hungary, Israel, Japan, and Romania—actually witnessed an overall increase in male AAA over the time period. Of these four countries, Hungary experienced the largest increase. In addition, the authors reveal that the decrease in AAA mortality was seen in both younger (<65 years) and older (>65 years) patients, and that the decrease in AAA mortality was more marked in the second decade of the 21st century (2011–2015) compared with the first decade (2001–2005 and 2006–2010). Considering the reasons behind these findings, Png, Choke, et al note that trends in AAA mortality positively correlated with smoking and hypertension,

while AAA mortality negatively correlated with obesity. There was no significant correlation with diabetes, they add. The authors recognise that the study has some limiting factors. For example, they acknowledge that “while the epidemiological study design allowed for large-scale comparisons across countries, relationships may not be generalisable to the individual”. They add that data collection disparities between countries “may affect interpretation of mortality and risk factor data”. They also identify a limitation regarding the included geographies. “Despite the original intent of this study,” they write, “the resulting pool of included

Aortic care needs to address specific geographical requirements Edward Choke Comment & Analysis Following the publication of a population-based study showing that abdominal aortic aneurysm (AAA) mortality has continued to decline in the second decade of the 21st century, and at a quicker pace than before, lead author Edward Choke discusses the findings and considers remaining questions on the topic. WE FIRST REPORTED GLOBAL declines in AAA deaths in 2014.1 With this current updated report, the good news is that AAA mortality has continued to decline. The even better news is that the decline may be faster. Whilst this paper was not designed to determine the reasons for the falling rates of AAA death, possible factors could be lower prevalence of AAA and lower propensity for AAA to rupture, with varying effects in different countries. Previous investigators, for example in Finland,2 have reported that, on a country-level analysis, a decrease in AAA mortality can be attributed to a decrease in AAA prevalence, a decrease in the incidence of AAA rupture, and a shift from open repair to endovascular aneurysm repair (EVAR) in the treatment of intact AAA, leading to lower 30day mortality. We have also previously reported that, in the UK,3 there has been a

decline in AAA ruptures. The lower rates of detection from screening programmes also suggest that the prevalence of AAAs is declining.4 As vascular specialists, it is an appealing notion that improvements in management of AAAs (e.g. EVAR or AAA screening) could also play a role in the global decline in AAA deaths. In fact, investigators have reported that EVAR was a likely contributory factor to declining AAA deaths in the USA.5 Ideally, we would have liked to investigate whether these were associated with declines in AAA mortality on a global level, but this was beyond the scope of the present paper. The heterogeneity in rates of decline between different countries gave us an opportunity to investigate some of the possible factors associated with the global decline. However, this was limited to factors in which reliable global data

countries sorely lacked representation from South American, African, and Asian countries”. They note in particular that China and India, the two most populous countries, did not meet the inclusion criterion regarding available mortality data and, as such, could not be included in the present analysis. Furthermore, Png, Choke, and colleagues remark that Israel and Japan were the only non-Western countries to meet the inclusion criteria. “This is significant because white people have been shown to have a 10-fold higher incidence of AAA than Asian people, and whether their mortality and risk profiles would be representative of nonwhite populations as well remains to be proven”, they comment. Considering future research, the authors advance that “a greater understanding of the epidemiology and risk factors at a population level will be helpful in informing future AAA-related healthcare policy strategies”.

A greater understanding of the epidemiology and risk factors at a population level will be helpful in informing future AAArelated healthcare policy strategies.”

were available—smoking, hypertension, obesity, and diabetes. The associations between smoking/ hypertension and a decline in AAA mortality do not imply causality. Nevertheless, these associations were consistent across countries and had strong statistical significance. In other words, countries with the largest reductions in smoking and hypertension demonstrated the largest reductions in AAA mortality. It is widely accepted that smoking is associated with development of AAAs, can accelerate AAA growth, and increases the risk of AAA rupture— plausible mechanisms to explain how reduction in smoking can lead to declines in AAA deaths. Public health policies to reduce smoking and hypertension in order to reduce cardiovascular deaths are already in place in many parts of the world. Our findings further affirmed the known links between smoking and hypertension to

The general trend is encouraging but there is still a long way to go in efforts to eradicate AAA mortality.” AAA and provide a strong argument that effective public health strategies against smoking and hypertension will probably reduce AAA mortalityin addition to other cardiovascular deaths. This is particularly pertinent for countries with trends of rising AAA mortality—which are contrary to the overall global trend. The general trend is encouraging but there is still a long way to go in efforts

to eradicate AAA mortality. Aortic specialists, with their respective vascular bodies or societies, should be aware of the trends in their countries and, based on these findings, target their policies to modifiable factors to further reduce their countries’ AAA mortality. For example, public health policies targeted at reducing smoking will be useful in countries with high smoking and high AAA prevalence. If AAA prevalence has decreased but incidence of AAA rupture remains high, then screening for AAA may be the solution. EVAR, by reducing perioperative mortality of AAA repair, may also contribute to reducing trends of AAA mortality; and aortic specialists play a key role in offering the best available treatments for their patients with AAAs. There may also be geographical variations in trends within each country; and aortic specialists should therefore be aware of the trends in their particular region so that healthcare can be efficiently organised in accordance with geographical requirements. References 1. Sidloff D, Stather P, Dattani N, et al. Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality. Circulation 2014 Feb 18;129(7):747–53. 2. Laine MT, Laukontaus SJ, Sund R, et al. A population-based study of abdominal aortic aneurysm treatment in Finland 2000 to 2014. Circulation 2017 Oct 31;136(18):1726–1734. 3. Choke E, Vijaynagar B, Thompson J, et al. Changing epidemiology of abdominal aortic aneurysms in England and Wales: older and more benign? Circulation 2012 Apr 3;125(13):1617–25. 4. Svensjö S, Björck M, Gürtelschmid M, et al. Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men indicates a change in the epidemiology of the disease. Circulation 2011 Sep 6;124(10):1118–23. 5. Schermerhorn ML, Bensley RP, Giles KA, et al. Changes in abdominal aortic aneurysm rupture and short-term mortality, 1995–2008: a retrospective observational study. Ann Surg 2012 Oct;256(4):651–8.

Edward Choke is a senior consultant vascular and endovascular surgeon at Sengkang General Hospital in Singapore. The author has no disclosures.

Issue 90 | July 2021

CX 2021

PERIPHERAL

CX audience supports call to change agency recommendations regarding paclitaxel use in peripheral interventions Addressing representatives from the US Food and Drug Administration (FDA) and UK Medicines and Healthcare products Regulatory Agency (MHRA) directly, Thomas Zeller (Universitäts— Herzzentrum Freiburg, Bad Krozingen, Germany) argued at the Charing Cross (CX) Digital Edition 2021 (19–22 April, online) that “it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions”. Moderators Andrew Holden (Auckland City Hospital, Auckland, New Zealand) and Gunnar Tepe (Rosenhein, Germany), Podium 1st presenters Gary Ansel (OhioHealth Heart & Vascular Physicians, Columbus, USA) and William Gray (Lankenau Medical Center, Wynnewood, USA), as well as a 71% majority of the CX audience, supported this view. WHILE THERE WAS AGREEMENT that it was right to be concerned about the paclitaxel mortality signal raised by Konstantinos Katsanos (University of Patras, Patras, Greece) et al in their December 2018 meta-analysis, there was strong consensus that the evidence is now clear there is no mortality effect when paclitaxel is used in the peripheral arteries. In addition, it was noted that several individual patient-level metaanalyses failed to confirm the high mortality signal flagged by Katsanos and colleagues. There was some discussion surrounding the place of limus as an alternative to paclitaxel, but experts agreed that there is no need to move to another drug—which would have its own set of challenges—given the proven safety and efficacy of paclitaxel. The takeaway message was clear: that, with proper caution and the correct dose, paclitaxel can and should be used in peripheral interventions.

More data find no mortality associated with paclitaxel

Patient safety has been at the centre of CX discussion on the paclitaxel issue since the Katsanos et al meta-analysis was published. This year, further data were presented that support the conclusion of vascular pathologist Elena Ladich (Memorial Healthcare System, Hollywood, USA) who two years ago at CX 2019 stated that there are “no causal links or mechanisms to explain the reported association of paclitaxel in the lower limbs and patient mortality”. Sabine Steiner (University of Leipzig, Leipzig, Germany) gave the first presentation on long-term paclitaxel data at CX 2021, outlining five-year results of the REAL-PTX study—an investigatorinitiated, prospective, European, multicentre randomised controlled trial (RCT) comprising 150 patients with femoropopliteal disease. Patients were randomised to treatment with either a drug-eluting stent (100% Zilver PTX, Cook) or a drug-coated balloon (DCB;

77.3% IN.PACT Admiral/IN.PACT Pacific, Medtronic; 21.3% Lutonix, BD). Steiner reported that mortality rates after five years were “comparable to prior reports investigating long-term outcomes for drug-eluting and non-drug-eluting devices”. Also presenting data in support of the safety of paclitaxel, Mårten Falkenberg (University of Gothenburg, Gothenburg, Sweden) gave the latest analysis and interpretation of the SWEDEPAD trial concerning mortality. “It is very unlikely that devices coated with paclitaxel used for the treatment of peripheral arterial disease [PAD] do increase late mortality”, he concluded. In a Podium 1st presentation on the topic, Holden, on behalf of coauthors Ramon Varcoe (Prince of Wales Hospital, Sydney, Australia) and Peter Schneider (University of California San Francisco, San Francisco, USA), revealed a five-year meta-analysis update regarding drug-coated technologies in femoropopliteal interventions and allcause mortality concerns that included the SWEDEPAD update. The data were also recently published online in the Journal of Endovascular Therapy. Holden stressed that there is a “clear benefit of paclitaxel-coated devices in femoropopliteal disease” and relayed that the investigators recommend the continued use of these devices in this patient population. “The time has arrived for regulators to provide updated and clear guidance on these devices for the benefit of patients globally”, he stated.

Three-quarters of CX audience support call to change agency recommendations With a growing pool of data showing no association between paclitaxel and mortality, representatives from the FDA and MHRA reiterated current agency positions on the topic. Sara Royce, team lead of the plaque modification devices team at the FDA, talked the CX audience through regulatory approaches to the

Clockwise from top left: Roger Greenhalgh (London, UK); Andrew Holden (Auckland, New Zealand); Gunnar Tepe (Rosenheim, Germany); Thomas Zeller (Bad Krozingen, Germany); Roopa Prabhakar (MHRA, London, UK); and Sara Royce (FDA, Silver Spring, USA).

next-generation of drug-coated devices for PAD. Roopa Prabhakar, senior medical devices specialist at the MHRA, offered a UK perspective on paclitaxel device regulation, saying the agency will “continue to assess the significance of any new data in relation to patient safety”. Following these presentations, Zeller argued that it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions. “Withholding such devices to patients with severe peripheral arterial occlusive disease may even harm them and result in increased global healthcare costs”, he stated, concluding that “the benefit outweighs the hypothetical risk”. Audience polling following Zeller’s talk revealed that 74% of the audience agree it is time to change the agency recommendations regarding paclitaxel use in peripheral interventions.

“What you do not leave behind is a suboptimal result” In a Podium 1st presentation, Gary Ansel (OhioHealth Heart & Vascular Physicians, Columbus, USA) announced results of the IN.PACT Global stented versus non-stented analysis, comprising 353 patients stented and 1,044 nonstented patients. The purpose of this study was to compare outcomes of standalone IN.PACT Admiral DCB usage versus IN.PACT Admiral DCB followed by provisional stenting. Ansel concluded that, in this complex lesion subset from the study, the IN.PACT Admiral DCB “demonstrates durable safety and effectiveness through five years”. He added: “In the event of suboptimal angioplasty results (i.e. persistent residual stenosis >50%, flow limiting dissection), the addition of a stent did not appear to decrease the optimal results through five years”.

The time has arrived for regulators to provide updated and clear guidance on these devices.”

In the discussion following Ansel’s presentation, the presenter stressed that, regardless of whether or not you leave a stent behind, “what you do not leave behind is a suboptimal result, just to not leave a prosthetic device in. That is the worst thing to leave behind.”

Time to look at “the whole patient”

Gray delivered another Podium 1st presentation, giving the five-year results from a patient-level meta-analysis of the ILLUMENATE RCTs. He told attendees how “The Stellarex DCB continues to consistently demonstrate no difference in mortality compared to percutaneous transluminal angioplasty (PTA) yearover-year through five years, both within individual RCTs and pooled analysis.” When asked by moderator Robert Hinchcliffe (University of Bristol, Bristol, UK) if this was “the definitive trial to put the paclitaxel issue to bed”, Gray commented: “When you ask a US physician what puts an issue to bed, that is when the FDA rescinds their statement about danger. In order for them to do that, I think we have to see a high quality, patient-level meta-analysis that includes all the original studies included in Katsanos’ meta-analysis, followed up to five years, plus all the other datasets that have come forward since that time. The key piece here, that we do not talk enough about but we need to recognise, is that the missing data, which were on the order of 20% of the original analysis, even at the patient level, are now only about 5%, as we have gone back and done all the vital statistics. I think that will make a big difference in the ultimate analysis.” Ansel chimed in to comment on the fact that mortality is largely due to cardiovascular issues or cancer. “I do not think we are really focussed on that,” he said. “Forget the paclitaxel, which has been really put to bed, and let us get back to good patient care and see if we can decrease those cardiovascular and cancer rates.” Gray agreed, saying that the “major message” was that cardiovascular risk factor modifications (smoking cessation, diabetes and hypertension management) were important to consider, and that it was time to look at “the whole patient”.

ISET 2021

July 2021 | Issue 90

PERIPHERAL

New tools for CLTI: ISET audience hears what developments they can expect for these challenging patients “I am going to give you reasons to be excited about your critical limb practice,” Peter Schneider (University of California San Francisco, San Francisco, USA) told delegates attending the International Symposium on Endovascular Therapy 2021 (ISET; 9–11 May, Miami, USA), in a talk focusing on innovative tools on the horizon for the treatment of chronic limb-threatening ischaemia (CLTI). “I think critical limb ischaemia has come to the forefront of our practices and of community awareness, and finally now the tools are starting to show that,” he opined.

overing developments in assessment (including monitoring, perfusion, and wound evaluation), reconstruction, and medication delivery, Schneider left his audience with an optimistic outlook for the future of CLTI treatment.

Assessment: Wearables, implantables, and artificial intelligence

Turning first to wearables and implantables, which he said “are just around the corner”, Schneider expanded: “[In terms of] implantables, there is a patent application for a stent with a sensor on it, which of course makes sense that someday that is how we will be doing our surveillance. “Wearables are available now, and are essentially a transfer from other types of technology.” Citing a JAMA Network Open article from late-2020, which looked at the association between wearable device– based measures of physical frailty and major adverse events following lower extremity revascularisation, Schneider said he expected to see “more articles like this one”, adding: “I am sure we are going to have [investigations into the use of wearable devices to assess frailty] for claudication patients on a regular basis as well.” In addition to wearables and implantables, he also directed the ISET audience’s attention towards the use of artificial intelligence (AI): “A couple of companies have taken it upon themselves to do a digitised wound evaluation, and then use AI to help the programme get smarter over time about identifying the cause of the wound and the progress of the wound. So much of what we are doing is an inexact science: when we think of screening, population management, treatment guidelines, we are thinking about the population as a whole, and just trying to do the right thing, but each of these patients comes having their own code and their own set-up, so the transfer of existing technology I think will help us to individualise the way we would like to.

Reconstruction: Modified balloons, new implants, alternative bypass, below-theankle angioplasty

“Below-the-knee [BTK] angioplasty is just sitting there waiting for us to really develop it,” Schneider stated, telling delegates listening in Miami and online that the medical community is now starting to see data showing improved wound healing. However, he noted that the patency data are “still unclear”, and, in his opinion, need to be further assessed. “But I think we are really developing [in this arena],” he concluded. The speaker first highlighted the lithotripsy with Shockwave. Lithotripsy waves travel outside the balloon, and disrupt both superficial and deep calcium. It is a way to improve vessel wall compliance prior to controlled, low pressure dilatation. “The question is how valuable is this going to be in BTK interventions?”

Schneider asked. “I think it remains to be seen, but it certainly is a technology for interrupting calcium.” Another technology Schneider considered was serration angioplasty. Noting his conflict of interest due to his involvement with Cagent Vascular, a developer of serration technology for vessel dilatation in endovascular interventions, Schneider explained how the novel Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter works: “The idea is that you poke little holes in the artery, and allow a stress relief line along the vessel so that it can be opened. I really believe that BTK angioplasty is due for a makeover by one method or another, and here is just an example of the flexibility of this tool.” The Serranator PTA serration balloon catheter is the first and only angioplasty balloon to receive US Food and Drug Administration (FDA) approval and the CE mark that embeds serration technology into a semi-compliant balloon for treating peripheral arterial disease (PAD). Earlier this year, results of Cagent Vascular’s PRELUDE-BTK study—a prospective, single-arm,

If percutaneous femoropopliteal bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR1 study, it could be a game changer for the way we treat complex, long-segment SFA disease today.” multicentre feasibility study investigating the safety and efficacy of serration angioplasty— were presented at the Leipzig Interventional Course (LINC; 25–29 January, online). Forty-six patients were treated with the Serranator device and 53 lesions were analysed by the core lab. The average final residual stenosis was 21.8%, with an average BTK arterial lumen gain of 1.55mm. These results were achieved with a low average maximum atmospheric pressure of six atmospheres. The bailout stent rate was 1.9%. A subset of lesions (n=10) were imaged with optical Peter Schneider

coherence tomography (OCT) and intravascular ultrasound (IVUS), and analysed by a core lab. All showed a serration effect. At 30 days, the freedom from primary safety events was 95.7%. Freedom from clinically-driven target lesion revascularisation (TLR) was 97.7%, and there were no serious adverse events related to the device. Following this discussion on modified balloons, Schneider turned to a new method of post-angioplasty dissection repair: focal dissection repair. He showcased a new implant, the Tack endovascular system (Intact Vascular), the first FDA-approved vascular implant for BTK post-angioplasty dissection repair. Regulatory approval for the device was based on data from Intact Vascular’s Tack optimised balloon angioplasty II BTK (TOBA II BTK) clinical trial, which met all primary endpoints with 100% acute dissection resolution. The TOBA II BTK results demonstrated 95.7% amputationfree survival, 87.3% target lesion patency, with significant improvement in toe-brachial index (TBI), and 92% freedom from clinically-driven reintervention at six months. Schneider mused: “The issue is; do we need IVUS? We know IVUS is more sensitive—all of the trials we did with focal dissection repair were angiographicallydriven. However, could the results have been better if we used IVUS routines? Just something to think about as BTK disease gets more sophisticated, what will the role of IVUS be?” Another implant Schneider explored in his presentation was a bioabsorbable vascular scaffold, the Abbott Esprit. This is an everolimus-eluting device, designed for the superficial femoral artery and iliac arteries. Recently-published data from Ramon Varcoe (Sydney, Australia) and colleagues show “excellent” patency out to five years. The LIFE-BTK randomised controlled trial, where participants will be randomised 2:1 Esprit versus PTA, is now enrolling in the USA. Lastly, in the “reconstruction” portion of his talk, Schneider mentioned percutaneous bypass. “The mean lesion length in the PQ bypass trial is in excess of 30cm, so we have not typically had an option for lesions of that length using percutaneous devices,” he announced. DETOUR II is a prospective, multicentre trial evaluating the Detour system (PQ Bypass) for percutaneous femoral-popliteal bypass in patients with extremely long, complex lesions in the SFA. The study enrolled 202 patients in 36 sites in the USA and Europe, and is assessing freedom from major adverse events (MAEs) within 30 days of the index procedure as the primary safety endpoint. The primary effectiveness is primary patency at 12 months. Speaking to Vascular News about the potential of percutaneous bypass, principal investigator Jihad Mustapha (Advanced Cardiac and Vascular Centers, Grand Rapids, USA) said at the end of 2020: “If percutaneous femoral-popliteal bypass is shown to be safe and effective, similar to the outcomes demonstrated in DETOUR I study, it could be a game changer for the way we treat complex, long-segment SFA disease today.”

Medication delivery: “Paclitaxel issue” opened the door wider for research into alternative drugs “We do not have any paclitaxel BTK drug-coated balloons (DCBs) in the USA,” Schneider said. While he noted that there are several paclitaxel DCB trials currently underway in the USA—

Issue 90 | July 2021

ISET 2021

he showed three of them: IN.PACT DEEP, Lutonix BTK, and BIOLUX P-II—he commented that “nothing is close to being approved”, though some show promise. “In particular, Medtronic has some preliminary data,” he said, before continuing: “My personal opinion is that the paclitaxel issue will fade over time. I think we have had such a hard time finding a danger signal in any subsequent data. Nevertheless, the whole issue has bought forward the concept of limus-based compounds.” The “paclitaxel issue” he is referring to here is the increased association with mortality reported by Konstantinos Katsanos (University of Patras, Patras, Greece) et al in December 2018 when paclitaxel devices are used in the lower leg, which caused an international furore about the safety of these devices. Since, multiple analyses have failed to replicate this signal, but, as Schneider pointed out at ISET, the publication opened the door wider for research and development into alternative drugs. “Here is just one,” Schneider said, showcasing the MEDAlliance Selution, a sirolimus-coated balloon from Swiss start-up MedAlliance. “This is their SFA device. It uses micro-reservoirs made out of biodegradeable polymer intermixed with sirolimus for sustained and controlled drug release—typically, the slow and difficult uptake has been the problem with sirolimus.” MedAlliance’s planned clinical programme includes specific trials focusing on BTK disease (SELUTION BTK IDE) and CLTI patients (PRESTIGE, PRESITINE, and STEP). Concept Medical, another start-up, from India, has recently published a first-in-human series from its XTOSI

study, demonstrating good six-month primary patency of its MagicTouch PTA sirolimus-coated balloon in the treatment of BTK arterial lesions, in addition to femoropopliteal lesions. In addition, the US-based company Surmodics has a BTK DCB (the Sundance DCB) currently in a first-in-human trial. “There is also a method of administering limus-based compounds using the Mercator Bullfrog catheter,” Schneider said, which has 510(k) clearance. The Bullfrog device delivers generic dexamethasone to the adventitia, reducing inflammation that can be caused by interventional revascularisation. Delivery is confirmed with the coadministration of contrast. The final technology Schneider mentioned is the “Eluviatype technology”, seen in the SAVAL BTK drug-eluting stent system from Boston Scientific, which utilises a polymer as well as paclitaxel, and has been successful in SFA trials. It is now being enrolled in BTK trials. The SAVAL BTK stent system was the first CLTI device to be recognised by the FDA breakthrough device programme.

Below-the-knee angioplasty is just sitting there waiting for us to really develop it. However, the data are still unclear.”

‘Expensive interventions do not necessarily correlate with good results’: Stenting found to significantly reduce mortality risk in PAD patients

Stenting reduced mortality risk in patients undergoing interventions for peripheral arterial disease (PAD) by more than 30% when compared to plain balloon angioplasty and 40% contrasted with atherectomy, a recent propensity-matched analysis found. THE VASCULAR QUALITY Initiative (VQI)-derived data drew sharp conclusions from lead investigator of the study, Dipankar Mukherjee, chief of vascular surgery at Inova Fairfax Hospital in Falls Church, USA, who probed the effects of PAD interventions on survival to most recent follow-up by highlighting that most of these procedures involve claudication patients. “Expensive interventions do not necessarily correlate with good results,” Mukherjee told attendees of the International Symposium on Endovascular Therapy (ISET) held in Miami (May 9–11), where he presented his findings. “What has been good for the bottom line of the OBL [office-based lab] may be fatal for the patient. We recommend a critical reappraisal of the treatment paradigm for PAD patients presenting with claudication. We believe the current CMS [Centers for Medicare & Medicaid Services] reimbursement for atherectomy has resulted in unintended consequences.” Mukherjee earlier set out the current context of PAD interventional practice: While PAD interventions double every

decade, the more severe form of the disease, critical limb ischemia (CLI), occurs in only a small percentage. More than a decade ago, there were CMS payment system changes governing the outpatient setting. That led to the rise of the OBL. Most PAD interventions are now carried out in OBLs. Atherectomy, most frequently performed in OBLs, is the most highly compensated PAD intervention at between $15,000 and $18,000. “This massive increase in OBL volume has not resulted in cost savings as it was originally intended,” Mukherjee added. To arrive at their conclusions, Mukherjee and colleagues, plumbed the VQI database for claudication and CLI interventions between May 2011 and February 2020, linking the data extracted with survival data from the Social Security death index—the primary outcome measure being survival to most recent follow-up. PAD interventions were classified as either balloon angioplasty alone, stenting with and without a balloon, and atherectomy with or without stenting or a balloon. The researchers compared three matched cohorts: those receiving

balloon angioplasty versus those who between balloon angioplasty and underwent stenting; patients who atherectomy (HR, 1.02; CI 0.88–1.19; received balloon angioplasty versus p=0.776 ). Meanwhile, stenting was patients undergoing atherectomy; and found to be superior to atherectomy those who had a stent placed versus the (HR, 0.6; CI, 0.48–0.75; p<0.001). atherectomy patients. When claudication patients were A total of 15,281 patients were separated from those with CLI, included in the study: 9,441 received Mukherjee and colleagues found a balloon angioplasty, 3,547 got a stent survival benefit in favor of stenting and 2,293 had atherectomy. After over balloon angioplasty (HR, 0.49; propensity matching, a group of CI 0.4–0.59; p<0.001). They detected 3,047 remained to compare between no difference between angioplasty and balloon angioplasty and stenting; atherectomy, but their data demonstrated 2,016 for comparison of angioplasty a “highly significant” HR of 0.55 and atherectomy; and in favor of stenting vs. 1,656 between stenting and atherectomy (CI, 0.43–0.69; atherectomy. p<0.001). Patients were almost “When we look at CLI equally divided between alone, there was a trend claudicants and CLI. toward significant, but with a Most interventions confidence interval exceeding were performed in the 1, these numbers are not Dipankar Mukherjee femoropopliteal-tibial considered statistically segment, with the exception of a larger significant,” Mukherjee added. proportion of stenting having been Discussing his findings, Mukherjee carried out in the aortoiliac segment. told ISET delegates have reported Results show a “highly, highly “almost universal evidence” of significant” hazard ratio (HR) of 0.7 in distal embolization with peripheral favor of stenting vs. balloon angioplasty atherectomy. “We know that intermittent (95% confidence interval [CI], 0.6–0.82; claudication has a relatively benign p<0.001), Mukherjee revealed. The course with a very small annual research team found no difference mortality risk. I have previously shown using ICD-9 billing data that the results of intervention with atherectomy for patients presenting with claudication symptoms were worse than the natural history of the condition.” Mukherjee conceded there were limitations to his study, primarily owing to its observational nature, but nevertheless concluded that he and colleagues had demonstrated “stenting has 30% better survival than angioplasty and 40% better than atherectomy after propensity matching.” Dipankar Mukherjee

We recommend a critical reappraisal of the treatment paradigm for PAD patients presenting with claudication.”

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* LifeStream™ Covered Stent achieved a high acute technical success rate of 98.3%. Acute Technical Success is defined as successful deployment of the LifeStream™ Covered Stent at the intended location, as determined by the investigator. BOLSTER Clinical Study. Data on File. Bard Peripheral Vascular, Inc., Tempe, AZ. The LifeStream™ Balloon Expandable Vascular Covered Stent is indicated for the treatment of atherosclerotic lesions in com mon and external iliac arteries with reference vessel diameters between 4.5 mm and 12.0 mm, and lesion lengths up to 100 mm. Please consult product labels and package inserts for indications, contraindications, hazards, warnings, precautions, and instructions for use. BD, the BD Logo, and LifeStream are trademarks of Becton, Dickinson and Company or its affiliates. © 2021 BD. All rights reserved. Illustrations by Mike Austin. Copyright © 2021. All Rights Reserved. Becton, Dickinson and Company | www.bd.com | 1 800 321 4254 | 1625 W. 3rd Street Tempe, AZ 85281 BD-14492

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Issue 90 | July 2021

Atherectomy 11

Results of two-year study show Zilver Vena Venous Stent is safe and effective

and 12 months—as well as patency, reintervention, clinical outcomes and The results of a two-year study support the continued safety and stent integrity through two years. effectiveness of the Zilver Vena Venous Stent (Cook Medical) in The Zilver Vena Venous Stent met treating symptomatic iliofemoral venous outflow obstruction, primary endpoints for both safety and according to findings presented at the 2021 meeting of the Society effectiveness, with a 96.7% rate of 30of Interventional Radiology (SIR; 20–26 March, online). day freedom from major adverse events and an 89.9% rate of 12-month primary THE STENT MET PRIMARY at some centres about stenting below quantitative patency. safety and effectiveness endpoints at one the inguinal ligament,” he said. “In this In addition, Hofmann said the mean month, and continued to do so through study, more than 20% of stents extended change (-3.0; p<0.0001) in VCSS from one- and two-year intervals during the into this region, and there were not any baseline was “significant” at one month VIVO Clinical Study. stent fractures.” and was sustained through 12 months In addition, the Zilver Vena Venous The VIVO Clinical Study took place (-4.2), and maintained at two years. Stent demonstrated high rates of patency between December 2013 and October Specifically, two-year outcomes included by ultrasound, freedom from clinically2016, and enrolled 243 high rates of patency by driven reinterventions and freedom patients (70% female; mean ultrasound (90.3%±2.2%), from reinterventions more generally age: 53±15 years) with freedom from clinically-driven throughout—all of which were clinical symptomatic obstruction reinterventions (93.2%±1.8%), outcomes being assessed in the study. of one iliofemoral venous and freedom from According to Lawrence “Rusty” segment. reinterventions (83.4%±2.5%). Hofmann, professor of interventional Data assessed during the “This landmark study radiology at Stanford Medicine (Stanford, study included baseline patient Lawrence Hofmann moves the ball forward in USA) and the study’s presenting author, characteristics, primary and the treatment of deep venous the stent’s integrity was also indicated secondary endpoints—such as 30-day disease,” Hofmann concluded. by the fact there were no core laboratory freedom from major adverse events, These two-year data follow reports of stent fractures across the two12-month primary quantitative patency, positive one-year data presented by year study period. and changes in venous clinical severity Anthony Comerota (Inova Fairfax “There has been concern over the years score (VCSS) from baseline to one month Hospital, Alexandria, USA) in a

“A new look at laser”: Positive initial data presented at ISET for the Auryon atherectomy system The Auryon atherectomy system (AngioDynamics) “represents an exciting new technology”, John Rundback (Advanced Interventional and Vascular Services, LLP, Teaneck, USA) opined at the International Symposium on Endovascular Therapies (ISET; 9–11 May, Miami, USA, and online), speaking on behalf of the Pathfinder I registry investigators. “I think it has really got a lot of traction; we found it a very useful tool across a wide range of plaque morphologies and vessel beds. Further iterations of this platform will hopefully improve its performance further.” THE PATHFINDER REGISTRY IS a post-market, prospective, multicentre, single arm, all-comers registry of 104 patients with femoropopliteal and tibial stenoses or occlusions or in-stent restenosis (ISR), with peripheral arterial disease (PAD) classified as Rutherford class 2–5. “Lesions of all levels, lesions of all types are included in this realworld registry,” Rundback said. Patients were treated with either the Auryon atherectomy system or adjuvant therapy. The primary endpoints were acute success (measured as ≤30% final residual stenosis by corelab evaluation) and freedom from peri-procedural major adverse events or complications through 30 days. Long-term results were collected through 24 months, including patency, major adverse events, target lesion revascularisation, and patientreported outcomes.

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Presenting the findings, Rundback said: “These are really important results I think. Across the board, the stenosis reduction or the luminal gain was between 24 and 31%; this is the laser-cut phenomenon that I think is unique to this laser. In CTOs [chronic total occlusions], there [is an average] 26% luminal gain. [In vessels with] moderate to severe calcium, there was a 27% luminal gain, [in vessels with] ISR, [there was a] 21% luminal gain, and above and below the knee, we see similar levels of luminal gain. So it does not matter what vessel, what vessel calibre, or what the plaque morphology is, this is a very precise, deliverable, controllable, and reproducible result.” In terms of safety, there was an absence of major adverse events in 99% of lesions. There was one dissection, which was after angioplasty alone, not

late-breaking session of the 2020 Vascular Interventional Advances conference (VIVA; 6–8 November, online). Responding to these results during VIVA 2020, fellow panellist Kenneth Cavanaugh (US Food and Drug Administration [FDA] Office for Cardiovascular Devices, Silver Spring, USA) was interested in the potential value of adding a comparator into these studies now that there are other stents in the market. This prompted Comerota to say that certain factors would need to be taken into account in any head-to-head comparison of venous stents, including the potential for lesion length to vary widely.

There has been concern over the years at some centres about stenting below the inguinal ligament. In this study, more than 20% of stents extended into this region, and there were not any stent fractures.”

after laser passage. perforations were There were two cases reported. There is also of distal embolization, less overall thermal one of which Rundback damage to the vessel said was “probably wall, he explained, attributed to the laser”, and the laser system and one of which was is agnostic to the following the treatment presence of contrast. It of an in-flow lesion also requires minimal that had angioplasty, warm-up time: “From a shockwave, and practical point of view, it atherectomy. There only needs a 15 second were a total of four warm-up; if you do not Auryon atherectomy system bailout stents, three of like where it is placed in which were for recoil the room, you can pick it and one of which was for dissection. up and move it to another spot.” There was one amputation, which Four catheters of varying sizes occurred 180 days after follow-up; the (0.9mm, 1.5mm, 2mm, and 2.35mm) can patient had Rutherford category 5 disease be used wih the system. and gangrene at baseline, and they failed The Pathfinder registry builds on to improve following treatment of their prior investigational device exemption 37cm-long lesion. (IDE) and CE studies, which combined The Auryon atherectomy system is investigated 147 patients with 163 a proprietary, solid-state laser with a lesions. These reported no distal emboli wavelength of 355nm (different to the events or perforations. Of 107 lesions currently-available 308nm laser). “What included in the IDE study, 16 were is really unique about this is it is not just minor (grades A or B). In terms of the wavelength, but it has a very short debulking, there was a 34% reduction pulse duration of 10ns, which results post-procedure (the FDA threshold for in a very precise, controllable, and efficacy is 20%). “Clinical results and reproducible laser energy delivery to the patient-reported outcomes were very vessel wall,” Rundback explained. favourable at 12 months,” Rundback He went on to describe how this said. particular wavelength (355nm) has Session moderator Daniel Clair a “very high” affinity for atheroma (Vascular Surgery, University of South compared to the vessel endothelium, Carolina, Columbia, USA) praised resulting in a reduced risk of perforation. Rundback for his talk, saying it offered, Indeed, in the Pathfinder I trial, no “A new look at laser”.

July 2021 | Issue 90

12 Peripheral arterial disease

PERIPHERAL

ACC.21: VOYAGER PAD analysis shows reduced risk of ischaemic events in PAD patients receiving rivaroxaban Rivaroxaban (Xarelto, Bayer/Janssen), in addition to low-dose aspirin, should be considered as an adjunctive therapy after lower extremity revascularisation to reduce first and subsequent adverse outcomes, analysis from VOYAGER PAD, presented during a late-breaking trial session at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual), indicates. The findings were simultaneously published online in the Journal of the American College of Cardiology (JACC).

upert Bauersachs, director of vascular medicine at the Darmstadt Clinic (Darmstadt, Germany) and lead author of the study, told ACC.21 attendees that the use of rivaroxaban significantly reduced the occurrence of total severe events of the heart, limb, or brain and issues related to other vascular complications in patients with symptomatic peripheral arterial disease (PAD) who underwent lower extremity revascularisation. The findings underscore the broad benefits of this strategy in this high-risk patient population, he said. “To our knowledge, this is the first time that the addition of low-dose rivaroxaban to aspirin has been clearly shown to reduce the occurrence of both first and total adverse events in patients with PAD who have undergone lower extremity revascularisation but remain at high risk for a heart attack, stroke or recurrent arterial blockage in a limb,” Bauersachs said. “The benefits we saw in the trial for total events were statistically significant and entirely consistent with those for first events. Rivaroxaban 2.5mg twice daily with aspirin should be considered as adjunctive therapy after revascularisation to reduce first and subsequent adverse outcomes.”

“A need for greater awareness that PAD is a distinct disease state”, ACC audience told

Recent data have shown that, after lower extremity revascularisation, there is a four-fold risk of acute limb ischaemia, Bauersachs told ACC.21 attendees, adding that this is associated with a high incidence of limbrelated complications. “There is a need for greater awareness that PAD is a distinct disease state and that patients with PAD have a high risk for cardiovascular adverse events and are generally a very vulnerable population, especially in the post-revascularisation setting,” Bauersachs said. “Care for these patients is often fragmented because the surgeon or interventionalist who performs the revascularisation may not follow them for complications or recurrences. They deserve to receive optimal treatment to reduce the risk of recurrences.”

The VOYAGER PAD trial

The randomised, double-blind VOYAGER PAD trial enrolled 6,564 patients in 34 countries who had PAD and had undergone lower extremity revascularisation. The patients’ median age was 67 years and 74% were men. Patients were randomly assigned to receive either rivaroxaban or a placebo in addition to daily aspirin. The trial’s primary endpoint was timed to the first event of a composite of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction (MI), ischaemic stroke or cardiovascular death. Another prespecified endpoint was the total number of vascular events, including recurrent primary endpoint events as well as other vascular events. The median follow-up time was 28 months after revascularisation. The research team reported in a late-breaking clinical

trial presented at ACC.20/WCC that VOYAGER PAD met its primary endpoint, with a 15% statistically significant reduction in the risk of a first major adverse limb or cardiovascular event seen in patients who received rivaroxaban compared with those who received the placebo. The current study reports on the total number of vascular events, with over 4,700 occurring in the 6,564 patients randomised across three years. “There were 342 fewer adverse events in the rivaroxaban group than in the placebo group, which translates to an absolute reduction in risk of 12.5%,” Bauersachs said. “In a high-risk population, that is a big gain in avoiding the need for patients to come back with vascular complications.” The 6,564 study participants experienced a total of 4,714 vascular events during the study period with 2,301—or about one third—experiencing at least one vascular event, Bauersachs said. “So, during approximately three years of follow-up,

To our knowledge, this is the first time that the addition of lowdose rivaroxaban to aspirin has been clearly shown to reduce the occurrence of both first and total adverse events in patients with PAD who have undergone lower extremity revascularisation but remain at high risk for a heart attack, stroke or recurrent arterial blockage in a limb.”

Rivaroxaban (Xarelto, Bayer/ Janssen)

about two-to-three out of six patients with PAD had a vascular event in spite of high utilisation of background medical therapy. This overall rate of vascular events is eye-opening and speaks to the high vulnerability of this patient population,” Bauersachs said. “First events are just the tip of the iceberg.”

Study limitations

A limitation of the study is that the trial was designed to assess the occurrence of first adverse events following lower extremity revascularisation, Bauersachs said. Therefore, in a double-blinded trial, patients may come off study treatment or go on to other therapies after an event, which can attenuate the

Rupert Bauersachs speaking at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21)

observed benefit. Assessment of the total number of adverse events, however, was a prespecified secondary endpoint and, despite this limitation, the findings were statistically significant and robust in absolute terms. VOYAGER PAD was funded by pharmaceutical companies Bayer and Janssen, who in a press release highlighting the presentation of the results, said that the analysis showed a very high burden of subsequent events and a consistent 14% reduction in both primary endpoint events and total vascular events over a median of 2.5 years. “The VOYAGER PAD trial is the first and only study of antithrombotic therapy in the past 20 years to demonstrate a significant benefit in patients with PAD after lower extremity revascularisation,” James List, global therapeutic area head, Cardiovascular & Metabolism, Janssen Research & Development, was quoted as saying in the release. “With these new data, we now have a full picture of evidence demonstrating the potential of Xarelto in treating patients through various stages of PAD— chronic, symptomatic, those requiring revascularisation and beyond,” he added. “Even years after revascularisation, patients with PAD continue to have a markedly high risk for future thrombotic events due to excessive thrombin generation and platelet aggregation,” added Marc P Bonaca, Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, (Aurora, USA). “This analysis from VOYAGER PAD looked beyond the first event and found subsequent thrombotic event reduction with rivaroxaban plus aspirin, underscoring the importance of long-term prevention in these highrisk patients.” Prior to this most recent ACC.21 presentation, another VOYAGER PAD analysis was presented by Connie Hess (University of Colorado, Aurora, USA) at the 2020 Vascular and Interventional Advances conference (VIVA; 6–8 November 2020, online), which found no excess mortality, and improved limb outcomes, with drug-coated device use in patients with PAD.

July 2021 | Issue 90

14 Imaging technology

AORTIC

Fiber Optic RealShape used in the USA for first time Vascular surgeons at the University of Massachusetts became the first in the USA to carry out procedures using the breakthrough imaging technology Fiber Optic RealShape (FORS; Philips), reporting a 75% decrease in radiation use after one of their earliest experiences of the system—a fenestrated endovascular aneurysm repair (FEVAR) of a thoracoabdominal aortic aneurysm (TAAA).

ndres Schanzer, professor and chief of Vascular Surgery at the University of Massachusetts Medical School in Worcester, USA, whose team is at the vanguard of the technology’s debut Stateside, describes the platform as representing “a transformative change” in how surgeons navigate vascular anatomy. FORS is currently available at a limited number of centres in Europe and the USA as it continues to undergo clinical study. The technology has CE mark approval in Europe and is US Food and Drug Administration (FDA) 510(k) cleared. The platform, which enables real-time 3D visualisation of the full shape of devices inside the body without the need for stepping on the fluoroscopy pedal, sends pulses of light through hair-thin optical fibres within minimally-invasive devices. Schanzer illustrates how a busy complex aortic practice at his institution currently depends on X-ray imaging for the entirety of procedures. “What FORS has enabled us to do is to really get away from using X-ray for all of the steps of the procedure,” he tells Vascular News in an interview shortly after undertaking his third procedure with the platform. “Fibre optic wires and catheters decrease our reliance on X-ray.” In addition to the decreased radiation and lowered procedure time FORS allows, Schanzer continues, another notable advantage includes an ability to work with completely new angles than those to which vascular surgeons are accustomed with X-ray. “There is no limitation on having to move a C-arm gantry around a patient,” he says. “You can be looking at several different angles, like a biplane view, at the same time. “I think it is going to change the way we look at all vascular interventions.” Quantifying the exact radiation reduction is going to take time and data to determine, Schanzer says. But by his third case, the four-vessel type II TAAA FEVAR, his team was able to decrease radiation use compared to their mean for that extent of repair from an average of 88 minutes down to just 22 minutes, or 75%. “We are at the very start of our learning curve,” Schanzer says, reporting that by the end of May he and colleagues should have completed six cases with FORS. “We are really trying to see exactly where it fits in and how to maximise its use, and maximise the benefits to patients.” FORS is expected to be rolled out to a total of five US centres as part of clinical trials, in addition to the same number in Europe. Shortly before FORS’ debut in the USA, during the Charing Cross (CX) 2021 Digital Edition (19–22 April, online), Gustavo Oderich, professor and chief of Vascular and Endovascular Surgery at the University of Texas’ McGovern Medical School in Houston, USA,

emphasised its potential, suggesting that “radiation will be a thing of the past” thanks to this new technology. “I have always had a really strong interest in imaging,” Schanzer comments. “I believe the imaging side of what we do is just as important as the device side. This is certainly the biggest leap forward that I have seen in my career with regards to the imaging.” Ultimately, the technology is at the start of its journey, he adds. “Currently, we have only used it in complex aortic procedures, but I very much see us broadening the applicability in all types of vascular cases.

topic of radiation, Oderich stated that FORS “addresses a major area of need, which is the ability to look at the anatomy on any view we want without being radiated”, highlighting that the technology offers both an ease of technical success and parallel reduction of radiation. Following Schermerhorn’s presentation, a Philips’ Meet the Experts session offered a deep dive into FORS technology, with a panel of users and experts discussing latest clinical experience and three-dimensional (3D) catheter agnostic guidance. Discussants were Tilo Kölbel (German Aortic Center and the University Heart Center, Hamburg, Germany), Geert Schurink (Maastricht University, Maastricht, The Netherlands), Joost van Herwaarden (UMC Utrecht, Utrecht, The Netherlands), and Schanzer, speaking a week ahead of when the system was installed at his institution. The first person to ever use the FORS technology both on a model and in humans, van Herwaarden offered his insights during the CX Digital Edition. “For the first time, it is possible to see your catheters and wires in 3D. When I was using this in models, my first thought was ‘We need to have this in patients’. It took many years, but we started using it in patients in 2018. We now only use one wire and two catheters; getting used to that one wire and two catheters has been a pleasure.” Clockwise from top left: Roger Greenhalgh (London, UK); Bijan Modarai (London, UK); Gustavo Oderich (Houston, USA); Marc Schermerhorn (Boston, USA); Konstantinos Spanos (Larissa, Greece); and Enrico Rinaldi (Milan, Italy).

“This is a first-generation technology, and I think there is still room for improvement as we expand the devices, the catheters, and the wires that are enabled with this technology. I think that is going to happen very quickly. This proof of concept we have already seen in a few cases that have been done around the world really shows the enormous value that this technology holds.” Oderich was speaking in his capacity as moderator during a livestreamed session where expert panellists deliberated crucial controversies in the abdominal aortic space, and his remarks were made in response to a presentation from Marc

I think it is going to change the way we look at all vascular interventions.” Schermerhorn (Havard Medical School, Boston, USA). Schermerhorn echoed Schanzers’ sentiments, calling the FORS technology “disruptive”. In an ensuing panel discussion on the

Kölbel, as the second user of the FORS system in humans, spoke next, commenting on its use in complex endovascular aneurysm repair (EVAR) cases. “It has almost been a year [since we first used this system in humans], but I also still remember my first experience with using FORS in a bench-top model and in an animal model some years ago. It was a mind-blowing experience. I had heard about it, and seen images, but really getting your catheter and wire displayed in 3D and colour was an almost-to-good-to-be-true feeling. It worked very well, and today we use this as a standard, almost, in complex aortic repair and fenestrated and branched abdominal cases. It is a significant change, not only for the operator. The whole team is, I think, excited about the introduction of the colour TV in the hybrid room. Maybe Gustavo [Oderich] is going to be proven right in a few years—in the same way no one notices colour TV anymore, as it is so normal, maybe FORS will become the ‘new normal’ in a few years.” Schurink added: “We started [using the FORS system] at the end of 2020. We have now performed about 25 cases using the technology—it is a completely new experience. It is not only about reducing radiation, but also the virtual biplane [which allows users to see two views simultaneously] is one of the top features of this system. It is very important, and offers a different way of looking at the patient.” Andres Schanzer

Video is revolutionising medical education Stay in touch with the vascular community, especially in these difficult times. The Vascular News in-house video production team can expertly help achieve and support your year-round digital education and video needs. Our team can remotely record and produce short, shareable video projects to emphasise the core messages from new research and developments in the field. We also conduct live and on-demand digital education projects and webinars on topics trending in the vascular and endovascular world. A snapshot of your latest research delivered straight into the heart of the vascular community Vascular News can offer a full distribution service to the vascular community on our website and social media platforms. Digital education as it should be We capture the latest news, views and practice trends from all the major global conferences in the vascular space. We work with physicians and industry partners. Can we help you realise your dream video project? Email: anthony@bibamedical.com

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AORTIC

PERIPHERAL

VENOUS

Issue 90 | July 2021

Aortic dissection 17

AORTIC

Female aortic dissection patients present later, have higher mortality Women who experience acute aortic dissection are older, have more advanced disease than men when they seek medical care, and are also more likely to die, according to research published online in The Annals of Thoracic Surgery.

“D

ata over the course of the last few decades demonstrate differences in both presentation and outcomes between men and women who have acute aortic dissection, with greater mortality among women,” said Thomas G Gleason (Brigham and Women’s Hospital, Boston, USA). “This study underscores the need for further interrogatories into these sex differences that may help provoke refined sex-directed strategies to further improve outcomes.” Lauren Huckaby (University of Pittsburgh, Pennsylvania, USA), alongside Gleason and colleagues, queried the Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) to explore sex-specific differences in presentation, operative approach, and outcomes in patients with type A acute aortic dissection (TAAD). IRAD is the largest consortium of centres worldwide (55 institutions in 12 countries) that collects and analyses data related to the clinical aspects of aortic dissection; the IVC was initiated to provide more detailed insight into surgical techniques and procedures for aortic dissection. The Stanford classification divides aortic dissections into two groups (A and B), depending on the location of the tear in the aorta. In type A dissection, the tear begins in the ascending aorta and frequently extends from the upper to lower sections of the aorta, compromising blood flow throughout the body. Type A aortic dissections have a high likelihood of migrating toward the heart, where they become deadly by rupturing into the pericardial sac that surrounds the heart. As many as 40% of people with aortic dissections die instantly, and the risk of death increases approximately 1% for every hour that the diagnosis and surgical repair are delayed, according to multisociety clinical practice guidelines. Within the IRAD-IVC database, the researchers identified 2,823 patients who experienced TAAD from 1996‒2018 and underwent operative repair or a surgical approach as part of a hybrid repair. Approximately 34% of the patients were women. Although less frequently affected by TAAD, female patients were significantly older than male patients (65.4 years vs. 58.6 years on average) and had different presenting symptoms, like hypotension and greater evidence of malperfusion, with a higher prevalence of shock (31.3% vs. 22.2%) and coma/altered

consciousness (11.5% vs. 7.5%). Benjamin A Youdelman (Maimonides Medical Center, New York, USA), who was not directly involved in the research, explained that these variances in clinical presentation indicate that women may be waiting longer to seek medical care compared to men. This may be due to female patients being “stoic,” not considering their symptoms as signs of a significant problem, and not prioritising their care, he said. “The result is presenting for medical care later, with a greater percentage of women in shock and mental status changes that are often attributed to a stroke, which can further delay the correct diagnosis of an aortic dissection as the cause,” said Youdelman, who works closely with the aortic disease awareness campaign—Think Aorta US. “All of this results in worse early outcomes after aortic dissection for women compared to men. It has been known for a long time that outcomes after aortic dissection are dependent on time to treatment: the faster a person is treated the better.” The researchers also found differences in imaging: female patients were more likely to experience intramural haematoma (19.4% vs. 13.2%), and complete (17.2% vs. 10.2%) or partial (24.8% vs. 19.4%) false lumen thrombosis. “The recognition that women present differently and later in the course suggests that they may be seeking emergency care in a more delayed fashion than men,” said Gleason. “Accordingly, clinicians should respond to these sometimes opaque signs and symptoms by considering aortic dissection early. These findings at presentation should raise suspicion among physicians into the possibility of aortic dissection, giving rise to immediate diagnosis to allow for more efficient surgical management. We should be hyper-vigilant in women to avoid any further delays in treatment.” The researchers noted that operative approaches were distinct between the sexes, with women being less likely than men to undergo aortic valve replacement, aortic root replacement, and/ or complete arch replacement. In fact, the less frequent use of complete arch replacement in female patients (15.2% vs. 20.6%) was highlighted by the researchers because worse outcomes after the operation historically have been demonstrated. They deduced that this more aggressive approach may be avoided in the treatment of older, female patients due to concerns for worse outcomes.

This study underscores the need for further interrogatories into these sex differences that may help provoke refined sex-directed strategies to further improve outcomes.”

Thomas G Gleason

Overall, women had increased mortality, although in the last few years, mortality between the sexes was comparable, which suggests recent improvements in care. According to Gleason, better recognition, earlier diagnosis, faster and more efficient care delivery, new and improved surgical techniques, and subsequent longitudinal surveillance have all contributed to more lives being saved. Youdelman explained that family medical history is also a critically-important factor for identifying patients at risk and saving lives. “Once this information is shared with the healthcare team, an evaluation by computed tomography (CT) scan to achieve definitive diagnosis and rapid treatment would result. Patients should start conversations with their families; it may save a life,” he said. Further study by the researchers is expected in order to better understand what is driving the development of acute aortic syndromes in each sex, as well as more accurately determine dissection risk and inform individualised treatment decisions.

40% As many as 40% of people with aortic dissections die instantly.

1% And the risk of death increases approximately 1% for every hour that diagnosis and surgical repair are delayed, according to multisociety clinical practice guidelines

July 2021 | Issue 90

20 Interview

Profile

Ali AbuRahma

“There is no doubt in my mind that working together rather than competing against each other will not only be for in best interests but also provide better patient care,” Ali AbuRahma tells Vascular News, contemplating his goal of encouraging multi-speciality involvement in vascular surgery when he assumes the role of Society for Vascular Surgery (SVS) president next year. AbuRahma details various aspects of his career so far, covering his early interest in cardiac surgery through to his involvement in the recently-published SVS guidelines on extracranial cerebrovascular disease management. Based on 40 years of experience, he also offers advice to younger surgeons in the field, encouraging an openmindedness towards new, evidence-based therapies and skills.

What led you to pursue a career in vascular surgery?

After I finished high school and began thinking of my future career, I was very interested in either becoming a maths teacher or engineer, since maths was always my top subject during school. However, my uncle, who was the principal of the school at that time, advised me differently, emphasising the fact that I came from a family that was not well-to-do financially, and he suggested I would not be able to survive and take care of the family being a maths teacher or even an engineer. He convinced me to go to medical school. During my medical school years in Alexandria, I was very impressed with the work of cardiac surgeons. However, I was also negatively impacted by the unsatisfactory outcomes after many of the cardiac surgeries I witnessed during those early years of my career. When I moved to the USA, I worked with a chair who was a cardiovascular surgeon during my surgical residency. He suggested I try vascular surgery because it would give me the career I wanted and had commonality with cardiac surgery. That is what eventually led me to pursue a career in vascular surgery, which I do not regret.

Who have been your professional mentors and what have they taught you?

For my technical skills in vascular surgery, I would give the credit to the late Edward Diethrich of the Arizona Heart Institute, who was a very gifted surgeon. For my clinical judgment and growth in my early career, I give the credit to the late James Boland, chair of surgery at West Virginia University at the Charleston campus for over 40 years. For my academic career and advances, I would give the credit to the late John Bergan and Bob Rutherford for encouraging an interest in academia. I looked to them as mentors and I tried to follow their footsteps in my early career. Also, I received a great deal of guidance and support from Frank Veith over the past 30 years.

How do you anticipate the field of vascular surgery might change in the next decade, and what developments would you most like to see realised? With endovascular intervention constituting a major portion of the vascular practice of many young vascular surgeons and a significant portion of senior vascular surgeons, endovascular intervention will continue to be a major part of our practice. Over the past decade, with the introduction of branched/fenestrated endovascular grafting for the treatment of complicated suprarenal and thoracoabdominal aortic aneurysms and aortic dissection, I can see endovascular therapy replacing a significant bulk of open surgery in this area.

What are the biggest challenges currently facing vascular surgery?

I believe the drive for endovascular intervention by some specialists from other disciplines such as interventional

radiology and interventional cardiology—who might not be qualified to do these procedures because of a lack of basic training during their fellowship or residency—will have an impact on the speciality and in particular on the quality of care for vascular patients. I would like to emphasise that this topic is of personal interest to me, to the degree that my assignment for the upcoming Crawford Session at the SVS Vascular Annual Meeting (VAM) 2021, which is assigned to the presidentelect, will be dedicated to “The role of multispecialty practice in vascular/endovascular surgery: can we work together?” I am hoping that we will encourage all specialists who have an interest in vascular/endovascular intervention to be trained and to dedicate at least one or two years to endovascular intervention so that we can do a better job for our vascular patients. There is no doubt in my mind that working together rather than competing against each other will not only be for in best interests but also provide better patient care.

What are your current areas of research? We just completed the Society for Vascular Surgery clinical practice guidelines for management of extracranial cerebrovascular disease and the Society for Vascular Surgery implementation document for management of extracranial cerebrovascular disease, which will update the reader and clinician on the most important items for caring of patients with cerebrovascular disease. These documents cumulated the hard work of 11 writing group members of the SVS

I want to achieve a common goal of encouraging all specialists who have a special interest in vascular/ endovascular intervention to work together in order to provide the best care possible for our vascular patients.” who were selected based on their interest, expertise, and publications in this field. I feel extremely proud of finishing this product just this past month. Both of these documents appeared recently on the Journal for Vascular Surgery website.

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

The Journal of Vascular Surgery Editor’s Choice paper “Endovascular interventions for claudication do not meet minimum standards for the Society for Vascular

Surgery efficacy guidelines” caught my attention this year. It is a very interesting article by Jonathan Bath (University of Missouri, Columbia, USA) et al that examines the outcomes of endovascular therapy of intermittent claudication in the Vascular Quality Initiative (VQI) and compares them with the SVS guidelines for treatment of intermittent claudication to determine whether real-world results are within the guidelines. They concluded that most patients who underwent endovascular therapy did not meet the SVS guidelines for long-term freedom from recurrent symptoms >50% at two years and several lacked preprocedure optimisation of medical management. They suggested that vascular specialists should be aware of the association between multivessel interventions and atherectomy with poorer long-term outcomes and counsel patients prior to intervention, even when risk factor modification is optimised prior to peripheral vascular intervention.

Issue 90 | July 2021

Interview 21

What do you hope to achieve as president of the SVS?

I want to achieve a common goal of encouraging all specialists who have a special interest in vascular/ endovascular intervention to work together in order to provide the best care possible for our vascular patients. I also want to make sure that each specialty involved in vascular surgery has the necessary training and qualifications in order to provide endovascular interventional care.

What advice would you give to someone starting their career in vascular surgery?

Vascular surgery is an evolving specialty, so be open minded towards new therapies and new endovascular skills. However, avoid jumping too quickly to these new technologies until you feel not only comfortable with them, but also find there is strong evidence for these advances. I would also recommend the younger generation to surround themselves with good mentors in order to mature and harness their skills, since you will always learn new things even after your residency.

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

During my first week of practice in vascular surgery, one of my senior colleagues felt I should handle a case that was referred to him for a patient with pararenal aortic aneurysm with bilateral renal artery stenosis. I was thrilled to take on this challenging case in my early career and in the first two hours of the procedure things were going very smoothly. However, when I took out the suprarenal aortic clamp the whole aorta broke apart. Whether that was secondary to the clamp or because I did not pick a good segment to clamp with less calcification, or a combination of both, I was not really sure. However, we lost so much blood and after moving the clamp into a higher location at least a couple of times, we still had a difficult time controlling the aortic disruption. A procedure that should have only taken a few hours ended up taking close to 10 hours and due to several complications the patient was in the intensive care unit for almost two weeks. At one stage, I did not think he would make it. However, he eventually improved and was discharged after a long hospitalisation. That case shook the heck out of me and made me question whether I picked the right specialty.

alisonlang.com

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

I greatly enjoy the travelling opportunities that my work allows. Over the past 10 years or so, travelling for work has become even more enjoyable as it has allowed me to spend extra time with my wife, since our children are now grown up and she is not worried about leaving them at home alone. Believe it or not, I also enjoy going to visit Disney World with my younger son, who is presently a resident at the University of Florida.

Fact file Current academic appointments

2012–present: Director, 0–5 Integrated Vascular Surgery Residency Program, Charleston Area Medical Center/West Virginia University, Charleston, USA 2009–present: Director, Vascular Surgery Fellowship Programme, Charleston Area Medical Center/West Virginia University 1991–present: Professor (tenure) and chief of vascular surgery, West Virginia University

1991–present: Director of surgery research, West Virginia University 1978–present: Medical Director, Vascular Laboratory, Charleston Area Medical Center

Current hospital appointments

2002–present: Co-director, Vascular Center of Excellence, Charleston Area Medical Center 1987–present: Chief of vascular surgery, Charleston Area Medical Center

Honours and awards (selected) 2020 American Heart Association Heart of Gold Award 2016 Society for Vascular Surgery (SVS) Presidential Citation Award, in recognition of dedicated service to SVS Foundation as Chair of the SVS Foundation Development Committee

July 2021 | Issue 90

22 Carotid artery stenosis

CAROTID

TCAR associated with “promising early and late outcomes”, pooled data suggest A systematic review and meta-analysis has found that transcarotid artery revascularisation (TCAR) is associated with “promising early and late outcomes” in patients with internal carotid artery stenosis, although symptomatic patients still carry a higher risk of early cerebrovascular events. This is the conclusion of George C Galyfos (Hippocration Hospital, Athens, Greece) and colleagues, whose work was published as an Editor’s Choice paper in the European Journal of Vascular and Endovascular Surgery (EJVES). THE AUTHORS STATE THAT either carotid endarterectomy (CEA) or transfemoral carotid stenting (tfCAS) are usually recommended for the treatment of significant carotid stenosis. However, they note that both techniques have certain limitations. “Open surgery is associated with higher surgical stress, and could be the cause of the higher cardiac risk compared with stenting,” they elaborate, while tfCAS, on the other hand, carries the risk of intraoperative embolisation and chronic renal insufficiency, among others. “[TCAR] offers an alternative strategy in patients where CEA or transfemoral stenting face difficulties,” Galyfos et al write. This review aimed to evaluate pooled data on patients undergoing TCAR and—in contrast to other similar reviews— evaluates both early and late outcomes as well as the effect of

preoperative symptoms on early stroke/ transient ischaemic attack (TIA), the authors detail. The investigators searched the Medline, Embase, Scopus, and Cochrane Library databases for eligible studies. For a study to be included in the review, it had to have been published online by September 2020 and to have reported 30-day mortality and stroke/TIA rates in patients undergoing TCAR. Data were pooled in a random effects model and the weight of effect for each study was also reported. Writing in EJVES, the authors relay that they included eighteen studies in their analysis, comprising a total of 4,852 patients or 4,867 procedures. In terms of the quality of the included studies, the research team specify that eight were of a high standard, with seven meeting the criteria for a medium-quality study, and

the remaining three a low-quality study. Galyfos and colleagues report that the pooled 30-day mortality rate was 0.7% (n=32; 95% confidence interval [CI], 0.5–1), the 30-day stroke rate 1.4% (n=62; 95% CI, 1–1.7), and the 30day stroke/TIA rate 2% (n=92; 95% CI, 1.4–2.7). They add that pooled technical success was 97.6% (95% CI, 95.9–98.8). In terms of other outcomes, the investigators communicate that the cranial nerve injury rate was 1.2% (n=14; 95% CI, 0.7–1.9) while the early myocardial infarction rate was 0.4% (n=16; 95% CI, 0.2–0.6). The haematoma/bleeding rate was 3.4% (n=135; 95% CI, 1.7–5.8), they convey, noting that one-third of these cases needing drainage or intervention. They also reveal that, within a follow-up for three to 40 months, the restenosis rate was 4% (n=64/530; 95% CI, 0.1–13.1) and death/stroke rate 4.5% (n=184/3,742; 95% CI, 1.8–8.4). Considering symptomatic patients specifically, Galyfos et al found that this subgroup had a higher risk of early stroke/TIA than asymptomatic patients (2.5% vs. 1.2%; odds ratio, 1.99; 95% CI, 1.01–3.92); p=0.046). The authors acknowledge some limitations of this review, including the retrospective nature of the majority of included studies—despite most being of medium to high quality—almost threequarters of the patients originating from the Vascular Quality Initiative (VQI), and

Added benefit of carotid revascularisation to modern medical care “needs to be revisited”, study concludes A pooled meta-analysis found that patients with symptomatic carotid stenosis enrolled in recent randomised controlled trials (RCTs) had a lower risk of stroke after randomisation than historical controls. According to authors Urs Fisch (University of Basel, Basel, Switzerland) and colleagues, their findings add to the current evidence that the risk of stroke associated with symptomatic carotid stenosis has decreased over time, potentially attributable to improved medical care and risk factor control.

“T

he added benefit of carotid revascularisation to modern medical care needs to be revisited in ongoing and future studies”, the authors write in a European Journal of Vascular and Endovascular Surgery (EJVES) Editor’s Choice paper. Until then, however, they urge that the data “should not deflect from current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment”. “Improvements in medical therapy over time may have lowered the risk of stroke in patients with symptomatic carotid stenosis”, write Fisch et al, who claim that the present study addressed this question by the first comparison of individual patient data from two historical series of large RCTs with very similar inclusion criteria. The authors detail that current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical

trials performed at a time when best medical therapy was “potentially less effective than today”. Therefore, they assessed the risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent RCTs and in medical arms of earlier RCTs. Fisch and colleagues compared the pooled data of

Improvements in medical therapy over time may have lowered the risk of stroke in patients with symptomatic carotid stenosis.”

there being insufficient data to conduct certain subgroup analyses, such as for diabetic patients. Galyfos and colleagues conclude that TCAR is a “promising method” for treating internal carotid artery disease as it is associated with a low rate of early death, stroke, and other complications. However, they stress that symptomatic patients have a higher risk of early cerebrovascular events when this technique is used. In closing, the authors consider the direction of future research: “Prospectively-designed studies comparing outcomes between TCAR and CEA in symptomatic patients are needed to further evaluate the benefit of this technique”.

Prospectivelydesigned studies comparing outcomes between TCAR and CEA in symptomatic patients are needed to further evaluate the benefit of this technique.”

individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA versus medical therapy. They note that the primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. The investigators included a total of 4,754 patients from recent trials and 1,227 from earlier trials. In recent trials, they relay in EJVES, patients were randomised a median of 18 days (interquartile range [IQR], 7–50) after the qualifying event. They report that 23 suffered a stroke while waiting for revascularisation (cumulative 120-day risk, 1.97%; 95% confidence interval [CI], 0.75–3.17) and that 61 patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk, 5%; 95% CI, 3.8–6.2). In addition, they communicate that stroke risk was lower in recent trials than in earlier trials when adjusted for time between qualifying event and randomisation, age, severity of qualifying event, and degree of carotid stenosis (hazard ratio, 0.47; 95% CI, 0.25–0.88; p=0.019). The authors acknowledge some limitations of their study, including the fact that the number of strokes in recent trials was low, which limited statistical power, and that the populations “may have differed in factors that were not accounted for”. Fisch et al stress, however, that the overarching strength of their analysis is the inclusion of data at individual patient level from two series of clinical trials with very similar inclusion criteria.

Issue 90 | July 2021

Carotid artery stenosis 23

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July 2020 | Issue 38 Thrombectomy proved efficacious in Latin America Page 10

Richard P Klucznik:

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COVID-19 causes | Issue 37 April 2020 “widespread disruption” to neuroendovascular Profile research around the globe

he study, recently published in the Journal of NeuroInterventional Surgery (JNIS), focused on randomised controlled trials (RCTs) and singlearm studies for acute ischaemic stroke and cerebral aneurysms. The survey was developed by a group of September subsequently sent to senior neurointerventionalists, 2020 Issue sites identified through the clinical |trials website, 39 study sponsors, and physician investigators. “The survey was sent to 101 institutions, with 65 responding,” state Rai et al, as they added that stroke RCTs were (prior to the pandemic) being conducted at Overall rate Trends after Page 10 www.neu Thomas 40 sites, aneurysm RCTs at 22 sites, stroke single-arm of in-hospital ronews.c Oxley unruptured om Endovascular mortality studies at 37 sites, and aneurysm single-arm studies at decreased aneurysm brain-computer 43 sites. “Widespread disruption of neuroendovascular trials occurred because of COVID-19,” Profile: treatment interfaces Meyers However, following COVID-19, the authors report conclude the investigators of a survey-based study examining the impact of the pandemic. Philip M Jens Fiehler Wang: page 7 that enrolment was suspended at 51 (78%) sites; Now, as sites begin to resume clinical research, first author Ansaar T Rai of West Virginia 0.9% Arthur 0.2% and Culture shifts 2006 completely at 21, and partially at 30. Moreover, missed University, Rockefeller Neuroscience Institute (Morgantown, USA), and colleagues amid 2016 York in medicin New throughout the USA call for steps4to mitigate similar challenges that may arise in the future. trial-related clinics, imaging follow-ups and protocol e Page COVID-19 page 14 deviations were reported by 27, 24, and 27 sites, brought respectively. Negative reimbursements were reported at 2 April cerebrova and (SNIS) on scular 17 sites. nal Surgery from Italy, China, chronic kidney accident, peripheral to terventio The majority of sites, Rai and colleagues note, were vascular disease, disease, , and how of NeuroIn neurosurgeons observed or between races.no significant difference forced to put new trials on hold. The team found that physician the Society and endovascular whether to intubate by each as ic’s s were “With respect hosted nalists many study coordinators (63%) worked from home, and who to treat, to presenting 9 were raised, A webinar of the pandem symptoms s such as COVID-1 neurointerventio SARS-Co , we found 31% reported a personal financial impact. While remote they known question V-2 together setting of no difference asymptom prior, had Important pathways in the atic consent was possible for some studies at 34 sites, only in exposure two weeks the USA. or vomiting, cases, fever, cough, history, post-care have done five sites reported that remote consent presented a dyspnea, nausea chills, malaise, optimise what they would American or lethargy. d cohort had option for all studies underway. The African disclose Twoviable a similar mean Institutes new studies effects. of Health the presente 51 sites with suspended trials, NIHSS [National devastating annualRegarding Stroke Scale] compared meeting d at with score the endovascular treatment without enrolment 14.9 in other (4–7 August) Society of of 16.3 related racial to-CT time races (p=0.63). NeuroIn , which was occurred at 61% of sites for stroke,was and dispariti The doorthe proportion also similar (23 vs. es among held virtuallyterventional Surgery 45% of sites for aneurysms. Rai and the 19 minutes), patients of patients (SNIS) 17th occlusion who experien this year, have and he first study presenting was not significant team found that this resulted in a total with describe from ce a large the strokes. 47%),” he North American d outcom Neurovasc vessel ly different added. of 277 patients with acute ischaemic ular e(40.7% versus COVID-1 Lastly, while presented (NAN-C) stroke, and a9 further 184Consortiu patients with terms of good by Adam the team observed University Dmytriw African American discharge m, score (Boston, USA), of Harvard modified Rankin cerebral aneurysms being treated (p=0.27). finds Ansaar patients receivedthat 14.8% of patients with compared specificall For mRS Scale (mRS) blind trial difference y examined to 31% in cord intravenou without consideration for stroke Rai COVID-1 that mortality 9. He told noted (14.8% 0–2, there was no other races, ised, double- oop spinal for not significant s tPA the online significant Dmytriw vs. 16.7%),” A random closed-l Continued on page 2 reported. However, ly different audience with COVID-1rates in African American he Addressin ally superior ed in this sample. said it was symptoma haemorrha ECAP-controlled g stroke patients tic intracrania races combined9 were significant compar ge (sICH) (SCS) statistic the preliminar the SNIS audience, l was significant higher for he reiterated in North Americaly higher than all stimulation nt of chronic pain,12-months, y data suggest participati African ly other that difference ng. among the vs. 3%, p<0.001), Americans (11.1% the treatmeop stimulation. At reached amongst stroke there may be a mortality hospitals the mortality Additionally, he said and American patients of the study patients rate of COVID-1 to open-lo backgroun African showed that significantly higher mortality was was greater d and closed-loop d afflicted in African Speculatin than previously 9–positive stroke compared >83% of responder threshol responder with COVID-1 American g on reasons COVID-1 to other patients reported in high s 9 or stroke 9. as “Underlyi 28.6%, p=0.03). races (51.9% vs. patients relief the ≥50% reliable storm,” Staats tells NeuroNews. the ≥80% and leg pain. alone.experienced ng biological to why, he said: with from The investigato patient , genetic, characteri back >56% reached tightness and dyspnea within five In terms of comorbidi As VNS has been demonstrated analysed or epigenetic stics can predispose patients positive rs chest in overall the North 69 cases of difference ties, Dmytriw threshold these results at Society’s for SARS-Co acute stroke He alsostated that diabetes minutes of using the stimulation. to block production of cytokines [people] to s,” but added Americanin n ing V-2, in health was patients including such as access that social , significant Present Neuromodulatio and observed an improved ability to clear hishigher in African sepsis in animal modelsincluding and in many 27 African 42 patients determina ly to healthcare American (23–26 January t Caucasian difference versus others othernVNS American , and geographi nts cases when heofused to manage his other medical conditions (including backgroun , lungs meeting Hispanic s pertaining presented (37% vs. 66.7%). Deer, presiden ds, However, and Asian. to 14 major and other to both population cal (NANS) annual PTSD, Sjogrens disease, rheumatoid location-b hospitals inat home. “All patients from regarding USA), Timothy Nerve Center 14 March–14 symptoms ased factors smoking, the USA and dependenceatrial fibrillation contributo Las Vegas, The Spine and USA, April“Avoidance arthritis, and stroke), Staats and his may also Canada, 14, 2020,” of ventilator “Regardin ry. of , prior be ton, g stroke functional stated anticoagul and CEO Dmytriw. in both cases and lack of hospitalisation team hypothesised that nVNS might , Charles difference ation, coronary Moving forward, of the best outcomes, between are “some of the Virginias the team, there wasattributedartery disease, congestive in case 2 cannot be causally provide clinical benefits in patients with African is co-led by American no that these our field and any heart failure, Ambooj Tiwariwhich and argued other races to nVNS, but its is reasonable to respiratory symptoms, such as those An article accepted withininto the journal Neuromodulation has New York of in hyperlipid hypertension, University results seen speculate that nVNS therapy may have exhibited in the novel coronavirus. concluded that, based on two case reports, non-invasive vagus emia, today”. (New York, USA) ion publicat aims to continue ECAP been a supporting factor, via either The information on the two case nerve stimulation (nVNS) might provide clinical benefits in patients Adam Dmytriw recruitmen the median t of found that mechanisms”. bronchodilation or inhibition of cytokine reports was obtained via email with COVID-19ALSO via “multiple ) amplitude across North more hospitals THE STUDY America, action potentials the in-clinic release,” argue Staats and colleagues. correspondence and phone interviews and compound n fell below clinic. Yet (evoked Continued They add, given the concerns about with the patients. known as a WHILE MOST COVID-19 stimulatiocases of the reaction—otherwise on page 2 outside with open-loop level storm”. were number of intensive care unit beds and According to the authors, in case “cytokine are mild, the authors, Peter Staats patients d the target target when maintaine that ventilators amid the pandemic, that it 1, the patient used nVNS to aid “While the search for an antiviral, or ged (electroCore, Basking Ridge, USA) and p group acknowled the closed-loo almosteffective for SARS-CoV-2, station of is “imperative to consider all viable his recovery at home after hospital a vaccine colleagues acknowledge that,aDeer minority . Moreover these afferent c range was of activation that receive closedinputs therapeutic options”. Thus, they put discharge, and was subsequently able the virus causing COVID-19, remains of patients develop to severe in the therapeuti large vessel with spentmoderate sensory informatio (neurons different— g, but so is the time evoked significant lar has yet to the mostwe also need to put resources forward that “the well-established safety to discontinue use Bilatera of opioids and cough a priority, respiratory symptoms, which tly they say devastatin is and significan n), endovascu nd be targeted it OVID l L4 dorsal vs. 47.9%), andsix J Mocco, motor responses phase 1 and phase for this purpose. Hence, Soloukey suppressant medications. the root effort to solving this cytokine appeardouble—a to be due to a hyperimmune Continued on page 16 shownIntocase 2, n (95.2% ai Health was an times 2 stroke,” declared with an MRC Mount-Sin evoke strong ganglion (DRG) and colleagues loop stimulatio cord activation level upper leg to determine eon from upper leg need an ≥4 for all those receiving muscles,” stimulat set out and reprodu neurosurg whether DRG report frequent spinalcohort, compared to This led to “Stroke patients can facilitate injury (SCI).in patients with chronic cible motor ion has been stimulatio s carried out a knee extensionthe authors. this York, USA. clinically spinal greater in In their paper strong enough responses relevant motor n many procedure motor completresponses in System, New movemen added, Sadaf Solouke behind this . in motor complete the t Arguing that semi-elective, he publishe mechanics open-loop weight bearing,to facilitate assisted case … But and or d in Neurom e spinal cord advocate.” Five patients The Netherla y and colleagu would indicate SCI. g about the to do that life work, are elective were implanted said: “This Speculatin quality of the team reportedthey added. Moreover DRG leads it is reasonable aneurysms or unruptured in hospitals and staying data, Deer to demons nds, refer to theires from Erasmus odulation, authors of them. placed bilaterally with is yes, then activation cases. You a lot of improving is not one that no significant , the ECAPs, issue. After MC, trate unruptured of cord study those difference Stroke timeL4 Rotterda the “There is for five days. reproducible as the “first wait. potential on level s in RMS to be doing the activation , is an important benign tumours, system’s of this highly for s that can Based values were tissue to us that of its kind” m, observed stimulatio procedure taking care ere is no reasonfrom your healthcare this particula and potentially of the DRG as a the neural between days of activation n protocols, on personalised to advocate AVM—th g the minority new weight-b in the zone quite knowing r cohort the study, say we . We need one and five the team aimed evoke dynamic subtractin We are in earing muscletarget for which indicated of patients population years of not the first time we can of are actually to (phase 1) to a lot of nearly 50 responses is . (phase recruitment sensitive patient and handle things.” Hospital, Beijing, THE TEAM SCS, this were reproducib that motor “This leads ability to ency Levitt, University in bilateral2) motor responses in isotonic IN ROTTER response to ECAPs.” He added: that do of Xuanwu Delving into le. , Michael non-emerg . For them.” write that the on the subject.” quadricep Tao Hong “For places agreement rationale behind current strategies DAM that in Beijing, s muscles. are activating for future research research, suspended one and five, Though in of afferent USA) asserted, equipment [PPE], recovery after designed to On days their Soloukey for motor s have been which, according China, confirmed (=sensory EMG-mea n (Seattle, et al state SCI aim to more discussion that the study was is “one of protective ) input mean square surements ge, nal procedure spinal cord Washingto Aspects motor performan that SCI n and do facilitate the team (root interventio right personal [RMS] values) using epidural to the 15 oid haemorrha Deer explained and minimise bias. fever, the to the human most devastating” injuries ce through on page muscle force stimulatio subarachn not have the time to go off the reservatio practice.” and clinical electrical Continued modulatio present with the patient’s central nervous n (EES). However, cases like measurem the of typical n preserve objectivity of it can lead commonly scoring) were ents (MRC DRG itself now is not the scope system, as the results while the to a multitude ndemic areas, treat. to Hong, now represents digital used to measure are outside including responses of problems, Hospital awaitsbefore performing the first relay things that y to COVID-e who to motor loss and their at Xuanwu g. test in terms of muscle atrophy,of autonomic control, Alluding specificall “In all patients, reproducibility. 9 screening and embolisin on page 2 continuum COVID COVID-1 hy (DSA) spasticity there is a the risk of DRG-stim Continued and motor and sensory Levitt said n angiograp is: What is ulation impairmen of leaving subtractio I look at it ts. According ? Is the risk “The way the risk to the population greater than answer Continued infection in two weeks the on page If for ? 18 alone the population something infection for of COVID

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Researchers propose optimisation of duplex velocity criteria for diagnosing ICA stenosis Writing in an online Vascular Medicine article, researchers from the Intersocietal Accreditation Commission (IAC) Vascular Testing division report findings from a multicentre study of duplex ultrasound for diagnosis of internal carotid artery (ICA) stenosis. THE STUDY WAS DEVELOPED in response to wide variability in the diagnostic criteria used to classify severity of ICA stenosis across vascular laboratories nationwide and following a survey of members of IAC-accredited facilities supporting efforts toward standardisation. The primary objective of the study was to evaluate the widely-used SRU Consensus Criteria (SRUCC) and,

if needed, to propose further optimisation to these criteria. Researchers found that carotid duplex interpretation using SRUCC produced significant overestimation of stenosis for both moderate (50–69%) and severe (>70%) ICA lesions as determined by catheter angiography. The authors conclude that laboratories currently using SRUCC should consider modification of existing criteria to incorporate more stringent and accurate parameters for ICA stenosis greater than 50% by increasing the peak systolic velocity (PSV) threshold to >180cm/sec or requiring the ICA/CCA PSV ratio >2 in addition to PSV of >125cm/sec. “This study reflects more than six years of work of a team of IAC staff and multispecialty volunteers with case study materials collected from 11 centres [in the USA]. While the SRUCC are broadly used, they had never been formally compared to the gold standard

of catheter angiography. We have shown that use of SRUCC overestimated degree of ICA stenosis and identify potential opportunities for modifications that can ultimately enable greater accuracy and consistency in ICA interpretation across vascular laboratories,” said lead investigator, Heather L Gornik (University Hospitals Harrington Heart and Vascular Institute, Cleveland, USA), IAC Vascular Testing Immediate pastpresident. “Through its use of real-world data from IAC-accredited vascular laboratories, this paper highlights the opportunity to improve the quality of care for patients with carotid disease,” said Tatjana Rundek (University of Miami Miller School of Medicine, Miami, USA), IAC Vascular Testing president. “By modifying existing criteria to incorporate more accurate parameters and implementing these criteria broadly, the accuracy of diagnostic ultrasound

Through its use of real-world data from IAC [Intersocietal Accreditation Commission]accredited vascular laboratories, this paper highlights the opportunity to improve the quality of care for patients with carotid disease”

testing can be improved across our vascular community.” As a next step, IAC Vascular Testing will disseminate a white paper document summarising the study results and providing guidance to vascular laboratories for implementation of criteria and further steps toward standardisation across the vascular testing community.

Heather Gornik

High-flow fistulas remain divisive, with uncertainty over reduction and outcomes

July 2021 | Issue 90

by Valenti on certain instances of acute death after abrupt fistula ligation, Rotmans also theorised that a medical device capable of closing a functional fistula gradually—over the course of one or several days, for example—may be useful in offsetting these potential risks. The ultimately contentious debate that followed this saw Gibbs argue in favour of reducing high flow first. His argument centred around the notion that “there is already evidence out there that high-flow Discussions at this year’s Charing Cross AVFs are bad for our patients, and we do not need (CX) Digital Edition (19–22 April, online) large, randomised trials to prove it”, and he cited indicated that high-flow arteriovenous multiple reports indicating that banding or revision fistulas (AVFs) remain one of the more using distal inflow (RUDI) procedures to reduce flow divisive topics in the field of vascular in AVFs can improve heart failure symptoms. Gibbs access. went on to argue that the absence of randomised controlled trials (RCTs) assessing the link between n the debate, the audience heard that high-flow high-flow fistulas and cardiovascular complications fistulas can lead to major cardiac consequences should not detract from other evidence that the two and existing evidence demonstrates the are causally linked, pointing to the fact that there prevalence of heart disease in renal patients, which have been no RCTs to investigate the commonlybegs the question: should flow be reduced in known, health-related consequences of smoking asymptomatic high-flow fistulas, or in transplant either. recipients, to prevent cardiac complications? In his counter argument, Shenoy emphasised many Renal and transplant surgeon Paul Gibbs (Queen of the lines that have been drawn between high flow Alexandra Hospital, Portsmouth, UK) argued in and cardiac symptoms to date are merely examples favour of the statement that “We should reduce flow of association, rather than direct correlation or in high-flow fistulas (>1,500ml)”. These points—and causation. He further claimed that existing studies the debate motion more generally—were contested indicating a trend between the two have either failed by transplant surgeon Surendra Shenoy (Washington to properly compare dialysis patients with an AVF to University School of Medicine, St Louis, USA), who regular, non-AVF dialysis patients, or have included argued against the need for routine flow reduction in many patients with underlying risks or prior history asymptomatic patients. of cardiovascular conditions like congestive heart The hour-long session on high flow in access failure (CHF). Shenoy concluded his presentation controversies, moderated by CX Executive Board by stating that, based on the currently-available data, members Nicholas Inston (Queen Elizabeth Hospital “there is no role for routine flow reduction” in AVFs Birmingham, Birmingham, UK) and Domenico with a flow greater than 1,500ml per minute—but Valenti (King’s College London, London, UK), that closer monitoring and early intervention in these began with a presentation from interventional patients may be an optimal, alternative strategy. nephrologist Theodore Saad (Christiana Care The precedent for this being a particularly Health System, Newark, USA). Saad introduced challenging, equivocal debate was set almost the audience to many of the existing challenges immediately by Inston following Gibbs’ and surrounding high-flow fistulas—including the fact Shenoy’s presentations, as he conceded that he was that they often go “under the radar” “still undecided” on the need due to complacency following to reduce high flow. Gibbs Clockwise from top left: Sophie Renton (London, UK), Nicholas Inston (Birmingham, UK), added to this by stating that fistula creation, as well as a lack of Domenico Valenti (London, UK), Surendra Shenoy (St Louis, USA), clear standards and uncertainties “we may be looking for the Paul Gibbs (Portsmouth, UK), and Joris Rotmans (Leiden, The Netherlands). over which specialists should be impossible study” when it responsible for them. comes to resolving the issue, Saad also alluded to the connection between outcomes, such as pulse oximetry or pain, may be although he also asserted that high-flow fistulas are high-flow fistulas and cardiovascular problems, the most appropriate comparator in future studies to “unnecessary”, and claimed: “If I had a fistula, I and suggested that a more defined algorithm for assess newer technologies for reducing high flow, would want it running as low as possible in order to managing and reducing flow in these structures is a statement that drew a strong endorsement from look after my heart long-term”. necessary—something he claimed he is currently Valenti. Rotmans, who had stated earlier that he feels working to develop. Inston concurred with many of Nephrologist Joris Rotmans (Leiden University “we should act far more aggressively than we Saad’s points, asserting that “the majority of renal Medical Center, Leiden, The Netherlands) followed currently are” to reduce high flow, argued that patients die from cardiovascular causes” and “we this discussion with a presentation on the “chronic preventative interventions similar to those used to should perhaps be designing some patient-related increase” an already-vulnerable patient’s cardiac treat cardiovascular disease should be deployed to outcomes that measure this more effectively”, as output goes through as a result of vascular access reduce the fistula’s “obvious detrimental effects”. well as asking about a point raised by vascular and creation for haemodialysis. This provided a fitting Shenoy countered this by reiterating his point that renal transplant surgeon David Kingsmore (NHS precursor to the CX debate on the question of many regular haemodialysis patients experience Greater Glasgow and Clyde, Glasgow, UK) that a reducing flow in high-flow fistulas, as Rotmans similar cardiac symptoms to those who undergo racing heart could be seen to be driving the fistula, stated that while AVFs and AV grafts alike can AVF creation and, as such, there is “no direct proof” rather than the other way around. Saad agreed on increase the risk of left ventricular hypertrophy linking them. both counts, but did also respond to Kingsmore’s (LVH) and pulmonary hypertension, “the negative In the discussion, Gibbs and Shenoy did agree on suggestion that the heart itself may be driving the effects of an AVF on the heart can be reversed by an the need to treat patients with high-flow fistulas who fistula in these patients, stating that the two are AVF ligation”. are presenting with symptoms, but remained split “obviously interrelated” and separating them is not He also concluded that it is currently unclear on asymptomatic cases—as did the audience in easy. whether cardiac events and related mortality attendance, with 50% voting for the motion, and 50% Subsequently, vascular and endovascular surgeon can be prevented through a greater emphasis on voting against, in a poll conducted at the end of the Robert Shahverdyan (Asklepios Klinik Barmbek, treating high-flow fistulas, but, when questioned session.

Hamburg, Germany) presented his initial clinical experience using the Frame FR external stent (Vascular Graft Solutions). He described the device as an external banding tool used to support the vein at the anastomosis, adding that—having used the stent for high-flow AVF repair in 43 patients— he believes it offers an additional, feasible, and effective treatment for aneurysm and flow reduction. Responding to a query from Valenti on the high number of cases with aneurysmal AVF in his patient cohort, which was 40 (93%), Shahverdyan stated: “How many patients actually get a follow-up to see if their fistula is high-flow or not? In the group I presented, four were kidney transplant patients and the rest were on active dialysis, and these patients come to ask if they can abandon their fistula. I would usually recommend reducing the flow instead of abandonment though. I know it is a controversial discussion over whether you should keep it or ligate it in kidney transplant patients—but I would reduce the flow and keep it in case the kidney transplant fails in the future”. When asked by Inston what they considered to be the current “gold standard” for flow reduction procedures, Shahverdyan and fellow vascular surgeon Gaspar Mestres (Hospital Clínic de Barcelona, Barcelona, Spain)—who presented his views on the relationship between high-flow fistulas and steal syndrome during the session— both conceded they were unsure that one even exists right now. Following this, Saad brought the discussion to a close by suggesting that patient-led

August 2021 Issue 01

www.renalinterventions.net

Discrimination and harassment are a common experience among those working in cardiology According to the findings from a global survey carried out by the American College of Cardiology (ACC), which have been published in the Journal of the American College of Cardiology ( JACC). Responses suggest that as many as 44% of cardiologists report experiencing a hostile work environment (HWE) including being subject to emotional or sexual harassment, or discrimination. Authors concluded that a renewed focus on organisational structure, processes, and practices to mitigate these problems in cardiology across the globe is critical to ensuring workforce wellbeing and optimal patient care. The report is the culmination of a 50-item online survey conducted by the ACC in September to October 2019, reaching 5,931 cardiologists in Africa, Asia, the Caribbean, Europe, the Middle East, Oceana, and North,

Central, and South America. Questions covered demographic information, practice environment, academic rank, discrimination, and harassment, with a particular focus placed on the professional and personal challenges of cardiologists. Author Garima Sharma ( Johns Hopkins School of Medicine, Baltimore, USA) noted that the incidences of HWE were more commonly reported among female (68%), Black (53%) and North American (54%) respondents. Gender was the most frequent cause of discrimination (44%), the study found, followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). Of the participants 77% were

Balloon angioplasty in critical time window central to endovascular success for the slowto-mature AV fistula Discrimination and harassment are a common experience among those working in cardiology, according to the findings from a global survey carried out by the American College of Cardiology (ACC), which have been published in the Journal of the American College of Cardiology ( JACC). Responses suggest that as many as 44% of cardiologists report experiencing a hostile work environment (HWE) including being subject to emotional or sexual harassment, or discrimination.

uthors concluded that a renewed focus on organisational structure, processes, and practices to mitigate these problems in cardiology across the globe is critical to ensuring workforce wellbeing and optimal patient care. The report is the culmination of a 50-item online survey conducted by the ACC in September to October 2019, reaching 5,931 cardiologists in Africa, Asia, the Caribbean, Europe, the Middle East, Oceana, and North, Central, and South America. Questions covered demographic information, practice environment, academic rank, discrimination, and harassment, with a particular focus placed on the professional and personal challenges of cardiologists. Author Garima Sharma ( Johns Hopkins School of Medicine, Baltimore, USA) noted that the incidences of HWE were more commonly reported among female (68%), Black (53%) and North American (54%) respondents. Gender was the most frequent cause of discrimination (44%), the study found, followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). Of the participants 77% were men (n=4,584), and 23% (n=1,347) were women. Survey participants predominantly identified as white (54%), followed by Asian (17%), Hispanic

(17%), and Black (3%); and 73% were ≤54 years of age. Most were married (75%); 12% were single, 7% were living with a partner, 3% were divorced, and 1% were separated. Cardiologists from the European Union represented the largest group of respondents (32%), followed by respondents from South America (18%), the Middle East, Eastern Europe and Asia (all 9%), Africa (8%), North America (7%), Central America (6%), and Oceana (2%). According to Sharma, the survey results indicate that . The report is the culmination of a 50-item online survey conducted by the ACC in September to October 2019, reaching 5,931 cardiologists in Africa, Asia, the Caribbean, Europe, the Middle East, Oceana, and North, Central, and South America. Questions covered demographic information, practice environment, academic rank, discrimination, and harassment, with a particular focus placed on the professional and personal challenges of cardiologists. Author Garima Sharma ( Johns Hopkins School of Medicine, Baltimore, USA) noted that the incidences of HWE were more commonly reported among female (68%), Black (53%) and North American (54%) respondents. Gender was the most frequent cause of discrimination (44%), the study found, followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). Of the participants 77% were men (n=4,584), and 23% (n=1,347) were women. Survey participants predominantly identified as white (54%), followed by Asian (17%), Hispanic (17%), and Black (3%); and 73% were ≤54 years of age. Most were married (75%); 12% were single, 7% were living with a partner, 3% were divorced, and 1% were separated. Cardiologists from the European Union represented the largest group of respondents (32%), followed by respondents from South America (18%), the Middle East, Eastern Europe and Asia (all 9%), Africa (8%), North America (7%), Central America (6%), and Oceana (2%). According to Sharma, the survey results indicate that The

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Wearable device for AV fistula remote monitoring shows promise—but faces commercial challenges A new wearable device designed to remotely monitor arteriovenous fistulas (AVFs) function in dialysis access patients uncovered promising data leading one set of researchers to conclude the technology offers hope for improved care and lower costs among a challenging patient population.

he SmartPatch monitoring system (Alio Medical)—which involves the extraction of real-time data through a series of sensors from a patch placed over an AVF, subsequent cloudbased machine learning, and then actionable clinical alerts—is currently undergoing testing in a series of pilot studies aimed at tackling the healthcare burden of kidney failure and vascular access failure. The first analysed dataset demonstrated the device “has the ability to measure haemoglobin, volumetric flow, and haemodynamically significant stenosis in AV fistulas,” Richard F Neville (Inova Heart and Vascular Institute, Falls Church, USA) revealed during the Society for Clinical Vascular Surgery (SCVS) annual meeting (13–17 March, Miami, USA). Neville and colleagues looked at 128 patients at three dialysis centres, with all study participants wearing a SmartPatch device over an AVF either in the upper or lower arm. “In this particular study, we utilised state-of-theart optical technology with a particular patented array that allows for better data acquisition,” explained Neville, who disclosed that he serves on the scientific board of Alio Medical. The intention of the study was to evaluate the ability of such a device to monitor AVF function, degree of stenosis, flow rate and the physiologic parameter of haemoglobin levels as a marker that impacts fluid management. All participants wore a SmartPatch for a week. Each of the three clinical centres involved focused on one of the three metrics. The location focused on haemoglobin analysis studied 57 patients, the facility looking at volumetric flow looked at 21, and the centre monitoring percentage stenosis evaluated 71 study participants. For each metric, Neville said, machine training algorithms were developed using the first 116 data streams from the device sensors. The algorithms were subsequently tested and correlated on the next 157 data streams, correlating with haemoglobin standard measurement, transonic flowmeters, and the standard fistulagram, he added. The resulting data, Neville et al found, showed that haemoglobin was measured with comparative accuracy “and only a standard deviation of 0.41 as compared to haemoglobin measurement using standard techniques.” The SmartPatch detected low volumetric flow—a potential indicator for access failure—with 100% sensitivity and 75% specificity, Neville continued. “Additionally, the degree of stenosis was also

July 2021 | Issue 90

detected, looking at haemodynamically significant stenosis of great than 50%, with 100% sensitivity and 100% sensitivity as compared to subsequent fistulagrams, and arteriographic and angiographic imaging.” He commented: “Therefore, we concluded in this study that this initial dataset shows us that this remote wearable monitoring system has the ability to measure haemoglobin, volumetric flow, and haemodynamically significant stenosis in AVFs. We are also hopeful that this remote monitoring system will allow us—and shows promise to allow us—to improve the care and lower the costs associated with other healthcare factors associated with this patient population.” Co-moderating the SCVS session in which Neville delivered his team’s findings, Jean Bismuth (Houston Methodist, Houston, USA) queried how placement of the patch might impact on the reliability of the data collected. Neville explained that Alio had “spent a lot of time” on the material involved in the patch to ensure it is not injurious to skin, and that it can be used and worn for extended periods of time, among other considerations. Meanwhile, W Charles Sternbergh (Ochsner Health, New Orleans, USA) who was co-moderating alongside Bismuth, questioned the path towards commercialisation of the technology. Among Medicare patients, Sternbergh said, “evaluation of how their fistula is doing is baked in” to evaluation and management (E/M) services conducted at dialysis centres. “Typically, it is not allowed to have prophylactic testing, and it would even be suggested

This remote wearable monitoring system has the ability to measure haemoglobin, volumetric flow, and haemodynamically significant stenosis in AV fistulas.”

SmartPatch

that that is fraudulent, as some freestanding centres that do fistulagrams every three months no matter what have found out.” Sternbergh asked: “How might this device intersect those issues?” Neville admitted this question got to the heart of the studied approach Alio has taken toward commercialisation. “The technology has evolved rapidly,” he said. “When we first started this project in the animal lab, there was one sensor, a photo acoustic sensor. Now there is an array of sensors, and that is why we are able to generate the variety of information that I showed you.” But, Neville continued, commercialisation remains an important step yet to be thrashed out. There are number of possibilities, he explained. One option might involve the device being given away for free, with an in-app-based subscription fee then applied for the data. Another would necessitate approaching dialysis companies with the benefits of keeping dialysis access fistulas functioning, and also keeping patients out of the emergency room, Neville said. “There were some initial cost savings shown in a dialysis population in the UK in the national health system there, where just monitoring the haemoglobin accurately allowed [doctors] to adjust erythropoietin—which is a very expensive medication—and possibly decrease it, saving money just on the medications that are used on these folks.” In the end, Neville added, he sees the device incorporated as a value-added part of care for the AV fistula patient population, as large dialysis companies realise close monitoring of access health and physiologic parameters “may actually save the overall cost of the patient in the long term.”

The monitoring system shows actionable clinical alerts

27 Issue 00 2021 July| Xxxxxxxxx 2021 | Issue 90 27

Balloon angioplasty in critical time window central to endovascular success for the slow-to-mature AV fistula Tackling the main culprit, stenosis in the arteriovenous anastomosis and outflow veins, with balloon angioplasty before it is “too late” can boost maturation rates in slow-tomature arteriovenous (AV) fistulas. Robert Jones, consultant interventional radiologist at the Queen Elizabeth Hospital, Birmingham, UK, set out his endovascular treatment strategy of balloon-assisted maturation at the Vascular Access Society of the Americas 2021 Spring Virtual Conference (VASA; 21–22 May, online). AV FISTULAS CAN HAVE HIGH rates of protracted maturation with up to 60% being reported in the literature as “slow to mature”. Best efforts at “precisely and quantitatively” defining these fistulas are covered by the statement that they “do not see increase in flow and diameter to adequately support dialysis,” explained Jones.

Relatively narrow window of time for optimising interventional success

“When and how do we best pick up a slow-to-mature fistula with a view to intervention?” asked Jones, who went on to frame the “relatively narrow window” for maturation interventions with the statement: “If a fistula has not matured by four to six weeks, it is unlikely to.” This time window charts the latest Kidney Disease Outcomes Quality Initiative (KDOQI) guideline that considers it reasonable for operators to evaluate for postoperative complications within two weeks [of access creation] and an appropriate member of the vascular access team to evaluate for AV fistula maturation by four to six weeks after. Jones also touched on an importantto-recognise later presentation scenario that could prompt endovascular intervention—when

maturation failure is identified later on by unsuccessful attempts at fistula cannulation.

Up to 50% of fistulas need help to mature

Postoperative AV access maturation rates can vary; according to Jones, but approximately half of fistulas will need at least one intervention before they are functional. Stenosis is the main offender in the slow-to-mature fistula and most commonly occurs in the in the juxtaanastomotic region. Accessory sidebranch veins can also be responsible for slow maturation in 30–50% of cases and can occur in isolation or in association with stenosis, he reported. Again, referring to the KDOQI guideline that states good quality studies comparing surgical and endovascular techniques for postoperative maturation are either lacking, or have conflicting results, Jones highlighted that an individualised patient approach with a first-line endovascular approach is customary in this nearly fact-free zone. “Despite there being little highquality data that directly compares maturation rates achieved using endovascular interventions against those achieved with surgery, balloon assisted maturation takes centrestage,

and I often consider using a brachial artery access using a micro-puncture kit to get a diagnostic fistulogram as a roadmap in the first instance at the time of intervention,” he said.

deep vasculature, use coils [to obliterate],” he said, illustrating with case examples that repeat interventions are often required to keep the circuit patent. “There is evidence indicating Robert Jones that repeated sequential angioplasty produces a good The road to balloon-assisted result, and this is often required to maturation achieve continuity in outflow from the Jones recommended an endovascular artery to the vein and a fairly uniform plan to treat maturation failure that vessel that will go on to mature.” begins with a physical exam to locate Complications can occur, and the type and level of the lesion. This include haematoma, extravasation is followed by an ultrasound exam to from rupture, and thrombosis. These confirm these findings; exclude any are most commonly seen in forearm thrombosis; and assess the depth of the fistulas according to the literature, fistula. “Ultrasound can also identify cautioned Jones. accessory veins,” clarified Jones. A Primary patency outcomes of fistulogram and intervention complete endovascular maturation are reported the pathway. “This [fistulogram] to be slightly inferior to those allows us to create a definitive achieved with surgery, as determined roadmap and anatomical assessment by Jan Tordoir and colleagues in a to map out where the stenosis and systematic review published in the accessory veins are, and the relevant European Journal of Vascular and lesion is then treated,” he said. Endovascular Surgery (EJVES) in Jones urged VASA attendees to 2018. The review also reported clinical consider the whole access circuit success rates with endovascular with the reminder that stenoses in the maturation procedures (angioplasty arterial circuit can occur proximally and vein obliteration) in the range of and so could need additional cross43–97%. sectional imaging in a small number Jones pressed home the importance of cases, especially when a peripheral of secondary patency in fistula lesion cannot be identified using intervention and the benefit that the standard assessment. minimally invasive balloon-assisted “I tend to start with an 0.018” maturation strategy conveys with balloon platform, then move to a rates reported to be 68–96% in the high-pressure balloon if necessary. systematic review. If unsuccessful, I move to a cutting “In summary, balloon-assisted balloon,” Jones stated. maturation can increase the number With regard to the management of functional fistulas: get in there of branch veins, Jones suggested early with a three-step management adopting a “watch and wait” approach involving the physical strategy to see how the fistula fares exam, ultrasound and then, finally, after balloon maturation. “Or, you intervention. Remember to consider could compress the branch vein the whole access circuit and you are under ultrasound to determine its looking to treat stenosis and accessory significance. If on compression of veins,” Jones stated. the branch vein there is improved Jones told Vascular News that more palpable thrill over the fistula itself, data is required in this area, and that the branch vein should ideally be it would be particularly interesting to occluded in the same episode. If it is determine the value of drug-coated superficial, consider suture ligation balloons (DCBs) in treating immature (or coiling), but if it is located in the fistulas.

BD gains FDA 510(k) clearance for Pristine long-term haemodialysis catheter

BD recently revealed that the company has received 510(k) clearance from the US Food and Drug Administration (FDA) for its Pristine long-term haemodialysis catheter—a new haemodialysis catheter with a unique side hole-free symmetric Y-tip distal lumen design.

he Pristine catheter, originally developed by Israeli firm Pristine Access Technologies, has been available in the USA from May 2021. Michael Tal (Assuta Hospital, Tel Aviv, Israel), inventor of the Pristine catheter, said: “A majority of haemodialysis patients in the USA start their treatment with a catheter and many of those

catheter-dependent patients will suffer a catheterrelated complication at some point during treatment, which can adversely impact the patient, and create additional healthcare system costs.” “The Pristine catheter was designed with haemodialysis patients in mind, and to help address some of these concerns.”

According to BD, haemodialysis catheters are often challenged by complications, as certain catheter tip designs can lead to positional occlusion, high recirculation rates and thrombus formation. These complications can potentially lead to reduced catheter patency and decreased catheter performance—but BD claims its Pristine catheter device is designed to help address these challenges. In a press release, the company added that the Pristine catheter’s side hole-free tip is designed to help minimise the thrombus adhesion that can be associated with side-hole catheters, as well as helping to facilitate blood clot aspiration prior to haemodialysis treatment. The symmetric tip is also designed to help minimise recirculation rates in both forward and reverse.

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July 2021 | Issue 90

30 Interview

VENOUS

Comprehensive, patientfriendly risk assessment “crucial” to VTE prevention From the first research linking heparin to a reduction in fatal pulmonary embolism (PE), to the development and refinement of risk assessment tools to lower the risk of thrombosis, Joseph Caprini (University of Chicago Pritzker School of Medicine, Chicago, USA) traces the development of thrombosis research. Caprini—who has dedicated his career to the understanding of venous thromboembolism (VTE)—outlines important milestones, addresses key unanswered questions, and considers the latest findings regarding COVID-19 and VTE.

What are the key milestones in thrombosis research to date?

One of the first important milestones can be dated to 1975, when The Lancet published a multicentre study by Vijay Kakkar and colleagues demonstrating that little doses of heparin given to surgical patients did not increase their bleeding, but caused a 66% reduction in fatal PE. A lot of people criticised that trial but, in 1988, Oxford scholar Rory Collins published 70 additional trials conducted around the world using the same protocol and produced exactly the same results. At this point, there were 15-year data on 20,000 surgical patients in 98 centres around the world showing that small doses of unfractionated heparin produced a 66% reduction in fatal PE, with no change in bleeding. In my opinion, to get a death from a prophylactic dose of anticoagulation, except in the case of an unusual type of allergic reaction, is a rarity. However, to have that prophylactic dose prevent a fatal PE is a reality, and that is the key. In 2005, Kakkar’s son, Ajay Kakkar, produced an excellent article with Sylvia Haas, a brilliant investigator from Germany. They wanted to show that their new drug, low molecular weight heparin (LMWH), was better than unfractionated heparin. Therefore, they constructed a trial with 23,000 surgical patients and decided that the endpoint should be autopsy-adjudicated fatal PE—the hardest endpoint you could get. Kakkar and Haas reported that the incidence of death in 23,000 patients was one-tenth of a percent, whether they got LMWH or unfractionated heparin, showing that the appropriate anticoagulation can prevent nearly all fatal blood clots. In 2012, the Chest guidelines were published, showing that LMWH was better than unfractionated heparin based on the results of 51 trials. The main point of all of this is that, of the 4,000 Kakkar patients in 1975, the 13,000 more patients assessed by Collins in 1988, the 23,000 more patients in 2005, and the 40,000 patients collected from the 51 trials in 2012, the period of prophylaxis was seven to 10 days, which is as important now as it ever was.

How has the world of VTE prevention developed?

A big improvement in VTE prevention came with the move from unfractionated heparin to LMWH, which is a much more specific, much smaller molecule of which 90% of the drug goes to clotting proteins, compared to just 50% with unfractionated heparin. Another key development was the introduction of direct oral anticoagulants (DOACs), which have revolutionised care. In fact, they are so good they do not need to be monitored under most circumstances. A lot of us who had been in the field for years were used to a culture of measuring, and so questioned how this could be safer. The answer was really very simple,

but it took a while to come out, and was that DOACs have a short half-life. Despite the fact that you do not measure them, they go away quickly, and so bleeding deaths were actually lower with these new drugs. In addition, it was finally recognised that you have to conduct a preoperative patient risk assessment. The community now understands that when you have surgery, it is not just the surgical procedure that is an issue, it is also the baggage you bring to the hospital with you, the risk assessment. In the beginning, the

Joseph Caprini

I want to emphasise that there are many roads to Rome in determining VTE risk, and what we have learned is to use your favourite tool in order to lower the risk of thrombosis.” guidelines talked about protecting patients according to type of surgery. The trials were organised according to type of surgery, and so it was very logical that the guidelines said the answer to thrombosis is related to the type of surgery. By 2012, the guidelines acknowledged the presence of risk and they put out two risk assessments: the Roger score and the Caprini score. While the Caprini score has my name on it, the only reason the score is there is due to a dedicated group of individuals. Everybody put their piece into the puzzle and came out with 40 risk factors of varying weights. This changed everything in the surgical world.

What are the latest findings regarding COVID-19 and VTE, and what should be the focus of future research in this area? There have been some interesting developments so far, one of the most significant being that full-

dose anticoagulation, instead of prophylactic anticoagulation, has been shown in a large, multinational trial to improve a patient’s results regarding their need for organ transplants, incidence of deep venous thrombosis (DVT), and death, but that is only in moderate-risk patients. In severe-risk patients in the intensive care unit (ICU), full-dose anticoagulation does not improve results. It has become clear that anticoagulation alone is not the answer in COVID-19 patients. I think the problem is that ‘clotters’ look at the clotting system, inflammatory doctors at their system, and immunologists at their system, but that is not how the body works. The body is a series of intricate pieces and it is only when they are put together that you get the whole puzzle, and that is where future research needs to go with COVID-19. Another thing that is missing is risk assessment. Alex Spyropoulos (Northwell Health and Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell, New York, USA) has taken the lead here, and has a brand-new publication showing that, by using a risk assessment tool, you can pick out the risk factors in those patients that are very high risk.

What are some of the key unanswered questions in the field of VTE prevention as a whole?

I think one of the key questions has to do with how we collect crucial patient data. What we have learned is that if you come into the hospital short of breath with a severe COVID-19 illness, if you are in a motor accident, or you have a stroke, nobody is going to find out if your aunt had a fatal PE, even though that may be a very important factor in determining your treatment. Therefore, you have got to collect the data ahead of time. One of the initiatives I am involved in is creating a patient-friendly, validated form. We are finding that patients want to be involved in their own medical care, and if you can get them to sit down with their family, they can put together a good picture of their medical history. I had the good fortune to be involved with the Global Thrombosis Forum, which is dedicated to including young people from around the world in projects involving thrombosis. We assigned two high school students to go to their schools with the Caprini score to give to their friends at school to take home to their families. In one month, we got 1,500 responses and the number one finding was that there was a 20% incidence of family history of thrombosis. The critics would say this is biased because the families were trying to help the students with their school work, but who cares? We are finding out really important data, and this is crucial to developing patient care. Research also needs to focus on adding risk factors to the current score, including sleep apnoea, diabetes requiring insulin, body mass index (BMI) of over 40, operations over three and four hours, AIDS, and COVID-19. I think that artificial intelligence and machine-learning tools will have a part to play here, and I envision eventually a universal forum where all of that data with all of the risk factors are there. Finally, we need to address the fact that there are still a lot of PE deaths. PE may be down, but death rates have not gone down. There are only two scores that I know of that track family history of thrombosis, and I do not know why because family history of thrombosis itself is very important, but one of those, besides the Caprini score, is the British National Health Tool in the UK, which is mandatory, and over a two-year period actually lowered the death rate. These are very powerful data. I want to emphasise that there are many roads to Rome in determining VTE risk, and what we have learned is to use your favourite tool in order to lower the risk of thrombosis. That, I think, is important.

Issue 90 | July 2021

COVID-19 and VTE 33

VENOUS

Further research will soon generate standardised approach to VTE in COVID-19 patients At VENOUS2021 (17–20 March, virtual), the annual meeting of the American Venous Forum, Geno Merli (Thomas Jefferson University Hospital, Philadelphia, USA) gave a keynote lecture on venous thromboembolism (VTE) in COVID-19 patients, detailing an “acute and extended” risk in this clinically vulnerable group.

roviding an overview of initial research into VTE and COVID-19, Merli first referenced a paper by Dawei Wang (Zhongnan Hospital of Wuhan University, Wuhan, China) and colleagues published in February 2020 in the Journal of the American Medical Association that looks at 138 hospitalised patients with COVID-19 and focuses on factors that determine prognosis. “If we look at the D-dimer levels in survivors and non-survivors, we can see that days after the onset of the disease, the higher the D-dimer level, the poorer the survival in this patient population,” he relayed to the VENOUS2021 audience. Wang et al’s paper also highlights that, as creatinine elevates, mortality increases in both survivors and nonsurvivors, Merli reported, commenting that D-dimer and creatinine levels are two factors that “all of us have experienced” in the management of COVID-19 patients. Also, in February 2020, the Journal of Thrombosis and Haemostasis published research by Ning Tang (Huazhong University of Science and Technology, Wuhan, China) and colleagues looking at elevated D-dimers and fibrin degradation products in 183 consecutive patients. Merli summarised that both factors were associated with an increased mortality in this patient group. Merli highlighted another paper, published the following month in The Lancet, in which Fei Zhou (Peking Union Medical College, Beijing, China) et al look again at D-dimer, but also at IL-6, lactate dehydrogenase, and high-sensitivity troponins, in 191 patients. The presenter conveyed Zhou and colleagues’ main conclusion: “The non-survivors who had high levels of these four areas had a poor outcome with respect to mortality.” Delving into the coagulopathy features of patients with COVID-19, Merli noted that Tang and colleagues look at the D-dimer levels and also the sepsis-induced coagulopathy (SIC) score in their paper. “If the SIC score was greater than four,” Merli explained, “the heparin users had a 40% 28-day morality versus 64% in the non-users, and if you looked at D-dimer levels above a six-fold upper limit of normal, the results were 32% mortality in the patients getting heparin versus 52% in the non-heparin users”. He remarked: “This does not tell you how to treat the patient, it just tells you [D-dimer and SIC scores] are predicting mortality.”

Key meta-analyses provide crucial data on acute and post-discharge populations

Turning the audience’s attention to meta-analyses, Merli referenced the work of David Jiménez (Hospital Ramon y Cajal, Madrid, Spain) et al, published in March 2021 in Chest, addressing the bleeding incidence in patients with COVID-19. The investigators reviewed the data of 18,000 patients assessed in 47 studies, noting a 17% incidence of VTE, he relayed. “If you break it down into DVT [deep

venous thrombosis] and PE [pulmonary embolism],” the presenter elaborated, “you can see a DVT rate of 21% compared to 7% for PE”. Major bleeding, “which we are most concerned about,” he added, was 3.9%. Merli noted that Jiménez also broke the results down further into setting, with the data showing that the intensive care unit (ICU) incidence of VTE was 27.9%, compared to an incidence on the ward of 7%. Merli cited another meta-analysis by Rui Zhang (Peking Union Medical College, Beijing, China) et al, published in March 2021 in the Journal of Vascular Surgery: Venous and Lymphatic Disorders. This study also looked at the prevalence of VTE, specifically in 13 studies in the ICU and five, non-ICU. Zhang and colleagues report a 31% incidence of VTE prevalence in the ICU population versus 7%. “When you break it down by setting, ICU and non-ICU,” Merli explained, “what you see is that the incidence of PE was 17% and 4% respectively, clearly showing that ICU obviously is a high-risk area and the patients are much sicker.” He added that the corresponding rates for DVT were 25% vs. 7%. Finally, Merli outlined the findings of a registry by Gregory Piazza (Harvard Medical School, Boston, USA) et al, published in November 2020 in the Journal of the American College of Cardiology. “What I like about this registry is the fact that every single one of the events is adjudicated, and so we know these events actually happen,” he remarked. Piazza and colleagues report that, in the symptomatic VTE group, the figures were 27% ICU and 2.2% non-ICU— numbers that Merli remarked look “pretty similar” to Zhang’s and Jiménez’s papers. The presenter also detailed research into the post-discharge patient population. He cited in particular a study by Richard Salisbury (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) et al published in Blood Advances in December 2020. In this retrospective analysis, Salisbury looked at the rate of symptomatic VTE in 152 patients discharged without any indication for anticoagulation. At 42 days post discharge, the rate was 2.6%. “If you look more closely at Salisbury’s paper,” Merli noted, “at patients that were intubated, patients on noninvasive ventilation, and then patients on just oxygen alone, the data clearly show that patients who had been ventilated had a lower survival rate than those patients that were not.”

greater than 25,000 are looked at based upon their creatinine clearance, which we have established is an important factor in predicting outcome”. He specified that if a patient’s creatinine clearance is greater than 30ccs, they are prescribed intermittent pneumatic compression plus enoxaparin, noting that enoxaparin is dosed based upon the kilogram weight of the patient. “If a patient’s creatinine clearance is impaired,” Merli continued, “the team use unfractionated heparin, also dosing this based upon the weight of the patient”. The presenter noted that, in patients who have a platelet count of less than 25,000, pneumatic compression sleeves without pharmacologic prophylaxis are used. “We decided to increase prophylaxis based upon the renal function and also the weight of the patient,” the presenter informed the VENOUS2021 audience. He noted that the team added rivaroxaban as part of their management of this patient population once they are transferred to the wards. Risk stratification is crucial to the approach at Jefferson Health System, Merli conveyed. In the patients going home, he specified that the team needed to risk-stratify based upon the IMPROVEDD VTE risk score and the IMPROVE bleeding risk score. “We thought this was very important because we know that the symptomatic incidence is low,” he remarked, “and therefore we had better select the right patient population.” A patient with a high VTE risk but low bleeding risk, as well as a creatinine clearance of greater than 30ccs, will receive enoxaparin to take at home, he described. On the other hand, if a patient’s liver function tests are normal, the team then use 10mg of rivaroxaban once daily for the post-discharge management of this patient. Finally, Merli detailed that patients at high risk of both VTE and bleeding need to have knee-high compression stockings.

Concluding his lecture, Merli outlined the recommendations of various organisations, including the American College of Chest physicians (ACCP), the International Society on Thrombosis and Haemostasis (ISTH), the National Institutes of Health (NIH), the Italian Society of Thrombosis and Haemostasis, and the Anticoagulation (AC) Forum. Detailing the guidelines of the ISTH, Merli explained that the society recommends intermediate dosing of low molecular weight heparin (LMWH) in this patient population if they are on ventilation, while in non-ventilated ICU patients “[the ISTH] were not very specific”. In the ward population, Merli said that the ISTH “did not specify particularly what the best approach would be”. For high-risk patients in the post-discharge population, the society recommends 14 days of LMWH versus a DOAC. The NIH, on the other hand, recommends standard dosing “across the board”, said Merli, and suggests prophylaxis in high-risk patients. “The AC Forum said intermediate dose for the ICU patients, standard prophylaxis for the ward population, and, for patients who had prolonged illness or were in rehab, LMWH,” he added. “You can see there are a number of approaches,” Merli summarised, noting that more studies are needed in order to reach standardisation.

More studies are needed in order to reach standardisation.”

Risk stratification central to Jefferson Health System approach

Relaying his own approach and that of the wider team at the Jefferson Health System, Merli explained: “Patients who come into the ICU with a platelet count

Variations in recommendations highlight need for more data

July 2021 | Issue 90

34 Market watch

Clinical News Philips announces positive two-year data from TOBA II BTK clinical trial

Royal Philips recently announced positive two-year results from the TOBA (Tack optimised balloon angioplasty) II below-the-knee (BTK) clinical trial. The data show the Philips Tack endovascular system (4F), a first-of-its kind dissection repair device, provides a sustained treatment effect and positive impact on quality of life for peripheral arterial disease (PAD) and chronic limbthreatening ischaemia (CLTI) patients at two years. George Adams (Rex Hospital, Chapel Hill, USA), co-principal investigator, presented the findings at the 2021 New Cardiovascular Horizons (NCVH) conference (1–4 June, New Orleans, USA). Across all patients in the TOBA II BTK clinical trial at two years, 73.6% had freedom from clinically-driven target lesion revascularisation (CDTLR) and did not require a repeat procedure for the treated artery segment. CD-TLR is a commonly used indicator of treatment efficacy durability. In the more complex CLTI patient population, which is typically associated with high rates of amputation and mortality, the data showed 94.7% target limb salvage (freedom from major amputation). “The global endovascular community is diligently working to better understand how to restore blood flow in small limb vessels, promote healing and ultimately preserve limbs for people with CLTI, one of the most vulnerable and critical patient populations,” said Adams. “These positive two-year data reiterate the clinical importance of below-the-knee dissection repair and validates the sustained durability of Tack-optimised interventions.” The two-year TOBA II BTK data also show sustained improvement in patients’ quality of life. In a patient questionnaire that assesses activity, pain, and overall health, patients report having more control of their health and increased

Tack endovascular system

improvement in mobility. The Tack endovascular system is currently available for sale in the USA and some European Union countries.

One-year outcomes from PROMISE I US study of LimFlow system published

LimFlow recently announced the publication of 12-month data from the full patient cohort in its PROMISE I study of the LimFlow percutaneous deep vein arterialisation (pDVA) system in the Journal of Vascular Surgery. Results showed sustained positive outcomes for both amputation-free survival and wound healing. The minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated

LimFlow stent

blood back into the foot via the veins in chronic limb-threatening ischaemia (CLTI) patients who are facing major amputation and have exhausted all other therapeutic options. PROMISE I is a multicentre, prospective, single-arm study of the LimFlow system. It was conducted at seven US centres and enrolled 32 endstage—or “no-option”—CLTI patients, 100% of whom had non-healing wounds on the target foot, 69% of whom had diabetes, and 34% of whom had renal insufficiency. No-option CLTI is defined as being ineligible for surgical or endovascular arterial revascularisation as adjudicated by an independent committee of vascular surgeons. “The publication of the PROMISE I results in the Journal of Vascular Surgery further validates the benefits of

the LimFlow system,” said Daniel Clair, PROMISE I principal investigator and chair of the department of surgery at the University of South Carolina (USC) and Prisma Health-USC Medical Group (Columbia, USA). “The LimFlow pDVA system was effective in treating no-option CLTI resulting in a high percentage of treated patients healing their wounds and surviving free of major amputation at 12 months.” In the PROMISE I study, 70% of patients achieved amputation-free survival at 12 months following treatment with the LimFlow system, and 75% had all wounds classified as healed or healing at 12 months as adjudicated by an independent core lab. Technical success was reported at 97%. “Given the unacceptable rates of major amputations globally we are encouraged by the publication of the 12-month PROMISE I data in the prestigious Journal of Vascular Surgery,” said LimFlow CEO Dan Rose. “We are making great strides in our currently enrolling PROMISE II pivotal trial in the USA and Japan, and we look forward to advancing our mission of leaving no limb left behind.”

EuroPCR 2021: Late-breaking data demonstrate longterm benefits of Medtronic radiofrequency renal denervation in real-world hypertensive patients

Medtronic today announced new clinical data from the Global SYMPLICITY registry (GSR) indicating that renal denervation with the Medtronic Symplicity renal denervation system was associated with clinically significant and sustained blood pressure reductions in a real-world hypertensive patient population through three years. Results from the prospective, single-arm, global, observational study are being presented as a late-breaking clinical trial at EuroPCR 2021 (18–20 May, virtual). The study analysed nearly 3,000 patients with uncontrolled hypertension (HTN) and other comorbidities typical in HTN patients (chronic kidney disease, diabetes). Patients were treated with the Symplicity renal denervation system utilising the single-electrode Symplicity catheter or the Symplicity Spyral multielectrode catheter, and their outcomes were analysed up to three years post procedure. Renal denervation with the radiofrequency-based Symplicity renal denervation system is a minimallyinvasive procedure intended to regulate overactivity of nerves that lead to and from the kidney, which play an important role in blood pressure control. The GSR study results demonstrated the Symplicity renal denervation system led to significant and clinically meaningful reductions in blood pressure that were sustained out to three years post procedure. Patients experienced a mean reduction of 16.7mmHg office systolic blood pressure (OSBP) at three years compared to baseline. Investigators also evaluated the benefit of renal denervation within various patient subgroups using

a clinical composite endpoint; a retrospective analysis comprised of both OSBP, 24-hour ambulatory blood pressure (ABPM), and medication burden. They found a consistent benefit of renal denervation in patients with versus without diabetes, chronic kidney disease, or patients who were aged 65 years and above. The similar clinical composite endpoint was used in a recent EuroIntervention publication that showed patients were nearly three times more likely to benefit from renal denervation compared to remaining on a regime of anti-hypertensive medications alone.

Symplicity renal denervation system

“As we continue to expand our clinical data around renal denervation for uncontrolled hypertension management, we wanted to broaden our understanding of the long-term benefits for our patients who suffer from multiple chronic conditions and are typically prescribed multiple medications,” said Felix Mahfoud, cardiologist at Saarland University Hospital in Homburg, Germany and principal investigator in the study. “With this new analysis, we can now help patients continue to see the real-world benefits of renal denervation.” • EuroPCR: New analysis on estimated risk reduction from Symplicity renal denervation system In addition to the late-breaking clinical trial results at EuroPCR, investigators also reported a new analysis estimating the reduction in clinical events in patients treated with the Symplicity renal denervation system. The analysis used the clinical events observed at three years in the Global SYMPLICITY registry and put these in perspective with a modelled control. The results showed a 26% relative risk reduction in major cardiovascular events (MACE) over three years for the full study cohort treated with renal denervation, and a 34% reduction for patients suffering from resistant hypertension over the same timeframe. • Medtronic expands renal denervation real-world data collection with the new GSRDEFINE study Building on the success of GSR and continuing its commitment to providing real-world evidence for the Symplicity Spyral renal denervation system, Medtronic has also announced the launch of the GSR-DEFINE study. This new phase of patient data collection aims to enrol an additional 2,000 patients suffering from uncontrolled hypertension, who will be treated with the Medtronic Symplicity Spyral multi-electrode renal denervation catheter. The study will collect data for a subgroup of

Issue 90 | July 2021

Market watch 35

Clinical News patients out to five years. Approved for commercial use in more than 60 countries around the world, the Symplicity Spyral renal denervation system is limited to investigational use in the USA, Japan, and Canada.

Two-year IN.PACT AV Access results presented at CX 2021 Medtronic recently announced the safety and effectiveness results through 24 months for the IN.PACT AV Access clinical study. The data, which were presented virtually as a Podium 1st at the Charing Cross (CX) 2021 Digital Edition (19–22 April, online) demonstrated that the IN.PACT AV drug-coated balloon (DCB) is the first and only DCB to show sustained and superior effectiveness through two years compared to standard percutaneous transluminal angioplasty (PTA) in end-stage renal disease (ESRD) patients with de novo or nonstented restenotic native arteriovenous fistulae (AVF) in the upper extremity. “A patient who receives haemodialysis will often need to have several reinterventions each year to maintain patency and keep critical access sites open and functioning properly,” said Andrew

Holden (Auckland Hospital and Auckland University, Auckland, New Zealand), who presented the results at CX 2021. “Being able to show these results at two years will ultimately impact standard of care for patients undergoing dialysis. For my patients, these durable results translate into fewer reinterventions and a better quality of life.” Over two years, the IN.PACT AV DCB group demonstrated a continued clinical benefit compared to the PTA control group. Key data highlights per KaplanMeier estimates for this dataset include: • Target lesion primary patency through 24 months was 52.2% in the IN.PACT AV DCB group compared to 36.2% IN.PACT AV DCB

in the PTA control group (log-rank p<0.001). • Access circuit primary patency through 24 months was 39.5% in the IN.PACT AV DCB group compared to 25.4% in the PTA control group (log-rank p<0.001). • Freedom from all-cause mortality through 24 months was 82.4% in the IN.PACT AV DCB study group and 82.8% in the PTA control group (logrank p=0.829). • About the IN.PACT AV Access study The IN.PACT AV Access study is a prospective, global, single-blinded, randomised controlled trial, which enrolled 330 patients at 29 sites in the USA, Japan, and New Zealand. Results of the six-month pivotal IN.PACT AV Access study were presented at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting in 2019 (7–11 September, Barcelona, Spain) and also

published in The New England Journal of Medicine in August 2020.

One-year results published from B Braun’s CONSEQUENT study

One-year findings from B Braun’s CONSEQUENT ALL COMERS observational study were recently published by principal investigator Ralf Langhoff (Sankt Gertrauden Hospital, Berlin, Germany) et al online in Angiology. The data were first presented earlier this year at LINC 2021 (The Leipzig Interventional Course; 25–29 January, online). In this prospective, single-arm, multicentre observational study, the SeQuent Please over-the-wire (OTW) drug-coated balloon (DCB; B Braun) was used in above-the-knee (ATK) and below-the-knee (BTK) peripheral arterial occlusive disease. The investigators report that, despite the high prevalence of comorbidities, target lesion revascularisation (TLR) and mortality rates were comparable to clinical outcomes of other contemporary DCBs. Langhoff and colleagues detail that the overall technical success rate of the 1,269 DCBs used was 99.6% (1.6±0.79 DCBs/patient), adding that 12-month TLR rates were 6.3% in patients with chronic limb-threatening ischaemia (CLTI) and 9.6% in claudicants, with a primary patency rate of 89.9% and 87.1%, respectively. They also write that all-cause mortality was 4.3%.

Issue 90 | July 2021

Market watch 37

Product News

Jade PTA balloon catheter

Cardiovascular Systems announces US commercial launch of Jade OTW noncompliant peripheral balloon catheters

Cardiovascular Systems has announced that the full line of OrbusNeich Jade percutaneous transluminal angioplasty (PTA) over-the-wire (OTW) balloon catheters is now available in the USA. Cardiovascular Systems is the exclusive US distributor of OrbusNeich balloon products. Jade is an OTW balloon catheter for PTA in the peripheral vasculature, including obstructed native arteries and synthetic arteriovenous dialysis fistulae, as well as for post-dilatation of balloon expandable and self-expanding stents. Jade is a non-compliant balloon designed for high pressure tolerance and balloon dilatation with even pressure distribution for the treatment of complex lesions. These balloons are compatible with standard 0.014”, 0.018”, and 0.035” guidewires, and with catheter working lengths ranging from 135cm to 200cm and balloon working lengths from 20mm to 240mm. Kousta Issa Foteh (Vital Heart and Vein, Humble, USA) and Siddhartha Rao (Vascular Solutions of North Carolina, Cary, USA), were two of the first physicians in the USA to adopt the full line of Jade in their respective practices. “I was eager to add the full line of Jade PTA balloons to my practice. The predictable, uniform inflation of these non-compliant balloons allows for accuracy in balloon sizing and reduces the potential for vessel recoil,” commented Foteh. Rao added: “The deliverability of the Jade balloons, whether it be on the 0.014”, 0.018”, or 0.035” platform, is exceptional. These balloons have consistently allowed me to cross and treat challenging lesions successfully in situations where I would have previously failed with other balloons.”

Boston Scientific and BD initiate venous stent recalls Boston Scientific and BD have both initiated recalls of venous stents. According to a US Food and Drug Administration (FDA) medical

device recall notice posted 21 May, Boston Scientific has recalled its Vici venous stent system (Vici SDS) and Vici RDS venous stent system. In a recall notification dated 12 May, BD announced that the company has expanded a safety notice issued earlier this year for the Venovo venous stent system. The FDA announcement regarding the Vici stent reads that Boston Scientific initiated the recall on 12 April “after reports indicate that the stents may migrate or move from where they are initially implanted”. The FDA has labelled this a Class I recall. Outlining the risks associated with stent migration, the statement reads: “A migrated stent may require another surgery or catheter procedure to retrieve it, which increases risks to the patient, including possible damage to the blood vessel, heart walls, or other organs. If the stent migrated to the heart, it could cause life-threatening injury.” There have been 17 complaints and

Vici and Venovo venous stents

reported injuries related to this issue, the notice states, which adds that no deaths have been reported. Boston Scientific has asked customers to “immediately discontinue use of the device” and “remove all affected units from inventory and secure them”. The FDA statement urges customers with questions to contact their Boston Scientific representative. BD has expanded the scope of the urgent medical device safety notice issued on 13 January for the Venovo venous stent system to include all sizes and lots within expiry date. “BD received reports on the Venovo venous stent system indicating that the proximal end of the stent does not

immediately expand upon deployment but remains connected to the stent cushion on the delivery system,” the 12 May statement reads. It details the potential consequences: “If the proximal end of the stent does not immediately expand upon deployment, over-manipulation or forcing the catheter delivery system, as well as use of other intravascular devices or techniques to assist the stent’s expansion, could potentially have a varying degree of harm associated with it.” According to BD, potential harm includes the following: “Prolonging the procedure, damaging or deformity of the stent, potential vascular injury and/or haemodynamic disruption affecting the blood flow and/or a thrombotic event.” In cases where the stent self-expanded, the notice adds, there is no incremental risk of harm. While this issue was initially observed on the 14mm diameter product offering, there have been reported complaints across other sizes of the product offering since the initial safety notice was published. To date, BD has received approximately 250 reported complaints across various sizes of the product offering.

Medtronic provides updated patient management recommendations regarding Valiant Navion recall

Medtronic announced that it has sent physicians updated patient management recommendations related to its voluntary recall of the Valiant Navion thoracic stent graft on 17 February. The original recall notice included the recommendation for physicians to follow best clinical practice and make best efforts to evaluate patients with at least annual follow-up according to the recommendations in the instructions for use (IFU). This guidance was based on the available information at the time as well as advice from an independent panel, Medtronic notes. The company is now recommending that physicians proactively contact patients implanted with the Valiant Navion and perform computed tomography (CT) imaging with contrast every six months, or as frequently as deemed appropriate by the physician’s medical judgement. It specifies that, while CT imaging with contrast is necessary for a full evaluation of the stent graft, non-CT is recommended for patients with contraindications to Valiant Navion thoracic stent graft

contrast. Moving forward, the company is requesting that physicians provide all prospective patients follow-up images for independent core lab review. Medtronic has also provided information for patients to help them understand the updated recommendations, with direction to consult their physician regarding concerns following implant of the Valiant Navion and to discuss the best approach for their ongoing care. The updated information was sent to physicians on 21 May.

MDR comes into effect across EU

The European Union (EU) Medical Devices Regulation (MDR) took effect from 26 May 2021. The MDR revises quality and safety standards and the range of regulated devices, and was first initiated in May 2017, with an initial three-year transition period applied. Implementation was delayed by 12 months due to the COVID-19 pandemic. According to the European Commission, there are more than 500,000 types of medical devices and in vitro diagnostic medical devices (IVDs) on the EU market. These have a “fundamental role in saving lives by providing innovative healthcare solutions for the diagnosis, prevention, monitoring, prediction, prognosis, treatment, or alleviation of disease” according to information on the Commission’s website. Separate regulations governing IVDs come into effect in May 2022. According to the Commission, the new regulations create a “robust, transparent, and sustainable” regulatory framework that will improve clinical safety and create fair market access conditions for manufacturers. The new regulations maintain the current grouping of devices into four classes—Class I, IIa, IIb, and III— although certain devices are reclassified and have a wider scope. The MDR also clarifies the respective obligations of manufacturers, authorised representatives, importers and distributors, with manufacturers required to put systems in place for risk and quality management, to conduct clinical or performance evaluations, and to draw up technical documentation and keep this up to date. Further to this, the regulations also require manufacturers to implement postmarket surveillance follow-up plans.

July 2021 | Issue 90

38 Market watch

Industry News Sectoral Asset Management makes US$9 million investment into Cagent Vascular

Cagent Vascular recently announced the investment of US$9 million by Sectoral Asset Management. Along with the investment, Marc-Andre Marcotte has joined the board of directors. The proceeds will be used to accelerate the commercialisation and scaling of manufacturing for the Serranator belowthe-knee (BTK) product. Further uses of proceeds include expanding the product offering to include larger sizes to treat the above-the-knee arteries.

Serranator PTA serration balloon catheter

The Serranator percutaneous transluminal angioplasty (PTA) serration balloon catheter is an angioplasty device with serrated metal strips embedded on a semi-compliant balloon. The Serranator’s unique technology is designed to create multiple longitudinal

lines of interrupted micro-serrations within the luminal surface to aid in arterial expansion. The result is predictable and controlled lumen gain using low atmospheres of pressure. “Our BTK product launch is going extremely well,” stated CEO Carol A Burns. Early commercial adoption and clinical outcomes are confirming the positive results seen in the PRELUDEBTK study. We are delighted to have a high-quality investor like Sectoral join our team. Their deep experience investing and advising device companies focused on peripheral vascular interventions will enable a more rapid expansion of our commercial efforts.” . Marc-Andre Marcotte, of Sectoral, added: “We have been very impressed by Cagent’s achievements thus far and are excited to partner with them. We are confident that the unique features and high-quality clinical data of Serranator will drive strong market adoption.” The Serranator’s differentiated mechanism of action is driving adoption. “The BTK space is in desperate need of innovation,” explained Sarang Mangalmurti interventional cardiology

specialist at Bryn Mawr Hospital (Philadelphia, USA). “These vessels are more challenging in terms of size, lesion length, and calcification and non drug-based balloon angioplasty is still the primary treatment. My experience with Serranator has been excellent and with its novel mechanism of action it has become an important tool in treating BTK disease. In the near future, I look forward to using this technology in vessels above the knee to further optimise my angioplasty results.”

Prytime Medical closes US$6 million funding round to support commercialisation growth

Prytime Medical has announced the closing of a US$6 million inside financing round to support commercialisation of its resuscitative endovascular balloon occlusion of the aorta (REBOA) haemorrhage control products. “REBOA is different now,” said Andrew Holman, chief commercialisation officer at Prytime. “Our new Plus and Pro catheters include many new technical advancements that are enabling a surge in REBOA adoption. As a result, demand is growing strongly. Based on the strength of our core business, our new product launches, and our new focus on relentless customer support and quality clinical

outcomes, the investor community responded overwhelmingly.” The oversubscribed funding round will also support a key shift in the company’s commercial focus away from simply product familiarisation towards deep customer support and quality clinical outcomes. “Our growth is based on experience from over four years of market engagement, and 7,500 clinical uses worldwide. We see two key characteristics of successful REBOA programmes,” said David Spencer, Prytime CEO. “The first is the practice of ‘Team REBOA’, and the second is the implementation of a rigorous ‘Early Access protocol’. This funding will enable us to support our customers, not just with our extensive REBOA knowledge base, but also by sharing the experience of other REBOA users. This new focus will support strong clinical outcomes more effectively and enable enhanced peer-to-peer knowledge sharing. It is strongly resonating with the user community.” Prytime’s latest product innovations and new approach to clinical support were designed in direct response to customer feedback. “Our customers want simultaneous truncal haemorrhage control and more controlled resuscitation in a much wider range of clinical scenarios than was previously possible,” continued Spencer.

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

18–21 August SVS Vascular Annual Meeting San Diego, USA

4–7 October VIVA: Vascular InterVentional Advances Las Vegas, USA

16–20 November VEITHsymposium 2021 Orlando, USA

25–28 September Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Annual Meeting 2021 Online

5–7 October CX Aortic Vienna Hold the date

2–4 December VERVE Symposium Sydney, Australia

www.vascular.org/vam

www.cirse.org.events/cirse2021

28–29 September European Society for Vascular Surgery (ESVS) 35th Hybrid Annual Meeting Rotterdam, The Netherlands and online

www.vivaphysicians.org/future-meetings

www.cxsymposium.com/cxaortic

www.veithsymposium.org

www.vervesymposium.com

21–23 October Paris Vascular Insights Paris, France

www.parisvascularinsights.com

www.esvs.org/events/35th-annual-meeting-2021

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2019 | Issue

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