Vascular News 80 – November 2018

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Societies’ expert consensus document highlights aortic arch treatment needs An expert consensus document updating current recommendations for treatments of aortic arch pathologies has pointed to a range of unmet needs in this area of cardiac and vascular surgery, making an effort to address them in the form of updated recommendations, terminology, and description of pathologies. Nevertheless, several unmet needs remain and a conclusion drawn by the consensus of two European surgical societies is that treatment of aortic arch disease is an area that warrants a specialised team and centralisation of care.

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Drug-eluting stents go head-to-head in IMPERIAL trial The Eluvia drug-eluting vascular stent system (Boston Scientific) shows superior primary patency compared to the Zilver PTX drug-eluting stent (Cook Medical), concludes the 12-month follow-up of the IMPERIAL randomised controlled trial. These data were presented for the first time at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018 meeting (22–25 September, Lisbon, Portugal).

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he last decade has substantially broadened treatment options for patients with thoracic aortic pathology involving the aortic arch,” Martin Czerny (Bad Kroezingen, Germany) and colleagues write in the consensus document, published on behalf of the European Association for CardioThoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) in the societies’ respective journals: the European Journal of Cardiothoracic Surgery and the European Journal of Vascular and Endovascular Surgery.

“Traditionally,” they continue, “treatment of aortic pathology was a domain of open cardiac surgery.

The advent of combined vascular and endovascular procedures opened a new field thereby enabling treatment in previously operated on and in less fit patients.” New technologies, such as branched arch stent grafts, and expanded treatment options with selective antegrade cerebral perfusion at warmer low body circulatory arrest times, as well as improvements in monitoring of organ function, have all contributed

to “excellent results in these still major operations”, the authors write. However, they explicitly note that neurological complications “remain a major concern of all procedures addressing aortic arch pathology, irrespective if open surgery or endovascular repair.”

Reducing neurological complications from thoracic aortic procedures

The EACTS and ESVS are not the first to highlight safety concerns related to neurological outcomes of thoracic aortic procedures. The STEP (Stroke from Thoracic Endovascular Procedures) study, an independent and interdisciplinary collaboration which pooled practice data from a number of high-volume centres, aimed to improve outcomes for patients undergoing thoracic endovascular aortic repair (TEVAR). The STEP collaborators similarly sought to identify best practices for endovascular procedures in the aortic arch, with the aim of lowering risks for cerebral embolism. Their initial results were presented Continued on page 4

THE STUDY WAS also presented at the Transcatheter Cardiovascular Therapeutics conference (TCT; 21–25 September, San Diego, USA) and are accompanied by simultaneous publication in The Lancet.

The IMPERIAL trial was a prospective, randomised, single-blinded, multicentre global study aimed at comparing the effectiveness and safety of the Eluvia with Zilver PTX for treatment of symptomatic femoropopliteal artery lesions (lesion length 30–140mm, Rutherford category 2–4).

Presenting the results, Stefan Müller-Hülsbeck (Flensburg, Germany; the European primary investigator) told the CIRSE audience: “Clinical outcome rates were similar between groups, but with half the revascularisation rate for Eluvia.”

For instance, the Eluvia stent had a target lesion revascularisation rate of 4.5%, in contrast to 9% observed within the Zilver PTX cohort.

Additionally, the Eluvia stent was found to be more effective than the Zilver PTX, with a primary Continued on page 6

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Aortic arch disease

Societies’ expert consensus document highlights aortic arch treatment needs Continued from page 1

in a dedicated session at the Charing Cross Symposium (CX; 24–27 April, London, UK) earlier this year.

Czerny et al write, “The reduction of neurological complications to a minimum will be one of the major tasks of the future.” Taking several steps to address these issues, the authors developed a range of Class I recommendations based on consensus of expert opinion.

One such instance details situations of delayed spinal cord injury, in which “selective secondary insertion of a cerebrospinal fluid drainage tube as part of a treatment bundle is recommended.” Speaking to Vascular News, Czerny and co-author Jürg Schmidli (Bern, Switzerland) comment that while “previous guidelines specifically focused on open aortic repair, this expert consensus document includes all treatment options.

Therefore, the components focusing on endovascular therapy are new. Spinal cord ischaemia and its clinical consequence—paraplegia—are so devastating that this additional rescue option deserves specific attention.” In defining the current main gaps in knowledge, they point to the need for increased evidence in the prevention of perioperative stroke, and suggest future clinical research in the field should attempt to bolster available knowledge in that regard.

Standardising terminology and defining an aortic specialty

Along with an extensive set of recommendations, the consensus document outlines an updated guide to current knowledge on the natural course of aortic arch disease and its underlying pathologies, as well as a standardised index of terminology. This, Czerny et al emphasise, is in an effort to “harmonise terminology in acute and chronic proximal thoracic aortic pathology.”

One of many contributions by the authors is the introduction of a dissection classification which builds on from the Stanford types A and B, but proposes that type B refers to aortic dissection where only the descending aorta is involved, and type A the original definition involving the ascending aorta. They propose a third classification, non-A-non-B dissection, to refer to dissection with arch involvement either by the most proximal tear or by retrograde extension. This addition is important, Czerny and Schmidli tell Vascular News, “as it highlights a newly defined subgroup of patients where the awareness of their clinical course was not sufficient to date. Many of them do develop complications such as malperfusion or retrograde type A aortic dissection, and will require early treatment either by TEVAR or even by the frozen elephant trunk

approach.”

Treating such pathologies—and indeed the decision making for treatment of any aortic arch pathologies— should be done by an aortic team, the authors state.

Similar to the STEP conclusions, an interdisciplinary approach is advised in order to draw from knowledge in a set of specialties that intersect in the aortic arch.

“Cross linking between cardiac and vascular surgery has amplified knowledge,” Czerny and colleagues explain.

“Interestingly enough, although dividing cardiac and vascular surgery into separate units was popular for a time, in many institutions they are being combined again to create aortic centres, a trend which should be interpreted as a plea to work together without creating borders between specialties.

“Our hope is that, in the future, treatment portfolios will be designed by a single group of people working together to understand the natural course of the disease where physicians are doing the right things when it comes to treatment and the entire aortic team follows an anticipative strategy to remain ahead of the disease process.”

Drawing from data which show that higher caseloads improves outcomes in several other cardiovascular pathologies and their treatments, Czerny et al go on to recommend centralisation of care for aortic arch pathologies. They conclude that elective treatment in this field should be performed in specialised aortic centres, providing open and endovascular cardiac and vascular surgery on site only.

Furthermore, for TEVAR procedures involving the aortic arch in particular, a hybrid room with a fixed imaging system is strongly recommended.

Guiding the future of aortic arch treatments

The document includes a streamlined and simplified 10-point guide to choosing between an endovascular or open surgery approach to treatment. In developing this guide, Czerny and Schmidli tell Vascular News that they and their colleagues “aimed at describing frequent clinical scenarios, where not only the anatomy of the patient plays a leading role in recommending one treatment option or the other, but also accompanying conditions one is often confronted with—it is meant as a companion during decision making.” They add that “very soon, there will be a companion document available to this expert consensus document” which details eight clinical scenarios, and gives guidance on which approach should be chosen.

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Such guidelines, and indeed a significant number of Class I recommendations provided in this consensus document, currently rest on what the authors describe as Level C evidence, i.e. the consensus of expert opinion and/or small studies, retrospective studies and registries. Moving forward, the Society of Thoracic Surgeons (STS) has created a task force on aortic surgery, to address the gaps in evidence identified thus far. This includes the “data-driven development and continuous adaptation” of a dedicated clinical prediction model. This is an unmet need of particular significance, Czerny and Schmidli tell Vascular News, stating: “Outcome of several underlying pathologies and their treatment options is mirrored by an adequate preoperative risk scoring system in aortic valve disease or coronary artery disease. This is important for both clinicians and patients to anticipate, to inform and to be informed about remaining risk. This is the gap to be closed in both open and endovascular surgery. If you want to improve outcomes, you have to understand which treatment options are applied in which group of patients and how this performs in individual scenarios also according to the specific risk factors patients are affected by.”

In the consensus document, the authors acknowledge that commonly used risk assessment modalities, such as STS PROM and EuroSCORE I and II, have been validated for cardiac surgery but not for aortic disease. They argue these tools are “inappropriate” risk prediction tools for aortic arch pathologies and procedures, thereby necessitating a dedicated clinical prediction model which is seen as “indispensable” for patients undergoing invasive procedures.

Overall, the document exposes the complexity of the subject, and points to a need for those who are planning to intervene in the aortic arch to be able to specify not only the pathology but the site of the pathology, as outcomes such as mortality and stroke will vary accordingly. Specialised centres and aortic teams may also facilitate more direct comparisons between open and endovascular approaches, as the ideal comparison will be made by surgeons who are equally competent in both methods, and lack preference for one or the other. While leading experts, institutions and societies such as the EACTS and ESVS continue the work to produce trials and data in this intricate field, consensus and guidelines based on expert opinion take on the important task of advising on best possible treatment and outcomes for aortic arch patients.

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

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ELUVIA™ Drug-Eluting Vascular Stent System

Sustained Release.

Superior Results.

1

1

vs

.

1. Superiority determined in Post Hoc Superiority Analysis. 12-Month Primary Patency rate of 86.8% in the Eluvia arm (n=309) vs. 77.5% in the Zilver PTX (n=156) arm (p-value= 0.0144) IMPERIAL IDE trial. BSC data on file.

Eluvia™ is a registered or unregistered trademark of Boston Scientific Corporation.

All cited trademarks are the property of their respective owners. CAUTION: The law restricts these devices to sale by or on the order of a physician.

Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. Material not intended for use in France.

PI-568109-AA © 2018 Boston Scientific Corporation or its affiliates. All rights reserved.

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Peripheral arterial disease

Drug-eluting stents go head-to-head in IMPERIAL trial Continued from page 1

vessel patency of 88.5% at 12-months versus 79.5% after the same time-frame. Primary vessel patency is defined as a core lab-assessed duplex ultrasound peak systolic velocity ratio of ≤2.4 in the absence of clinically-driven target lesion revascularisation or bypass of the target lesion.

Both the Eluvia stent system and the Zilver PTX— which are designed to restore blood flow in the superficial femoral and proximal popliteal arteries— feature a drug-polymer combination intended to allow for the sustained release of paclitaxel. This drug can prevent restenosis of the vessel.

However, the presence of a polymer (a biostable fluorinated polymer matrix) contained within the Eluvia stent allows for a lower dose of paclitaxel, which is indicative of the main difference between the two stents.

Speaking to the CIRSE audience about the reasons for the findings, Müller-Hülsbeck alluded to the presence of the

polymer being the “key to success”.

“These impressive clinical outcomes suggest that sustained elution of paclitaxel, delivered by the Eluvia stent, better matched the timing of restenosis in the SFA that can occur months later, thereby reducing the need for repeat interventions,” said William Gray, co-principal investigator of the IMPERIAL trial. “Based on these findings, we believe that the Eluvia stent can be a preferred therapy option when treating patients with arterial blockages in the superficial femoral or proximal popliteal arteries.”

Off the back of data from the MAJESTIC trial, which evidenced long-term freedom from revascularisation at three years, the Eluvia stent system received the CE mark in early 2016. With a primary patency rate of more than 96%, the MAJESTIC trial results represented the highest 12-month primary patency reported for an interventional treatment of femoropopliteal artery lesions among comparable trials, according to Boston Scientific.

The Zilver PTX drug-eluting stent also has a wealth of strong clinical data supporting its efficacy. In 2009, the device was the first CE mark-approved drug-eluting stent designed specifically to treat severe blockages in the superficial femoral artery. Five-years results from the largest and longest-running clinical trial of a drugeluting stent for treating peripheral arterial disease, published in 2014, evidenced long-term patency for patients treated with the Zilver PTX. This 2014 study compared the Zilver PTX with a bare metal stent, and confirmed the “sustained benefit” of the paclitaxeleluting stent.

These impressive clinical outcomes suggest that sustained elution of paclitaxel [..] better matched the timing of restenosis in the SFA that can occur months later, thereby reducing the need for repeat interventions.

Stefan Müller-Hülsbeck

VOYAGER PAD continues after planned interim analysis The VOYAGER PAD trial investigating the efficacy and safety of rivaroxaban to reduce the risk of major thrombotic vascular events in patients with symptomatic peripheral arterial disease (PAD) undergoing lower extremity revascularisation procedures is continuing after a scheduled interim analysis in September, with an estimated final results date in early 2020.

H

enrik Sillesen (University of Copenhagen, Copenhagen, Denmark) explained that the continuation of the trial is “good news” and it means that “there was not overwhelming effect in order for the trial to be stopped, but there is obviously some effect, because had there been no effect, the trial would have of course been stopped” for lack of efficacy.

Sillesen, one of the trial’s investigators, presented the update during a late-breaking trials session at the European Society for Vascular Surgery’s annual meeting (ESVS; 25–28 September, Valencia, Spain).

An international, multicentre, randomised, double-blind, placebocontrolled phase 3 trial, the purpose of the VOYAGER PAD study is to test whether rivaroxaban added to standard of care treatment, when compared to placebo, has the potential to reduce the incidence of the clinical events related to the clots and complications of the heart and brain (cardiovascular death, myocardial infarction, or stroke) or the legs (acute limb ischaemia or major amputation) in patients who have undergone a recent procedure to improve the blood flow of their legs.

VOYAGER PAD, Sillesen explained, is similar to the COMPASS

trial, which found that in PAD patients, the addition of low dose rivaroxaban to aspirin, compared with aspirin alone, reduced cardiovascular death, stroke or heart attack by 28%, and limb-threatening ischaemia, including amputation, by 46%; and considering both outcomes together, COMPASS showed that rivaroxaban and aspirin lowered major adverse cardiovascular or limb events by 31%.

VOYAGER PAD is looking at patients undergoing infrainguinal revascularisation, including common femoral artery endarterectomy. It is an endpoint driven trial, powered after gaining 1,015 events in 6,500 patients randomised to either the regime of 2.5mg of rivaroxaban twice daily, plus 100mg of aspirin, or to 100mg of aspirin only.

The primary outcome measure is the time from randomisation to the first occurrence of any of the following major thrombotic vascular events: myocardial infarction, ischaemic stroke, cardiovascular death, acute limb ischaemia, and major amputation, with a time frame of approximately two years due to vascular aetiology.

The primary safety endpoint is the time from randomisation to the first occurrence of major bleeding events according to the Thrombolysis

in Myocardial Infarction (TIMI) classification in order to evaluate the overall safety and tolerability.

To be included in the trial, patients had to be >50 years, have symptomatic and haemodynamic peripheral arterial disease, and a technically successful peripheral infrainguinal revascularisation within seven days prior to randomisation.

Patients were excluded if they had asymptomatic PAD or mild claudication, major tissue loss or gangrene beyond the forefoot, prior revascularisation within eight weeks, acute limb ischaemia within two weeks, planned dual anti-platelet therapy (DAPT) >30 days, planned

We have seen more MALE than MACE, which is the opposite of COMPASS and makes us optimistic for this trial.

DAPT for any other indication or systemic anticoagulation.

Enrolment in the study was completed at the end of 2017, with the majority of patients enrolled in Eastern and Western Europe. Of the 6,566 patients enrolled, 65% underwent endovascular procedures, and 35% open surgical reconstructions.

“What is very interesting about this trial is the proportion of individual endpoints, where limb efficacy events are dominating. This is in contrast to the COMPASS trial where limb events were quite rare and cardiac events were dominating. This should not come as a surprise to vascular surgeons that when we operate it is the legs that tend to get problems afterwards with the reconstruction, and this is certainly being confirmed, and this is extremely exciting that we are actually trying to prevent trouble that happens with our reconstructions,” Sillesen explained.

He added that in terms of bleeding events, the number of events adjudicated as TIMI major are “almost negligible”, while minor bleeding events have been more substantial.

“In conclusion, we have seen many events, but not more than were projected. We have seen more MALE [major adverse limb events] than MACE [major adverse cardiovascular events], which is the opposite of COMPASS and makes us optimistic for this trial. It has been challenging to enrol patients and to retain patients in the trial, largely due to the number of minor bleeding events, where patients question whether they should stay on the drug, and so far, approximately 20% have come off the drug,” Sillesen stated.

He added that following the only scheduled interim analysis in September, the trial has not been stopped, indicating that there is some effect, and that the final results are expected to be reported in early 2020.

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Radiation

Essential radiation protection for the modern vascular surgeon and the skin. Therefore, protective glasses should be tailored to each operator, with close fit and large protection area.

Kevin Mani

Additional risk and options

Comment & Analysis Addressing the importance of radiation protection for the modern vascular surgeon, Kevin Mani writes about the need for knowledge and training in radiation protection for vascular surgeons, and radiation protection as an integrated part of vascular surgical training.

T

he majority of vascular surgical procedures are today performed with endovascular techniques.

The massive increase in the number of endovascular procedures, as well as the increasing complexity of these procedures, necessitates that specific attention is paid to the risks associated with radiation exposure in relation to endovascular surgery. The repetitive exposure of modern vascular surgeons to high radiation doses is of major concern. Several pioneers in the vascular surgeon-interventionalist community have paid a high price for the developments made in endovascular surgery during their time in practice due to excessive radiation exposure, with development of radiation induced cataract as well as neoplasms. Although knowledge regarding the true risks with occupational radiation exposure is still scarce, recent studies indicate that measurable DNA damage among operators occurs already after a simple EVAR procedure.1 Additionally, there are indications of higher prevalence of left-sided brain tumours among physicians with occupational exposure to interventional radiation.

Strategies

Measures to reduce occupational radiation exposure during endovascular procedures are twofold: 1) reducing the radiation dose, and 2) applying adequate protection to reduce scatter radiation. Reduction of radiation dose adheres to the “as low as reasonably achievable” (ALARA) principle, which mandate medical use of X-rays to be limited to the lowest possible dose. In endovascular surgery, this is based on cautious and meticulous x-ray technique as well.

Measures to reduce radiation dose include application of adjusted low dose programmes with minimum pulse frequency and radiation energy which are tailored for the type of endovascular procedure being performed. Such targeted fluoroscopy and angiography algorithms can be developed together with interested hospital physicists in collaboration with the major providers of imaging equipment. Adequate use of beam collimation, digital image magnification, 2D-3D fusion and image overlay are other methods proven to reduce the exposed field and required radiation.2 Reduction of the radiation dose has important benefit both for the patient as well as for the personnel. Real-time dosimeters used by the operating room personnel offers a possibility for direct feedback regarding radiation exposure, in order to increase awareness and modify behaviour.

Adequate protection

In addition to the reduction of radiation dose, use of adequate protection is key to reduce occupational radiation exposure during endovascular procedures.

Radiation protection measures can be classified into two groups: 1) radiation shields placed close to the patient, reducing scatter radiation from the patient in general, and 2) radiation

Figure 1. The ZeroGravity radiation suite in use during a branched endovascular aortic repair at Uppsala University Hospital.

protection placed close to or worn by the personnel.

Ceiling suspended shields, table mounted shields and disposable radiation-absorbing surgical drapes such as RadPad all encompass radiation protection close to the patient. A properly used combination of these shields can successfully reduce scatter radiation with >80%. The functionality of shields placed close to the patient is however highly dependent on adequate positioning of the shields. Challenges to correct use of these protective shields during complex endovascular surgery include collision of ceiling mounted shields and operating light or flat panel detector, lack of adequate shielding during lateral projection fluoroscopy/angiography, and lack of protection on the patient’s left side during interventions performed, e.g. from left brachial or axillary access.

Basic protective shielding for personnel includes use of a lead apron and thyroid shield, complemented with protective glasses. Considering that the eye lens is the most radiation sensitive organ, eye protection should be a key element for all endovascular operators. Interestingly, experimental data suggest that the dose reduction effect of protective eye glasses varies significantly between different models, with majority of the commercially available eye glasses offering a moderate 10–15% dose reduction at left eye. The dose reduction effect is highly dependent on the size of the gutters between the protective glass

Even with standard lead apron and eye glasses, significant body areas including the arms, shins and head remain unprotected to scatter radiation, which may pose a risk especially for the primary operator closest to the source of scatter radiation. The landmark study by El Sayed et al showing radiation-induced DNA damage in EVAR operators could also verify that DNA damage can be reduced by additional use of radiation-protective shin guards. Optimal radiation protection would include protection for all exposed body areas. However, additional shielding may also be cumbersome and result in excessive weight, potentially with negative effects such as back pain and lumbar hernias. The suspended lead suit radiation protection system (ZeroGravity radiation suit) is an attempt to offer near to full radiation shielding without additional weight on the operator’s body. The system is based on a thick lead suit with a curved lead-acrylic head shield that is suspended either from a ceiling mounted monorail, repositionable floor unit, or a hinged swing arm. The ZeroGravity system offers excellent radiation protection for the primary operator, with significant reduction of the radiation exposure to the head, upper arms, and legs, in addition to what is today achieved with standard lead apron, Figure 1. In a recent assessment of the system in neuro-endovascular intervention, the suspended lead suit resulted in an additional 75% reduction in the operator-received total dose compared to standard protection including lead apron, glasses, ceiling and table-mounted shields.3 There is however, still potential for further development. In our experience, the weight of the floor mounted ZeroGravity system may hinder repositioning possibilities. Additionally, a relatively high cost of acquiring the system may limit its use to high-volume endovascular centres.

Awareness

The increasing number of endovascular procedures in the field of vascular surgery is likely to continue in the future. This results in a need for knowledge and training in radiation protection for modern vascular surgeons, and radiation protection is increasingly an integrated part of vascular surgical training. Although basic protection is achieved with adherence to the ALARA principle and use of regular protective shields, the risk of repetitive occupational radiation exposure for vascular surgeons remains a concern.

Further innovation in endovascular surgery and radiation protection will play an important role in achieving the ultimate goal of zero radiation exposure during these procedures.

Kevin Mani is associate professor of vascular surgery at the Department of Surgical Sciences, Uppsala University, Uppsala, Sweden References: 1. El-Sayed T, Patel AS, Cho JS, Kelly JA, Ludwinski FE, Saha P, Lyons OT, Smith A, Modarai B, Guy’s and St Thomas’ Cardiovascular Research C. Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair. Circulation. 2017;136:2406-2416.

2. Hertault A, Maurel B, Midulla M, Bordier C, Desponds L, Saeed Kilani M, Sobocinski J and Haulon S. Editor’s Choice - Minimizing Radiation Exposure During Endovascular Procedures: Basic Knowledge, Literature Review, and Reporting Standards. Eur J Vasc Endovasc Surg. 2015;50:21-36.

3. Haussen DC, Van Der Bom IM and Nogueira RG. A prospective case control comparison of the ZeroGravity system versus a standard lead apron as radiation protection strategy in neuroendovascular procedures. Journal of neurointerventional surgery. 2016;8:1052-5.

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Peripheral arterial disease

Fractional flow reserve superior to standard methods in predicting functional significance of peripheral arterial lesions A study presented at the European Society of Vascular Surgery’s annual meeting (ESVS; 25–28 September, Valencia, Spain) has found that fractional flow reserve (FFR) measures functional severity of peripheral arterial stenoses and discriminates the clinical significance of lesions, and their effect on tissue perfusion, better than standard techniques. The results were presented by Mostafa Albayati (Guy’s and St Thomas’ Hospital, London, UK).

Mostafa Albayati

CURRENT INVESTIGATION OF peripheral arterial disease are based on angiography which provides a visual estimation of stenosis severity, and duplex ultrasound which provides some haemodynamic information at rest. However, Albayati pointed out, these modalities do not provide any functional haemodynamic information to guide treatment decisions.

In the coronary circulation, seminal work facilitated by 0.014” pressure sensor guidewires has enabled the measurement of FFR. This describes the trans-stenotic pressure gradient across a stenosis during maximum hyperaemia, indicating the functional haemodynamic compromise of the lesion. Albayati added, “put simply, FFR indicates the amount of blood flow the vessel can deliver on demand in the presence of a stenosis similar to that occurring during exercise, which in the landmark FAME trials was shown to improve lesion selection and outcomes after percutaneous coronary intervention than

angiographically-guided treatment alone”.

Albayati and colleagues hypothesised that their conventional methods of assessing lesion severity, based on stenosis diameter from duplex ultrasound and angiographic information, do not correlate with direct functional measurements. The aims of their study were twofold—firstly, to measure the functional severity of peripheral arterial stenoses; and secondly, to relate these functional measurements to duplex ultrasound and angiographic estimations of severity, tissue perfusion, symptoms and restenosis on follow-up.

In the study, patients underwent preoperative duplex ultrasound and CT scanning as part of their standard care. Following that, patients underwent blood oxygenation level dependent (BOLD) magnetic resonance (MR) scanning of their legs prior to intervention. During intervention, trans-stenotic FFR measurements (before and after treatment) of the culprit lesion were acquired. Patients finally underwent a second BOLD MR scan as well as duplex ultrasound to assess patency on follow-up after treatment.

Albayati explained that to obtain invasive FFR measurements, a catheter was placed in the distal aorta from the non-diseased contralateral side providing pressure measurements proximal to the index stenosis. Using the example of a common iliac artery stenosis, he showed that a dual sensor wire is then positioned distal to the stenosis, providing both pressure and flow velocity measurements at this level.

These measurements were acquired at rest and during hyperaemia, which was provoked by intra-arterial adenosine administered via the femoral sheath.

In the study of 52 stenoses in 41 patients assessed

by FFR, Albayati said “when looking at the pressureflow relationship of these lesions, we found that during

resting flow the trans-stenotic pressure gradients are clustered together and are of similar value, particularly for those intermediate lesions in the 30–80% diameter stenosis category. These lesions required hyperaemic flow conditions in order to amplify their pressure gradients and unmask their true haemodynamic severity.

In contrast, those tighter stenoses above 80% had higher resting flow pressure gradients that were similar to their hyperaemic FFR values, therefore resting flow conditions were sufficient to unmask their severity”.

Next, the investigators sought to ascertain whether FFR related better to symptom severity compared to duplex ultrasound or angiographic-based measurements of diameter stenosis. “We found that FFR was far superior to our standard methods for predicting patients who had intermittent claudication versus those with critical limb ischaemia, with an area under the curve value of 0.96”. Their study also found that functional measurement of FFR correlated more strongly to BOLD MR tissue perfusion than duplex ultrasound and angiographic measurements of stenosis diameter.

“All patients were followed up after treatment for six months, and an FFR value of >0.82 discriminated those patients who had symptom resolution and those who had persistent symptoms. In addition to this, post-treatment duplex ultrasound surveillance found that a post-treatment FFR value of <0.88 predicted those patients who went on to have significant stenosis on follow-up, with a sensitivity and specificity of 75%,” Albayati reported.

He concluded his presentation by emphasising that FFR measures the functional severity of peripheral arterial stenoses and discriminates the clinical significance of such lesions, and their effect on tissue perfusion, better than standard techniques. It also appears, he added, that FFR can objectively measure treatment success. However, he pointed out, this still requires invasive arterial access of lesions that may be haemodynamically non-significant. Therefore, Albayati announced, the next phase of his work is aimed at noninvasively predicting FFR using computational fluid dynamics.

Three-year results from global study confirm the safety of the IN.PACT drug-coated balloon The largest prospective, independently-adjudicated study of drugcoated balloons (DCBs) in a broad range of lesions in real-world patients confirms the safety and performance of the IN.PACT Admiral DCB (Medtronic) in the treatment of femoropopliteal artery disease. This is the conclusion presented by Gunnar Tepe, professor of Radiology at the Academic Hospital RoMed in Rosenheim, Germany, during the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting (22–25 September, Lisbon, Portugal).

T

hese three-year real-world data show that freedom from clinically-driven target lesion revascularisation (CDTLR) was achieved in 76.9% of patients, indicating that this global trial continues to confirm the safety of the IN.PACT Admiral DCB for treatment of femoropopliteal artery disease.

IN.PACT Global was a prospective, multicentre, single arm study conducted at 64 international sites. A total of 1,535 patients, with 1,773 lesions between them, were enrolled in this trial. A wide variety of lesions were included in this study, including: bilateral disease, multiple lesions, TASC (Trans-Atlantic Inter-Society Consensus Document), de novo in-stent

stenosis, long lesions (≥150mm), and chronic total occlusions (≥50mm).

The primary safety endpoint that was measured at 12-months showed that no major adverse events were attributed to the DCB itself. Additionally, major limb amputation only occurred in 10 patients out of the entire cohort.

Tepe pointed towards the importance of subgroups to validate findings. For example, the data showed that diabetics (comprising 39.9% of patients in the study) treated within the IN.PACT trial demonstrated “consistent and durable results” through three years, with freedom from CD-TLR at 74.7%, similar to the rate of non-diabetics (78.4%).

The majority of patients in this study (67.8%) were male, and the mean age was 68.6±10.1 years. The mean lesion length was 12.09±9.54cm, including 18% in-stent stenosis, 35.5% total occlusions, and 68.7% calcified lesions.

Back in January 2019, data presented at the Leipzig Interventional Course (LINC; 30 January–2 February, Leipzig, Germany) demonstrated the durability and consistency in clinical outcomes of the IN.PACT Admiral drug-coated balloon. Thus was the result of the twoyear MDT-2113 study (IN.PACT SFA Japan), as well as data from a critical limb ischaemia subgroup analysis of the IN.PACT Global study.

In Germany earlier this year, vascular surgeon Michel Reijnen (Rignstate Hospital, the Netherlands) presented the one year results from the critical limb ischaemia subset of the IN.PACT Global study: data showed comparable effectiveness with a freedom from CDTLR based on Kaplan-Meier Estimate of 86.6% (Rutherford category 4), and 85.5%

Gunnar Tepe

in Rutherford category 5 (p<0.001).

These present data are an extension of the IN.PACT Global study, and corroborates the earlier findings of the subgroup analysis presented at LINC. Tepe maintained that the data presented so far greatly “reflect the clinical reality,” and noted that follow-up is due to continue for a further two years; allowing for five-year outcomes to be measured.

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Research

Stem cell therapy is the future of critical limb ischaemia management Sanjiv Sharma Comment & Analysis Addressing the audience at the 34th annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 22–25 September, Lisbon, Portugal), Sanjiv Sharma asks: “If you can have a drug eluting stent, why can’t you have a stem cell eluting stent?” Here, Sharma argues that a paradigm shift in the management of critical limb ischaemia is on the horizon, with stem cell therapies proving safe, effective, and less costly than surgical or endovascular revascularisation.

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anagement strategies for critical limb ischaemia (CLI) are constantly evolving due to issues and challenges with the image morphologies in below-the-knee vessels and rapidly changing device technologies, mostly with unmet longterm outcome expectations. Many times, a strategy for surgical or endovascular revascularisation may not be feasible due to an anatomically irreparable disease. New endovascular techniques and devices may improve short-term outcomes but fail progressively with time, and eventually are not much better than conventional techniques over the long term, despite major cost escalation.

Therapeutic angiogenesis using cell based (stem cell) therapies has emerged as a new frontier in this treatment and has the potential to rewrite the treatment algorithms in patients with critical or chronic limb ischaemia.1–3

Stem cell characteristics

These stem cells have three characteristic properties that make them well suited for this treatment: plasticity, homing and engraftment. Stem cells derived from early human embryos are pluri-potent and can generate all committed cell types. These generated cells are higher in number, and have better expansion potential and differentiation abilities when compared with stem cells from adult tissues, but have issues related to adverse effects and ethical concerns.

Hence, the clinical experiences are largely restricted to the use of autologous adult stem cells in various disease states.

The migration, differentiation and growth of stem cells are mediated by the nature of the tissue, degree of injury and the type of stem cells involved. Damaged tissue releases factors that induce homing of these cells to the site of injury.

In ischaemic tissues, endogenous biochemical agents are released, stimulating angiogenesis. The angiogenesis is developed by vascular cell proliferation and new capillary formation. Pre-clinical studies have shown that angiogenic growth

factors promote the development of collateral arteries, a process that is termed therapeutic angiogenesis. This angiogenesis can be achieved either by growth factors or genes encoding these proteins. Endothelial progenitor cells in the CD34+ stem cell fraction of adult human peripheral blood and bone marrow cells also take part in postnatal neo-vascularisation after mobilisation from bone marrow, and contribute to this angiogenesis.

Stem cells can be extracted from various sites, including the bone marrow, peripheral blood and adipose tissue.

These can be administered to the affected area by intra-arterial or intra-muscular delivery. Both these routes of delivery have shown clinical benefit in multiple

seen in all patients in the treatment arm.

This benefit was not dependent on the dose of injected stem cells beyond a threshold dose. Whereas in the control arm, no improvement was seen in any patient; CLI improved in all patients in the treatment group who received three graded doses of stem cells. No adverse effects related to the treatment were seen in any patient.

Subsequently, we conducted a randomised first-in-human placebo controlled double blind clinical trial that included 80 patients with no option CLI not suited for any form of revascularisation. There was a 1:1 randomisation in control and treatment arms, and the patients were followed for at least six months after this treatment.

All patients received an injection, either of stem cells, or a sham injection indistinguishable from the stem cells.

Both the operator and the physician who evaluated the patients during follow-up were blinded to the mode of therapy.

This trial was recently concluded and the results have established the safety and efficacy of autologous stem cell therapy for limb salvage in these patients.

Evidence of therapeutic angiogenesis as evidenced by a demonstrable increase in collateral density after stem cell therapy and 0% amputation rates in the treatment arm was observed.

There is some evidence to suggest that the effect of this therapy may be more pronounced in Berger’s disease than in atherosclerosis.4 The barriers to the development of stem cell therapy relate

The therapeutic potential of stem cells may be enhanced by combining this treatment with gene therapy. studies.4–6 Preclinical studies have proven the safety of this treatment method and a variable efficacy in terms of relief of induced ischaemia. Current research revolves around establishing the most suitable source of autologous stem cells, the optimal route of delivery, the right dose of cells, as well as the role of single versus multiple injections for the desired clinical outcomes, the optimal method for assessment of clinical and imaging outcomes, and the role of adjunct therapies in potentiating the effects of cell based therapies.

Stem cell treatment proven safe and effective in “no option” patients

We conducted a pilot project using graded doses of stem cells in a group of patients with CLI and showed that a benefit, in terms of relief of rest pain and healing of ischaemic ulcers, was

to the autologous cell population that is often heterogeneous and may lead to varied responses. Also, to obtain the large cell numbers needed for transplantation, ex vivo cell expansion may be required, which leads to regulatory concerns and increased cost and time. Advanced disease also has the problem of cytokine resistance. Furthermore, the cell engraftment efficiency is typically low upon transplantation and may require multiple injections.

The potential of gene therapy The therapeutic potential of stem cells may be enhanced by combining this treatment with gene therapy. This is likely to overcome insufficient paracrine release, poor cell survival upon engraftment, and lack of cell homing by controlling cell behaviour at the intracellular signalling level.7 To reduce the occurrence of in-stent

restenosis, stents have been reshaped and improved in many aspects with the development of drug and growth factor eluting stents. Stem cells as a source of seeding cells for coating the stents have also been reported.8 In a recent study, mesenchymal stem cells derived from the bone marrow of New Zealand white rabbits were used as seeding cells and the authors observed that intimal hyperplasia and in-stent restenosis were significantly inhibited by the mesenchymal stem cell coated stent.

Although proof from large randomised trials for the above therapies is still inconsistent, these treatments have shown the ability to improve perfusion in selected patients. We have established the safety and efficacy of autologous stem cells in the treatment of “no-option patients” with critical limb ischaemia. Pre-clinical studies utilising a combination of cell and gene therapy have also shown encouraging results.

This may be an alternative option to address the limited number and function of progenitor cells in elderly patients, those with co-morbidities, and the challenge of cytokine resistance. Further research will define their role in suitable patients. The evidence for cell-based therapies is encouraging. There is a need for optimised trials to define the treatment algorithms in these patients.

Sanjiv Sharma is professor and head of the Department of Cardiovascular Radiology and Endovascular Interventions at the All India Institute of Medical Sciences, New Delhi, India.

References: 1. Chochola M, Pytlik R, Kobylka P, Skalicka L, Kideryova L, Beran S, et al. Autologous intraarterial infusion of bone marrow mononuclear cells in patients with critical leg ischemia. Int Angiol.

2008;27(4):281-90.

2. Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, et al. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J. 2008;156(5):1010-8.

3. Amann B, Luedemann C, Ratei R, Schmidt-Lucke JA. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant.

2009;18(3):371-80.

4. Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease metaanalysis and systematic review of the literature.

Atherosclerosis. 2010;209(1):10-7.

5. Rigato M, Monami M, Fadini GP. Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies. Circ Res. 2017;120(8):1326-40.

6. Bura A, Planat-Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, et al. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy. 2014;16(2):24557.

7. Makarevich P, Rubina Rubina KA, Diykanov Diykanov DT, Tkachuk Tkachuk VA, Parfyonova Parfyonova YV. Therapeutic Angiogenesis Using Growth Factors: Current State and Prospects for Development. Vol. 9_2015. 2015. 59 p.

8. Bompais H, Chagraoui J, Canron X, Crisan M, Liu XH, Anjo A, et al. Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells. Blood. 2004 Apr 1;103(7):2577–84.

9. Wu X, Zhao Y, Tang C, Yin T, Du R, Tian J, et al.

Re-Endothelialization Study on Endovascular Stents Seeded by Endothelial Cells through Up- or Downregulation of VEGF. ACS Appl Mater Interfaces.

2016 Mar 23;8(11):7578–89.

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Peripheral arterial disease

Real-world insights into smoking behaviour in PAD patients highlight the need for cessation support A recent study provides the first real-world insights into smoking behaviour and smoking cessation practices in patients with peripheral arterial disease (PAD). The data were recently published in the Journal of American Heart Association.

KRISHNA K PATEL (University of Missouri-Kansas City, Kansas City, USA) and colleagues drew from the international PORTRAIT registry to study longitudinal smoking behaviour in patients with PAD. The majority of smoking patients with PAD continued smoking a year later, and more than a third of those who quit initially relapsed by a year; highlighting the need for repeated, ongoing smoking cessation support in this particular patient population.

The authors reported that PAD affects 202 million adults worldwide and is associated with significant morbidity and mortality. Smoking is the most important risk factor for PAD, and smokers with PAD have higher rates of disease progression as well as a greater risk of complications such as amputations and failure of procedural treatment.

According to Patel, stopping smoking could halt the disease progression, improve and reverse some of these risks. Thus, smoking cessation is the cornerstone for managing patients with PAD. However, the authors observed that despite the key role that has been attributed to smoking as a risk factor in PAD, few contemporary studies described the prevalence of smoking in patients with PAD as well as physician’s efforts to encourage smoking cessation.

To address this gap in the literature, Patel and colleagues used the PORTRAIT (Patient-centred outcomes related to treatment practices in peripheral arterial disease: investigating trajectories) registry¬—an international, multicentre registry of patients presenting to speciality clinics with symptoms of PAD—to assess the smoking behaviour in patients with PAD over the period of one year.

Interviews collected smoking status and cessation interventions at baseline, as well as three, six, and 12 months.

Additionally, Patel and colleagues used transition state models to analyse smoking transitions at each time point and identified factors associated with quitting and relapse.

They found that smoking behaviour is very dynamic in patients with PAD, and a large majority of patients who smoke continue smoking or have a relapse after attempting to quit. Among 1,272 patients that presented to vascular specialty clinics with PAD related symptoms (new or worsening claudication), over a third (37.3%) patients were active smokers, 660 (51.9%) former, and 138 (10.8%) patients had never been smokers. Of importance, the authors reported that very few doctors emphasised smoking cessation. The predominant strategy used by providers to help their smoking patients to quit was simply “to tell them to stop”, while only 16% had been referred to cessation counselling and 11% had received pharmacologic treatment or nicotine replacement therapy.

The investigators maintained that perhaps, as a result, these patients either continue smoking or have a very high rate of relapse if they make an attempt to quit. At three months, Patel and colleagues found that the probability of quitting smoking was 21%; among those continuing to

smoke at three months, the probability of quitting during the next nine months varied between 11% and 12% (p<0.001).

Furthermore, they noted that the probability of relapse among initial quitters was 36%, while, at 12 months, 72% of all smokers continued to smoke.

In summary, more than one third of patients with claudication consulting a PAD provider were active smokers, with very few having received evidence-based cessation interventions. Patients appear to be most likely to quit early in their treatment course, yet many quickly relapse and 72% of all patients smoking at baseline were found to be still smoking at 12 months.

As the investigators followed the patients through to 12 months, they stressed that the current study provides “the first insight into these [treatment and smoking behaviour] patterns over time.” However, Patel and colleagues noted a couple of shortcomings, one being the use of patient-reported smoking status that could have resulted in a misclassification in status. Furthermore, the findings only reflect cessation activities conducted at the PAD clinic, meaning they may not reflect the general PAD population, such as those never referred for speciality care and asymptomatic patients.

Irrespective of these limitations, Patel and colleagues concluded that the study provided important insights into the smoking behaviour in patients with PAD over time. They note that doctors and other health care providers taking care of these patients should treat smoking as any other chronic addiction problem, and provide consistent, repeated and continuous smoking cessation support to their smoking patients with at every opportunity they get with them.

Additionally, the authors emphasised the need for future research to identify barriers in providing adequate smoking cessation support for this high-risk population. They also highlighted the need to identify collaborative strategies on a health system level to provide high-quality tailored smoking cessation support to patients with PAD.

Interim results of 4F and 6F access site complications advocate for an ambulatory approach for treatment of PAD The results of a study seeking to compare access site complications in 4F and 6F devices with regards to the treatment of peripheral arterial disease (PAD) report that ambulatory treatment presents a valid option for endovascular procedures in lower limb arteries, with the additional benefit of both the 4F and 6F devices negating the need for a vascular closure device. These interim data were presented by Marianne Brodmann from Medizinische Universtität Graz, Graz, Austria, at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting (22–25 September, Lisbon, Portugal).

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ccording to Brodmann, ambulatory treatment is becoming more frequent, with peripheral vascular interventions as well as coronary interventions—now carried out using radial access—becoming more commonplace in outpatient settings.

Brodmann acknowledged this trend, suggesting that ambulatory treatment is growing not only for vascular interventions, but in every medical field.

However, she reported that the main concern related to ambulatory treatment is access site complications. Previous data from the 4 EVER trial that used a 4F puncture system reported a puncture site complication rate of 3.3%, indicating that it is possible to achieve such low rates.

Therefore, Brodmann and colleagues sought to compare the rate of access site complications in 4F versus 6F femoral access devices for endovascular treatment of lower-extremity PAD in an ambulatory setting. The investigators conducted a

multicentre, prospective, controlled trial aimed at demonstrating non-inferiority of the primary endpoint (access site complications) with a non-inferiority margin of 2%; assuming an access site complication rate of 5% in 6F and 3% in 4F. In total, 792 patients suffering from infrainguinal PAD are to be treated; with 388 patients so far assigned to either the 4F or 6F device, per physician’s discretion. The primary endpoint includes both peri- and post-procedural access site complications (including homeostasis strategy failure), with post-procedural outcomes defined as within 30-days post-intervention. Secondary endpoints include procedural success, sub-evaluation of access site complications according to severity, ambulatory failures, time to haemostasis, and time to discharge.

The endpoints reported so far have been adjudicated by a clinical event committee.

Regarding the preliminary results, a total of 576 lesions have so far been treated, covering all kinds of lesions, including:

common femoral, superficial femoral artery, popliteal artery and below-the-knee lesions, using an ambulatory approach. More belowthe-knee procedures were carried out using the 4F system (19.5%) compared to the 6F (12.1%), while more SFA procedures were carried out using the 6F system (54.1% vs.

45.8% for 4F).

The main difference between the cohorts was that a vascular closure device was used in 6.6% of the 4F patients, but in over 80% of the 6F patients. Further differences include that a compression device was used in 48% of the 4F patients compared to the 29.9% of 6F patients, while both manual compression time and time to haemostasis was doubled in the 4F patients when compared with the 6F (from 4.8±8.437 to 10.92±9.718mins, and 7.17±10.301 to 13.49±13.66mins, respectively). Brodmann attributed this finding to the predominant use of vascular closer devices in the 6F patient cohort. Additionally, the diameter of common femoral artery at the puncture

site was slightly lower in the 4F cohort (6.51±1.81 vs. 6.9±1.169mm2 for the 6F cohort).

Time to patient discharge (8.15±11.006 hours for 4F and 8.57±14.147 hours for 6F) and procedural success (95.1% for 4F and 95.5% for 6F) was similar in both cohorts.

Furthermore, discharge that occurred the same day as the procedure occurred at a similar rate for both cohorts.

Although Brodmann acknowledged that further evaluation of the full cohort is needed to draw more concrete conclusions, she concluded that within the range of the current study, ambulatory treatment is a valid option for endovascular procedures in lower limb arteries. Elaborating, she maintained that 4F compatible products show similar results when compared to the already well-established 6F devices—and so remain a valid alterative based on patient need and physician reference—with the additional benefit in that they negate the need of a vascular closure device.

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Abdominal aortic aneurysms

Ruptured abdominal aortic aneurysm mortality sees decrease over past two decades The incidence of ruptured abdominal aortic aneurysm (AAA) and associated mortality has decreased over the past 20 years in Sweden, indicating that altered smoking patterns have had an impact on overall AAA prevalence and aneurysm rupture and that endovascular aneurysm repair (EVAR) has helped to improve overall survival. However, more attention needs to be placed on improving the outcome of ruptured AAA in women.

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hese are the findings from a nationwide assessment of the epidemiology of ruptured AAA over 20 years, which point to increasing surgical rate and improved survival of ruptured AAA patients. The results of the assessment were presented by Kim Gunnarsson (Uppsala University, Uppsala, Sweden) at the European Society for Vascular Surgery’s annual meeting (ESVS; 25–28 September, Valencia, Spain).

According to Gunnarsson, the epidemiology of ruptured AAA, as well as the clinical management, has changed over recent decades due to a number of factors, including changes in smoking habits, cardiovascular disease management, the introduction of EVAR, as well as screening for aortic aneurysms. Most assessments of ruptured AAA epidemiology, he pointed out, focus on the patients undergoing surgical intervention, however, historical cohorts indicate that only half of the patients with ruptured AAA are hospitalised and only a selection of those patients undergo surgery.

In this population-based study, Gunnarsson and colleagues aimed to investigate the modern epidemiology of ruptured AAA. The study includes an assessment of the total incidence of ruptured AAA, including ruptures resulting in death prior to hospitalisation, the proportion of ruptured AAA patients presenting alive to hospital and operated on and the total mortality rate for ruptured AAA. Thanks to a unique personal identification number for each individual in Sweden, data captured from 1994–2013 in three national registries could be included in this study: the National Patient Registry, capturing all hospital episodes with a diagnosis of AAA; the Cause of Death Registry; and the Swedish Vascular Registry, including all operations performed for ruptured AAA. The investigators captured all ruptured AAA occurring in individuals above 50 years of age in all three registries.

The total cohort included 18,726 cases, of which 74% were men, and 34% of the men and 53% of the

Total incidence and mortality due to ruptured AAA has decreased over the past two decades, [with] an increasing proportion of patients with ruptured AAA being operated on with an improved survival.

women were above 80 years of age.

To evaluate the change in the incidence of ruptured AAA, Gunnarsson and colleagues used a linear regression model which described the incidence per 100,000 population above the age of 50 years.

They found that among men the decrease was 45%, but in women, on the other hand, there was no change over time. Further, the research showed that the proportion of ruptured AAA patients that presented to hospitals alive and therefore having a chance to be operated on increased over time. In men, there was an increase from 65–72% over the two decades, and in women there was an increase from 51–58%.

In this cohort, Gunnarsson reported, there was a significant amount of patients over 80 years of age, and they observed a “drastic” increase in the number of patients in this group being operated on. In men, there was a relative increase of 45% and in women a relative increase of 50%.

This increase, he pointed out, had an association with an increased use of EVAR for ruptured AAA. The first use of EVAR for ruptured AAA was recorded in 1995, and from 2009– 2013, 60% of all patients over 80 years of age who underwent surgery for a ruptured AAA were treated with EVAR. When analysing the mortality rate, the study found a decrease in overall ruptured AAA-related mortality, but for women, even though there was a slight decrease over time, between 2009 and 2013, the rate of mortality

was still 82%, compared to 89% from 1994–1998, a relative decrease of 7% over 20 years. In men, the rupturerelated mortality decreased from 76% in the 1994–1998 period to 65% in the 2009–2013 period, a relative decrease of 15%.

The strengths of this study, Gunnarsson said, lie in the fact that it is a national population-based study, including all ruptured AAA cases from three cross-linked registries.

The limitations, he admitted, are the risk of coding errors and an autopsy rate of just 10%, resulting in the risk for misdiagnosis of sudden deaths.

However, he said, “as the autopsy rate is stable, one can assume that the error rate related to miscoding was also stable over time”.

“In conclusion, the total incidence and mortality due to ruptured AAA has decreased over the past two decades in Sweden. There is also an increasing proportion of patients with ruptured AAA presenting to hospital and being operated on with an improved survival. And women have a very high mortality rate in ruptured AAA compared to men,” Gunnarsson said.

The interpretation of these findings, he added, suggest that the reduction in prevalence of AAA, much thanks to altered smoking patterns, is mirrored in rupture incidence, and EVAR has resulted in a more active intervention in elderly patients with ruptured AAA, thus improving overall ruptured AAA survival. Finally, Gunnarsson noted that this study indicates that there is a need for focused efforts to improve the outcome of ruptured AAA in women.

Thirty-day results of the E-liac stent graft system in patients with common iliac aneurysms Jotec has announced 30-day results of the PLIANT study, which was an observational, prospective, non-randomised, multicentre, international study conducted in 12 hospitals throughout Europe. This study enrolled 45 patients who were due to undergo implantation with the E-liac stent graft system.

ONE OF THE MAJOR anatomical challenges of endovascular aortic repair (EVAR) in patients with AAA are concomitant iliac artery aneurysms. The Jotec E-liac stent graft system was introduced to address this issue and is indicated for patients with aortoiliac or isolated iliac aneurysms.

The primary endpoint was aneurysm exclusion (no type I, III, IV endoleak) with primary patency of the internal and external iliac arteries on the E-liac implantation side. Peri-procedural primary patency rate of the internal and external iliac arteries on the E-liac implantation side was 100%. Four patients had clinically relevant type Ia endoleak, three located in the infrarenal aorta and one in the

common iliac artery. Two type Ia endoleaks were related to mismatch diameters of the graft and the respective landing zones.

Thirty-day clinical success was achieved in 43/45 patients (96%) and three successful endovascular re-interventions were performed within 30-day follow-up. Primary patency at 30 days was 100% for the internal iliac artery and 98% for the external iliac artery with 100% primary assisted patency in the latter.

The high clinical success rate, low number of re-interventions (2%) and excellent patency rate demonstrate the safety and feasibility of the E-liac Stent Graft System.

E-liac Stent Graft System

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Peripheral arterial disease

Similar outcomes for severely versus nonseverely calcified lesions following Stellarex DCB

Data from a study seeking to determine the impact of severe calcification and 12-month outcomes of femoropopliteal disease treatment using the Stellarex drug-coated balloon (DCB; Phillips) were presented by Fabrizio Fanelli, Careggi University Hospital, Florence, Italy, at CIRSE (Cardiovascular and Interventional Radiological Society of Europe) 2018 meeting (22–25 September, Lisbon, Portugal). Remarkably similar outcomes were achieved with the device in severely calcified lesions that were amenable to pre-dilation, versus those without severe calcium.

“W

e know that calcium is the enemy for all endovascular procedures,” noted Fanelli. He acknowledged that although the implications of severe calcification are known—in relation to the occurrence of suboptimal dilation and the ability of calcium to act as a barrier for drugs—the impact of calcium on DCB performance has yet to be fully examined. For instance, previous trials have demonstrated calcium to be a potential barrier to optimal drug absorption; circumferential calcium being the strongest contributor, resulting in the

reduction of patency rates.

The authors carried out a prospective study in which patients were pooled from the ILLUMENATE Global (full cohort of the single-arm study; n=371) and ILLUMENATE Pivotal (DCB arm of the randomised trial; n=200). Patency, determined by duplex ultrasound, was assessed at 12 months.

Both trials included independent oversight by a Clinical Events Committee and core laboratories analysed angiographic and duplex ultrasound images.

At 12-months, primary patency

Stellarex

rates were similar between groups; 82% in the non-severely calcified group compared with 80% in the severely calcified group (log-rank p=0.06). Additional outcomes mirror this similarity; freedom from primary safety events was 93% and the rate of clinically-driven target lesion revascularisation (TLR) was 7% in both cohorts. The rate of 12-month major adverse events was 7.3% and 7.8% (in non-severely and severely calcified lesions, respectively).

Regarding the procedural characteristics, pre-dilatation maximum pressure was higher (9.5 vs. 8.8atm, p=0.005) and the total DCB inflation time was longer (3.4 vs. 3.9 minutes, p=0.005) in the severely calcified group. Additionally, dissection (>grade C) and provisional stenting rates were found to be similar between groups.

Overall, 556 patients were included in the study, with 242 severely calcified and 314 non-severely calcified lesions.

No significant demographic differences

were observed in the two groups.

However, patients with severely calcified lesions were older and tended to have a higher rate of comorbidities.

Severe calcification, prior to contrast injection or digital subtraction angiography, was prospectively defined as “radioopacities noted on both sides of the arterial wall and extending more than one cm of length”.

In light of the findings, Fanelli concluded that similar 12-month outcomes can be achieved with the Stellarex DCB in severely calcified lesions that are amenable to predilatation. The study also confirmed that severe calcium requires longer and stronger inflation, and by doing so, similar stenting rates can be achieved regardless of whether a lesion is severely or non-severely calcified.

Speaking to the CIRSE audience about reasons for the similar patency rates that were observed, Fanelli said: “This can be attributed to the better preparation of the vessel [and] to the characteristics of the balloon itself”.

Five-year evaluation of Zilver PTX stent in a real-world population continues to show favourable outcomes

Five-year results from a Japanese post-market surveillance study aimed at evaluating the Zilver PTX drug-eluting stent (DES) in a real-world population show consistently positive outcomes. The findings were presented for the first time at the Cardiovascular and Interventional Radiological Society of Europe 2018 meeting (CIRSE; 22–25 September, Lisbon, Portugal), by Kimihiko Kichikawa, Nara Medical University Hospital, Kashihara, Japan.

ACCORDING TO KICHIKAWA, the use of the Zilver PTX DES (Cook Medical) in treating patients with femoropopliteal lesions have so far elicited favourable outcomes. Therefore, Kichikawa and colleagues took a multicentre, prospective approach to the post-market surveillance study that evaluated the DES in a real-world patient population.

A total of 904 patients with 1080 lesions were enrolled in 95 institutions in Japan and consecutively treated.

Comorbidities were present in the patient population, including a high incidence of diabetes (59%), chronic kidney disease (44%), and critical limb ischaemia (21%).

Stent integrity was assessed by radiography, with site-reported fractures reviewed by a radiographic core laboratory for classification of fracture type. The investigators noted any clinically driven target lesion revascularisation, defined as re-intervention performed for ≥50% diameter stenosis after recurrent clinical

symptoms of peripheral arterial disease.

Furthermore, clinical benefit was defined as freedom from the following; persistent or worsening claudication, rest pain, ulcers, or tissue loss.

The investigators found that lesions were complex; their average length at 14.6mm, with 44% found to be totally occluded and an additional 19% involving in-stent restenosis. Clinical follow-up that occurred through five years was obtained for >90% of eligible patients.

The five-year outcomes indicated that the rates of freedom from target lesion revascularisation were 74.2%, while the clinical benefit indicated for the patient population was 68.2%.

Speaking to the CIRSE audience, Kichikawa said these figures were indicative of: “Consistently good results in a challenging patient population including those with diabetes, renal failure, long lesions, in-stent restenosis, no runoff or critical limb ischaemia.” The ankle-brachial index and Rutherford scores further indicated that clinical improvement was

Patient population and lesion characteristics become more challenging in real-world, all-comer studies.

Zilver PTX

maintained over-time, after the rapid increase in Rutherford scores one year into the trial.

In conclusion, Kichikawa said: “Patient population and lesion characteristics become more challenging in real-world, all-comer studies.” However, he reiterated that the results of the study continue to show positive long-term outcomes and demonstrate the benefit of the Zilver PTX DES across a broad patient population.

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Peripheral arterial disease

Novel approach in treating stenotic peripheral arteries shown to be safe and effective Twelve-month data prove that intravascular lithotripsy; a novel approach using pulsatile sonic pressure waves to modify intimal and medium calcium in stenotic peripheral arteries, is a safe and effective treatment option. This is the result of the DISRUPT PAD II trial, presented by Andrew Holden, Auckland Hospital, Auckland, New Zealand, for the first time at the Cardiovascular and Interventional Radiological Society of Europe annual meeting (CIRSE; 22–25 September 2018, Lisbon, Portugal).

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peaking to the CIRSE audience, Holden explained that acute results were strong, with compelling safety data showing a final residual stenosis of 24.2%, with a high acute gain of 3mm and minimal vascular complications. In addition, Holden implied that the primary safety profile was “very good”, given that the only major adverse event through to 12 months was a dissection that occurred at the time of procedure.

DISRUPT PAD II was a non-randomised, multicentre study that enrolled 60 patients with complex, calcified peripheral arterial stenosis at eight sites. Patients were treated with the peripheral intravascular lithotripsy system (Shockwave Medical), and followed out to 12 months.

Calcium burden was significant, with 85% of the patient cohort exhibiting severe calcification involving both sides of the arterial wall (using the PARC definition; 50% of patients had severe calcification using the pre-defined Core Lab definition) and an average length of calcification of 98.1mm.

The study investigators report high acute gain (following low pressure) in terms of the reduction of pre-procedural severity of stenosis, as well as cross-sectional area gain. This resulted in low dissections and minimal use of stents in this calcified population.

Additionally, 12-month primary patency was 54.5%, with a freedom from target lesion revascularisation rate of Andrew Holden 79.3% in a stand-alone therapy.

Primary patency outcomes were shown to improve by optimising the procedural technique: appropriate balloon sizing and intravascular lithotripsy therapeutic coverage resulted in the increased primary patency of 62.9% at 12-month follow-up, with freedom from target lesion revascularisation being 91.4%.

Target lesion patency; the primary effectiveness endpoint, defined as freedom from ≥50% restenosis, was found to be

69.8% (30/43 patients), as measured by duplex ultrasound.

Clinically, improvements in functional outcomes were sustained through to 12-months, in terms of both the anklebrachial index and the Rutherford score.

In conclusion, the DISRUPT PAD II trial remains the first and only core lab adjudicated study to exclusively enrol patients with heavily calcified lesions and follow up to 12 months. Holden maintained that when intravascular lithotripsy is utilised as a stand-alone therapy in this complex patient population, primary patency outcomes improve.

Regarding the next steps in clinical development, Holden stated: “Importantly, the DISRUPT PAD III trial is recruiting… a much larger, 400 patient trial looking to evaluate the role of intravascular lithotripsy in the setting of drug-coated therapy.” Specifically, patients have been randomised to intravascular lithotripsy in combination with the IN.PACT drug-coated balloon (Medtronic; the treatment arm) or plain balloon angioplasty and drugcoated balloon (the control arm), in order to address plaque modification in heavily calcified arteries. “This will be a very important trial to establish the benefit of intravascular lithotripsy in the DCB era,” Holden concluded.

Study points to discrepancy between instruments used to measure QoL versus health status post-amputation A prospective study observed that health status did not improve after amputation using a common questionnaire, yet improved quality of life appeared to be possible when using the WHOQOL-BREF (the World Health Organisation Quality of Life Instruments). Chloe Peters (Amphia Hospital, Breda, the Netherlands) presented the data at the European Society for Vascular Surgery (ESVS; 25–28 September, Valencia, Spain), emphasising that the findings highlight a discrepancy between the instruments attempting to measure health status and quality of life.

FOR PATIENTS WITH critical limb ischaemia, revascularisation is considered the first-line treatment to prevent major limb amputation. Peters emphasised that amputation is an unwanted outcome, not only because it precedes poor physical functioning, but due to the high mortality and significant costs following the procedure. However, Peters questioned whether these traditional outcomes are equally important for both the middle aged and the elderly.

With the current ageing population, Peters noted that patient reported outcome measurements have become more important in vascular surgery today. Although the main goal to prevent major limb amputation remains the same, it may be beneficial to understand how elderly patients experience amputation in the short term.

Peters pointed to one example of a patient reported outcome measurement, the SF-12 questionnaire: a widely used instrument used to assess health status. It consists of 12 questions, assessing both physical and mental health. However, Peters questioned whether the subjective questions such as “does your health limit you in climbing several flights of stairs?” included within this measurement objectify a patient’s health, or whether they simply measure the patient’s opinion of their health.

Another measurement Peters described

was the WHOQOL-BREF. According to Peters, this instrument was not designed to measure symptoms or conditions, but focusses on the effects of the disease, as well as the impact of health interventions on quality of life. “It is a subjective appraisal of health, and asks if the patient is satisfied with their function, [therefore] expressing the perception of functioning, but not the objective level,” said Peters.

Highlighting a problem within the literature, Peters noted that the SF12 has been incorrectly presented as a measurement of quality of life, consequently resulting in a lack of subjective quality of life measurements in previous critical limb ischaemia patients.

Therefore, the aim of the current prospective observational study was to evaluate the health status (SF-12) in relation to quality of life (WHOQOLBREF) in elderly patients with critical limb ischaemia undergoing major limb amputation.

Patients older than 70 with critical limb ischaemia were included, while patients with malignancy, lack of Dutch language skills and cognitive impairment were excluded from the study.

In a multidisciplinary vascular centre, 200 patients were selected for treatment by femoral experts. Patients were placed into one of four treatment groups: endovascular revascularisation, surgical

revascularisation, conservative treatment and primary amputation.

Patients were followed for a duration of a year, during which self-reported questionnaires were completed five times (including both the SF-12 and the WHOQOL-BREF). After one year, the patient cohort was divided into two groups: non-amputees (n=154) and amputees (n=46).

The values of the physical domain of the SF-12 questionnaire were compared to the normal value in the healthy elderly Dutch population; a value of 44. When comparing the baseline values within the physical domain to the norm, it became clear that patients at baseline were already impaired, given their score of 28.

However, for patients that had not undergone major limb amputation, a statistically significant improvement in physical health status first occurred at six weeks’ follow-up. Furthermore, after major limb amputation, there was no statistically significant decrease or increase in health scores.

In relation to the results of the WHOQOL-BREF, values were again compared to the norm for the physical quality of life of the same aged peers; at 14.87. Through this comparison, it was clear that at baseline, quality of life was impaired for both non-amputees and amputees (given the average scores of

10.7 and 11.3, respectively). Nonetheless, for non-amputees, an instant statistically significant improvement in physical quality of life appeared only one week after (with the score rising to 12 from baseline).

Furthermore, there was also a significant improvement in quality of life for the amputee cohort. For instance, the quality of life score reached the norm at six-months (14.7) and remained at this level through to 12 months.

When using the SF-12 questionnaire in the amputee elderly patient cohort, health status showed no improvement following major limb amputation. However, quality of life was found to have increased after amputation, when using the WHOQOLBREF. These findings led Peters to conclude that in elderly patients, health status does not improve after amputation using a common questionnaire, yet improved quality of life appears to be possible after major limb amputation, when using the WHOQOL-BREF. She stated that, “if there is one thing worth highlighting, it is the discrepancy between the health status instrument (the SF-12) and the quality of life instrument (the WHOQOL-BREF).”

Lastly, Peters noted that distinctive and subjective quality of life questionnaire’s, such as the WHOQOL-BREF, may provide very important measurements in terms of short-term outcomes.

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Innovation

BIBABriefings

Strong investment in clinical trials is key for leadership in drug-elution According to the Peripheral Usage and Attitudes Survey, physicians in Western Europe see strong investment in current and future clinical trials as the most important factor when considering which companies are the leaders in drug-elution technology (see Figure 1). Other important factors reported were having an expansive peripheral drug technology portfolio and providing clinical training/educational programmes.

Similarly, randomised controlled trial data was the most important driver in choice of device for managing superficial femoral artery lesions—whether the device was a bare metal stent, a drug-coated balloon, or a covered stent— and personal clinical experience was the second most important driver.

Benefits of Credence BtK bioresorbable scaffold apparent at six months

Speaking at an innovation session at TCT 2018 dedication to peripheral interventions, Gireesh Warawdekar (Holy Family Hospital, Mumbai, India) outlined the initial results for a novel below-theknee bioresorbable scaffold (Credence BtK, Meril). He reported that peripheral bioresorbable scaffolds had “intuitive promise” because they “leave nothing behind”, adding that the sirolimus-eluting Credence BtK scaffold was designed to degrade within two to three years. The scaffold has, Warawdekar commented, a PLLA strut thickness of 100μm, high vessel conformability, and optimal sidebranch access.

A first-in-human study is exploring the

safety and efficacy of the scaffold for the management of de novo lesions (length ≤56mm) in 30 patients with critical limb ischaemia. The safety endpoints are the absence of complications at one-month post procedure and scaffold thrombosis as per the Academic Research Consortium (ARC) criteria at five years; the performance endpoints include technical success at 48 hours and clinical success at each followup, limb salvage rates at six and 12 months, and primary patency rates at one month and at one, two, three, four, and five years.

According to Warawdeker, there was no ischaemia-driven target lesion revascularisation, ischaemia-driven target vessel revascularisation or scaffold thrombosis at 30 days or six months.

However, there was one limb amputation.

“The benefit of this novel Credence BtK bioresorbable scaffold was apparent at 30 days and at six months where distinctive improvements in both Rutherford Class and the ankle-brachial index were observed in all patients,” he noted.

Two other peripheral technologies were discussed at the TCT 2018 peripheral innovation session: the BlueLeaf percutaneous device (Intervene) for managing deep vein reflux, and the Soundbite Active Wire (Soundbite Medical) for chronic total occlusions in the peripheral arteries. Neither the Soundbite Active Wire nor the BlueLeaf device are approved for use in the USA, but the Soundbite device received CE mark approval in April this year.

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Increased used of FEVAR in 2018 A survey—Short Neck EVAR Usage and Attitudes Survey—indicates that the use of fenestrated endovascular aneurysm repair (FEVAR) for short neck aneurysms (<15mm) in Western Europe will increase in 2018.

Respondents (172 overall) reported that in 2017, they used FEVAR in 46% of procedures for short neck aneurysms 0–10mm and in 23% procedures for short neck aneurysms 10–15mm. However, they estimated that these figures would change to 50% and 26%, respectively, in 2018. Use of EVAR plus EndoAnchors (Medtronic) may also increase this year. The survey shows that they were used in 9% and 13%, respectively, for procedures for short neck aneurysms 0–10mm and 10–15mm in 2017 but, according to the predictions of respondents, will be used in 13% and 19% of such procedures this year.

Figure 2 outlines the primary treatment of short neck aneurysms 0–10mm in 2017 versus that in 2018.

Alternative to animal testing launched at TCT 2018

The 2018 Transcatheter Cardiovascular Therapeutics (TCT) meeting (21–25 September, San Diego, USA) saw the launch of the Replicator PRO (Vascular Simulators), a vascular replication system designed to help device development, demonstration and testing. The system can be used replicate both endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) procedures.

According to a press release, the Replicator PRO provides a better alternative to animal testing. The press release reports that 92% of successful drug trials in animals fail at the human trial stage, adding that a more representative system of human

BIBA Briefings

anatomy that can provide accurate feedback is needed.

Apostolos Tassiopoulos (Stony Brook Hospital, Stony Brook, USA) comments: “By giving the user the ability to perform a simulated procedure that takes place in the same haemodynamic conditions as it would in real life, there is an added fidelity component to the simulated procedure and it, therefore, makes the educational experience as close to reality as possible.

“In animal reliance testing, you never have the specific anatomy you are trying to treat, so Replicator PRO offers a much more relevant anatomical and haemodynamic environment.”

Replicator PRO will be available for shipment globally in the first quarter of 2019.

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America.

The platform also reviews data and news.

The aim of each report is to give an overview of the key information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact Laura James laura@bibamedical.com

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Profile

Gustavo Oderich

Originally from Porto Alegre in the south of Brazil, Gustavo Oderich speaks to Vascular News about his journey to the Mayo Clinic in Minnesota, his career mentors who taught him the value of both open and endovascular treatment, as well as his current research interests.

What drew you to medicine and to vascular surgery in particular?

I had to make an “educated guess” to go into medicine when I was 17-years-old. In Brazil, we have to sign up for the university entrance examination immediately after high school, so there is no transitional period to mature your decision. Clearly, I was not completely sure and debated a bit whether architecture should be my final call. In retrospect, I got it right and could not imagine myself doing anything else. Although my parents and close relatives were not physicians, I admired several of their friends who were surgeons or highly regarded doctors. Some were professors at the medical school. I had a strong sense I wanted to help people and I to use my hands. After I entered medical school it became clear that I had made the correct choice.

All my hard and important decisions were marked by serendipity and a bit of luck. I again struggled when I had to decide to go into surgery, but thought that working with my hands in the operating room environment and being able to change the natural course of diseases with an operation was appealing. I was correct again, and could not imagine myself prescribing pills all day long—surgery became a part of me. Finally, the decision to go into vascular surgery and to come to the United States came together in 1997. I was fascinated by the start of the endovascular revolution and the prospects of a changing specialty with fast incorporation of new technology. The finesse of open vascular reconstructions attracted me more than any other specialty.

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

I have been blessed with many “vascular surgery giants” during my training; perhaps I can say I had the best of the open and endovascular worlds. The major influences in my open surgical training were by Drs Peter Gloviczki and Tom Bower. Dr Peter Gloviczki is the consummate master academic surgeon. Not only is he exceptionally skilled and a magician inside and outside the operating room, he is a gentleman, an impressive educator and the most compassionate surgeon I have worked with. He has accumulated the highest accolades that an academic vascular surgeon can aim for, and continues to this date to promote my career with numerous opportunities. He has certainly set the bar very high for us at the Mayo Clinic.Tom Bower is a masterful clinician and surgeon. He had major influence on the way I conduct an open operation. He leaves no stone unturned, is exceptionally skilled, meticulous, and has attention to detail that is second to none. He taught me how to plan and conduct major open reconstructions. Tim Sullivan is responsible for my introduction to endovascular surgery. He is exceptionally skilled and showed that you can be an excellent open and endovascular surgeon. In addition to many teachings, he has been a great mentor academically, a friend and continues to be a major supporter in my career.

But my advanced endovascular skills were really awakened by Roy Greenberg. He really made me think outside of the box. Roy was a friend and a model. He opened my eyes to something I could not imagine before and everything really changed after my experience with Roy at the Cleveland Clinic. He taught me that the aorta is really an organ; prone to diffuse pathology, progression, and that aortic disease should be handled with an eye on how we manage the failure of our treatment, which will come if the patient survives long enough. I consider him the “Yoda” of endovascular aortic repair and credit him for my advanced fenestrated and branched techniques. Most

importantly, he made me realise how creative we can be with new techniques, so I continued to evolve a lot after I finished my experience with Roy. His organisation of clinical research and device trials formed the basis for our programme at the Mayo Clinic. Finally, Roy has influenced many of the thought leaders that I admire in our specialty, and of whom I continue to learn through discussions, publications and meetings. To mention a few, Stéphan Haulon, Tilo Kölbel, Matt Eagleton, Tim Resch and Tara Mastracci.

What have been your proudest moments?

My family is my greatest legacy and proudest achievement. My wife Thanila is my coach and “cheerleader” and my children, Gabriel (14) and Victoria (10), are the fuel that keep me wanting to pursue excellence. In my career, the proudest moment or lifechanging event was the chance I was given to train at the Mayo Clinic and to become a consultant. This really changed everything for me. In that moment I entered a new league. I think everything else was a consequence of drive, passion and dedication to perfect the techniques I have learned over the years.

Your research is focused on complex aortic disease – what have been the major advances and what is the greatest need?

Management of complex aortic disease is evolving at a fast pace, making it one of the most exciting areas to practice.

Advances have encompassed endovascular devices, ancillary tools, imaging applications, along with extensive experiences from many centres around the world.

The current state is to disseminate these techniques and adopt newer generation devices that aim to facilitate the procedures even further. We are still working on approving devices, training physicians and defining best practices.

Over the last decade, several centres published extensive experiences that have helped us better understand different aspects of the procedure, such as learning curve, patient selection, spinal cord injury and results of fenestrations versus branches. Newer ancillary tools have facilitated the technique, making it simpler and faster. Coupled with the technical advances, fixed imaging is totally different than a decade ago. Fusion and immediate assessment with cone beam computed tomography have been instrumental to reduce radiation exposure, facilitate implantation and allow identification of technical problems.

Despite these developments, only a few physicians have access to advanced technology. I am truly hopeful that this will change and that multiple devices by different companies will become available. Finally, we still need refinements in the bridging stents, which are an integral part of these devices and have been neglected in the past.

How have you seen the field develop during the course of your career?

Everything has changed since my foundation years, from how we manage venous, peripheral, carotid or aortic disease. I am privileged to have lived (during my training) through the endovascular revolution and the many changes that occurred in our practice from open to endovascular repair. While I started my career at the Mayo Clinic as an open surgery enthusiast, my practice is currently dedicated to aortic procedures and is 95% endovascular.

I believe the specialty of vascular surgery is one of the

most exciting in the field of surgery because of its fastevolving nature. I also believe that vascular surgeons are uniquely positioned to incorporate new technology in their practices, while still being able to perform open or hybrid procedures. As educators in vascular surgery, our concern has shifted to understand how we can develop higher level of open surgical skills among younger surgeons. I cannot emphasise enough the importance of mastering open surgical skills and understanding the concepts of anatomical dissection and open vascular reconstructions.

I believe the learning curve for open reconstructions is substantially steeper as compared to endovascular. Open cases are less reproducible and you need to see and do a lot to become a masterful surgeon. With less and less cases, we have increasingly relied on simulation, advanced

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What is the most interesting paper or presentation that you have seen recently?

The Group from Guy’s and St Thomas’ Hospital in London, UK, led by Bijan Modarai published a landmark paper in Circulation last year (El-Sayed T et al, Circulation 2017; 136(25): 2406-2416). The article highlighted eye opening findings on radiation-induced DNA damage in operators performing complex endovascular aortic repair. I think the authors are to be congratulated for their methodology and for bringing light on the deleterious effects of radiation. In that paper, acute DNA damage was blunted by leg shielding and this was incorporated into our practice.

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What are your current research interests?

At the Mayo Clinic we have built an advanced clinical research program that is responsible for designing and conducting several prospective studies, many in conjunction with industry. We currently have a team that involves a research manager, two coordinators and two advanced post-doctoral clinical research fellows.

We also offer a hands-on three-month advanced training on fenestrated and branch endografting. Our team helps conduct over 25 device trials and two physiciansponsored device exemption protocols, which have enrolled nearly 300 patients in a prospective study.

Our goal is to provide the highest possible quality of clinical data and level of evidence. We have investigated changes in quality of life and noticed that patients with thoracoabdominal aneurysms have major decline in physical metrics that do not quite return to baseline, even one year after the repair. Our job now is to identify why and how we can change that. We have also analysed a protocol to prevent spinal cord injuries using neuromonitoring, near-infrared spectroscopy and selective temporary aneurysm sac perfusion. Recently, we have presented at the Vascular Annual Meeting (VAM) a comparison of digital subtraction angiography, cone beam computed tomography (CT) and postoperative CT angiography. In that study, cone beam CT detected nearly all technical problems and decreased early reintervention compared to our historical results.

We are currently investigating the use of cone beam CT as the only method of immediate surveillance imaging.

We hope to present this second phase in the next VAM.

What advice do you hope your mentees/ fellows will always follow?

First never take shortcuts in your education just to finish your training a few years earlier. Your formative years are essential to building a foundation for you to continue to grow. To me, the secret of a successful career in surgery is drive, opportunity and determination. Without these three it is difficult or impossible to succeed at a higher level. Your training never ends and you need to adapt. Finally have the patient in the focus of your attention and always aim to do the best for the patient. I assure you will have failures, but at least you will have the comfort of a peaceful mind. training paradigms and teams that are dedicated to advance open or endovascular techniques.

What new vascular technology are you watching closely and why?

Our basic tools continue to be stents, wires, balloons and catheters, all under fluoroscopic guidance. And we are still battling bad complications such as stroke, paralysis and dialysis. This has to change. I think we will start seeing newer ways to treat vascular disease that are currently only in our imagination. Can we create stents that are living objects and that will progressively replace or strengthen the aorta, and not be subjected to the fatigue that fabricmetal combination has? Can we go away completely from fluoroscopy and perform these procedures with more precise imaging that does not even involve radiation? All these ideas are still investigational but I believe we will still see a new phase of endovascular therapy that will change our current paradigm. Our job is to stay attentive to change and to be willing to adapt and not become obsolete.

What are your interests outside of medicine?

I am from Porto Alegre, south Brazil, in the state of Rio Grande do Sul, land of gauchos. I am passionate about sailing. As a teenager and young adult, I was a very competitive sailor, representing Brazil in several South American and world championships in the classes of optimist, Snipe and 470s. I now I sail for leisure whenever I can (which is not easy in the Minnesota winter). Next, I am also a surfer; growing up in south Brazil I started surfing at age of eight and can surf reasonably well…but also not easy to surf in Minnesota. I am always doing some sort of fitness exercise. I went through P90X, Insanity, T25 and cross training programmes. In the last several years, I have been an avid runner, completing half and full marathons. I would say that is what I currently do more often, but when I see the water and a boat, I give up on the running right away!

My main interest is my family, Thanila and our two kids—Gabriel and Victoria. We are always together whenever we have any free time doing family activities.

I love music and cinema and have an eclectic taste for the classic and the 1990s in general.

Current appointment

Chair of the Division of Vascular and Endovascular Surgery, Department of Surgery, Mayo Clinic, Rochester, USA

Professional career (all present)

Consultant, Division of Vascular and Endovascular Surgery, Department of Surgery, Mayo Clinic Professor of surgery, Mayo Clinic College of Medicine and Science Programme director, Vascular Surgery Integrated Residency, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science Programme director, Vascular Surgery Fellowship Program, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science Programme director, Vascular Surgery Advanced Aortic Fellowship, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science Director, Aortic Center, Department of Surgery, Division of Vascular and Endovascular Surgery

Professional highlights

Chair, Reporting Standards Fenestrated and Branched Endografts, Society for Vascular Surgery Associate editor, Annals of Vascular Surgery National principal investigator, Cook Thoracoabdominal Branch Stent Graft Trial and ZFEN Plus Stent Graft Trial

Editorial board:

Journal of Vascular Surgery Journal of Endovascular Therapy Vascular Surgery Perspectives in Vascular Surgery and Endovascular Therapy Indian Journal of Vascular and Endovascular Surgery Brazilian Journal of Vascular Surgery Spanish Journal of Surgery Research and Annals of Vascular Surgery

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World’s largest multicentre DCB arteriovenous registry data prove Lutonix balloon is safe

New interim data from the first and only global drug-coated balloon (DCB) multicentre arteriovenous registry demonstrate that the Lutonix DCB is a safe and effective treatment of dysfunctional arteriovenous fistulae. Panagiotis Kitrou (Patras University Hospital, Patras, Greece) presented this finding on behalf of the global principal investigator Dimitrios Karnabatidis (also Patras, Greece) at the 2018 annual meeting of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE; 22–25 September, Lisbon, Portugal).

Lutonix

THE PROSPECTIVE, MULTICENTRE, single arm, real-world registry investigated the clinical use and safety of the Lutonix drug-coated balloon percutaneous transluminal angioplasty (PTA) catheter (BD) for the treatment of dysfunctional native and synthetic arteriovenous fistulae. Three hundred and thirty-six patients have been enrolled in the study across 25 international sites, representing a heterogeneous patient population.

At baseline, approximately one quarter of the patients enrolled in this trial had synthetic grafts.

Kitrou told delegates that it was “very important to see how this patient cohort respond to DCB treatment.”

Approximately half of the cases were in the upper arm, one third in the forearm, and the remaining patients had fistulae in the antecubital fossa. Just under half of the patients enrolled in the study (47.6%) had restenotic lesions, in-stent restenosis occurred in 11.4% of patients, and central veins were also included in 11.6% of the cases. Of these lesion characteristics, Kitrou said, “This is what we come across in our everyday practice.”

The primary safety endpoint of freedom from any serious adverse event involving the arteriovenous access circuit through 30 days was achieved in 99.4% of the cases. Interim results from 77 patients at 180 days’ follow-up show an average target lesion primary patency of 74.9%. The target lesion primary patency rate represents the primary efficacy endpoint of the study. Kitrou noted that these positive results are aligned with other Lutonix arteriovenous studies, including the data presented by Scott Trerotola (Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, USA) at CIRSE, and a retrospective analysis conducted in Kitrou’s department.

The interim access circuit primary patency with the

same 77 patients at six months’ follow-up was similar to the target lesion primary patency, at 70.9%.

Commenting on his use of the Lutonix DCB in clinical practice in light of these results, Kitrou commented, “If you look at all the studies published so far, I think the data give you approximately 500 patients treated with DCB. So I think it is a bit early to start doing analyses on which lesion is better and which type of access site is better for DCB. So in our practice, whenever there is an angioplasty, it is followed by a DCB, excluding the synthetic graft—plain and simple.”

All patients in this study were treated per standard of care when using the Lutonix DCB, and the DCB procedure was performed per the instructions for use.

Follow-up visits, through 12 months, were also done per standard of care. Patients with arteriovenous fistulae or grafts, presenting with any clinical, physiological or haemodynamic abnormalities warranting angiographic imaging as defined in the K/DOQI guidelines were included. Among the exclusion criteria were patients participating in an investigational drug or device study which has not yet reached its primary endpoint or had a non-controllable allergy to contrast were excluded.

In our practice, whenever there is an angioplasty, it is followed by a drug-coated balloon— plain and simple.

Clinicians in the UK building “first-ofits-kind” vascular access graft registry The Vascular Access Graft Registry is a new initiative to provide a database dedicated to the early and long term outcomes of vascular access grafts in the UK. James Gilbert of the Oxford University Hospitals NHS Trust in Oxford, UK, spoke about the registry and why it is needed, at the Vascular Access Society of Britain and Ireland annual meeting (VASBI; 27–28 September, Portsmouth, UK).

“THERE ARE LOTS of grafts on the market”, Gilbert emphasised, and depending on “what you believe in scientifically as a surgeon”, as well as on any potential connections in the industry, he argues these are the opinions and motivations which largely will dictate which graft a surgeon uses. In itself, Gilbert does not see this as an issue. However, he noted, problems arise for a number of reasons.

“Current published literature on the outcomes of grafts is retrospective and small volume, there is huge variability in reported data about the grafts inserted and infection rates, probably a slight reporting bias by some clinicians, there is no detailed data about the grafts inserted, there is no standardised approach—all surgeons do things differently—and I think the key thing is, we do not really know which is the best graft to use and for what kind of patient.”

The Vascular Access Graft Registry is striving to produce a database for clinicians in the UK to record key early and long term outcomes, and collect data regarding graft insertions. Such a database will facilitate multivariate analyses and larger retrospective studies, as well as provide information for the wider access community, including industry.

Gilbert presented one such retrospective review, using data entered to date from 2015 to 2018. This included 146 patients with arteriovenous grafts, and a total of 329 procedures. Three hundred and fifty-four grafts have thus far been registered, and although Gilbert encouraged clinicians around the country to use the registry and to keep recording data, in order to produce a larger database, there are some things the registry could already show.

Overall, Gilbert noted, perioperative death was low, at 0.6%, and perioperative graft loss rate was 2.8%. At least one follow-up episode was recorded for 72% of patients, and long term reported death rate was 19.4%.

Concluding, Gilbert said that although it is “a painful business putting in data, and an even bigger pain to analyse it”, the effort of recording outcomes perioperatively and in the long term will continue to shape our understanding of vascular access grafts.

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A case for algorithms in dialysis access Nicholas Inston

Designing the dialysis algorithm

Comment & Analysis Decision making in vascular access appears to be simple.

Guidelines are clear and consistent. It is widely acknowledged that an arteriovenous fistula (AVF) is the gold standard and should be placed in a distal position on the non-dominant arm in patients prior to starting dialysis. Radiocephalic and brachiocephalic arteriovenous fistulas are preferred to brachiobasilic transpositions and arteriovenous grafts (AVG).

Central venous catheters (CVC) should be avoided at all costs in all patients.

T

he rationale behind these standards is that patients commencing dialysis on a mature autologous fistula have better patency rates, require less of interventions, have lower rates of access related sepsis and the overall morbidity and mortality is much lower when compared to AVG and central venous haemodialysis catheters. As a consequence, the decision for the referring nephrologist appears easy: an arteriovenous fistula should be booked as soon as a decision for dialysis is considered.

But is decision making in patients approaching end stage kidney disease as straightforward as this?

Before referral, difficult discussions regarding the best and most appropriate renal replacement therapy are required.

Pre-emptive transplantation, particularly living donor transplantation, peritoneal dialysis, haemodialysis and conservative care are all options, but may not be all suitable for a particular patient. Studies have shown that patients’ choices differ greatly from clinicians’ choices but in many cases the availability of each option may be limited.1 For many patients a transplant will not be an option. In the USA, 100,000 patients are listed for kidney transplant, yet only 17,000 kidney transplants occur per year, with a third from living donors. In the UK, 3,596 transplants were performed last year, with a waiting list of 7,738. On closer inspection, the active waiting list is 4,757, with almost 3,000 patients suspended on the waiting list. Of the transplants performed, less than a third were performed pre-emptively on

80% are functionally cannulated within one month.

It is clear that dialysis access decision making is complex. There are at least 20 anatomical sites for surgical placement of dialysis access giving upwards of 300 options. There are multiple techniques described for formation and maintenance. Preoperative enhancement is claimed to improve outcomes and prepare the veins for maturation. Perioperative pharmacological agents may play a role. Post-operative ultrasound and surveillance, interventions such as assisted maturation and various approaches as to when and how to cannulate, all have an impact on outcomes.

patients who had not started dialysis.

Less than 30% of patients requiring maintenance renal replacement therapy do so with a transplant. Only a fifth of patients in the USA will be listed for a transplant. Similarly, in the UK around 30,000 people are on dialysis, yet only a sixth are active on the waiting list for a kidney.2,3,4 In the majority of patients reaching end stage kidney disease, haemodialysis will be the treatment by default as peritoneal dialysis accounts for only 11% of global dialysis.5 Haemodialysis requires vascular access, and the decision for the type of vascular access must be considered as should the site of the access and when it should be formed.

Evidence varies widely as to what sites are most suitable. In general, the outcomes of wrist fistulae are worse than elbow fistulas; smaller vessels do worse than larger vessels; younger patients do better than older; males have better outcomes than females and pre-dialysis does better than those on dialysis. Comorbidities should also be considered, as diabetes, hypertension and peripheral vascular disease all have impact on fistula outcomes.

Whilst guidelines clearly advocate a distal-first policy, the outcomes of these fistulae are poor in the USA but the rates of radiocephalic fistulae have dramatically declined from 70% to 32% over the past 20 years. Despite this, the outcomes of new fistulae is poor and only 64% of all new AVFs are successfully used.6 The primary failure of radiocephalic fistulas is high, even with selection bias.7 In Japan, the picture is different, with 95% of fistulas in the forearm and over

In systems with multiple options the use of algorithms can be applied to navigate through complex interactions.

An algorithm can be defined as “a sequence of instructions that are followed to complete a task” and the application of available evidence to produce guidelines and apply these to dialysis access pathways is attractive.

An algorithm is a set of inputs which through a series of operations (yes/no; and/or) lead to outputs or solutions.

In designing a dialysis algorithm, a reductionist approach is required and the framing questions need to be concise and clear. For example, “What is the best choice of dialysis modality?” depends on many inputs such as is the patient pre-dialysis, already on dialysis or a failing transplant. The outputs are limited as only peritoneal dialysis, haemodialyis, transplantation and conservative/end of life care will be possible.

includes prevention of progression of end stage renal disease, several types of renal transplantation, counselling for mode of dialysis before it is needed, vein preservation and type and site of dialysis access at the appropriate time.

The timing of access formation is particularly problematic. The rate of decline of kidney function is difficult to predict and results in many unused fistulas, unnecessary interventions, patient (and surgeon) fatigue and loss of confidence.

The availability of devices also influences decisions. Due to marketing and regulatory differences a number of devices are available in the EU prior to the USA and vice versa.

Examples include biological grafts and endovascular fistula devices where an algorithm cannot be applied as the options are not universal. In many situations financial factors affect decisions. This may be patient or physician based or a broader political edict.

So, can a single unifying algorithm can be constructed for dialysis access?

The variation of patient scenarios, the chronicity of disease and the multiple options to treat make this unlikely.

The possibility of more discrete algorithms for specific situations is more attractive and may serve to break down the overwhelming complexity.

Is decision making in vascular access easy? The answer clearly is no. Outcomes remain poor with wide variation globally. Guidelines may be useful, but evidence based algorithmic tools may be a better approach with potential benefit to both the expert and the enthusiast, whilst still maintaining patient-centred choices.

The possibility of more discrete algorithms for specific situations is attractive and may serve to break down the overwhelming complexity.

More specific algorithms can also be developed and may be more useful. An example could be “What is the option for a young haemodialysis patient requiring vascular access with no upper limb veins on mapping and bilateral central stenosis?” In this case the inputs may include the results of vein mapping, the specific central venous stenosis classification, local expertise and patient factors such as body mass index, age and prognosis. Outputs from this algorithm include loop thigh graft, HeRO graft, permanent central venous catheter and withdrawal from dialysis and palliative care.

In designing an algorithm for dialysis access a number of important factors must be incorporated. The chronicity of renal disease requires that the pathway reflects a lifelong strategy which

Nicholas Inston is the chairman of the Vascular Access Masterclass at the annual Charing Cross Symposium (CX) in London, UK, and a consultant renal transplant vascular access surgeon at the University Hospitals Birmingham in Birmingham, UK. References 1. van der Veer SN, Haller MC, Pittens CA, Broerse J, Castledine C, Gallieni M, Inston N, Marti Monros A, Peek N, van Biesen W. Setting Priorities for Optimizing Vascular Access Decision Making--An International Survey of Patients and Clinicians.

PLoS One. 2015 7;10(7):e0128228.

2. https://www.odt.nhs.uk 3. https://unos.org 4. https://www.kidney.org 5. Jain AK, Blake P, Cordy P, Garg AX. Global Trends in Rates of Peritoneal Dialysis. J Am Soc Nephrol.

2012; 6. Allon M. Lessons from International Differences in Vascular Access Practices and Outcomes. Am J Kidney Dis. 2018 ;71(4):452–4.

7. Wilmink T, Hollingworth L, Powers S, Allen C, Dasgupta I. Natural History of Common Autologous Arteriovenous Fistulae: Consequences for Planning of Dialysis Access. European Journal of Vascular and Endovascular Surgery. 2016.

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Covered stent provides greater patency rate than angioplasty alone The Covera vascular covered stent (BD) has a superior six-month primary patency rate than standard balloon angioplasty, with an equivalent safety at 30 days, when used in the treatment of stenotic lesions in arteriovenous (AV) fistula patients. Data from AVeNEW, the first level-one clinical trial on the use of a covered stent to treat these patients, were reported at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 22–25 September, Lisbon, Portugal).

PRINCIPAL INVESTIGATOR BART Dolmatch (Department of Radiology, Palo Alto Medical Foundation, Mountain View, USA) told delegates: “The primary endpoint was six-month target lesion primary patency [TLPP], and in the covered stent group the primary patency was 78.7%, whereas in the angioplasty group it was 47.9%; that is greater than 30% difference at six months, with a p value that was highly significant at <0.001.”

The primary safety endpoint was measured by freedom from an event resulting in intervention, hospitalisation, or death at 30 days. The study found that use of the vascular covered stent was non-inferior to percutaneous transluminal angioplasty (PTA) alone.

Dolmatch said: “You can see a comparable safety profile for both the covered stent group and the angioplasty group, with a high significance for showing non-inferiority of the Covera stent graft compared to angioplasty.”

The prospective, international multicentre study randomised 280 patients (1:1) to receive either balloon angioplasty or angioplasty plus the Covera stent graft for the treatment of stenotic lesions in the venous outflow of upper extremity AV access circuits in patients dialysing with an autogenous fistula. The Covera vascular covered stent is a polytetrafluoroethylene- (ePTFE) covered self-expanding stent. Patients were treated at 24

Covera

centres in the USA, Europe, Australia, and New Zealand, and exhibited greater than 50% stenosis in the venous outflow of the AV access circuit, with clinical or haemodynamic evidence of fistula dysfunction.

Dolmatch explained: “The study included the typical sort of dialysis patients we see across the globe, with a mean age of about 62 to 63 years, slightly more weighted towards males than females, and about 30% of patients had a BMI [body mass

index] that was… in the obese or heavy range. The patients had typically brachial cephalic or brachial basilic fistulae.”

Secondary measures included access circuit primary patency and the number of reinterventions needed to maintain patency. The number of target lesion re-interventions for the covered stent group was 0.3 for the six-month period, compared to 0.8 for the angioplasty group. Acute technical and procedural success rates were also high in the stent group, at 100% and 98.6%. “Overall,” said Dolmatch, “the procedure was extremely successful, with a very low complication rate.”

He added: “All of the stent graft sub-analyses showed superior outcomes compared to balloon angioplasty—for instance, the use of treatment in the cephalic vein arch, with much better outcomes with the stent graft group compared to angioplasty.”

The vascular covered stent had a success rate of 78.7% in the cephalic vein arch versus 38.3% for PTA alone, a difference of 37%. TLPP was maintained in 86% of de novo lesions and 77.7% of restenosed lesions in the stent group, compared to 65.6% and 40%, respectively, for angioplasty alone.

The most commonly used diameters of stent graft used in the study were 9mm and 10mm, and stent graft lengths were typically between 40 and 60mm.

Follow up in the AveNEW trial is ongoing for two years, and Dolmatch expressed his optimism about future results. “The divergence [in primary patency] is really starting at about 60 days and continuing on to 180 days. This is six-month data.

We are looking forward to seeing 12-month, 18-, and 24-month data showing the superiority of stent graft treatment of the stenoses in fistulae, compared to angioplasty.”

Consecutive use of Lutonix DCB for treatment of dysfunctional dialysis access found to be safe A study has concluded that the Lutonix drug-coated balloon (BD) for the treatment of dysfunctional dialysis was safe to use consecutively in the same lesion. Panagiotis Kitrou from the University Hospital of Patras, Patras, Greece also reported that there was no significant difference in target lesion primary patency between the first and second procedure, although a numerical improvement was observed in favour of the second procedure. These data were presented by Kitrou at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting (22–25 September, Lisbon, Portugal).

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revious studies had published data on the safety and effectiveness of drug coated balloons (DCBs) in over 500 patients across randomised controlled trials, registries, and retrospective audits. According to Kitrou, those results suggested a consistent safety profile and a high level of technical immediate success, provided that “proper vessel preparation” is performed.

However, no data existed on the impact of consecutive DCB treatments on the same target lesion. Therefore, Kitrou and colleagues set out to evaluate the outcome of two or more consecutive treatments using a Lutonix DCB. The investigators performed a single centre retrospective longitudinal analysis over a period of three years (January 2015 to December 2017), evaluating a consecutive approach to treating dysfunctional arteriovenous (AV)

dialysis access; both fistulae (present in 60.5% of the patient population) and grafts (39.5%).

In the 165 patients that were treated in total, 339 Lutonix DCBs were used in 257 procedures. A large proportion of the patients were male (73.7%).

Among the 38 patients that underwent a minimum of two procedures, 112 procedures were performed (with 22 patients treated twice and the remainder treated more; up to six times) using 133 devices. The mean balloon diameter was 8.13mm (3–12mm) and mean length was 63.16mm (40–150mm) with the majority of consecutive treatments carried out on the left side, predominantly involving cephalic vein stenosis.

There were two primary outcome measures, i.e. safety—defined as freedom from any reported serious adverse event involving the AV access circuit up to 30days following the procedure—as well as

effectiveness based on the non-inferiority hypothesis that the second treatment will be as effective as the first regarding postintervention primary patency.

The mean lesion follow-up was 617 days (ranging from 175 days to 1,100 days). The authors noted that there were no minor or major complications correlated with the device or the procedure in any of the cases within the first 30 days following the procedure, so safety was reached in all cases (112/112 procedures).

Median target lesion primary patency was 216 days for the first intervention and 280 days for the second consecutive intervention, demonstrated through a Kaplan-Meier survival analysis (p=0.37).

According to Kitrou, if patients that only had two procedures (22/38) are included in the analysis, then a significant difference is observed, in favour of the second intervention (p=0.03).

The investigators concluded that

Panagiotis Kitrou

consecutive use of the Lutonix DCB for the treatment of dysfunctional dialysis exhibited a promising safety profile. Additionally, when taking into account all of the patients, no significant difference in target lesion primary patency between the first and second procedure was found, although a numerical improvement was observed in favour of the second procedure. Yet, Kitrou and colleagues noted that the results show consistent target lesion primary patency regardless of the ageing arteriovenous access.

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Paclitaxel DCB no better than placebo to treat stenosis in patients with arteriovenous fistulae In a study evaluating the efficacy of a paclitaxel drug-coated balloon (DCB) in inhibiting restenosis and in ensuring long-term patency in patients with an arteriovenous fistulae (AVF), the paclitaxel DCB did not show superiority to a placebo high pressure balloon at 12 months’ follow-up. Manuela Moreno-Ramírez (Department of Nephrology, Juan Ramón Jiménez Hospital, Huelva, Spain) presented these results of the EffPac AVF trial at the Cardiovascular and Interventional Radiology Society of Europe annual meeting (CIRSE; 22–25 September, Lisbon, Portugal).

THE TRIAL WAS an investigatorinitiated, prospective, multicentre, double blind, randomised study conducted across four Spanish hospitals.

One hundred and seventy-eight dialysis patients included in the study were divided into two groups: those treated

with a paclitaxel DCB—the CE-marked Passeo-Lux 18 (Biotronik)—and those treated with an uncoated high pressure balloon, who were recipients of a placebo.

The placebo involved the use of a safe and biocompatible non-hydrophilic excipient called butyryl-tri-hexyl (BTHC) that

facilitates the delivery and absorption of the drug from the vessel wall.

Moreno-Ramírez emphasised the need for new procedures to treat stenosis, telling the CIRSE audience that “Difficulties with vascular access are an important source of morbidity and mortality in haemodialysis

patients. Stenosis could be treated with percutaneous transluminal angioplasty (PTA), but the primary patency rate is only 40–50% at one year—hence, new procedures are needed.” Thus, the study investigators were interested in researching the paclitaxel DCB as a possible alternative treatment strategy.

However, neither the primary nor the secondary endpoints of this study were met, with the paclitaxel DCB failing to demonstrate superiority over the placebo.

In addition to the primary endpoints of safety and efficacy, Moreno-Ramírez and colleagues sought to determine differences in survival rates. They found none. Despite the mean survival in the DCB group being higher, at 265 days versus 237, this was not statistically significant. There were therefore no statistically significant differences in survival at 12 months’ follow-up in terms of stenosis location, type of arteriovenous fistulae, or previous angioplasty. MorenoRamírez summarised: “We think this result is not clinically relevant.”

This finding is the same as that of another multicentre clinical trial with a significant sample size, conducted

by Scott Trerotola and colleagues (Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, USA).

Trerotola concluded in 2018 that, despite finding a slight improvement in survival using the Lutonix DCB (BD) compared to a placebo at six months’ follow-up, the difference was not statistically significant. However, several other previous studies, such as the IN.PACT trial by Panagiotis Kitrou (University of Patras, Patras, Greece) and colleagues—investigating at the Admiral DCB (Medtronic) versus a placebo—contradict this conclusion, finding a definite improvement in survival with a DCB compared to uncoated alternatives.

However, Moreno-Ramírez does believe it is important to note that the global survival rates in her team’s study at 12 months are superior to that in previously published studies, at almost 60%. Moreno-Ramírez attributes this to the use of a high pressure balloon for angioplasty.

Clarifying her methodology, MorenoRamírez explains that for every patient enrolled in the present study, both those in the DCB arm and the placebo arm, the first angioplasty utilised a high pressure balloon. Next, MorenoRamírez and colleagues carried out a fistulography to discover if the first angioplasty had been effective.

Allocation into the two different randomised groups occurred then, before a second angioplasty.

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Farewell to a trail blazer

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In memorium

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The field of vascular surgery has said goodbye to one of its greats with the passing of Bert Eikelboom.

A former president of the European Society for Vascular Surgery (ESVS), Eikelboom demonstrated his commitment to the field when he continued with his research, international commitments, and society duties, even after a Parkinson’s disease diagnosis meant that his operating days were over.

orn on 4 January, 1947 in the Netherlands, the son of a general practitioner, Eikelboom chose medicine and economics as his path of study at the University of Utrecht.

He was a most active student and spent a year in South America.

Later, Eikelboom took a Fullbright scholarship to New York.

Upon returning to the Netherlands, Eikelboom became chief of Vascular Surgery at St Antonius and a founder of the Netherlands Society for Vascular Surgery. Eikelboom had a genuine interest in the applications of non-invasive vascular diagnostic instruments, as well as minimally invasive vascular interventions.

A trail blazer, Eikelboom commenced one the first carotid surgery randomised controlled trials in 1982. At the time, he was also one of the few European surgeons to contribute more than once to the Society for Vascular Surgery (SVS) in the USA. Further, Eikelboom was involved with the creation of the European Society for Vascular Surgery, and presented many paper at the annual meetings over the years.

Eikelboom will be remembered for the way he used his personal knowledge of Parkinson’s disease to the benefit of the management of his own patients by creating a more patientfriendly environment in his clinic. There could be few who have done more for the standards of vascular surgery in Europe than Bert Eikelboom.

Bert Eikelboom was featured as the profiled physician in issue 1 of Vascular News

Medtronic co-founder Earl Bakken passes away at age 94 Medtronic has announced that its co-founder, Earl E Bakken, passed away peacefully on 21 October, 2018 at his home on Kiholo Bay on the Big Island of Hawaii, USA. He was 94 years old.

“TODAY WE ARE saddened by the passing of Earl Bakken, but we also honour and will forever cherish the life of a beloved man whose brilliance and vision have improved the lives of millions of people around the world,” said Omar Ishrak, Medtronic chairman and chief executive officer. “The contributions Earl made to the field of medical technology simply cannot be overstated. His spirit will live on with us as we work to fulfil the Mission he wrote nearly 60 years ago—to alleviate pain, restore health, and extend life.”

In 1949, Bakken founded Medtronic with his brother-in-law, Palmer J Hermundslie. Before retiring as chairman in 1989, Bakken led Medtronic for 40 years, guiding the company from humble roots into one of the world’s premiere medical technology company.

Born in Columbia Heights, USA, Bakken graduated from high school in 1941 and enlisted in the Army Signal Corps where he served in World War II as a radar instructor. After leaving the Army, he attended the University of Minnesota, earning a degree in electrical engineering. While a graduate student,

Bakken did part-time work repairing delicate lab equipment at Northwestern Hospital in Minneapolis.

Demand for these services grew, and on 29 April, 1949, Bakken and Hermundslie formed a business partnership. They called the company Medtronic, with its headquarters in a modified garage in northeast Minneapolis.

While installing and servicing devices used during early open-heart surgeries, Bakken and Hermundslie built relationships with physicians at University Hospitals, Minneapolis. The late C Walton Lillehei, a young staff surgeon at the time, was pioneering procedures to help “blue babies” born with oftenlethal heart defects. Following a power outage in the Twin Cities that caused the death of an infant, Lillehei asked Bakken to find a solution. Bakken responded by building the world’s first wearable, transistorised pacemaker. He adapted a circuit described for an electronic transistorised metronome in the magazine Popular Electronics. This milestone is viewed by many as the “birth” of Medtronic. Pacemakers, however,

were only one product in a growing, but increasingly diverse, product line.

In 1960, in an effort to more clearly define Medtronic’s areas of concentration and its values, Bakken wrote the Medtronic Mission, which has guided the company and remains unchanged.

In Dec. 2007, at age 83, Bakken became the first recipient of an honorary Medical Degree from the University of Minnesota, recognising his contributions in the medical field. During his life, he also received honorary doctorates from the Universities of Hawaii, Tulane, and the Albany College of Pharmacy. In 1995, Bakken was named to the Minnesota Inventors Hall of Fame and received an Outstanding Achievement Award from the University of Minnesota in 1981. In 1984, his cardiac pacemaker was named one of the 10 most outstanding engineering achievements of the last half century by the National Society of Professional Engineers. In 2014, Bakken received the Lifetime Achievement Award from the Advanced Medical Technology Association.

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Juxtarenal aneurysms

Endovascular approach beats open surgery for juxtarenal aneurysms in CIRSE vote Open repair compared with endovascular techniques for the treatment of juxtarenal abdominal aortic aneurysms (AAAs) remains a hotly debated topic in aortic interventions, especially because there are no randomised controlled trials reporting direct comparisons.

But to what extent can the desirable mortality rates observed with open repair be attributed simply to patient selection bias? At the Cardiovascular and Interventional Radiological Society of Europe annual meeting (CIRSE; 22–25 September, Lisbon, Portugal), notable demographic discrepancies, secondary re-intervention rates and long-term mortality for the two treatments were all debated at length.

Before the debate began, an audience poll indicated that 80% of CIRSE delegates were in favour of endovascular repair, with only 20% agreeing that open surgery is better for juxtarenal aneurysms.

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ttempting to sway their stance, Stefano Michelagnoli from San Giovanni di Dio Hospital, Florence, Italy, pointed to data that indicated encouraging short- and longterm outcomes for the conventional surgical repair of pararenal AAAs. The study—inclusive of 200 patients, 78% of whom had juxtarenal aneurysms— reported a 30-day mortality rate of 2.5%. The authors (Angela M R Ferrante and colleagues) also reported that late renal failure was observed in 6.2% of the patients, however, this was not a predictor of mortality.

Michelagnoli also highlighted a more recent retrospective analysis, conducted

by Alessandro Desole et al over a period of 10 years, published in Annals of Vascular Surgery, which reported a 30-day mortality rate of 0.6% following open repair. The paper concluded that open repair of juxtarenal AAAs remains safe, effective and durable; both in the long-term and in relation to patients with multiple cardiovascular risk factors.

However, Andy Winterbottom (Addenbrooke’s Hospital Cambridge, Cambridge, UK) argued that endovascular repair is better for the treatment of juxtarenal AAAs and speculated that these low mortality rates observed following open repair may be attributed to patient selection bias. After noting that careful patient selection for open repair leaves the “unfit” patients to undergo fenestrated endovascular aortic repair (FEVAR), Winterbottom nonetheless presented the CIRSE audience with systematic reviews that reported respective 30-day mortality rates following FEVAR procedures.

For example, a paper by Sergio Quilici Belczak published in Clinics, observed a 30-day mortality rate of 2.5% for open repair, yet only 0.9% for FEVAR. A further systematic review conducted by Ian M Nordon et al reported a rate of 1.4% (as opposed to 3.6% for open surgery; published in the European Journal of Vascular and Endovascular Surgery); adding to the profile of promising outcomes, which Winterbottom said are also reproduced throughout single centre reviews.

Nonetheless, Michelagnoli maintained that despite many advances in EVAR technology, the need for open surgical conversion persists. Importantly, he noted that one has to consider open repair in case of a type Ia endoleak. He referred to a paper by Salvatore T Scali et al, published in the Journal of Vascular Surgery, that reported a one-year survival rate of 83% for open surgical conversion

(from EVAR), and 91% for open juxtarenal aneurysm repair. This led the authors to conclude that while elective open surgical conversion for type Ia endoleak can be technically challenging, it is not associated with an increased mortality compared with open juxtarenal aneurysm repair in appropriately selected patients. The authors further suggested that these findings should be considered before pursuing complex endovascular remediation of EVAR failures.

In review of the aforementioned evidence, Michelagnoli concluded that open surgery for juxtarenal aneurysms is better for high-volume centres with high specialisation for the treatment of complex aortic aneurysms. Furthermore, he stated that the “modern” vascular surgeon should know how to perform this kind of surgical procedure in order to be ready for early and late conversion of EVAR. Lastly, Michelagnoli maintained that renal function should be a key consideration in the early and long-term period of patients undergoing suprarenal clamping.

Winterbottom pursued his argument for EVAR procedures, however he acknowledged the issue of secondary re-intervention rates. Regardless, he said that open repair patients do have significant problems with longer stay and in certain circumstances, significant increases in major adverse events.

Continuing, he argued that even amongst smaller centres, FEVAR demonstrated compelling 30-day mortality rates, as well as freedom form all-cause mortality through five years. Winterbottom pointed to a particular paper—published in the European Journal of Vascular and Endovascular Surgery—that reported a 30-day mortality rate of 0.7% for FEVAR; a finding which led the authors to conclude that FEVAR as a first-line strategy was associated with high technical success and low operative mortality.

In rebuttal of another argument against EVAR—that physicians are carrying out more complex aneurysm repair—Winterbottom presented a source that compared standard twovessel fenestrated stents with the more complex (three or four vessel) type and found no difference in 30-day mortality rates (0.5% for both standard EVAR and complex).

Regarding the long term follow-up of FEVAR, Winterbottom pointed to a study published in Journal of Vascular Surgery that reported 12-year survival rates following fenestrated endografts

for juxtarenal AAAs. Although the rate at eight years was only 20%, aneurysm-related mortality was only 2%. Addressing the CIRSE audience, Winterbottom said that follow-up can become difficult, “and one must take into account that the population has been pre-selected… if they are not fit for open repair”.

Winterbottom highlighted a systematic review of chimney graft data. A study conducted by Bengt Lindblad and colleagues published in the European Journal of Vascular and Endovascular Surgery reported a 30-day mortality rate of 4% overall— which Winterbottom noted was not as encouraging as the fenestrated data.

However, he also acknowledged that these patients were unfit for open repair, and most probably turned down for FEVAR, making them a select group of patients.

However, referring to both the PROTAGORAS and the PERICLES

especially as results are better in older, sicker patients. FEVAR is the preferred option for juxtarenal aneurysms—even when considering the complexity—as similar outcomes are achieved regardless. Lastly, chimney EVAR is an option for urgent cases, or when the anatomy is not suitable for fenestrated repair.

During discussion with the CIRSE audience, questions relating to fitness and patient selection in terms of the potential bias this causes in the literature were raised. “The problem is that mortality in very old and sick patients is terrible, so this kind of [open repair] surgery is not for everyone,” said Michelagnoli. Regardless, he suggested that it is important to reflect on endovascular techniques, primarily because although favourable results are more immediate (compared with open surgery), the outcomes following the procedures can become more problematic down the line.

The debate ended with an audience vote, with 64% of delegates voting that endovascular repair is better for juxtarenal aneurysms. study—the latter of which encompasses real-world all-comers from many different centres—he presented respective mortality rates following the use of chimney grafts (30-day mortality at 0.8% and all-cause mortality at 17.2% for the PROTAGORAS study).

In relation to the cost-effectiveness of FEVAR, Winterbottom found that very few studies met inclusion criteria for analysis. However, a French multicentre prospective trial, carried out by Morgane Michel et al, reported that FEVAR was more expensive in comparison to open surgery (€38,212 versus €16,497). Winterbottom argued that in this trial in particular, length of stay for FEVAR reached 14 days, meaning that this figure cannot be generalised to all patients. According to Winterbottom, the paper also reported that permanent haemodialysis was 5.6% for FEVAR compared with 20.8% for open repair, yet the authors did not include this in their cost analysis, even at follow-up after two years.

Concluding his argument, Winterbottom stated that endovascular repair is better for juxtarenal aneurysm,

The moderators questioned Winterbottom on whether there were any particular patients in his unit that would benefit from open repair. He said, “they would have to be the really young, fit patients… [physicians would have to be] confident that the patient is just going to have a suprarenal clamp, or a short infrarenal neck seal, not supraceliac or re-implanting a renal... so again, it is a real cherry-picking of the very best of the patients”.

On the topic of randomised controlled trials, a moderator asked if one could ever be carried out in this field. Quick to reply, with patient selection bias in mind, Winterbottom surmised, “I am not sure we will get there.”

The debate ended with another audience vote, with 64% of delegates voting that endovascular repair is better for juxtarenal aneurysms, and 36% voting for open surgery; resulting in a slight shift in favour of open repair from the initial vote, yet a clear majority remaining certain that “endovascular repair is better for the treatment of juxtarenal abdominal aortic aneurysms.”

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Societies

Invitation to celebrate the 10th anniversary of the World Federation of Vascular Societies Alberto Muñoz, current president of the World Federation of Vascular Societies, writes for Vascular News about the history of the Federation and its importance to the field of vascular surgery. He also issues an invitation for this year’s World Congress which will take place on 5–8 December in Montevideo, Uruguay.

VASCULAR SURGERY IS today a mature speciality, with a big scope of areas for practice that include noninvasive diagnosis, medical treatment, open surgery and endovascular therapy of arteries, veins and lymphatics.

Vascular surgeons see and treat patients with a wide range of disease affecting all the tissues and organs of the body. The speciality developed rapidly during the last century and the importance of scientific exchange at a national and international level was identified.

In March of 1950, Henry Haimovici took the initiative to promote the concept of an International Society of Angiology and in Atlantic City, 9 June, 1951, with pioneers René Leriche, Michael DeBakey, Geza deTakats, Alton Ochsner, Leo Loewe, Harry Shumacker, Saul Samuels, Fernando Martorell and Ralph Deterling, founded the first international vascular society. The International Society of Angiology had North American, South American, and European chapters, becoming the international body with a focus on diseases of blood vessels. The history of vascular and cardiac surgery in the world corresponds to that of this society. Since then, a world congress was held every two years. In 1957, the Society changed its name to International Cardiovascular Society, and in 1981, the name was changed again to The International Society for Cardiovascular Surgery (ISCVS). By then, the ISCVS had a central chapter and seven regional chapters: European, North American, Latin American, Asian, Australian/New Zealander, Middle Eastern/ North African and South African. The regional chapters were integrated by the national societies. In the new millennium, the ISCVS faced different problems

New Zealand Society for Vascular Surgery (ANZSVS), Japanese Society for Vascular Surgery (JVS), Vascular Society of Asia (ASVS), Vascular Society of Southern Africa (VASSA), Vascular Society of India (VSI), and the Latin American Association for Vascular Surgery and Angiology (ALCVA). The first president of the WFVS was Jan Brunkwall from Germany (ESVS) followed by Peter Glovicski from USA (SVS), who in his presidential address in San Diego, June 2008 said: “The WFVS is a new and ambitious organisation with the mission of uniting vascular societies around the world to share information, solve common problems, and ensure the future of our specialty worldwide.

The foundation of this federation is international collaboration. I want to remind you that our history and heritage are international and that our clinical practice, education, and research are also universal for very simple reasons: this profession has no boundaries, and the science and art of vascular surgery has no country”.

A Symposium of the World Federation is held annually at the same time and place as the congress of one of the member societies. This is an important issue since it is not necessary to create another meeting, but to give strength to one of its member society’s meeting by inviting the vascular community around the world to participate and exchange experiences, ideas and their research results.

The Robert B Rutherford lecture is the highlight of the WFVS annual meeting and was developed to honour the contribution to vascular surgery made by Robert Rutherford. The first Robert B Rutherford Lecture was given at the WFVS annual meeting held in 2008

From left to right: Kimihiro Komori, JSVS, Pramook Mutirangura, ASVS, Tanyani Mulaudzi, VASSA, Varinder Bedi, councilor VS, Nobuyoshi Azuma, councilor JSVS, Martin Björk, ESVS, Alberto Muñoz, President WFVS, Arkadiusz Jawien, ESVS, Thodur Vasudevan, ANZSVS, Michel Mackaroun, councilor SVS, Thiruvengadam Vidyasagaran, Secretary General, William Jordan, SVS

that led to legal dissolution, but with the idea that an International Society of Vascular Specialists would reorganise the world international society, centred in vascular surgery and not cardiac.

The World Federation of Vascular Societies (WFVS) was established in Madrid in 2007 by the major vascular societies of the world, represented by the founders, Renald Barry, Jan Brunkwall (ESVS), Peter Gloviszki (SVS), John Harris (ANZSVS), Hiroshi Shigematsu (JSVS), Henrik Sillesen (ESVS), Kumud Rai (VSI), and Martin Veller (VASSA). Its member societies that represent the major geographic regions of the world are: Society for Vascular Surgery (SVS), European Society for Vascular Surgery (ESVS), Australian and

in San Diego, by Jonathan Beard (ESVS): “Which is the best revascularisation for critical limb ischaemia: Endovascular or open surgery?”

As time has passed, the symposiums of the WFVS have been generating more interest among vascular surgeons and societies. The meeting in San Diego, was followed by Oslo 2009, Kyoto 2010, Chicago 2011, Melbourne 2012, Budapest 2013. In 2014, VASSA hosted a congress devoted to the WFVS in Stellenbosch, South Africa. In 2016 in Bangalore, India the second congress of the WFVS was hosted by the Vascular Society of India.

The last Symposium was held during the ESVS 2017 in Lyon, organised by Martin Bjorck, from Sweden,

past president of the ESVS and councillor of the WFVS. The topic was “Vascular Surgery in the Era of Terror”.

He considered that terror attacks turned epidemic and have been spreading over the globe, so invited speakers from the member societies of the WFVS, from all over the world. The aim of the symposium was to share experiences that could encourage colleagues in other countries to help future victims in the best way.

The symposium took place in the main auditorium at the Lyon Convention Center. There was a large audience, with the room almost full. The focus was terrorist attacks and the experience in vascular trauma management and the logistical organisation of the health system and hospitals. The Robert B Rutherford lecture: “Vascular trauma due to terror attacks and war on the borders of India, 30 years of experience” was given

by Varinder Bedi, India, past president of the Vascular Society of India and the WFVS. Other presentations of the session were the terrorist attacks in the Boston Marathon, Manchester Train station, Paris, Turkey and Colombia.

This year, the WFVS is organising the III World Congress, from 5–8 December 2018, with the XXXII Latin American Congress of the Latin American Association of Vascular Surgery and Angiology (ALCVA) and the IV International Conference of the Uruguayan Society of Vascular and Endovascular Surgery (SUCIVE). The topics of the meeting are Future of the Vascular Specialist and Societies in the world, Endovascular therapy and open surgery are complementary, Aortic disease and aneurysms, Chronic Limb Threatening Ischaemia Update in Stroke and carotid arteries, AV Access, Diabetic Foot, Non-invasive vascular diagnosis, Varicose vein diagnosis and treatment, Vascular trauma, Deep venous thrombosis and pulmonary embolism and miscellaneous vascular topics. These topics will be distributed in a Masterclass of Peripheral Arterial Disease, Diabetic Foot Course, Radioprotection Course, I Latin American Meeting for Vascular Surgery Residents, Vascular Access of the Americas (VASA) Symposium, Latin-American Endovascular Surgeons from Latin-America (CELA) Symposium, I International Symposium of Non Invasive Vascular Diagnosis (ADIVANI), International Union of Phlebology Symposium, Latin-American Venous Forum Symposium and Carotid Body Tumour Symposium.

Another highlight of Orbis Vascular 2018 is the LatinAmerican Society for Vascular Surgery Forum, where a topic will be presented by a delegate of each of the 16 Vascular Societies from the region and an update of the status of vascular surgery in every Latin-American country. Guidelines to be presented are the European Guidelines for AAA, mesenteric ischaemia and the NICE Guidelines for AAA. The Robert B Rutherford lecture will be presented by Martin Bjorck: “Open or endovascular repair of aneurysms? What is the evidence?”

The WFVS Symposium will include the presentation of The New Global Vascular Guidelines developed by the SVS, ESVS and the WFVS and a session of Pioneers of Vascular and Endovascular Surgery, that will be a session devoted to the origins of Vascular and Endovascular Surgery, in recognition of the pioneers and of course the celebration of the 10th anniversary of the World Federation of Vascular Societies.

More information at www.orbisvscular2018.org and we will be happy to welcome you in Montevideo.

Alberto Muñoz is assistant professor of Surgery at the National University of Colombia, director of the Bogotá Vascular Clinic, and current president of the World Federation of Vascular Societies.

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First patient in Europe receives implant of Gore Excluder Conformable AAA Endoprosthesis with Active Control System

Gore has announced the first European patient implant of the Gore Excluder Conformable AAA Endoprosthesis with Active Control System. This nextgeneration endovascular aneurysm repair (EVAR) device is indicated to treat the broadest range of abdominal aortic aneurysms (AAA) in patients with challenging anatomies. Physicians now have an EVAR solution designed to treat patients previously excluded due to challenging proximal aortic necks.

The successful procedure took place on 11 September at Catharina Hospital in Eindhoven, the Netherlands by Marc van Sambeek. The patient was also the first enrolment in an investigator initiated post-market European registry, known as Excel (Excluder Conformable real life), of which van Sambeek is the principal investigator.

“Before this device, EVAR was reserved for patients whose aorta fell within a standard shape and size,” says van Sambeek. “The conformability of the new Gore Excluder Conformable device in combination with the angulation control of the new delivery system will allow us to offer a less invasive, lowerrisk alternative to open surgery to more AAA patients than ever before. The Excel registry will track the real-world effectiveness and safety of the device, and I look forward to enrolling additional patients with challenging, highly angulated aortic anatomies and seeing the long-term value of this device.”

The Excel registry will enrol 150 patients from up to 11 European sites.

Data from the registry will assess safety and treatment success of the Gore Excluder Conformable AAA device for the treatment of infrarenal AAA in a broad range of anatomic presentations.

The device is also currently being evaluated in a pivotal investigational US study, in which the first patient was enrolled on 19 December, 2017.

The Gore Excluder Conformable AAA device builds on the proven clinical performance of the Gore Excluder AAA Endoprosthesis, which represents over 20 years of worldwide experience and more than 300,000 patients treated, a history unmatched by currently available AAA stent grafts. The new device leverages the limb design of the Gore Excluder device which has demonstrated exceptional

clinical performance as evidenced by 0.5% limb occlusion through threeyear follow-up. The limbs, a unique combination of proprietary ePTFE graft material and a fully supported, nested, nitinol stent, are designed to prevent kinking and occlusion.

The new device introduces the Gore Active Control System in AAA treatment.

This new delivery system includes a conformable stent graft, enhanced device positioning, and optional angulation control. To enhance positioning, the device is deployed partially constrained and the physician has the option to reconstrain the proximal end of the device to aide in achieving optimal device placement. During the deployment process, the physician may use the optional angulation control to angle the device to achieve orthogonal placement to the aortic blood flow lumen and to maximise device conformability and seal.

Cardiovascular Systems announces launch of Peripheral Orbital Atherectomy System outside the USA

Cardiovascular Systems Inc. (CSI), a medical device company developing and commercialising interventional treatment systems for patients with peripheral and coronary artery disease, has announced that the first patient in Hong Kong has been treated with its Stealth 360 Peripheral Orbital Atherectomy System (OAS). The Hong Kong case is the first commercial use of Peripheral OAS outside of the USA. Bryan Yan, associate professor, Chinese University of Hong Kong, who treated the first patient in Hong Kong, said, “Patients with severely calcified peripheral arteries can be difficult to treat due to the limitations of traditional angioplasty or stenting.

This can also place patients at risk for subsequent complications including repeat interventions and amputation.

The commercialisation of the Stealth 360 OAS in Hong Kong provides physicians with a minimally invasive treatment option for this complex patient population. I am very satisfied with the procedural outcome for my patient because I was able to avoid implanting a stent in the distal superficial femoral artery and I look forward to continuing treatment of similar patients with this technology.”

Scott Ward, chairman, president and CEO of CSI, said, “We are pleased that the first patient treated with OAS in conjunction with our international distribution partner, OrbusNeich, was a success. This positive outcome demonstrates our mutual mission to support physicians in treating patients with peripheral artery disease.”

Scott Addonizio, senior vice president and chief operating officer of OrbusNeich, concluded, “Our experienced sales force is thrilled to bring

CSI’s orbital atherectomy technology to Hong Kong. This first procedure occurred only two months after becoming CSI’s international distribution partner. We look forward to introducing CSI’s atherectomy technology to physicians in new markets in the months and years ahead.”

In July 2018, CSI announced that it had signed an exclusive international distribution agreement with OrbusNeich to sell its coronary and peripheral OAS outside of the USA and Japan.

Additionally, in January 2018, CSI announced that it was the exclusive US distributor for OrbusNeich balloon products. Ultimately, CSI will offer a full line of semi-compliant, non-compliant and specialty balloons for both coronary and peripheral vascular procedures.

OrbusNeich PCI balloons include the Sapphire II Pro, the first and only 1mm coronary balloon available in the USA. In November 2016, CSI announced that Medikit, signed an exclusive distribution agreement to sell its coronary and peripheral OAS in Japan.

Boston Scientific receives US FDA approval for Eluvia drugeluting stent

Boston Scientific has announced that the US Food and Drug Administration (FDA) has approved its Premarket Approval (PMA) application to market the Eluvia Drug-Eluting Vascular Stent System, specifically developed for the treatment of peripheral arterial disease (PAD). The stent utilises a drug-polymer combination to offer sustained release of the drug paclitaxel for a one-year timeframe,

release to clinicians and the millions of patients suffering from this terrible disease.”

The FDA’s approval is based on findings from the IMPERIAL trial, in which the stent demonstrated superior results in the first superficial femoral artery head-to-head drug-eluting stent trial. In this trial, patients treated with the Eluvia stent experienced a significantly greater 12-month primary patency of 88.5%, compared to 79.5% in patients treated with Zilver PTX (p=0.0119). In addition, patients treated with the Eluvia stent experienced half the target lesion revascularisation rate of Zilver PTX at 12 months, a 4.5% TLR rate for Eluvia versus 9% TLR rate for the Zilver PTX cohort.

“In the IMPERIAL trial, the Eluvia stent demonstrated landmark vessel patency and freedom from target lesion revascularisation rates, preventing more than 95% of patients from needing a reintervention after one year,” said William Gray, system chief, Division of Cardiovascular Diseases and president, Lankenau Heart Institute at Main Line Health in Wynnewood, USA, and coprincipal investigator of the IMPERIAL trial. “The Eluvia stent is a breakthrough therapy that marks a significant step forward in the treatment of peripheral arterial disease, and now with its approval and commercial availability, it has the potential to make an immediate impact on the quality and value of care that physicians can provide to their patients.”

The Eluvia stent system is built on the Innova Stent System platform, a self-expanding nitinol stent that has been designed for use in the superficial femoral and proximal popliteal arteries, the main arteries that supply blood to the legs. The Eluvia stent system received CE Mark in 2016.

Vascular Simulations launches Replicator PRO for realistic replication in endovascular simulations

Eluvia

designed to prevent tissue regrowth that might otherwise block the stented artery.

“Over the past decade, we have seen significant advancements in the treatment of peripheral arterial disease, yet clinical and economic outcomes still present an opportunity for innovation and to improve patient care,” said Jeff Mirviss, senior vice president and president, Peripheral Interventions, Boston Scientific. “With the FDA’s approval of the Eluvia stent, we can now bring the transformative power of sustained drug

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Medical technology company Vascular Simulations has released Replicator PRO, a realistic vascular replication system, at the 2018 Transcatheter Cardiovascular Therapeutics meeting (TCT; 21–25 September, San Diego, USA).

Aiming to be a better alternative to device reliance animal testing, Replicator Pro empowers device development, demonstration, and training for engineers, educators, and physicians. The company states in a recent press release that with this system it seeks to address the disparities between animal and human vascular systems, which can lead to in-human trial failures following successful animal reliance testing.

Replicator PRO is a platform for medical device validation which recreates a realistic haemodynamic environment.

Through its treated silicone vasculature, the system provides the necessary tactile feedback for interventional device track and navigation, allowing devices to behave the same way they would

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Product News in human vessels. For researchers and engineers, this technology is suitable for optimising device design and performance and provides an efficient testing platform. For physicians and clinical directors, Replicator PRO is a versatile training and preparation platform.

“By giving the user the ability to perform a simulated procedure that takes place in the same hemodynamic conditions as it would in real life, there is an added fidelity component to the simulated procedure and it therefore makes the educational experience as close to reality as possible,” says director of Vascular and Endovascular Surgery, Apostolos Tassiopoulo of Stony Brook Hospital, Stony Brook, USA. “In animal reliance testing, you never have the specific anatomy you are trying to treat,” continues Tassiopoulos, “so Replicator PRO offers a much more relevant anatomical and haemodynamic environment.”

Physicians expand their insight with no added risk through the power of Replicator PRO’s realism both through haemodynamic and clinical experience. In addition to matched aortoiliac vasculature, the model includes a 4-chamber silicone heart with a replaceable, physiologically functioning aortic valve. This 3D-printed anatomy works in harmony with the endovascular-responsive terrain and system control unit to give the system its advanced haemodynamics. In addition to replicating the hemodynamic environment, Replicator PRO mimics the clinical environment through angiographic compatibility, giving physicians the ability to track and map their procedures.

Cook Medical receives FDA approval for first 5mm diameter SFA drug-eluting stent

Cook Medical have announced that a new 5mm diameter version of Zilver PTX was approved by the US Food and Drug Administration (FDA). It is the first 5mm drug-eluting stent in the USA with lengths available up to 140mm that is indicated to treat vessels as small as 4mm in diameter. The range of Zilver PTX stent diameters now available will address treatment of vessel sizes from 4–7mm in diameter. The new diameter is better sized for smaller anatomy than previous sizes of the stent and provides an additional option to treat patients with lesions in their superficial femoral arteries (SFAs).

“We spend a lot of time listening to physicians to understand their clinical needs. Time and time again, they ask for more treatment options for peripheral artery disease,” said Mark Breedlove, vice president of Cook Medical’s Vascular division. “We’re excited to continue to develop the Zilver PTX line

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to answer those needs and help more patients around the world.”

The new size is the only 5mm drug-eluting stent on the US market for peripheral artery disease (PAD) and provides another treatment option for lesions in patients with smaller superficial femoral arteries.

Zilver PTX1 was the USA’s first drug-eluting stent used in the treatment of PAD and is the only drug-eluting SFA stent with five-year published data.

Zilver PTX has also been shown to cut re-interventions by nearly half through five years, compared to a combination of bare-metal Zilver stents and percutaneous transluminal angioplasty (PTA).

Last year, Cook Medical introduced the 140mm-length stent in both six and 7mm stent diameters and received expanded indications to treat lesions up to 300mm per patient. Zilver PTX also received an extended shelf life of two years by the FDA.

FDA classifies previous Endologix AFX safety notice as Class I Recall

Endologix, a developer and marketer of treatments for aortic disorders, has announced that the US Food and Drug Administration (FDA) has classified a voluntary recall action that Endologix took in July of this year, as a Class I recall. The July recall involved the company’s issuance of a safety notice to healthcare professionals using the AFX Endovascular AAA System.

The safety notice, dated 20 July 2018, provided updated information on comparative AFX Type III endoleak rates, patient-tailored surveillance recommendations, and recommendations for intervening through an AFX device or re-intervening on an AFX device. No product was removed from the field as part of this recall.

The July 2018 Safety notice followed several earlier communications. Safety notices from Endologix issued in late 2016 and early 2017 requested that all remaining AFX Strata devices be returned from the field and emphasised that Endologix had not manufactured AFX Strata grafts since 2014. On 28 September, 2017, the FDA issued a letter to healthcare professionals to raise awareness of an increased occurrence of Type III endoleaks after endovascular aneurysm repair (EVAR). On 19 June, 2018, the FDA issued an updated letter to healthcare professionals indicating the increased risk for Type III endoleak appears to be specific to one device at this time, the AFX with Strata device.

“As outlined at our Investor Day on 2 October, 2018, the AFX Strata product was removed from global inventory in the first half of 2017. Our current commercially available versions of the AFX system, the AFX Duraply and AFX2 products, are manufactured using a different ePTFE processing

Zilver PTX

methodology and include additional product improvements,” noted John Onopchenko, chief executive officer of Endologix. “These AFX Duraply and AFX2 products, while part of the July 2018 Safety Notice providing updated recommendations to healthcare professionals on how to re-intervene on or through these products, were not the subject of the voluntary product removal actions in December 2016/January 2017. Furthermore, AFX Duraply and AFX2 products were not the subject of the 19 June, 2018 FDA letter to healthcare professionals. Through our comprehensive system of post-market surveillance, anonymised registry data, and the only randomised trial to compare EVAR systems (the LEOPARD trial), we have a strong and growing evidence base that supports the use of the AFX Duraply and AFX2 systems for patients with AAA. We are proud of, and committed to, advancing our collaborative work with the FDA on behalf of our patients, customers, and the broader clinical community.”

BioMimics 3D stent receives US FDA premarket approval

UK-based Veryan Medical has announced that the company has received premarket approval (PMA) for their BioMimics 3D vascular stent system from the US Food & Drug Administration (FDA). The device is approved for the treatment of symptomatic de novo or restenotic lesions in the native superficial femoral

BioMimics 3D stent

artery and/or proximal popliteal artery.

The BioMimics 3D stent has a unique three-dimensional helical shape, designed to impart natural curvature to the diseased femoropopliteal artery, to promote swirling flow and elevate wall shear, which has a protective effect on the endothelium. Key components of the PMA application were the 12-month interim safety and effectiveness results from the company’s MIMICS-2 clinical study conducted under an FDA-approved Investigational Device Exemption (IDE)

in patients with peripheral arterial disease undergoing endovascular intervention in the femoropopliteal artery. BioMimics 3D represents an innovative approach to the requirement for durable support for the arterial lumen after intervention.

The helical centreline stent is designed to not only promote swirling blood flow but also to accommodate the complex biomechanical challenge associated with stenting this anatomically mobile artery.

The MIMICS-2 study enrolled 271 participants across 43 investigational sites in the USA, Japan and Germany.

The principal investigators are Timothy M Sullivan (Minneapolis, USA), Masato Nakamura (Tokyo, Japan) and Thomas Zeller (Bad Krozingen, Germany).

Both primary endpoints in the MIMICS-2 study, safety and effectiveness, were met. Freedom from major adverse events at 30 days was 99.6% (268/269) and Kaplan-Meier estimates of freedom from loss of primary patency and clinically-driven target lesion revascularisation were 83% and 88%, respectively, at 12-months; no stent fractures were detected in core laboratory imaging review.

Chas Taylor, Veryan’s chief executive officer comments: “We are delighted with the US FDA premarket approval, which is a major milestone for Veryan as we build towards global commercialisation of our BioMimics 3D Swirling Flow stent. I thank FDA for their invaluable support throughout the IDE/PMA process and applaud the hard work of all our staff in making this approval process so swift and straightforward.

“The compelling MIMICS-2 results reinforce those from our earlier Mimics randomised clinical trial and the combined results support our belief that BioMimics 3D stands to become a first-choice nitinol stent for both primary and complementary stenting in the femoropopliteal artery.”

Eximo Medical receives FDA clearance for B-Laser atherectomy system to treat peripheral arterial disease

Eximo Medical has announced it has received 510(k) clearance from the US Food & Drug Administration (FDA) for its B-Laser atherectomy system for peripheral arterial disease (PAD).

B-Laser is a transformative 355nm wavelength laser technology designed to address unmet clinical needs for treating multiple vascular indications. The specific indication cleared by the FDA is: “The B-Laser atherectomy system is intended for use in the treatment, including atherectomy, of infrainguinal stenoses and occlusion, including in-stent restenosis (ISR).”

“This clearance represents a significant milestone for Eximo, as we can now offer the B-Laser atherectomy system for PAD in the USA. This is the first 355nm laser system cleared in the USA for this purpose and, according to the clinical results and the feedback that we received from physicians, it seems that this wavelength provides significant advantages over traditional 308nm excimer lasers in term of safety, efficacy, cost and ease

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Product News of use,” says Yoel Zabar, CEO of Eximo Medical. “We also plan to leverage our B-Laser platform technology to develop additional devices to address significant unmet needs in other vascular indications, including lead extraction (for which we have completed a proof of concept), coronary artery disease, thrombectomy and venous disease. Additionally, we are developing an add-on diagnostic tool and disruptive medical device for interventional gastrointestinal procedures.”

Clinical evaluation of the B-Laser device in the intended population was performed in a prospective, single-arm, multicentre, open-label, non-randomised pilot clinical study in 50 subjects in Europe, as well as in a pivotal, prospective, single-arm, multicentre, open-label, non-randomised IDE clinical study in 97 patients in USA and Europe.

In the pilot clinical study, the results presented 100% success in crossing the target with no device related peri-operative clinically significant adverse events and no complications requiring intervention. There were no major adverse events (MAE) at one month or six months following the procedure, and only two cases (4.3%) of target lesion revascularisation among 46 patients who completed the one-year post procedure follow-up. In the pivotal study, the safety and efficacy primary endpoints

were achieved with high margins and the six-month data was consistent with the pilot study results.

“I used the B-Laser in challenging procedures during the pivotal study and found the device easy to set up and use, and a valuable addition to our treatment portfolio,” says the national principal investigator, John Rundback, interventional radiologist and director of the Interventional Institute at Holy Name Medical Centre, Teaneck, USA. “The enrolment in both US and Europe was quick (6.5 months), and the study results up to six months have been very impressive despite treating diverse lesions such as calcium, thrombus, and restenosis (including in-stent restenosis), both above and below the knee.”

Rivaroxaban gets FDA approval for treatment in CAD or PAD Rivaroxaban, brand name Xarelto (Janssen), has received approval by the US Food and Drug Administration (FDA) to reduce the risk of major cardiovascular events, such as cardiovascular death, myocardial infarction and stroke, in people with chronic coronary or peripheral arterial disease (CAD/PAD). Rivaroxaban is now the first and only Factor Xa inhibitor approved for patients living with these conditions.

This new indication is based on results from the landmark COMPASS trial, which showed a significant 24% reduction of the risk of major cardiovascular events in patients with chronic CAD and/or PAD with a 2.5mg vascular dose of rivaroxaban twice daily plus aspirin 100mg once daily, compared to aspirin alone. This finding was driven by a 42% reduction in stroke, 22% reduction in cardiovascular death and 14% reduction in heart attack. The risk of major bleeding was significantly higher in patients taking the rivaroxaban/aspirin regimen compared to aspirin alone, with no significant increase in fatal or intracranial bleeds.

“Despite the use of guidelinerecommended therapies, patients with chronic CAD and/or PAD remain at risk of having a devastating and irreversible cardiovascular event,” says Paul Burton, vice president, Medical Affairs, Internal Medicine, Janssen Scientific Affairs, LLC. “The new Xarelto vascular 2.5mg dose, when used with aspirin, represents a true breakthrough for patients with chronic CAD and PAD.” “Treating patients with aspirin only is simply not enough to address the underlying thrombotic risk that comes with chronic CAD and PAD,” said Kelley Branch, associate professor in Cardiology, University of Washington, Seattle, USA. “As we saw in the COMPASS trial, the dual pathway approach of aspirin and the 2.5mg, twice-daily dose of Xarelto can help significantly reduce the risk of cardiovascular events in these populations.”

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Avinger receives CE marking approval for Pantheris SV

Avinger, a developer of treatments for peripheral arterial disease (PAD), has announced Conformité Européenne (CE) Marking approval of Pantheris SV (Small Vessel), a product line extension of the Lumivascular atherectomy system. CE Marking allows for distribution of Pantheris SV in the European Union (EU) and certain other countries that recognize the CE Marking. Pantheris SV is not available commercially in the USA at this time.

Designed with a lower profile and longer length, Pantheris SV is intended to expand the addressable market for Pantheris by allowing physicians to treat lesions in smaller diameter vessels (2 to 4 millimeters) and more distal regions of the vasculature. Pantheris SV incorporates key improvements from the next generation Pantheris launched in the US market in June 2018, including a stiffer shaft for increased pushability, a refined OCT imaging system, and an enhanced cutter design. ”We believe that Pantheris SV represents a substantial market expansion opportunity for our technology, and having CE Marking for the device represents an important first step towards broader commercialisation,” commented Jeff Soinski, Avinger’ president and CEO. ”The longer length and smaller profile of this new device should increase the number of lesions available for treatment by Pantheris, and we believe the safety profile enabled by our image-guidance system should enhance the confidence of physicians applying directional atherectomy to smaller vessels.”

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FDA submission and PRELUDE-BTK study in the first half of 2019.

Industry News

US$60 million raised to fund sirolimus-coated balloon investigational trial

Teleflex acquires Essential Medical

Teleflex Incorporated has announced that it has acquired Essential Medical, a privately-held medical device company that has developed and commercialised the CE marked Manta vascular closure device specifically designed for closure of large bore arteriotomies following procedures utilising devices or sheaths ranging in size from 10F to 18F (with maximum outer diameters up to 25F).

In its CE Mark study, the Manta device demonstrated rapid and reliable haemostasis with its resorbable collagen-based technology and complication rates that were noninferior to surgical and suture-based closure methods.

“We are very excited to announce this acquisition, which expands our presence in the structural heart and endovascular aneurysm repair markets,” says Liam Kelly, president and chief executive officer of Teleflex.

Kelly adds, “The Manta vascular closure device represents a truly innovative solution to address closurerelated complications and high costs associated with many large and rapidly growing interventional procedure categories, such as transcatheter aortic valve replacement, endovascular aneurysm repair and ventricular assist device implantation. Physician adoption of the Manta device in international markets has been impressive, with over 8,100 procedures completed to date across a number of countries in the EU. We believe we can leverage our strong presence in the interventional cardiology market to accelerate adoption and growth of this breakthrough technology worldwide.

Following the anticipated FDA premarket approval of the vascular closure device in 2019, we expect the acquisition will be modestly accretive to our constant currency revenue growth and gross margins over a multiyear period.”

“The combination of Teleflex and Essential Medical provides an excellent opportunity to maximize physician and patient access to the Manta vascular closure device ,” states Greg Walters, Essential Medical’s cofounder, president and CEO. “We are delighted to become an important part of Teleflex’s interventional cardiology business.”

The Manta device is not approved for sale or distribution in the USA.

Cagent Vascular appoints Brian Walsh as chairman of the board

Cagent Vascular, a developer of next-generation angioplasty balloons using proprietary serration technology, announces Brian Walsh to serve as chairman of the Board.

Brian Walsh has held several

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executive level positions in cardiovascular and ophthalmology specialties within the medical device industry. Walsh currently serves as the president and CEO of Iantech Medical, a medical device company dedicated to solutions for micro-interventional cataract surgery. Walsh was the former CEO of Transcend Medical which, while under his leadership, was sold to Novartis. He currently serves on the Board of Directors at Iantech Medical.

Brian Walsh has held various sales and marketing roles at Xtent, Ventrica (acquired by Medtronic), Artemis Medical (acquired by Johnson & Johnson), Cardiovations, Division of Ethicon, a Johnson & Johnson company, Heartport, (acquisition by Johnson & Johnson) and Guidant Corporation.

Carol A Burns, Cagent Vascular’s president and CEO, adds, “Mr Walsh’s experience in marketing and corporate strategy will be invaluable as we advance our Serranator product line into additional indications. His expertise will add to the already impressive scientific, financial and business acumen of our board team.”

“Peripheral arterial disease (PAD) is a debilitating disease affecting millions of people around the world. Although advances in treatment have helped improve lives, there is still significant progress and innovation needed to treat the more advanced stage, critical limb ischaemia (CLI), that can lead to significant decrease in mobility, tissue loss and amputation. The company’s Serranator platform is a significant advancement in angioplasty technology for opening diseased arteries,” adds Walsh.

The Serranator 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 with low pressure balloon dilatation to aid in arterial expansion. The result is predictable and controlled lumen gain. The company’s first device, the Serranator Alto, performed well in the above-the-knee PRELUDE study, especially in a subset of patients with severe calcium. The Serranator Bass balloon for treatment of infrapopliteal arteries is in development with planned

Concept Medical Inc. has approached the FDA for an investigational device exemption (IDE) for their sirolimus-coated balloon (DCB). To support this process, they have raised US$60 million (for an undisclosed valuation) from cardiologist and serial entrepreneur Kiran Patel (Tampa, USA). An IDE will allow the device to be used in a clinical study to collect safety and effectiveness data.

The funds will also be utilised to augment clinical data and clinical registries to qualify for reimbursement in the European markets, where the company has commercially launched the product.

Concept Medical Inc. (CMI), headquartered in Florida, has a manufacturing subsidiary in India, by the name Envision Scientific Pvt. Ltd. (ESPL), where all their products are made. A portion of the funds will also be utilised to bolster the manufacturing operations to meet the increasing demand for their products globally.

MagicTouch

Their global distribution and marketing network are operated from offices in India, Singapore, the Netherlands and Brazil. ESPL also has an India-focused marketing and distribution business.

The companies (CMI and ESPL), which were established about 10 years ago, have developed innovative and disruptive platform technologies in drug-delivery systems to address the unmet medical needs in interventional cardiology. They have 96 patents granted (with another 40 currently in process) around the world.

The companies have previously commercialised their first product, Abluminus-DES coronary stent, which uses their proprietary drug delivery and coating systems. MagicTouch-DEB, a sirolimus-coated balloon with application in coronary and peripheral arterial disease, is commercially sold in many European countries as well as South Africa, Mexico, Malaysia, Indonesia, Singapore, and in the MENA region.

Extended applications of MagicTouchDEB in renal transplant, erectile dysfunction, and arteriovenous fistulae and grafts for renal dialysis patients are currently in on-going clinical trials.

CMI raised the funds from the family office of Kiran Patel and Pallavi Patel.

With the fresh infusion of funds, both CMI and ESPL aim to bolster their

operations in the existing and new markets.

Kiran Patel, a staunch supporter of innovative and disruptive medical technologies, says, “Cardiovascular diseases (CVDs) are the number one cause of death globally, representing 31% of all global death and it is increasing due to changes in lifestyle and increase in hypertension amongst the young and old.

I am excited to be a part of CMI whose research and innovative technologies will meet a major unmet need in patients with diabetes and cardiovascular diseases.

This venture enables me to contribute to the millions of hearts beating around the world.”

Flow Forward Medical exceeds US$8 million investments, awarded grant from NIH

Flow Forward Medical, a medical device company focused on improving outcomes for haemodialysis patients through the rapid creation of high-quality vascular access sites, has announced it has raised an additional US$1.2 million in Series A financing from a group of investors, including Mid-America Angels, bringing the total funding raised to date to more than US$8 million.

Additionally, Flow Forward announced that the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) recently awarded the company a US$225,000 Phase 1 SBIR grant to continue the development of the company’s Arteriovenous Fistula Eligibility (AFE) System, a medical device that uses rapid non-pulsatile blood flow to dilate peripheral veins prior to the creation of arteriovenous fistula (AVF) vascular access sites. The company states that it is currently preparing for a first-inhuman clinical trial.

“Currently, there are 2.5 million haemodialysis patients worldwide and a majority of these patients will experience difficulties establishing or maintaining vascular access sites,” stated Laura McCoolidge Classen, managing director of Mid-America Angels. “Each site failure puts patients at risk for a cycle of difficult and expensive repair or replacement procedures. We believe that Flow Forward’s approach to addressing the long-standing medical need to develop better vascular access sites has the potential to be a powerful solution for patients.”

“We are grateful for the support from our investors and the National Institutes of Health as we work to develop innovative products to establish high-quality vascular access sites for haemodialysis,” stated F Nicholas Franano, president and CEO of Flow Forward. “These additional resources will support the advancement of the AFE System into a first-in-human clinical trial, which we plan to initiate in 2019, and where we hope to show the potential of the AFE System to help physicians rapidly create fully mature and usable AVF vascular access sites that are reliable and long-lasting.”

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Events

Calendar of events 5–8 November

VIVA 2018 Las Vegas, USA W vivaphysicians.org 13–17 November

VEITHsymposium New York, USA W www.veithsymposium.org 5–8 December

Orbis Vascular Montevideo, Uruguay W www.orbisvascular2018.org 6–8 December

8th Munich Vascular Course Munich, Germany W www.mac-conference.com 6–8 December

VERVE Symposium Sydney, Australia W http://www.vervesymposium.com 6–8 December

43rd Annual Northwestern Vascular Symposium Chicago, USA W www.northwestern.cloud-cme.com

7–8 December

CIV World Paris, France W www.civ-world.com 13–15 December

15–17 February American Society of Diagnostic and

Interventional Nephrology: ASDIN Atlanta, USA W www.asdin.org

Aortic Surgery, Peripheral & Venous HTDI– How to do it 2018 Milan, Italy W www.aorticsurgery.it

10–12 March

22–25 January

12–13 March

7–9 February

27–29 March

LINC: Leipzig Interventional Course Leipzig, Germany W www.linc2019.com

EVC: European Vascular Course Maastricht, the Netherlands W www.vascular-course.com LINC Asia-Pacific Hong Kong W www.linc-around-the-world.com

CACVS: Controversies and Updates in Vascular Surgery Paris, France W www.cacvs.org

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

13–15 February

11–12 April

3rd Maastricht Consensus Conference on Thrombosis Maastricht, The Netherlands W www.mcct.eu

11th Congress of the Vascular Access Society Rotterdam, The Netherlands W www.vas2019.com 15–18 April

Charing Cross Symposium London, UK W www.cxsymposium.com

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