Venous News Issue 14 – June 2020

June 2020 | Issue 14 Andrew Doyle and Narayan Karunanithy:

Michael Lichtenberg: Mechanical thrombectomy and DVT

IVC filters in 2020

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Page 7

Compression stockings might not be needed to prevent blood clots after surgery Compression stockings might be unnecessary to prevent venous thromboembolism in most patients undergoing non-emergency (elective) surgery, finds a clinical trial recently published by The BMJ.

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he results of the GAPS (Graduated compression stockings as adjuvant to pharmacothromboprophylaxis in elective surgical patients) randomised controlled trial suggest that giving anticlotting drugs alone is just as effective and, as such, the researchers say current guidelines based on historical data should be revised.

Current guidelines recommend using a combination of graduated compression stockings (GCS) and anti-clotting drugs for patients undergoing elective surgery who are at moderate or high risk of venous thromboembolism (VTE).

However, in recent years, rates of VTE after surgery have fallen significantly due to improved care and drug therapy, leading some doctors to suggest that this combination might no longer be necessary.

Consequently, a team of UK researchers, including lead author Joseph Shalhoub and senior author Alun H Davies (both Imperial College, London, UK), set out to investigate whether the use of graduated compression stockings offers any additional benefit to anti-clotting drugs to prevent VTE in patients undergoing elective surgery.

Their findings are based on 1,858 adult patients at moderate or high risk of VTE who underwent nonemergency surgery at seven NHS hospitals across the UK between May 2016 and January 2019.

Patients were randomly split into two groups. A total of 937 patients were only given anti-clotting drugs (low-molecular-weight heparin or LMWH) during their hospital stay and were asked not to wear any kind of compression stocking for 90 days after surgery. The

Joseph Shalhoub

Alun Davies

The trial should prompt the review of guidelines around prevention of hospital acquired thrombosis.” remaining 921 patients were given the same anti-clotting drugs and were asked to wear graduated compression stockings during their hospital stay.

The main outcome was a scan showing deep vein thrombosis or pulmonary embolism within 90 days of surgery. Other measures included quality of life, adverse reactions to anti-clotting drugs, and death from any cause.

Continued on page 2

Paul Gagne: IVUS based therapies for venous leg ulcers

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CX 2020 LIVE

CX 2020 LIVE brings superficial venous thrombosis to the forefront For the first venous session of CX 2020 LIVE (26 May–25 June), 759 attendees from 79 different countries tuned in. Each audience member could submit their name, country, and a question or point to the speaker in real-time, enabling interaction, discussion, and polling.

Roger Greenhalgh (London, UK) chaired the session, with Stephen Black (London, UK) moderating, as participants from five continents learnt about the latest developments in superficial venous disease. Panellists fielded questions from 29 different countries, including the USA, Brazil, Ukraine, Kenya, Mexico, Spain, Saudi Arabia, Egypt, Argentina, Moldova, and the Russian Federation.

THE FIRST THREE talks of the session teased forthcoming, as-yet-unpublished guidelines from the European Venous Forum (EVF), the European Society for Vascular Surgery (ESVS), and the American Venous Forum (AVF)/Society for Vascular Surgery (SVS). These presentations were given

by Armando Mansilha (Porto, Portugal), Manj Gohel (Cambridge, UK), and Lowell Kabnick (New York, USA), respectively. Additionally, a clinical assessment and work-up of patients with Continued on page 4

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June 2020 | Issue 14

Compression stockings

Compression stockings might not be needed to prevent blood clots after surgery Continued from page 1

The researchers found that VTE occurred in 16 out of 937 (1.7%) patients in the drugs only group compared with 13 out of 921 (1.4%) patients in the drugs plus stockings group.

Both deep vein thrombosis and pulmonary embolism occurred in two out of 937 (0.2%) patients in the drugs only group compared with one out of 921 (0.1%) in the drugs plus stockings group.

Little or no differences between groups were found for other measures including quality of life up to 90 days after surgery, adverse drug reactions or deaths.

The researchers point to some limitations, such as the possibility of missed scans, but say this would probably not have influenced the overall findings. Results were also similar after further analyses, suggesting that the findings withstand scrutiny. As such, they say that in patients who have elective surgical procedures and are at moderate or high risk of venous thromboembolism, preventive drug treatment alone is “non-inferior” to a combination of drug treatment and GCS. Shalhoub and Davies spoke to Venous News about the results of the GAPS trial. They commented on the significance of the study: “VTE following surgery is a major concern and this has rightly lead to the development of numerous guidelines. The use of mechanical thromboprophylaxis, particularly graduated compression stockings, are a prominent feature amongst many guideline recommendations. Recently, questions have been raised in relation to the benefit of GCS, particularly when used in combination with pharmacological thromboprophylaxis.”

Commenting on how the trial may influence practice, they suggested that “the trial should prompt the review of guidelines around prevention of hospital acquired thrombosis”.

They continued: “We feel that, based on the trial results, GCS are no longer indicated in this surgical patient group. The impact for these patients is that they will no longer need to wear GCS, which many find uncomfortable and have been associated with complications.”

Considering the implication for health systems, Shalhoub and Davies remarked that “cost savings in relation to providing and applying GCS to medium and high VTE risk elective surgical patients have been estimated as being more

than £63 million per year in England alone; funding and resources which may be re-allocated for patient benefit.”

Finally, they commented that “the trial indicates the role of GCS for thromboprophylaxis in other patient groups should also be looked at.”

Cliff Shearman (University of Southampton and University Hospital Southampton Foundation Trust, Southampton, UK), vice president of the Royal College of Surgeons (RCS) commented on the results of the trial: “We welcome this well-designed trial, which suggests that there is no need to wear compression stockings in hospital following surgery to prevent VTE. Patients find stockings inconvenient and fitting them takes up valuable nurse time. This study suggests we can save the NHS money and also save staff time by making a simple change, that improves perioperative practice.”

Many patients find graduated compression stockings uncomfortable and they have been associated with complications.”

News in brief

The latest stories from the venous world

n MECHANICAL THROMBECTOMY VERSUS THROMBOLYSIS META-ANALYSIS: A recent systematic review and meta-analysis showed that, in patients with iliofemoral deep vein thrombosis (DVT), percutaneous mechanical thrombectomy was associated with a higher cumulative six-month primary patency and a lower incidence of major bleeding compared to thrombolysis alone. These findings were recently published online in the European Journal of Vascular Medicine (VASA)

by Michael Lichtenberg (right) and colleagues.

For more on this story go to page 5 n IVC FILTERS: Following the publication of a paper on the use of inferior vena cava (IVC) filters, two of its authors Andrew Doyle and Narayan Karunanithy speak to Venous News about the ongoing controversy surrounding the devices, highlighting that while “there is a lack of high-level evidence”, their use “should be considered on a case-by-case basis for patients where thromboprophylaxis is required”.

For more on this story go to page 7 n VARICOSE VEIN GUIDELINES: A debate on whether current international guidelines are accurate to define the best interventional technique for varicose veins was held at the Controversies and Updates in Vascular Surgery 2020 meeting, with Thomas Proebstle and Armando Mansilha arguing for and against the motion, respectively.

While Proebstle pondered whether there is anything else specialists might need in order to determine the best interventional technique for varicose veins—and questioned whether current guidelines have been implemented widely enough—Mansilha emphasised that there are many factors beyond the parameters of current guidelines that should be considered.

For more on this story go to page 8

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June 2020 | Issue 14

CX 2020

CX 2020 LIVE

CX 2020 LIVE addresses latest developments in superficial venous disease Continued from page 1

possible pelvic vein incompetence was presented

by Aleksandra Jaworucka-Kaczorowska (Gorzów Wielkopolski, Poland), followed by a network metaanalysis on the use of cyanoacrylate glue, from Raghu Kolluri (Columbus, USA), audience polling, and, finally, an edited case from Kathleen Gibson (Bellevue, USA).

Spontaneous superficial vein thrombosis “far from a benign pathology”

Traditionally, superficial vein thrombosis (SVT) was treated with surgical management due to the perceived increased risk of deep vein thrombosis (DVT), which in turn could cause pulmonary embolism (PE), associated with a higher risk of death. Interestingly, it emerged in the CX 2020 LIVE discussion that surgical intervention is no longer mandatory. Instead, venous experts are searching for factors that explain a possible underlying hypercoagulable state that can lead to spontaneous thrombosis. One possible therapeutic option that is emerging for the treatment of SVT is the administration of anticoagulants. SVT is therefore no longer seen as requiring emergency surgery, but is indicative of an underlying condition that can be treated medically.

Manj Gohel (Cambridge, UK) told the CX 2020 LIVE audience that SVT is “far from a benign pathology”, discussing how the latest set of recommendations from the ESVS are set to pave the way for new approaches to treating this specific type of blood clot.

Though acknowledging that venous thrombosis is an “enormously varied topic”, Gohel said the writing committee felt strongly that superficial vein thrombosis should be included in the new guidelines, as it is “largely neglected” in other recommendations worldwide. “It is important to realise,” he added, “that it is a very common condition, frequently encountered in clinical practice.”

Gohel said: “Anticoagulation, rather than antibiotics, is going to be the mainstay of treatment for most patients”. While he stated that “there will be a role for ablation of superficial venous reflux”, he clarified that he thought that this will probably not play a part in the treatment of acute thrombosis in the superficial vein.

A question posed to Gohel from a CX audience member from Iraq asked: “After treating superficial vein thrombosis, how long do you suggest waiting before treating the varicose vein in absence of any other contraindications?”

In his reply, Gohel highlighted the importance of treating the underlying superficial reflux. “All too often these patients have been treated and seen in thrombosis clinics, they have been told there is no DVT, and almost forgotten about. Repeat imaging should be performed with the aim of ablating residual superficial reflux at around three months, once the acute inflammation has settled”.

Multidisciplinary team important for managing pelvic vein incompetence In her talk, Jaworucka-Kaczorowska looked at the clinical assessment and work-up of patients with possible pelvic vein incompetence. She showcased some extreme examples that she has encountered in

Roger Greenhalgh (top left), Stephen Black (top right), Armando Mansilha (bottom left), Manj Gohel (bottom middle), and Lowell Kabnick (bottom right)

Roger Greenhalgh (top left), Stephen Black (top right), Aleksandra Jaworucka-Kaczorowska (bottom left), Raghu Kolluri (bottom middle), and Kathleen Gibson (bottom right)

When a physician can see a problem, the answer is that it is a multidisciplinary team that they require.” her work as a gynaecologist, all the while emphasising the importance of drawing upon multiple skillsets in the treatment of these patients.

In particular, Jaworucka-Kaczorowska—noting she was a gynaecological surgeon—stated that she referred patients to a relevant centre with the appropriate radiological experience if they required percutaneous embolisation. Responding to this, Greenhalgh observed: “I think we have learned that when a physician can see a problem, the answer is that it is a multidisciplinary team that they require.”

Cyanoacrylate: A “good technique”, but “not a panacea”

The discussion next turned to the use of cyanoacrylate glue. Delivering his Podium 1st presentation, Kolluri said the VenaSeal closure system (Medtronic), a type of cyanoacrylate glue, is “a promising therapeutic option” with high rates of anatomic success, improved pain scores, and a low occurrence of adverse events compared with alternative treatment modalities. He made this conclusion based on the six-month results

of a network meta-analysis published in the May issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, comparing different interventions for chronic venous insufficiency (CVI) management. Following his talk, Gibson provided a step-by-step guide to cyanoacrylate closure using VenaSeal.

The discussion following the two cyanoacrylatefocused talks highlighted that this new technique may be particularly useful in carefully selected patients, but was not suitable for all veins.

When asked: “Are you a fan of cyanoacrylate glue?”

61% of CX 2020 LIVE respondents answered “no”.

Gibson summarised her take-home message: “It is not going to replace endothermal ablation. I think it is an advance; I think there are some situations where it is extremely good. For example, in the elderly population, where they have a very low incidence of hypersensitivity.”

Kolluri concurred, stating that his patients, who benefit from the use of cyanoacrylate glue, have quite severe disease, with multiple comorbidities, and are at high risk of bleeding.

Turning to the other panellists, Greenhalgh invited each to provide their take on the technique. Gohel: “It is not a panacea; it is not going to replace everything”; Kabnick: “Thermal is still the gold standard”; Mansilha: “One more good technique. The strategy is the point”.

Moderator Black concluded the session: “I think like all new techniques, you learn the good and the bad, and this will find a good place in the long term”.

Issue 14 | June 2020

Mechanical thrombectomy

Addition of mechanical thrombectomy signals patency and bleeding benefits compared to thrombosis alone

A recent systematic review and meta-analysis showed that, in patients with iliofemoral deep vein thrombosis (DVT) percutaneous mechanical thrombectomy was associated with a higher cumulative six-month primary patency and a lower incidence of major bleeding compared to thrombolysis alone. These findings were recently published online in the European Journal of Vascular Medicine (VASA).

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he authors, Michael KW Lichtenberg (Venous Center Klinikum Arnsberg, Arnsberg, Germany) and colleagues, conclude: “Our meta-analysis of thrombolysis alone versus mechanical thrombectomy with or without thrombolysis in patients with iliofemoral DVT revealed similar incidences of acute successful thrombus removal. However, mechanical thrombectomy increased six-month cumulative primary patency and, subject to publication bias, decreased frequency of major bleeding.”

They add that no differences across groups became obvious with regard to valvular reflux or pulmonary embolism and that the level of risk and clinical relevance of haemolysis resulting from mechanical thrombectomy “needs to be evaluated in future studies”.

Detailing the rationale behind the study, Lichtenberg et al outline that iliofemoral DVT accounts for about 25% of lower limb DVT. Patients with acute iliofemoral DVT carry a high risk of developing potentially chronic debilitating post-thrombotic syndrome (PTS). Residual thrombus may increase the risk of PTS as well as recurrent DVT, and pulmonary embolism, they note.

Whether early thrombus removal in addition to standard care of anticoagulation and compressive therapy decreases the risk of PTS has not been clarified yet, the authors write.

Lichtenberg and colleagues identified observational and randomised trial published between January 2001 and February 2019 using MEDLINE. They included studies on DVT treated with either thrombolysis alone or percutaneous mechanical thrombectomy adjunctive to conventional anticoagulation and compressive intervention.

The investigators then conducted a meta-analysis of proportions to assess effectiveness outcomes of successful lysis and primary patency, post-thrombotic symdrome, valvular reflux, recurrent DVT, as well as safety outcomes of major bleeding, haematuria, and pulmonary embolism.

Lichtenberg et al identified 77 records, of which 17 studies comprising 1,417 patients were eligible

for inclusion.

They report that pooled proportion of successful lysis was similar between groups (thrombolysis alone: 95% [I2=68.4%]; percutaneous mechanical thrombectomy: 96% [I2=0%]; Qbet [Cochran’s Q between groups] 0.3, p=0.61). However, pooled proportion of six-month primary patency was lower after thrombolysis alone than after percutaneous mechanical thrombectomy (68% [I2=15.6%] vs. 94%; Qbet 26.4, p<0.001).

In addition, they found that considerable heterogeneity between groups did not allow for between-group comparison of thrombolysis alone and recurrent DVT. Major bleeding was more frequent after thrombolysis alone than after percutaneous mechanical thrombectomy (6% [I2=0%] vs. 1% [I2=0%]; Qbet 12.3, p<0.001).

Incidence of haematuria was lower after thrombolysis alone as compared to percutaneous mechanical thrombectomy (2% [I2=56%] vs. 91.3% [I2=91.7%]; Qbet 714, p<0.001).

Finally, the incidences of valvular reflux and pulmonary embolism were similar across groups (thrombolysis alone: 61% versus percutaneous mechanical thrombectomy: 53%; Qbet 0.7, p=0.39 and thrombolysis alone: 2% versus percutaneous mechanical thrombectomy: 1%; Qbet 1.1, p=0.3, respectively).

In the discussion of their findings, Lichtenberg and colleagues consider how these results might affect practice. “On one hand, thrombolysis supports standard treatment of anticoagulation by means of improved thrombus clearance, but on the other, long lasting infusion of up to 72 hours and the need of intensive care unit monitoring due to an increased risk of bleeding is necessary,” they begin.

Deep venous stenting presents advantage over ablation in achieving better ulcer healing rates “Venous leg ulcers (VLUs) secondary to deep venous stenosis represents a distinct class of patients who require a unique treatment paradigm,” stated Abhisekh Mohapatra (University of Pittsburgh Medical Center, Pittsburgh, USA), presenting results of a multicentre retrospective study of patients presenting with VLUs— between 2013 and 2017—that favoured deep venous stenting over ablation techniques.

SPEAKING TO ATTENDEES at the annual meeting of the American Venous Forum (AVF 2020; 3–6 March, Amelia Island, USA), Mohapatra noted that the aim of the study, which included data

for 832 patients across 11 centres in the USA, was not only to determine whether the presence of deep venous stenosis affects the wound healing trajectory of VLU patients, but also to understand

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The authors continue: “Percutaneous mechanical thrombectomy is shown to accelerate thrombus maceration and removal and to effectively decrease residual thrombus burden by means of aspiration. Thus, with rapid reperfusion by percutaneous mechanical thrombectomy, thrombolytic medication can be reduced or completely avoided. It is therefore to be expected that the incidence of bleeding decreases without compromising effectiveness.”

Lichtenberg et al acknowledge some limitations to their study. Firstly, they note that comparison is based on study-level results from small to medium scale studies with different patients and procedure characteristics such as additional stenting in varying frequencies. For example, the percutaneous mechanical thrombectomy group included studies that applied mechanical thrombectomy alone as well as studies that combined mechanical thrombectomy. “This approach might have increased heterogeneity,” Lichtenberg et al comment.

Percutaneous mechanical thrombectomy is shown to accelerate thrombus maceration and removal.”

Furthermore, they note that outcome definitions, including primary patency, recurrent DVT, and severity of post-thrombotic syndrome as well as follow-up time were not consistent across studies and that evidence is limited by moderate to considerable confounding factors, selection, misclassification, or information bias of included studies.

In addition, because of the small number of studies regarding lysis, primary patency, recurrent DVT, and pulmonary embolism, “publication bias must be interpreted with caution,” they remark.

Finally, due to the differences in the mechanisms of action for the analysed percutaneous mechanical thrombectomy devices, the investigators caution that “it may not be correct to group the findings and assume the results can be consistently assumed for each device i.e. class effect”.

which treatment strategies affect ulcer healing in those diagnosed with deep venous stenosis.

Of the 832 patients in the dataset, 16.1% (n=134) had stenosis in the deep venous system. Those with deep venous stenosis, compared to patients without,

When deep venous stenting is performed, it can significantly improve venous hypertension in the leg and aid in wound healing.”

Michael Lichtenberg

were more likely to have a history of deep venous thrombosis (47% vs. 23.6%; p<0.001), have a hypercoagulable state (27.6% vs. 10.7%; p<0.001), and be receiving anticoagulation (71.6% vs 25.5%; p<0.001).

Mohapatra continued, adding that all patients with deep venous stenosis had concomitant superficial vein reflux, while 26.1% (n=35) had refluxing perforator veins. Out of the 134 deep venous stenosis patients, stenting was performed in 70.9% (n=95), truncal ablation in 44.8% (n=60) and perforator ablation in 20.9% (n=28); when both stenting and truncal ablation were performed, stenting was undertaken first in 53.5% of cases.

Turning his attention to wound healing, the speaker revealed that patients who underwent deep venous stenting healed faster than those with untreated deep venous stenosis (hazard ratio 2.46; 95% CI, 1.49–4.06; p<0.001).

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June 2020 | Issue 14

COVID-19

COVID-19: Reflections on VTE, patient risk assessment, and therapeutic challenges Joseph Caprini Comment & Analysis Joseph A Caprini considers venous thromboemolism (VTE), patient risk assessment, and therapeutic challenges in the wake of the COVID-19 pandemic.

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ovid-19 was linked to pneumonia, which was associated with mortality of 11.5%. Coronavirus pneumonia patients who died were found to have elevated D-dimer and fibrin degradation product levels (FDP) on admission and in late stages of the disease prolonged prothrombin (PT) and partial thromboplastin times (PTT).

Criteria for disseminated intravascular coagulation (DIC) were found in 71% (15) of non-survivors and only 0.6% of survivors. Chronic diseases were found in 41% of the patients. During the late stages of the disease, fibrinogen and antithrombin levels were decreased, along with markedly increased D dimer and FDP levels. Sepsis and consumptive coagulopathy were frequently seen.

It was postulated that these coagulation changes were based on a cascade of events beginning with inflammation and sepsis releasing inflammatory cytokines, which caused increased circulating thrombin, reflected in the D-dimer levels. The response to these changes was activation of the fibrinolytic system resulting in an elevation of FDP. This process involving inflammation activates coagulation resulting in increased circulating thrombin generation. Fibrinogen is converted into fibrin that coats bacteria and viruses to physically entrap them and prevent their dissemination.

The increased thrombotic state can manifest as a variety of clinical presentations. The patient may exhibit evidence of a hypercoagulable state with development of clinical VTE. DIC may evolve into consumptive coagulopathy, and as the clotting factors are used up, the PT and PTT will become prolonged.

This chain of events may become impossible to manage due to bleeding, and all resources must be brought to bear, including stopping or lowering the dose of anticoagulant drugs. Transfusion of blood, platelets, or plasma products may be necessary, as well as a trial of anti-fibrinolytic drugs. Extracorporeal membrane oxygenation (ECMO) as a last resort has been used selectively.

In a retrospective case series from Italy, involving 1,591 coronavirus patients, they found that 99% of 1,300 patients with available respiratory support data required respiratory support, 88% required intubation, and noninvasive ventilation was necessary in 11%. The intensive care unit (ICU) mortality was 26% Coagulation changes representing various stages of hypercoagulability due to the presence of inflammation, sepsis, and/or pneumonia are not the only pathophysiologic issues in these patients. Most Covid-19 hospitalised patients are at high risk of VTE as a result of principles proposed in 1856 by Virchow, a brilliant German pathologist.

He introduced the concept known as Virchow’s triad, describing three factors associated with development of venous thrombosis. These include venous stasis, endothelial injury, and hypercoagulability. The risk is highest when all three factors are present.

Patients who are at bed rest, particularly due to hypotension, shock, coma, sedation, or when mechanical ventilation is necessary, are at risk.

Marked reduction of blood flow from

clotting. Compounding this increased clotting activity is the individual patient’s degree of infection, sepsis, or pneumonia.

A thorough thrombosis risk assessment is particularly important in the comprehensive treatment of these coronavirus patients. The Caprini score is a comprehensive history and physical examination involving 40 elements. The weight of each element present (risk factor; e.g., 1,2,3,5) contributing to a thrombotic event is totalled to produce a final score. This score is plotted against the clinical incidence of VTE and a nonlinear increase in clinical events with increasing score has been observed. More than five million patients in more than 150 clinical trials have documented this association. Coronavirus patients may be assessed with less complex scores, but the Padua and Improve scores do not record family history of thrombosis or past obstetrical complications that may indicate the patient is a carrier of anticardiolipin antibodies or a beta2 glycoprotein abnormality.

The Caprini score can classify patients into low-risk, high-risk, or very-high-risk. Low-risk patients (scores 0–4) should not receive anticoagulant prophylaxis because it does not further lower the incidence of thrombosis, only increases bleeding complications. It should be noted that this principle does not apply to coronavirus patients due to their high baseline thrombotic risk. In surgical patients without the virus, highrisk patients (scores 5–8) benefit from a course of anticoagulation of at least seven to 10 days, and very-high-risk patients (scores 9+) benefit from anticoagulant prophylaxis for up four weeks.

Patients admitted with coronavirus are all at increased risk of thrombosis and benefit from anticoagulant prophylaxis. These patients should receive anticoagulant prophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH) unless there is increased risk of bleeding.

Mechanical methods are relied upon in patients where anticoagulation is not suitable. The presence of respiratory involvement automatically dictates LMWH prophylaxis because it has previously been shown to result in a 75%

An aggressive approach for patients exhibiting clinical or laboratory features associated with DIC may be lifesaving.” the legs due to inactivity occurs. This phenomenon, known as venous stasis, results in pooling of venous blood while arterial inflow is not altered. Eventually, veins become engorged with blood, and this results in cracks in the venous lining (endothelial injury). This process exposes the blood to sub-endothelial collagen, triggering clotting as the blood is exposed to this foreign surface. Finally, hypercoagulability exists in the calf leg veins compounded by waste products from normal muscle metabolism that become trapped and further stimulate

reduction of VTE events.

The purpose of scoring is to identify very high-risk individuals with multiple risk factors present before the onset of the viral infection. It has been reported by Tang that 41% of patients have existing chronic disease. Common examples include patients with a family history or past history of VTE, morbid obesity with a BMI over 35, or existing thrombophilia.

Individuals with obesity frequently suffer from sleep apnea, hypertension, diabetes requiring insulin, and cardiovascular disease. It is recommended that these

individuals, along with those with a score of 8+, be given twice the normal dose of anticoagulation. There are no randomised trials to substantiate this practice; however, the tendency of these high-risk patients to develop fatal and nonfatal thrombotic events plus the additional thrombotic risks associated with the virus appear to justify this approach.

The Caprini score is a dynamic instrument and needs to be updated as complications during hospitalisation occur. Rescoring of the patient during hospitalisation as complications develop may push patients with lower scores into the very high-risk group. At this point then, doubling the anticoagulant prophylaxis should be considered.

Increasing the score by three points occurs when patients develop a positive D-dimer. Some investigators use therapeutic anticoagulation for those with three times or more elevation of the D-dimer levels. There is a one-point increase when inadequate ambulation occurs. The definition of ambulation has been suggested by the data to mean that walking 30 feet at one time decreases the incidence of VTE by 50%. Unfortunately, going to the bathroom does not qualify as ambulation using these criteria.

A final Caprini score should be completed before discharge and those with a score of 8+, including those with a positive D-dimer, may benefit from six weeks of anticoagulation facilitated by use of one of the new oral anticoagulants.

Coumadin should be avoided due to the personal contact required for monitoring.

Haematologic changes signalling severe disease and a poor prognosis include one or more of the following: elevated D-dimer, elevated fibrinogen or FDP, prolonged PT or PTT, and thrombocytopenia.

Some investigators have suggested screening patients who develop these changes with ultrasonography to detect subclinical thrombosis. Point-of-care ultrasound screening (POTUS) using a hand-held instrument at the bedside is advised. Limited examination including two-point ultrasound involving the femoral and popliteal veins is a practical approach. Others feel that scanning should be reserved for those with clinical indications.

In conclusion, accurate thrombosis risk assessment for all coronavirus patients is advised. Thrombosis prophylaxis is indicated for most patients and traditional anticoagulants help prevent most fatal thrombotic events. Appropriate VTE screening for select very-high-risk patients based on haematologic or clinical criteria is also advised. An aggressive approach for patients exhibiting clinical or laboratory features associated with DIC may be lifesaving.

References for this article can be found online at www.venousnews.com.

Joseph A Caprini is a senior clinician educator at the Pritzker School of Medicine at the University of Chicago in Chicago, USA. He is also an Emeritus physician at NorthShore University HealthSystem in Evanston, USA.

Issue 14 | June 2020

IVC filters

Reviewing evidence for and against IVC filters in 2020 Following the publication of “Another nail in the coffin of vena cava filters” in the British Journal of Surgery, which considered potential problems with the use of inferior vena cava (IVC) filters, authors Andrew Doyle and Narayan Karunanithy (Guy’s and St Thomas’ Hospital, London, UK) speak to Venous News about the existing evidence available for IVC filters, patients in whom they remain an option, and potential advances in technology that could make them viable again.

What is the current evidence for IVC filters in 2020?

A recently published multicentre randomised controlled trial (RCT) evaluating IVC filter use in severe trauma patients demonstrated no overall survival benefit (defined as a composite of all cause 90-day mortality and symptomatic pulmonary embolism [PE]).1-2 The rate of late presentation PE was significantly lower in the filter group. These results are in line with other studies, including PREPIC 1 and 2, which have demonstrated that use of IVC filters results in lower rates of symptomatic PE but no overall survival benefit, as well as an increase in the rate of caval and lower limb deep vein thrombosis (DVT).

The problem with filters is confounded by the failure to remove them when no longer needed. Even in the setting of an RCT, the failure-to-retrieve rate was 31%.2 Hence, centres placing IVC filters must have a robust filter removal programme, as failure to do so increases long-term complications including caval thrombosis, recurrent DVT, filter migration, and caval perforation.

Are there any specific patients in whom an IVC filter should be implanted, in particular those at high risk of bleeding with anticoagulation?

There is lack of high-level evidence to support the routine use of IVC filters. However, their use should be considered on a case-by-case basis for patients where thromboprophylaxis is required and alternative pharmacological and mechanical options have been considered and deemed unsuitable. Typical scenarios in our practice include those diagnosed with acute venous thromboembolism (VTE) that cannot be anticoagulated, owing to major active bleeding or imminent major surgery.

Do you think that the atmosphere of litigation in certain countries, such as the USA, and a focus on the importance of removing IVC filters, will stop physicians from implanting IVC filters in patients who might really need one?

Clinicians are generally making more measured decisions about their use, which is reflected in our own clinical practice where we have seen fewer filter insertions. The decisions are also being made upon consensus opinion between relevant specialities including haematology, interventional radiology, and vascular surgery.

In patients for whom the implantation of an IVC filter is unsuitable, what other options are available for thromboprophylaxis?

The alternative options are pharmacological

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beexplored further. They are extensively used in patients following stroke, but recent studies have shown no additional benefit in the critical care setting when used in conjunction with anticoagulation. In the immediate perioperative period, they can be a useful option until anticoagulation can be restarted.

Are you optimistic about the potential of advanced IVC filters that bioconvert in the vessel and how can this innovation solve a problem?

Andrew Doyle

Narayan Karunanithy

thromboprophylaxis, typically with either unfractionated or low-molecular-weight heparin, and/or mechanical thromboprophylaxis with intermittent pneumatic compression devices.

With pharmacological thromboprophylaxis, continued clinical assessment is key. Heparin should be introduced as early as possible, once the bleeding risk has reduced sufficiently. For example, following emergency surgery, anticoagulation can potentially be introduced after six to eight hours—cautiously at up titrating doses—rather than avoiding its use.

Mechanical thromboprophylaxis can also be considered in the setting of VTE prevention. The role of intermittent pneumatic compression devices needs to

The problem with filters is confounded by the failure to remove them when no longer needed.”

We are cautiously optimistic of the initial results of Sentry Bioconvertible IVC filter device study. A multicentre study has shown the rate of symptomatic PE was 0% at one year and 2.4% at two years.3 Successful filter bioconversion rate was 95.7%, 96.4%, and 96.5% at six months, one year, and two years, respectively.

Caval thrombosis was low at 1.6%. Larger scale studies and longer-term data are awaited.

References: 1. Doyle AJ, Karunanithy N, Hunt BJ. Another nail in the coffin of vena cava filters? Br J Surg. 2020 Jan; 107(1): 9-10 2. Ho KM, Rao S, Honeybul S. et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25; 381(4):328-337 3. Dake MD, Murphy TP, Krämer AH. et al. Final two-year outcomes for the sentry bioconvertible inferior vena cava filter in patients requiring temporary protection from pulmonary embolism. J Vasc Interv Radiol. 2020 Feb; 31(2):221-230

Andrew Doyle is a senior clinical research fellow in haemostasis at Guy’s and St Thomas’ NHS Foundation Trust, London, UK. Narayan Karunanithy is an honorary senior lecturer at the School of Biomedical Engineering and Imaging Sciences, King’s College London, UK, and a consultant interventional radiologist at Guy’s and St Thomas’ NHS Foundation Trust, London, UK. The authors have no disclosures.

First-in-man trial of prosthetic VenoValve demonstrates promise for improving clinical outcomes INITIAL RESULTS OF an ongoing first-in-man study in Colombia, that saw the implantation of a prosthetic venous valve in 15 patients, have demonstrated an improvement in clinical outcomes and quality of life.

The promising findings were presented at the Southern Association for Vascular Surgery (SAVS) annual meeting (8–11 January 2020, Palm Beach, USA).

According to trial investigator Jorge H Ulloa (Universidad de los Andes, Bogota, Colombia), there was also a marked reduction in pain among “a complex and difficult-to-treat patient population”. In the USA, 2.4 million people are affected with chronic venous insufficiency, Ulloa et al noted. Moreover, one million are treated for venous stasis ulcers, with few options available to patients who develop postthrombotic disease secondary to deep venous reflux.

The new venous prosthetic valve, known as the VenoValve, is a combination of a stainless-steel frame and porcine aortic monocusp leaflet, and was developed to be surgically implanted into the deep venous system—the femoral popliteal vein—of patients with C5–C6 disease.

Endpoints of the study were to evaluate safety, “which is very important in a first-in-man study,” said Ulloa. He continued: “These [endpoints] include reflux by duplex ultrasound and femoral popliteal vein, as well as clinical assessment by a vascular surgeon.

Also, pain scoring, the visual analogue scale (VAS) score and quality of life outcomes were evaluated by the patients during this study.”

In the trial, researchers included actual venous reflux greater than one second in C5 and C6 patients.

“Superficial reflux was controlled or ablated prior to patients enrolling into this study,” Ulloa said. “All of

[the patients] were able to walk by themselves and peripheral arterial disease (PAD) was ruled out by alternating blood flow (ABF).” Ulloa went on to explain that just three weeks prior to his presentation at the SAVS podium, the research team had completed its 11th case.

He drew attention to six patients who averaged at least six months of follow-up. “We have seen a 40% reduction in reflux, a 61% improvement in [the] Venous Clinical Severity Score (VCSS) or significant clinical improvement, and all patients at six months have noted a significant reduction in their pain by the VAS score. Patient six increased the VAS and VCSS due to poor anticoagulation therapy and by lack of compliance.”

Ulloa added: “All cases have demonstrated a marked improvement in the reflux, with most of them reaching baseline except in patient six. Significant clinical improvements were also observed. Many patients went from moderate to severe to mild disease by clinical assessment.”

Summing up his findings, Ulloa concluded: “We had an overall improvement in reflux by 40%, a clinical improvement by 61% with an average of 8.4 points and a 57% pain improvement. The implantation technique has evolved a great deal since the first case was performed, with an average timing of 40 minutes.

Our results of this feasibility study are on the way.”

“We will evolve to a second phase, which will include a pivotal trial with more recruiting centres and increasing the number of cases to assess the performance of this prosthetic valve as an option for patients with C4B to C6 disease. Reflux quality calculations will be included in the next phase.”

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June 2020 | Issue 14

Profiles

A year in profiles 2019–20 In the past year, Venous News has profiled some of the most prominent figures currently working in the venous field. In this regular feature, the four conversation leaders below have offered their opinion and outlook on a range of challenging issues currently impacting the space, as well as reflecting on what they have discovered about themselves and the wider venous community throughout their careers.

Fedor Lurie LOOKING BACK ON a journey which has taken him from Ekaterinburg, Russia to the “professional honour” of leading the American Venous Forum (AVF) as president, Fedor Lurie spoke with Venous News about his career and the many “mysteries” which have fascinated him over the years.

“I dreamed of travelling the world, finding the Loch Ness monster, discovering lost tribes of the Amazon jungle, solving the secret of the Bermuda triangle, and flying to other worlds in search of extraterrestrial intelligent life,” Lurie revealed, before explaining that his interest in science and maths developed with his discovery of science fiction.

A medical career surely followed and, with the support of good friend and mentor Robert L Kistner, so did Lurie’s passion for treating venous disease. “At first, I was overwhelmed by how much one needs to learn to be able to practice.

But, the very first clinical rotation confirmed exactly what led me to choose a medical career—every single patient is a mystery that is challenging to solve.

Seeing pain and suffering strengthened my desire to solve those mysteries for as

many patients as I can.”

Having distinguished himself as a venous specialist, Lurie has been directly involved in a number of key developments within the space.

This includes an updated guidelines document on compression therapy, for which he was principal author. “The key recommendations are specific to the treatment modality, and the disease stage. Although the level of evidence deserves major improvements, it is clear that compression therapy remains a key component of comprehensive venous care, especially in advanced stages of chronic venous disease.”

Seeing pain and suffering strengthened my desire to solve those mysteries for as many patients as I can.”

Kurosh Parsi DESPITE THE FACT that medicine was initially his “second or third choice”, current president of the International Union of Phlebology (UIP), Kurosh Parsi, has enjoyed a successful career in the venous field, helping to grow the practice of phlebology and dermatology, as well as leading the space in such procedures as catheter-guided sclerotherapy.

“Over the years, I developed an interest in venous thrombosis and wanted to study the interaction of sclerosants with the coagulation system,” Parsi stated. “As a dermatologist and phlebologist, I became interested in vascular anomalies, joined the International Society for the Study of Vascular Anomalies (ISSVA) and met Prof BB Lee,” he added, describing Lee as one of his “true mentors over the years”.

Regarding the most significant ways in which the venous field has changed throughout his career, Parsi pointed to the French school of phlebology and how the development of ultrasoundguided sclerotherapy (UGS), pioneered

by Michel Schadeck and Frederic Vin, changed the field of phlebology forever.

“UGS became a much more effective procedure with the introduction of foam sclerosants pioneered by Juan Cabrera (Spain) and Lorenzo Tessari (Italy).

Again, foam has made a huge difference in our treatment outcomes thanks to the genius of Juan and Lorenzo,” he commented.

The discussion soon turned to his UIP presidency, with Parsi pledging that “my mandate is to make the UIP processes crystal clear, structured, fair, simple, efficient, non-factional, non-political and highly organised”.

Moreover, Parsi asserted the importance of having the full support of the phlebology community in the next four years to achieve tangible results.

Looking to the future of the practice, Parsi also gave advice to those starting a career in phlebology. “Think outside the box. Do not believe everything you read in the textbooks, especially the older ones. When people tell you, ‘I have been doing this for 20 years and have never had any problems’, remember they may have been doing it badly for 20 years and the patients were the ones who had the problems! Question everything and think independently.”

Issue 14 | June 2020

Profiles

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John Kaufman ONE OF TWO course directors of The VEINS at VIVA profiled in the past 12 months, John Kaufman represents the crucial relationship between the venous speciality and interventional radiology (IR). Speaking to Venous News on how the IR field has transformed over the years, Kaufman highlighted some key areas of innovation to look out for in the future.

“We are all watching machine learning and artificial intelligence (AI) with intense interest,” he posited. “On the face of it, one might assume that proceduralists may be less impacted than imagers, but AI will become integral to our decision-making processes before, during, and after interventions. It is less likely that computers will do the actual procedures; instead, they will analyse images, laboratory results, and symptoms.”

While there is much to come in the future, Kaufman also reflected on how the field has changed since its inception. “The first major change is that image-guided procedures have become mainstream, such that medicine without them is now inconceivable. Take the transjugular intrahepatic portosystemic shunt (TIPS) procedure for complications of portal hypertension, developed by Josef Rosch from my institution; modern

hepatology cannot function without it.”

He continued: “The second major change is the broad application of the scientific method when bringing new technologies and procedures forward.

Although the process is now slower than in the past, it is the right way to move ahead. The third is the recognition that the patient is the focus, not the technology or the physician or their specialty.”

On the challenge of gaining recognition for IR as a speciality in the USA, Kaufman told Venous News that “the transition from sub-specialty of diagnostic radiology (DR) to a primary specialty followed many of the classic steps of implementing major changes: refinement of the message, initial champions, engagement of key stakeholders, early adopters, and all that follows”.

Kaufman also revealed an even more personal investment in the future of IR, emphasising his pride in daughter and interventional radiologist Claire Kaufman. Describing the moment of her graduation from medical school, which in his mind “supplanted hanging my medical school diploma on the wall”, he said: “It is fantastic, truly awesome, and she is going to make me look like a back-bencher.”

Raghu Kolluri

As the USA’s population ages, and the prevalence of vascular disease increases, there is going to be a shortage of vascular specialists.”

WORKING ALONGSIDE JOHN Kaufman, as course director of The VEINS at VIVA, Raghu Kolluri has also been a key figure in the venous field.

In a profile, following his appointment as president of the Society for Vascular Medicine (SVM), Kolluri highlighted why future trials should focus on “technical success” and underlined some key areas of research that should be of interest to venous specialists.

“I am very excited about some of the advances in duplex imaging,” said Kolluri. “Multi-row array technology allows a lot more elements to be packed into the new ultrasound probe, leading to exceptionally high-resolution images.

Visualisation of slow flow and deep structures is fascinating. 3D ultrasound imaging and ultrasound contrast may have some future vascular applications.”

“Point-of-care ultrasound is another area of interest, and I believe this will change the way physicians practice and examine patients,” he added, before suggesting the need for “increased utilisation of simultaneous extravascular and intravascular ultrasound in cath labs”, as well as highlighting the potential of thrombectomy devices for pulmonary embolism and deep vein thrombosis management.

Responding to the findings of recent trials, Kolluri agreed that “we must focus on technical success in deep venous interventional trials”. However, he said,

“appropriate assessment of technical success is equally important.” Kolluri added that “patient-reported outcomes are as important as anatomic success; ultimately, the patient needs to feel better”.

On the topic of his appointment as SVM president, Kolluri stated: “SVM is my professional home, and it is an honour to lead this society, which consists of incredible vascular specialists from all training backgrounds. Although we are not a large organisation, we certainly are mighty. In my opinion, no single specialty can provide comprehensive vascular care.

“As the USA’s population ages, and the prevalence of vascular disease increases, there is going to be a shortage of vascular specialists. We will explore all options to increase training programmes in vascular medicine in the next few years.”

Like Parsi, Kolluri also gave some advice to new venous specialists entering the field, encouraging them to “understand the disease process and the pathophysiology of venous disease”. He said: “This is more important than focusing on techniques and technologies,” adding that “it is also important to remember that manifestations of venous disease result from complex venolymphatic and cardiovascular interactions. Unless you think outside of the vascular box, you will not be able to help all patients.”

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June 2020 | Issue 14

IVUS based therapies

The future of IVUS based therapies for venous leg ulcers

not meet statistical significance, likely due to a type II statistical error, this benefit in the stented VLU patients is consistent with the available literature.

The VIDIO trial recruited 100 patients with cCEAP 4–6 LECVI to undergo evaluation with multiplanar venogram (MPV) and IVUS to identify IFOO.4 IVUS identified a significant iliac or common femoral vein stenosis in 42% of the 300 vein segments (CIV, EIV, CFV) assessed. Half of these lesions were not identified with MPV. A 50% CSA stenosis was diagnosed more frequently with IVUS and resulted in treatment with stents in these severe LECVI patients.

The overall patient cohort stented had a decrease in their revised Venous Clinical Severity Scores (rVCSS) at one month that persisted at six months compared to baseline (p<0.001) More specifically, patients with VLUs (i.e. cCEAP 6) and IFOO who underwent stent placement had a decrease in VLU size at 1 and 6 months compared to baseline (p=0.017) Patients with VLUs who were not stented due to no identified IFOO, did not improve at 6 months (p>0.05) in spite of continued best medical therapy. This suggests that IVUS guided treatment of IFOO can favorably address the venous pathophysiology of VLU patients, improve their LECVI and expedite ulcer healing.

Though in its infancy, the evolving venous valve technologies, require the exact measurements and detailed, and sometimes real-time, imaging available with IVUS. Though the algorithms for the use of IVUS in planning and executing venous valve interventions are still developing, the experience of the

guided stenting of IFOO can promote VLU healing in selected patients. Our understanding of which patients to evaluate for clinically meaningful IFOO is evolving, but it seems that patients with LECVI and ulceration and diffuse skin and lower extremity soft tissue injury are most likely to have a significant central vein outflow obstruction.

Patients who fail to heal their VLUs after compression and appropriate superficial and perforator vein ablation are also likely to have IFOO. The potential benefit of early IVUS guided stenting in VLU patients with IFOO is to achieve expedited ulcer healing, decrease patient suffering, decrease the medical costs associated with prolonged wound care and eliminate the social costs of disability.

The current literature supports evaluating chronic and recurrent VLU patients for IFOO and stenting as appropriate. However, some members of the medical community as well as payors remain skeptical to the benefit of routine IVUS guided stenting of IFOO to promote VLU healing.

To evolve the management of VLUs across the spectrum of vested clinicians and payors will require a prospective randomised controlled trial (RCT) examining the added benefit of treatment with IVUS guided stenting of IFOO when compared to standard of care treatment alone. Though many vascular interventionalists believe in the benefit of stenting IFOO in VLU patients, it will require a RCT to drive this new paradigm into wound centres, societal treatment guidelines, national health plans and insurance coverage policies.

Figure 1: Large and expanding VLU due to chronic weeping and maceration from IFOO

Figure 2: VLU with circumferential inflammation and skin damage, calf

Figure 3: Small, focal, non-healing VLU in distribution of greater saphenous vein

of the time following IFOO treatment with angioplasty and stent.2 However, since clinical improvement is not uniform, there is still uncertainty regarding which VLU patients will benefit from treatment of their IFOO. Rossi et al have reported that in a double-blinded randomised controlled trial, patients who failed to achieve VLU healing with conservative measures had a 90% ulcer healing rate following stenting of a 50% IVUS diagnosed iliac vein stenosis, compared to a 40% ulcer healing rate with continued best medical therapy.3 Though this positive trend did

last decade has shown the advantages of IVUS in planning and performing deep vein endotherapies. The future of vein valve interventions in patients with symptomatic LECVI will likely begin with cCEAP 5 and 6 patients who have had all other forms of their LECVI treated with limited or inadequate clinical response. Though there is clearly going to be a role for IVUS in this space, how this imaging of the deep veins will best be used will become clearer in the next few years.

What the available literature and world experience indicates is that IVUS

Though studies to date of IVUS guided stenting have moved the ball far down the field, an RCT will move the ball across the goal line and change the paradigm.

Paul Gagne Comment & Analysis Writing for Venous News, Paul Gagne considers the future of intravascular ultrasound (IVUS) based therapies for venous leg ulcers (VLUs). He concludes that while studies of IVUS guided stenting to date “have moved the ball far down the field,” a randomised controlled trial “will move the ball across the goal line and change the paradigm”.

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atients with an active or healed VLU can have a single dominant or multiple contributing venous pathologies. Superficial, perforator, and deep vein valvular incompetence (VVI) as well as deep vein occlusive disease (i.e. post-thrombotic scar or extrinsic compression) can be singularly or collectively the cause of the non-healing wound. Additionally, patient and wound specific factors can be additive factors in promoting both the formation and delayed healing of VLUs. A sedentary lifestyle, calf muscle pump dysfunction, wound infection and cellular senescence have all been implicated in impeding VLU healing. Though compression therapy is part of the VLU treatment algorithm, both patient compliance and tolerance as well as compression effectiveness are quite variable.

Finally, all VLUs are not the same.

A small focal ulcer (Figure 1) with a dilated, and incompetent axial superficial vein in the ulcer bed, especially in the absence of diffuse skin damage, often heals and doesn’t recur following ablation of the superficial vein and resolution of the associated VVI. Limbs with VLUs and diffuse, near or totally circumferential induration, inflammation, drainage or lipodermatosclerosis (Figures 2 and 3) often do not respond to axial or perforator vein ablation alone for VLU healing, and if they do heal, the VLU recurrence rate is high in the near term. These patients often have iliac and common femoral vein outflow obstruction (IFOO) that must be treated if prolonged VLU healing is to be achieved.

Over the last 15 years recognition of the frequent role of IFOO in the pathophysiology of lower extremity chronic venous insufficiency (LECVI) and chronic venous ulcers has developed.

Marston et al evaluated 78 patients with cCEAP 5&6 disease for IFOO and found 37% had a 50% stenosis and 23% had a >80% stenosis based on computed tomography (CT) angiogram or magnetic resonance (MR) angiogram.1 Female gender, a history of DVT and reflux in the deep venous system predicted a >80%

stenosis in the iliac veins. This report suggested that IFOO can be a commonly present contributing factor in the pathophysiology of VLU patients. Our understanding of IFOO in these cCEAP 6 patients has expanded with the regular use of IVUS in deep vein imaging.

IVUS is more sensitive for detecting the variety of occlusive pathologies (i.e. compression, intraluminal scar, intramural scar, or a combination) that can interfere with normal iliac and common femoral vein function.

Analyses in large cohort studies have shown that patients with clinical CEAP 6 LECVI and IFOO heal their VLUs 75%

References 1. Marston W et al, J Vasc Surg, May 2011 1. Raju S and Neglen, P, J Vasc Surg 2006;44 3. Rossi et al, Vasc Surg Venous Lymphat Disord, March, 2018 4. J Vasc Surg Venous Lymphat Disord, 2017 Sep;5(5): 678–687

Paul Gagne is a vascular surgeon in Darien, USA. The author is a consultant for Philips, Boston Scientific, and Bard BD.

Issue 14 | June 2020

Lymphoedema

Chronic venous insufficiency identified as a leading cause of lower extremity lymphoedema A retrospective analysis of patients diagnosed with lower extremity lymphoedema, and treated in a cancer-affiliated physical therapy department, has found that chronic venous insufficiency (or phlebolymphoedema) is the “predominant cause of lower extremity lymphoedema”. Published online in the Journal of Vascular Surgery: Venous and Lymphatic Disorders, it was also revealed by investigators that one in four patients studied had more than one cause of lymphoedema.

“ALTHOUGH MALIGNANT DISEASE is ubiquitously documented as the dominant cause of lower extremity lymphoedema, our study challenges this doctrine by finding chronic venous insufficiency the prevailing cause,” write first author Steven M Dean (Wexner Medical Center, The Ohio State University, Columbus, USA) and colleagues.

According to the authors, “lower extremity lymphoedema is frequently encountered in the vascular clinic”. They explain that cancer is understood to be the most common cause of this condition in Western countries, with chronic venous sufficiency “overlooked” as a possible factor as to why lower extremity lymphoedema develops. “Moreover, lymphoedema is typically ascribed to a single cause, yet multiple causes can coexist,” Dean et al add.

Citing the “dearth of definitive studies” comparing the frequency and importance of clinical characteristics of the most frequent causes, the investigators state: “The purpose of this study was to retrospectively document the prevalence and manifestations of the four most commonly encountered causes of lower extremity lymphoedema in 440 patients who

presented to an oncology-affiliated physical therapy lymphoedema centre”.

In order to investigate the demographic and clinical characteristics of eligible patients, a three-year retrospective chart review was conducted from January 2012 to December 2015, including patients with lower extremity lymphoedema who underwent complex decongestive lymphatic physiotherapy (n=524). A proportion of patients (n=84) were excluded from the final analysis, note Dean et al, due to an infrequent or rare cause of lymphoedema, inadequate data to definitively substantiate the principal cause, and the presence of secondary causes or associated clinical variables.

“After exclusion, 440 eligible patients were initially divided into […] four principal diagnostic categories, reflecting the predominant cause of leg swelling,” the authors detail. These categories included chronic venous insufficiency causing lymphoedema, cancerrelated lymphoedema, primary lymphoedema, and lipoedema with lymphoedema. Dean and colleagues continue: “Patients within each of the four principal diagnoses were analysed by demographic and baseline

Revision of CEAP classification recognises new predictors and definitions for venous disease Incorporating evidence collected since 2004, the latest revision of the CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification system has underlined a number of key updates relating to descriptions of chronic venous disease patients. “There has been a lot of information that has come out over the last 15 years that required parts of CEAP to change,” said Marc Passman (University of Alabama, Birmingham, USA), presenting at the annual meeting of the American Venous Forum (AVF 2020; 3–6 March, Amelia Island, USA).

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evealing the new CEAP classification for 2020 alongside first author Fedor Lurie (Jobst Vascular Institute, Toledo; University of Michigan, Ann Arbor, USA), Passman continued by emphasising the “wide acceptance for the CEAP system across all venous societies internationally”, as well as the fact that this revision aims to “enhance our collective understanding of venous disease and elevate scientific standards for published literature”.

“The challenge for our taskforce was to figure out how to change the system while maintaining the integrity of the 2004 version, but also provide meaningful updates to move CEAP forward. Also important was the need to avoid time delay for research and evidence synthesis,” he added.

During the session chaired by Passman

and Lurie, in which the latter also outlined the methodology of the update, each of the team leaders—who focused and led a review on one of the four components of the CEAP classification— explained the most significant changes, if any, to the system.

With regard to the “Clinical” element, Mark Meissner (University of Washington School of Medicine, Seattle, USA) asserted that CEAP is reproducible, evidence-based, and places a low burden on practicing clinicians, as well as noting two additions to “C”.

Corona phlebectatica will now be recognised as “a predictor of ulceration similar to other advanced skin changes (C4c)”, while recurrent disease will also be recognised as part of the system (e.g.

C2r for recurrent varicose veins and C6r for recurrent venous ulcer).

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characteristics including age, sex, ethnicity, weight, body mass index (BMI), and anatomic distribution.”

Summarising the results, the investigators underline that chronic venous insufficiency was the most common cause of the condition, as demonstrated in 41.8% of the cohort. Cancer-related lymphoedema followed (33.9%), with primary lymphoedema (12.5%) third and lipoedema with secondary lymphoedema (11.8%) fourth.

Other findings of the analysis, as described by Dean et al, showed that “the collective cohort was more likely to be female (71.1%; p<0.0001), to be white (78.9%; p<0.0001), to demonstrate bilateral distribution (74.5%; p<0.0001), and to have involvement of the left leg (bilateral, 69.1% [p<0.0001]; unilateral, 58.9% [p=0.0588])”. Morbid obesity was also considered to be “nearly universal” (mean weight and body mass index, 115.8 kg and 40.2 kg/m2, respectively) among the cohort studied.

Dean et al conclude: “Although lymphoedema is typically ascribed to a single cause, we identified heterogeneous causation in one in four patients.

Chronic venous insufficiency was the entity most likely to complicate pre-existing lymphoedema and was especially prevalent in cases of lipoedema and, unexpectedly, primary lymphoedema. Morbid obesity was pervasive and correlated with a higher lymphoedema stage, and likely the predisposition to bilateral limb involvement.

“Other notable findings included the predilection for left leg involvement, female sex proclivity, and confirmation of cellulitis susceptibility, which affected half of the chronic venous insufficiency and primary lymphoedema subsets. Total knee arthroplasty was the most common cause of non-cancer surgery-mediated worsening of pre-existing lymphoedema. An unexpected finding was the higher proportion of black patients in the primary lymphoedema cohort.”

Elna Masuda of the venous valve and/ (University of Hawaii, or venous wall, leading to Honolulu, USA) floppy valve or vein wall presented a revision of the weakness, resulting in “Etiology” component, some cases with venous which included changes reflux”—has also been to descriptions of venous established. disease. For “None” (En), Finally, secondary which was previously venous disease has been attributed to patients with separated into intravenous no venous abnormality, (Esi) and extravenous those who possess clinical Marc Passman (Ese), with the former signs typically associated a condition causing with venous disease can now come under venous wall and/or valve damage, the parameters of this description, if no and the latter a pathology affecting other typical venous aetiology is found. venous haemodynamics, locally or In “Congenital” (Ec) cases, an systematically.

In major revisions to the “Anatomy” section of CEAP, detailed by Harold Welch (Lahey Hospital and Medical Center, Burlington, USA), it has been affirmed that any limb being reported for venous disease “should be identified as Right(R) or Left (L)”. Moreover, Welch stressed the need to use specific anatomic abbreviations instead of numbers.

On the “Pathophysiology” element, Ruth Bush (University of Houston College of Medicine, Houston, USA) commented that although there were no significant changes as part of this revision, “contributing factors that may stand alone adjustment, from “congenital abnormality as pathophysiological mechanisms or in which may be apparent at birth or can be conjunction with valvular incompetence recognised later”, to “condition present or reflux” include a BMI of less than at birth, but manifested later in life”, 30kg/m2, right heart failure, impaired was made. A new definition for primary calf muscle pump function, or valvular venous disease—a “degenerative process incompetence in smaller veins.

The challenge for our taskforce was to figure out how to change the system while maintaining the integrity of the 2004 version.”

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June 2020 | Issue 14

Market watch

Product News Geko device represents an alternative to IPC devices during COVID-19

Aspire MAX

FDA clears Aspire MAX mechanical thrombectomy system

Control Medical Technology has announced that the US Food and Drug Administration (FDA) has cleared its Aspire MAX 7–11F mechanical thrombectomy platform to remove blood clots from peripheral vessels.

“This FDA clearance quadruples our product offering and improves our ability to help patients,” said Shawn Fojtik, president of Control Medical Technology in Park City, USA. “The Aspire MAX 7–11F mechanical thrombectomy system includes 20 new large-lumen, flexible, and kinkresistant catheters with dilators powered by the Aspire aspirator and/or an electromechanical pump.”

During a procedure, clinicians typically access the femoral artery or vein, track a catheter over a guidewire to the thrombus, and then apply lowperformance suction with a basic syringe or pulsed continual high-performance vacuum with an Aspire mechanical aspirator or an electromechanical pump.

“Blood clots range from soft-fresh clots to hard-aged thrombus,” continued Fojtik. “Clinicians need more costeffective tools to remove blood clots.

We plan to introduce more catheter and electromechanical pump innovations for use in peripheral, coronary, and neurovascular procedures.”

The new Aspire MAX 7–11F mechanical thrombectomy system includes 7F (0.090″) outer diameter (OD) to 11F (0.140″) OD catheters with flexible dilators for improved tracking. Catheters may be connected to the Aspire aspirator and/or an electromechanical pump for increased speed, force, volume, and control.

Control Medical’s platform also includes the Aspire MAX 5–6F mechanical thrombectomy system with over-the-wire catheters for peripheral vasculature and the Aspire RX-LP mechanical thrombectomy system with rapid exchange catheters for peripheral and coronary vasculature.

Data were recently published using the Aspire RX-LP mechanical thrombectomy system to remove blood clots from total occlusions during heart attack [Adams G, Cavros N, Tai Z, “Novel mechanical thrombectomy device for treatment of acute myocardial infarction: A retrospective report,” Journal of Invasive Cardiology, 2020;32(4):142–146].

extremely challenging circumstances, which are being further complicated by an abnormally high VTE risk and high bleed risk in immobile, critically ill COVID-19 patients. Production to provide an uninterrupted supply of Geko devices to help prevent these life-threatening blood clots is scaling to meet demand. Continuity of supply is paramount.”

Sky Medical Technology highlights a publication on 5 May 2020 in the Journal of Thrombosis and Inari Medical plans initial Haemostasis showing the incidence of public offering venous thromboembolism (VTE) in Inari Medical announced that it will 198 hospitalised COVID-19 patients. conduct an initial public offering (IPO) The overall rate was 42% at 21 days of shares of its common stock and has including patients in the intensive care launched a roadshow promoting the unit (ICU) and the general medical IPO. ward.

Inari has developed two catheterWith VTE recognised as a major based mechanical thrombectomy contributor to COVID-19 multidevices that are designed to remove organ failure, anticoagulation is large clots from large vessels and critical and drug prophylaxis is the eliminate the need for thrombolytic primary intervention, especially for drugs. The ClotTriever system has immobile patients on ventilators received 510(k) clearance from the at risk of VTE in ICU. Similar US Food and Drug Administration increases in thrombotic risk were (FDA) for thrombectomy in the seen with H1N1m influenza (Swine peripheral vessels to treat deep Flu). vein thrombosis. The FlowTriever However, there are COVID-19 system is cleared for the treatment patients, at this same high risk of pulmonary embolism. of VTE, suffering from internal Inari’s IPO, which is expected bleeding. For these patients, to be priced between US$14 and drug prophylaxis causes further US$16 per share, will be composed bleeding. Clinicians therefore rely of 7,333,000 shares of common on mechanical prophylaxis for these stock. In addition, Inari expects patients—either using intermittent to grant the underwriters a 30pneumatic compression (IPC) or, day option to purchase up to an Geko additional 1,099,950 shares of its more recently, the geko device to prevent VTE and minimise the common stock. The Inari shares are risk of bleeding with or without drug expected to trade on the Nasdaq Global prophylaxis.

Market under the symbol “NARI.” According to a Sky Medical press The proposed offering will be made release, the Geko device represents by prospectus available from Bank of an alternative to IPC devices during America Securities and Morgan Stanley.

COVID-19. The Geko device runs A registration statement relating to these a much lower risk of virus cross securities has been filed with the US contamination because it is a singleSecurities and Exchange Commission use device that is discarded after but has not yet become effective, each patient use. The Geko device advised the company. is less labour intensive than IPC devices on patients with fragile skin or Argon Medical announces cardiovascular related contraindications. launch of two new IVC filter The Geko device is seeing increased retrieval kits demand from clinicians in the NHS to Argon Medical Devices has announced reduce the risk of blood clots in high the commercial launch of its Singlerisk COVID-19 patients. The device has loop and Triple-loop retrieval kits for been in use in the UK for three years sale in the USA. The Single-loop and in blood clot prevention of high-risk Triple-loop Retrieval Kits are intended acute stroke patients and has sold over for percutaneous removal of retrievable 700,000 individual device units to date. inferior vena cava (IVC) filters that Bernard Ross, founder and CEO at are no longer medically required, via a Sky Medical said, “We are now gearing- jugular approach. up globally to provide Geko devices “We are excited to improve the IVC to support the prevention of high VTE filter retrieval options available to our risk and bleeding risk in critically ill customers with the introduction of these COVID-19 patients, when drug or other new products,” said George A Leondis, mechanical compression methods of president and CEO of Argon Medical.

VTE prevention are contraindicated, According to a statement, Argon impractical or inaccessible. The Medical’s Single-loop and Triple-loop disposable, single-use Geko devices retrieval kits were designed with the require no sterilisation or reuse between rigour of IVC filter retrieval in mind, patients, taking just 60 seconds to fit. offering the following key features: This requires less nurse-to-patient A coil-reinforced outer sheath with contact time and less viral load the strength needed to detach filter exposure.” legs from the IVC wall Ross concluded, “We are grateful Radiopaque bands on the distal end to all healthcare providers around of the inner sheath, outer sheath the world for what they are doing in and the snare catheter for enhanced

visualisation A 15-degree curve at the distal tip of the snare catheter for directional control “IVC filters are a safe and effective treatment for the prevention of pulmonary embolism, however they should be removed when the need for the filter subsides,” said David Trost (Weill Cornell Medical Center, New York, USA). “I like that Argon’s new retrieval kits can be used on all retrievable IVC filters, regardless of brand, from the jugular vein, providing unique versatility,” he added.

Biolitec reveals new ELVeS Radial 2ring Pro laser fibre for severely tortuous veins

Biolitec has added another laser fibre to its ELVeS Radial 2ring laser fibre family: the ELVeS Radial 2ring Pro enables the minimally invasive endovenous laser treatment of severely tortuous veins.

According to a press release, the ELVeS Radial 2ring Pro fibre has an additional canal into which saline solution can be injected directly up to the tip of the fibre using a simple Luer Lock connection at the rear end of the fibre. The pressure of the incoming saline solution straightens bent areas and thus stretches strong windings. The laser fibre can then be pushed forward in a continuous movement.

This additional function also washes residual blood from the vein compressed after tumescent local anaesthesia (TLA), resulting in optimal closure of the vein.

This is especially advantageous for veins with a large diameter. A further advantage is the avoidance of additional punctures in complex vein structures.

A maximum of 100cm of a vein can be treated with the ELVeS Radial 2ring Pro fibre. The laser fibre can be easily inserted into the vein with a standard 6FR insertion set.

With the first radial fibre ELVeS Radial, which Biolitec launched more than 10 years ago, the company heralded a new era in endovenous laser therapy for varicosis. Due to the 360 degree irradiation of the inner vein walls, which is achieved in the LEONARDO laser devices of Biolitec with a wavelength of 1470nm, surrounding tissue remains undamaged. With the ELVeS Radial 2ring laser fibres, available in two different fibre diameters, truncal veins, perforating veins and smaller lateral branches can be treated equally well.

Penumbra wins FDA clearance for Indigo Aspiration System

Penumbra has announced US Food and Drug Administration (FDA) 510(k) clearance for expanded indication of the Indigo Aspiration system. As part of the system, Indigo Aspiration catheters and separators are indicated for the removal of fresh, soft emboli and thrombi from vessels of the peripheral arterial and venous systems, and now for the treatment of pulmonary embolism (PE).

Penumbra introduced the Indigo system in 2014.

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June 2020 | Issue 14

Market watch

Clinical News Positive two-year data from ALPS registry of LimFlow system published

LimFlow SA has announced publication of positive two-year data from the ALPS registry of the LimFlow percutaneous deep vein arterialisation (pDVA) system. Results were published online in the Journal of Endovascular Therapy and will also appear in the August print issue of the journal.

The ALPS Registry is the largest study to date of no-option chronic limbthreatening ischaemia (CLTI) patients treated with the LimFlow system reporting mid- and long-term results.

“In this complex group of patients, pDVA using the LimFlow device has shown to be feasible and safe with high technical success and good amputationfree survival at six months up to 24 months coupled with good wound healing,” said the paper’s lead author, Andrej Schmidt, head of the Angiology CathLab at Leipzig University Hospital, Leipzig, Germany. “In selected patients with no-option CLTI, pDVA is a safe and effective treatment to prevent amputation and heal wounds.”

“Patients with this disease suffer with chronic ulcers, often including gangrene, recurrent pain, and a very poor quality of life. CLTI is associated with poor mid- and long-term survival, and no-option patients often face the worst outcomes,” said Roberto Ferraresi, chief of the Peripheral Interventional Unit at the San Carlo Clinic, Milan, Italy, co-author of the paper, and a pioneer in the interventional treatment of CLTI. “These patients desperately need an option to avoid amputation and improve their life, and LimFlow offers a very promising alternative for them.”

The ALPS Registry is a multicentre, retrospective study conducted at centres in Alkmaar, the Netherlands; Leipzig, Germany; Paris, France; and Singapore encompassing 32 end-stage—or “nooption”—CLTI patients.

All patients had non-healing wounds on the target foot and no arterial target for surgical or endovascular revascularisation. Among them, 66% had diabetes, 53% had renal insufficiency, and 16% were dialysis dependent. The majority of patients had experienced failed prior attempts

at revascularisation. The registry reported major amputation-free survival of 84%, 71%, and 67% at six months, one year and two years, respectively. Additionally, a positive trend of successful wound healing was demonstrated, with 73% of wounds completely healed at two years.

Technical success was 97%.

When all other therapeutic options have been exhausted and a CLTI patient is facing major amputation, the minimally-invasive LimFlow system is designed to bypass blocked arteries in the leg and deliver oxygenated blood back into the foot via the veins. For many patients, restoring perfusion in the lower limbs resolves chronic pain, improves quality of life, enables wound healing and prevents major amputation.

“It is very gratifying to see these durable results being demonstrated by the LimFlow system in a real-world setting with consecutive patients,” said LimFlow CEO Dan Rose. “For these no-option patients, the next intervention for their leg was going to be major amputation, with the associated morbidity and high mortality risk that comes with amputation. Instead, two years later, the vast majority of patients are alive, with almost three-quarters of them experiencing completely healed wounds. This registry adds to the building clinical evidence that LimFlow

therapy is an effective solution for nooption patients.”

SUNSET sPE trial completes enrolment phase

The “Standard versus ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism” (SUNSET sPE) trial, a randomised, single-blinded clinical trial comparing ultrasoundassisted thrombolysis (USAT) to standard catheter-directed thrombolysis (SCDT), has completed enrolment. The trial is designed to address the controversial role of ultrasound in improving clot reduction during catheter-directed thrombolysis for acute submassive pulmonary embolism.

The study, launched in 2016, began as an institutional trial at the University of Pittsburgh Medical Center, Pittsburgh, USA. Efthymios Avgerinos (University of Pittsburgh Medical Center) presented interim results of the overall outcomes at the SVS 2019 Vascular Annual Meeting (VAM; 12–15 June, National Harbor, USA). It was shown that catheter thrombolytic techniques can achieve a significant and quick thrombus and RV/ LV ratio reduction, and are safe and effective. With enrolment complete, follow-up data and analyses are pending, and comparative results will be announced within the forthcoming months.

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

26 May–25 June CX 2020 LIVE

30 July–1 August Venous Symposium

Virtual event

Virtual event

31 October–2 November The VEINS at VIVA Las Vegas, USA

cxsymposium.com/cx-2020-live

www.venous-symposium.com

www.vivaphysicians.org/veins-

28–29 May 2021 VIC: Minimally Invasive Venous Surgery Vienna, Austria

programming

www.veinsinternational.com

Virtual event

2–5 September German Society of Phlebology Leipzig, Germany

23–27 February 2021 VEITHsymposium New York, USA

www.ivcmiami.com

www.phlebologie-2020.de

www.veithsymposium.org

4–5 June 2021 Benelux Society of Phlebology Leuven, Belgium

9–11 July IVC: International Vein Congress

www.phlebologybenelux.org

September

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2019 | Issue

11

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Profile

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