Publications by authors named "Tim Sebastian"

33 Publications

Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

Lancet Haematol 2022 Aug 30;9(8):e585-e593. Epub 2022 Jun 30.

Department of Angiology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.

Background: COVID-19 is a viral prothrombotic respiratory infection. Heparins exert antithrombotic and anti-inflammatory effects, and might have antiviral properties. We aimed to investigate whether thromboprophylaxis with enoxaparin would prevent untoward hospitalisation and death in symptomatic, but clinically stable outpatients with COVID-19.

Methods: OVID was a randomised, open-label, parallel-group, investigator-initiated, phase 3 trial and was done at eight centres in Switzerland and Germany. Outpatients aged 50 years or older with acute COVID-19 were eligible if they presented with respiratory symptoms or body temperature higher than 37·5°C. Eligible participants underwent block-stratified randomisation (by age group 50-70 vs >70 years and by study centre) in a 1:1 ratio to receive either subcutaneous enoxaparin 40 mg once daily for 14 days versus standard of care (no thromboprophylaxis). The primary outcome was a composite of any untoward hospitalisation and all-cause death within 30 days of randomisation. Analysis of the efficacy outcomes was done in the intention-to-treat population. The primary safety outcome was major bleeding. The study was registered in ClinicalTrials.gov (NCT04400799) and has been completed.

Findings: At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions. Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53-62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs 8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37-2·56; p=0·96). All hospitalisations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group.

Interpretation: These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates.

Funding: SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation.
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http://dx.doi.org/10.1016/S2352-3026(22)00175-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243568PMC
August 2022

Impact of concomitant popliteal vein thrombosis in patients with acute iliofemoral deep vein thrombosis treated with endovascular early thrombus removal.

Vasa 2022 Jul 1. Epub 2022 Jul 1.

Department of Internal Medicine, HFR Fribourg - Cantonal Hospital, Fribourg, Switzerland.

Catheter-based thrombus removal (CBTR) reduces the risk of moderate to severe post-thrombotic syndrome (PTS) in patients with acute iliofemoral deep vein thrombosis (IF-DVT). However, the impact of concomitant popliteal DVT on clinical and duplex sonographic outcomes is unknown. In this post-hoc analysis including the entire cohort of the randomized controlled BERNUTIFUL trial (48 patients), we compared clinical (incidence/severity of PTS assessed by Villalta score and revised venous clinical severity scores, rVCSS), disease-specific quality-of-life (QOL, CIVIQ-20 survey) and duplex sonographic outcomes (patency, reflux, post-thrombotic lesions) at 12 months follow-up between patients with IF-DVT and concomitant popliteal DVT treated by CBTR. Overall, 48 IF-DVT patients were included (48% men, median age of 50 years), of whom 17 (35%) presented popliteal DVT. At baseline, patients popliteal DVT were older, had a higher body mass index and more important leg swelling. At 12 months, freedom from PTS (93% vs 87%, P=0.17), median total Villalta score (1 vs 1.5; P=0.46), rVCSS (2 vs 1.5, P=0.5) and disease-specific QOL (24 points vs 24 points, P=0.72) were similar between patient and popliteal DVT, respectively. Duplex sonographic outcomes were similar, except for more frequent popliteal post-thrombotic lesions and reflux (P=0.02) in patients popliteal DVT. Relevant clinical outcomes 1 year after successful CBTR were favorable, regardless of the presence or absence of concomitant popliteal DVT. However, post-thrombotic popliteal vein lesions and reflux are more frequent in IF-DVT patients with popliteal involvement. Their impact on long-term outcomes remains to be investigated.
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http://dx.doi.org/10.1024/0301-1526/a001017DOI Listing
July 2022

Major adverse limb events in patients with femoro-popliteal and below-the-knee peripheral arterial disease treated with either sirolimus-coated balloon or standard uncoated balloon angioplasty: a structured protocol summary of the "SirPAD" randomized controlled trial.

Trials 2022 Apr 21;23(1):334. Epub 2022 Apr 21.

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

Background: Peripheral arterial disease is a progressive atherosclerotic disease with symptoms ranging from an intermittent claudication to acute critical limb ischemia and amputations. Drug-coated balloons and stents were developed to prevent neo-intimal proliferation and restenosis after percutaneous transluminal angioplasty. Randomized controlled trials showed that drug-coated, notably paclitaxel-coated, devices reduce restenosis, late lumen loss, and the need for target lesion re-vascularization compared with uncoated ones. However, the size of these trials was too small to prove superiority for "hard" clinical outcomes. Moreover, available studies were characterized by too restrictive eligibility criteria. Finally, it remains unclear whether paclitaxel-coated balloons may impair long-term survival. Alternative drug-coated balloons, the so-called limus-based analogs, have been approved for clinical use in patients with peripheral arterial disease. By encapsulating sirolimus in phospholipid drug nanocarriers, they optimize adhesion properties of sirolimus and provide better bioavailability.

Methods: In this investigator-initiated all-comer open-label phase III randomized controlled trial, we will evaluate whether sirolimus-coated balloon angioplasty is non-inferior and eventually superior, according to a predefined hierarchical analysis, to uncoated balloon angioplasty in adults with infra-inguinal peripheral arterial disease requiring endovascular angioplasty. Key exclusion criteria are pregnancy or breastfeeding, known intolerance or allergy to sirolimus, and participation in a clinical trial during the previous 3 months. The primary efficacy outcome is the composite of two clinically relevant non-subjective "hard" outcomes: unplanned major amputation of the target limb and endovascular or surgical target lesion re-vascularization for critical limb ischemia occurring within 1 year of randomization. The primary safety outcome includes death from all causes.

Discussion: By focusing on clinically relevant outcomes, this study will provide useful information on the efficacy and safety of sirolimus-coated balloon catheters for infra-inguinal peripheral arterial disease in a representative ("all-comer") population of unselected patients. As regulatory agencies had raised safety concerns in patients exposed to paclitaxel-coated devices (versus uncoated ones), collect mortality data up to 5 years after randomization will be collected.

Trial Registration: ClinicalTrials.gov NCT04238546.
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http://dx.doi.org/10.1186/s13063-022-06242-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027348PMC
April 2022

A novel management strategy for treatment of pelvic venous disorders utilizing a clinical screening score and non-invasive imaging.

Vasa 2022 May 13;51(3):182-189. Epub 2022 Apr 13.

Department of Angiology, University Hospital Zurich, Switzerland.

Treatment of pelvic venous disorders (PVD) including pelvic congestion syndrome (PCS) are often delayed due to its varying clinical manifestations. Patient referral was based on a literature- and personal experience-derived clinical "PCS screening score" (higher score points indicate greater likelihood with a maximum score of 10 points). We studied consecutive women who were (i) referred for vascular assessment and treatment to the University Hospital Zurich (2017-2021), (ii) had a PCS score ≥3 points, (iii) had evidence of obstructive or non-obstructive PVD by duplex sonography or cross-sectional imaging, and (iv) underwent endovascular therapy. The primary outcome was change in symptom severity after endovascular therapy: (i) freedom from symptoms, (ii) improvement with residual symptoms, (iii) no improvement. We included 43 women (mean age 36 years): 81% had previous pregnancy, 19% endometriosis. The median PCS score was 7 (IQR 5-9) points. Chronic lower-abdominal pain was the leading symptom in 86% patients, followed by recurrent leg (9%) and vulvar (5%) varicosities. The main PVD pathologies were ovarian vein insufficiency (61%), internal iliac vein insufficiency (9%), or a combination of both (30%), whereas 42% had a deep venous obstruction of the inferior vena cava, common iliac or left renal veins. Endovascular therapy included ovarian vein embolization (86%), internal iliac vein embolization (9%), and venous stent placement (35%). After a median of 4 (IQR 1-8) months from endovascular treatment, 40 (93%) patients reported improvement of the leading symptom, and 14 (33%) were symptom-free. Complications included re-intervention for stent stenosis (13%, all post-thrombotic), coil-migration into the left renal vein (7%, all retrieved), and transient pelvic sclerotherapy-induced thrombophlebitis (2%). Endovascular therapy following a diagnostic approach, which included a PCS screening tool and non-invasive imaging, appeared to be highly effective and was associated with a low rate of complications.
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http://dx.doi.org/10.1024/0301-1526/a001001DOI Listing
May 2022

Role of age, sex, and specific provoking factors on the distal versus proximal presentation of first symptomatic deep vein thrombosis: analysis of the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Intern Emerg Med 2022 04 3;17(3):799-803. Epub 2021 Nov 3.

Department of Angiology, University Hospital Zurich, Raemistrasse 100, RAE C 13, 8091, Zurich, Switzerland.

We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80-4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20-3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33-3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29-5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.
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http://dx.doi.org/10.1007/s11739-021-02878-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018645PMC
April 2022

Clinical Uses and Short-Term Safety Profile of Ethiodized Poppy Seed Oil Contrast Agent in the Diagnosis and Treatment of Vascular Anomalies and Tumors.

Diagnostics (Basel) 2021 Sep 27;11(10). Epub 2021 Sep 27.

Department of Radiology and Vascular Anomalies Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Background: There is a sparsity of data on the use of ethiodized poppy seed oil (EPO) contrast agent (Lipiodol) in patients. We investigated the safety of EPO in children, adolescents, and some adults for diagnostic and therapeutic interventions.

Methods: All patients who underwent procedures with EPO between 1995 and 2014 were retrospectively included. Demographic characteristics, diagnosis, dose, route of administration, preparation of EPO in combination with other agents, and complications were recorded.

Results: In 1422 procedures, EPO was used for diagnostic or treatment purposes performed in 683 patients. The mean patient age was 13.4 years (range: 2 months-50 years); 58% of patients were female. Venous malformations ( = 402, 58.9%) and arteriovenous malformations ( = 60, 8.8%) were the most common diagnosis. Combined vascular anomalies included capillary-lymphatic-venous malformations, fibroadipose vascular anomalies ( = 54, 7.9%), central conducting lymphatic anomalies ( = 31, 4.5%), lymphatic malformations ( = 24, 3.5%), aneurysmal bone cysts ( = 22, 3.2%), and vascularized tumors ( = 11, 1.6%). In 1384 procedures (96%), EPO was used in various combinations with sclerosing and embolization agents, including sodium tetradecyl sulfate, ethanol, and glue. The mean volume of EPO used in interventions was 3.85 mL (range: 0.1-25 mL) per procedure with a mean patient weight of 45.9 kg (range: 3.7-122.6 kg) and a weight-adjusted dose of 0.12 mL/kg (range: 0.001-1.73 mL/kg). In 56 procedures (4%), EPO was used as a single agent for diagnostic lymphangiography. The mean volume was 4.8 mL (range: 0.3-13 mL) per procedure with a mean patient weight of 27.4 kg (range: 2.4-79.3 kg) and a weight-adjusted dose of 0.2 mL/kg (range: 0.04-0.54 mL/kg). Procedural-related complications occurred in 25 (1.8%) procedures. The 20 minor and 5 major complications were related to the primary treatment agents. None of them were directly related to EPO. No allergic reactions were noted.

Conclusion: The use of an ethiodized poppy seed oil contrast agent in children, adolescents, and adults for diagnostic or therapeutic purposes is safe.
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http://dx.doi.org/10.3390/diagnostics11101776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534402PMC
September 2021

Pulmonary embolism and deep vein thrombosis: Similar but different.

Thromb Res 2021 Oct 19;206:88-98. Epub 2021 Aug 19.

Institute of Pharmacology, University of Bern, Switzerland. Electronic address:

Introduction: Pulmonary embolism (PE) and deep vein thrombosis (DVT), the two clinical manifestations of venous thromboembolism (VTE), constitute a major global burden of cardiovascular disease. They are often referred to as one disease but several patient characteristics, risk factors, real-world treatment, and clinical outcomes may differ substantially between PE and DVT alone.

Materials And Methods: We conducted a narrative review of the state-of-the-art literature on the topic of PE and DVT alone using PubMed, Google scholar, and MEDLINE databases and the most established international consensus statement guidelines for the management of VTE, focusing on the recommendations for diagnosis and treatment but also including epidemiological and clinical characteristics of VTE, highlighting similarities and differences between PE and DVT alone.

Results: Several patient characteristics, risk factors, clinical manifestations, and outcomes differ substantially between PE versus DVT alone. Nevertheless, recommendations for both diagnosis and treatment are strikingly similar in the current guidelines for the management of DVT and PE, except for the indication for advanced reperfusion therapies.

Conclusions: The differences in risk factors, clinical manifestations, and clinical outcomes between patients with PE versus DVT alone are only marginally addressed in the current consensus guidelines. More data is needed allowing proposal of evidence-based adjustments in the diagnostic and therapeutic strategies for these two manifestations of VTE. Tailored risk stratification and individualized management strategies for patients with PE and DVT alone may lead to a better prognosis, less recurrence and complications, and possibly to a gain of quality-adjusted life years in patients with VTE.
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http://dx.doi.org/10.1016/j.thromres.2021.08.015DOI Listing
October 2021

[Trends in mortality related to pulmonary embolism in the DACH countries].

Med Klin Intensivmed Notfmed 2021 Aug 24. Epub 2021 Aug 24.

Centrum für Thrombose und Hämostase (CTH), Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland.

Background: Pulmonary embolism (PE)-related mortality is decreasing worldwide.

Aim: Little is known about the burden imposed by pulmonary embolism for Germany, Austria and Switzerland (DACH countries).

Materials And Methods: We aimed to assess pulmonary embolism-related mortality and time trends for the DACH countries based on data from the WHO Mortality Database. Deaths were considered pulmonary embolism-related if the International Classification of Disease-10 code for acute pulmonary embolism or any code for deep or superficial vein thrombosis was listed as the primary cause of death.

Results: Between 2000 and 2015, age-standardized annual pulmonary embolism-related mortality rates decreased linearly from 15.6 to 7.8 deaths per 1000 population. In the 5‑year period between 2012 and 2016, an average of 9127 pulmonary embolism-related deaths occurred annually in the DACH countries with a population of 98,273,329. Interestingly, pulmonary embolism-related mortality rates were considerably higher among women aged 15-55 years compared to age-matched men.

Conclusion: The observed decreasing trends in pulmonary embolism-related mortality might reflect improved management of the disease including new treatment options as well as advances in imaging technologies. However, pulmonary embolism remains a substantial contributor to total mortality, especially among women aged 15-55 years. For this reason, campaigns to increase physician and public awareness are urgently required to further improve the management and treatment of this preventable thrombotic disorder, which still remains the leading preventable cause of death.
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http://dx.doi.org/10.1007/s00063-021-00854-9DOI Listing
August 2021

Reversal of cardiopulmonary exercise intolerance in patients with post-thrombotic obstruction of the inferior vena cava.

Thromb Res 2021 Dec 9;208:219-225. Epub 2021 Apr 9.

Clinic for Angiology, University Hospital Zurich, Switzerland. Electronic address:

Background: It is unclear whether cardiopulmonary exercise intolerance in patients with chronic obstruction of the inferior vena cava (IVC) is reversible following endovascular IVC reconstruction.

Methods: In 17 patients (mean age 45 ± 15 years, 71% men) with post-thrombotic syndrome due to IVC obstruction and preserved left ventricular ejection fraction (mean 58 ± 3%), we performed cardiopulmonary exercise testing before and 3 months after IVC reconstruction (mean 4.1 ± 1.5 implanted stents). The median time from latest episode of deep vein thrombosis to intervention was 150 (interquartile range 102-820) days.

Results: At baseline, 12 (71%) patients reported New York Heart Association (NYHA) class II or III symptoms, 76% did not achieve >85% of predicted oxygen uptake at peak exercise (mean 61.8 ± 13.7%). After IVC reconstruction, the following changes were observed at anaerobic threshold: work rate increased by 14.6 W, 95%CI (-0.7; 30.0), oxygen uptake increased by 1.8 ml/kg, 95%CI (0.3; 3.3). Oxygen pulse increased by 1.95 ml per beat, 95%CI (1.12; 2.78), corresponding to a mean relative increase of 22.5%, 95%CI (12.4; 32.7) (p < 0.001). The following changes were observed at peak exercise: work rate increased by 48.1 W, 95%CI (27.8; 68.4), oxygen uptake increased by 6.4 ml/kg, 95%CI (3.8; 9.1). Oxygen pulse increased by 2.68 ml per beat, 95%CI (1.60; 3.76), corresponding to a mean relative increase of 29.4%, 95%CI (17.7; 41.2) (p < 0.001). At follow-up, 5 (29%) patients remained in NYHA class II.

Conclusions: In patients with chronic IVC obstruction, cardiopulmonary exercise intolerance as a result of impaired cardiac filling is at least partially reversible following endovascular IVC reconstruction.

Study Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.
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http://dx.doi.org/10.1016/j.thromres.2021.03.025DOI Listing
December 2021

Self-Expandable Nitinol Stents for the Treatment of Nonmalignant Deep Venous Obstruction.

Circ Cardiovasc Interv 2020 12 4;13(12):e009673. Epub 2020 Dec 4.

Clinic for Angiology, University Hospital Zurich, Switzerland (T.S., S.G., L.M., R.K., S.B., N.K.).

Background: Angioplasty with stent placement is a therapeutic option for patients with acute thrombotic, postthrombotic, and nonthrombotic obstruction of the iliofemoral veins or inferior vena cava. Previous studies of steel-alloy stents described variable patency rate across indications.

Methods: The prospective Swiss Venous Stent Registry includes patients treated with self-expandable nitinol stents for deep venous obstruction. Routine follow-up visits include serial duplex ultrasound for stent patency assessment. The primary outcome was primary stent patency. The secondary outcome was venous thromboembolisms. We studied the rate of stent occlusion and potentially contributing factors.

Results: We included 379 patients: 160 with acute thrombotic, 193 with postthrombotic, and 26 with nonthrombotic deep vein obstruction. The mean age was 46±18 years; 55% were women. The cumulative 3-year primary patency rate was 80.5% (95% CI, 73.0%-88.0%) for acute thrombotic, 59.2% (95% CI, 50.4%-68.0%) for postthrombotic, and 100% for nonthrombotic obstruction (log-rank, <0.0001). Annualized rates of stent occlusion or venous thromboembolism were 7.8 (acute thrombotic), 15.0 (postthrombotic), and 0 (nonthrombotic) events/100 patient-years. In a multivariable Cox regression model, postthrombotic femoral veins at baseline (hazard ratio, 2.64 [95% CI, 1.53-4.56]) and the number of stents (hazard ratio, 1.22 [95% CI, 1.06-1.40]) were associated with stent occlusion after conditioning for age, sex, and clinically relevant factors.

Conclusions: The rate of stent occlusion (patency loss) and venous thromboembolism varies substantially across indications, also with dedicated venous nitinol stents. Patients with postthrombotic femoral veins and those who received multiple stents were characterized by the highest risk. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02433054.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009673DOI Listing
December 2020

Clinical Outcomes of Incidental Venous Thromboembolism in Cancer and Noncancer Patients: The SWIss Venous ThromboEmbolism Registry (SWIVTER).

Thromb Haemost 2021 May 17;121(5):641-649. Epub 2020 Nov 17.

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

Objective:  In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer.

Methods And Results:  We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental ( = 131; 52% without cancer) and symptomatic ( = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49-2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39-2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67-2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30-3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33-5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09-4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not.

Conclusion:  In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer.
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http://dx.doi.org/10.1055/s-0040-1720977DOI Listing
May 2021

Lemierre syndrome: Current evidence and rationale of the Bacteria-Associated Thrombosis, Thrombophlebitis and LEmierre syndrome (BATTLE) registry.

Thromb Res 2020 12 8;196:494-499. Epub 2020 Oct 8.

Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

Lemierre syndrome is a rare but potentially fatal condition characterized by septic thrombophlebitis of the head and neck district, preferentially affecting adolescents and young adults and manifesting as a complication of a local bacterial infection - typically, a pharyngotonsillitis or an abscess. It is historically associated with the Gram-negative anaerobic rod Fusobacterium necrophorum and with thrombophlebitis of the internal jugular vein. However, its definition has never been firmly established, and its spectrum within the continuum of bacteria-associated thrombophlebitis may be larger than what presumed so far. Recent evidence suggests that its prognosis remains serious even one hundred years after its first description, with considerable rates of in-hospital complications, death, and long-term sequelae. There are no specific guidelines on its management other than usual antibiotic stewardship, with ongoing debate on the potential role of therapeutic-dose anticoagulation. We provide an overview of current evidence on the definition, epidemiology, clinical presentation, prognosis and management of this condition and present the background and rationale of the Bacteria-Associated Thrombosis/Thrombophlebitis and LEmierre syndrome (BATTLE) registry: an ambispective, disease-specific, non-population based, multicentre clinical registry of global reach and multidisciplinary scope, specifically designed to address the limitations of current evidence and to provide patients and physicians with clinically viable information to guide management and improve the outcomes of those affected by these conditions.
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http://dx.doi.org/10.1016/j.thromres.2020.10.002DOI Listing
December 2020

Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial.

Trials 2020 Sep 9;21(1):770. Epub 2020 Sep 9.

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

Objectives: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation.

Trial Design: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial.

Participants: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis:  a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke,  b. previous VTE,  c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 10 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals.

Intervention And Comparator: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation.

Main Outcomes: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization.

Secondary Outcomes: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment.

Randomisation: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24).

Blinding (masking): In this open-label study, no blinding procedures will be used.

Numbers To Be Randomised (sample Size): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-β = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group.

Trial Status: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021.

Trial Registration: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04678-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479300PMC
September 2020

Braided or laser-cut self-expanding nitinol stents for the common femoral vein in patients with post-thrombotic syndrome.

J Vasc Surg Venous Lymphat Disord 2021 05 2;9(3):760-769. Epub 2020 Sep 2.

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Chronic obstruction of the common femoral vein in patients with post-thrombotic syndrome after iliofemoral or iliocaval deep vein thrombosis has remained a challenge for endovascular treatment. The patency rates and clinical outcomes of laser-cut and braided nitinol stents extending to the common femoral vein have not yet been studied.

Methods: From the Swiss and Arnsberg Venous Stent Registries, we included 150 patients with post-thrombotic syndrome (mean age, 44 ± 16 years; 48% women) with laser-cut (n = 101) or braided nitinol (n = 49) stents placed into the common femoral vein across the inguinal ligament. Routine follow-up included duplex ultrasound examinations and assessment of clinical scores. The primary study outcomes were the primary and secondary patency rates at 12 months.

Results: Overall, the mean number of implanted stents was 2.6 ± 1.7. The proximal stent landing zone was the inferior vena cava in 32 patients (21%), the iliac vein in 106 patients (76%), and the common femoral vein in 5 patients (3%). The primary patency rate was 67.3% (95% confidence interval [CI], 58.0%-76.6%) in the laser-cut group and 86.7% (95% CI, 75.3%-98.1%) in the braided stent group (log-rank, P = .016). The corresponding secondary patency rates were 93.9% (95% CI, 89.2%-98.6%) and 100% (log-rank, P = .10). The median improvement in the Villalta score from baseline to the latest follow-up was 4 points (interquartile range, 2-6 points), without significant differences between the two groups. Symptomatic common femoral vein stent fractures were observed in four patients (4%) with laser-cut stents but in no patient with braided stents.

Conclusions: The use of braided nitinol stents for common femoral vein obstruction appeared to be associated with favorable primary patency rates at 12 months compared with laser-cut nitinol stents. Further studies are needed to confirm that braided nitinol stents remain patent and might be less prone to fractures in the long term.
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http://dx.doi.org/10.1016/j.jvsv.2020.08.027DOI Listing
May 2021

How to Differentiate Recurrent Deep Vein Thrombosis from Postthrombotic Syndrome.

Hamostaseologie 2020 Aug 29;40(3):280-291. Epub 2020 Jul 29.

Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.

Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Accuracy of diagnosis is thus of vital importance. Failure to diagnose VTE increases the risk of progression and complications. Conversely, anticoagulation as a result of an incorrect diagnosis exposes patients to the associated hazards of bleeding. The diagnostic management of recurrent deep vein thrombosis (DVT) and postthrombotic syndrome (PTS) is especially challenging due to the lack of well-established diagnostic standards. Particularly, the differentiation between the two is notoriously difficult as symptoms, clinical signs, and diagnostic test findings largely overlap. This review highlights the current diagnostic and management strategies for recurrent DVT and PTS with a focus on clinical findings and imaging modalities. We also discuss current open questions for clinicians in the field, anticipating future directions and predictions for the year 2050.
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http://dx.doi.org/10.1055/a-1171-0486DOI Listing
August 2020

Prevalence of carotid plaque stenosis after head and neck radiotherapy - an observational study of 156 survivors.

Vasa 2020 Oct 17;49(6):467-473. Epub 2020 Jul 17.

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

: Radiotherapy for head and neck cancer (HNC) represents a well-known predisposing factor for asymptomatic carotid artery lesions and acute cerebrovascular accidents. Our aim is to provide contemporary estimates on the prevalence, severity, and characteristics of carotid artery lesions in HNC survivors. : We prospectively included HNC patients who underwent radiotherapy and were free from the disease at the time of duplex ultrasound evaluation. Patients were re-contacted telephonically and those who agreed to participate were invited for an ambulatory visit when the investigators collected clinical information and performed duplex ultrasound examination based on a predefined protocol. : A total of 156 patients were included and underwent duplex ultrasound examination after a mean of 65.2 months from the last session of radiotherapy. A total of 36 patients (23.1%) had normal carotid arteries; mild, non-stenotic lesions were observed in 49.4% (n = 77) of patients; severe stenotic plaques were found in 27.5% (n = 43) of patients. One patient found with an asymptomatic occlusion of the left ICA. The prevalence of major cardiovascular risk factors and high radiation dose increased proportionally with plaque severity. Low echogenicity plaque was found in 59 (37.8%) patients on the right side and 57 (36.5%) on the left side; long segment plaque in 49 (31.4%) patients on the right side and in 47 (30.1%) on the left side; an atypical location of the lesions in 42 (26.9%) patients on the right side and in 48 (30.8%) on the left side. : The prevalence of occlusion and severe stenosis after radiotherapy for HNC was very low in our study population. Low echogenicity plaque, long segment plaque, and an atypical location were common findings. Classic cardiovascular risk factors appear to have had a causative role: a routine screening of radiotherapy-treated patients might be necessary only in patients with concomitant cardiovascular risk factors or exposed to high-dose neck radiation.
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http://dx.doi.org/10.1024/0301-1526/a000896DOI Listing
October 2020

Duplex Ultrasound Investigation for the Detection of Obstructed Iliocaval Venous Stents.

Eur J Vasc Endovasc Surg 2020 Sep 27;60(3):443-450. Epub 2020 Jun 27.

Clinic for Angiology, University Hospital Zurich, Switzerland. Electronic address:

Objective: Duplex ultrasound (DUS) is used for routine surveillance of stents in iliocaval veins, but direct visualisation is often challenging. Duplex ultrasound criteria for detecting venous stent obstruction (VSO) have not been defined to date.

Methods: A nested case control study of 120 patients (42 ± 17 years, 53% women, mean 2.7 ± 1.8 stents) was performed, and the performance of various duplex parameters for detecting VSO (defined as > 50% lumen diameter reduction or occlusion) was tested, confirmed by biplane venography or intravascular ultrasound (IVUS). Forty patients with VSO (25 with stent occlusion, 15 with >50% in stent stenosis) were matched to 80 control patients by age, gender and index diagnosis who fulfilled the following criteria: (1) ongoing symptom control (Villalta score < 5), (2) good image quality of entire stent segment, (3) spontaneous colour Doppler signal > 50% of lumen in entire stent segment, (4) at least two DUS where the baseline DUS was obtained within 24 h after successful venous intervention.

Results: The best test was the combination of peak flow velocity and flow pattern analysis at the stent inlet. A peak flow velocity >10 cm/s and a flow pattern spontaneously modulated by respiration ruled out VSO with a specificity of 93.7% (95% CI 86.0%-97.3%). A peak flow velocity ≤10 cm/s or any Doppler flow pattern other than spontaneously modulated by respiration was 92.1% (95% CI 79.2%-97.3%) sensitive to detect VSO.

Conclusion: The combination of peak flow velocity and analysis of Doppler flow pattern at the stent inlet is accurate to diagnose or rule out stent occlusion. Indirect criteria should always be combined with direct visualisation of iliocaval stents since those may be less sensitive for detecting stent stenosis.
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http://dx.doi.org/10.1016/j.ejvs.2020.05.011DOI Listing
September 2020

Reperfusion treatment for high-risk pulmonary embolism associated with COVID-19.

Vasa 2020 06;49(4):257-258

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1024/0301-1526/a000884DOI Listing
June 2020

Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.

Thromb Res 2020 07 23;191:9-14. Epub 2020 Apr 23.

Clinic for Angiology, University Hospital Zurich, Zurich, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

Background: Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.

Methods: We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC).

Results: We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients.

Conclusions: The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.
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http://dx.doi.org/10.1016/j.thromres.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177070PMC
July 2020

Early clinical outcomes for treatment of post-thrombotic syndrome and common iliac vein compression with a hybrid Oblique self-expanding nitinol stent - the TOPOS study.

Vasa 2020 Jun 6;49(4):301-308. Epub 2020 Apr 6.

Clinic for Angiology, University Hospital Zurich, Zurich, Switzerland.

: Physical attributes of onventional stents used in the ilio-caval territory are often unfavorable in the presence of external compression close to the bifurcation. A hybrid oblique stent was developed for the treatment of common iliac vein compression without compromising the contralateral iliac vein inflow. : The ongoing international monitored TOPOS study enrolled 60 patients with post-thrombotic syndrome (PTS) treated with the sinus-Obliquus stent (optimed) and provisional distal stent extension. At 3-month follow-up, patency rates were obtained from duplex ultrasound, and clinical outcomes were assessed by the Villalta score, revised venous severity score (rVCSS), pain intensity score and chronic venous disease quality of life questionnaire (CIVIQ-20). : Mean age was 46.6 ± 14.9 years (68.3 % women). Mean number of implanted stents was 1.9 ± 0.6; 12 (20 %) patients received the hybrid oblique stent only. Forty-eight (80 %) patients had distal stent extension, and 42 (70 %) had stents below the inguinal ligament. Four (7 %) patients (all with stent extension) developed stent thrombosis. Primary and secondary patency rates at 3 months were 93.1 % (95 %CI 83.3-98.1 %), and 100 % (95 %CI 93.8-100 %), respectively. Improvement in Villalta, rVCSS, CIVIQ-20, and pain intensity score from baseline to 3-month follow-up was 6.9 ± 1.4 points (95 %CI 4.1-9.8; p < 0.0001), 3.4 ± 1.0 points (95 %CI 1.3-5.4 points; p < 0.01), 13.6 ± 2.7 points (95 %CI 8.2-19.0 points; p < 0.0001), and 2.4 ± 0.5 (95 %CI 1.4-3.3; p < 0.0001), respectively. At follow-up, 38 (63 %) patients were free from the PTS and none developed contralateral deep vein thrombosis. : In patients with PTS and common iliac vein compression, treatment with the hybrid oblique stent with provisional stent extension resulted in high patency rates and improvement in PTS severity and quality of life at 3-month. Two-year results of TOPOS will assess the durability of this treatment.
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http://dx.doi.org/10.1024/0301-1526/a000857DOI Listing
June 2020

Death from, with, and without pulmonary embolism.

Eur J Intern Med 2020 03 9;73:25-26. Epub 2020 Feb 9.

Clinic of Angiology, University Hospital Zurich, Rämistrasse 100, RAE C 04, 8091 Zurich, Switzerland.

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http://dx.doi.org/10.1016/j.ejim.2020.01.029DOI Listing
March 2020

Incidence of Stent Thrombosis after Endovascular Treatment of Iliofemoral or Caval Veins in Patients with the Postthrombotic Syndrome.

Thromb Haemost 2019 Dec 28;119(12):2064-2073. Epub 2019 Oct 28.

Clinic for Angiology, University Hospital of Zurich, University of Zurich, Switzerland.

Background:  Patients with postthrombotic syndrome (PTS) treated with stents are at risk of stent thrombosis (ST). The incidence of ST in the presence and absence of anticoagulation therapy (AT) is unknown. Risk factors are not well understood.

Patients And Methods:  From the prospective Swiss Venous Stent registry, we conducted a subgroup analysis of 136 consecutive patients with PTS. Incidence of ST was estimated from duplex ultrasound or venography, and reported for the time on and off AT. Baseline, procedural, and follow-up data were evaluated to identify factors associated with ST.

Results:  Median follow-up was 20 (interquartile range [IQR] 9-40) months. AT was stopped in 43 (32%) patients after 12 (IQR 6-14) months. Cumulative incidence of ST was 13.7% (95% confidence interval [CI] 7.8-19.6%) and 21.2% (95% CI 13.2-29.2%) during the first 6 and 36 months, respectively. The time-adjusted incidence rate was 11.2 (95% CI 7.7-16.2) events per 100 patient-years, 11.3 (95% CI 7.3-17.3) for the period on, and 11.2 (95% CI 5.3-23.6) for the period off AT. May-Thurner syndrome (MTS) was associated with decreased incidence of ST (hazard ratio [HR] 0.37, 95% CI 0.15-0.91), whereas age < 40 years (HR 2.26, 95% CI 1.03-4.94), stents below the common femoral vein (HR 3.03, 95% CI 1.28-7.19), and postthrombotic inflow veins (HR 2.92, 95% CI 1.36-6.25) were associated with increased incidence.

Conclusion:  The 6-month incidence of ST was considerably high. Beyond 6 months, consecutive annual incidence rates persisted at 4.1 and 3.4% per year thereafter. Patients with higher incidence of ST were younger, had stents below the common femoral vein, postthrombotic leg inflow veins, and less often MTS. Incidence rates for the period on and off AT must be interpreted with caution.

Clinical Trial Registration:  The study is registered on the National Institutes of Health Web site (ClinicalTrials.gov; identifier NCT02433054).
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http://dx.doi.org/10.1055/s-0039-1697955DOI Listing
December 2019

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Semin Thromb Hemost 2019 Nov 17;45(8):851-858. Epub 2019 Oct 17.

Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94;  = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00;  = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.
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http://dx.doi.org/10.1055/s-0039-1698770DOI Listing
November 2019

Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

Vasa 2019 Jul 22;48(4):331-339. Epub 2019 Jan 22.

1 Clinic for Angiology, University Hospital Zurich, Switzerland.

The optimal duration of anticoagulation therapy (AT) following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) with stent placement is unknown. Theoretically, resolving the underlying obstructive iliac vein lesion by a stent may eliminate the main trigger for recurrence, the post-thrombotic syndrome (PTS), and the need for extended-duration AT. From 113 patients with acute IFDVT who underwent endovascular thrombus removal and stent placement, we compared patency rates and clinical outcomes between 58 patients on limited-duration AT (3-12 month) and 55 patients on extended-duration AT (> 12 months). Mean follow-up duration was 26 ± 18 (range 3-77) months; it was 24 ± 18 (range 3-69) months after cessation of AT in the limited-duration AT group. In comparison to patients with extended-duration AT, patients with limited-duration AT were younger (38 versus 54 years; p < 0.001), more often female (74 % versus 49 %; p = 0.01), and had less often prior venous thromboembolism (VTE) (9 % versus 35 %; p = 0.001). May-Thurner syndrome was more frequent in the limited-duration AT group (66 % versus 38 %; p = 0.004). Overall, primary and secondary patency rates at 24 months were 80 % (95 % CI, 70-87 %) and 95 % (95 % CI, 88-98 %), respectively, with no difference between the groups. Overall, 17 (15 %) patients developed recurrent VTE, of which 14 (82 %) events were thrombotic stent occlusions, and 13 (76 %) events occurred during AT. In the limited-duration AT group, 98 % patients were free from the PTS at two years with a VTE recurrence rate of 3.5 per 100 patient years after cessation of AT. In selected patients with acute IFDVT and patent venous stent, particularly in younger and otherwise healthy patients with May-Thurner syndrome, it appears to be safe to discontinue AT 3-12 months after endovascular treatment. The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).
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http://dx.doi.org/10.1024/0301-1526/a000774DOI Listing
July 2019

Rivaroxaban or vitamin-K antagonists following early endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

Thromb Res 2018 12 26;172:86-93. Epub 2018 Oct 26.

Medical Faculty, University of Bern, Switzerland; Division of Angiology, Cantonal Hospital Fribourg, Fribourg, Switzerland.

Background: The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown.

Methods: From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months.

Results: Mean follow-up duration was 24 ± 19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ± 98 days versus 284 ± 199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter.

Conclusions: In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar.

Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).
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http://dx.doi.org/10.1016/j.thromres.2018.10.027DOI Listing
December 2018

Outcomes of endovascular reconstruction of the inferior vena cava with self-expanding nitinol stents.

J Vasc Surg Venous Lymphat Disord 2018 05 15;6(3):312-320. Epub 2018 Mar 15.

Clinic for Angiology, University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Occlusion of the inferior vena cava (IVC) often causes venous claudication, leg swelling, or skin changes. We hypothesized that the outcome of nitinol stents for endovascular reconstruction of the IVC is similar to the outcome reported for steel alloy stents.

Methods: From the prospective Bern Venous Stent Registry, we investigated technical success, patency rates, and clinical outcome in consecutive patients with endovascular IVC reconstruction. During routine follow-up visits, stent patency was assessed by duplex ultrasound. Clinical outcomes were evaluated using the Bozkaya score, Villalta score, and revised Venous Clinical Severity Score.

Results: Of the 62 patients (mean age, 46 ± 18 years), 33 (53%) patients were treated for the post-thrombotic syndrome, 17 (27%) for acute thrombosis, and 12 (19%) for nonthrombotic IVC occlusion. Technical success was achieved in 61 (98%) patients, with a mean of 4.5 ± 1.9 stents (iliac kissing stents in 84%). During follow-up (mean, 21 months), 22 (36%) underwent endovascular reintervention for symptomatic stent stenosis (13 [21%] with complete stent occlusion). Primary, primary assisted, and secondary patency rates at 24 months were 57% (95% confidence interval [CI], 50%-73%), 76% (95% CI, 65%-86%), and 87% (95% CI, 80%-95%), respectively. None developed new ulcers, and all eight patients with venous ulcers at baseline had complete healing. Twenty-nine (48%) patients showed significant clinical improvement, and another 26 (43%) were free from any symptoms or signs of venous hypertension. Patients with post-thrombotic venographic changes of the femoral veins at baseline or a history of thrombosis were more likely to lose primary patency compared with patients with normal leg inflow veins and no history of thrombosis (19 [48%] vs 3 [16%]; P = .02).

Conclusions: The clinical outcome of endovascular reconstruction of the IVC with nitinol stents was favorable. However, approximately one-third of the patients required reintervention to maintain stent patency, most likely because of the impaired venous inflow.
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http://dx.doi.org/10.1016/j.jvsv.2017.11.012DOI Listing
May 2018

Endovascular treatment of post-thrombotic and non-thrombotic iliofemoral venous outflow obstructions with self-expanding nitinol stents.

Vasa 2018 Jun 7;47(4):319-325. Epub 2018 Mar 7.

4 Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.

Background: The aim of the study was to investigate venous patency and clinical outcomes for endovascular treatment of iliofemoral venous obstruction in patients with post-thrombotic syndrome (PTS) and non-thrombotic iliac vein lesion (NIVL) with dedicated self-expanding nitinol stents.

Patients And Methods: Data were collected from the prospective Swiss Venous Stent Registry, enrolling consecutive patients with a standardized follow-up procedure since January 2008. Patency was evaluated by duplex sonography and clinical outcome by various scores including the Villalta score at baseline, three, six, and 12 months, and then annually after endovascular therapy.

Results: Overall, 93 patients (64 PTS, 29 NIVL) were analysed. Mean follow-up time was 20 ± 16 (range 3-70) months. A total of 11 (12 %) patients had a stent occlusion, all of which occurred in the PTS group, and 13 (14 %) patients had a symptomatic stent stenosis. Primary patency was 79 % (95 % CI 68-87 %) at 12 months and 72 % (95 % CI 59-82 %) at 24 months. In PTS patients, primary patency at 12 months was 75 % (95 % CI 61-84 %) vs. 89 % (95 % CI 63-97 %) in NIVL patients (p = 0.10). Secondary patency at 24 months was 94 % (95 % CI 84-98 %) in PTS and 100 % in NIVL, p = 0.19). Overall, 62 (67 %) patients were free from PTS at the latest follow-up with a Villalta score < 5 points. Predictive factors for the loss of primary patency were stents placed below the inguinal ligament (OR 2.59, 95 % CI, 0.99-6.84, p = 0.05).

Conclusions: In symptomatic patients with chronic iliofemoral vein obstruction, endovascular therapy with self-expanding nitinol stents was associated with favourable patency rates and clinical improvement in the majority of patients.
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http://dx.doi.org/10.1024/0301-1526/a000697DOI Listing
June 2018

Patency of the arterial pedal-plantar arch in patients with chronic kidney disease or diabetes mellitus.

Ther Adv Cardiovasc Dis 2018 May 12;12(5):145-153. Epub 2018 Feb 12.

Clinical and Interventional Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.

Background: Patency of the pedal-plantar arch limits risk of amputation in peripheral artery disease (PAD). We examined patients without chronic kidney disease (CKD)/diabetes mellits (DM) [PAD-control], those with DM without CKD, and those with CKD without DM.

Method: Uni- and multivariate logistic regression was used to assess association of CKD with loss of patency of the pedal-plantar arch and presence of tibial or peroneal vessel occlusion. Multivariate models adjusted for age, sex, hypertension, hyperlipidemia and smoking.

Results: A total of 419 patients were included [age 75.2 ± 10.3 years, 288 (69%) male]. CKD nearly doubled the unadjusted odds ratio (OR) for loss of patency of the pedal-plantar arch. After adjustment, association remained significant for severe CKD [estimated glomerular filtration rate (eGFR) ≤ 29 ml/min compared with eGFR ≥ 60 ml/min, adjusted (adj.) OR 8.24 (95% confidence interval {CI} 0.99-68.36, p = 0.05)]. CKD was not related to risk of tibial or peroneal artery occlusion [PAD-control versus CKD, adj. OR 1.09 (95% CI 0.49-2.44, p = 0.83)] in contrast to DM [PAD-control versus DM, adj. OR 2.41 (95% CI 1.23-4.72, p = 0.01), CKD versus DM, adj. OR 2.21 (95% CI 0.93-5.22); p = 0.07)].

Conclusions: Below the knee (BTK) vascular pattern differs in patients with either DM or CKD alone. Severe CKD is a risk factor for loss of patency of the pedal-plantar arch.
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http://dx.doi.org/10.1177/1753944718756605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941675PMC
May 2018

Endovascular extraction of a migrated large self-expanding laser-cut renal venous stent from the right ventricle.

J Vasc Surg Cases Innov Tech 2017 Jun 4;3(2):79-82. Epub 2017 May 4.

Clinic for Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Endovascular stent placement for decompression of an entrapped left renal vein (LRV) between the aorta and superior mesenteric artery is an alternative to surgical decompression for treating the nutcracker syndrome. However, an interventional approach may be challenging because of the unfavorable configuration of the LRV, leading to insufficient stent anchoring. We provide a case of a life-threatening stent migration from the LRV into the right ventricle 2 days after stent placement and its endovascular retrieval.
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http://dx.doi.org/10.1016/j.jvscit.2017.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757773PMC
June 2017
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