Varicose vein surgery after acute isolated superficial vein thrombosis in daily practice: INSIGHTS-SVT study.

OBJECTIVE: The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association with the occurrence of venous thromboembolism (VTE) and bleeding events. METHODS: INSIGHTS-SVT, a prospective, non-interventional, multicenter study in Germany, investigated the management and outcomes of patients with acute SVT who received conservative and/or invasive treatments at the discretion of the treating physician. RESULTS: Among the 872 patients with 12-month data, 657 had medical therapy only, and 215 patients underwent vascular surgery (70 within three months of SVT diagnosis, 136 between months 4 and 12, and 9 had an intervention in both periods). The most commonly performed procedures included endovenous thermal ablation (EVTA), ligation of the saphenofemoral or saphenopopliteal junction (SFJ/SPJ), and vein stripping. The primary outcome of symptomatic VTE was observed in 5.8% of conservatively treated patients and 6.3% of those who underwent surgical intervention. Additionally, the secondary outcome of recurrent or extended SVT was documented in 4.7% of conservatively treated patients and 5.3% of invasively treated patients. Bleeding events occurred in 1.4% of conservatively treated patients and 2.1% of surgically treated patients. These differences were statistically not significant. Furthermore, our analysis indicated a potential protective effect associated with surgical treatments, such as ligation of the SFJ/SPJ, stripping and EVTA, concerning the endpoint of VTE for patients when applied after 3 months from the index SVT event. CONCLUSIONS: In line with previous research, our study suggests that surgical interventions are not frequently employed in the management of SVT, although they may be warranted in select cases. Nevertheless, additional research is essential to gain a deeper understanding of the indications, criteria and benefit of surgical interventions in the treatment of SVT.

Compression Therapy in Acute Deep Venous Thrombosis of the Lower Limb and for the Prevention of Post-Thrombotic Syndrome.

BACKGROUND: After an acute deep venous thrombosis (DVT) of the lower limb, 20% to 63% of patients develop post-thrombotic syndrome (PTS). In this review, we address the efficacy of compression therapy in the treatment of acute DVT of the lower limb, and for the prevention of PTS. METHODS: 12 randomized controlled trials (RCTs) and one meta-analysis, with a total of 3751 patients, were identified in a structured literature search. RESULTS: Two RCTs showed that adding compression therapy to drug treatment in the first 9 days of the acute phase of lower limb DVT led to more rapid pain relief (p<0.050) and less swelling (remaining difference in circumference, 1 cm versus 3 cm, p<0.050). As for the prevention of PTS, four RCTs showed a short-term benefit or no benefit of compression therapy. In three further RCTs, medical compression stockings (MCS) brought about a 16% to 27% absolute reduction of the frequency and severity of PTS (47% vs. 20 %, p<0.001; 40% vs. 21% (95% confidence intervals [29.9; 50.1] and [12.7; 29.5], respectively; and 58% vs. 42%, relative risk [RR] 0.73 [0,55; 0.96]). The benefit of MCS was also confirmed in a recent meta-analysis (RR 0.66 [0.44; 0.99], I2 = 88%). Thigh-length MCS were not superior to knee-length MCS for the prevention of PTS (33% vs. 36%, hazard ratio [HR] 0.93 [0.62; 1.41]). Individual, symptomoriented tailoring of the duration of treatment was not inferior to a fixed treatment duration of 24 months (29% vs. 28%; odds ratio [OR] 1.06 [0.78;1.44]). CONCLUSION: Compression therapy relieves symptoms in acute DVT and lessens the frequency and severity of PTS. It is therefore recommended as standard treatment.

Sex disparities in popliteal artery aneurysms.

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.

Determinants of Late Venous Thromboembolic Events After Acute Isolated Superficial Vein Thrombosis in Daily Practice: 12 Month Results of the INSIGHTS-SVT Study.

OBJECTIVE: Long term incidence of symptomatic venous thromboembolism (VTE) and bleeding events in patients with superficial vein thrombosis (SVT) was investigated. METHODS: In this prospective, observational study, patients with acute SVT were treated at the discretion of the responsible physician. The primary efficacy outcome was symptomatic VTE including deep vein thrombosis (DVT), pulmonary embolism (PE), and recurrent or extending SVT. The primary safety outcome was clinically relevant bleeding, recorded at periodic clinic visits over a 12 month period. RESULTS: The mean age of 872 patients with 12 month follow up was 60.6 ± 14.5 years, 64.5% were female, 80.1% had chronic venous disease (defined as chronic venous insufficiency and or varicose veins), and 41.9% had a history of VTE. They were receiving fondaparinux in 62.1% (mean duration 34.9 ± 15.7 days), low molecular weight heparin (LMWH) in 25.0% (mean duration 26.2 ± 23.2 days), any other anticoagulants in 6.2%, and no anticoagulant in 6.7%. At 12 months, 108 patients (14.3%) achieved the primary efficacy outcome. The most common VTE event was recurrent or extending SVT in 11.0%, followed by symptomatic DVT in 2.7%, symptomatic PE in 2.4%, hospitalisation due to VTE in 1.8%, and death in 1.1%. Clinically relevant bleeding events occurred in 2.1% of patients, and major bleedings in 0.3%. By drug, the rate of the primary efficacy outcome was highest in the LMWH group (22.4%) and lowest in the fondaparinux group (10.4%). In a multivariable model, patients with events between three months and 12 months were significantly more likely to have higher BMI (hazard ratio [HR] 1.06; p = .002), history of VTE (HR 2.89; p = .002), and severe systemic infections (HR 7.59; p = .006). CONCLUSION: The risk of symptomatic VTE remained elevated over 12 months of follow up. Therefore, anticoagulation beyond 45 days may be considered in patients with risk factors. [ClinicalTrials.gov identifier: NCT02699151.].

Radiofrequency Thermal Ablation for the Treatment of Chronic Insufficiency of the Saphenous Vein-A Comparative Retrospective Study.

OBJECTIVES: The broad spectrum of chronic venous disease encompasses varicose veins, edema, hyperpigmentation and venous ulcers. Radiofrequency thermal ablation is indicated for the treatment of superficial venous reflux of the lower limb. Our research is a comparative clinical study that aims to identify the most effective and safest therapeutic method in the management of chronic venous insufficiency of the lower limbs. MATERIALS AND METHODS: Patients admitted to the Department of Surgery of the University of Medicine and Pharmacy in Cluj-Napoca, Romania, with the clinical diagnosis of varicose veins of the lower limbs, treated by thermal ablation with radiofrequency or by open surgical techniques during the year 2022, were included. RESULTS: A percentage of 50.9% of the patients were treated by the radiofrequency thermal ablation procedure and 49.1% by surgical treatment. More than half of them were hospitalized for 2 days. The duration of hospitalization was significantly longer in patients who had postoperative complications (p < 0.001). The chance of being treated by open surgical treatment for a small saphenous vein is 10.11 times higher than by radiofrequency thermal ablation. CONCLUSION: According to the applied tests, there is no statistical difference between the group treated by radiofrequency thermal ablation and the one surgically treated in terms of sex, age, origin, CEAP clinical stage at hospitalization, clinical diagnosis at hospitalization and affected lower limb.

Management and Outcomes of Patients with Isolated Superficial Vein Thrombosis under Real Life Conditions (INSIGHTS-SVT).

OBJECTIVE: Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions. METHODS: Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding. RESULTS: A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m2). SVT was below the knee in 54.5%, above the knee in 26.7%, above and below the knee in 18.8%. At baseline, 93.6% received pharmacological treatment (65.7% fondaparinux, 23.2% heparins, 4.3% direct oral anticoagulants [DOACs], 14.5% analgesics), 77.0% compression treatment, and 1.9% surgery; 6.4% did not receive any anticoagulation. The primary outcome occurred in 5.8%; 4.7% had recurrent or extended SVT, 1.7% DVT, and 0.8% PE. Clinically relevant non-major bleeding occurred in 1.2% and major bleeding in 0.3%. Complete clinical recovery of SVT was reported in 708 patients (62.4%). Primary outcome adjusted by propensity score and for treatment duration was lower with fondaparinux compared with low molecular weight heparin (4.4% vs. 9.6%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.3 - 0.9; p = .017). On multivariable analysis, associated factors for primary outcome included another SVT prior to the present SVT event (HR 2.3), age per year (HR 0.97), duration of drug treatment per week (HR 0.92), and thrombus length (HR 1.03). CONCLUSION: At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation.

Risk and protective factors for post-thrombotic syndrome after deep venous thrombosis.

OBJECTIVE: The most frequent complication of deep venous thrombosis (DVT) is post-thrombotic syndrome (PTS). We recently showed inhibition of varicose vein development by atorvastatin and rosuvastatin. The aim of this study was to test the influence of lipid-lowering therapy with statins on PTS development. METHODS: All patients between January 2002 and June 2018 with diagnosed DVT were enrolled in this study and analyzed retrospectively. Documentation was performed using the standardized system M1 (CompuGroup Medical, Koblenz, Germany) throughout the observation period. Patients received therapeutic anticoagulation and compression stockings. In case of recurrent DVT, patients received lifelong therapeutic anticoagulation. All patients received clinical examination and duplex ultrasound evaluation 3 to 6 months after primary diagnosis and annually thereafter. RESULTS: A total of 579 patients with DVT were enrolled in this study. Of these patients, 414 (71%) developed PTS (337/414 [81%] presented with the mild version; mean Villalta score, 5.79). Risk factors for PTS development were recurrent DVT (P = .001) and malignant disease (P = .001). Protective factors were therapy with platelet aggregation inhibitors (P = .049) and lipid-lowering therapy with statins (P = .001). After multivariable analysis, the only risk factor was recurrent DVT (P = .001), and the only protective factor was lipid-lowering therapy (P = .001). CONCLUSIONS: Post-thrombotic changes might be reduced by lipid-lowering therapy.

Treatment of popliteal vein aneurysms.

OBJECTIVE: Popliteal vein aneurysms are associated with high risk for deep venous thrombosis (DVT) and pulmonary embolism. The goal of this study was to report treatment strategies for popliteal vein aneurysms and their outcome after long-term follow-up. METHODS: All patients between June 1993 and June 2018 with diagnosed popliteal vein aneurysm were enrolled in this study and analyzed retrospectively. They received regular surveillance alone or treatment. Patients were offered aneurysm resection or lifelong anticoagulation if they had aneurysm size of twice normal vein diameter. All patients received clinical examination and duplex ultrasound examination 3 to 6 months after operation or primary diagnosis and annually thereafter. RESULTS: A total of 39 patients (aneurysm size, mean 23.3 mm) were treated by either operation or anticoagulation (31/39 [79%]) or surveillance alone (8/39 [21%]). Patients with an aneurysm >20 mm in diameter had a significantly higher incidence of turbulent flow on duplex ultrasound examination with higher risk for development of DVT (P = .029). Of the 31 patients with a therapeutic approach, 29 (94%) preferred resection, whereas 2 (6%) patients were treated with lifelong anticoagulation and compression. Mean follow-up was 57.9 ± 12.5 months. CONCLUSIONS: According to these results, it seems that patients with large popliteal vein aneurysms experience DVT more frequently. Therefore, popliteal vein aneurysms >20 mm should be considered for surgical treatment or lifelong anticoagulation, depending on the patient's preference.

Complex treatment of vascular prostheses infections.

Infections after vascular reconstructions are very rare; however, when they occur, they are associated with a high risk of morbidity. In order to obtain the best results possible, the treatment needs to be initiated as early as possible, from the very first signs of infection, and it needs to be carried out in centers specializing in vascular surgery. The aim of the present study was to assess the incidence of infections in a single university center.This retrospective analysis over a 2-year period is based on the medical reports of hospitalized patients who were diagnosed with infection following revascularization.From 2013 to 2014, a number of 151 open reconstructive surgical procedures were performed. 15 patients suffered from infection (10%) of the vascular reconstruction. Of these patients, 40% have had an aorto-bifemoral bypass, 53%-a femoro-popliteal bypass, and 7% (n = 1)-an axillo-femoral bypass. According to the Samson classification, the patients were categorized as follows: group 2: 6 cases, group 3: 2 cases, group 4: 4 cases, and group 5: 3 cases. The most frequent bacteria found were methicillin-resistant Staphylococcus aureus (MRSA) (n = 6, 40%), followed by S aureus (n = 5, 33%). The treatment options were: application of antibiotics alone without any invasive treatment in 3 patients, local irrigation and debridement in 6 patients, complete explantation of the prosthesis with a new extra-anatomic bypass in 6 cases, and partial excision of the prosthesis, which was replaced and covered with muscle flap, in 3 cases. The amputation rate in our study was 18%, which corresponds to the rates published in the literature.The treatment of infections in vascular surgery needs to be complex and adapted to each individual patient, because infections being in a permanent dynamic state. The treatment needs to be performed in specialized centers that have large experience in vascular surgery, in order for the patient to have the best chances of survival and protection from amputation.

[Recommendations for the Use of Indirect and Direct Anticoagulants for Long-Term Prophylaxis after Venous Thromboembolism]. / Empfehlungen zur Anwendung der indirekten und direkten Antikoagulanzien zur langfristigen Sekundärprophylaxe nach venösen Thromboembolien.

In routine clinical work, the dosage of direct oral anticoagulants for long-term maintenance therapy after acute deep vein thrombosis and pulmonary embolism is often made on an individual basis. As two doses are available for the preparations apixaban and rivaroxaban and no separate indication spectra have been specified. The working group of practising vascular physicians and surgeons in Germany has therefore developed this position paper. Patients with a clearly identified and temporary trigger factor for venous thromboembolism (e.g. trauma, operation, acute internal disease, oral contraception or pregnancy or isolated thrombosis of veins in the lower leg have a lower risk of recurrence and are generally not given permanent anticoagulation. If there is a high risk of recurrence with unchanged trigger factor (e.g. active malignancy, unambiguous antiphospholipid syndrome or deficiency of a clotting factor, such as Protein C, Protein S or antithrombin with a positive family history of venous thromboembolism, first occurrence of a pulmonary embolism, multiple recurrence of VTE) prolonged maintenance therapy is indicated, unless this is contraindicated by a very high risk of bleeding. For all patients with former VTE and whose anticoagulation phase has in principle been completed, prolonged prophylaxis can be continued, as these patients too are at increased risk of VTE.

Rationale, design, and methodology of the observational INSIGHTS-SVT study on the current state of care and outcomes of patients with superficial vein thrombosis.

OBJECTIVE: Superficial vein thrombosis (SVT) is a common disease in clinical practice. In terms of pathophysiology and outcomes, the condition is related to venous thromboembolism, bearing a potential for severe thromboembolic complications if it is not treated adequately. A wide range of treatment approaches (including oral and injectable anticoagulants, pain medication, nondrug therapy including compression therapy, and no treatment at all) are applied in clinical practice, but there is sparse information about selection of patients for therapies, current treatment pathways, and drug use as well as outcomes. The INvestigating SIGnificant Health TrendS in the management of Superficial Vein Thrombosis (INSIGHTS-SVT) study aims to close this gap by collecting representative data on the current treatment of SVT. METHODS: The observational prospective study of about 1200 patients is carried out by up to 120 clinical and office-based physicians who regularly treat patients with SVT and are capable of conducting appropriate compression ultrasound diagnostics, such as vascular physicians, phlebologists, internists, vascular surgeons, and general practitioners. Patients are eligible for inclusion if they have ultrasound-confirmed acute, isolated SVT of the lower extremities. Documentation about the characteristics of the patients, diagnostics, comorbidities, and medical and nonmedical treatment is collected at baseline, at 10 ± 3 days or at approximately 45 days (depending on treatment), at approximately 3 months, and at approximately 12 months. Patients are requested to fill in quality of life questionnaires (on pain, Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms [VEINES-QOL/Sym], EuroQol-5 Dimension 5-Level [EQ-5D-5L]) at baseline and at approximately 3 months. Interventions are not stipulated by the trial protocol. RESULTS: The primary efficacy outcome is the incidence of venous thromboembolism at 3 months; the primary safety outcome is the combined incidence of major and clinically relevant bleeding events at 3 months. As quality measures, plausibility checks at data entry, queries based on statistical analyses that focus on outliers and distribution of values, monitoring visits, and adjudication procedures will be applied. CONCLUSIONS: This large study is expected to provide a comprehensive picture of patients with SVT under clinical practice conditions in Germany.

Varicose Remodeling of Veins Is Suppressed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors.

BACKGROUND: Despite the high prevalence of chronic venous insufficiency and varicose veins in the Western world, suitable pharmaceutical therapies for these venous diseases have not been explored to date. In this context, we recently reported that a chronic increase in venous wall stress or biomechanical stretch is sufficient to cause development of varicose veins through the activation of the transcription factor activator protein 1. METHODS AND RESULTS: We investigated whether deleterious venous remodeling is suppressed by the pleiotropic effects of statins. In vitro, activator protein 1 activity was inhibited by two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, rosuvastatin and atorvastatin, in stretch-stimulated human venous smooth muscle cells. Correspondingly, both statins inhibited venous smooth muscle cell proliferation as well as mRNA expression of the activator protein 1 target gene monocyte chemotactic protein 1 (MCP1). In isolated mouse veins exposed to an increased level of intraluminal pressure, statin treatment diminished proliferation of venous smooth muscle cells and protein abundance of MCP1 while suppressing the development of varicose veins in a corresponding animal model by almost 80%. Further analyses of human varicose vein samples from patients chronically treated with statins indicated a decrease in venous smooth muscle cell proliferation and MCP1 abundance compared with samples from untreated patients. CONCLUSIONS: Our findings imply that both atorvastatin and rosuvastatin effectively inhibit the development of varicose veins, at least partially, by interfering with wall stress-mediated activator protein 1 activity in venous smooth muscle cells. For the first time, this study reveals a potential pharmacological treatment option that may be suitable to prevent growth of varicose veins and to limit formation of recurrence after varicose vein surgery.

Three-year European follow-up of endovenous radiofrequency-powered segmental thermal ablation of the great saphenous vein with or without treatment of calf varicosities.

BACKGROUND: Radiofrequency segmental thermal ablation (RSTA) has become a commonly used technology for occlusion of incompetent great saphenous veins (GSVs). Midterm results and data on clinical parameters are still lacking. METHODS: A prospective multicenteral trial monitored 295 RSTA-treated GSVs for 36 months. Clinical control visits included flow and reflux analysis by duplex ultrasound imaging and assessment of clinical parameters according to the CEAP classification and Venous Clinical Severity Score (VCSS). RESULTS: A total of 256 of 295 treated GSVs (86.4%) were available for 36 months of follow-up. At 36 months, Kaplan-Meier survival analysis showed the probability of occlusion was 92.6% and the probability of no reflux was 95.7%, and 96.9% of legs remained free of clinically relevant axial reflux. If complete occlusion was present at the 12-month follow-up, the risk of developing new flow by 24 and 36 months of follow-up was 3.7% and 4.1%, respectively. Diameters of the GSV measured 3 cm distal to the saphenofemoral junction reduced from 5.8 ± 2.1 mm at screening to 2.2 ± 1.1 mm at 36 months. The average VCSS score improved from 3.9 ± 2.1 before treatment to 0.9 ± 1.5 at 3 months (P < .0001) and stayed at an average <1.0 during the complete 36 months of follow-up. Only 41.1% of patients were free of pain before treatment; at 36 months, 251 (98.0%) reported no pain and 245 (95.7%) did not experience pain during the 24 months before. At 36 months, 189 of 255 legs (74.1%) showed an improvement in CEAP class compared with the clinical assessment before treatment (P < .001). Stages C(3) and C(4) combined to 46% before treatment and dropped constantly to a combined level of 8% at 36 months. However, the proportion of C(2) legs that dropped from 52.3% before treatment to <10% at 12 months showed a constant increase thereafter, reaching 33.3% at 36 months. CONCLUSION: RSTA showed a high and durable success rate in vein ablation in conjunction with sustained clinical efficacy.