Diagnosis of chronic iliac venous obstruction

Stenting has become the first line of treatment for symptomatic chronic iliofemoral venous obstruction in patients with quality-of-life impairing clinical manifestations who have failed conservative therapy. Patient selection for such intervention is however dependant on clear identification of relevant clinical manifestations and subsequent testing to confirm the diagnosis. In this regard the physician engaged in management of such patients need to be well aware of symptoms and signs of chronic iliofemoral venous obstruction (CIVO), instruments used to grade chronic venous insufficiency (CVI) and determine quality of life in addition to diagnostic tests available and their individual roles. This review serves to provide an overview of the diagnosis of CIVO and patient selection for stenting.

Diagnosis of chronic iliac venous obstruction.

Stenting has become the first line of treatment for symptomatic chronic iliofemoral venous obstruction in patients with quality-of-life-impairing clinical manifestations who have failed conservative therapy. Patient selection for such intervention is, however, dependent on clear identification of relevant clinical manifestations and subsequent testing to confirm the diagnosis. In this regard, the physician engaged in management of such patients needs to be well-aware of symptoms and signs of chronic iliofemoral venous obstruction, and instruments used to grade chronic venous insufficiency and determine quality of life, in addition to diagnostic tests available and their individual roles. This review serves to provide an overview of the diagnosis of chronic iliofemoral venous obstruction and patient selection for stenting.

A mapping review of Pacific Vascular Symposium 6 initiatives.

OBJECTIVE: The 2010 Pacific Vascular Symposium 6 (PVS6) brought venous disease content experts together with a goal of addressing critical issues collated together in the next decade with concrete plans to achieve these goals. This mapping review aims to provide a broader representation of how progress in critical issues of chronic venous disease has been made by extrapolating scientific publications related to the PVS6 initiatives. METHODS: We performed a mapping review identifying original or systematic review/meta-analysis articles related to PVS 6 initiatives (aims) that addressed one of the following key objectives: scales to measure chronic venous disease, effectiveness of interventional deep venous thrombus removal, development of a deep venous valve, and biomarkers related to venous disease. Searches were undertaken in PubMed, Ovid Medline, Cochrane Library, Embase (Elsevier), CINAHL (EBSCO), and Scopus. We extracted descriptive information about the studies and predefined variables for each specific aim, showing what and where research exists on the aims included. RESULTS: A total of 2138 articles were screened from 3379 retrieved articles from six electronic databases. We mapped 186 included articles, finding that the total number of publications significantly increased after the 2010 PVS6 meeting. Aim results were visually summarized. The largest body of data addressed catheter-based thrombus removal strategies for acute iliofemoral deep venous thrombosis. Primary research on artificial venous valves and venous biomarkers remained limited. No new post-thrombotic syndrome (PTS) score has been developed. CONCLUSIONS: This mapping review identified and characterized the available evidence and gaps in our knowledge of chronic venous disease that exist visually, which may guide where more significant investments for the future should be targeted.

Systematic literature review and expert meeting report on health-related quality of life in chronic venous disease.

INTRODUCTION: Chronic venous disease (CVD) can lead to considerable morbidity and impact health-related quality of life (HRQoL). The aim of this review was twofold: (i) to provide a deeper understanding of how CVD affects HRQoL (physical, psychological and social functioning), and (ii) to review the impact of evidence-based veno-active drugs (VADs) on HRQoL. EVIDENCE ACQUISITION: For the effect of CVD on HRQoL, information was gathered during an Expert Consensus Meeting, during which data were presented from both the patient and physician perspective assessed with validated quality-of-life measures. For the impact of VADs on HRQoL, a systematic literature review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases were searched for real world evidence or randomized-controlled trials (RCT) vs. placebo, reporting data on the influence of VADs on HRQoL in patients with CVD. EVIDENCE SYNTHESIS: CVD can negatively affect daily life in a number of areas related to pain, physical function and social activities. The impact of CVD on HRQoL begins early in the disease and for patients the emotional burden of the disease is as high as the physical burden. In contrast, physicians tend to overestimate the physical impact. The database search yielded 184 unique records, of which 19 studies reporting on VADs and HRQoL in patients with CVD met the inclusion criteria (13 observational and 6 RCTs). Micronized purified flavonoid fraction (MPFF) was the most represented agent, associated with 12/19 studies (2 RCTs and 10 observational). Of the 6 RCTs, only MPFF, aminaphthone and low-dose diosmin provided statistically significant evidence for improvement on HRQoL compared with placebo; for the other VADs improvements in HRQoL were not statistically different from placebo. MPFF was also associated with improvements in HRQoL in the observational studies, across all CEAP clinical classes, as monotherapy or in combination with other conservative therapy, and for all aspects of HRQoL: physical, psychological, and social. Real-world data for the other VADs were scarce. Ruscus extract, sulodexide and a semi-synthetic diosmin were each represented by a single observational study and these limited data were associated with statistically significant improvements compared with baseline in overall and subdomain scores across the range of CEAP clinical classes. CONCLUSIONS: CVD can impair patients' HRQoL significantly at all stages of the disease. MPFF has the greatest evidence base of clinical use in both RCT and real-world observational studies for effectiveness on HRQoL and is recognized by international guidelines. The complete video presentation of the work is available online at www.minervamedica.it (Supplementary Digital Material 1: Supplementary Video 1, 5 min, 194 MB).

Cardiovascular Insights for the Appropriate Management of Chronic Venous Disease: A Narrative Review of Implications for the Use of Venoactive Drugs.

Evidence suggests that chronic venous disease (CVD) may be a cardiovascular disorder, as patients with CVD are prone to developing arterial (atherosclerosis) and venous (thromboembolism) diseases. This may be partly explained by shared risk factors. Thus, patients with CVD or cardiovascular disease require careful history-taking and physical assessment to identify coexisting pathologies and risk factors. This article summarises a symposium at the XIX World Congress of the International Union of Phlebology held in Istanbul, Turkey, in September 2022. Common pathophysiological features of CVD and cardiovascular disease are endothelial injury, hypercoagulability and systemic inflammation. In CVD, inflammation primarily affects the microcirculation, with changes in capillary permeability, vein wall and valve remodelling and increase in oxidative stress. Once patients develop symptoms/signs of CVD, they tend to reduce their physical activity, which may contribute to increased risk of cardiovascular disease. Data show that the presence of CVD is associated with an increased risk of cardiovascular disease, including peripheral arterial disease and heart failure (HF), and the risk of adverse cardiovascular events increases with CVD severity. In addition, patients with cardiovascular disease, particularly those with HF, are at increased risk of venous thromboembolism (VTE) and should be assessed for VTE risk if they are hospitalised with cardiovascular disease. Therefore, CVD management must include a multi-specialty approach to assess risk factors associated with both the venous and arterial systems. Ideally, treatment should focus on the resolution of endothelial inflammation to control both CVD and cardiovascular disease. International guidelines recommend various conservative treatments, including venoactive drugs (VADs), to improve the symptoms/signs of CVD. Micronized purified flavonoid fraction (MPFF) is a VAD, with high-quality evidence supporting its use in relieving symptoms/signs of CVD and improving quality of life. Moreover, in large-scale observational studies, MPFF has shown superior effectiveness in real-world populations compared with other VADs. Video Abstract. (MP4 97173 kb).

Blood vessel disease can affect both arteries and veins; when it affects arteries, it is called cardiovascular disease, and when it affects veins, it is called chronic venous disease (CVD). In most cases, the underlying disease process is similar, irrespective of the type of blood vessels affected, and the risk of both CVD and cardiovascular disease is increased by age, smoking, overweight/obesity and diabetes. If cardiovascular disease affects arteries in the legs, the symptoms can be similar to that of CVD, with pain, feelings of leg heaviness or tiredness and skin changes. CVD and cardiovascular disease are usually treated by different specialists. A symposium was held at the XIX World Congress of the International Union of Phlebology in Istanbul, Turkey, in September 2022, to raise awareness of the relationship between the two conditions. The speakers described the common disease processes in CVD and cardiovascular disease, and how patients with CVD are at increased risk of cardiovascular disease, and vice versa. They reiterated the importance of thoroughly assessing patients with either cardiovascular disease or CVD to see if both arterial and venous disease were present. When patients have CVD, international treatment guidelines recommend various conservative treatments, including venoactive drugs, to improve symptoms and signs. There is high-quality evidence to support the use of the venoactive drug, micronized purified flavonoid fraction (MPFF), to improve quality of life and relieve a broad range of CVD symptoms/signs. Large-scale observational studies support the effectiveness of MPFF in a real-world population of patients with CVD compared with other venoactive drugs.

Improving Chronic Venous Disease Management with Micronised Purified Flavonoid Fraction: New Evidence from Clinical Trials to Real Life.

Chronic venous disease (CVD) develops in the microvessels, and is perpetuated by a vicious cycle of inflammation and endothelial activation, structural and functional changes to vessels and valves, and progressive venous hypertension. Data from animal models indicate that micronised purified flavonoid fraction (MPFF) has beneficial effects on a range of pathophysiological processes that contribute to CVD, including inflammation, micro-vessel permeability, valve and vessel wall remodelling, and reflux in microvalves. These effects explain its beneficial effects on the signs and symptoms of CVD, which have been seen across the spectrum of Clinical, Etiological, Anatomical and Pathophysiological (CEAP) categories of CVD severity. This includes patients with symptoms but no detectable anatomical or pathophysiological anomalies (C0s or C1) and patients with varicose veins (C2). In addition to symptomatic improvement, MPFF has been shown to reduce oedema in patients with C3 CVD, resolve skin symptoms in patients with C4 CVD, and accelerate the healing of venous ulcers in patients with C6 CVD. MPFF is highly recommended in international guidelines of CVD management and is the only veno-active drug to receive guideline endorsement for an improvement in patient quality of life.

Calf muscle pump pressure-flow cycle during ambulation.

OBJECTIVE: Calf muscle pump (CMP) failure contributes to the severity and progression of chronic venous disease. Attempts to improve CMP function through resistance exercise have failed to improve chronic venous disease severity or quality of life, partially because the selection of the type of exercise was based on the assumption that the CMP ejects blood from the intramuscular venous sinuses (VSs), which has never been tested in humans. In the present study, we investigated the real-time changes in the pressure and size of the VS during the entire gait cycle of ambulation. METHODS: We studied 12 lower extremities of nine healthy volunteers at rest and while walking on a treadmill at three different speeds (60, 90, and 120 steps/min). The changes in the VS cross-sectional area (CSA) and pressure were measured. Myography of the gastrocnemius muscle (GCM) and anterior tibial muscle (ATM) was used to register muscle activity. The relationship between the phases of the gait cycle and the measured parameters was analyzed using video records of all experiments. RESULTS: The observed timing of events was consistent among all limbs studied. At rest, with the participants standing still, the VS pressure and CSA was 70.3 ± 4.2 mm Hg and 23.3 ± 14.6 mm2, respectively. During ambulation, at the first half of the stance, the GCM and ATM eccentrically contract, and the pressure is low (17 ± 8 mm Hg, 20 ± 12 mm Hg, and 29 ± 13 mm Hg at 1, 1.5, and 2 Hz, respectively), and the VS is collapsed. When the heel starts rising (the second half of the stance), the GCM concentrically contracts, the pressure increases, reaching its maximum value (143 ± 37, 134 ± 46, and 128 ± 41 mm Hg), and the VS opens, reaching its maximal size (1.8 ± 1.4 and 2.3 ± 2.2 mm2 at 1 and 1.5 Hz, respectively), followed by collapse of the VS. During the swing phase, the GCM relaxes, and the ATM concentrically contracts, resulting in a rapid decrease in pressure (2.6 ± 4.7, 1.1 ± 6.2, and -4.7 ± 3.2 mm Hg). The VS CSA remained negligible. CONCLUSIONS: The GCM concentric contraction was associated with a simultaneous increase in VS pressure and CSA. GCM relaxation with ATM concentric contraction coincided with a decrease in VS pressure to negative values. The VSs do not fill but remain empty during the swing phase of ambulation, acting, not as a reservoir, but as a conduit, transferring blood from the network of intramuscular veins to the axial deep veins.

Fake-news-free evidence-based communication for proper vein-lymphatic disease management.

Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.

Salvage of a megafistula causing high-output cardiac failure in a young adult with aneurysmorrhaphy and banding.

We present the case of a 21-year-old male with significant lengthening and aneurysmal degeneration of his brachiocephalic arteriovenous fistula resulting in a megafistula and high-output cardiac failure. A computed tomography angiogram showed narrowing at the cephalic arch. Further evaluation during the operation revealed kinking and elongation of the fistula in addition to compression of the cephalic arch in the deltopectoral groove leading to outflow obstruction. The aneurysmal fistula was treated successfully with aneurysmorrhaphy of the remaining conduit and banding of the inflow. This case demonstrates a unique etiology of venous outflow obstruction for a fistula and describes the surgical approach to its treatment in a young patient suffering from cardiac failure.

Extended anticoagulation for venous thromboembolism: A survey of the American Venous Forum and the European Venous Forum.

OBJECTIVE: Extended anticoagulation therapy should always be considered after standard treatment of an unprovoked episode of venous thromboembolism (VTE). It can also be considered for selected patients with provoked VTE. However, the evidence-based protocols suggested by some clinical guidelines and risk assessment tools to guide this practice are limited and ambiguous. The goal of the present survey research was to analyze current practices in applying extended anticoagulation therapy for patients with VTE among members of the American Venous Forum (AVF) and European Venous Forum (EVF). METHODS: An online survey was created by the AVF Research Committee. The survey consisted of 16 questions to identify the country of practice, specialty, experience of the participating physicians, and their clinical practice patterns in applying extended anticoagulation therapy for VTE patients. The survey was distributed via e-mail to the members of the AVF and EVF. RESULTS: A total of 144 practitioners, 48 AVF members (33%) and 96 EVF members (66%), participated in the survey. Most of the respondents identified themselves as vascular specialists with primary certification in vascular surgery (70%), vascular medicine or angiology (9%), and venous disease or phlebology (3%). Of the 144 respondents, 72% believed that the risk of VTE recurrence will generally overweigh the risk of bleeding for patients with unprovoked VTE. Extended anticoagulation therapy might be used by 97% of providers. Different patterns in real world clinical practice were identified. More than one half of the practitioners estimated the VTE recurrence and bleeding risk subjectively. The antithrombotic drugs most commonly used for secondary prophylaxis were rivaroxaban, apixaban, warfarin, dabigatran, and aspirin, in decreasing order of frequency. Among the reasons selected for not regularly considering extended anticoagulation therapy were the lack of specific clinical practice guidelines (24%), lack of reported evidence (9%), and absence of valid VTE and/or bleeding risk prediction calculators (8%). Twelve participants (8%) stated that extended anticoagulation therapy would not be beneficial for most patients with VTE. Ten participants (7%) indicated that prescribing extended anticoagulation therapy was outside the scope of their specialty. CONCLUSIONS: Different practice patterns exist regarding extending anticoagulation therapy beyond the standard treatment for patients with VTE. Major gaps in knowledge remain a serious challenge at least partially explaining the inaccuracy and inconsistency in long-term VTE management. Appropriately designed studies are needed to evaluate risk stratification tools when contemporary best medical therapy is used, accurately predict VTE recurrence and its long-term outcomes, and tailor safe and effective secondary prophylaxis.

Defining the role of risk stratification and duplex ultrasound in the diagnosis of acute lower extremity deep vein thrombosis.

OBJECTIVE: Risk stratification using the plasma D-dimer level and Wells score has been proposed as a safe strategy to rule out acute lower extremity deep vein thrombosis (DVT) and limit the use of duplex ultrasound (DUS) for low-risk patients. A widely used diagnostic protocol defining the role of pretest probability and D-dimer testing in lieu of DUS has not been reported. Our aim was to define the risk of DVT in a standard population of emergency department patients who had presented with acute lower extremity symptoms and determine the role of DUS for these patients. METHODS: Outpatients presenting to the emergency department with symptoms concerning for lower extremity DVT were prospectively enrolled. All the patients underwent whole leg DUS and clinical and laboratory assessments for DVT using the Wells criteria and plasma D-dimer testing. The patients were stratified into three groups according to the combination of their Wells score and plasma D-dimer level. The prevalence of DVT and the statistical performance of the combined Wells score and plasma D-dimer were compared. RESULTS: A total of 3087 patients were enrolled. Most of the patients had had a negative plasma D-dimer level and Wells score (n = 2290 patients). A total of 222 patients had had a positive plasma D-dimer level and Wells score. The overall prevalence of acute DVT in the present study was 7.3%. Of the 2290 patients with a negative Wells score and negative plasma D-dimer level, 4 had had a diagnosis of DVT (negative predictive value, 99.8%). In contrast, DVT was present in 181 of 222 patients (81.5%) with a positive Wells score and plasma D-dimer level (positive predictive value, 81.5%). The plasma D-dimer level also correlated with the DVT location, and the D-dimer levels were highest for the patients with proximal DVT. CONCLUSIONS: The combination of a negative Wells score and negative plasma D-dimer level can safely exclude the presence of DVT. Patients with a negative Wells score and negative plasma D-dimer level are unlikely to benefit from DUS. In contrast, patients with a positive D-dimer level and positive Wells score will benefit from whole leg DUS to rule out the presence of high-risk DVT.

The American Venous Forum, American Vein and Lymphatic Society and the Society for Vascular Medicine expert opinion consensus on lymphedema diagnosis and treatment.

BACKGROUND: Lymphedema imposes a significant economic and social burden in modern societies. Controversies about its risk factors, diagnosis, and treatment permeate the literature. The goal of this study was to assess experts' opinions on the available literature on lymphedema while following the Delphi methodology. METHODS: In December of 2019, the American Venous Forum created a working group tasked to develop a consensus statement regarding current practices for the diagnosis and treatment of lymphedema. A panel of experts was identified by the working group. The working group then compiled a list of clinical questions, risk factors, diagnosis and evaluation, and treatment of lymphedema. Fifteen questions that met the criteria for consensus were included in the list. Using a modified Delphi methodology, six questions that received between 60% and 80% of the votes were included in the list for the second round of analysis. Consensus was reached whenever >70% agreement was achieved. RESULTS: The panel of experts reached consensus that cancer, infection, chronic venous disease, and surgery are risk factors for secondary lymphedema. Consensus was also reached that clinical examination is adequate for diagnosing lymphedema and that all patients with chronic venous insufficiency (C3-C6) should be treated as lymphedema patients. No consensus was reached regarding routine clinical practice use of radionuclide lymphoscintigraphy as a mandatory diagnostic tool. However, the panel came to consensus regarding the importance of quantifying edema in all patients (93.6% in favor). In terms of treatment, consensus was reached favoring the regular use of compression garments to reduce lymphedema progression (89.4% in favor, 10.6% against; mean score of 79), but the use of Velcro devices as the first line of compression therapy did not reach consensus (59.6% in favor vs 40.4% against; total score of 15). There was agreement that sequential pneumatic compression should be considered as adjuvant therapy in the maintenance phase of treatment (91.5% in favor vs. 8.5% against; mean score of 85), but less so in its initial phases (61.7% in favor vs. 38.3% against; mean score of 27). Most of the panel agreed that manual lymphatic drainage should be a mandatory treatment modality (70.2% in favor), but the panel was split in half regarding the proposal that reductive surgery should be considered for patients with failed conservative treatment. CONCLUSION: This consensus process demonstrated that lymphedema experts agree on the majority of the statements related to risk factors for lymphedema, and the diagnostic workup for lymphedema patients. Less agreement was demonstrated on statements related to treatment of lymphedema. This consensus suggests that variability in lymphedema care is high even among the experts. Developers of future practice guidelines for lymphedema should consider this information, especially in cases of low-level evidence that supports practice patterns with which the majority of experts disagree.

Outcomes of Popliteal Stent-Graft Placement at the Artery Hinge Point for Popliteal Artery Aneurysm.

BACKGROUND: To assess whether stent-grafts crossing the hinge point (HP) in the popliteal artery are associated with increased complications and decreased patency rates, after endovascular treatment of the popliteal artery aneurysm. METHODS: This was a single-center, case-control study. Patients were allocated to either the HP group (subjects with stent-grafts crossing the HP) or the control group (subjects with stent-grafts above and/or below the HP) based on stent-graft location in the femoropopliteal artery. HP was defined as the main curve in the popliteal artery in the most acute angle toward the femur that appeared during knee flexion, which was identified by reviewing postoperative angiograms. Independent, blinded reviews were performed for all imaging data. Graft evaluation by CTA or duplex ultrasound was performed at 1, 3, 6, and 12 months and annually thereafter. Outcomes measured included: stent-graft patency, stent-graft fracture, other stent-related complications, and major adverse events, including reintervention, death, amputation, stroke, and myocardial infarction. RESULTS: A total of 44 limbs treated with placement of heparin-bonded Viabahn endoprostheses were included in this study. Twenty and twenty-four patients were allocated to the HP group and the control group, respectively. Primary patency rates of the HP group at 1, 2, 3, and 5 years were 84.1 ± 8.4%, 84.1 ± 8.4%, 84.1 ± 8.4%, and 72.1 ± 13.3%, respectively. The primary patency rates of the control group were 87.0 ± 7.0%, 82.4 ± 8.0%, 82.4 ± 8.0%, and 82.4 ± 8.0%, respectively. There was no significant difference between the 2 groups (P = 0.81). No reintervention was performed in the control group. In the HP group, 5 limbs (25.0%) developed endoleak, 3 (15.0%) developed thrombosis, and 1 (5.0%) developed a stent fracture followed by thrombosis. Thrombosis occurred in 2 limbs (8.3%) of the control group, and stent-graft migration was observed in another 2 cases (8.3%). Neither group demonstrated stent-graft infection or acute popliteal artery embolism. Overall, incidence of stent-related complications were significantly higher in the HP group (P= 0.04). Event-free survival rates of the HP group at 1, 2, 3, and 5 years were 75.0 ± 9.7%, 69.6 ± 10.4%, 61.9 ± 11.8%, and 29.0 ± 12.8%, respectively. Corresponding rates in the control group were 79.2 ± 8.3%, 79.2 ± 8.3%, 79.2 ± 8.3%, and 79.2 ± 8.3%, respectively. The difference was not statistically significant between the 2 groups (P = 0.20) CONCLUSIONS: crossing the HP with femoropopliteal artery stent-grafts increased the risk of stent-related complications and reinterventions but did not decrease stent patency or event-free survival.