Final 3-Year Study Outcomes from the Evaluation of the Zilver Vena Venous Stent for the Treatment of Symptomatic Iliofemoral Venous Outflow Obstruction (The VIVO Clinical Study).

PURPOSE: To report 3-year outcomes from a prospective, multicenter, nonrandomized, single-arm study designed to assess the safety and effectiveness of the Zilver Vena Venous Stent for the treatment of symptomatic iliofemoral venous outflow obstruction. MATERIALS AND METHODS: The VIVO study included patients with symptomatic obstruction of 1 iliofemoral venous segment (ie, 1 limb), characterized by a Clinical, Etiological, Anatomic, Pathophysiology (CEAP) clinical classification of ≥3 or a Venous Clinical Severity Score (VCSS) for pain of ≥2. Patients were retrospectively grouped based on baseline clinical presentation as postthrombotic syndrome (PTS), nonthrombotic iliac vein (NIVL) obstruction, or acute deep vein thrombosis (aDVT). Clinical improvement was assessed by change in VCSS, Venous Disability Score, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) scores, and CEAP C classification. Stent performance was evaluated by rates of patency by ultrasound (US), freedom from clinically driven reintervention, and freedom from stent fracture. RESULTS: The 3-year results for the 243 patients in the VIVO cohort included a 90.3% rate of patency by US and a 92.6% rate of freedom from clinically driven reintervention. The 3-year rates of patency by US for the NIVL, aDVT, and PTS groups were 100%, 84.0%, and 86.1%, respectively. Sustained clinical improvement through 3 years was demonstrated by changes in VCSS, Venous Disability Score, CIVIQ-20, and CEAP C classification. No stent fractures were observed. CONCLUSIONS: The VIVO study demonstrated sustained high rates of patency and freedom from clinically driven reintervention and improvements in venous clinical symptoms through 3 years. Each patient group (NIVL, aDVT, and PTS) showed clinical improvement and sustained patency through 3 years; some variation existed among groups (eg, only the NIVL group had a 100% patency rate).

Editor's Choice - Management of Lower Extremity Venous Outflow Obstruction: Results of an International Delphi Consensus.

OBJECTIVE: The endovascular treatment of venous obstruction has expanded significantly in recent years. Best practices for optimal patient outcomes are not well established and the evidence base is poor. The purpose of this study was to obtain consensus on management criteria for patients with lower extremity venous outflow obstruction. METHODS: The study was conducted as a two round Delphi consensus. Statements addressed imaging, symptoms and other baseline measures, differential diagnosis, treatment algorithm, indications for stenting, inflow and outflow assessment, successful procedural outcomes, post-procedure therapies and stent surveillance, and clinical success factors. Statements were prepared by six expert physicians (round 1, 40 statements) and an expanded panel of 24 physicians (round 2, 80 statements) and sent to a pre-identified group of venous experts who met qualifying criteria. A 9 point Likert scale was used and consensus was defined as ≥ 70% of respondents rating a statement between 7 and 9 (agreement) or between 1 and 3 (disagreement). Round 1 results were used to guide rewording and splitting compound statements for greater clarity in round 2. RESULTS: In round 1, 75 of 110 (68%) experts responded, and 91 of 121 (75%) experts responded in round 2. Round 1 achieved consensus in 32/40 (80%) statements. Consensus was not reached in the treatment algorithm section. Round 2 achieved consensus in 50/80 (62.5%). Statements reaching consensus were imaging (2/3, 66%), symptoms and other baseline measures (12/24, 50%), differential diagnosis (2/8, 25%), treatment algorithm (10/17, 59%), indications for stenting (10/10, 100%), inflow and outflow assessment (2/2, 100%), procedural outcomes (2/2, 100%), post-procedure therapies and stent surveillance, (5/7, 71%), and clinical success factors (5/7, 71%). CONCLUSION: This study demonstrated that considerable consensus was achieved between venous experts on the optimal management of lower extremity venous outflow obstruction. There were multiple domains where consensus is lacking, highlighting important areas for further investigation and research.

Midterm and Long-Term Outcomes following Dedicated Endovenous Nitinol Stent Placement for Symptomatic Iliofemoral Venous Obstruction: Three- to 5-Year Results of the VIRTUS Study.

PURPOSE: To assess the midterm patency and long-term safety of placement of a dedicated venous stent (Vici Venous Stent System) for the treatment of venous lesions of the iliofemoral outflow tract. MATERIALS AND METHODS: Patients with unilateral obstructive disease of the iliofemoral veins and a Clinical, Etiological, Anatomical, Pathophysiological class of 3 or higher or a Venous Clinical Severity Score of 2 or greater were enrolled in this prospective, multicenter, single-arm study at 23 sites in the United States and Europe. The patients were followed up for 36 months after the index procedure for the assessment of patency and up to 60 months for the assessment of safety. The clinical outcomes in 11 patients with a stent fracture were assessed. RESULTS: A total of 200 patients enrolled in 2 cohorts (ie, feasibility cohort, n = 30; pivotal cohort, n = 170) were combined for this analysis. The overall 36-month primary patency rate was 71.7% (86/120), and the 36-month primary patency rate was 96.4% (27/28) for the nonthrombotic group and 64.1% (59/92) for the postthrombotic group. The freedom from major adverse events was 81.2% (53/65) through 60 months. The 60-month Kaplan-Meier estimate of freedom from target vessel revascularization (TVR) was 84.3%. In 9 of the 11 patients who had a stent fracture (1 patient with nonthrombotic etiology and 10 patients with postthrombotic etiology) identified at 12 months, the stents extended into the common femoral vein. The TVR rates and clinical outcomes were similar between patients with and without a stent fracture. CONCLUSIONS: The results of the VIRTUS study demonstrated good midterm patency and long-term safety following the placement of a dedicated venous stent for iliofemoral obstruction.

Endovascular mechanical thrombectomy versus thrombolysis in patients with iliofemoral deep vein thrombosis - a systematic review and meta-analysis.

Background: This study sought to compare effectiveness and safety of percutaneous mechanical thrombectomy (PMT) and thrombolysis alone (THR) in patients with acute or subacute iliofemoral deep vein thrombosis (IfDVT). Patients and methods: Observational and randomized trials, published between January 2001 to February 2019 were identified by searching MEDLINE. Studies on deep venous thrombosis (DVT) treated with either THR or PMT adjunctive to conventional anticoagulation and compressive intervention were included. Meta-analysis of proportions was conducted to assess effectiveness outcomes of successful lysis and primary patency, post-thrombotic syndrome (PTS), valvular reflux, recurrent DVT, as well as safety outcomes of major bleeding, hematuria, and pulmonary embolism. Results: Of 77 identified records, 17 studies including 1417 patients were eligible. Pooled proportion of successful lysis was similar between groups (THR: 95 % [I2 = 68.4 %], PMT 96 %, [I2 = 0 %]; Qbet [Cochran's Q between groups] 0.3, p = 0.61). However, pooled proportion of 6-month primary patency was lower after THR than after PMT (68 % [I2 = 15.6 %] versus 94 %; Qbet 26.4, p < 0.001). Considerable heterogeneity within groups did not allow for between-group comparison of PTS and recurrent DVT. Major bleeding was more frequent after THR than after PMT (6.0 % [I2 = 0 %] versus 1.0 % [I2 = 0 %]; Qbet 12.3, p < 0.001). Incidence of hematuria was lower after THR as compared to PMT (2 % [I2 = 56 %] versus 91.3 % [I2 = 91.7 %]; Qbet 714, p < 0.001). Incidences of valvular reflux and pulmonary embolism were similar across groups (THR: 61 % versus PMT: 53 %; Qbet 0.7, p = 0.39 and THR: 2 % versus PMT: 1 %; Qbet 1.1, p = 0.30, respectively). Conclusions: In patients with iliofemoral DVT, percutaneous mechanical thrombectomy was associated with a higher cumulative 6-month primary patency and a lower incidence of major bleeding compared to thrombolysis alone. Risk of hemolysis from mechanical thrombectomy needs further consideration.

A Multicenter, Retrospective Study of the Effectiveness of the Trellis-8 System in the Treatment of Proximal Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) occurs in up to 600,000 patients in the United States annually and can lead to long-term morbidity because of the post-thrombotic syndrome. The multicenter isolated-pharmacomechanical thrombolysis device (ISOL-8) study was designed to determine the safety and efficacy of the Trellis™-8 peripheral infusion system when used as the primary intervention to achieve DVT thrombolysis in patients with proximal lower-extremity occlusive DVT, and track the incidence and severity of the post-thrombotic syndrome (PTS) symptoms in patients 2 years after treatment. METHODS: Data were collected retrospectively from 6 centers on patients treated with the Trellis-8 system, an isolated-pharmacomechanical thrombolysis device (IPMTD). Patients with occlusive lower-extremity DVT involving at least the iliac and/or common femoral vein were included. Patient demographics, medical history, procedure outcomes, complications, and follow-up venous duplex and Venous Clinical Severity Score (VCSS) were collected through 24 months. Data analysis of outcomes were performed at 1 and 12 months. A 24-month analysis was not performed because of the small number of patients for whom 24-month data could be collected. RESULTS: A total of 151 limbs in 139 patients were treated with IPMTD. The mean ± standard deviation (SD) procedure time was 122.6 ± 63.4 min. Single session treatment was delivered in 69.9% (93 of 133) of cases. Occlusive DVT extended from the femoral into the external and/or common iliac vessel segments in most of the cases (113 of 151 limbs; 74.8%). Before treatment, 23.2% (35 of 151) of the treated limbs, based on a history of prior ipsilateral DVT or preoperative imaging revealing chronic venous scar, were expected to have some chronic venous disease despite presenting with acute symptoms. After treatment, 43.7% (66 of 151) of the limbs showed evidence of chronic thrombus. The average amount (mean ± SD) of thrombolysis, as determined by venogram, was highest in patients who had acute thrombus (81 ± 19.7%), compared with subacute thrombus (61 ± 22.5%) and complex cases involving acute and/or subacute thrombus on chronic scar (56 ± 26.5%). VCSS scoring showed the number of patients with none and/or mild pain, varicose veins, and skin changes at 1-month remained stable at 12 months whereas the percent of patients with none and/or mild venous edema improved from 71.7% at 1 month (38 of 53) to 86.8% (46 of 53) at 12 months. Twenty-four-month follow-up data were available for only 15% (23 of 151) of patients. No clinically significant pulmonary emboli or major periprocedural bleeding events were reported. CONCLUSIONS: Patients with acute lower-extremity DVT involving the proximal veins can be safely and successfully treated with IPMTD. Major procedural bleeding was absent. The occurrence of severe PTS after primary treatment with Trellis-8 system IPMTD is low. Further long-term follow-up data are needed to confirm the benefit of intervention for thrombus removal compared with standard medical management.

Consensus Statement on the Management of Nonthrombotic Iliac Vein Lesions From the VIVA Foundation, the American Venous Forum, and the American Vein and Lymphatic Society.

A nonthrombotic iliac vein lesion is defined as the extrinsic compression of the iliac vein. Symptoms of lower extremity chronic venous insufficiency or pelvic venous disease can develop secondary to nonthrombotic iliac vein lesion. Anatomic compression has been observed in both symptomatic and asymptomatic patients. Causative factors that lead to symptomatic manifestations remain unclear. To provide guidance for providers treating patients with nonthrombotic iliac vein lesion, the VIVA Foundation convened a multidisciplinary group of leaders in venous disease management with representatives from the American Venous Forum and the American Vein and Lymphatic Society. Consensus statements regarding nonthrombotic iliac vein lesions were drafted by the participants to address patient selection, imaging for diagnosis, technical considerations for stent placement, postprocedure management, and future research/educational needs.

Twelve-month end point results from the evaluation of the Zilver Vena venous stent in the treatment of symptomatic iliofemoral venous outflow obstruction (VIVO clinical study).

BACKGROUND: In the present study, we evaluated the safety and effectiveness of the Zilver Vena venous stent in the treatment of patients with symptomatic iliofemoral outflow obstruction. METHODS: The VIVO clinical study was a prospective, nonrandomized, multicenter study that enrolled patients with symptomatic obstruction of one iliofemoral venous segment. Included were patients with Clinical, Etiological, Anatomical, Pathophysiological (CEAP) clinical classification of ≥3 or a Venous Clinical Severity Score (VCSS) pain score of ≥2. All patients received a self-expanding venous stent (Zilver Vena venous stent; Cook Ireland Ltd, Limerick, Ireland). The primary safety end point was 30-day freedom from major adverse events. The primary effectiveness end point was the 12-month rate of primary quantitative patency by venography as determined by the core laboratory. The secondary end point was the change in the VCSS from baseline to 1 and 12 months. Additional measures included freedom from clinically driven reintervention; change in the CEAP C classification, Venous Disability Score (VDS), and Chronic Venous Disease Quality of Life Questionnaire (CIVIQ) scores from baseline to 12 months; and stent durability measures. RESULTS: Between December 2013 and October 2016, 243 patients (70% female; mean age, 53 ± 15 years; 67.5% with current or previous deep vein thrombosis) were enrolled at 30 institutions. Iliac vein compression by the iliac artery (n = 191; 78.6%) was the primary indication for stent placement. The mean lesion length was 98.6 ± 69.8 mm. The 30-day freedom from major adverse events rate was 96.7%, greater than the literature-defined performance goal of 87% (95% confidence interval [CI], 93.5%-98.6%; P < .0001). The 12-month primary quantitative patency rate was 89.9%, greater than the literature-defined performance goal of 76% (95% CI, 85.1%-93.4%; P < .0001). The change in the VCSS from baseline was -3.0 (95% CI, -3.5 to -2.6; P < .0001) at 1 month and -4.2 (95% CI, -4.7 to -3.7; P < .0001) at 12 months, demonstrating clinical improvement. Similarly, significantly (P < .0001) fewer symptoms over time (from preprocedure through 12 months) were measured using the clinical measures of VDS, CEAP C classification, and CIVIQ. The 12-month rate of freedom from clinically driven reintervention was 95.8% ± 1.3%. Through 12 months, no stent fractures and one clinical migration (Clinical Events Committee adjudicated the latter as technique-related due to device undersizing at placement) had occurred. CONCLUSIONS: The 12-month results of the VIVO study have demonstrated the safety and effectiveness of the Zilver Vena venous stent for the treatment of symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared with baseline.

Pivotal Study of Endovenous Stent Placement for Symptomatic Iliofemoral Venous Obstruction.

BACKGROUND: Chronic venous insufficiency is characterized by inadequate venous return from the lower extremities, which may arise from intravenous obstruction after deep vein thrombosis or from extrinsic venous compression. The purpose of this study was to determine the safety and effectiveness of a dedicated endovenous stent for symptomatic iliofemoral venous obstruction. METHODS: The VIRTUS trial (VIRTUS Safety and Efficacy of the Veniti Vici Venous Stent System [Veniti, Inc] When Used to Treat Clinically Significant Chronic Non-Malignant Obstruction of the Iliofemoral Venous Segment) was a prospective, international, single-arm, pivotal study of endovenous stent placement in patients with symptomatic iliofemoral venous obstruction. Patients included those with ≥50% obstruction on venography and Clinical, Etiology, Anatomic, Pathophysiology clinical classification ≥3, or at least moderate leg pain with a Venous Clinical Severity Score of 2 or greater. All patients were treated with a self-expanding nitinol stent developed for dedicated use in the venous system (Vici Venous Stent System, Veniti, Inc/Boston Scientific, Marlborough, MA). Patients returned for clinical and imaging follow-up visits at 1 month, 6 months, and 1 year. The primary safety outcome was freedom from major adverse events at 30 days. The primary effectiveness outcome was venographic primary patency at 1-year. Adverse events were adjudicated by a Clinical Events Committee, and all imaging including venograms, intravascular ultrasound, and Doppler examinations were assessed by respective core laboratories. RESULTS: Between March 2015 and November 2016, 170 patients (127 chronic post-thrombotic, mean age 54 years, 56.4% female) at 22 sites underwent endovenous stent placement. Mean diameter stenosis was 78%, with 31.2% total occlusions. Mean lesion length was 111.3 mm, range 10 to 260 mm (mean 125.3 mm for post-thrombotic patients and 70.2 mm for nonthrombotic patients). Freedom from a major adverse event through 30 days was 98.8%. The 1-year primary patency rate for the entire group was 84.0%. Venographic patency rates for the nonthrombotic and chronic post-thrombotic groups were 96.2% and 79.8%, respectively. At 12 months, 64% (85/132) of patients demonstrated at least a 3-point reduction in Venous Clinical Severity Score. CONCLUSIONS: Twelve-month safety and effectiveness were demonstrated with the use of a dedicated venous stent to treat symptomatic iliofemoral venous obstructions, with reductions in clinical symptoms and improvements in quality of life, through 1-year follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02112877.

Long-term clinical outcomes and technical factors with the Wallstent for treatment of chronic iliofemoral venous obstruction.

BACKGROUND: Factors affecting long-term clinical outcome and stent patency after iliofemoral venous stenting remain complex and ill-defined. Also, consensus is lacking among clinicians regarding the continuing role for the Wallstent (Boston Scientific, Marlborough, Mass) as dedicated nitinol-based venous stents become available. We undertook this study to review our long-term results using Wallstents and to evaluate the potential role of this stent in the future. METHODS: From 2007 to 2014, there were 77 limbs in 67 consecutive patients that received Wallstents for chronic iliofemoral vein obstruction. Intravascular ultrasound (IVUS) and venography were used to assess lesion type and extent. Baseline clinical severity was assessed with Venous Clinical Severity Score (VCSS) and Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification. Clinical improvement was assessed with VCSS at 12, 24, and 36 months. VCSS change ≥4 points was considered significant improvement. Patency was assessed with duplex ultrasound. A retrospective review of patients' records and imaging was conducted to assess baseline and procedural factors associated with long-term clinical outcomes. RESULTS: Lesions were nonthrombotic in 42 limbs (55%) and left-sided in 48 limbs (62%). Ten patients were treated for bilateral venous disease. Patients were predominantly male (55%); median age was 63 years (range, 47-83 years). Median baseline VCSS was 9 (range, 3-23). IVUS and venography estimated equal vessel compromise length in 37 limbs (48%). IVUS estimated a longer lesion in 32 limbs (42%). Stenting correlated with venography and IVUS in 37 limbs (48%) and more closely aligned with IVUS in 35 limbs (45%). Stents extended into the common femoral vein (CFV) in 17 limbs (22%) and into the inferior vena cava in 6 limbs (8%). Sixty-five (97%) patients had available imaging follow-up (median, 50 months). At 72 months, primary patency in the overall cohort was 87%; assisted primary patency and secondary patency were both 95%. In the nonthrombotic subset, assisted primary patency and secondary patency were 100%; primary patency was 97%. In the post-thrombotic subset, primary patency was 75%; assisted primary patency and secondary patency were 88%. Three early failures occurred. Eight patients required reintervention (range, 0.5-80 months); five interventions were to maintain patency. Cox multivariate regression identified that CFV disease predicted later complications. At last VCSS follow-up per patient (median, 26 months), 52 patients (68%) showed ≥4-point VCSS improvement. None had score worsening. CONCLUSIONS: Venous stenting with Wallstents for iliofemoral post-thrombotic or compressive obstruction proved safe and effective through long-term follow-up, with excellent patency rates. The majority of patients exhibited significant clinical improvement. CFV occlusive disease predicts increased complications.

Matrix metalloproteinases in critical limb ischemia.

Critical limb ischemia (CLI) is most commonly the result of arterial occlusive disease, specifically atherosclerotic plaque formation and rupture within the infrainguinal arteries. The physiological response to CLI is partial limb reperfusion via the distinct processes of angiogenesis and arteriogenesis. Matrix metalloproteinases (MMPs) are extracellular matrix-remodeling enzymes that play an important role in both the occlusion and reperfusion processes associated with CLI. This article provides a review of the recent literature, summarizing the current understanding of the role of MMPs in both the arterial occlusion and limb reperfusion associated with CLI. Specifically, the functions of MMPs in atherosclerosis, angiogenesis, and arteriogenesis are discussed.

Disruption of endothelial cell interactions with the novel HU177 cryptic collagen epitope inhibits angiogenesis.

PURPOSE: The importance of cellular communication with the extracellular matrix in regulating cellular invasion is well established. Selective disruption of communication links between cells and the local microenvironment by specifically targeting non-cellular matrix-immobilized cryptic extracellular matrix epitopes may represent an effective new clinical approach to limit tumor-associated angiogenesis. Therefore, we sought to determine whether the HU177 cryptic collagen epitope plays a functional role in regulating angiogenesis in vivo. EXPERIMENTAL DESIGN: We examined the expression and characterized the HU177 cryptic collagen epitope in vitro and in vivo using immunohistochemistry and ELISA. We examined potential mechanisms by which this cryptic collagen epitope may regulate angiogenesis using in vitro cell adhesion, migration, proliferation, and biochemical assays. Finally, we examined the whether blocking cellular interactions with the HU177 cryptic epitope plays a role in angiogenesis and tumor growth in vivo using the chick embryo model. RESULTS: The HU177 cryptic epitope was selectively exposed within tumor blood vessel extracellular matrix, whereas little was associated with quiescent vessels. An antibody directed to this cryptic site selectively inhibited endothelial cell adhesion, migration, and proliferation on denatured collagen type IV and induced increased levels of cyclin-dependent kinase inhibitor p27(KIP1). Systemic administration of mAb HU177 inhibited cytokine- and tumor-induced angiogenesis in vivo. CONCLUSIONS: We provide evidence for a new functional cryptic regulatory element within collagen IV that regulates tumor angiogenesis. These findings suggest a novel and highly selective approach for regulating angiogenesis by targeting a non-cellular cryptic collagen epitope.

Early results for below-knee bypasses using Distaflo.

In patients who require lower extremity revascularization, prosthetic graft is a reasonable alternative in the absence of a suitable autologous vein conduit. However, prosthetic bypass grafts have limited patency, especially for infrageniculate reconstruction. Polytetrafluoroethylene grafts were geometrically modified at the distal end to increase their patency. The authors reviewed their experience with the Distaflo graft in patients who required lower extremity below-knee popliteal and tibial bypasses when no suitable autologous vein conduit was available. Chart review was conducted of the 57 patients who underwent 60 lower extremity bypasses over a 3-year period between June 2003 and April 2006. Twenty-four revascularizations were constructed to the tibial outflow sites, whereas the remaining grafts were placed to the below-knee (28) and above-knee (8) popliteal artery, respectively. Study endpoints were primary, assisted primary, secondary patency, and limb salvage at the time of follow-up. Distaflo bypass was performed at the infrageniculate level in 86.7% of cases (28 below-knee popliteal, 24 tibial). Mean follow-up time was 12 months (range, 0.5-37.5 months). At 1 year, primary, assisted primary, and secondary patencies and limb salvage rates for below-knee popliteal bypasses were 83.5%, 89.5%, 94.7%, and 94.4%, respectively. Primary, assisted primary, and secondary patencies and limb salvage rates for tibial bypasses were 44.4%, 44.4%, 63.2%, and 74.9%, respectively. Distaflo precuffed graft is a good alternative conduit for below-knee popliteal and tibial lower extremity reconstructions in the absence of an autologous vein and appears to have promising early patency and limb salvage rates even when used for tibial bypasses.

Analysis of threshold stenosis by multiplanar venogram and intravascular ultrasound examination for predicting clinical improvement after iliofemoral vein stenting in the VIDIO trial.

BACKGROUND: Selecting patients for iliofemoral vein stenting has traditionally relied on the identification and quantification of stenotic lesions with imaging such as multiplanar venography. Recently, intravascular ultrasound (IVUS) imaging has become more available. However, to date, the usefulness of these imaging modalities using the customary >50% treatment threshold for diameter (multiplanar venography) and area (IVUS) stenosis of iliofemoral veins has not been validated prospectively within the context of clinical improvement. METHODS: The multicenter Venogram Versus Intravascular Ultrasound for Diagnosing and Treating Iliofemoral Vein Obstruction (VIDIO) trial prospectively enrolled 100 symptomatic patients (Clinical Etiologic Anatomic Pathophysiologic [CEAP] classification of 4-6) with suspected iliofemoral venous outflow disease. Venous stenting for presumed significant iliofemoral vein stenosis, based on imaging and clinical findings, was performed on 68 patients. Based on imaging, stenosis was characterized as nonthrombotic in 48 patients and post-thrombotic in 20 patients. Each underwent baseline and poststenting venography and IVUS to compare the diagnostic and clinical usefulness of the tests. The revised Venous Clinical Severity Score was used to assess clinical patient outcome. A >4-point reduction in the revised Venous Clinical Severity Score between baseline and 6 months was used as an indicator of clinically meaningful improvement. Receiver operating characteristic curve analysis was used to determine the optimal diameter and area thresholds for prediction of clinical improvement. RESULTS: Clinical improvement after stenting was best predicted by IVUS baseline measurement of area stenosis (area under the curve, 0.64; P = .04), with >54% estimated as the optimal threshold of stenosis indicating interventional treatment. With measurement of lumen gain from baseline to after the procedure, the optimal reduction in vein stenosis correlative of later clinical improvement was >41%; IVUS measurement of area stenosis was most predictive (area under the curve, 0.70; P = .004). Venographic measurements of baseline stenosis and stenotic change were not predictive of later improvement. In a 48-patient nonthrombotic subset analysis, IVUS diameter rather than area measurements of baseline stenosis were significantly predictive of clinical success, but indicated a higher optimal threshold of stenosis (>61%) may be necessary. CONCLUSIONS: This study suggests that IVUS shows significant usefulness at predicting when stenting iliofemoral vein stenosis in patients clinical-etiologic-anatomic-pathophysiologic classification of 4-6 will result in significant symptom improvement. Our findings corroborate the conventional >50% cross-sectional area threshold by IVUS as defining a clinically significant iliofemoral stenosis that, when stented, has significant predictive value for symptom improvement. In nonthrombotic patients, however, a threshold of >61% diameter stenosis by IVUS may better predict clinical improvement.

Relationship of Common Vascular Anatomy to Cannulated Catheters.

Superficial veins of the upper extremity are the primary location for placement of peripheral IV catheters (PIVC). It is believed that a significant portion of PIVCs placed may cross or abut valves and branching veins or occlude a significant portion of the vein, limiting the ability to aspirate blood from the PIVC. Two separate clinical investigations using ultrasound were performed to understand the potential interaction between PIVCs and the vein lumen and the venous valves and branches of the superficial veins of the upper extremity. One study with 35 adult volunteers interrogated 210 vein segments where a PIV would likely be placed. A second pediatric study evaluated 35 vein segments central to indwelling PIVCs. The combined data from the two studies showed that over 80% of adult veins and 85% of pediatric veins can properly accommodate 20-gauge and 22-gauge PIVC, respectively. Venous valves are frequent findings, either immediately peripheral to branching veins or at periodic 5 to 7 cm points. Antegrade blood flow can be restricted by a placed PIVC, while retrograde flow is very likely to be restricted by venous valves. Together, these findings may explain the difficulty in reliable aspiration of blood from PIVC.

Venography versus intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction.

OBJECTIVE: The Venogram vs IVUS for Diagnosing Iliac vein Obstruction (VIDIO) trial was designed to compare the diagnostic efficacy of intravascular ultrasound (IVUS) with multiplanar venography for iliofemoral vein obstruction. METHODS: During a 14-month period beginning July 2014, 100 patients with chronic Clinical, Etiologic, Anatomic, and Pathophysiologic clinical class C4 to C6 venous disease and suspected iliofemoral vein obstruction were enrolled at 11 U.S. and 3 European sites. The inferior vena cava and common iliac, external iliac, and common femoral veins were imaged. Venograms were measured for vein diameter; IVUS provided diameter and area measurements. Multiplanar venograms included three views: anteroposterior and 30-degree right and left anterior oblique views. A core laboratory evaluated the deidentified images, determining stenosis severity as the ratio between minimum luminal diameter and reference vessel diameter, minimal luminal area, and reference vessel area. A 50% diameter stenosis by venography and a 50% cross-sectional area reduction by IVUS were considered significant. Analyses assessed change in procedures performed on the basis of imaging method and concordance of measurements between each imaging method. RESULTS: Venography identified stenotic lesions in 51 of 100 subjects, whereas IVUS identified lesions in 81 of 100 subjects. Compared with IVUS, the diameter reduction was on average 11% less for venography (P < .001). The intraclass correlation coefficient was 0.505 for vein diameter stenosis calculated with the two methods. IVUS identified significant lesions not detected with three-view venography in 26.3% of patients. Investigators revised the treatment plan in 57 of 100 cases after IVUS, most often because of failure of venography to detect a significant lesion (41/57 [72%]). IVUS led to an increased number of stents in 13 of 57 subjects (23%) and the avoidance of an endovascular procedure in 3 of 57 subjects (5%). Overall, IVUS imaging changed the treatment plan in 57 patients; 54 patients had stents placed on the basis of IVUS detection of significant iliofemoral vein obstructive lesions not appreciated with venography, whereas 3 patients with significant lesions on venography had no stent placed on the basis of IVUS. CONCLUSIONS: IVUS is more sensitive for assessing treatable iliofemoral vein stenosis compared with multiplanar venography and frequently leads to revised treatment plans and the potential for improved clinical outcome.

Total-contact casting as an adjunct to promote healing of pressure ulcers in amputees.

Partial foot amputations have become increasingly prevalent among long-lived diabetic patients. These patients have lower extremity neuropathy and are prone to ulceration at their amputation site. These ulcers are difficult to heal, and they place a significant financial and resource burden on the healthcare system. We examined the efficacy of total-contact casts (TCC) in diabetic amputees with nonhealing partial foot amputation site neuropathic ulcers. Data were collected retrospectively on all patients with amputations who were treated with a total-contact cast between December 2000 and December 2003. Seventeen patients (13 men, 4 women) with amputation site ulceration were identified. All patients were diagnosed with neuropathy secondary to diabetes and none had wound healing compromised by ischemia. The initial ulcer averaged 1,169 mm(2) with a depth of 2.77 mm. Patients were treated with an average of 7.9 cast applications over 8.4 weeks; 47% (8/17) of ulcers healed, but 29% (5/17) of patients were unable to complete their recommended treatment course secondary to complications from the TCC. Of the patients who were able to complete their treatment course, the healing rate was 66.7% (8/12). The recurrence rate for healed ulcers was 63% (5/8). Partial foot amputations with neuropathic ulcers present a very difficult problem to the vascular surgeon. Patient compliance and underlying medical comorbidities limit the success rate. In patients who can complete a TCC treatment course, good short term results can be expected. However, recurrence rates are high following discontinuation of mechanical TCC off-loading.

Minimally invasive revascularization strategies for chronic lower limb ischemia.

Lower extremity wounds resulting from ischemia are increasingly becoming a common indication for surgical revascularization. Techniques in minimally invasive vascular surgery for the treatment of lower extremity chronic ischemia have expanded rapidly in recent years. The current standard of care with which all new modalities should be compared is the restoration of arterial flow via direct arterial revascularization using the autogenous reversed saphenous vein that can yield limb salvage rates of approximately 95%. Percutaneous transluminal angioplasty and stenting (PTA/S), cryoplasty, catheter-directed atherectomy, laser-assisted PTA/S, drug-eluting stents, and subintimal angioplasty are emerging minimally invasive modalities used for the treatment of lower extremity ischemia. Early success rates using many of these techniques have been promising. The outcomes of randomized controlled trials with long-term follow-ups are needed to make confident remarks about the effectiveness of these techniques.

Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures.

BACKGROUND: The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. METHODS AND RESULTS: EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% (P<0.01) and inversely correlated with patient levels of hemoglobin A1C (P<0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-alpha (TNF-alpha) (P<0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls (P<0.05). CONCLUSIONS: These findings suggest that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events.

Arterial injuries from femoral artery cannulation with port access cardiac surgery.

Although minimally invasive (MI) cardiac surgery reduces blood loss, hospital stay, and recovery time, some MI approaches require femoral arterial cannulation, which introduces a heretofore unknown risk of femoral arterial injury. This study was performed to examine the risk of femoral arterial injury after Port Access MI cardiac surgery (PA-MICS) with femoral cannulation. Data were prospectively obtained on 739 consecutive patients who had PA-MICS with femoral cannulation between June 1996 and April 2000, identifying any patient with new (<30 days postoperative) arterial insufficiency from the cannulation site. Patient characteristics (gender, age, height, weight, body surface area, smoking, peripheral vascular disease, diabetes) and operative variables (cannula size, cross-clamp time) were examined with univariate and multivariate analysis to identify risk factors for arterial injury. Injuries were defined and classified by radiologic and intraoperative assessment, and follow-up was obtained by patient examination and from the medical records. Femoral arterial occlusion (FAC) occurred in 0.68% (5/739) of patients (4 women, 1 man; age range 26-74 years). The risk of femoral injury was higher in women: 1.31% vs 0.23% (p = 0.07). One patient had intraoperative limb ischemia from iliofemoral dissection and was treated by axillopopliteal bypass. Four patients presented postoperatively with claudication. Three of these had iliofemoral arterial occlusion or localized iliofemoral dissection and were treated with iliofemoral bypass, and 1 patient had localized femoral artery stenosis treated by angioplasty. With a mean follow-up of 17.8 months (range 13-26 months) limb salvage was achieved in all patients. Secondary or tertiary interventions were required in 40% (2/5), both in patients with iliofemoral occlusion, and 1 patient (20% of femoral injuries, 0.135% of overall series) has chronic graft occlusion and long-term claudication. The risk of arterial injury after femoral arterial cannulation and perfusion for Port Access surgery was low (0.68%). This risk is increased in women and is unpredictable. Initial vascular repair has a significant failure rate, and secondary interventions are often necessary. Although the femoral cannulation and perfusion technique is safe overall, the risk must be clearly recognized.