Three-Year Outcomes of the Abre Venous Self-Expanding Stent System in Patients with Symptomatic Iliofemoral Venous Outflow Obstruction.

PURPOSE: To report 36-month outcomes and subgroup analysis of the ABRE study evaluating the safety and effectiveness of the Abre venous self-expanding stent system for the treatment of symptomatic iliofemoral venous outflow obstruction disease. METHODS: The ABRE study was a prospective, multicenter, nonrandomized study that enrolled and implanted Abre venous stents in 200 participants (mean age 51.5 years [SD ± 15.9], 66.5% women) with symptomatic iliofemoral venous outflow obstruction at 24 global sites. Outcomes assessed through 36 months included patency, major adverse events, stent migration, stent fracture, and quality-of-life changes. Adverse events and imaging studies were adjudicated by independent clinical events committee and core laboratories, respectively. RESULTS: Primary, primary-assisted, and secondary patency through 36 months by Kaplan-Meier estimates were 81.6%, 84.8%, and 86.3%, respectively. The cumulative incidence of major adverse events through 36 months was 10.2%, mainly driven by 12 thrombosis events. Subgroup analyses demonstrated a primary patency of 76.5% in the acute deep vein thrombosis group, 70.4% in the postthrombotic syndrome group, and 97.1% in the nonthrombotic iliac vein lesion group through 36 months. The overall mean lesion length was 112.4 mm (SD ± 66.1). There were no stent fractures or migrations in this study. Quality of life and venous functional assessments demonstrated significant improvements from baseline to 36 months across all patient subsets. CONCLUSIONS: Results from the ABRE study demonstrated sustained patency with a good safety profile after implantation of a dedicated venous stent in patients with symptomatic iliofemoral venous outflow obstruction disease.

Objective Performance Goals Based on a Systematic Review and Meta-Analysis of Clinical Outcomes for Bare-Metal Stents and Percutaneous Transluminal Angioplasty for Hemodialysis-Related Central Venous Obstruction.

PURPOSE: To use safety and efficacy outcomes following treatment with percutaneous transluminal angioplasty (PTA) and/or stent placement for thoracic central venous obstruction in hemodialysis-dependent patients to establish objective performance goals (OPGs). METHODS: A systematic literature review and meta-analysis were conducted for articles published between January 1, 2000, and August 31, 2021. Efficacy outcomes included primary patency rates at 6 and 12 months, and safety outcomes included adverse events (AEs) categorized as access loss, procedure-related AEs, and serious AEs (SAEs). OPGs were derived from the upper and lower bounds of the 95% confidence intervals for primary patency and SAE rates. RESULTS: Of 66 articles reviewed, 17 met the inclusion criteria (PTA, n = 4; stent placement, n = 5; PTA/stent, n = 8). The 6- and 12-month primary patency rates for PTA were 50.9% and 36.7%, respectively. Based on these findings, the proposed 6- and 12-month primary patency OPGs identifying superiority against PTA were 66.5% and 52.6%, respectively, and those for noninferiority were 39.0% and 25.7%, respectively. For stent placement, the 6- and 12-month primary patency rates were 69.7% and 47.9%, respectively. The proposed 6- and 12-month primary patency OPGs identifying superiority were 82.1% and 64.1%, respectively, and those for noninferiority were 59.3% and 35.8%, respectively. SAE rates for PTA and stent placement were 3.8% and 8.1%, respectively. Proposed safety OPGs for noninferiority versus superiority for PTA and stent placement were 10.1% versus 1.4% and 13.6% versus 4.8%, respectively. CONCLUSION: The OPGs derived from real-world studies of PTA and stent placement may serve as a benchmark for future interventions indicated for this patient population.

Editor's Choice - Quality of Life after Stenting for Iliofemoral Venous Obstruction: A Randomised Controlled Trial with One Year Follow Up.

OBJECTIVE: Deep venous obstruction (DVO) is a great burden on the healthcare system and patients' quality of life (QoL). Case series show stenting is safe and effective, however most studies lack control groups and QoL changes have not been compared with conventional treatment. The aim was to assess the difference in QoL changes from baseline to 12 months between stent and conventionally treated patients with DVO. METHODS: Subjects > 18 years old with DVO due to post-thrombotic (PTS) or non-thrombotic iliac vein lesions (NIVLs) in a tertiary hospital were prospectively randomised to best medical therapy (BMT) or stent placement with BMT in a ratio 2:1, stratified for PTS or NIVL. The primary outcome was the between group difference in VEINES-QoL scores change from baseline to 12 months after treatment. Secondary outcomes included the difference in score changes for EuroQoL 5-Dimension 5 Level (EQ-5D-5L), Pain Disability Index (PDI), Venous Clinical Severity Score (VCSS), and the Villalta score. RESULTS: After three years, the inclusion rate dropped to almost zero, therefore the study had to be stopped. Sixty-three patients were randomised to either the stent (n = 42) or control group (n = 21). Overall, 50 patients had available data for primary outcome analysis. The adjusted mean difference between 12 month scores for VEINES-QoL and VEINES-Sym was 8.07 (95% CI 3.04 - 13.09) and 5.99 (95% CI 0.75 - 11.24) (p = .026), respectively, in favour of the stent group. The differences were significant, but a pre-defined meaningful 14 point improvement in QoL was not reached. The mean difference between 12 month scores for VCSS was -2.93 (95% CI -5.71 - 0.16, p = .040), -11.83 (95% CI -20.81 - 2.86, p = .011) for PDI, 0.015 (95% CI -0.12 - 0.15, p = .82) for the EQ-5D index, and -2.99 (95% CI -7.28 - 1.30, p = .17) for the Villalta score. CONCLUSION: Symptomatic patients with DVO who received dedicated venous stents had significantly higher VEINES-QoL/Sym scores at 12 months compared with the control group, but the between group difference was lower than the pre-specified clinically relevant QoL difference of at least 14 points. STUDY REGISTRATION NUMBER: NCT03026049.

Temsirolimus Adventitial Delivery to Improve ANGiographic Outcomes Below the Knee.

BACKGROUND: Current endovascular treatments of below the knee (BTK) popliteal or tibial/peroneal arteries including investigational drug-coated balloons have limited long-term efficacy. OBJECTIVES: This Phase 2 trial assessed the feasibility of adventitial deposition of temsirolimus to reduce neointimal hyperplasia and clinically relevant target lesion failure (CR-TLF) 6 months after BTK arterial revascularization. METHODS: This prospective, multicenter, double-blinded, comparative, dose-escalation trial enrolled 61 patients with Rutherford 3 to 5 symptoms undergoing endovascular revascularization of ≥1 angiographically significant BTK lesions. Perivascular infusion after completion of arterial revascularization was randomized into control (saline) vs low-dose (0.1 mg/mL) temsirolimus groups for the first 30 patients. In the second part of the trial, patients were randomized to control versus high-dose (0.4 mg/mL) temsirolimus groups. Primary and secondary efficacy endpoints were target lesion (TL) transverse-view vessel area loss percentage (TVAL%) and CR-TLF at 6 months, respectively. CR-TLF was defined as a composite of ischemia-driven major amputation of the target limb, clinically driven target lesion revascularization (CD-TLR), and clinically relevant TL occlusion. The primary safety endpoint was freedom from major adverse limb events or perioperative death (MALE+POD) at 30 days. RESULTS: There was no discernable difference in effect between temsirolimus doses; therefore, the low- and high-dose cohorts were pooled for the analyses. The principal analysis on the per protocol (PP) group of 53 patients revealed superior primary efficacy of the treatment arm, with reduction in TVAL% of 13.9% absolute (37.3% relative) and the rate of CR-TLF reduced by 27.1% absolute (51.3% relative), at 6 months. Subgroup analysis of all Trans-Atlantic Inter-Society Consensus (TASC) B to D lesions (N=36) revealed TVAL% reduction of 22.3% absolute (48.3% relative) and the rate of CR-TLF reduced by 39.2% absolute (56.6% relative). Freedom from 30-day MALE+POD was 100% in all groups. CONCLUSIONS: This hypothesis-generating trial suggests that adventitial infusion of temsirolimus in BTK arteries improves TVAL% and CR-TLF with no adverse safety signals through 6 months, supporting the move to a Phase 3 trial. CLINICAL IMPACT: There remain gaps in the endovascular treatment of patients with atherosclerotic lesions of below-the-knee (BTK) arteries. The TANGO trial evaluated the use of sub-adventitial temsirolimus with the Bullfrog micro-infusion device during BTK interventions. The therapy was safe and effective. Compared with controls, vessel lumen area patency was improved, and target lesion failure was less frequent. The effects were most appreciable in subjects with higher baseline TASC lesions (B, C, or D). Sub-adventitial temsirolimus offers the potential to improve the results of BTK interventions in this challenging patient population.

Single-Session Treatment of Patients with Symptomatic Iliocaval and Iliofemoral Deep Vein Thrombosis: Technical Results of a Prospective Pilot Study.

PURPOSE: To investigate the short-term results of single-session treatment of iliocaval and iliofemoral DVT using a single thrombectomy device. MATERIALS AND METHODS: This prospective pilot study analyzed patients with acute iliocaval or iliofemoral DVT treated in a single session using the JETi thrombectomy system. All analyses were performed on an intention-to-treat basis. The cohort consisted of 53 limbs in 47 patients (27 women), with a mean age of 57 years (range, 16-88 years). The primary safety and efficacy endpoints were freedom from major adverse events (MAEs) and reestablishment of unobstructed flow in a single session, respectively. RESULTS: The mean duration of symptoms was 8.5 days ± SD 9.2, with 10 patients (11 limbs, 21.3%) presenting with a symptom duration of >14 days. Twelve (25.5%) patients had thrombosis of the inferior vena cava and the iliofemoral segments. During the index procedure, unobstructed flow was reestablished in 47 of 53 (88.6%) limbs in 41 of 47 (87.2%) patients (primary endpoint) with no MAEs through 30 days. Overall, unobstructed flow was restored in 50 of 53 (94.3%) limbs and in 44 of 47 (93.6%) patients. CONCLUSIONS: Successful single-session treatment of patients with acute iliocaval and iliofemoral DVT is feasible with a high rate of efficacy and a low rate of adverse events. Such patients may be treated on an outpatient basis.

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.

A Real-Time Blood Flow Measurement Device for Patients with Peripheral Artery Disease.

PURPOSE: To evaluate the feasibility of a new optical device that measures peripheral blood flow as a diagnostic and monitoring tool for patients with peripheral artery disease (PAD). MATERIALS AND METHODS: In this prospective study, 167 limbs of 90 patients (mean age, 76 y; 53% men) with suspected PAD were evaluated with the FlowMet device, which uses a new type of dynamic light-scattering technology to assess blood flow in real time. Measurements of magnitude and phasicity of blood flow were combined into a single-value flow-waveform score and compared vs ankle-brachial index (ABI), toe-brachial index (TBI), and clinical presentation of patients per Rutherford category (RC). Receiver operating characteristic curves were constructed to predict RC. Area under the curve (AUC), sensitivity, and specificity were compared among flow-waveform score, ABI, and TBI. RESULTS: Qualitatively, the FlowMet waveforms were analogous to Doppler velocity measurements, and degradation of waveform phasicity and amplitude were observed with increasing PAD severity. Quantitatively, the flow, waveform, and composite flow-waveform scores decreased significantly with decreasing TBI. In predicting RC ≥ 4, the flow-waveform score (AUC = 0.83) showed a linear decrease with worsening patient symptoms and power comparable to that of TBI (AUC = 0.82) and better than that of ABI (AUC = 0.71). Optimal sensitivity and specificity pairs were found to be 56%/83%, 72%/81%, and 89%/74% for ABI, TBI, and flow-waveform score, respectively. CONCLUSIONS: The technology tested in this pilot study showed a high predictive value for diagnosis of critical limb ischemia. The device showed promise as a diagnostic tool capable of providing clinical feedback in real time.

Effect of Stent Strut Interval on Neointima Formation After Venous Stenting in an Ovine Model.

OBJECTIVE: The impact of stent design on venous patency is not well studied. The purpose of this study was to investigate the effect of stent material burden on endothelial coverage of stented venous segments, which may contribute to vessel healing and patency. METHODS: Segmented self expanding bare nitinol stents (18 × 50 mm) comprising 5 mm long attached metallic rings separated by 2, 5, or 8 mm gaps were implanted in the inferior vena cava (IVC) of 10 sheep. These stents were designed and manufactured for the purposes of this study. At six, 12, and 24 weeks after implantation the animals were euthanised and the stented vessels harvested for histomorphometric analysis. Three sections from the metallic part as well as the gaps between the struts were reviewed for quantification of endothelialisation after six, 12, and 24 weeks. The intimal thickness over and between the stent struts was measured. The endothelialisation score (graded from 1 for complete luminal endothelialisation to 5 for absence of endothelial cells) was determined. RESULTS: All stents were successfully deployed and all 10 sheep survived until the time of harvesting. Macroscopic inspection after 24 weeks showed only partial endothelialisation over stents with 2 mm and 5 mm skipped segments, whereas the stents with 8 mm skipped segments were totally incorporated into the vein wall. After 24 weeks, the mean (SD) neointimal thicknesses over stent struts with 2 mm, 5 mm, and 8 mm skipped segments were 254.0 (51.6), 182.2 (98.1), and 194.6 (101.1) µm, respectively. Comparison of endothelialisation scores of stents over time showed statistically significantly better endothelialisation over stents with 8 mm gaps after 12 and 24 weeks. CONCLUSION: Stent designs providing structural support to veins with larger gaps between the scaffold material appear to lead to faster and more complete endothelialisation as well as a thinner intimal layer.

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.

Outcome of stenting in central venous obstruction of benign etiology.

Background: The aim of this study is to evaluate long term outcome in patients treated for benign superior vena cava (SVC) syndrome by endovascular techniques. Patients and methods: Between 2015 and 2018, 62 patients suffering from central venous obstruction of benign etiology underwent balloon angioplasty with stent placement for venous obstruction in our department. Patency was assessed clinically, using duplex ultrasound in all patients or with CT-phlebography in selected cases. Results: Median age was 60 years (23-83), forty-one patients (66%) had central venous devices. Swelling of the arm and face were the main symptoms (71%). During the median follow up of 22 months (9-38), cumulative primary patency was 71% after venous stenting. The cumulative assisted primary and the secondary patency were 85% and 92%, respectively. Conclusions: Recanalization and stenting of central vein obstruction has turned out to be the technique of reference and provides satisfactory mid-term patency rates. After adjusting for the risk factors, presence of AV-fistula remained a significant risk factor for recurrent stenosis or loss of patency after intervention.

Mortality Assessment of Paclitaxel-Coated Balloons: Patient-Level Meta-Analysis of the ILLUMENATE Clinical Program at 3 Years.

BACKGROUND: A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients. METHODS: We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling. RESULTS: Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23). CONCLUSIONS: The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.

Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis.

BACKGROUND: The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) previously reported that pharmacomechanical catheter-directed thrombolysis (PCDT) did not prevent postthrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis. In the current analysis, we examine the effect of PCDT in ATTRACT patients with iliofemoral deep vein thrombosis. METHODS: Within a large multicenter randomized trial, 391 patients with acute deep vein thrombosis involving the iliac or common femoral veins were randomized to PCDT with anticoagulation versus anticoagulation alone (No-PCDT) and were followed for 24 months to compare short-term and long-term outcomes. RESULTS: Between 6 and 24 months, there was no difference in the occurrence of PTS (Villalta scale ≥5 or ulcer: 49% PCDT versus 51% No-PCDT; risk ratio, 0.95; 95% CI, 0.78-1.15; P=0.59). PCDT led to reduced PTS severity as shown by lower mean Villalta and Venous Clinical Severity Scores ( P<0.01 for comparisons at 6, 12, 18, and 24 months), and fewer patients with moderate-or-severe PTS (Villalta scale ≥10 or ulcer: 18% versus 28%; risk ratio, 0.65; 95% CI, 0.45-0.94; P=0.021) or severe PTS (Villalta scale ≥15 or ulcer: 8.7% versus 15%; risk ratio, 0.57; 95% CI, 0.32-1.01; P=0.048; and Venous Clinical Severity Score ≥8: 6.6% versus 14%; risk ratio, 0.46; 95% CI, 0.24-0.87; P=0.013). From baseline, PCDT led to greater reduction in leg pain and swelling ( P<0.01 for comparisons at 10 and 30 days) and greater improvement in venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life unit difference 5.6 through 24 months, P=0.029), but no difference in generic quality of life ( P>0.2 for comparisons of SF-36 mental and physical component summary scores through 24 months). In patients having PCDT versus No-PCDT, major bleeding within 10 days occurred in 1.5% versus 0.5% ( P=0.32), and recurrent venous thromboembolism over 24 months was observed in 13% versus 9.2% ( P=0.21). CONCLUSIONS: In patients with acute iliofemoral deep vein thrombosis, PCDT did not influence the occurrence of PTS or recurrent venous thromboembolism. However, PCDT significantly reduced early leg symptoms and, over 24 months, reduced PTS severity scores, reduced the proportion of patients who developed moderate-or-severe PTS, and resulted in greater improvement in venous disease-specific quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00790335.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

Sex-Related Differences in the Long-Term Outcomes of Patients with Femoropopliteal Arterial Disease Treated with the IN.PACT Drug-Coated Balloon in the IN.PACT SFA Randomized Controlled Trial: A Post Hoc Analysis.

PURPOSE: To evaluate sex-related disparities in long-term outcomes of patients with peripheral artery disease (PAD) treated with IN.PACT drug-coated balloon (DCB) or percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: A post hoc analysis of the IN.PACT SFA trial was performed. Participants with Rutherford Clinical Classification 2-4 PAD and femoropopliteal artery lesions up to 18 cm long were randomly assigned to treatment with DCB (n = 220) or PTA (n = 111). Effectiveness outcomes were evaluated, including 36-month primary patency (freedom from binary restenosis and freedom from clinically driven [CD] target lesion revascularization [TLR]). RESULTS: In the DCB group, women were significantly older (69.4 y ± 9.9) than men (66.4 y ± 9.1; P = .025). Mean reference vessel diameter (RVD) was significantly smaller in women (4.4 mm ± 0.68) compared with men (4.8 mm ± 0.89, P < .001). Primary patency was 65.4% in women and 71.8% in men (P = .302). Freedom from CD-TLR was 81.1% in women and 86.4% in men (P = .285). Women treated with PTA were older (70.4 y ± 8.3) than men (66.9 y ± 9.5; P = .063). Mean RVD was significantly smaller in women (4.2 mm ± 0.77) compared with men (4.9 mm ± 0.77, P < .001). Primary patency was 42.3% in women and 46.7% in men (P = .551). Freedom from CD-TLR was 59.4% in women and 75.5% in men (P = .109). No significant differences were noted in safety and mortality outcomes. CONCLUSIONS: In both groups, women were older and had smaller vessels. Particularly in the PTA group, women had worse clinical outcomes, though not reaching statistical significance. Further evaluation is necessary to understand the disparate nature of disease progression and outcomes following endovascular treatment in women compared with men.

Correlation between Post-Procedure Residual Thrombus and Clinical Outcome in Deep Vein Thrombosis Patients Receiving Pharmacomechanical Thrombolysis in a Multicenter Randomized Trial.

PURPOSE: To evaluate relationships between immediate venographic results and clinical outcomes of pharmacomechanical catheter-directed thrombolysis (PCDT). MATERIALS AND METHODS: Venograms from 317 patients with acute proximal deep vein thrombosis (DVT) who received PCDT in a multicenter randomized trial were reviewed. Quantitative thrombus resolution was assessed by independent readers using a modified Marder scale. The physician operators recorded their visual assessments of thrombus regression and venous flow. These immediate post-procedure results were correlated with patient outcomes at 1, 12, and 24 months. RESULTS: PCDT produced substantial thrombus removal (P < .001 for pre-PCDT vs. post-PCDT thrombus scores in all segments). At procedure end, spontaneous venous flow was present in 99% of iliofemoral venous segments and in 89% of femoral-popliteal venous segments. For the overall proximal DVT population, and for the femoral-popliteal DVT subgroup, post-PCDT thrombus volume did not correlate with 1-month or 24-month outcomes. For the iliofemoral DVT subgroup, over 1 and 24 months, symptom severity scores were higher (worse), and venous disease-specific quality of life (QOL) scores were lower (worse) in patients with greater post-PCDT thrombus volume, with the difference reaching statistical significance for the 24-month Villalta post-thrombotic syndrome (PTS) severity score (P = .0098). Post-PCDT thrombus volume did not correlate with 12-month valvular reflux. CONCLUSIONS: PCDT successfully removes thrombus in acute proximal DVT. However, the residual thrombus burden at procedure end does not correlate with the occurrence of PTS during the subsequent 24 months. In iliofemoral DVT, lower residual thrombus burden correlates with reduced PTS severity and possibly also with improved venous QOL and fewer early symptoms.

Iliocaval Skip Stent Reconstruction Technique for Chronic Bilateral Iliocaval Venous Occlusion.

PURPOSE: To report safety and efficacy of a skip stent technique using nitinol stents in patients with chronic bilateral iliocaval venous occlusions. MATERIALS AND METHODS: A retrospective analysis of 48 consecutive patients (32 men; mean age, 40.7 years; age range, 18-68 years) with chronic bilateral iliocaval obstructions treated using a nonoverlapping stent technique was conducted at a single center. None of the patients had May-Thurner syndrome. Iliocaval confluence was treated by deploying a nitinol stent in inferior vena cava (IVC) and a nitinol stent in each common iliac vein close to the caval stent. Patency of stents was assessed by duplex US at 2 weeks, 3 months, and 6 months and yearly thereafter. RESULTS: Recanalization and stent reconstruction was technically successful in 47 (98%) patients. The sinus-XL venous stent was used to treat IVC (95 [100%]). Common iliac and external iliac veins were treated with sinus-Venous and VENOVO stents (80 [83%] and 16 [17%] limbs, respectively). External iliac and common femoral veins were treated with sinus-Venous and VENOVO stents (83 [92%] and 7 [18%] limbs, respectively). Early thrombosis (< 30 days) of the iliac vein with stent occurred in 2 limbs. Cumulative primary, assisted primary, and secondary patency rates at 30 months were 74%, 83%, and 97%. CONCLUSIONS: Findings of this study suggest that leaving a skipped lesion at the level of iliocaval confluence may not adversely affect stent patency. Patency rates were comparable with other reported techniques of stent reconstruction at the level of iliocaval confluence.

Total IN.PACT drug-coated balloon initiative reporting pooled imaging and propensity-matched cohorts.

OBJECTIVE: Randomized controlled trials have shown that drug-coated balloons (DCBs) provide superior results compared with percutaneous transluminal angioplasty (PTA) for the treatment of femoropopliteal artery disease. However, these trials have generally included short lesions, few occlusions, and small sample sizes. The present study was an individual-level pooled analysis of duplex ultrasonography (DUS) core laboratory-adjudicated and clinical events committee-adjudicated IN.PACT Admiral DCB subjects across two randomized controlled trials and two single-arm prospective studies to characterize the safety and effectiveness of DCB compared with PTA. METHODS: The subjects were treated with DCB (n = 926) or PTA (n = 143). The end points through 12 months included DUS core laboratory-adjudicated primary patency and clinically driven target lesion revascularization (CD-TLR) using Kaplan-Meier estimates and primary safety using proportions. A propensity-matched analysis of DCB (n = 466) to PTA (n = 136) was conducted to address confounders. RESULTS: At 12 months, DCB compared with PTA had significantly greater primary patency (88.8% vs 53.9%; P < .001), freedom from CD-TLR (94.3% vs 80.2%; P < .001), and better primary safety composite end point (94.1% vs 78.0%; P < .001). After propensity-matched analysis, DCB remained superior to PTA at 12 months for primary patency (90.5% vs 53.8%; P < .001), freedom from CD-TLR (96.9% vs 80.7%; P < .001), and the primary safety composite end point (96.3% vs 78.4%; P < .001). Across multiple prespecified subgroup analyses, including provisional stenting, DCB remained persistently superior to PTA. CONCLUSIONS: In the largest, DUS core laboratory-adjudicated, multiethnic, pooled DCB series to date, the IN.PACT Admiral DCB demonstrated significantly greater primary patency, freedom from CD-TLR, and better composite safety at 12 months compared with PTA.

Relationships between the use of pharmacomechanical catheter-directed thrombolysis, sonographic findings, and clinical outcomes in patients with acute proximal DVT: Results from the ATTRACT Multicenter Randomized Trial.

Few studies have documented relationships between endovascular therapy, duplex ultrasonography (DUS), post-thrombotic syndrome (PTS), and quality of life (QOL). The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial randomized 692 patients with acute proximal deep vein thrombosis (DVT) to receive anticoagulation or anticoagulation plus pharmacomechanical catheter-directed thrombolysis (PCDT). Compression DUS was obtained at baseline, 1 month and 12 months. Reflux DUS was obtained at 12 months in a subset of 126 patients. Clinical outcomes were collected over 24 months. At 1 month, patients who received PCDT had less residual thrombus compared to Control patients, evidenced by non-compressible common femoral vein (CFV) (21% vs 35%, p < 0.0001), femoral vein (51% vs 70%, p < 0.0001), and popliteal vein (61% vs 74%, p < 0.0001). At 12 months, in the ultrasound substudy, valvular reflux prevalence was similar between groups (85% vs 91%, p = 0.35). CFV non-compressibility at 1 month was associated with higher rates of any PTS (61% vs 46%, p < 0.001), a higher incidence of moderate-or-severe PTS (30% vs 19%, p = 0.003), and worse QOL (difference 8.2 VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study on Quality of Life) points; p = 0.004) at 24 months. Valvular reflux at 12 months was associated with moderate-or-severe PTS at 24 months (30% vs 0%, p = 0.01). In summary, PCDT results in less residual thrombus but does not reduce venous valvular reflux. CFV non-compressibility at 1 month is associated with more PTS, more severe PTS, and worse QOL at 24 months. Valvular reflux may predispose to moderate-or-severe PTS. ClinicalTrials.gov Identifier NCT00790335.

SAVI SCOUT as a Novel Localization and Surgical Navigation System for More Accurate Localization and Resection of Pulmonary Nodules.

Background. Current techniques for localization and resection of lung nodules carry many intraoperative challenges for surgeons. This article proposes a new localization method for diagnosis and treatment of pulmonary nodules, which provides a navigational system for more accurate lung resection. Methods. We report the case of a 77-year-old female with a pulmonary nodule of the right lower lobe. A nonradioactive localization technology, known as SAVI SCOUT (Cianna Medical Inc, Aliso Viejo, CA), was placed by interventional radiology under computed tomography guidance preoperatively. Using the SCOUT Wire-Free Radar Localization System, the pulmonary nodule was robotically localized and resected. SCOUT removal was confirmed using the Trident Specimen Radiology System. The efficacy of this procedure was evaluated in terms of ease of use and procedure time by interventional radiology, surgical resection accuracy, diagnostic accuracy, simplicity, and ease to implement this technology in an existing hospital. Results. The SCOUT system allowed for the first reported case of successful SCOUT placement in lung tissue, targeted the pulmonary nodule intraoperatively, and facilitated accurate lung resection. Conclusions. The SCOUT system shows promising advancements in the ability to eliminate many challenges currently seen with lung nodule localization and resection.