Clinical, Functional, and Quality of Life Outcomes after Computer Assisted Vacuum Thrombectomy for Pulmonary Embolism: Interim Analysis of the STRIKE-PE Study.

PURPOSE: To report 90-day results from the first interim analysis of the STRIKE-PE study, which is evaluating safety, effectiveness, and functional and quality of life (QoL) outcomes of Computer Assisted Vacuum Thrombectomy (CAVT) with the Indigo Aspiration System for the treatment of acute pulmonary embolism (PE). METHODS: STRIKE-PE is a prospective, international, multicenter study that will enroll 600 adult patients with acute PE of ≤14 days and a right ventricle/left ventricle (RV/LV) ratio of ≥0.9 who receive first-line endovascular treatment with CAVT. Primary endpoints are change in RV/LV ratio and incidence of composite major adverse events (MAEs) within 48 hours. Secondary endpoints include functional and QoL assessments. RESULTS: The first 150 consecutive patients were treated with Lightning 12 CAVT. Mean age was 61.3 years, 54.7% were men, 94.7% presented with intermediate-risk PE, and 5.3% presented with high-risk PE. Median thrombectomy and procedure times were 33.5 minutes and 70 minutes, respectively, resulting in a mean reduction in systolic pulmonary artery pressure of 16.3% (P < .001). Mean RV/LV ratio decreased from 1.39 before thrombectomy to 1.01 at 48 hours, a 25.7% reduction (P < .001). Four patients (2.7%) experienced a composite MAE within 48 hours. At 90-day follow-up, patients exhibited statistically significant improvements in the Borg dyspnea scale and QoL measures, and the NYHA class distribution returned to that reported before the index PE. CONCLUSION: These interim results demonstrate a rapid reduction in RV/LV ratio, achieved with a fast thrombectomy time while maintaining safety. This is accompanied by improvements in 90-day functional and QoL outcomes.

Twelve Years of Drug Prioritization to Help Accelerate Disease Modification Trials in Parkinson's Disease: The International Linked Clinical Trials Initiative.

In 2011, the UK medical research charity Cure Parkinson's set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson's disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.

Trends in Percutaneous Device Use for the Treatment of Venous Thromboembolism Over Time in the PINC AI Healthcare Database and the National Inpatient Sample.

The number of different methods of reperfusion therapy to treat venous thromboembolism (VTE) has increased substantially. Nevertheless, investigation of data representativeness and device-level use in administrative databases has been limited. Using the National Inpatient Sample (NIS) and the PINC AI Healthcare Database (PHD), all hospital encounters with a diagnosis code of VTE were identified between January 1, 2016 and December 31, 2020. Patient demographics and trends in treatment modalities were evaluated over time. An algorithm was developed to identify specific devices used for VTE treatment in the PHD cohort. A total of 145,870 patients with VTE treated with reperfusion therapy were identified in the NIS (pulmonary embolism [PE] 88,725, isolated deep vein thrombosis [iDVT] 57,145) and 39,311 in the PHD (PE 25,383, iDVT 13,928). Patient demographics were qualitatively similar in the NIS and PHD. Over time, there was a significant increase in the use of mechanical thrombectomy in the PE and iDVT populations (p <0.05 in both databases), with catheter-directed thrombolysis use plateauing in PE (p = 0.83 and p = 0.14 in NIS and PHD, respectively) and significantly decreasing for the iDVT population (p <0.05 in both databases). In the PHD cohort, specific reperfusion devices were identified in 14,105 patients (PE 9,098, iDVT 5,007). In conclusion, the use of mechanical thrombectomy for the treatment of VTE has increased over time, whereas the rates of catheter-directed thrombolysis therapy have remained stagnant or decreased. Further research is needed to understand the uptake of these treatment modalities and the unique abilities of the PHD to study specific device therapy in the VTE population.

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.

Comparison of anticoagulation vs mechanical thrombectomy for the treatment of iliofemoral deep vein thrombosis.

OBJECTIVE: To compare the comparative effects of treatment with contemporary mechanical thrombectomy (MT) or anticoagulation (AC) on Villalta scores and post-thrombotic syndrome (PTS) incidence through 12 months in iliofemoral deep vein thrombosis (DVT). METHODS: Patients with DVT in the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) randomized trial and the ClotTriever Outcomes (CLOUT) registry were included in this analysis. Both studies evaluated the effects of thrombus removal on the incidence of PTS. Patients with bilateral DVT, isolated femoral-popliteal DVT, symptom duration of >4 weeks, or incomplete case data for matching covariates were excluded. Propensity scores were used to match patients 1:1 who received AC (from ATTRACT) with those treated with mechanical thrombectomy (from CLOUT) using nearest neighbor matching on nine baseline covariates, including age, body mass index, leg treated, provoked DVT, prior venous thromboembolism, race, sex, Villalta score, and symptom duration. Clinical outcomes, including Villalta score and PTS, were assessed. Logistic regression was used to estimate the likelihood of developing PTS at 12 months. RESULTS: A total of 164 pairs were matched, with no significant differences in baseline characteristics after matching. There were fewer patients with any PTS at 6 months (19% vs 46%; P < .001) and 12 months (17% vs 38%; P < .001) in the MT treatment group. Modeling revealed that, after adjusting for baseline Villalta scores, patients treated with AC had significantly higher odds of developing any PTS (odds ratio, 3.1; 95% confidence interval, 1.5-6.2; P = .002) or moderate to severe PTS (odds ratio, 3.1; 95% confidence interval, 1.1-8.4; P = .027) at 12 months compared with those treated with MT. Mean Villalta scores were lower through 12 months among those receiving MT vs AC (3.3 vs 6.3 at 30 days, 2.5 vs 5.5 at 6 months, and 2.6 vs 4.9 at 12 months; P < .001 for all). CONCLUSIONS: MT treatment of iliofemoral DVT was associated with significantly lower Villalta scores and a lower incidence of PTS through 12 months compared with treatment using AC. Results from currently enrolling clinical trials will further clarify the role of these therapies in the prevention of PTS after an acute DVT event.

Safety and efficacy of mechanical aspiration thrombectomy for patients with acute lower extremity ischemia.

OBJECTIVE: Acute limb ischemia (ALI) is associated with high rates of amputation and consequent morbidity and mortality. The objective of this study is to report on the safety and efficacy of aspiration thrombectomy using the Indigo Aspiration System in patients with lower extremity (LE) ALI. METHODS: The STRIDE study was an international, multicenter, prospective, study that enrolled 119 participants presenting with LE-ALI. Patients were treated firstline with mechanical thrombectomy using the Indigo Aspiration System, before stenting or angioplasty, or other therapies as determined by treating physician. The primary end point was target limb salvage at 30 days after the procedure. Secondary end points within 30 days included technical success, defined as core laboratory-adjudicated Thrombolysis in Myocardial Infarction (TIMI) 2/3 flow rate immediately after the procedure, changes in modified Society for Vascular Surgery runoff score, improvement of Rutherford classification compared with before the procedure, patency, rate of device-related serious adverse events, and major periprocedural bleeding. Secondary end points that will be evaluated at 12 months include target limb salvage and mortality. RESULTS: Of the 119 participants enrolled at 16 sites, the mean age was 66.3 years (46.2% female). At baseline (n = 119), ischemic severity was classified as Rutherford I in 10.9%, Rutherford IIa in 54.6%, and Rutherford IIb in 34.5%. The mean target thrombus length was 125.7 ± 124.7 mm. Before the procedure, 93.0% (of patients 107/115) had no flow (TIMI 0) through the target lesion. The target limb salvage rate at 30 days was 98.2% (109/111). The rate of periprocedural major bleed was 4.2% (5/119) and device-related serious adverse events was 0.8% (1/119). Restoration of flow (TIMI 2/3) was achieved in 96.3% of patients (105/109) immediately after the procedure. The median improvement in the modified Society for Vascular Surgery runoff score (before vs after the procedure) was 6.0 (interquartile range, 0.0-11.0). Rutherford classifications also improved after discharge in 86.5% of patients (83/96), as compared with preprocedural scores. Patency at 30 days was achieved in 89.4% of patients (101/113). CONCLUSIONS: In the STRIDE (A Study of Patients with Lower Extremity Acute Limb Ischemia to Remove Thrombus with the Indigo Aspiration System) study, aspiration thrombectomy with the Indigo System provided a safe and effective endovascular treatment for patients with LE-ALI, resulting in a high rate (98.2%) of successful limb salvage at 30 days, with few periprocedural complications.

Mechanical Thrombectomy vs. Pharmacomechanical Catheter Directed Thrombolysis for the Treatment of Iliofemoral Deep Vein Thrombosis: A Propensity Score Matched Exploratory Analysis of 12 Month Clinical Outcomes.

OBJECTIVE: To compare thrombus removal and residual venous symptoms and signs of disease following interventional treatment of iliofemoral deep vein thrombosis (DVT) with mechanical thrombectomy (MT) and pharmacomechanical catheter directed thrombolysis (PCDT). METHODS: Retrospective cohort analysis of propensity score matched subgroups from the multicentre prospective MT ClotTriever Outcomes registry and the PCDT arm of the randomised Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter Directed Thrombolysis trial. Patients with bilateral DVT, symptom duration greater than four weeks, isolated femoral-popliteal disease, or incomplete case data were excluded. Patients with iliofemoral DVT were propensity score matched (1:1) on 10 baseline covariables, including race, sex, age, body mass index, leg treated, prior thromboembolism, Marder score, symptom duration, provoked deep vein thrombosis status, and Villalta score. Reduction in post-procedure thrombus burden (i.e., Marder scores), assessment of venous symptoms and signs (i.e., Villalta scores) at 12 months, and healthcare resource utilisation were compared between subgroups. RESULTS: Propensity score matching resulted in 130 patient pairs with no significant differences in baseline characteristics between the MT and PCDT groups. MT was associated with a greater reduction in Marder scores (91.0% vs. 67.7%, p < .001), and a greater proportion of patients at 12 months with no post-thrombotic syndrome (83.1% vs. 63.6%, p = .007) compared with matched patients receiving PCDT. No differences in rates of adjunctive stenting or venoplasty were identified (p = .27). Higher rates of single session treatment were seen with MT (97.7% vs. 26.9%, p < .001), which also showed shorter mean post-procedure hospital stays (1.81 vs. 3.46 overnights, p < .001), and less post-procedure intensive care unit utilisation (2.3% vs. 52.8%, p < .001). CONCLUSION: Compared with PCDT, MT was associated with greater peri-procedural thrombus reduction, more efficient post-procedure care, and improved symptoms and signs of iliofemoral vein disease at 12 months.

Six-Month Outcomes of Mechanical Thrombectomy for Treating Deep Vein Thrombosis: Analysis from the 500-Patient CLOUT Registry.

PURPOSE: Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein. MATERIALS AND METHODS: The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality of life scores through 6 months were analyzed. Adverse events were identified and independently adjudicated. RESULTS: All-cause mortality at 30 days was 0.9%, and 8.6% of subjects experienced a serious adverse event (SAE) within the first 30 days, 1 of which (0.2%) was device related. SAE rethrombosis/residual thrombus incidence was 4.8% at 30 days and 8.0% at 6 months. Between baseline and 6 months, venous flow increased from 27.2% to 92.5% of limbs (P < 0.0001), and venous compressibility improved from 28.0% to 91.8% (P < 0.0001), while median Villalta scores improved from 9.0 at baseline to 1.0 at 6 months (P < 0.0001). Significant improvements in venous symptom severity, pain, and quality of life were also demonstrated. Outcomes from iliofemoral and isolated femoral-popliteal segments showed similar improvements. CONCLUSION: Outcomes from the CLOUT study, a large prospective registry for DVT, indicate that mechanical thrombectomy is safe and demonstrates significant improvement in symptoms and health status through 6 months. Level of Evidence 3: Non-randomized controlled cohort/follow-up study.

Neuroprotective role for RORA in Parkinson's disease revealed by analysis of post-mortem brain and a dopaminergic cell line.

Parkinson's disease (PD) is almost twice as prevalent in men, which has largely been attributed to neuroprotective effect of oestradiol in women. RORA (retinoic acid receptor-related orphan receptor alpha) regulates the transcription of central aromatase, the enzyme responsible for local oestradiol synthesis, simultaneously, RORA expression is regulated by sex hormones. Moreover, RORA protects neurones against oxidative stress, a key mechanism contributing to the loss of dopaminergic neurones in PD. Therefore, we hypothesized that there would be sex differences in RORA expression in the substantia nigra pars compacta (SNpc), which could contribute to sex differences observed in PD prevalence and pathogenesis. In a case control study, qPCR and western blot analyses were used to quantify gene and protein expression in the SNpc of post-mortem brains (n = 14 late-stage PD and 11 age and sex matched controls). The neuroprotective properties of a RORA agonist were then investigated directly using a cell culture toxin-based model of PD coupled with measures of viability, mitochondrial function and apoptosis. RORA was expressed at significantly higher levels in the SNpc from control females' brains compared to males. In PD, we found a significant increase in SNpc RORA expression in male PD compared to female PD. Treatment with a RORA agonist showed a significant neuroprotection in our cell culture model of PD and revealed significant effects on intracellular factors involved in neuronal survival and demise. This study is the first to demonstrate a sex specific pattern of RORA protein and gene expression in the SNpc of controls post-mortem human brains, and to show that this is differentially altered in male and female PD subjects, thus supporting a role for RORA in sex-specific aspects of PD. Furthermore, our in vitro PD model indicates mechanisms whereby a RORA agonist exerts its neuroprotective effect, thereby highlighting the translational potential for RORA ligands in PD.

Six-Month Deep Vein Thrombosis Outcomes by Chronicity: Analysis of the Real-World ClotTriever Outcomes Registry.

PURPOSE: To analyze the first 250 patients from the prospective, multicenter, industry-sponsored ClotTriever Outcomes (CLOUT) registry, assessing the safety and effectiveness of mechanical thrombectomy for acute, subacute, and chronic deep vein thrombosis (DVT). MATERIALS AND METHODS: Real-world patients with lower extremity DVT were treated with the ClotTriever System (Inari Medical, Irvine, California). Adjuvant venoplasty, stent placement, or both were performed at the physician's discretion. Thrombus chronicity was determined by visual inspection of removed thrombus, categorizing patients into acute, subacute, and chronic subgroups. Serious adverse events (SAEs) were assessed through 30 days. Clinical and quality-of-life (QoL) outcomes are reported through 6 months. RESULTS: Thrombus chronicity was designated for 244 of the 250 patients (acute, 32.8%; subacute, 34.8%; chronic, 32.4%) encompassing 254 treated limbs. Complete or near-complete (≥75%) thrombus removal was achieved in 90.8%, 81.9%, and 83.8% of the limbs with acute, subacute, and chronic thrombus, respectively. No fibrinolytics were administered, and 243 (99.6%) procedures were single sessions. One (0.4%) patient in the subacute group experienced a device-related SAE, a fatal pulmonary embolism. On comparing baseline and 6-month data, improvements were demonstrated in median Villalta scores (acute, from 10 to 1; subacute, from 9 to 1; chronic, from 10 to 3; for all, P < .0001) and mean EuroQol group 5-dimension (EQ-5D) self-report questionnaire scores (acute, 0.58 to 0.89; subacute, 0.65 to 0.87; chronic, 0.58 to 0.88; for all, P < .0001). There were no significant differences in outcomes across the subgroups. CONCLUSIONS: Mechanical thrombectomy using the ClotTriever System with adjunctive venoplasty and stent placement is safe and similarly effective for acute, subacute, and chronic DVT.

Continuous mechanical aspiration thrombectomy performs equally well in main versus branch pulmonary emboli: A subgroup analysis of the EXTRACT-PE trial.

INTRODUCTION: The EXTRACT-PE trial evaluated the safety and performance of the Indigo Aspiration System (Penumbra Inc.) with an 8F continuous mechanical aspiration thrombectomy system for the treatment of pulmonary embolism (PE). This subgroup analysis evaluates performance outcomes of patients with main pulmonary artery (PA) emboli versus discrete unilateral or bilateral PA emboli without main PA involvement. METHODS: The EXTRACT-PE trial was a prospective, single-arm, multicenter trial that enrolled 119 patients with acute submassive PE. Emboli location was collected at the time of enrollment, CT obstruction was measured and assessed by a Core Lab, and patients were grouped on whether emboli involved the main PA (with or without branch vessels) or not (branch vessels alone). Procedural device time, changes in the right ventricle to left ventricle (RV/LV) ratio, and systolic PA pressure from pre-and posttreatment were compared between the two groups. RESULTS: Out of the 119 patients enrolled, 118 had core lab-assessed clot locations. Forty-five (38.1%) had emboli that involved the main PA and 73 (61.9%) had only branch emboli. No significant difference was observed between these groups for 30-day mortality, procedural device time, changes in RV/LV ratio, reduction in CT Obstruction Index, or for systolic PA pressure from pre-and posttreatment. The mean absolute reduction in clot burden was significant in both groups. CONCLUSION: Continuous mechanical aspiration thrombectomy with the 8F Indigo Aspiration System was effective at improving clinical outcomes for submassive PE patients regardless of emboli location, and clot burden was significantly reduced in both groups.

Iron, Neuroinflammation and Neurodegeneration.

Disturbance of the brain homeostasis, either directly via the formation of abnormal proteins or cerebral hypo-perfusion, or indirectly via peripheral inflammation, will activate microglia to synthesise a variety of pro-inflammatory agents which may lead to inflammation and cell death. The pro-inflammatory cytokines will induce changes in the iron proteins responsible for maintaining iron homeostasis, such that increased amounts of iron will be deposited in cells in the brain. The generation of reactive oxygen and nitrogen species, which is directly involved in the inflammatory process, can significantly affect iron metabolism via their interaction with iron-regulatory proteins (IRPs). This underlies the importance of ensuring that iron is maintained in a form that can be kept under control; hence, the elegant mechanisms which have become increasingly well understood for regulating iron homeostasis. Therapeutic approaches to minimise the toxicity of iron include N-acetyl cysteine, non-steroidal anti-inflammatory compounds and iron chelation.

Outcomes from the ClotTriever Outcomes Registry show symptom duration may underestimate deep vein thrombus chronicity.

OBJECTIVE: The all-comer ClotTriever Outcomes registry assessed indicators of thrombus chronicity in patients with acute, subacute, and chronic lower extremity deep vein thrombosis (DVT). The effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) by chronicity subgroup was also assessed and reported here in this subanalysis. METHODS: All-comer patients with lower extremity DVT were enrolled, with no limitation based on the patients' symptom duration. Chronicity was assessed three times and compared: before the procedure based on symptom duration, during the procedure based on available pre-thrombectomy imaging, and visual inspection of the extracted thrombus morphology after thrombectomy. Patients were grouped into acute, subacute, and chronic subgroups according to their post-thrombectomy thrombus chronicity based on thrombus morphology. Analyses on baseline and procedural characteristics along with thrombus removal were performed across subgroups. The effectiveness of thrombus removal was determined by Marder scores adjudicated by an independent core laboratory, with a prespecified primary effectiveness end point of complete or near-complete (≥75%) thrombus removal. RESULTS: Of the 260 treated limbs from 250 patients, using symptom duration alone, 70.7% were considered acute, 20.9% subacute, and 8.4% chronic. Upon visual inspection, the extracted thrombus chronicity was approximately one-third in each subgroup: 32.7% had acute thrombus, 35.4% subacute thrombus, and 31.9% chronic thrombus. Chronicity assessed using symptom duration alone mismatched the post-thrombectomy chronicity in 55.1% of limbs (P < .0001) with 49.0% being more chronic than suggested by the patients' duration of symptoms. Chronicity assessed using pre-thrombectomy imaging mismatched the post-thrombectomy chronicity in 17.5% of limbs (P < .0001). No patients received thrombolytics and 99.6% were treated in a single session. Complete or near-complete thrombus removal was achieved in a high percentage of limbs regardless of thrombus chronicity: 90.8%, 81.9%, and 83.8% in limbs with acute, subacute, and chronic thrombus, respectively. CONCLUSIONS: This subanalysis from the all-comer ClotTriever Outcomes registry demonstrates that extracted thrombus in DVT may be more chronic than suggested by the patients' duration of symptoms. The addition of imaging is helpful to determine the ability of thrombus to respond to therapy. Irrespective of thrombus chronicity, the ClotTriever system can be effective at removing acute, subacute, and chronic thrombus in a single-session procedure without the need for thrombolytics.

Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry.

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients. METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days and clinical outcomes include post-thrombotic syndrome severity, symptoms, pain, and quality of life through 6 months. RESULTS: The median age was 62 years and 40% of patients had contraindications to thrombolytics. A range of thrombus chronicity (33% acute, 35% subacute, 32% chronic) was observed. No patients received thrombolytics and 99.6% were treated in a single session. The median thrombectomy time was 28 minutes. The primary effectiveness end point was achieved in 86% of limbs. Through 30 days, one device-related serious adverse event occurred. At 6 months, 24% of patients had post-thrombotic syndrome. Significant and sustained improvements were observed in all clinical outcomes, including the Revised Venous Clinical Severity Score, the numeric pain rating scale, and the EuroQol Group 5-Dimension Self-Report Questionnaire. CONCLUSIONS: The 6-month outcomes from the all-comer CLOUT registry with a range of thrombus chronicities demonstrate favorable effectiveness, safety, and sustained clinical improvements.

Pivotal Study Evaluating the Safety and Effectiveness of the Abre Venous Self-Expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction.

BACKGROUND: Iliofemoral venous obstruction is recognized with increasing frequency as the underlying cause of lower extremity symptoms including edema, pain, skin changes, and, in advanced cases, ulceration. This study sought to evaluate the safety and effectiveness of the Abre venous self-expanding stent system for the treatment of symptomatic iliofemoral venous outflow obstruction. METHODS: The ABRE Study (A Multi-Center, Non-Randomized Study to Evaluate the Safety and Effectiveness of the Abre Venous Self-Expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction) is a single-arm, multicenter, prospective study that included 200 subjects from 24 global sites. The primary end points were 12-month primary patency and major adverse events within 30 days. Secondary end points included lesion and procedure success, primary-assisted and secondary patency, major adverse events, stent migration, stent fracture, and quality of life changes. End point-related adverse events and imaging studies were adjudicated by independent clinical events committee and core laboratories, respectively. RESULTS: Venous obstruction cause was classified as acute deep vein thrombosis (16.5%, 33/200), post-thrombotic syndrome (47.5%, 95/200), or nonthrombotic iliac vein lesion (36.0%, 72/200). The common iliac and external iliac veins were stented in 96.0% (192/200), 80.5% (161/200) of subjects, respectively. Stent implant into the common femoral vein was required in 44.0% (88/200). Primary patency at 12 months was 88.0% (162/184). Four (2.0%) major adverse events occurred within 30 days. Twelve-month primary-assisted and secondary patency were 91.8% (169/184) and 92.9% (171/184), respectively. No stent fractures or migrations were reported. Mean target limb Villalta score decreased from 11.2±5.6 at baseline to 4.1±4.8 at 12 months, and the mean target limb revised Venous Clinical Severity Score decreased from 8.8±4.7 at baseline to 4.3±3.6 at 12 months. Clinically meaningful improvements in quality of life and venous functional assessment scores from baseline were demonstrated through 12 months in all measures. CONCLUSIONS: Symptomatic iliofemoral venous obstruction can be successfully treated with an Abre venous stent. Study outcomes demonstrated a high patency rate with a good safety profile. Patients demonstrated a significant reduction in clinical symptoms and improvement in quality of life that was maintained through 12-month follow-up. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03038438.

Impact of thoracic endovascular aortic repair timing on aortic remodeling in acute type B aortic intramural hematoma.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is increasingly utilized in the management of acute type B aortic intramural hematoma (TBIMH). Optimal timing for intervention has not been described. The aim of this study was to evaluate TEVAR timing on postoperative aortic remodeling. METHODS: A retrospective chart review was performed on patients who underwent TEVAR for TBIMH from January 2008 to September 2018. Imaging was reviewed pre- and postoperatively. Primary data points included true lumen diameter (TLD) and total aortic diameter (TAD) at the site of maximal pathology. Primary endpoint was aortic remodeling evidenced by a TAD/TLD ratio closest to 1.0. Secondary outcome was occurrence of aortic-related adverse events and mortality (AREM): aortic rupture, aortic-related death, progression to dissection, or need for aortic reintervention within 12 months. Patients undergoing emergent TEVAR (within 24 hours, 'eTEVAR') were compared with the remainder - delayed TEVAR ('dTEVAR'). RESULTS: We analyzed 71 patients that underwent TEVAR for TBIMH; 25 underwent emergent TEVAR and 46 patients underwent dTEVAR (median, 5.5 days; range, 2-120 days). There were no differences in demographics and comorbidities, and patients did not differ in presenting IMH thickness (12.6 ± 3.1 vs 11.3 ± 4.1 mm; P = .186) nor presenting TAD/TLD ratio (1.535 ± 0.471 vs 1.525 ± 0.397; P = .928) for eTEVAR and dTEVAR groups, respectively. eTEVAR patients had larger average presenting maximal descending aortic diameter (45.8 ± 14.3 vs 38.2 ± 7.5 mm; P = .018) and higher incidence of penetrating aortic ulcer on presenting computed tomography angiography (52.0% vs 21.7%; P = .033). Thirty-day mortality was 2 of 25 (8.0%) for eTEVAR and 2 of 45 (4.4%) for dTEVAR (P = .602). Postoperative aortic remodeling was more complete in the dTEVAR group (1.23 ± 0.12 vs 1.33 ± 0.15; P = .004). Case-control matching (controlling for presenting descending aortic diameter and penetrating aortic ulcer) on 30 patients still showed better aortic remodeling in the dTEVAR group (1.125 ± 0.100 vs 1.348 ± 0.42; P < .001). The incidence of AREM was higher in the eTEVAR (6/25; 24.0%) group compared with the dTEVAR group (2/46; 4.3%). At 12 months, freedom from AREM was higher in the dTEVAR group (95.7% vs 76.0%; P = .011). Postoperative TAD/TLD ratio was the best predictor for late aortic-related adverse events (area under the receiver operator characteristic = 0.825; P = .003). CONCLUSIONS: TEVAR for acute TBIMH within 24 hours of admission is associated with lower aortic remodeling and higher occurrence of late AREM. Delaying TEVAR when clinically possible could improve aortic remodeling and aortic-related outcomes.

A more proximal landing zone is preferred for thoracic endovascular repair of acute type B aortic dissections.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has become first-line therapy for complicated acute type B aortic dissection (aTBAD). However, the strategy for optimal proximal landing zone remains to be determined. We compared early outcomes and late aortic-related adverse events in patients undergoing TEVAR for complicated aTBAD with endograft deployment in proximal landing zone 2 vs 3. METHODS: We performed a retrospective chart review of adult patients undergoing TEVAR for complicated aTBAD within 6 weeks of diagnosis from January 2008 to December 2018. We excluded patients with connective tissue disorders and prior type A repair. Patients were divided into landing zone 2 TEVAR (Z2T) and zone 3 TEVAR (Z3T) groups. Z2 patients were divided between left subclavian artery (LSA) revascularization (Z2R) vs LSA coverage without revascularization (Z2C). Groups were compared for the need for aortic reintervention within 36 months of initial admission and freedom from aortic-related adverse events and mortality (AREM), defined as the need for aortic reintervention, aortic-related death, or rupture. RESULTS: Eighty-three patients underwent TEVAR for complicated aTBAD within a mean of 4.1 ± 7.8 days; 89.5% of patients had less than 2 cm of healthy proximal descending thoracic aorta. The landing zone was Z3T in 35 patients and 48 underwent Z2T: 10 Z2C and 38 Z2R. There were no differences between Z2T and Z3T in time from diagnosis to TEVAR, demographics, comorbidities, and diameter aortic measurements. The 30-day survival was 87.8%-89.5% for Z2R, 88.6% for Z3, and 80.0% for Z2C (P = .610). The postoperative spinal cord ischemia rate was 3.7%-2.7% for Z2R, 0% for Z3T, and 20.0% for Z2C (P = .012). The postoperative thoracic aortic rupture was 2.2% in Z2 and 0 in Z3. The need for aortic reintervention at 36 months after TEVAR was lower for Z2T (10.4%) vs Z3T (31.4%; P = .025). Freedom from AREM at 36 months was higher in Z2T vs Z3T (87.5% vs 68.6%; P = .048). The freedom from proximal reintervention was higher in Z2T (95.8%) compared with Z3T (80.0%; P = .019). Z3T deployment was predictive for AREM (odd ratio, 3.648; 95% confidence interval, 1.161-11.465; P = .027) and need for proximal reintervention (odds ratio, 5.542; 95% confidence interval, 1.062-28.927; P = .042). CONCLUSIONS: Most patients with aTBAD have less than 2 cm of proximal healthy descending thoracic aorta. In patients treated for complicated aTBAD, Z2T is associated with a lower need for aortic reintervention and aortic-related adverse events than Z3T. Patients may benefit from a more aggressive proximal landing zone with similar perioperative morbidity when Z2T is done with LSA revascularization.

Correction: Data Sharing Goals for Nonprofit Funders of Clinical Trials.

[This corrects the article DOI: 10.2196/23011.].

A novel approach to high-grade carotid stenosis with concomitant extracranial carotid aneurysms using transcarotid artery revascularization.

We present the novel application of transcarotid artery revascularization (TCAR) in two high-risk patients with high-grade internal artery stenosis and concomitant atherosclerotic extracranial carotid artery aneurysms (ECAAs). ECAAs account for <1% of arterial aneurysms and are usually clinically silent at presentation. Historically, the treatment of ECAAs has been via open reconstruction or stent grafting. TCAR is an effective alternative for carotid revascularization in high-risk patients with high-grade carotid stenosis, but has not been widely used for aneurysmal management. We report two cases to describe our management of concomitant carotid stenoses and ECCA with TCAR.