Faculty Bibliography

Objective: Genicular artery embolization (GAE) is a novel, minimally invasive procedure for treatment of knee osteoarthritis (OA). This meta-analysis investigated the safety and effectiveness of this procedure. Design: Outcomes of this systematic review with meta-analysis were technical success, knee pain visual analog scale (VAS; 0"“100 scale), WOMAC Total Score (0"“100 scale), retreatment rate, and adverse events. Continuous outcomes were calculated as the weighted mean difference (WMD) versus baseline. Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) rates were estimated in Monte Carlo simulations. Rates of total knee replacement and repeat GAE were calculated using life-table methods. Results: In 10 groups (9 studies; 270 patients; 339 knees), GAE technical success was 99.7%. Over 12 months, the WMD ranged from −34 to −39 at each follow-up for VAS score and −28 to −34 for WOMAC Total score (all p "‹< "‹0.001). At 12 months, 78% met the MCID for VAS score; 92% met the MCID for WOMAC Total score, and 78% met the SCB for WOMAC Total score. Higher baseline knee pain severity was associated with greater improvements in knee pain. Over 2 years, 5.2% of patients underwent total knee replacement and 8.3% received repeat GAE. Adverse events were minor, with transient skin discoloration as the most common (11.6%). Conclusions: Limited evidence suggests that GAE is a safe procedure that confers improvement in knee OA symptoms at established MCID thresholds. Patients with greater knee pain severity may be more responsive to GAE.

OBJECTIVES: Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

PURPOSE/OBJECTIVE:To compare 30-day readmission and in-hospital outcomes from the Nationwide Readmission Database for catheter-directed thrombolysis (CDT) versus systemic intravenous thrombolysis (IVT) as treatments for acute submassive or massive pulmonary embolism (PE) . MATERIALS AND METHODS/METHODS:The Nationwide Readmission Database was queried from 2016 to 2019 for adult patients with non-septic acute PE who underwent IVT or CDT. Massive PE was distinguished from submassive PEs if patients had concurrent ICD codes corresponding to mechanical ventilation, vasopressors, or shock. Propensity score matched analysis was conducted to infer the association of CDT versus IVT in unplanned 30-day readmissions, non-routine discharge, GI bleeding (GIB), and intracranial hemorrhage (ICH). These results are demonstrated as average treatment effects (ATE) of IVT compared to CDT. RESULTS:37,116 patients with acute PE were studied. 18,702 (50.3%) underwent CDT and 18,414 (49.7%) underwent IVT. 2,083 (11.1%) and 3,423 (18.6%) were massive PEs in the two groups, respectively (p<0.001). The ATE of IVT was higher compared to CDT regarding unplanned 30-day readmissions (ATE: 0.019; p<0.001), GIB (ATE: 0.012; p<0.001), ICH (ATE: 0.003; p=0.017) and non-routine discharge (ATE: 0.022; p=0.006). Subgroup analysis of submassive PE patients demonstrated that IVT had higher ATE regarding unplanned 30-day readmission (ATE: 0.028; p<0.001), GIB (ATE: 0.008; p=0.003), ICH (ATE: 0.002; p=0.035) and non-routine discharge (ATE: 0.019; p=0.022) compared to CDT. CONCLUSION/CONCLUSIONS:CDT had a lower likelihood of unplanned 30-day readmissions, including when stratified by submassive PE subtype. Additionally, complications including ICH and GIB were more likely among those who received IVT compared to CDT.

OBJECTIVES/OBJECTIVE:This study sought to evaluate the efficacy and safety of tissue-plasminogen activator (t-PA) infused via a Pharmacomechanical catheter-directed thrombolysis (PM-CDT) device called the Bashir Catheter in intermediate-risk acute pulmonary embolism (PE) patients. BACKGROUND:Catheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels like the pulmonary artery (PA) with lower doses of t-PA. METHODS:Patients with symptoms of acute PE with CT evidence of RV dilatation were enrolled. The Bashir Catheter was used to deliver 7 mgs of t-PA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory assessed change in CTA-derived right ventricular/left ventricular (RV/LV) diameter ratio at 48 hours and the primary safety endpoint was serious adverse events including major bleeding at 72 hours. RESULTS:At 18 US sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT the RV/LV ratio decreased by 0.56 (33.3%: p<0.0001). The PA obstruction as measured by the Refined Modified Miller Index (RMMI) was reduced by 35.9% (p <0.0001). One patient (0.92%) had two serious adverse events (SAE) which included a retroperitoneal bleed (procedure-related) and iliac vein thrombosis (device-related). Two other procedure-related SAEs included epistaxis, and non-access site hematoma with anemia. CONCLUSIONS:PM-CDT with the Bashir endovascular catheter is associated with significant reduction in RV/LV ratio and a very low rate of adverse events or major bleeding in intermediate-risk acute PE patients. The notable finding was a significant reduction in PA obstruction with low dose t-PA. (Recombinant tPA by Endovascular Administration for the treatment of Submassive pulmonary embolism using pharmaco-mechanical Catheter directed thrombolysis for the redUction of thrombus burdEn - The RESCUE Study IDE # G200009 NCT - 04248868).

INTRODUCTION/UNASSIGNED:There are no randomized trials studying the outcomes of mechanical aspiration thrombectomy (MAT) for management of pulmonary embolism (PE). METHODS/UNASSIGNED:We performed a systematic review and meta-analysis of existing literature to evaluate the safety and efficacy of MAT in the setting of PE. Inclusion criteria were as follows: studies reporting more than five patients, study involved MAT, and reported clinical outcomes and pulmonary artery pressures. Studies were excluded if they failed to separate thrombectomy data from catheter-directed thrombolysis data. Databases searched include PubMed, EMBASE, Web of Science until April, 2021. RESULTS/UNASSIGNED:Fourteen case series were identified, consisting of 516 total patients (mean age 58.4 ± 13.6 years). Three studies had only high-risk PE, two studies had only intermediate-risk PE, and the remaining nine studies had a combination of both high-risk and intermediate-risk PE. Six studies used the Inari FlowTriever device, five studies used the Indigo Aspiration system, and the remaining three studies used the Rotarex or Aspirex suction thrombectomy system. Four total studies employed thrombolytics in a patient-specific manner, with seven receiving local lysis and 17 receiving systemic lysis, and 40 receiving both. A random-effects meta-analyses of proportions of in-hospital mortality, major bleeding, technical success, and clinical success were calculated, which yielded estimate pooled percentages [95% CI] of 3.6% [0.7%, 7.9%], 0.5% [0.0%, 1.8%], 97.1% [94.8%, 98.4%], and 90.7% [85.5%, 94.3%]. CONCLUSION/UNASSIGNED:There is significant heterogeneity in clinical, physiologic, and angiographic data in the currently available data on MAT. RCTs with consistent parameters and outcomes measures are still needed.

Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, post-procedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data as well as incomplete mechanistic understanding of the critical factors driving long-term patency. Post-interventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis due to procedural or patient factors. The additive benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual and/or triple agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of non-thrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single- or multi-agent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize post-procedural antithrombotic therapy in patients receiving venous interventions.

Purpose: To determine the safety and effectiveness of genicular artery embolization (GAE) in reducing knee pain in patients with mild to moderate knee osteoarthritis (OA), as measured by validated patient reported outcome measures, and to characterize pre/post-procedural trends in multiple OA-associated serum biomarkers
Material(s) and Method(s): In an ongoing, prospective, single-arm clinical trial, patients with mild to moderate (Kellgren-Lawrence grade 2-3) symptomatic knee OA, without prior surgery and who failed conservative therapy, were included. Pre-intervention imaging (plain radiographs and MRI), patient-reported outcome measures (KOOS, WOMAC, VAS), and serum biomarkers (IL-1Ra, CRP, Hyaluronan, COMP, VEGF, CCL2-MCP-1) were obtained. Each patient underwent transcatheter arterial embolization of one or more genicular arteries in the affected knee using 250-mum microspheres (Embozene, Varian). One- and three-month post-intervention patient-reported outcome measures and serum biomarkers were obtained. Baseline and follow-up outcomes were compared using paired Wilcoxon signed-rank tests.
Result(s): The first 7 patients (4 male, mean age 68 +/- 6y, mean BMI 30 +/- 2) recruited into this trial were included in this preliminary analysis. Technical success was 100%. There were no adverse events. By 3 months, VAS pain scores decreased from 56 to 21 (63% decrease); WOMAC pain scores decreased from 8 to 4 (50% decrease); and KOOS pain scores (for which higher scores indicate less pain) increased from 57 to 81 (42% increase), all P >0.05. Baseline and 3-month mean biomarker values were: IL-1Ra (471 +/- 276 vs 590 +/- 320 pg/mL), CRP (1.81 +/- 1.78 vs 3.24 +/- 4.25 mg/L), Hyaluronan (92 +/- 66 vs 166 +/- 102 ng/mL), COMP (942 +/- 336 vs 1057 +/- 462 ng/mL), VEGF (372 +/- 283 vs 303 +/- 101 pg/mL), and CCL2-MCP-1 (335 +/- 90 vs 323 +/- 69 pg/mL), all P >0.05.
Conclusion(s): Patient-reported pain scores demonstrated a trend in improvement 3 months after GAE at our interim analysis. There were no significant changes between baseline and 3-month follow-up in serum OA biomarkers in this small sample size. Full study analysis will further delineate trends in serum biomarkers after GAE.
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