Introduction: The COVID-19 pandemic had an unprecedented impact on cardiovascular clinical research. The decision-making and state of study operations in cardiovascular trials 1-year after interruption has not been previously described. Methods: In the spring of 2020, we created a pandemic impact task force to develop a landscape of use case scenarios from 17 device trials of peripheral artery disease (PAD) and coronary artery disease (CAD) interventions. In conjunction with publicly available (clinictrials.gov) study inclusion criteria, primary endpoints and study design, information was shared for this use-case landscape by trial leadership and data owners. Results: A total of 17 actively enrolling trials (9 CAD and 8 PAD) volunteered to populate the use case landscape. All 17 were multicenter studies (12 in North America and 5 international). Fifteen studies were industry-sponsored, of which 13 were FDA approved IDEs, one was PCORI-sponsored and two were sponsored by the NIH. Enrollment targets ranged from 150 to 9000 pts. At the time of interruption, 5 trials were <20 % enrolled, 9 trials were 50-80 % enrolled and 3 trials were>80 % enrolled. At 1 year, the majority of studies were continuing to enroll in the context of more sporadic but ongoing pandemic activity. Conclusions: At 1 year from the first surge interruptions, most trials had resumed enrollment. Trials most heavily interrupted were trials early in enrollment and those trials not able to pivot to virtual patient and site visits. Further work is needed to determine the overall impact on vascular intervention trials disrupted during the COVID-19 pandemic. (c) 2022 Elsevier Inc. All rights reserved.

Treatment of below-the-knee (BTK) lesions with endovascular methods is plagued by restenosis. While information can be obtained about patency of arteries using ultrasound at follow-up in BTK disease, the study of methods to enhance durability of endovascular treatment can be greatly enhanced with

BACKGROUND: Malignant airway obstruction (MAO) occurs in 30% of patients with advanced-stage lung cancer, leading to debilitating dyspnea, cough, and hemoptysis. Other than recanalization of the airways, these patients lack long-lasting palliative therapy. The goal of this study was to determine the safety and feasibility of local injection of paclitaxel into the airway wall with a novel microinjection catheter. METHODS: In this multicentered prospective trial, 23 patients with non-small cell lung cancer and MAO were enrolled from July 2014 through June 2016 to undergo rigid bronchoscopy with recanalization, followed by injection of 1.5 mg of paclitaxel with a novel injection catheter. Primary end points consisted of safety (adverse events, severe adverse events, and unanticipated adverse device effects) as well as feasibility (number of injections, injection success). Secondary end points consisted of airway patency improvement, quality of life metrics, and need for further interventions and/or stenting. RESULTS: Nineteen patients underwent rigid bronchoscopy with successful recanalization and paclitaxel injection. There were no adverse events, severe adverse events, or unanticipated adverse device effects. There was an average of 3.4 injections given for a total dose of 1.5 mg of paclitaxel in all patients. There was significantly less stenosis postprocedure vs preprocedure (25%-50% vs 75%-90%; P < .001), which was unchanged at 6 weeks (25%-50%). None of the participants required further interventions or airway stenting. CONCLUSIONS: The injection of paclitaxel after recanalization of MAO in patients with non-small cell lung cancer is safe and feasible, using a novel airway injection device.

Restenosis following endovascular treatment is associated with inflammatory and proliferative responses produced in the artery wall at the time of the procedure which may be ameliorated through delivery of anti-inflammatory or anti-proliferative compounds into the adventitia of the vessel at the

ABSTRACTBackground and objectiveIntratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side‐effect profiles are poorly understood.MethodsBronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28 days post‐injection.ResultsInjection of generic PTX directly into the bronchial wall at doses up to 1.5 mg/mL only caused minimal tissue injury. Dose‐limiting tissue reaction was observed at 2.5 mg/mL. Plasma PTX was detectable for up to 5 days but not at 28 days, with area under the curve (AUC)(0‐5d) 20‐ to 50‐fold lower than the AUC(0‐∞) of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days post‐injection, bronchial PTX tissue concentrations were above a 10‐nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX.ConclusionResults of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7 days but tissue concentrations remained therapeutic throughout the follow‐up period.

BACKGROUND:An endobronchial infusion catheter introduced through a flexible bronchoscope channel has not been previously described. The aim of this study was to evaluate the technical feasibility of a new device.METHODS:Four porcine models underwent bronchoscopy with the infusion catheter. In the first experiment, methylene blue was injected into airway in volumes of 0.1, 0.3, or 1.0 mL into 2 animals. One animal was killed at 1 hour and the other at 24 hours after the procedure and gross dye diffusion was visually assessed. In the second experiment, a mixture of 80% sterile normal saline and 20% contrast media was injected into the airway in volumes of 0.3, 1.0, and 3.0 mL into 2 animals. One animal was killed at 7 days and the other at 20 days. Histologic evaluations were performed according to a bronchial damage scoring system.RESULTS:There was no perioperative morbidity. In the first experiment, infusion volumes of 0.1, 0.3, and 1.0 mL resulted in dye surrounding 67%±29%, 55%±17%, and 80%±20% of the infusion-site circumference, and longitudinal distribution of 4.0±1.7, 8.1±4.1, and 18.0±3.0 mm each, respectively. In the second experiment, infusion of 0.3 to 3.0 mL resulted in mild injury, inflammation, and hemorrhage/fibrin/thrombus at 7 and 20 days after surgery.CONCLUSIONS:Endobronchial infusion of dye and contrast media by the endobronchial drug delivery catheter showed that the media spread in a dose-dependent manner macroscopically and histologically. Further investigation will be required to assess the catheter as a new tool for localized drug delivery into the airway.

Introduction: Balloon angioplasty of peripheral arteries induces a substantial inflammatory response and has a high rate of restenosis. Our hypothesis was that peri-adventitial injection of the antiproliferative, immunosuppressant drug rapamycin would reduce luminal stenosis in a porcine femoral artery model of balloon angioplasty injury. Methods: 16 male crossbred swine had a balloon angioplasty overstretch injury of the femoral artery followed by peri-adventitial injection of saline or 500μg of nanoparticle albumin-bound (nab) rapamycin with an intraluminal microinfusion catheter. Qualitative and quantitative assessments of the femoral arteries, including histomorphometric measurements, were performed on H&E, Masson’s trichrome or immunohistochemistry stained sections. Blood and tissue rapamycin concentration were assessed by liquid chromatography and mass spectrometry at 1h, 3d, 8d and 28d. Results: There was 100% procedural success with periadventitial injection. At 28 days, femoral arteries treated with nab-rapamycin had a 42% reduction in luminal stenosis, 19.5 ± 3.3% vs 11.4 ± 0.84%, p=0.01 t-test (figure). Nab-rapamycin also significantly reduced medial fibrosis by qualitative analysis, p<0.0001 t-test, and media cell proliferation by Ki-67 staining, p=0.02 t-test. There were significantly fewer adventitial leukocytes at 3 days, p=0.03 t-test, but no difference at 28 days. One hour after injection, the perivascular concentration of nab-rapamycin was 1500-times higher than serum and rapamycin persisted in the tissue for at least 8 days. Rapamycin was not detectable in serum or tissue at 28 days. There was no difference in endothelial coverage or regeneration by Factor VII and H&E staining at 3, 8 or 28 days. Conclusions: A single periadventitial dose of nab-rapamycin significantly reduced luminal stenosis in a porcine model of femoral artery balloon angioplasty injury. The observed reduction in early adventitial infiltration by leukocytes and decrease in medial cell proliferation and fibrosis at 28 days suggests a mechanism by which nab-rapamycin may have an effect. Adventitial injection with an intraluminal microinfusion catheter is safe and efficient and represents an alternative to stent- or balloon-based local drug delivery.

Restenosis following peripheral intervention is in part an inflammatory disease. We hypothesize that a non-stent-based local drug delivery of the anti-inflammatory corticosteroid dexamethasone (DEX) would mitigate intervention-associated inflammation and thus improve long-term arterial patency. This was an investigator initiated pilot study to determine if percutaneous adventitial drug delivery was safe and feasible in human peripheral arteries. Following successful intervention, an adventitial micro-infusion catheter (MIC) was advanced over a 0.014” wire to the treated segment. Its micro-needle was deployed into the adventitia to deliver DEX (4 mg/mL) mixed with contrast agent providing fluoroscopic visualization. The safety outcome was freedom from vessel dissection, thrombosis or extravasation, while the primary efficacy outcome was duplex-determined binary restenosis defined as PSVR >2.4 of the treated segment. 21 patients with Rutherford classification 2-5 enrolled in this study and followed for a median of 335 days. Mean age was 65.9 and 57.1% were diabetic. Treated lesion length was 8.7 ± 5.2 cm and 48% were chronic total occlusions. 80% of treated lesions were in the distal SFA/popliteal artery. The average preoperative Rutherford score was 3.77 ± .8. All lesions were treated by balloon angioplasty with provisional stenting for suboptimal result. 11.5 ± 5.7 mg of dexamethasone was injected into the adventitia of the treated lesions. There was 100% technical success of drug delivery and no procedural or drug-related adverse events. Rutherford score at last available follow-up was .46 ± .74 (P < .001) and ABI improved from .68 ± .15 to .95 ±.18 (P < .001). Postprocedural C-reactive protein (CRP) was not significantly different from baseline CRP (P = .13). Two patients developed binary restenosis of the index lesion during the follow-up period. Adventitial drug delivery via the MIC is a safe and feasible alternative to intimal-based methods. These preliminary data suggest that perivascular DEX treatment may improve outcomes following angioplasty to the distal femoro-popliteal segment. Further study is warranted to establish efficacy for anti-inflammatory treatment following angioplasty.

Introduction: Direct injection of an anti-cancer agent into airway malignancy to maintain airway is one of the palliative interventional options. We have previously reported a new endobronchial injection catheter through a flexible bronchoscope (Seward, K. P. et al. CHEST 2010;138:420A ,421A). Normal tissue reaction against anti-cancer agent must be evaluated in vivo prior to the human application. Aim: The purpose of the study was to assess the bronchoscopic and histopathological findings of porcine airway 1 week after injecting varying concentrations of paclitaxel (PTX). Methods: Diluted PTX was infused through the Blowfish™ Transbronchial Micro-Infusion catheter in 1 ml volume for each treatment. The animals underwent bronchoscopic evaluation prior to sacrifice on day 7. Histological findings were evaluated by according to the semi-quantitative bronchial damage scoring system. Results: PTX concentration of 0.05 mg/ml was injected into 13 sites (n=1), 0.5 mg/ml was injected into 13 sites (n=1), 2.5 mg/ml was injected into 5 sites (n=1), respectively. In the animal receiving 2.5 mg/ml, there was immediate injection reaction with whitening of the bronchial wall surrounded by hyperemic area which was subsequently covered by white yellowish necrotic tissue on day 7. Mild inflammation and minimal epithelium loss were observed in 0.05 mg/ml and 0.5 mg/ml injection group, moderate inflammation and significant epithelial loss were observed in 2.5 mg/ml animal. Conclusion: A 2.5 mg/ml PTX injection developed mucosal ulceration, while 0.05 and 0.5 mg/ml injections were well tolerated. Local tissue and systemic plasma drug concentration will be analyzed.