Treatment of Thoracoabdominal Aortic Aneurysmal Degeneration Following Aortic Dissections at a Single Surgical Center Using a Physician-Assembled Branched Endovascular Stent Graft.

BACKGROUND: Aneurysmal degeneration of aortic dissection portends significant morbidity and mortality consequences in the subacute and chronic phases of aortic dissection. This article describes the use of a multibranched stent graft system for the treatment of thoracoabdominal aneurysmal degeneration of dissections with visceral segment involvement and reports upon the 30-day and 1-year outcomes for the first 18 patients treated with this design configuration. METHODS: The in-hospital, 30-day and 1-year morbidity and mortality outcomes of 18 consecutive patients treated with the physician-assembled visceral manifold or unitary manifold stent graft systems between 2013 and 2022 were evaluated. RESULTS: A total of 18 patients were treated for aneurysmal changes after aortic dissection. A total of 71 visceral vessels were successfully stented. There were no acute procedural failures. There were no episodes of paraplegia, reinterventions for type I or III endoleaks, patency-related events or mortalities reported in the first 30 days following treatment. One-year, all-cause mortality demonstrated 2/11 (18.2%). CONCLUSIONS: The aneurysmal degeneration of aortic dissection poses significant risks to patients with medically managed aortic dissections and those under surveillance. When these aneurysms develop in the thoracoabdominal region, treatment becomes even more challenging given the problem of visceral vessel patency, as these vessels can originate off the true or false lumens. The physician-designed endovascular stent graft system reported upon here has been successfully deployed in 18 patients with no acute procedural failures and promising clinical results. This treatment modality may offer utility to vascular surgeons whose patients with thoracoabdominal aneurysmal degeneration following aortic dissection have historically had limited endovascular repair prospects.

Incidence of Acute and Chronic Renal Failure Following Branched Endovascular Repair of Complex Aortic Aneurysms.

BACKGROUND: The purpose of this study was to examine the incidence of acute kidney injury and chronic renal impairment following branched endovascular aneurysm repair (BEVAR) of complex thoracoabdominal aortic aneurysms (TAAA) using the Medtronic Valiant Thoracoabdominal Aortic Aneurysm stent graft system (MVM), the physician-modified Visceral Manifold, and Unitary Manifold stent graft systems. The objective was to report the acute and chronic renal function changes in patients following complex TAAA aneurysm repair. METHODS: This is an analysis of 139 patients undergoing branched endovascular repair for complex TAAAs between 2012 and 2020. Patient renal function was evaluated using serum creatinine and estimated glomerular filtration rate at baseline, 48 hr, discharge, 1 month, 6 months, and annually to 2 years. Patients on dialysis prior to the procedure were excluded from data analysis. RESULTS: A total of 139 patients (mean age 71.13; 64.7% male) treated for TAAA with BEVAR met inclusion criteria and were evaluated. A total of 530 visceral vessels were stented. A majority of patients (n = 131, 94.2%) underwent a single procedure while 8 required staged procedures. Thirty-day, 1-year and 2-year all-cause mortality rates were 5.8%, 25.2%, and 32.4%, respectively. Primary and secondary patency rates at a median follow-up of 26.9 months (95% CI; 21.1 - 32.7) were 96.2% and 97.5% for all vessels and 95.4% and 96.9% for renal arteries, respectively. Postoperative acute kidney injury (AKI) was identified in 22 (15.8%) patients. At discharge, 16 patients (11.6%) had an increase in CKD stage with 3 requiring permanent dialysis. Five additional patients required permanent dialysis over the 2-year follow-up period for a total of 8 (5.8%). Increasing age (HR = 1.0327, P= 0.0477), hemoglobin < 7 prior to procedure (HR = 2.4812, P= 0.0093), increasing maximum aortic diameter (HR = 1.0189, P= 0.0084), presence of AKI (HR = 2.0757, P= 0.0182), and increase in CKD stage (HR = 1.3520, P= 0.002) at discharge were significantly associated with decreased patient survival. CONCLUSIONS: Postoperative AKI and a chronic decline in renal function continue to be problematic in endovascular repair of complex aortic aneurysms. This study found that BEVAR using the manifold configuration resulted in immediate and mid-term renal function that is comparable to similar analyses of branched and/or fenestrated grafts.

Short-term Cost Comparison of Systemic Heparin Therapy vs. Catheter Directed Thrombolysis for the Treatment of Massive and Submassive Pulmonary Embolism with Long-Term Chronic Pulmonary Hypertension Cost Model.

INTRODUCTION: Pulmonary embolism (PE) is a significant disease process that affects an estimated 117 cases per 100,000 person-years. Chronic pulmonary hypertension (CPH) is a long-term complication associated with acute PE which has a significant cost to treat, ranging from $98,000-117,000. METHODS: A retrospective chart review of 341 patients from January 2011 to November 2018 who presented with massive or submassive PE and were treated with either systemic heparin therapy or catheter directed thrombolysis (CDT). The results of the short-term cost analysis and pulmonary hypertension rates from data collected was then used in a long-term cost model using a standardized 100 patient model. RESULTS: Treatment with CDT resulted in fewer bleeding complications (4.2 percent vs. 13.8 percent, p=0.005), a shorter length of stay, a greater percentage of patients returning to their prior living conditions (89.0 percent vs. 79.3 percent, p=0.042), and a lower rate of chronic pulmonary hypertension at 12 months (6.3 percent vs. 15.9 percent, p=0.030) than those treated with systemic heparin. The expense of treatment utilizing CDT was greater than those undergoing systemic heparin treatment with a difference of approximately $31,000 (p=0.001) though our cost model showed the heparin group to have a higher cost over time. CONCLUSIONS: For patients with massive or submassive PE, this study demonstrated a significant long-term cost savings and improved outcomes for patients treated with catheter directed thrombolysis when compared to systemic heparin administration.

Development of drug-coated balloon for the treatment of multiple peripheral artery segments.

OBJECTIVE: Peripheral artery disease is the second most common cardiovascular disease. It can often occur in complex form when there is a presence of long, diffuse, and multiple lesions. Current treatments use either single long drug-coated balloons (DCBs) or multiple DCBs; however, treatment success is limited. The purpose of this study was to investigate the preclinical feasibility of our multiple-release Tailored Medical Devices DCB (MR-TMD-DCB) to treat multiple arterial segments using a single DCB. METHODS: The MR-TMD-DCBs were developed using a two-layer coating approach. The DCBs were developed in a certified Current Good Manufacturing Practices facility using presterilized materials and reagent and then characterized for coating morphology, thermal and chemical changes, and in vitro particulate shedding. The drug loss, tissue uptake, and undelivered drug amounts were analyzed using an in vitro peripheral artery flow model and explanted pig arteries. Then, an in vivo survival study was performed using a healthy porcine model to measure the short-term drug uptake (seven swine; 14 treatments at day 1) and retention (seven swine; 14 treatments at day 7) in two different arterial segments after treatment with a single MR-TMD-DCB. RESULTS: The coating on the MR-TMD-DCB was smooth and homogeneous with paclitaxel molecularly dispersed in its amorphous state. A negligible number of particulates were shed from the MR-TMD-DCB coating. A similar amount of drug was accurately delivered into two separate explanted arteries using a single MR-TMD-DCB during the in vitro flow model testing (707 ± 109 ng/mg in the first explanted artery and 783 ± 306 ng/mg in the second explanted artery). The MR-TMD-DCB treatment resulted in equivalent drug amounts in the two arterial segments at day 1 (63 ± 19 ng/mg in the first treatment site and 59 ±19 ng/mg in the second treatment site) and at day 7 (9 ± 6 ng/mg in the first treatment site and 10 ± 6 ng/mg in the second treatment site). In addition, the drug levels at each time point were in the clinically relevant range to prevent neointimal hyperplasia. CONCLUSIONS: The MR-TMD-DCBs provided equivalent and clinically relevant drug retention levels into two different arterial segments. Thus, MR-TMD-DCBs can be used to accurately deliver drug into multiple arterial segments with the use of a single DCB. The clinical outcomes of these findings need further investigation. Future long-term pharmacokinetics and safety studies will be performed to evaluate the safety and efficacy of the MR-TMD-DCB.

In vitro particulate and in vivo drug retention study of a novel polyethylene oxide formulation for drug-coated balloons.

OBJECTIVE: The purpose of this study was to investigate the newly developed drug-coated balloon (DCB) using polyethylene oxide (PEO) as a platform and to compare it directly with a commercially available DCB in a preclinical experimental setting. METHODS: The PEO balloon was characterized for coating morphology and degree of paclitaxel (PAT) crystallinity. PAT tissue levels were then measured up to 30 days in a healthy porcine model (10 swine, 20 vessels) after treatment with either a PEO balloon or a commercially available DCB. An in vitro bench-top model was used to compare the particulates released from the PEO balloon and commercially available DCB. RESULTS: The coating on the PEO balloon was smooth and homogeneous with PAT in its amorphous state. From the porcine survival study, the PAT tissue levels were comparable between PEO balloon and commercially available DCB after 7 days of treatment. Both the PEO balloon and the commercially available DCB retained therapeutic drug up to 30 days. During the simulated in vitro model, the PEO balloon shed significantly fewer particulates that were smaller than those of the commercially available DCB. Most important, the PEO balloon shed 25 times fewer large particulates than the commercially available DCB. CONCLUSIONS: The amorphous PAT in the PEO balloon provided comparable drug tissue retention levels to those of the commercially available DCB and fewer particulates. Thus prepared PEO balloon proved to be safe and effective in the preclinical experimental setting. The clinical outcomes of these findings need further investigation.

Shear accumulation as a means for evaluating risk of thromboembolic events in novel endovascular stent graft designs.

OBJECTIVE: This study proposes to establish a simulation-based technique for evaluating shear accumulation in stent grafts and to use the technique to assess the performance of a novel branched stent graft system. METHODS: Computational fluid dynamics models, with transient boundary conditions, particle injection, and rigid walls, simplifying assumptions were developed and used to evaluate the shear accumulation in various stent graft configurations with a healthy aorta as comparison. RESULTS: Shear streamlines are presented for the various configurations. Shear accumulation was also calculated for each configuration. The number of particles with shear accumulations >3.5 Pa-s for each configuration was compared with the shear accumulation values of commercially available mechanical aortic valves from the literature. CONCLUSIONS: The stent graft configuration with the diaphragm does have particles with shear accumulation >3.5 Pa-s. However, the percentage of particles with shear accumulation above 3.5 Pa-s is less than the two commercially available mechanical aortic valves, and more surprisingly, is smaller than in the healthy aorta.

In vitro and in vivo evaluation of effect of excipients in local delivery of paclitaxel using microporous infusion balloon catheters.

Drug-infusion balloons are one of the currently used local drug delivery devices for preventing restenosis after endovascular treatments. An antiproliferative drug (paclitaxel, PAT) is infused through the balloon using a cremophor-based formulation to control restenosis. However, the major limitations of this approach are poor in vivo drug uptake and a limit in the amount of PAT delivered because of cremophor toxicity. In this study, we have investigated the use of different excipients for effectively infusing PAT out of the balloon for improved drug uptake in the tissue. The excipients include nanoparticle albumin-bound PAT (nab-PAT, a nanobiomaterial used in cancer therapy), urea (a hydrophilic agent used for faster drug transfer), iodixanol (a contrast agent used for coronary angiography), and cremophor-PAT (the most commonly used PAT formulation). An in vitro drug release, smooth muscle cell (SMC) response, endothelial cell (EC) response, and in vivo drug uptake were investigated for all the different excipients of PAT infused through the balloon. The nab-PAT was as effective as cremophor in infusing out of the balloon and inhibiting SMC growth. Also, nab-PAT showed a significantly greater amount of in vivo PAT uptake than that of cremophor-PAT. Urea and iodixanol were not effective in delivering a clinically relevant dose of PAT due to the poor solubility of PAT in these excipients. Urea eradicated all the SMCs and ECs, suggesting a toxic effect, which impedes its use in balloon-based therapy. Thus, this study demonstrated that nab-PAT is an effective formulation to locally deliver PAT through infusion balloons. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 376-390, 2017.