Outcomes of Arterial Bypass With the Human Acellular Vessel for Chronic Limb-Threatening Ischemia Performed Under the FDA Expanded Access Program.

OBJECTIVE: To report outcomes of the human acellular vessel (HAV) implanted for limb salvage through the Food and Drug Administration (FDA) Expanded Access Program for patients with chronic limb-threatening ischemia with no autologous conduit. METHODS: The HAV is a bioengineered vascular conduit designed with human vascular smooth muscle cells. The product is under regulatory study. From April 2019 to November 2021, the HAV was implanted in 14 patients (12 men; mean age, 62±14 years) at 3 US centers. Each case was performed with a single-use investigational new drug Expanded Access Program issued by the FDA. Institutional review board approval was obtained; technical and clinical outcomes were analyzed. RESULTS: A single 6-mm-diameter (40-cm-long) HAV was implanted in 9 patients; 5 patients required 2 HAVs sewn together as a composite. Technical success was 100%. Median follow-up was 12 (range, 1 to 41) months. Primary and secondary patency rates were 72% and 81% at 12 months; assisted primary patency was attained in 4 patients. Amputation-free survival was 93% at 6 months and 77% at 12 months. All patients with a patent HAV experienced clinical improvement with no HAV-related infections or adverse events. There were 4 deaths in the cohort, late mortality unrelated to the HAV. CONCLUSION: The HAV is a safe and effective "off-the-shelf" biologic conduit. This experience from the FDA Expanded Access Program in this population with few alternative limb salvage options will help guide regulatory deliberations for patients with lower extremity ischemia and no autologous bypass conduit options.

Ischemia Duration and Lower Limb Salvage.

Management of acute limb ischemia is complex and time sensitive, and delays in diagnosis and treatment may lead to irreversible tissue damage. Current data challenge the commonly accepted 6-hour ischemic threshold for acute limb ischemia, although variations in practice remain. Patients with chronic peripheral artery disease may tolerate longer ischemia time due to presence of collateral circulation. Here the authors discuss the presentation, workup, management, and postoperative care of patients with acute limb ischemia, with a focus on how management is altered depending on the duration and degree of ischemia.

A Novel Sutureless Anastomotic Device in a Swine Model: A Proof of Concept Study.

INTRODUCTION: Vascular reconstruction requires technical expertise and is often time consuming. As a novel alternative to traditional hand-sewn vascular anastomoses, the VasoLock (VL), is a nonabsorbable, sutureless anastomosis device with traction anchors designed to hold free artery ends together. These anchors do not penetrate the vessel wall but adhere by leveraging the elasticity of the vessels to fasten blood vessels together. This pilot study assesses the performance and patency of this novel device in a porcine model of femoral artery injury. METHODS: Female swine (n = 7) underwent femoral artery exposure for a total of 10 VL implanted. Study animals underwent hemodilution to a target hematocrit of 15% and ROTEM was used to assess coagulopathy, followed by an arterial injury via transection. The VL was inserted without any sutures. Flow-probe monitors were positioned proximal and distal to the device and flow rates were measured continuously for a total of 90 min. Flow was analyzed and presented as a ratio of distal to proximal flow with the slope of this ratio across time subsequently determined. Angiographic assessment was completed to evaluate for patency and technical complications after 90 min of implant. RESULTS: The average animal weight was 44.1 ± 3.2 kg. The average mean arterial pressure at the time of implant was 51.2 ± 7.8 mmHg, median heart rate was 77.4 (IQR = 77.25-157.4) beats per minute, and average temperature was 36.1 ± 1.5°C. The baseline hematocrit was 13.5 ± 3.0%, average pH was 7.20 ± 0.1, average clotting time was 154.1 ± 58.7 s and average clot formation time was 103.4 ± 10.9 s all demonstrating the acidotic, hypothermic, and coagulopathic state of the swine at the time of insertion. During the 90-min observation period, the average flow gradient identified across the VL was 0.99 ± 0.24, indicating no significant change in flow across the VL. The average slope of the gradients was 0.0005 (P = 0.22), suggesting the ratio of proximal and distal flow did not change over the 90 min. Following 90 min of dwell time, all VL were patent without technical complication. Angiographic assessment at 90 min demonstrated no evidence of dissection, device migration, arterial extravasation, or thromboembolism with any of the 10 devices. CONCLUSIONS: This pilot study demonstrated technical feasibility of the novel VL device over a 90-min observation period. All VL were patent and no negative events or complications were identified. This technology demonstrated significant promise in a coagulopathic state: additional investigation, involving long-term survival, is warranted for further validation.

Evaluation of novel hemostatic agents in a coagulopathic swine model of junctional hemorrhage.

BACKGROUND: Hemostatic dressings are used extensively in both military and civilian trauma to control lethal noncompressible hemorrhage. The ideal topical hemostatic agent would provide reliable hemostasis in patients with profound acidosis, coagulopathy, and shock. This study aimed to compare next-generation hemostatic agents against the current military standard in a translational swine model of vascular injury and coagulopathy. METHODS: Female Yorkshire swine were randomized to eight groups (total n = 63; control n = 14, per group n = 7) of hemostatic agents and included: QuikClot Combat Gauze (Teleflex, Morrisville, NC), which served as the control; BloodSTOP IX (LifeScience Plus, Mountain View, CA); Celox Rapid (Medtrade Product, Crewe, United Kingdom); ChitoSAM 100 (Sam Medical, Tualatin, OR); EVARREST Fibrin Sealant Patch (Ethicon, Raritan, NJ); TAC Wrapping Gauze (H&H Medical, Williamsburg, VA); ChitoGauze XR Pro (Tricol Biomedical, Portland, OR); and X-Stat 30 (RevMedX, Wilsonville, OR). Hemodilution via exchange transfusion of 6% hetastarch was performed to induce acidosis and coagulopathy. An arteriotomy was created, allowing 30 seconds of free bleeding followed by application of the hemostatic agent and compression via an external compression device. A total of three applications were allowed for continued/recurrent bleeding. All blood loss was collected, and hemostatic agents were weighed to calculate blood volume loss. Following a 180-minute observation period, angiography was completed to evaluate for technical complication and distal perfusion of the limb. Finally, the limb was ranged five times to assess for rebleeding and clot stability. RESULTS: All swine were confirmed coagulopathic with rotational thromboelastography and acidotic (pH 7.2 ± 0.02). BloodSTOP IX allowed a significant increase in blood loss and number of applications required to obtain hemostasis compared with all other groups. BloodSTOP IX demonstrated a decreased survival rate (29%, p = 0.02). All mortalities were directly attributed to exsanguination as a result of device failure. In surviving animals, there was no difference in extravasation. BloodSTOP IX had an increased rebleeding rate after ranging compared with QuikClot Combat Gauze ( p = 0.007). CONCLUSION: Most novel hemostatic agents demonstrated comparable efficacy compared with the currently military standard hemostatic dressing, CG.

Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties.

INTRODUCTION: The 6-hour threshold to revascularization of an ischemic limb is ubiquitous in the trauma literature, however, contemporary evidence suggests that this threshold should be less. This study aims to characterize the relationship between the duration of limb ischemia and successful limb salvage following lower extremity arterial trauma. METHODS: This is a cohort study of the United States and UK military service members injured while serving in Iraq or Afghanistan between 2003 and 2013. Consecutive patients who sustained iliac, femoral, or popliteal artery injuries, and underwent surgery to attempt revascularization, were included. The association between limb outcome and the duration of limb ischemia was assessed using the Kaplan-Meier method. RESULTS: One hundred twenty-two patients (129 limbs) who sustained iliac (2.3%), femoral (56.6%), and popliteal (41.1%) arterial injuries were included. Overall, 87 limbs (67.4%) were successfully salvaged. The probability of limb salvage was 86.0% when ischemia was ≤1 hour; 68.3% when between 1 and 3 hours; 56.3% when between 3 and 6 hours; and 6.7% when >6 hours ( P <0.0001). Shock more than doubled the risk of failed limb salvage [hazard ratio=2.42 (95% confidence interval: 1.27-4.62)]. CONCLUSIONS: Limb salvage is critically dependent on the duration of ischemia with a 10% reduction in the probability of successful limb salvage for every hour delay to revascularization. The presence of shock significantly worsens this relationship. Military trauma systems should prioritize rapid hemorrhage control and early limb revascularization within 1 hour of injury.

Preliminary Experience With the Human Acellular Vessel: A Descriptive Case Series Detailing Early Use of a Bioengineered Blood Vessel for Arterial Repair.

BACKGROUND: An infection-resistant, immediately available conduit for trauma and urgent vascular reconstruction remains a critical need for successful limb salvage. While autologous vein remains the gold standard, vein-limited patients and size mismatch are common issues. The Human Acellular Vessel (HAV) (Humacyte, Inc., Durham, NC) is a bioengineered conduit with off-the-shelf availability and resistance to infection, ideal characteristics for patients with challenging revascularization scenarios. This report describes HAV implantation in patients with complex limb-threatening ischemia and limited conduit options who may have otherwise faced limb loss. METHODS: The Food and Drug Administration (FDA) expanded-access program was used to allow urgent implantation of the HAV for arterial reconstruction. Electronic medical records were reviewed with extraction of relevant data including patient demographics, surgical implantation, patency, infectious complications, and mortality. RESULTS: The HAV was implanted in 8 patients requiring vascular reconstruction. Graft or soft tissue infection was present in 2 patients. One patient with severe penetrating pelvic injury had 4 HAV placed to repair bilateral external iliac artery and vein injuries. There was 1 technical failure due to poor outflow, 2 patients died unrelated to HAV use, and 5 lower extremity bypasses maintained patency at an average of 11.4 months (range: 4-20 months). No HAV infectious complications were identified. CONCLUSIONS: This report is the first United States series describing early outcomes using the HAV under the FDA expanded-access program for urgent vascular reconstruction. The HAV demonstrates resistance to infection, reliable patency, and offers surgeons an immediate option when confronted with complex revascularization scenarios. Assessment of long-term outcomes will be important for future studies.

Surgical Deep Vein Arterialization: Adding to the Armamentarium of Complex Limb Salvage.

BACKGROUND: Patients with severe peripheral arterial disease with limited or nonexistent arterial runoff, the so-called "desert foot", challenge efforts at limb preservation. Deep vein arterialization (DVA) involves incorporating a venous target as an outflow to achieve revascularization in these complex patients. We report outcomes in an initial series of patients undergoing DVA as a component of surgical bypass. METHODS: Over a 2-year period, 10 patients underwent bypass incorporating DVA due to severely disadvantaged runoff using a heparin-bonded expanded polytetrafluoroethylene conduit. Indications for surgery included tissue loss (8) or ischemic rest pain (2) in patients who had failed endovascular (3) or surgical (7) revascularization. Inflow arteries for bypass ranged from external iliac to below knee popliteal. Outflow anastomoses incorporated a common ostium arteriovenous fistula between anterior tibial (5), posterior tibial (2), peroneal (1) or plantaris pedis (2) arteries, and corresponding tibial veins. Prior to anastomotic completion, tibial vein valves were lysed to allow venous arterialization by a way of retrograde flow. Postoperative medical regimen included dual antiplatelet (2), antiplatelet plus anticoagulation (7), or anticoagulation alone (1). RESULTS: Primary patency was maintained in 7 of 10 grafts (average: 4.1 months, range: 1-18 months). Limb salvage was achieved in 8 of 10 patients (average: 6 months, range: 1-18 months). Two below knee amputations were performed after graft occlusion due to extensive tissue loss and infection, whereas 1 patient maintained limb salvage despite graft occlusion after successful wound healing. CONCLUSIONS: This initial experience describes surgical DVA using a prosthetic conduit in conjunction with an arteriovenous fistula at the distal anastomosis in patients with threatened limb loss and severely disadvantaged tibial runoff. Although evidence for long-term efficacy is uncertain, preliminary outcomes warrant further investigation as this technique may allow for surgical revascularization resulting in limb preservation for patients with no other alternative than amputation.

Targeted Regional Optimization in Action: Dose-dependent End-organ Ischemic Injury with Partial Aortic Occlusion in the Setting of Ongoing Liver Hemorrhage.

INTRODUCTION: Targeted regional optimization (TRO) describes partial resuscitative endovascular balloon occlusion of the aorta strategy that allows for controlled distal perfusion to balance hemostasis and tissue perfusion. This study characterized hemodynamics at specific targeted distal flow rates in a swine model of uncontrolled hemorrhage to determine if precise TRO by volume was possible. METHODS: Anesthetized swine were subjected to liver laceration and randomized into TRO at distal flows of 300 mL/min (n = 8), 500 mL/min (n = 8), or 700 mL/min (n = 8). After 90 min, the animals received damage control packing and were monitored for 6 h. Hemodynamic parameters were measured continuously, and hematology and serologic labs obtained at predetermined intervals. RESULTS: During TRO, the average percent deviation from the targeted flow was lower than 15.9% for all cohorts. Average renal flow rates were significantly different across all cohorts during TRO phase (P < 0.0001; TRO300 = 63.1 ±â€Š1.2; TRO500 = 133.70 ±â€Š1.93; TRO700 = 109.3 ±â€Š2.0), with the TRO700 cohort having less renal flow than TRO500. The TRO500 and TRO700 average renal flow rates inverted during the intensive care unit phase (P < 0.0001; TRO300 = 86.20 ±â€Š0.40; TRO500 = 148.50 ±â€Š1.45; TRO700 = 181.1 ±â€Š0.70). There was higher blood urea nitrogen, creatinine, and potassium in the TRO300 cohort at the end of the experiment, but no difference in lactate or pH between cohorts. CONCLUSION: This study demonstrated technical feasibility of TRO as a strategy to improve outcomes after prolonged periods of aortic occlusion and resuscitation in the setting of ongoing solid organ hemorrhage. A dose-dependent ischemic end-organ injury occurs beginning with partial aortic occlusion that progresses through the critical care phase, with exaggerated effect on renal function.

Advanced partial occlusion controller allows for increased precision during targeted regional optimization in a porcine model of hemorrhagic shock.

BACKGROUND: Targeted regional optimization (TRO), a partial resuscitative endovascular balloon occlusion of the aorta strategy, may mitigate distal ischemia and extend the window of effectiveness for this adjunct. An automated device may allow greater control and precise regulation of flow past the balloon, while being less resource-intensive. The objective of this study was to assess the technical feasibility of the novel advanced partial occlusion controller (APOC) in achieving TRO at multiple distal pressures. METHODS: Female swine (n = 48, 68.1 ± 0.7 kg) were randomized to a target distal mean arterial pressure (MAP) of 25 mm Hg, 35 mm Hg, or 45 mm Hg by either manual (MAN) or APOC regulation (n = 8 per group). Uncontrolled hemorrhage was generated by liver laceration. Targeted regional optimization was performed for 85 minutes, followed by surgical control and a 6-hour critical care phase. Proximal and distal MAP and flow rates were measured continuously. RESULTS: At a target distal MAP of 25 mm Hg, there was no difference in the MAP attained (APOC: 26.2 ± 1.05 vs. MAN: 26.1 ± 1.78 mm Hg) but the APOC had significantly less deviance (10.9%) than manual titration (14.9%, p < 0.0001). Similarly, at a target distal MAP of 45 mm Hg, there was no difference in mean pressure (44.0 ± 0.900 mm Hg vs. 45.2 ± 1.31 mm Hg) but APOC had less deviance (9.34% vs. 11.9%, p < 0.0001). There was no difference between APOC and MAN in mean (34.6 mm Hg vs. 33.7 mm Hg) or deviance (9.95% vs. 10.4%) at a target distal MAP of 35 mm Hg, respectively. The APOC made on average 77 balloon volume adjustments per experiment compared with 29 by manual titrations. CONCLUSION: The novel APOC consistently achieved and sustained precisely regulated TRO across all groups and demonstrated reduced deviance at the 25 mm Hg and 45 mm Hg groups compared with manual titration.

Novel Therapies for Critical Limb-Threatening Ischemia.

PURPOSE OF REVIEW: This review intends to discuss the latest endovascular and surgical advancement in the treatment of critical limb-threatening ischemia (CLTI). RECENT FINDINGS: We discuss novel endovascular technological advancements such as intravascular lithotripsy, the Tack endovascular stent, the PQ Bypass DETOUR system, and the LimFlow System for deep venous arterialization (DVA) in the very high risk "no-option" CLTI population. We also discuss the increasing adoption of radial and pedal approaches for endovascular revascularization and the tibiopedal arterial minimally invasive (TAMI) technique. On the surgical front, we discuss the distal vein patch technique and surgical and hybrid DVA. Recent advancements in the treatment options of CLTI will likely lead to reducing the rate of major amputations if they are adopted in a collaborative environment in order to apply the most appropriate treatment option to each individual patient based on the anatomy, comorbidities, functional status, and local expertise.

Carotid Endarterectomy for Ocular Ischemic Syndrome: A Case Report and Review of the Literature.

Ocular ischemic syndrome is a rare complication of carotid arterial disease that can lead to irreversible vision loss. The disease is related to ocular hypoperfusion secondary to carotid stenosis. Carotid endarterectomy (CEA) has been proven to reduce the risk of embolic stroke in specific patient populations; however, the role of CEA in the treatment of ocular ischemic syndrome or other flow-related symptoms is less well defined. We present a case of ocular ischemic syndrome successfully treated with carotid endarterectomy, and summarize the current literature regarding management of ocular ischemic syndrome.