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We investigated the prevalence of vascular calcification in different zones of the aorta and pelvic arteries using computerized tomography angiography reconstructions and have applied machine learning to determine how calcification is affected by demographics, risk factors, and morphometry. The presented data can help identify patients at higher risk of developing vascular calcification that may lead to cardiovascular events.

Poor outcomes of peripheral arterial disease stenting are often attributed to the inability of stents to accommodate the complex biomechanics of the flexed lower limb. Abrasion damage caused by rubbing of the stent against the artery wall during limb movement plays a significant role in reconstruction failure but has not been characterized. Our goals were to develop a method of assessing the abrasiveness of peripheral nitinol stents and apply it to several commercial devices. Misago, AbsolutePro, Innova, Zilver, SmartControl, SmartFlex, and Supera stents were deployed inside electrospun nanofibrillar tubes with femoropopliteal artery-mimicking mechanical properties and subjected to cyclic axial compression (25%), bending (90°), and torsion (26°/cm) equivalent to five life-years of severe limb flexions. Abrasion was assessed using an abrasion damage score (ADS, range 1-7) for each deformation mode. Misago produced the least abrasion and no stent fractures (ADS 3). Innova caused small abrasion under compression and torsion but large damage under bending (ADS 7). Supera performed well under bending and compression but caused damage under torsion (ADS 8). AbsolutePro produced significant abrasion under bending and compression but less damage under torsion (ADS 12). Zilver fractured under all three deformations and severely abraded the tube under bending and compression (ADS 15). SmartControl and SmartFlex fractured under all three deformations and produced significant abrasion due to strut penetration (ADS 20 and 21). ADS strongly correlated with clinical 12-month primary patency and target lesion revascularization rates, and the described method of assessing peripheral stent abrasiveness can guide device selection and development. STATEMENT OF SIGNIFICANCE: Poor outcomes of peripheral arterial disease stenting are related to the inability of stents to accommodate the complex biomechanics of the flexed lower limb. Abrasion damage caused by rubbing of the stent against the artery wall during limb movement plays a significant role in reconstruction failure but has not been characterized. Our study presents the first attempt at assessing peripheral stent abrasiveness, and the proposed method is applied to compare the abrasion damage caused by Misago, AbsolutePro, Innova, Zilver, SmartControl, SmartFlex, and Supera peripheral stents using artery-mimicking synthetic tubes and cyclic deformations equivalent to five life-years of severe limb flexions. The abrasion damage caused by stents strongly correlates with their clinical 12-month primary patency and target lesion revascularization rates, and the described methodology can be used as a cost-effective and controlled way of assessing stent performance, which can guide device selection and development.

The Impella is a percutaneously placed intra-arterial flow pump positioned across the aortic valve for circulatory support. A limitation of the Impella is that it lacks a central wire channel, to maintain intra-arterial wire access when removing the device. Open surgical arterial cutdown is needed for the removal of the Impella CP placed emergently, without the use of preclose sutures. This case review describes an alternative removal method for the aforementioned occasions.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) was first described in the 1950s, but early attempts at REBOA faced several technical challenges. Subsequent advances in endovascular technologies led to renewed interest in employing REBOA for management of hemorrhagic shock. However, REBOA usage remains infrequent, and indications for REBOA implementation remain unclear. We evaluated current opinions of trauma surgeons toward the use of REBOA for control of trauma-related hemorrhage and other causes of hemorrhagic shock. We hypothesize, that despite heightened interest in REBOA, implementation remains limited. A 25-question survey was thus created to query institutional and surgeon-specific training and practice patterns related to REBOA usage. The anonymized survey was distributed via email to a national trauma surgeon database and responses were recorded online. 992 subjects were invited to participate, of whom 31% (n=311) responded. Of these, 89% reported to be a trauma or acute care surgeon at a Level I trauma center, 50% reported practicing for ≥20 years. Two-thirds (68%) reported REBOA use at their institution, and the majority (59%) employed REBOA at least once. However, most (78%) performed ≤5 REBOA placements last year. Respondents supported REBOA usage in non-trauma causes of shock including gastrointestinal bleeding (60%), post-partum hemorrhage (83%), and ruptured abdominal aortic aneurysm (69%). A significant minority (20.3%) reported either only slight confidence or no confidence in their ability to deploy REBOA, and thus 21% reported being 'very interested' in attending a REBOA skills course.We thus conclude that REBOA has gained wide interest among trauma surgeons. However, placement remains infrequent with most providers placing a few annually. Educational courses are needed to disseminate the necessary skills for REBOA utilization.

Aortic mechanical and structural characteristics have profound effects on pathophysiology, but many aspects of physiologic stress-stretch state and intramural changes due to aging remain poorly understood in human tissues. While difficult to assess in vivo due to residual stresses and pre-stretch, physiologic stress-stretch characteristics can be calculated using experimentally-measured mechanical properties and constitutive modeling. Mechanical properties of 76 human descending thoracic aortas (TA) from 13 to 78-year-old donors (mean age 51±18 years) were measured using multi-ratio planar biaxial extension. Constitutive parameters were derived for aortas in 7 age groups, and the physiologic stress-stretch state was calculated. Intramural characteristics were quantified from histological images and related to aortic morphometry and mechanics. TA stiffness increased with age, and aortas became more nonlinear and anisotropic. Systolic and diastolic elastic energy available for pulsation decreased with age from 30 to 8 kPa and from 18 to 5 kPa, respectively. Cardiac cycle circumferential stretch dropped from 1.14 to 1.04, and circumferential and longitudinal physiologic stresses decreased with age from 90 to 72 kPa and from 90 to 17 kPa, respectively. Aortic wall thickness and radii increased with age, while the density of elastin in the tunica media decreased. The number of elastic lamellae and circumferential physiologic stress per lamellae unit remained constant with age at 102±10 and 0.85±0.04 kPa, respectively. Characterization of mechanical, physiological, and structural features in human aortas of different ages can help understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs. Statement of significance This manuscript describes mechanical and structural changes occurring in human thoracic aortas with age, and presents material parameters for 4 commonly used constitutive models. Presented data can help better understand aortic pathology, inform the development of animal models that simulate human aging, and assist with designing devices for open and endovascular aortic repairs.

Mechanical properties of vascular grafts likely play important roles in healing and tissue regeneration. Healthy arteries are compliant at low pressures but stiffen rapidly with increasing load, ensuring sufficient volumetric expansion without overstretching the vessel. Commercial synthetic vascular grafts are stiff and unable to expand under physiologic loads, which may result in altered hemodynamics, deleterious cellular responses, and compromised clinical performance. The goal of this study was to develop an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned nonlinear compliance and compare its healing responses to conventional expanded polytetrafluoroethylene (ePTFE) grafts in a porcine iliac artery model. Human and porcine iliac arteries were mechanically characterized, and an ENG with similar properties was created by utilizing residual strains within electrospun nanofibers. The ENG was tested for implantation suitability and implanted onto n = 5 domestic swine iliac arteries, with control ePTFE grafts implanted onto the contralateral iliac arteries. After two weeks in vivo, all iliac arteries and grafts remained patent with no signs of thrombosis or dilation. The mechanically tuned ENG implants exhibited a more confluent CD31-positive cell monolayer (1.53 ± 0.73 µm2/mm vs 0.52 ± 0.55 µm2/mm, p = 0.042) on the graft lumenal surface and a higher fraction of αSMA-positive cells (16.2 ± 8.6% vs 1.4 ± 0.7%, p = 0.018) within the graft wall than the ePTFE controls. Despite heavy cellular infiltration, the ENG retained its artery-like mechanical characteristics after two weeks in vivo. These short-term results demonstrate potential advantages of mechanically tuned biomimetic vascular grafts over standard ePTFE grafts. Statement of Significance Off-the-shelf synthetic vascular grafts are often the only option available for treating advanced stages of vascular disease. Despite significant efforts devoted to improving their biochemical characteristics, synthetic peripheral arterial grafts continue to demonstrate poor clinical outcomes leading to costly reinterventions. Here, we hypothesized that a synthetic vascular graft with elastomeric mechanical properties tuned to a healthy peripheral artery promotes better healing responses than a synthetic stiff graft. To test this hypothesis, we developed an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned mechanical properties and compared its performance to a commercial ePTFE graft in a preclinical porcine iliac artery model. Our results suggest that mechanically tuned ENGs can offer better healing responses, potentially leading to better clinical outcomes for peripheral arterial repairs.

Supplemental Digital Content is available in the text., Objective: The recessive disease arterial calcification due to deficiency of CD73 (ACDC) presents with extensive nonatherosclerotic medial layer calcification in lower extremity arteries. Lack of CD73 induces a concomitant increase in TNAP (tissue nonspecific alkaline phosphatase; ALPL), a key enzyme in ectopic mineralization. Our aim was to investigate how loss of CD73 activity leads to increased ALPL expression and calcification in CD73-deficient patients and assess whether this mechanism may apply to peripheral artery disease calcification. Approach and Results: We previously developed a patient-specific disease model using ACDC primary dermal fibroblasts that recapitulates the calcification phenotype in vitro. We found that lack of CD73-mediated adenosine signaling reduced cAMP production and resulted in increased activation of AKT. The AKT/mTOR (mammalian target of rapamycin) axis blocks autophagy and inducing autophagy prevented calcification; however, we did not observe autophagy defects in ACDC cells. In silico analysis identified a putative FOXO1 (forkhead box O1 protein) binding site in the human ALPL promoter. Exogenous AMP induced FOXO1 nuclear localization in ACDC but not in control cells, and this was prevented with a cAMP analogue or activation of A2a/2b adenosine receptors. Inhibiting FOXO1 reduced ALPL expression and TNAP activity and prevented calcification. Mutating the FOXO1 binding site reduced ALPL promoter activation. Importantly, we provide evidence that non-ACDC calcified femoropopliteal arteries exhibit decreased CD73 and increased FOXO1 levels compared with control arteries. Conclusions: These data show that lack of CD73-mediated cAMP signaling promotes expression of the human ALPL gene via a FOXO1-dependent mechanism. Decreased CD73 and increased FOXO1 was also observed in more common peripheral artery disease calcification.

Thoracic endovascular aortic repair (TEVAR) has evolved as a first-line therapy for trauma patients. Most trauma patients are young, and their aortas are compliant and longitudinally pre-stretched. We have developed a method to include longitudinal pre-stretch in computational models of human thoracic aortas of different ages before and after TEVAR. Finite element models were built using computerized tomography angiography data obtained from human subjects in 6 age groups 10–69 years old. Aortic properties were determined with planar biaxial testing, and pre-stretch was simulated using a series of springs. GORE C-Tag stent-graft was computationally deployed in aortas with and without pre-stretch, and the stress–strain fields were compared. Pre-stretch had significant qualitative and quantitative effects on the aortic stress–strain state before and after TEVAR. Before TEVAR, mean intramural aortic stresses with and without pre-stretch decreased with age from 108 kPa and 83 kPa in the youngest age group, to 60 kPa in the oldest age group. TEVAR increased intramural stresses by an average of 73 ± 15 kPa and 48 ± 10 kPa for aortas with and without pre-stretch and produced high stress concentrations near the aortic isthmus. Inclusion of pre-stretch in young aortas increased intramural stresses by 30%, while in > 50-year-old subjects it did not change the results. Computational modeling of aorta-stent-graft interaction that includes pre-stretch can be instrumental for device design and assessment of its long-term performance, and in the future may help more accurately determine the stress–strain characteristics associated with TEVAR complications.

Introduction: Femoropopliteal artery (FPA) disease is common and therapeutic interventions and reconstructions leave significant room for improvement. Models of arterial growth and remodeling can help better understand the pathophysiology of FPA disease, but they require detailed data on arterial structural composition to produce accurate predictions. The goal of this work was to quantify intramural collagen and elastin in human FPAs and determine how these constituents change with age. Methods: FPAs were obtained from 32 tissue donors without hallmarks of peripheral artery disease (average age 50±18 years, age range 15-72 years). Longitudinal pre-stretch, wall thickness and lumen diameter were used to calculate in situ volume of tissue in a 1cm-long arterial segment. Arteries were fixed in formalin and sectioned in both transverse and longitudinal directions. Elastin and collagen contents were quantified with image analysis using Verhoeff-Van Gieson and Masson’s Trichrome stained slides scanned at 10x. Results: Ageing was associated with an increase in in situ tissue volume of 31mm 3 per decade of life, and increases in the overall wall and tunica media thicknesses of 94μm and 19μm per decade of life respectively (p=0.01). Volume fraction of elastin did not change with age (p=0.49) and remained at 4.8±1.6%, although elastic fibers did become more fragmented (p Conclusions: In human FPAs, arterial walls thicken and collagen content increases with age. Though total elastin content remains stable, elastic fiber architecture deteriorates with aging. Quantification of intramural structural changes in human FPAs across age groups can be instrumental for developing models of arterial growth and remodeling that can help better understand the pathophysiology of peripheral artery disease.