Mechanical, structural, and physiologic differences between above and below-knee human arteries.

Peripheral Artery Disease (PAD) affects the lower extremities and frequently results in poor clinical outcomes, especially in the vessels below the knee. Understanding the biomechanical and structural characteristics of these arteries is important for improving treatment efficacy, but mechanical and structural data on tibial vessels remain limited. We compared the superficial femoral (SFA) and popliteal (PA) arteries that comprise the above-knee femoropopliteal (FPA) segment to the infrapopliteal (IPA) anterior tibial (AT), posterior tibial (PT), and fibular (FA) arteries from the same 15 human subjects (average age 52, range 42-67 years, 87 % male). Vessels were imaged using µCT, evaluated with biaxial mechanical testing and constitutive modeling, and assessed for elastin, collagen, smooth muscle cells (SMCs), and glycosaminoglycans (GAGs). IPAs were more often diseased or calcified compared to the FPAs. They were also twice smaller, 53 % thinner, and significantly stiffer than the FPA longitudinally, but not circumferentially. IPAs experienced 48 % higher physiologic longitudinal stresses (62 kPa) but 27 % lower circumferential stresses (24 kPa) and similar cardiac cycle stretch of <1.02 compared to the FPA. IPAs had lower longitudinal pre-stretch (1.12) than the FPAs (1.29), but there were no differences in the stored elastic energy during pulsation. The physiologic circumferential stiffness was similar in the above and below-knee arteries (718 kPa vs 754 kPa). Structurally, IPAs had less elastin, collagen, and GAGs than the FPA, but maintained similar SMC content. Our findings contribute to a better understanding of segment-specific human lower extremity artery biomechanics and may inform the development of better medical devices for PAD treatment. STATEMENT OF SIGNIFICANCE: Peripheral Artery Disease (PAD) in the lower extremity arteries exhibits distinct characteristics and results in different clinical outcomes when treating arteries above and below the knee. However, their mechanical, structural, and physiologic differences are poorly understood. Our study compared above- and below-knee arteries from the same middle-aged human subjects and demonstrated distinct differences in size, structure, and mechanical properties, leading to variations in their physiological behavior. These insights could pave the way for creating location-specific medical devices and treatments for PAD, offering a more effective approach to its management. Our findings provide new, important perspectives for clinicians, researchers, and medical device developers interested in treating PAD in both above- and below-knee locations.

Structural and Mechanical Properties of Human Superficial Femoral and Popliteal Arteries.

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions.

Effect of Two Years of Doxycycline Treatment on Infrarenal Aortic Neck Diameter.

Objective: Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Neck diameter is the primary anatomical determinant of EVAR eligibility and device durability. Doxycycline has been proposed to stabilise the proximal neck after EVAR. This study explored doxycycline mediated aortic neck stabilisation in patients with small AAA, monitored by computed tomography over two years. Methods: This was a multicentre prospective randomised clinical trial. Subjects from the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT, NCT01756833) were included in this secondary a priori analysis. Female baseline AAA maximum transverse diameter was between 3.5 and 4.5 cm, and male was between 3.5 and 5.0 cm. Subjects were included if they completed pre-enrolment and two year follow up computed tomography (CT) imaging. Proximal aortic neck diameter was measured at the lowest renal artery, and 5, 10, and 15 mm caudal to this point; mean neck diameter was calculated from these values. Unpaired, two tailed parametric t test analysis with post hoc Bonferroni correction was used to detect differences between neck diameters in subjects treated with placebo vs. doxycycline at baseline and two years. Results: One hundred and ninety-seven subjects (171 male, 26 female) were included in the analysis. All patients, regardless of treatment arm, demonstrated larger neck diameter caudally, a slight increase in diameter at all anatomical levels over time, and greater growth caudally. There was no statistically significant difference in infrarenal neck diameter between treatment arms at any anatomical level at any time point, nor mean change in neck diameter over two years. Conclusion: Doxycycline does not demonstrate infrarenal aortic neck growth stabilisation in small AAA followed for two years by thin cut CT imaging using a standardised acquisition protocol and cannot be recommended for mitigation of growth of the aortic neck in patients with untreated small abdominal aortic aneurysms.

A method of assessing peripheral stent abrasiveness under cyclic deformations experienced during limb movement.

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.

Calcification prevalence in different vascular zones and its association with demographics, risk factors, and morphometry.

Vascular calcification is associated with a higher incidence of cardiovascular events, but its prevalence in different vascular zones and the influence of demographics, risk factors, and morphometry remain insufficiently understood. Computerized tomography angiography scans from 211 subjects 5-93 yr old (mean age 47 ± 24 yr, 127 M/84 F) were used to build 3D vascular reconstructions and measure arterial diameters, tortuosity, and calcification volumes in six vascular zones spanning from the ascending thoracic aorta to the pelvic arteries. A machine learning random forest algorithm was used to determine the associations between calcification in each zone with demographics, risk factors, and vascular morphometry. Calcification appeared during the fourth decade of life and was present in all subjects after 65 yr. The abdominal aorta and the iliofemoral segment were the first to develop calcification, whereas the ascending thoracic aorta was the last. Demographics and risk factors explained 33-59% of the variation in calcification. Age, creatinine level, body mass index, coronary artery disease, and hypertension were the strongest contributors, whereas the effects of sex, race, tobacco use, diabetes, dyslipidemia, and alcohol and substance use disorders on calcification were small. Vascular morphometry did not directly and independently affect calcium burden. Vascular zones develop calcification asynchronously, with distal segments calcifying first. Understanding the influence of demographics and risk factors on calcium prevalence can help better understand the disease pathophysiology and may help with the early identification of patients that are at higher risk of cardiovascular events.NEW & NOTEWORTHY 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.

Safe balloon inflation parameters for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Noncompressible hemorrhage is a leading cause of preventable death in civilian and military trauma populations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising method for controlling noncompressible hemorrhage, but safe balloon inflation parameters are not well defined. Our goal was to determine the balloon inflation parameters associated with benchtop flow occlusion and aortic/balloon rupture in ex vivo human aortas and test the hypothesis that optimal balloon inflation characteristics depend on systolic pressure and subject demographics. METHODS: Aortic occlusion parameters in human thoracic aortas (TAs) and abdominal aortas (AAs) from 79 tissue donors (median ± SD age, 52 ± 18 years [range, 13-75 years]; male, 52; female, 27) were recorded under 100/40, 150/40, and 200/40 mm Hg flow pressures for ER-REBOA and Coda balloons. Rupture tests were done with Coda balloons only without flow. RESULTS: In the TA, the average balloon inflation volumes and pressures resulting in 100/40 mm Hg flow occlusion were 11.7 ± 3.8 mL and 174 ± 65 mm Hg for the ER-REBOA, and 10.6 ± 4.3 mL and 94 ± 57 mm Hg for the Coda balloons. In the AA, these values were 6.2 ± 2.6 mL and 110 ± 47 mm Hg for the ER-REBOA, and 5.9 ± 2.2 mL and 71 ± 30 mm Hg for the Coda. The average balloon inflation parameters associated with aortic/Coda balloon rupture were 39.1 ± 6.5 mL and 1,284 ± 385 mm Hg in the TA, and 27.7 ± 7.7 mL and 1,410 ± 483 mm Hg in the AA. Age, sex, and systolic pressure all had significant effects on balloon occlusion and rupture parameters. CONCLUSION: Optimal balloon inflation parameters depend on anatomical, physiological, and demographic characteristics. Pressure-guided rather than volume-guided balloon inflation may reduce the risk of aortic rupture. These results can be used to help improve the safety of REBOA procedures and devices.

Mechanically tuned vascular graft demonstrates rapid endothelialization and integration into the porcine iliac artery wall.

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.

Endovascular Repair of Blunt Thoracic Aortic Trauma is Associated With Increased Left Ventricular Mass, Hypertension, and Off-target Aortic Remodeling.

BACKGROUND: Aortic elasticity creates a cushion that protects the heart from pressure injury, and a recoil that helps perfuse the coronary arteries. TEVAR has become first-line therapy for many aortic pathologies including trauma, but stent-grafts stiffen the aorta and likely increase LV afterload. OBJECTIVE: Test the hypothesis that trauma TEVAR is associated with LV mass increase and adverse off-target aortic remodeling. METHODS: Computed Tomography Angiography (CTA) scans of 20 trauma TEVAR patients (17 M/3 F) at baseline [age 34.9 ±â€Š18.5 (11.4-71.5) years] and 5.1 ±â€Š3.1 (1.1-12.3) years after repair were used to measure changes in LV mass, LV mass index, and diameters and lengths of the ascending thoracic aorta (ATA). Measurements were compared with similarly-aged control patients without aortic repair (21 M/21 F) evaluated at similar follow-ups. RESULTS: LV mass and LV mass index of TEVAR patients increased from 138.5 ±â€Š39.6 g and 72.35 ±â€Š15.17 g/m2 to 173.5 ±â€Š50.1 g and 85.48 ±â€Š18.34 g/m2 at the rate of 10.03 ±â€Š12.79 g/yr and 6.25 ±â€Š10.28 g/m2/yr, whereas in control patients LV characteristics did not change. ATA diameters of TEVAR patients increased at a rate of 0.60 ±â€Š0.80 mm/yr, which was 2.4-fold faster than in controls. ATA length in both TEVAR and control patients increased at 0.58 mm/yr. Half of TEVAR patients had hypertension at follow-up compared to only 5% at baseline. CONCLUSIONS: TEVAR is associated with LV mass increase, development of hypertension, and accelerated expansile remodeling of the ascending aorta. Although younger trauma patients may adapt to these effects, these changes may be even more important in older patients with other aortic pathologies and diminished baseline cardiac function.

The "two-cut monorail" technique, for the over-the-wire removal of the Impella CP device.

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.

Dysregulation of FOXO1 (Forkhead Box O1 Protein) Drives Calcification in Arterial Calcification due to Deficiency of CD73 and Is Present in Peripheral Artery Disease.

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.

Effects of longitudinal pre-stretch on the mechanics of human aorta before and after thoracic endovascular aortic repair (TEVAR) in trauma patients.

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.

Mechanical and structural changes in human thoracic aortas with age.

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 stresses associated with flattening of human femoropopliteal artery specimens during planar biaxial testing and their effects on the calculated physiologic stress-stretch state.

Planar biaxial testing is commonly used to characterize the mechanical properties of arteries, but stresses associated with specimen flattening during this test are unknown. We quantified flattening effects in human femoropopliteal arteries (FPAs) of different ages and determined how they affect the calculated arterial physiologic stress-stretch state. Human FPAs from 472 tissue donors (age 12-82 years, mean 53 ± 16 years) were tested using planar biaxial extension, and morphometric and mechanical characteristics were used to assess the flattening effects. Constitutive parameters for the invariant-based model were adjusted to account for specimen flattening and used to calculate the physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy for the FPAs in seven age groups. Flattened specimens were overall 12 ± 4% stiffer longitudinally and 19 ± 11% stiffer circumferentially when biaxially tested. Differences between the stress-stretch curves adjusted and non-adjusted for the effects of flattening were relatively constant across all age groups longitudinally, but increased with age circumferentially. In all age groups, these differences were smaller than the intersubject variability. Physiologic stresses, stretches, axial force, circumferential stiffness, and stored energy were all qualitatively and quantitatively similar when calculated with and without the flattening effects. Stresses, stretches, axial force, and stored energy reduced with age, but circumferential stiffness remained relatively constant between 25 and 65 years of age suggesting a homeostatic target of 0.75 ± 0.02 MPa. Flattening effects associated with planar biaxial testing are smaller than the intersubject variability and have little influence on the calculated physiologic stress-stretch state of human FPAs.

Mechanical damage characterization in human femoropopliteal arteries of different ages.

Endovascular treatment of Peripheral Arterial Disease (PAD) is notorious for high failure rates, and interaction between the arterial wall and the repair devices plays a significant role. Computational modeling can help improve clinical outcomes of these interventions, but it requires accurate inputs of elastic and damage characteristics of the femoropopliteal artery (FPA) which are currently not available. Fresh human FPAs from n = 104 tissue donors 14-80 years old were tested using planar biaxial extension to capture elastic and damage characteristics. Damage initiation stretches and stresses were determined for both longitudinal and circumferential directions, and their correlations with age and risk factors were assessed. Two and four-fiber-family invariant-based constitutive models augmented with damage functions were used to describe stress softening with accumulating damage. In FPAs younger than 50 years, damage began accumulating after 1.51 ±â€¯0.13 and 1.49 ±â€¯0.11 stretch, or 196 ±â€¯110 kPa and 239 ±â€¯79 kPa Cauchy stress in the longitudinal and circumferential directions, respectively. In FPAs older than 50 years, damage initiation stretches and stresses decreased to 1.27 ±â€¯0.09 (106 ±â€¯52 kPa) and 1.26 ±â€¯0.09 (104 ±â€¯59 kPa), respectively. Damage manifested primarily as tears at the internal and external elastic laminae and within the tunica media layer. Higher body mass index and presence of diabetes were associated with lower damage initiation stretches and higher stresses. The selected constitutive models were able to accurately portray the FPA behavior in both elastic and inelastic domains, and properties were derived for six age groups. Presented data can help improve fidelity of computational models simulating endovascular PAD repairs that involve arterial damage. STATEMENT OF SIGNIFICANCE: This manuscript describes inelastic, i.e. damage, behavior of human femoropopliteal arteries, and provides values for three constitutive models simulating this behavior computationally. Using a set of 104 human FPAs 14-80 years old, we have investigated stress and stretch levels corresponding to damage initiation, and have studied how these damage characteristics change across different age groups. Presented inelastic arterial characteristics are important for computational simulations modeling balloon angioplasty and stenting of peripheral arterial disease lesions.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Cross-sectional pinching in human femoropopliteal arteries due to limb flexion, and stent design optimization for maximum cross-sectional opening and minimum intramural stresses.

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb flexion. One of these deformations, cross-sectional pinching, has a direct effect on blood flow, but is poorly characterized. Intra-arterial markers were deployed into n = 50 in situ cadaveric FPAs (80 ± 12 years old, 14F/11M), and limbs were imaged in standing, walking, sitting and gardening postures. Image analysis was used to measure marker openings and calculate FPA pinching. Parametric finite element analysis on a stent section was used to determine the optimal combination of stent strut amplitude, thickness and the number of struts per section to maximize cross-sectional opening and minimize intramural mechanical stress and low wall shear stress. Pinching was higher distally and increased with increasing limb flexion. In the walking, sitting and gardening postures, it was 1.16-1.24, 1.17-1.26 and 1.19-1.35, respectively. Stent strut amplitude and thickness had strong effects on both intramural stresses and pinching. Stents with a strut amplitude of 3 mm, thickness of 175 µm and 20 struts per section produced pinching and intramural stresses typical for a non-stented FPA, while also minimizing low wall shear stress areas, and ensuring a stent lifespan of at least 107 cycles. These results can help guide the development of improved devices and materials to treat peripheral arterial disease.

Nitinol Stents in the Femoropopliteal Artery: A Mechanical Perspective on Material, Design, and Performance.

Endovascular stenting has matured into a commonly used treatment for peripheral arterial disease (PAD) due to its minimally invasive nature and associated reductions in short-term morbidity and mortality. The mechanical properties of the superelastic Nitinol alloy have played a major role in the explosion of peripheral artery stenting, with modern stents demonstrating reasonable resilience and durability. Yet in the superficial femoral and popliteal arteries, even the newest generation Nitinol stents continue to demonstrate clinical outcomes that leave significant room for improvement. Restenosis and progression of native arterial disease often lead to recurrence of symptoms and reinterventions that increase morbidity and health care expenditures. One of the main factors thought to be associated with stent failure in the femoropopliteal artery (FPA) is the unique and highly dynamic mechanical environment of the lower limb. Clinical and experimental data demonstrate that the FPA undergoes significant deformations with limb flexion. It is hypothesized that the inability of many existing stent designs to conform to these deformations likely plays a role in reconstruction failure, as repetitive movements of the leg and thigh combine with mechanical mismatch between the artery and the stent and result in mechanical damage to both the artery and the stent. In this review we will identify challenges and provide a mechanical perspective of FPA stenting, and then discuss current research directions with promise to provide a better understanding of Nitinol, specific features of stent design, and improved characterization of the biomechanical environment of the FPA to facilitate development of better stents for patients with PAD.

Prevalence of Calcification in Human Femoropopliteal Arteries and its Association with Demographics, Risk Factors, and Arterial Stiffness.

OBJECTIVE: Arterial calcification and stiffening increase the risk of reconstruction failure, amputation, and mortality in patients with peripheral arterial disease, but underlying mechanisms and prevalence are unclear. APPROACH AND RESULTS: Fresh human femoropopliteal arteries were obtained from n=431 tissue donors aged 13 to 82 years (mean age, 53±16 years) recording the in situ longitudinal prestretch. Arterial diameter, wall thickness, and opening angles were measured optically, and stiffness was assessed using planar biaxial extension and constitutive modeling. Histological features were determined using transverse and longitudinal Verhoeff-Van Gieson and Alizarin stains. Medial calcification was quantified using a 7-stage grading scale and was correlated with structural and mechanical properties and clinical characteristics. Almost half (46%) of the femoropopliteal arteries had identifiable medial calcification. Older arteries were more calcified, but small calcium deposits were observed in arteries as young as 18 years old. After controlling for age, positive correlations were observed between calcification, diabetes mellitus, dyslipidemia, and body mass index. Tobacco use demonstrated a negative correlation. Calcified arteries were larger in diameter but had smaller circumferential opening angles. They were also stiffer longitudinally and circumferentially and had thinner tunica media and external elastic lamina with more discontinuous elastic fibers. CONCLUSIONS: Although aging is the dominant risk factor for femoropopliteal artery calcification and stiffening, these processes seem to be linked and can begin at a young age. Calcification is associated with the presence of certain risk factors and with elastic fiber degradation, suggesting overlapping molecular pathways that require further investigation.