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.

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.

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.

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.

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.

Limb flexion-induced axial compression and bending in human femoropopliteal artery segments.

BACKGROUND: High failure rates of femoropopliteal artery (FPA) interventions are often attributed in part to severe mechanical deformations that occur with limb movement. Axial compression and bending of the FPA likely play significant roles in FPA disease development and reconstruction failure, but these deformations are poorly characterized. The goal of this study was to quantify axial compression and bending of human FPAs that are placed in positions commonly assumed during the normal course of daily activities. METHODS: Retrievable nitinol markers were deployed using a custom-made catheter system into 28 in situ FPAs of 14 human cadavers. Contrast-enhanced, thin-section computed tomography images were acquired with each limb in the standing (180 degrees), walking (110 degrees), sitting (90 degrees), and gardening (60 degrees) postures. Image segmentation and analysis allowed relative comparison of spatial locations of each intra-arterial marker to determine axial compression and bending using the arterial centerlines. RESULTS: Axial compression in the popliteal artery (PA) was greater than in the proximal superficial femoral artery (SFA) or the adductor hiatus (AH) segments in all postures (P = .02). Average compression in the SFA, AH, and PA ranged from 9% to 15%, 11% to 19%, and 13% to 25%, respectively. The FPA experienced significantly more acute bending in the AH and PA segments compared with the proximal SFA (P < .05) in all postures. In the walking, sitting, and gardening postures, average sphere radii in the SFA, AH, and PA ranged from 21 to 27 mm, 10 to 18 mm, and 8 to 19 mm, whereas bending angles ranged from 150 to 157 degrees, 136 to 147 degrees, and 137 to 148 degrees, respectively. CONCLUSIONS: The FPA experiences significant axial compression and bending during limb flexion that occur at even modest limb angles. Moreover, different segments of the FPA appear to undergo significantly different degrees of deformation. Understanding the effects of limb flexion on axial compression and bending might assist with reconstructive device selection for patients requiring peripheral arterial disease intervention and may also help guide the development of devices with improved characteristics that can better adapt to the dynamic environment of the lower extremity vasculature.

Age and disease-related geometric and structural remodeling of the carotid artery.

BACKGROUND: Carotid artery geometry has been suggested as a risk factor for atherosclerotic carotid artery disease (ACD). Although normal aging and development of disease can both lead to geometric changes in the artery, whether geometric changes in a given artery actually predispose to disease or are just a consequence of remodeling during aging is unclear. We investigated carotid artery geometric changes with aging to identify geometric features associated with the presence of ACD. METHODS: Carotid artery geometry was quantified by measuring carotid artery diameter, tortuosity, and bifurcation angle using three-dimensional reconstructions of thin-section computed tomography angiography scans in 15 healthy individuals (average age, 43 ± 18 years; range, 15-64 years). The same geometric features were measured in 17 patients (68 ± 10 years old) with unilateral ACD. Geometric features associated with presence of ACD were determined by using the nondiseased contralateral carotid artery as an intrinsic control. Elastin-stained carotid arteries were analyzed to assess age-related structural changes in 12 deceased individuals. RESULTS: Increases were noted in bulb diameter (0.64 mm), bifurcation angle (10°), and tortuosity of the common carotid (CCA; 0.03) and internal carotid arteries (ICA; 0.04) for every decade of life. Density and continuity of circumferential and longitudinal elastin in the CCA and ICA decreased with age. Compared with normal carotid arteries, those with ACD demonstrated larger bulb diameters (P = .001) but smaller bifurcation angles (P = .001). CCA tortuosity (P = .038) increased in ACD arteries compared with normal carotid arteries, but ICA tortuosity was decreased (P = .026). CONCLUSIONS: With increasing age, bulb diameter, tortuosity, and bifurcation angle increases in carotid arteries. These geometric changes may be related to degradation and fragmentation of intramural elastin. Arteries with atherosclerotic occlusive disease demonstrate decreased ICA tortuosity and smaller bifurcation angles compared with nondiseased carotid arteries.

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.

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.

Preoperative anemia is an independent predictor of postoperative mortality and adverse cardiac events in elderly patients undergoing elective vascular operations.

OBJECTIVE: The objective of this study was to assess the impact of preoperative anemia (hematocrit <39%) on postoperative 30-day mortality and adverse cardiac events in patients 65 years or older undergoing elective vascular procedures. BACKGROUND: Preoperative anemia is associated with adverse outcomes after cardiac surgery, but its association with postoperative outcomes after open and endovascular procedures is not well established. Elderly patients have a decreased tolerance to anemia and are at high risk for complications after vascular procedures. METHODS: Patients (N = 31,857) were identified from the American College of Surgeons' 2007-2009 National Surgical Quality Improvement Program-a prospective, multicenter (>250) database maintained across the United States. The primary and secondary outcomes of interest were 30-day mortality and a composite end point of death or cardiac event (cardiac arrest or myocardial infarction), respectively. RESULTS: Forty-seven percent of the study population was anemic. Anemic patients had a postoperative mortality and cardiac event rate of 2.4% and 2.3% in contrast to the 1.2% and 1.2%, respectively, in patients with hematocrit within the normal range (P < 0.0001). On multivariate analysis, we found a 4.2% (95% confidence interval, 1.9-6.5) increase in the adjusted risk of 30-day postoperative mortality for every percentage point of hematocrit decrease from the normal range. CONCLUSIONS: The presence and degree of preoperative anemia are independently associated with 30-day death and adverse cardiac events in patients 65 years or older undergoing elective open and endovascular procedures. Identification and treatment of anemia should be important components of preoperative care for patients undergoing vascular operations.

A mathematical evaluation of hemodynamic parameters after carotid eversion and conventional patch angioplasty.

Carotid endarterectomy has a long history in stroke prevention, yet controversy remains concerning optimal techniques. Two methods frequently used are endarterectomy with patch angioplasty (CEAP) and eversion endarterectomy (CEE). The objective of this study was to compare hemodynamics-related stress and strain distributions between arteries repaired using CEAP and CEE. Mathematical models were based on in vivo three-dimensional arterial geometry, pulsatile velocity profiles, and intraluminal pressure inputs obtained from 16 patients with carotid artery disease. These data were combined with experimentally derived nonlinear, anisotropic carotid artery mechanical properties to create fluid-structure interaction models of CEAP and CEE. These models were then used to calculate hemodynamic parameters thought to promote recurrent disease and restenosis. Combining calculations of stress and strain into a composite risk index, called the integral abnormality factor, allowed for an overall comparison between CEAP and CEE. CEE demonstrated lower mechanical stresses in the arterial wall, whereas CEAP straightened the artery and caused high stress and strain concentrations at the suture-artery interface. CEAP produced a larger continuous region of oscillatory, low-shear, vortical flow in the carotid bulb. There was a more than two-fold difference in the integral abnormality factor, favoring CEE. In conclusion, in a realistically simulated carotid artery, fluid-structure interaction modeling demonstrated CEE to produce less mechanical wall stress and improved flow patterns compared with CEAP. Clinical validation with larger numbers of individual patients will ultimately be required to support modeling approaches to help predict arterial disease progression and comparative effectiveness of reconstruction methods and devices.

Development of a risk index for prediction of mortality after open aortic aneurysm repair.

OBJECTIVE: Open infrarenal abdominal aortic aneurysm (oAAA) repair is associated with significant morbidity and mortality. Although there has been a shift toward endovascular repair, many patients continue to undergo an open repair due to anatomic considerations. Tools currently existing for estimation of periprocedural risk in patients undergoing open aortic surgery have certain limitations. The objective of this study was to develop a risk index to estimate the risk of 30-day perioperative mortality after elective oAAA repair. METHODS: Patients who underwent elective oAAA repair (n = 2845) were identified from the American College of Surgeons' 2007 to 2009 National Surgical Quality Improvement Program (NSQIP), a prospective database maintained at >250 centers. Univariable and multivariable analyses were performed to evaluate risk factors associated with 30-day mortality after oAAA repair and a risk index was developed. RESULTS: The 30-day mortality after oAAA repair was 3.3%. Multivariable analysis identified six preoperative predictors of mortality, and a risk index was created by assigning weighted points to each predictor using the ß-coefficients from the regression analysis. The predictors included dyspnea (at rest: 8 points; on moderate exertion: 2 points; none: 0 points), history of peripheral arterial disease requiring revascularization or amputation (3 points), age >65 years (3 points), preoperative creatinine >1.5 mg/dL (2 points), female gender (2 points), and platelets <150,000/mm(3) or >350,000/mm(3) (2 points). Patients were classified as low (<7%), intermediate (7%-15%), and high (>15%) risk for 30-day mortality based on a total point score of <8, 8 to 11, and >11, respectively. There were 2508 patients (88.2%) patients in the low-risk category, 278 (9.8%) in the intermediate-risk category, and 59 (2.1%) in the high-risk category. CONCLUSIONS: This risk index has excellent predictive ability for mortality after oAAA repair and awaits validation in subsequent studies. It is anticipated to aid patients and surgeons in informed patient consent, preoperative risk assessment, and optimization.

Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy.

OBJECTIVE: The latest guidelines recommend performance of carotid endarterectomy (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the combined perioperative stroke, myocardial infarction (MI), or death risk is ≤3%. Our objective was to develop and validate a risk index to estimate the combined risk of perioperative stroke, MI, or death in asymptomatic patients undergoing elective CEA. METHODS: Asymptomatic patients who underwent an elective CEA (n = 17,692) were identified from the 2005-2010 National Surgical Quality Improvement Program, a multicenter, prospective database. Multivariable logistic regression analysis was performed with primary outcome of interest being the composite of any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping was used for internal validation. A risk index was created by assigning weighted points to each predictor using the ß-coefficients from the regression analysis. RESULTS: Fifty-eight percent of the patients were men with a median age of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n = 167), 0.6% (n = 108), and 0.4% (n = 72), respectively. The combined 30-day stroke, MI, or death incidence was 1.8% (n = 324). On multivariable analysis, six independent predictors were identified and a risk index created by assigning weighted points to each predictor using the ß-coefficients from the regression analysis. The predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point; ≥80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3 points), previous peripheral revascularization or amputation (3 points), recent angina within 1 month (4 points), and dependent functional status (5 points). Patients were classified as low (<3%), intermediate (3%-6%), or high (>6%) risk for combined 30-day stroke, MI, or death, based on a total point score of <4, 4-7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the high-risk category. CONCLUSIONS: The validated risk index can help identify asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death after CEA, thereby aiding patient selection.

In-hospital and postdischarge venous thromboembolism after vascular surgery.

OBJECTIVE: Recent single-center reports demonstrate a high (up to 10%) incidence of postoperative venous thromboembolism (VTE) after major vascular surgery. Moreover, vascular patients rarely receive prolonged prophylaxis despite evidence that it reduces thromboembolic events after discharge. This study used a national, prospective, multicenter database to define the incidence of overall and postdischarge VTE after major vascular operations and assess risk factors associated with VTE development. METHODS: Patients with VTE who underwent elective vascular procedures (n = 45,548) were identified from the 2007-2009 National Surgical Quality Improvement Program (NSQIP) database. The vascular procedures included carotid endarterectomy (CEA; n = 20,785), open thoracoabdominal aortic aneurysm (TAAA) repair (n = 361), thoracic endovascular aortic repair (TEVAR; n = 732), open abdominal aortic (OAA) surgery (n = 6195), endovascular aneurysm repair (EVAR; n = 7361), and infrainguinal bypass graft (BPG; n = 10,114). Univariable and multivariable analyses were performed to ascertain risk factors associated with VTE. RESULTS: VTE was diagnosed in 187 patients (1.3 %) who underwent aortic surgery, with TAAA repair having the highest rate of VTE (4.2%), followed by TEVAR (2.2%), OAA surgery (1.7%), and EVAR (0.7%). In this subgroup, pulmonary embolisms (PE) were diagnosed in 52 (0.4%) and deep venous thrombosis (DVT) in 144 (1%). VTE rates were 1.0% and 0.2% for patients who underwent a BPG or CEA, respectively. Forty-one percent of all VTEs were diagnosed after discharge. The median (interquartile range) number of days from surgery to PE and DVT were 10 (5-15) and 10 (4-18), respectively. On multivariable analyses, type of surgical procedure, totally dependent functional status, disseminated cancer, postoperative organ space infection, postoperative cerebrovascular accident, failure to wean from ventilator ≤48 hours, and return to the operating room were significantly associated with development of VTE. In those experiencing a DVT or PE, overall mortality increased from 1.5% to 6.2% and from 1.5% to 5.7% respectively (P < .05 for both). CONCLUSIONS: Postoperative VTE is associated with the type of vascular procedure and is highest after operations in the chest and abdomen/pelvis. About 40% of VTE events in elective vascular surgery patients were diagnosed after discharge, and the presence of VTE was associated with a quadrupled mortality rate. Future studies should evaluate the benefit of DVT screening and postdischarge VTE prophylaxis in high-risk patients.

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.

Predictive factors for mortality after open repair of paravisceral abdominal aortic aneurysm.

OBJECTIVE: The use of fenestrated and branched stent graft technology for paravisceral abdominal aortic aneurysms (PAAA) is on the rise; however, its application is limited in the United States to only a few selected centers. Most PAAAs are currently repaired using an open approach. The objective of this study was to determine which patients are at highest risk with open PAAA repair and might benefit most from endovascular repair using fenestrated or branched stent grafts. METHODS: This was a retrospective cohort study using data from American College of Surgeons National Surgical Quality Improvement Program (NSQIP) hospitals. We identified 598 patients (27.5% women) who underwent elective open PAAA repair from the 2007 to 2009 NSQIP, a prospective database maintained at >250 centers. The main outcome measure was 30-day postoperative mortality. RESULTS: The median patient age was 73 years. The 30-day major morbidity rate was 30.1%, and the mortality rate was 4.5%. Major complications included reintubation (10.0%), sepsis (10.7%), return to operating room (9.2%), new dialysis requirement (5.9%), cardiac arrest or myocardial infarction (4.5%), and stroke (1.2%). Multivariate analyses identified four predictors of postoperative mortality after open PAAA repair: peripheral arterial disease (PAD) requiring revascularization or amputation, chronic obstructive pulmonary disease (COPD), anesthesia time, and female sex. PAD and COPD were present in only 5.2% and 20.4% of patients but were associated with a 16.1% and 9.0% mortality rate, respectively. The mortality rate in women was 7.3% vs 3.5% for men (P = .045). CONCLUSIONS: PAD, COPD, and female sex are major risk factors for postoperative mortality after open PAAA repair. Fenestrated or branched stent graft repair may be a more valuable alternative to open repair for patients with one or more of these characteristics who have suitable access vessels.

Development and validation of a risk calculator for prediction of mortality after infrainguinal bypass surgery.

OBJECTIVE: For peripheral arterial disease, infrainguinal bypass grafting (BPG) carries a higher perioperative risk compared with peripheral endovascular procedures. The choice between the open and endovascular therapies is to an extent dependent on the expected periprocedural risk associated with each. Tools for estimating the periprocedural risk in patients undergoing BPG have not been reported in the literature. The objective of this study was to develop and validate a calculator to estimate the risk of perioperative mortality ≤30 days of elective BPG. METHODS: We identified 9556 patients (63.9% men) who underwent elective BPG from the 2007 to 2009 National Surgical Quality Improvement Program data sets. Multivariable logistic regression analysis was performed to identify risk factors associated with 30-day perioperative mortality. Bootstrapping was used for internal validation. The risk factors were subsequently used to develop a risk calculator. RESULTS: Patients had a median age of 68 years. The 30-day mortality rate was 1.8% (n = 170). Multivariable logistic regression analysis identified seven preoperative predictors of 30-day mortality: increasing age, systemic inflammatory response syndrome, chronic corticosteroid use, chronic obstructive pulmonary disease, dependent functional status, dialysis dependence, and lower extremity rest pain. Bootstrapping was used for internal validation. The model demonstrated excellent discrimination (C statistic, 0.81; bias-corrected C statistic, 0.81) and calibration. The validated risk model was used to develop an interactive risk calculator using the logistic regression equation. CONCLUSIONS: The validated risk calculator has excellent predictive ability for 30-day mortality in a patient after an elective BPG. It is anticipated to aid in surgical decision making, informed patient consent, preoperative optimization, and consequently, risk reduction.

Nonlinear mechanical behavior of the human common, external, and internal carotid arteries in vivo.

BACKGROUND: The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA), and internal (ICA) carotid arteries over the cardiac cycle in vivo. METHODS: Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA, and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semiautomatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and strain-induced stiffness of the arterial wall (stiffening in response to the increase of intraluminal blood pressure) for each patient. RESULTS: The diameter and wall thickness of the segments (CCA, ECA, and ICA) of the carotid bifurcation were found to decrease and strain-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25 ± 7 to 63 ± 23 kPa (CCA), from 22 ± 7 to 57 ± 19 kPa (ECA), and from 28 ± 8 to 67 ± 23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40 ± 0.25 to 1.50 ± 2.05 MPa (CCA), from 0.49 ± 0.34 to 1.14 ± 0.52 MPa (ECA), and from 0.68 ± 0.31 to 1.51 ± 0.69 MPa (ICA). The strain-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared with end-diastole. CONCLUSIONS: The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries--CCA, ECA and ICA--exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.

Three-dimensional geometry of the human carotid artery.

Accurate characterization of carotid artery geometry is vital to our understanding of the pathogenesis of atherosclerosis. Three-dimensional computer reconstructions based on medical imaging are now ubiquitous; however, mean carotid artery geometry has not yet been comprehensively characterized. The goal of this work was to build and study such geometry based on data from 16 male patients with severe carotid artery disease. Results of computerized tomography angiography were used to analyze the cross-sectional images implementing a semiautomated segmentation algorithm. Extracted data were used to reconstruct the mean three-dimensional geometry and to determine average values and variability of bifurcation and planarity angles, diameters and cross-sectional areas. Contrary to simplified carotid geometry typically depicted and used, our mean artery was tortuous exhibiting nonplanarity and complex curvature and torsion variations. The bifurcation angle was 36 deg ± 11 deg if measured using arterial centerlines and 15 deg ± 14 deg if measured between the walls of the carotid bifurcation branches. The average planarity angle was 11 deg ± 10 deg. Both bifurcation and planarity angles were substantially smaller than values reported in most studies. Cross sections were elliptical, with an average ratio of semimajor to semiminor axes of 1.2. The cross-sectional area increased twofold in the bulb compared to the proximal common, but then decreased 1.5-fold for the combined area of distal internal and external carotid artery. Inter-patient variability was substantial, especially in the bulb region; however, some common geometrical features were observed in most patients. Obtained quantitative data on the mean carotid artery geometry and its variability among patients with severe carotid artery disease can be used by biomedical engineers and biomechanics vascular modelers in their studies of carotid pathophysiology, and by endovascular device and materials manufacturers interested in the mean geometrical features of the artery to target the broad patient population.

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.