Percent Thrombus Predicts Popliteal Artery Aneurysm Related Limb Threatening Events.

OBJECTIVE: The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events. SUMMARY BACKGROUND DATA: Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence. METHODS: This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture. RESULTS: There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status. CONCLUSION: Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Vasa vasorum interna in the carotid wall of active forms of Takayasu arteritis evidenced by ultrasound localization microscopy.

Introduction: Takayasu arteritis (TA) is associated with microvascularization of the wall of large arteries and is related to inflammation. Ultrasound localization microscopy (ULM), combining ultrafast ultrasound imaging with microbubble (MB) injection, can track the path of MBs within the arterial wall and thus provide imaging of the vasa vasorum. From the analysis of MB tracks in the common carotid arteries of patients with active TA, we report the presence of microvessels in connection with the carotid lumen (i.e., vasa vasorum interna [VVI]). Methods: ULM maps were obtained on five patients with active disease in the observational single-center series of the TAK-UF study. MB tracks connected to the carotid lumen were automatically identified, allowing the reconstruction of VVI. Results: MB tracking allows us to observe a microvascular network on the inner part of the wall, with some vessels in communication with the carotid lumen. This type of vessel was identified in all patients with active TA (n = 5) with a median of 2.2 [1.1-3.0] vessels per acquisition (2D longitudinal view of 3 cm of the common carotid artery). The blood flow within these vessels is mainly centrifugal; that is, toward the adventitia (88% [54-100] of MB tracks with flow directed to the outer part of the wall). Conclusion: VVI are present in humans in the case of active TA and emphasize the involvement of the intima in the pathological process. ClinicalTrials.gov Identifier: NCT03956394.

Popliteal artery aneurysm ultrasound criteria for reporting characteristics.

INTRODUCTION: Duplex ultrasound (DUS) is the modality of choice for surveillance of popliteal artery aneurysms (PAAs). However, noninvasive vascular laboratories have no standard guidelines for reporting results. This study assessed reports of PAA DUS for inclusion of information pertinent to operative decision-making and timing of surveillance. METHODS: This study was a retrospective review of a multi-institutional repository that was queried for all patients with a PAA from 2008 to 2022 and confirmed via manual chart review. DUS reports were abstracted and images were individually annotated for features of interest including dimensions, flow abnormalities, and percent thrombus burden. RESULTS: A total of 166 PAAs in 130 patients had at least one DUS available for viewing. Postoperative surveillance of PAAs was performed at several intervals: the first at 30 months (IQR 3.7-113, n = 44), the second at 64 months (IQR 20-172, n = 31), and the third at 152 months (IQR 46-217, n = 16) after the operation. The largest diameter of operative PAAs (median 27.5 mm, IQR 21.8-38.0) was significantly greater than nonoperative PAAs (median 20.9 mm, IQR 16.7-27.3); p < 0.01. Fewer than 33 (21%) reports commented on patency of distal runoff. We calculated an average percent thrombus of 60% (IQR 19-81) in nonoperative PAAs, which is significantly smaller than 75% (IQR 58-89) in operative PAAs; p < 0.01. CONCLUSION: In this multi-institutional retrospective study, PAAs are often not followed at intervals recommended by the Society for Vascular Surgery guidelines and do not include all measurements necessary for clinical decision-making in the multi-institutional repository studied. There should be standardization of PAA DUS protocols performed by all noninvasive vascular laboratories to ensure completeness of PAA DUS images and inclusion of characteristics pertinent to clinical decision-making in radiology reports.

Occurrence of Major Local Lower Limb Events in Type 2 Diabetic Patients with Lower Extremity Arterial Disease: Impact of Metformin.

BACKGROUNDS: Patients with type 2 diabetes mellitus (T2DM) are particularly at risk of developing major adverse cardiovascular events (MACE) and peripheral artery disease (PAD) due to an acceleration of the atherosclerotic process linked to hyperglycemia and inflammation with a greater risk of local complications. We aimed to identify the predictive factors for major adverse limb events (MALE) in T2DM patients with PAD to manage modifiable factors at an early stage. METHODS: This is a prospective study in which T2DM patients with PAD were included from November 2017 to May 2018 and followed over 12 months. The predictive factors for the onset of MALE, MACE, and death from all causes have been identified. RESULTS: A total of 100 patients were included; 37% of the patients developed a MALE. After multivariate analysis, metformin was associated with a decrease of MALE (odds ratio (OR) = 0.26; 95% confidence interval (CI) [0.10; 0.68]; P = 0.007), and a history of the treatment of intravenous iloprost was associated with an increased risk of MALE (OR = 5.70; 95% CI [1.31; 31.93]; P = 0.029). Regular physical activity was associated with a decreased risk of MACE (OR = 0.07; 95% CI [0; 0.44]; P = 0.021). A history of stroke and a history of venous thromboembolism were associated with an increased all-cause mortality risk with OR = 3.68; 95% CI [1.17; 11.5]; P = 0.025 and OR = 3.78; 95% CI [1.16; 12.3]; P = 0.027. CONCLUSIONS: Metformin is protective against local complications in people with diabetes with PAD and should be prescribed to diabetic patients with PAD at an early stage.

Atorvastatin Effect on Clopidogrel Efficacy in Patients with Peripheral Artery Disease.

BACKGROUND: Both clopidogrel and atorvastatin metabolism are rooted in hepatic cytochrome p450 activation. There are published reports of atorvastatin interfering with clopidogrel metabolism by inhibiting the activation of clopidogrel. This in turn would decrease the therapeutic effect of clopidogrel potentially resulting in an increase in thrombotic events in patients who are taking both medications. The emergence of viscoelastic assays, such as Thromboelastography with platelet mapping (TEG-PM), has been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. The aim of this prospective, observational study was to delineate the differences in platelet function between patients on clopidogrel alone versus those on clopidogrel and atorvastatin in patients that are undergoing peripheral revascularization. METHODS: All patients undergoing revascularization between December 2020 and August 2022 were prospectively evaluated. Patients on clopidogrel and atorvastatin were compared to those on clopidogrel alone. Serial perioperative TEG-PM analysis was performed up to 6 months postoperatively and the platelet function in terms of percent inhibition was evaluated in both groups. Statistical analysis was performed using unpaired t-test to identify differences in platelet function. RESULTS: Over the study period, a total of 182 patients were enrolled. Of this cohort 72 patients met study criteria. 87 samples from the 72 patients were analyzed. 31 (43.05%) patients were on clopidogrel alone and 41 (56.94%) were on clopidogrel and atorvastatin. Patients on clopidogrel alone showed significantly greater platelet inhibition compared to those on clopidogrel and atorvastatin [49.01% vs. 34.54%, P = 0.03]. There was no statistical difference in platelet inhibition between groups in terms of aspirin use alone versus aspirin and atorvastatin. CONCLUSIONS: Patients on clopidogrel and atorvastatin showed significantly less platelet inhibition compared to those on clopidogrel alone, supporting the concept that atorvastatin may interfere with the therapeutic effect of clopidogrel. Patients taking atorvastatin may require an alternative antiplatelet therapy regimen that does not include clopidogrel to achieve adequate thromboprophylaxis.

Wall shear rate and energy loss coefficient measures using conventional Doppler ultrasound do not predict carotid plaque progression.

Background: The rate of carotid plaque progression is believed to be related to blood flow hemodynamics and shear stress. Our objective was to determine if wall shear rate (WSR) and the energy loss coefficient (ELC) measured by Doppler ultrasound could predict atherosclerotic carotid disease progression. Patients and methods: Patients at a large tertiary center with an initial ultrasound between 2016 and 2018 with a significant carotid plaque were included if they had at least one 6 months follow-up comparative study. Stenosis progression was assessed according to the NASCET (The North American Symptomatic Carotid Endarterectomy Trial) percentage criterion. Results: The average annual progression rate for the 74 plaques included was 5.7% NASCET per year. We identified 18 plaques with ≥10% NASCET progression and 56 plaques without significant progression <10% NASCET. Among the plaques with progression, only four plaques had progression greater than 20% NASCET. Median WSR was 6266 s-1 [5813-8974] in plaques with progression and 6564 s-1 [5285-8766] in stable plaques (p=0.643). Median ELC was 3.86 m2 [2.78-5.53] in plaque with progression and 4.32 m2 [3.42-6.81] in stable plaques (p=0.296). Conclusions: Although it is a widely accepted hypothesis that shear stress and hemodynamics of the carotid bifurcation contribute to plaque progression, we found that WSR and ELC estimated by Doppler ultrasound do not reliably predict atherosclerotic plaque progression in the carotid artery. Other ultrasound modalities, such as 3D imaging, may be used to assess the influence of plaque geometry and hemodynamics in plaque progression.

Severe triple vessel disease secondary to IgG4-related coronary periarteritis.

BACKGROUND: Immunoglobulin G4-related disease is a rare systemic inflammatory disease that can lead to vascular manifestations such as periarteritis. CASE PRESENTATION: A 41-year-old man with stress angina was referred for coronary bypass surgery due to triple vessel coronary disease. CONCLUSIONS: Operative findings revealed significant adhesions and dense peri-coronary and periaortic thickening, also involving the left internal mammary artery. The IgG4-associated disease was confirmed by aortic pathology. The stress angina subsequently improved with the initiation of treatment with prednisone and rituximab.

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. OBJECTIVES: To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. METHODS: Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. RESULTS: Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels. CONCLUSION: VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.

Wall Shear Stress Measurement by Ultrafast Vector Flow Imaging for Atherosclerotic Carotid Stenosis.

OBJECTIVE: Carotid plaque vulnerability assessment could guide the decision to perform endarterectomy. Ultrafast ultrasound imaging (UF) can evaluate local flow velocities over an entire 2D image, allowing measurement of the wall shear stress (WSS). We aimed at evaluating the feasibility of WSS measurement in a prospective series of patients with carotid stenosis. METHODS: UF acquisitions, performed with a linear probe, had an effective frame rate of 5000 Hz. The flow velocity was imaged over the entire plaque area. WSS was computed with the vector field speed using the formula: with the blood velocity and µ, the blood viscosity. The WSS measurement method was validated using a calibrated phantom. In vivo, WSS was analyzed in 5 areas of the carotid wall: common carotid artery, plaque ascent, plaque peak, plaque descent, internal carotid artery. RESULTS: Good correlation was found between in vitro measurement and the theoretical WSS values (R2 = 0.95; p < 0.001). 33 patients were prospectively evaluated, with a median carotid stenosis degree of 80 % [75-85]. The maximum WSS value over the cardiac cycle follows the shape of the plaque with an increase during the ascent, reaching its maximum value of 3.25 Pa [2.26-4.38] at the peak of the plaque, and a decrease after passing of the peak (0.93 Pa [0.80-1.19]) lower than the WSS values in the non-stenotic areas (1.47 Pa [1.12-1.77] for the common carotid artery). CONCLUSION: UF allowed local and direct evaluation of the plaque's WSS, thus better characterizing local hemodynamics to identify areas of vulnerability. KEY POINTS: · Ultrafast vector Doppler allows calculation of the wall shear stress (WSS) by measuring velocity vectors over the entire 2D image.. · The setup to measure the WSS has been validated in vitro on a linear flow phantom by comparing measurements to in silico calculations.. · Applying this method to carotid plaque allows us to better describe the hemodynamic constraints that apply along the entire length of the plaque..

Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients.

BACKGROUND: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis. OBJECTIVES: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. METHODS: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. RESULTS: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers. CONCLUSION: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.

Management of carotid stenosis for primary and secondary prevention of stroke: state-of-the-art 2020: a critical review.

Carotid atherosclerotic plaque is encountered frequently in patients at high cardiovascular risk, especially in the elderly. When plaque reaches 50% of carotid lumen, it induces haemodynamically significant carotid stenosis, for which management is currently at a turning point. Improved control of blood pressure, smoking ban campaigns, and the widespread use of statins have reduced the risk of cerebral infarction to <1% per year. However, about 15% of strokes are still secondary to a carotid stenosis, which can potentially be detected by effective imaging techniques. For symptomatic carotid stenosis, current ESC guidelines put a threshold of 70% for formal indication for revascularization. A revascularization should be discussed for symptomatic stenosis over 50% and for asymptomatic carotid stenosis over 60%. This evaluation should be performed by ultrasound as a first-line examination. As a complement, computed tomography angiography (CTA) and/or magnetic resonance angiography are recommended for evaluating the extent and severity of extracranial carotid stenosis. In perspective, new high-risk markers are currently being developed using markers of plaque neovascularization, plaque inflammation, or plaque tissue stiffness. Medical management of patient with carotid stenosis is always warranted and applied to any patient with atheromatous lesions. Best medical therapy is based on cardiovascular risk factors correction, including lifestyle intervention and a pharmacological treatment. It is based on the tri-therapy strategy with antiplatelet, statins, and ACE inhibitors. The indications for carotid endarterectomy (CEA) and carotid artery stenting (CAS) are similar: for symptomatic patients (recent stroke or transient ischaemic attack ) if stenosis >50%; for asymptomatic patients: tight stenosis (>60%) and a perceived high long-term risk of stroke (determined mainly by imaging criteria). Choice of procedure may be influenced by anatomy (high stenosis, difficult CAS or CEA access, incomplete circle of Willis), prior illness or treatment (radiotherapy, other neck surgery), or patient risk (unable to lie flat, poor AHA assessment). In conclusion, neither systematic nor abandoned, the place of carotid revascularization must necessarily be limited to the plaques at highest risk, leaving a large place for optimized medical treatment as first line management. An evaluation of the value of performing endarterectomy on plaques considered to be at high risk is currently underway in the ACTRIS and CREST 2 studies. These studies, along with the next result of ACST-2 trial, will provide us a more precise strategy in case of carotid stenosis.

Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is associated with arterial ruptures due to a mutant gene encoding collagen type III (Col-III). To better understand the role of Col-III, we aimed at evaluating aortic stiffness and dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice) or a qualitative Col-III defect (col3KI mice). MATERIALS AND METHODS: Abdominal aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared to their respective wild type (WT) littermates using a 15 MHz ultrafast ultrasonic transducer. A carotid catheter continuously monitored pressure changes due to phenylephrine injections. PWV1, generated at diastolic blood pressure (DBP), and PWV2, at systolic blood pressure (SBP) were recorded. Difference between PWV2 and PWV1 (Delta-PWV) normalized by the pulse pressure (PP), corresponding to the aortic stiffening over the cardiac cycle, were compared between mutant and WT mice, as well as the regression slope of PWV as a function of pressure. RESULTS: Delta-PWV/PP was lower in col3KO (p = 0.033) and col3KI mice (p < 0.001) vs. WT-mice regardless of the pressure level. The slope of PWV1 with DBP increase showed a lower arterial stiffness in mutant mice vs. controls in both models. This difference was amplified when evaluating stiffness at systolic blood pressure levels with PWV2. CONCLUSION: In both vEDS mouse models, aortic stiffening was reduced, mainly driven by a lower stiffness at systolic blood pressure. Defective Col-III may be responsible for this, as it is utilized when pressure rises. These pre-clinical data could explain vascular fragility observed in vEDS patients.

Evaluation of a new model of hind limb ischemia in rabbits.

OBJECTIVE: Various animal models of critical limb ischemia have been developed in the past. However, there is no animal model that can undergo endovascular treatment, while providing reproducible true critical limb ischemia with arterial ulcers and rest pain. We evaluated the efficacy of a new model of rabbit hindlimb ischemia created through a percutaneous approach using embolization with calibrated particles. METHODS: Through a percutaneous transauricular artery approach and selective catheterization of the superficial femoral artery, embolization of distal limb vessels was performed using a mixture of 300- to 500-µm calibrated microparticles (Embosphere, Merit Medical, Salt Lake City, Utah), saline solution, and iodine contrast. Clinical and ultrasound imaging-based blood flow evaluation was performed before embolization and during follow-up. Histologic evaluation was performed at humane killing 14 days after the procedure. RESULTS: The model was successfully created in 10 rabbits (10 limbs). One rabbit died of sudden death at 8 days after the procedure. The nine surviving rabbits developed hind ulcers. All rabbits had a higher pain score in the follow-up compared to baseline value (P < .0001). Blood flow in the saphenous artery decreased significantly after the procedure and later at 14 days follow-up (baseline value 63.4 ± 31.3 µL per cardiac cycle vs 32.0 ± 28.4 µL per cardiac cycle postprocedure [P = .0013] and 32.0 ± 28.4 µL per cardiac cycle at 14 days [P = .0015]). Pathology showed signs of severe limb ischemia in all rabbits with subacute and chronic injury patterns. CONCLUSIONS: A rabbit hind limb ischemia model created by percutaneous transauricular distal femoral artery embolization with calibrated particles may overcome some of the limitations of existing animal models. As such, this model could prove useful for assessing therapies designed to improve arterial perfusion and collateral growth.