Feasibility study of Syngo iFlow in predicting hemodynamic improvement post-endovascular procedure in peripheral artery disease.

OBJECTIVE: This study endeavors to examine the feasibility of predicting the clinical outcomes of patients suffering from peripheral artery disease (PAD) who undergo endovascular intervention, by employing the Syngo iFlow technology. METHODS: Retrospectively enrolling 76 patients from December 2021 to May 2023, yielding a total of 77 affected limbs, this study employs clinical outcomes (improvement or otherwise) as the gold standard. Two physicians conducted visual assessments on both DSA and iFlow images to gauge patient improvement and assessed inter-observer consistency for each image modality. The Time to Peak (TTP) of regions of interest (ROI) at the femoral head, knee joint, and ankle joint was measured. Differences in pre- and post-procedure TTP were juxtaposed, and statistically significant parameter cutoff values were identified via ROC analysis. Employing these cutoffs for TTP classification, multivariate logistic regression and the C-statistic were utilized to assess the predictive value of distinct parameters for clinical success. RESULTS: Endovascular procedure exhibited technical and clinical success rates of 82.58 and 75.32%, respectively. Diagnostic performance of iFlow image visual assessment surpassed that of DSA images. Inter-observer agreement for iFlow and DSA image evaluations was equivalent (κ = 0.48 vs 0.50). Post-classification using cutoff values, multivariate logistic regression demonstrated the statistical significance of ankle joint TTP in post-procedure iFlow images of the endovascular procedure for clinical success evaluation (OR 7.21; 95% CI 1.68, 35.21; P = 0.010), with a C-statistic of 0.612. CONCLUSION: Syngo iFlow color-encoded imagery holds practical value in assessing the technical success of post-endovascular procedures, offering comprehensive lower limb arterial perfusion visualization. Its quantifiable parameters exhibit promising potential for prognosticating clinical success.

Risk Factor Analysis for Crossing Failure in Primary Antegrade Wire-Catheter Approach for Femoropopliteal Chronic Total Occlusions.

INTRODUCTION: Antegrade wire-catheter crossing remains the primary approach for femoropopliteal interventions. Nonetheless, data reporting on crossing failure are limited. Aim of this study is to identify risk factors for antegrade crossing failure in patients with femoropopliteal chronic total occlusions (CTOs). METHODS: This is a single-center, retrospective analysis. Patients with femoropopliteal CTOs treated between May 2018 and February 2020 were included into this study. Primary endpoint of this analysis was primary crossing success defined as successful antegrade crossing without the use of retrograde access, crossing or re-entry devices. The assisted crossing success was additionally analyzed. A logistic regression analysis identified risk factors for failed primary antegrade crossing. RESULTS: Data from 300 patients were analyzed. The majority (n=183, 61%) presented with lifestyle limiting claudication. The mean lesion length was 180 mm [interquartile range (IQR) 100-260 mm], whereas the median CTO length was 100 mm (IQR=50-210 mm). A chronic total occlusion crossing approach based on plaque morphology (CTOP) type I configuration was observed in 9% (n=26) of the lesions, type II in 61% (n=183), type III in 8% (n=25), and type IV in 66 CTOs (n= 66, 22%). Severe calcification based on the Peripheral Arterial Calcium Scoring Scale (PACSS), Peripheral Academic Research Consortium (PARC), and 360° grading systems was identified in 17%, 24%, and 28% of the lesions, respectively. A contralateral femoral access was used in 278 cases (93%). The primary crossing success amounted to 70% (n=210). The use of a re-entry device in 28 patients (9%) or of a combined antegrade-retrograde approach in 11% (n=34) of the cases increased the assisted crossing success to 89% (n=267). The presence of calcification (odds ratio [OR]=4.2, 95% CI=1.7-10.2) or of circumferential calcium (OR=2.5, 95% CI=1.3-4.9), a CTOP class ΙΙΙ or ΙV (OR=1.9, 95% CI=1.4-2.6), a proximal superficial femoral artery (SFA) occlusion (OR=3.5, 95% CI=1.7-7.4) and a CTO at P3 (OR=4.1, 95% CI=1.5-10.8) were associated with an increased risk for antegrade crossing failure. CONCLUSIONS: In this study, chronic total occlusions (CTO) morphology, calcification burden, and lesion's location were identified as independent risk factors for failed antegrade crossing. Nonetheless, the use of alternative crossing strategies significantly increased the overall crossing success.

Twelve-Month Clinical Outcomes of Percutaneous Deep Venous Arterialization with Alternative Techniques and Ordinary Endovascular Therapy Devices for Patients with Chronic Limb-Threatening Ischemia: Results of the DEPARTURE Japan Study.

PURPOSE: A dedicated treatment strategy is not yet established for patients with no-option chronic limb-threatening ischemia. This study aimed to evaluate the clinical outcomes of percutaneous deep venous arterialization in Japanese patients with no-option chronic limb-threatening ischemia. MATERIALS AND METHODS: Data of 18 consecutive patients with chronic limb-threatening ischemia (18 limbs; mean age: 75.5 ± 8.5 years; 14 men) who underwent percutaneous deep venous arterialization between January 2016 and November 2020 were retrospectively reviewed. The limb salvage, amputation-free survival, and wound healing rates were evaluated using the Kaplan-Meier method. RESULTS: Among 18 patients, 14 (77.8%) had diabetes, 6 (33.3%) had a non-ambulatory status, 16 (88.9%) received hemodialysis, and 15 (83.3%) had wound, ischemia, and foot infection of clinical stage 4. Rutherford 5 was observed in 33.7% of the patients and Rutherford 6 in 66.7%. The technical success rate of percutaneous deep venous arterialization was 88.9%. Four patients required major amputation within 30 days; percutaneous deep venous arterialization failed in two of these patients. At 6 and 12 months, the limb salvage rates, amputation-free survival rates, and complete wound healing rates were 72.2 and 72.2%, 55.6 and 49.4%, and 23.0 and 53.2%, respectively. The median time to complete wound healing was 234 (interquartile range, 127-306) days. CONCLUSION: This study presented the clinical outcomes of patients with chronic limb-threatening ischemia who underwent percutaneous deep venous arterialization in Japan. Acceptable, safe, and efficacious results were reported. Before major amputation, percutaneous deep venous arterialization can be considered for patients with no-option chronic limb-threatening ischemia. LEVEL OF EVIDENCE: Level 3. Non-randomized, follow-up study.

Multi-Level Lower Extremity Arterial Revascularization Via Retrograde Pedal Access Under Local Anesthesia in a Patient With Severe Cardiopulmonary Comorbidities: A Case Report.

BACKGROUND: Chronic limb-threatening ischemia is a severe form of peripheral artery disease that leads to high rates of amputation and mortality if left untreated. Bypass surgery and antegrade endovascular revascularization through femoral artery access from either side are accepted as conventional treatment modalities for critical limb ischemia. The retrograde pedal access revascularization is an alternative treatment modality useful in specific clinical scenarios; however, these indications have not been well described in literature. This case report highlights the use of retrograde pedal access approach as primary treatment modality in a patient with an extensive comorbidities precluding general anesthesia nor supine positioning. CASE PRESENTATION: The patient is a 60-year-old female with multiple severe cardiopulmonary comorbidities presenting with dry gangrene of the right great toe. Her comorbidities and inability to tolerate supine positioning precluded her from receiving open surgery, general anesthesia or monitored sedation, or percutaneous femoral access. Rather, the patient underwent ankle block and retrograde endovascular revascularization via dorsalis pedis artery access without post-operative complications. DISCUSSION: The prevalence of comorbidities related to peripheral artery disease is increasing and with it the number of patients who are not optimal candidates for conventional treatment methods for critical limb ischemia. The retrograde pedal access revascularization as initial treatment modality offers these patients an alternative limb salvaging treatment option.

Head-to-head comparison of sirolimus- versus paclitaxel-coated balloon angioplasty in the femoropopliteal artery: study protocol for the randomized controlled SIRONA trial.

BACKGROUND: Endovascular revascularization has established as the first-line therapy of femoropopliteal artery disease. Paclitaxel-coated balloon angioplasty proved to be superior to plain old balloon angioplasty (POBA) regarding prevention of restenosis and need for recurrent revascularization. Over the past years, paclitaxel was the only active drug to inhibit neointimal proliferation which could be processed to an appropriate balloon coating. The purpose of this study is to assess whether efficacy and safety of sirolimus-coated balloon angioplasty is noninferior to paclitaxel-coated balloon angioplasty. METHODS: This randomized controlled, single-blinded, multicentre, investigator-initiated noninferiority trial aims to enrol a total of 478 participants with symptomatic femoropopliteal artery disease of Rutherford category 2 to 4 due to de novo stenosis or restenosis. After pre-dilation, participants will be allocated in a 1:1 ratio to either sirolimus- or paclitaxel-coated balloon angioplasty. Post-dilation with the drug-coated balloon (DCB) used or standard balloon is mandatory in case ≥ 50%, and optional in case of ≥ 30% residual diameter stenosis. Bailout stenting with bare-metal nitinol stents should be conducted in case of flow-limiting dissection. Primary noninferiority endpoints are primary patency and the composite of all-cause mortality, major target limb amputation, and clinically driven target lesion revascularization at 12 months. Secondary outcomes are clinical and hemodynamic improvement, change in health-related quality of life, and safety throughout 60 months. DISCUSSION: Although concerns about long-term safety of paclitaxel-coated devices were not confirmed by recent patient-level data analyses, conflicting evidence contributed to a loss of confidence among patients and physicians. Therefore, sirolimus, known for a broader therapeutic range than paclitaxel, may serve as a welcome alternative. This will be justified if noninferiority of sirolimus-coated balloon angioplasty against the current standard of paclitaxel-coated balloon angioplasty can be demonstrated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04475783 . Registered on 17 July 2020 EUDAMED No. CIV-20-11-035172, DRKS00022452.

Hyperbaric oxygen therapy and fluorescence angiography in arterial insufficiency secondary to injection of crushed hydromorphone.

INTRODUCTION: Foreign body emboli can lead to acute arterial insufficiency. We present a case report of upper extremity arterial insufficiency in an intravenous (IV) drug user secondary to intra-arterial injection of crushed tablet particles successfully treated with hyperbaric oxygen (HBO2) therapy. CASE: A 37-year-old right-hand-dominant male developed pain and swelling of the left hand after attempting to inject crushed hydromorphone tablets into his venous circulation. Angiography revealed incomplete distal filling of the proper digital arteries, princeps pollicis, and radialis indicis branches of the left hand. The patient was treated with HBO2 for acute arterial insufficiency, secondary to these findings. Fluorescence angiography was performed prior to, during and after completion of HBO2, which showed improved perfusion of the hand upon completion of serial imaging. The patient underwent subsequent partial amputation of the left second digit and removal of the thenar and third finger pads. DISCUSSION: Much of the literature on treatment of arterial insufficiency with HBO2 are in relation to chronic problem wounds. However, there is limited data on adjunctive treatment with HBO2 for foreign body embolism. Fluorescence angiography and clinical exam were used to track tissue perfusion and progression throughout course of therapy with HBO2. CONCLUSION: Acute arterial insufficiency induced by foreign body embolism was successfully treated with HBO2 and provided increased tissue salvage of the patient's hand. The use of fluorescence angiography as a secondary measure of perfusion can provide additional insight regarding qualitative tissue oxygenation and may be a viable tool to track patient progress during HBO2 treatment.

Improving Limb Salvage for Chronic Limb-Threatening Ischemia With Spinal Cord Stimulation: A Retrospective Analysis.

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease (PAD). Up to a third of CLTI patients are not eligible to receive first-line treatments such as bypass surgery or endovascular interventions. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculatory blood flow and relieve ischemic pain in CTLI patients. The aim of the study was to evaluate limb salvage, ulcer closure, and clinical changes of SCS implanted CTLI patients at 1-year follow-up. METHODS: Eligible patients had end-stage lower limb PAD unresponsive to medical therapy and not amenable to surgical reconstruction. Patients were candidates for amputation, but limb loss was not inevitable (Fontaine stage III and IV). Pain intensity and skin temperature in the ischemic area (visual analogue scale), quality of life (WHOQoL-BREF), and ankle/brachial blood pressure index (ABI) were recorded at routine follow-up visits. Data were analyzed retrospectively. RESULTS: 29 patients underwent SCS implantation at one vascular center. The minimum follow-up period was 30 months. Limb survival at 1-year follow-up was 97% (28/29) and 73% (11/15) had complete closure of limb ulcers. Pain intensity, skin temperature, and quality of life progressively improved up to 12 months after implant, with Fontaine stage III patients improving more substantially than Fontaine stage IV patients. SCS therapy did not affect ABI measurement. No complications related to the device or procedure occurred. CONCLUSIONS: SCS is a valid alternative in patients unsuitable for revascularization. The quality of results depends on both a strict selection of patients by vascular specialists and the frequency of follow-up controls. The therapy may be more beneficial in patients classified as Fontaine stage III.

Intracranial and systemic atherosclerosis in the NAVIGATE ESUS trial: Recurrent stroke risk and response to antithrombotic therapy.

BACKGROUND: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. METHODS: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. RESULTS: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). CONCLUSIONS: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

Exercise therapy in routine management of peripheral arterial disease and intermittent claudication: a scoping review.

BACKGROUND: Little is known about the extent to which routine care management of peripheral arterial disease (PAD) and intermittent claudication (IC) align with best practice recommendations on exercise therapy. We conducted a scoping review to examine the published literature on the availability and workings of exercise therapy in the routine management of patients with PAD and IC, and the attitude and practice of health professionals and patients. METHODS: A systematic search was conducted in February 2018. The Cumulative Index of Nursing and Allied Health Literature, Ovid MEDLINE, Allied and Complementary Medicine Database, ScienceDirect, Web of Science and the Directory of Open Access Repositories were searched. Hand searching of reference lists of identified studies was also performed. Inclusion criteria were based on study aim, and included studies that reported on the perceptions, practices, and workings of routine exercise programs for patients with IC, their availability, access, and perceived barriers. RESULTS: Eight studies met the eligibility criteria and were included in the review. Studies conducted within Europe were included. Findings indicated that vascular surgeons in parts of Europe generally recognize supervised exercise therapy as a best practice treatment for IC, but do not often refer their patients for supervised exercise therapy due to the unavailability of, or lack of access to supervised exercise therapy programs. Available supervised exercise therapy programs do not implement best practice recommendations, and in the majority, patients only undergo one session per week. Some challenges were cited as the cause of the suboptimal program implementation. These included issues related to patients' engagement and adherence as well as resource constraints. CONCLUSION: There is a dearth of published research on exercise therapy in the routine management of PAD and IC. Available data from a few countries within Europe indicated that supervised exercise is underutilized despite health professionals recognizing the benefits. Research is needed to understand how to improve the availability, access, uptake, and adherence to the best exercise recommendations in the routine management of people with PAD and IC.

Quality of Life and Traditional Outcome Results at 1 Year in Elderly Patients Having Critical Limb Ischemia and the Role of Conservative Treatment.

INTRODUCTION: Revascularization is the cornerstone of the treatment of critical limb ischemia (CLI), but the number of elderly frail patients increase. Revascularization is not always possible in these patients and conservative therapy seems to be an option. The goals of this study are to analyze the 1-year quality of life (QoL) results and mortality rates of elderly patients with CLI and to investigate if conservative treatment could be an acceptable treatment option. METHODS: Patients with CLI ≥70 years old were included in a prospective observational cohort study in 2 hospitals in the Netherlands between 2012 and 2016 and were divided over 3 treatment modalities: endovascular therapy, surgical revascularization, and conservative treatment. The World Health Organization Quality of Life (WHOQoL-Bref) instrument, a generic QoL assessment tool that includes components of physical, psychological, social relationships and environment, was used to evaluate QoL at baseline, 6 months, and 1 year. RESULTS: In total, 195 patients (56% male, 33% Rutherford 4, mean age of 80) were included. Physical QoL significantly increased after surgical (10.4 vs 14.9, P < .001), endovascular (10.9 vs 13.7, P < .001), and conservative therapy (11.6 vs 13.2, P = .01) at 1 year. One-year mortality was relatively low after surgery (10%) compared to endovascular (40%) and conservative therapy (37%). CONCLUSION: The results of this study could not be used to designate the superior treatment used in elderly patients with CLI. Conservative treatment could be an acceptable treatment option in selected patients with CLI unfit for revascularization. Treatment of choice in elderly patients with CLI is based on multiple factors and should be individualized in a shared decision-making process.

Utilization and Outcomes of Local Anesthesia and Peripheral Nerve Block for Hybrid Lower Extremity Revascularization.

Purpose: To investigate the utilization of local anesthesia or peripheral nerve block with monitored anesthesia care (LPMAC) and its impact on the perioperative outcomes of hybrid lower extremity revascularization (LER) compared with general anesthesia (GA). Materials and Methods: A search of the ACS-NSQIP database between 2005 and 2017 identified 9430 patients who underwent hybrid LER for peripheral artery disease. Excluding 449 ineligible cases left 8981 hybrid LER patients for analysis. The patients were dichotomized based on the anesthetic technique: 8631 (96.1%) GA and 350 (3.9%) LPMAC. The GA patients were matched 3:1 based on propensity scores to patients in the LPMAC group based on gender, age, race, functional status, transfer status, chronic obstructive pulmonary disease (COPD), dialysis status, American Society of Anesthesiologists (ASA) class, emergent surgery, preoperative sepsis, indication, and type of open and endovascular procedure. Outcomes including complications, mortality, procedure time, and hospital length of stay were compared between the matched groups (801 GA vs 267 LPMAC). Results: Comparing the unmatched groups, those treated under LPMAC were older (72.7±9 vs 68±8.4 years, p<0.001) and had higher rates of COPD (24.3% vs 17%, p=0.001), dialysis dependence (8.1% vs 4.2%, p=0.002), preoperative sepsis (6.6% vs 4.2%, p=0.029), and ASA class ≥IV (29.1% vs 24.1%, p=0.036) than in the unmatched GA cohort. In the matched comparison, LPMAC was associated with lower overall morbidity (25.5% vs 32.3%, p=0.042) and shorter operating time (202.7±98 vs 217.7±102 minutes, p=0.034) compared with GA. The rate of myocardial infarction was lower (1.1% vs 2.4%) and ventilator use for >48 hours was less frequent (0.4% vs 2.6%) for LPMAC patients, though statistical significance was not reached. There was no difference in mortality or hospital length of stay. Conclusion: LPMAC is an infrequent anesthetic technique for hybrid LER and is primarily used for patients with a high burden of comorbidities. LPMAC is associated with reduced overall morbidity and operating time. Further studies are needed to identify which patients undergoing hybrid LER benefit most from LPMAC.

Long-Term Clinical and Angiographic Outcomes After Implantation of New-Generation Drug-Eluting Stents for Patients on Maintenance Hemodialysis.

Prior research has revealed poorer clinical outcomes after drug-eluting stent (DES) implantation for hemodialysis patients. This study aims to investigate the long-term clinical and angiographic outcomes after new-generation DES implantation for hemodialysis patients.We retrospectively enrolled 91 consecutive patients (118 lesions) who underwent successful new-generation DES (everolimus-, zotarolimus-, and biolimus-eluting stents) implantation for the first time. We measured the serum calcium and phosphorus levels in the blood samples obtained just before hemodialysis. The follow-up period of clinical events was, at least, 1.5 years. In this study, major adverse cardiac and cerebrovascular events (MACCE) and clinically driven target lesion revascularization were reported in 36 (39.6%) and 11 (12.1%) patients, respectively. The prevalence of peripheral artery disease was significantly higher in the MACCE group (41.7% versus 14.5%, P = 0.006). The serum calcium level was significantly higher in the MACCE group (9.34 ± 0.92 mg/dL versus 8.77 ± 0.88 mg/dL; P = 0.004). The multivariate Cox proportional hazards model revealed that the serum calcium level (hazard ratio, 1.86; 95% confidence interval [CI]: 1.26-2.77; P = 0.002), suboptimal (over 55 mg2/dL2) calcium-phosphorus product (hazard ratio, 3.27; 95% CI: 1.41-7.61; P = 0.006) and the coexistence of peripheral artery disease (hazard ratio, 3.15; 95% CI: 1.49-6.65; P = 0.003) were independent predictors of MACCE.For hemodialysis patients, MACCE remains a frequent occurrence after new-generation DES implantation and is associated with calcium-phosphate metabolism and peripheral artery disease.

External applicability of the COMPASS trial: the Western Denmark Heart Registry.

AIMS: In the COMPASS trial, combined aspirin and rivaroxaban treatment reduced ischaemic events in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We estimated the proportion of COMPASS eligible patients among unselected patients undergoing coronary angiography (CAG) and compared outcome rates among COMPASS eligible and non-eligible patients. METHODS AND RESULTS: We applied the COMPASS study criteria on patients undergoing CAG in Western Denmark (2004-11). Both COMPASS eligible and non-eligible patients had CAD/PAD and met no exclusion criteria, but only COMPASS eligible patients met the inclusion criteria. We assessed the COMPASS primary endpoint of cardiovascular death, ischaemic stroke, haemorrhagic stroke, or myocardial infarction (MI). We computed event rates and adjusted incidence rate ratios (aIRRs). Of 80 071 patients undergoing CAG, 27 939 did not have CAD or PAD and were not considered. Of the 52 132 patients remaining, 11 930 were COMPASS eligible. Rates of the primary endpoint were 4.8 (95% confidence interval 4.6-5.0) events per 100 person-years among COMPASS eligible patients and 2.3 (2.2-2.4) among COMPASS non-eligible patients [aIRR 1.7 (1.6-1.9)]. COMPASS eligible patients also had higher risks of cardiovascular death [aIRR 2.5 (2.1-3.0)], ischaemic stroke [aIRR 1.4 (1.2-1.6)], and MI [aIRR 1.9 (1.7-2.1)]. CONCLUSION: In this all-comers CAG cohort, 15% were eligible for combined aspirin and rivaroxaban treatment. COMPASS eligible patients had up to 2.5-fold higher rates of cardiovascular events than non-eligible patients. The higher incidence of ischaemic events in COMPASS eligible patients highlights an unmet need for additional preventive measures.

Ultrasound imaging and on-demand therapy of peripheral arterial diseases using H2O2-Activated bubble generating anti-inflammatory polymer particles.

Muscles of peripheral artery disease (PAD) patients are under oxidative stress associated with a significantly elevated level of reactive oxygen species (ROS) including hydrogen peroxide (H2O2). Curcumin is a major active constituent of turmeric and is well known for its highly potent antioxidant, anti-inflammatory and angiogenic effects. We previously reported antioxidant vanillyl alcohol-incorporated copolyoxalate (PVAX) which is designed to rapidly scavenge H2O2 and release bioactive vanillyl alcohol and CO2 in a H2O2-triggered manner. In this work, we developed curcumin-loaded PVAX (CUR-PVAX) nanoparticles as contrast-enhanced ultrasound imaging agents as well as on-demand therapeutic agents for ischemic injuries based on the hypothesis that PVAX nanoparticles generate echogenic CO2 bubbles through H2O2-triggered oxidation of peroxalate esters and the merger of curcumin and PVAX exerts H2O2-activatable synergistic therapeutic actions. CUR-PVAX nanoparticles also displayed the drastic ultrasound signal in ischemic areas by generating CO2 bubbles. CUR-PVAX nanoparticles exhibited significantly higher antioxidant and anti-inflammatory activities than empty PVAX nanoparticles and equivalent curcumin in vascular endothelial cells. A mouse model of ischemic injury was used to evaluate the potential of CUR-PVAX nanoparticles as ultrasound imaging agents and on-demand therapeutic agents. CUR-PVAX nanoparticles significantly suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Moreover, CUR-PVAX nanoparticles significantly enhanced the level of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1, also known as CD31), leading to blood perfusion into ischemic tissues. We, therefore, believe that CUR-PVAX nanoparticles hold great translational potential as novel theranostic agents for ischemic diseases such as PAD.

Critical limb ischemia: current challenges and future prospects.

Critical limb ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. In this review, we presented a complete overview about physiopathology, diagnosis and holistic management of CLI. Revascularization is the first-line treatment, but several challenging cases are not treatable by conventional techniques. Unconventional techniques for the treatment of complex below-the-knee arterial disease are described. Furthermore, the state-of-the-art on gene and cell therapy for the treatment of no-option patients is reported.

In Patients with Severe Peripheral Arterial Disease, Revascularization-Induced Improvement in Lower Extremity Ischemia Can Be Detected by Laser Speckle Contrast Imaging of the Fluctuation in Blood Perfusion after Local Heating.

BACKGROUND: We previously reported the utility of the perfusion value (PV) fluctuation slope for detecting severe ischemia in the lower limb. Our approach was based on a thermal load test mimicking the well-known physiological reaction termed "cold-induced vasodilation," which is known to occur as a 3-phase phenomenon. The slope parameter quantifies the decrease in PVs accompanying the relative cooling (third phase) following the transient increase in blood flow (second phase) induced by the applied thermal load. This phenomenon of "relative" cold-induced vasodilation (rCIVD) can be monitored using laser speckle contrast imaging (LSCI) after applying the thermal load (LTL test). Here, we aimed to determine whether the slope parameter obtained via the LTL test also reflects the improvement in hemodynamics after revascularization. METHODS: The study enrolled 16 patients (18 limbs), who underwent revascularization for peripheral arterial disease (PAD). The measurements were performed at 2 sites in each limb (in total, 34 sites; 2 sites in one patient were excluded because of significant movement during the measurement). For each site, we recorded the slope describing the behavior of PVs (decrease or plateau) in the third phase of rCIVD, following the initial, heating-induced increase in perfusion (second phase of rCIVD). The plateau group (group P), which included patients with an abnormal rCIVD, and the decrease group (group D), which included patients with a normal rCIVD, were defined based on perfusion slope values of <0.20 and ≥ 0.20 perfusion units/min, respectively. We also quantified the transient increase in perfusion (from baseline to peak) as a descriptor of perfusion behavior during the second phase of rCIVD. RESULTS: In group P, the change in median values (25-75%) of the slope, transcutaneous oxygen tension, and ankle-brachial index (ABI) from before to after operation was (-0.02 [-0.04 to 0.02]; 4 [1-11]; and 0.08 [0-0.27]) to (0.39 [0.32-0.59]; 46 [37-54]; and 0.81 [0.72-0.90]). Conversely, in group D, the change in the median values of the slope, transcutaneous oxygen tension, and ABI between before and after operation was (0.38 [0.32-0.49]; 40.5 [35-45]; and0.58 [0.57-0.65]) to (0.44 [0.30-0.64]; 52 [43-56]; and 0.92 [0.81-0.99]). Sites exhibiting perfusion pattern of group D in the third phase of rCIVD showed no significant change in slope after revascularization (P = 0.21), whereas the slope in group P increased significantly after revascularization, becoming similar to the postoperative slopes in group D (P = 0.81). The amount of transient increase in perfusion, which quantified the behavior in the second phase of rCIVD, showed a similar behavior. Preoperatively, all patients in group P had rest pain and/or ulcer of the foot, whereas only few patients in group D had such symptoms. CONCLUSIONS: Normal rCIVD response in the LTL test indicates less-than-severe ischemia, while abnormal rCIVD response measured via the LTL test indicates severe ischemic symptoms, such as critical limb ischemia. Notably, patients with an abnormal rCIVD response can develop a normal rCIVD response following revascularization, thereby reflecting an improvement in blood flow. The LTL test assessing rCIVD response can be useful for detecting severe limb ischemia, such as critical limb ischemia (CLI), and determining the departure from severe limb ischemia by revascularization.

Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures.

OBJECTIVE: Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. METHODS: This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. RESULTS: There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. CONCLUSIONS: Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results.

Intra- and Inter-rater Reliability of Peripheral Arterial Blood Flow Velocity by Means of Doppler Ultrasound.

OBJECTIVE: Although it is possible to find studies that analyze the velocity of blood flow in different arteries, the reliability of Doppler ultrasound on peripheral arteries has not yet been completely established. Our objective was to evaluate intra- and inter-rater reliability of the measurement of blood flow velocity by Doppler ultrasound of brachial, radial, popliteal, and posterior tibial arteries. METHODS: Fifty healthy individuals of both genders, aged between 18 and 45 years, were included in the study. For the evaluation of arterial blood flow velocity, a portable Doppler ultrasound device was used to measure the mean and maximum blood flow velocity of posterior tibial, popliteal, brachial, and radial arteries. Two examiners performed assessments of the same volunteers independently and twice, with an interval of 1 week between them. RESULTS: We found good to very good reliability for measuring the mean and maximum blood flow velocity of the arteries evaluated. The intraclass correlation coefficients ranged between 0.501 and 0.866, standard error of measurement ranged between 0.81 and 9.45 cm/s, and minimum detectable change ranged between 2.25 and 26.13 cm/s. CONCLUSION: The assessment of mean and maximum blood flow velocity of the brachial, radial, popliteal, and posterior tibial arteries by means of Doppler ultrasound presents acceptable reliability values, which supports the use of this evaluation method in research and clinical practice.