Lower Limb Peripheral Arterial Disease Research Articles

Modelling lower-limb peripheral arterial disease using clinically available datasets: impact of inflow boundary conditions on hemodynamic indices for restenosis prediction

Background and ObjectivesThe integration of hemodynamic markers as risk factors in restenosis prediction models for lower-limb peripheral arteries is hindered by fragmented clinical datasets. Computed tomography (CT) scans enable vessel geometry reconstruction and can be obtained at different times than the Doppler ultrasound (DUS) images, which provide information on blood flow velocity. Computational fluid dynamics (CFD) simulations allow the computation of near-wall hemodynamic indices, whose accuracy depends on the prescribed inlet boundary condition (BC), derived from the DUS images. This study aims to: (i) investigate the impact of different DUS-derived velocity waveforms on CFD results; (ii) test whether the same vessel areas, subjected to altered hemodynamics, can be detected independently of the applied inlet BC; (iii) suggest suitable DUS images to obtain reliable CFD results. MethodsCFD simulations were conducted on three patients treated with bypass surgery, using patient-specific DUS-derived inlet BCs recorded at either the same or different time points than the CT scan. The impact of the chosen inflow condition on bypass hemodynamics was assessed in terms of wall shear stress (WSS)-derived quantities. Patient-specific critical thresholds for the hemodynamic indices were applied to identify critical luminal areas and compare the results with a reference obtained with a DUS image acquired in close temporal proximity to the CT scan. ResultsThe main findings indicate that: (i) DUS-derived inlet velocity waveforms acquired at different time points than the CT scan led to statistically significantly different CFD results (p<0.001); (ii) the same luminal surface areas, exposed to low time-averaged WSS, could be identified independently of the applied inlet BCs; (iii) similar outcomes were observed for the other hemodynamic indices if the prescribed inlet velocity waveform had the same shape and comparable systolic acceleration time to the one recorded in close temporal proximity to the CT scan. ConclusionsDespite a lack of standardised data collection for diseased lower-limb peripheral arteries, an accurate estimation of luminal areas subjected to altered near-wall hemodynamics is possible independently of the applied inlet BC. This holds if the applied inlet waveform shares some characteristics – derivable from the DUS report – as one matching the acquisition time of the CT scan.

Patient Factors Influencing Prescription of Antithrombotic Medication After Lower Limb Endovascular Intervention

There is significant practice variation in the use of antithrombotic therapy after endovascular intervention for lower limb peripheral arterial disease, with differences in medication choice and duration. Prescriber decision making is complex, and patient factors have been shown to substantially contribute to prescribing variation. To determine the influence of patient factors on antithrombotic prescribing, a discrete choice experiment was distributed to vascular surgeons and trainees across Australia and Aotearoa New Zealand. After pilot testing, the discrete choice experiment questionnaire was distributed to 300 vascular surgeons and trainee members of the Australian and New Zealand Society for Vascular Surgery. Multinomial logistic regression models were used to analyse patient factors that had the most influence on decisions to prescribe a second antithrombotic agent, and the preferred choice of antithrombotic (clopidogrel 75 mg daily or rivaroxaban 2.5 mg twice daily) in addition to aspirin 100 mg daily. The odds ratio (OR) with 95% confidence interval (CI) reported preference strength. A total of 44 questionnaires were completed between September and October 2023, reaching the 15% targeted response rate. Prescribing a second antithrombotic was more likely after femoropopliteal stenting compared with angioplasty (OR 1.89, 95% CI 1.20 - 2.13), and in chronic limb threatening ischaemia compared with intermittent claudication (OR 1.58, 95% CI 1.20 - 2.13). Most respondents preferred clopidogrel over rivaroxaban (62%), with over a third of respondents exclusively prescribing clopidogrel. Patients with stents (OR 1.77, 95% CI 1.32 - 2.37) or moderate bleeding risk (OR 1.38, 95% CI 0.97 - 1.84) were more likely to receive clopidogrel than rivaroxaban. This study demonstrates that vascular surgeons primarily prioritise antithrombotic prescribing decisions by procedure type. Clopidogrel is more likely to be prescribed than rivaroxaban as a second agent in combination with aspirin, especially after stenting. Knowing these clinician preferences can target implementation strategies towards supporting decision making in subgroups of patients according to individual risk profiles.

A Systematic Review and Meta-Analysis of Heparin-Bonded Expanded Polytetrafluoroethylene Grafts for Below-The-Knee Femoral Bypass Surgery

Heparin-bonded expanded polytetrafluoroethylene (hb-ePTFE) synthetic grafts are an alternative to autologous vein grafts (AVG) for surgical bypass interventions in lower limb peripheral arterial disease (LLPAD). However, the clinical benefits of hb-ePTFE grafts have not been reviewed systematically for patients undergoing below-the-knee (BK) surgical bypass. This study aimed to meta-analyze available data on the utility of hb-ePTFE in patients undergoing BK surgical bypass. Medline, Embase, and Cochrane databases were searched, restricted to material in English with no date restriction. In addition, proceedings from relevant congresses were screened going back 2years. The search was performed in December 2021. Eligible studies included prospective or retrospective comparative studies or prospective single-arm cohorts with an hb-ePTFE arm. Methodological quality was assessed with the ROBINS-I criteria. Outcomes included primary patency, amputation/limb salvage, and overall survival. Clinical outcomes were expressed as event rates. Studies were compared using meta-analysis to generate a standardized mean event rate for each outcome, with its 95% confidence interval (95% CI), using a random-effects model. Following deduplication, 10,263 records were identified and 261 were assessed as full texts. No prospective comparative studies were identified. The level of evidence was uniformly low. Seventeen publications describing data from 9 individual patient cohorts met the inclusion criteria. These cohorts included a total of 1,452 patients undergoing BK surgical bypass with hb-ePTFE. The primary patency rate was 78.9% [95% CI: 72.2-85.7%] at 1year, 68.2% [95% CI: 62.8-73.6%] at 2years, decreasing to 48.0% [95% CI: 27.3-68.7%] at 5years. The secondary patency rate was 84.8% [95% CI: 77.0-92.5%] at 1year and 68.9% [95% CI: 43.0-94.9%] at 3years; the 1-year limb salvage rate was 88.3% [95% CI: 79.6-97.1%] at 1year and 79.0% [95% CI: 56.7-100%] at 3years. In patients undergoing BK bypass surgery, hb-ePTFE synthetic grafts, compared to uncoated grafts, perform well for patency and limb salvage. However, the quality of the evidence is low, and well-performed randomized clinical trials are needed to inform clinical decision-making on the choice of synthetic graft.

Rationale and Design of the Latin-American Registry of Peripheral Interventions: Insights From SOLACI Peripheral

BackgroundChronic limb-threatening ischemia (CLTI) represents the most advanced stage of lower extremity peripheral artery disease (PAD). The aim of this manuscript is to provide an overview of the demographic and clinical characteristics of patients with lower-limb peripheral artery disease, as well as the procedural and technical aspects of peripheral endovascular interventions in Latin-America. MethodsThe SOLACI peripheral registry is a prospective, multi-center, observational, and hospital-based registry of patients with lower-limb PAD, who are treated with endovascular interventions across Latin American countries. ResultsA total of 1057 independent procedures (997 patients) were analyzed in this report. The most common clinical presentation was CLTI (61.2%): Advanced stage of the disease was common, and the symptomatic classification was predominately Rutherford V (minor tissue loss) in 37.6%. Index endovascular procedures mainly treated femoral-popliteal and infrapopliteal regions. Disease extending across multiple vascular territories was common and 27.6% of patients underwent angioplasty of multiple regions during the same procedure. There was a high prevalence of cardiovascular risk factors and concomitant comorbidities: hypertension (84.5%), dyslipidemia 67.4%), diabetes mellitus (64.7%), myocardial infarction (17%) and stroke (8.4%). Major adverse events during hospitalization included death from any cause (1.3%), cardiovascular death (0.7 %), myocardial infarction (0.4%), stroke (0.1%) and bleeding (0.8%). ConclusionsReal-world data on lower limb-PAD in Latin American countries will help us identify unmet needs and generate evidence-based recommendations to facilitate the development of more effective preventive and treatment strategies according to each country’s necessities and resources.

Spectrum of Findings in Lower Limb Doppler Ultrasonography in UBTH, Benin City

Objectives: Doppler ultrasonography (USS) is a relatively new radiological procedure in our environment but gradually gaining recognition in assessment of lower limb pathologies. This study aims to assess the pattern of referrals for lower limb Doppler USS and the outcome of the procedure at the University of Benin teaching hospital&#x0D; Materials and Methods: This was a retrospective study carried out at the University of Benin teaching hospital, between January 2018 and June 2019. The request forms and Doppler scan results of patients done within this period were retrieved and relevant information were obtained and analyzed using statistical package for social sciences, version 23.&#x0D; Results: A total of 204 patients comprising of 125 females (61.3%) and 79 males (38.7%) were analyzed in this study. Mean age of study population was 55.25±17.02 years. The commonest indication for lower limb Doppler scan was leg swelling (70, 22.8%) while the least was peripheral arterial disease (PAD) (14, 4.6%) The commonest Doppler ultrasound finding was PAD (74, 44.3%), followed by DVT (39, 23.4%). The least findings on Doppler ultrasound of the lower limb was arterio-venous malformation (AV) malformation (1, 0.6%). Arterial wall calcification (100%) was the commonest Doppler finding in patients with PAD. DVT occurred more in the left lower limb (67.7%) than right limb (32.3%) and superficial femoral vein (27.8%) was most affected.&#x0D; Conclusion: This study has shown that Doppler scan is quite relevant in lower limb pathologies and peripheral artery disease is the commonest diagnosis in the lower limb.

Mortality in a Nationwide Practice-Based Cohort Receiving Paclitaxel-Coated Devices for Lower Limb Peripheral Artery Disease

BackgroundAccording to a meta-analysis of randomized clinical trials, paclitaxel-coated devices (PCDs) for lower limb endovascular revascularization may be associated with increased risk of late mortality. ObjectivesThe purpose of this study was to determine whether PCDs are associated with all-cause mortality in a real-world setting. MethodsDETECT is a nationwide, exhaustive retrospective cohort study using medico-administrative data from the French National Healthcare System representing >99% of the population. The main selection criterion was the first procedure of interest: endovascular revascularization for lower limb peripheral artery disease involving ≥1 balloon and/or stent performed between October 1, 2011, and December 31, 2019. Patients with or without PCDs were compared for all-cause mortality until December 31, 2021. ResultsA total of 259,137 patients were analyzed, with 20,083 (7.7%) treated with ≥1 PCD. After a median follow-up of 4.1 years (Q1-Q3: 2.3-6.4 years), a total of 5,385 deaths/73,923 person-years (PY) (7.3/100 PY) and 109,844 deaths/1,060,513 PY (10.4/100 PY) were observed in the PCD and control groups, respectively. After adjustment for confounding factors, PCD treatment was associated with a lower risk of mortality in multivariable Cox analyses (HR: 0.86; 95% CI: 0.84-0.89; P < 0.001). Similar results were observed using propensity score matching approaches based on either nearest-neighbor or exact matching. ConclusionsIn a nationwide analysis based on large-scale real-world data, exposure to PCDs was not associated with a higher risk of mortality in patients undergoing endovascular revascularization for lower limb peripheral artery disease. (The DETECT Project; NCT05254106)

Comparative study of arterial doppler with digital subtraction angiography in lower limb peripheral arterial disease: a protocol

Background One of the serious cardiovascular conditions is peripheral arterial disease; in which distinctive feature is diminished blood supply towards the lower extremities, frequently because of atherosclerotic occlusive disease. Methods We will compare arterial Doppler with digital subtraction angiography in peripheral lower limb occlusive arterial sickness; to determine Peripheral Arterial Disease along with its location and stenosis severity on Duplex Ultra-Sonography and Digital Subtraction Angiography; and to determine the segment-to-segment agreement of the arterial tree within Duplex Ultra-Sonography and Digital Subtraction Angiography. Implications This will encourage the participants for periodic investigation and proper use of medications which will improve hospital/facility outcome. It will be helpful for older individuals how are more susceptible to peripheral artery disease. A fair accurate treatment options will be given to patients. Limitations Findings will only be applicable to our organization because the study will be done at one tertiary care hospital, limiting their external validity and generalizability.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Asymptomatic Lower Limb Peripheral Arterial Disease and Intermittent Claudication

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Asymptomatic Lower Limb Peripheral Arterial Disease and Intermittent Claudication

Screening for Peripheral Artery Disease Using an Automated Four-Limb Blood Pressure Monitor Equipped with Toe-Brachial Index Measurement.

Toe-brachial index (TBI) measurement helps to detect peripheral artery disease (PAD) in patients with incompressible ankle arteries due to medial arterial calcification, which is most frequently associated with diabetes. We aimed to evaluate how an automated four-limb blood pressure monitor equipped with TBI measurement could contribute to PAD screening. In 117 patients (mean age 63.2 ± 12.8 years), ankle-brachial index (ABI) measurement was performed using the Doppler-method and the MESI mTablet. TBI was obtained via photoplethysmography (MESI mTablet, SysToe) and a laser Doppler fluxmeter (PeriFlux 5000). Lower limb PAD lesions were evaluated based on vascular imaging. A significant correlation was found between Doppler and MESI ankle-brachial index values (r = 0.672), which was stronger in non-diabetic (r = 0.744) than in diabetic (r = 0.562) patients. At an ABI cut-off of 0.9, Doppler (AUC = 0.888) showed a sensitivity/specificity of 67.1%/97.4%, MESI (AUC 0.891) exhibited a sensitivity/specificity of 57.0%/100%; at a cut-off of 1.0, MESI demonstrated a sensitivity/specificity of 74.7%/94.8%. The TBI values measured using the three devices did not differ significantly (p = 0.33). At a TBI cut-off of 0.7, MESI (AUC = 0.909) revealed a sensitivity/specificity of 92.1%/67.5%. Combining MESI ABI and TBI measurements recognised 92.4% of PAD limbs. Using an ABI cut-off level of 1.0 and sequential TBI measurement increases the sensitivity of the device in detecting PAD. The precise interpretation of the obtained results requires some expertise.

Sensitivity and Specificity of Pulse Oximetry for Identification of Peripheral Artery Disease: A Systematic Review.

Lower limb peripheral artery disease (PAD) is associated with poor outcomes including ulceration, gangrene, amputations, and mortality. Clinicians therefore routinely perform point-of-care tests in high-risk populations to identify PAD and subsequently implement cardiovascular management and appropriate interventions. Pulse oximetry has been suggested as a useful adjunct test for identifying PAD. The aim of this systematic review was to determine the sensitivity and specificity of pulse oximetry in the lower limb for identifying PAD. MEDLINE, EMBASE, and CINAHL were searched up until January 10, 2023, to identify studies of sensitivity and specificity of pulse oximetry that used criterion standard diagnostic imaging as a reference standard. Two authors screened articles for inclusion and appraised quality of included studies using the Quality Appraisal for Diagnostic Accuracy Studies, version 2. A total of 6371 records were screened, and 4 were included. The included studies had a total of 471 participants, with an age range of 41 to 80.6 years. All studies were cross-sectional and conducted in hospital settings. Sensitivity values for pulse oximetry compared with diagnostic imaging in identifying PAD ranged from 44% to 76%, and specificity values ranged from 85% to 96%. There was no consensus regarding measurement techniques and diagnostic thresholds for pulse oximetry, which precluded meta-analysis. There is currently inadequate evidence to support the use of pulse oximetry for identifying PAD. Current evidence suggests that pulse oximetry has low levels of sensitivity and is therefore likely to miss PAD when it is present.

Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease: protocol for a systematic review and network meta-analysis of randomised controlled trials

IntroductionThe optimal antithrombotic regimen to reduce the risk of vascular events in patients with peripheral arterial disease (PAD) is contentious. This systematic review and network meta-analysis (NMA) aims to define...

Performance of systolic pressure index for lower limb peripheral arterial disease in a group of elderly in sub-Saharan Africa

BackgroundThe automatic measurement of the ankle-brachial index (ABI) constitutes a reliable, simple, safe, rapid, and inexpensive alternative diagnostic screening test compared with the Doppler method for peripheral arterial disease (PAD). We aimed to compare the diagnostic performance of automatic ABI measurement tests to Doppler ultrasound for PAD in a group of patients aged 65 years and above, in Sub-Saharan Africa. MethodsThis was an experimental comparative study of the performance of Doppler ultrasound to the automated ABI test in the diagnosis of PAD in patients aged ≥ 65 years followed-up at the Yaoundé Central Hospital, Cameroon between January to June 2018. An ABI threshold < 0.90 is defined as a PAD. We compare the sensitivity, and specificity of the high ankle-brachial index (ABI-HIGH), low ankle-brachial index (ABI-LOW), and the mean ankle-brachial index (ABI-MEAN) for both tests. ResultsWe included 137 subjects with an average age of 71.7 ± 6.8 years. In the ABI-HIGH mode, the automatic device had a sensitivity of 55% and a specificity of 98.35% with a difference between the two techniques of d = 0.024 (p = 0.016). In the ABI-MEAN mode, it had a sensitivity of 40.63% and a specificity of 99.15%; d = 0.071 (p < 0.0001). In the ABI-LOW mode, it had a sensitivity of 30.95% and a specificity of 99.11%; d = 0.119 (p < 0.0001). ConclusionThe Automatic measurement of systolic pressure index has a better diagnostic performance in the detection of Peripheral Arterial Disease compared to the reference method by continuous Doppler in sub-Saharan African subjects aged ≥ 65 years.

Clinical characteristics and frequency of anticoagulation in patients with atrial fibrillation and heart failure: results of a retrospective big data analysis

Aim. To evaluate the clinical characteristics and frequency of prescribed anticoagulant therapy for patients with atrial fibrillation (AF) and heart failure (HF) in subjects of the Russian Federation based on a retrospective big data analysis using artificial intelligence technologies.Material and methods. For retrospective analysis, information was obtained from the Webiomed predictive analytics platform, which includes depersonalized data from electronic health records of outand/ or inpatients in 6 subjects of the Russian Federation, extracted using artificial intelligence technologies. From the database of patients with AF (n=144431), a group of individuals (n=20970) with an established diagnosis of HF and information on left ventricular ejection fraction (LVEF) was selected.Results. Patients with AF and HF (men, 43,7%; age 72,1±13,2 years; LVEF, 58,9±11,0%) had a history of smoking in 36,6% of cases, hypertension — in 86,7%, type 2 diabetes — in 26,6%, gout — in 2,7%, stage III and IV-V chronic kidney disease — in 50,9 and 15,6%, lower limb peripheral arterial disease — in 15,8%. The incidence of ischemic stroke, LV myocardial infarction and pulmonary embolism was 8,8, 14,7 and 2,4%, respectively. Anticoagulants, including direct oral ones, were administered to patients with AF and HF in 62,5% and 32,0% of cases, respectively. The frequency of their appointment did not significantly differ depending on LVEF.Conclusion. Patients with AF and HF are characterized by significant comorbidity, a higher incidence of cardiovascular events compared with the group of individuals with AF without HF, and an unsatisfactory percentage of anticoagulant therapy.

Lower-limb peripheral arterial disease and amputations in people with diabetes: Risk factors, prognostic value and management

Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. In patients with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and dyslipidaemia, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few randomized controlled trials have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes.

Subclinical lower limb Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus: A cross-sectional study.

Background: Peripheral artery disease (PAD) is highly prevalent in patients with diabetes mellitus. The ankle-brachial index (ABI) measurement is used to diagnose peripheral arterial disease, and little is known about its prevalence in asymptomatic type 2 Diabetic patients. This study aimed to determine the prevalence of subclinical peripheral artery disease in patients with type II diabetes mellitus.&#x0D; Methodology: It was a descriptive study conducted at the Peshawar Institute of Medical Sciences, from Feb 2022 to Aug 2022. Two hundred sixty-four patients with type II diabetes (for more than three years) with no clinical features of peripheral arterial disease were assessed by measuring ankle brachial pressure index for subclinical peripheral arterial disease. Reading less than 0.9 was positive for peripheral artery disease in the lower limbs.&#x0D; Results: Peripheral Arterial Disease was present in 115 (43.6%) patients and absent in 149 (56.4%) patients. The peripheral artery disease was significantly more in males, those with age greater than 55 years, smokers, and hypertensive patients (p-value ≤ 0.05) but was not associated with the duration of diabetes or BMI of the patient (p-value &gt; 0.05)&#x0D; Conclusion: There was a high prevalence of asymptomatic peripheral artery disease in Type 2 Diabetic patients using ankle-brachial pressure index measurement. Those with ages greater than 55 years, smokers, hypertensive, and males were particularly at higher risk.

The Role of Neutrophils in Lower Limb Peripheral Artery Disease: State of the Art and Future Perspectives.

In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFβ. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

Praliciguat Promotes Ischemic Leg Reperfusion in Leptin Receptor-Deficient Mice.

Lower-limb peripheral artery disease is one of the major complications of diabetes. Peripheral artery disease is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. Despite major medical advances in the treatment of diabetes, a substantial therapeutic gap remains in the peripheral artery disease population. Praliciguat is an orally available sGC (soluble guanylate cyclase) stimulator that has been reported both preclinically and in early stage clinical trials to have favorable effects in metabolic and hemodynamic outcomes, suggesting that it may have a potential beneficial effect in peripheral artery disease. We evaluated the effect of praliciguat on hind limb ischemia recovery in a mouse model of type 2 diabetes. Hind limb ischemia was induced in leptin receptor-deficient (Leprdb/db) mice by ligation and excision of the left femoral artery. Praliciguat (10 mg/kg/day) was administered in the diet starting 3 days before surgery. Twenty-eight days after surgery, ischemic foot perfusion and function parameters were better in praliciguat-treated mice than in vehicle controls. Improved ischemic foot perfusion was not associated with either improved traditional cardiovascular risk factors (ie, weight, glycemia) or increased angiogenesis. However, treatment with praliciguat significantly increased arteriole diameter, decreased ICAM1 (intercellular adhesion molecule 1) expression, and prevented the accumulation of oxidative proangiogenic and proinflammatory muscle fibers. While investigating the mechanism underlying the beneficial effects of praliciguat therapy, we found that praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression in cultured myoblasts and that conditioned medium form praliciguat-treated myoblast decreased ICAM1 mRNA expression in endothelial cells. These results suggest that praliciguat therapy may decrease ICAM1 expression in endothelial cells by downregulating Cxcl12 in myocytes. Our results demonstrated that praliciguat promotes blood flow recovery in the ischemic muscle of mice with type 2 diabetes, at least in part by increasing arteriole diameter and by downregulating ICAM1 expression.

A cross-sectional study on coronary artery disease diagnosis in patients with peripheral artery disease

PurposeCompared with healthy individuals, patients with peripheral artery disease (PAD) generally have a very high risk of subclinical Coronary artery disease (CAD) and cardiovascular events. To determine the correlation between CAD in PAD patients, thereby promoting the lifetime of PAD patients and reducing the serious impacts of CAD. MethodsThis clinical-based cross-sectional study comprised 100 consecutive patients in India from 2014 to 2016. In this research, PAD patients were screened for CAD by treadmill stress test and cardiac colour Doppler examination. In addition, this study performed coronary angiography followed by peripheral angiography for patients who could not perform the treadmill test. ResultsWith the statistical results, the study observed a high prevalence of CAD in PAD patients that can be detected only with angiography. Further, 30.93% of asymptomatic CAD prevalence was observed in PAD patients. The study strengthens the need for coronary angiography in all symptomatic lower limb PAD cases to detect early CAD, particularly in patients with diabetes and dyslipidemia. ConclusionThere exists a strong correlation between PAD and CAD. Hence, precise diagnosis followed by supervision of PAD patients is significant for avoiding local progression of cardiovascular risk.

Frailty predicts poor longer-term outcomes in patients following lower limb open surgical revascularization.

Frailty in vascular surgery patients is increasingly recognized as a marker of poor outcome. This provides particular challenges for patients with lower limb peripheral arterial disease who require surgical revascularization. This study aimed to assess the impact of frailty on short- and long-term outcome in this specific patient group using a specialty specific frailty score. Patients undergoing open surgical revascularization for chronic limb ischemia (January 2015-December 2016) were assessed. Demographics, mode of admission, diagnosis, and site of surgery were recorded alongside a variety of frailty-specific characteristics. We calculated the previously validated Addenbrookes Vascular Frailty Score (AVFS) and Long AVFS (LAVFS). Primary outcome was 3-year mortality. Two hundred and sixty-one patients (75% men, median age 69 years) were studied. The median length of stay was 6 days with a 3-year mortality of 23%. The predictive power of vascular frailty scores showed that for 3-year mortality, area under the receiver operator curve values (AUROC) were specific for both the AVFS score (AUROC: 0.724, 95% CI: 0.654-0.794) and LAVFS Score (AUROC: 0.741, 95%CI: 0.670-0.813). Furthermore, the cumulative AVFS and LAVFS scores both predicted mortality over the follow-up period (P=0.0001) with increased mortality among patients with higher scores. Incremental worsening of frailty, determined using a specialty specific frailty score, predicts mortality risk in patients undergoing lower limb surgical revascularization.