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Introduction Varicose veins (VV) negatively impact quality of life (QoL) and have risks of major complications including bleeding, ulceration and phlebitis. During the COVID-19 pandemic, the VSGBI (Vascular Society of Great Britain and Ireland) and GIRFT (Get It Right First Time) classified VVs as lowest priority for intervention. Objective This study aims to determine harm caused and the impact on the QoL on patients waiting for their VVs procedures for more than 1 year. Methods This was a prospective study conducted at the Norfolk and Norwich University Hospital (NNUH). Patients with VVs awaiting intervention for >1 year were included in the study. Patients with CEAP C6 disease were considered to be too high risk to be invited for treatment during the Covid-19 pandemic. Patients were sent QoL questionnaires and underwent a telephone consultation to assess harm. Both generic (EQ-VAS and EQ-5D) and disease-specific (AVVQ and CIVIQ-14) instruments were utilised. There were no control groups available for comparison. Results 275 patients were identified (37.1% male) with median time on waiting list of 60 weeks (IQR 56–65). 19 patients (6.9%) came to major harm, including phlebitis (3.6%), bleeding (1.8%) and ulceration (1.8%). Fifty-two patients (18.9%) had minor harm, including worsening pain (12.7%) and swelling (6.2%). 6.9% reported psychological harm. Rising CEAP stage was also associated with worsening level of harm in patients with C5-6 disease ( p < 0.0001). Only 8.7% stated they would decline surgery during the pandemic. 104 QoL questionnaires were returned. Median EQ-VAS and EQ-5D was 75 (IQR: 60–85) and 0.685 (0.566–0.761), respectively. Median AVVQ score was 23.2 (14.9–31.0) and CIVIQ-14 score was 33 (21–44). ConclusionsThis study highlights the impact of delaying VVs surgery during a pandemic. A significant rate of both major and minor as well as psychological harm was reported. In addition, VVs had a significant detriment to quality of life.

Endovascular aortic aneurysm repair (EVAR) is the preferred method for elective abdominal aortic aneurysm (AAA) repair. However, the success of this technique depends greatly on the technologies available. Intra-operative imaging is essential but can come with limitations. More complex interventions lead to longer operating times, fluoroscopy times, and greater contrast doses. A number of intra-operative imaging modalities to quality assure the success of EVAR have been developed. A systematic literature search was performed with separate searches conducted for each imaging modality in the study: computed tomography (CT), digital subtraction angiography (DSA), fusion, ultrasound, intra-operative positioning system (IOPS), and non-contrast imaging. CT was effective at detecting complications but commonly resulted in increased radiation and contrast dose. The effectiveness of DSA can be increased, and radiation exposure reduced, through the use of adjunctive technologies. We found that 2D-3D fusion was non-inferior to 3D-3D and led to reduced radiation and contrast dose. Non-contrast imaging occasionally led to higher doses of radiation. Ultrasound was particularly effective in the detection of type II endoleaks with reduced radiation and contrast use but was often operator dependent. Unfortunately, no papers made it past full text screening for IOPS. All of the imaging techniques discussed have advantages and disadvantages, and clinical context is relevant to guide imaging choice. Fusion and ultrasound in particular show promise for the future.

Objective Duplex ultrasound surveillance (DUS) is commonly used following infrainguinal vein bypass. The role of DUS following endovascular revascularisation is as yet unclear. This study focuses on the role of DUS in a contemporary group of patients undergoing infrainguinal bypass or stent insertion. Methods All patients undergoing either an infrainguinal vein graft bypass or stent insertion into the femoro-popliteal segment (November 2014 - January 2017) were identified. Patients were followed up for 2 years. Data on entry into DUS, pre-operative characteristics, adjunctive pharmacotherapy and reintervention were collated. The primary outcomes were major lower limb amputation and mortality at 2 years post revascularisation. Results One hundred and thirty-five patients underwent infrainguinal vein bypass and 100 patients underwent stent insertion. 107 patients in the bypass cohort and 58 patients in the stent cohort entered DUS. For the bypass cohort, entering DUS was associated with a lower mortality rate ( P = .003) but was not associated with an improvement in amputation rates. The odds ratio of major amputation or mortality was greater in the no surveillance group (4.58, 95% CI: 1.855 – 11.364). In the stent cohort, DUS was not associated with a significant improvement in either major amputation or death (odds ratio 2.13 (95% CI 0.903 – 5.051; P = .081). Conclusion DUS was associated with improved survival rates in patients undergoing lower limb bypass but had no benefit in those patients undergoing stent insertion. The role of DUS following stent insertion in the femoropopliteal segment needs to be better defined.

Objective The quality of patient information relating to intermittent claudication (IC) and peripheral arterial disease (PAD) on the World Wide Web was assessed. Methods The quality of websites and YouTube videos was assessed using the search terms “intermittent claudication” and “peripheral arterial disease”. The first 50 hits screened for each search term from the three largest search engines by market share, and the first 20 videos from YouTube were screened. Website quality was scored using the University of Michigan Consumer Health Website tool (maximum score 80). Readability was calculated using the Flesch Reading Ease (FRE) score (maximum score 100). Videos were classified by content and upload source. Video reliability was assessed using the JAMA benchmark criteria. Video educational content was assessed using the Global Quality Score (GQS). Subjective content assessment was undertaken. Results Seventy-six websites were analysed. The majority of websites for both IC (51.7%) and PAD (72.3%) were rated as weak. The median Michigan score for IC (27; interquartile range [IQR] 15, 32.5) was lower that the score for PAD (31; IQR 25.5, 38.8; p = .030). The majority of websites for both IC (69%) and PAD (68.1%) were rated as requiring an above average reading level. The overall median FRE score was 55.9 (IQR 46.6, 60.6) for IC and 55.3 (IQR 44.6, 59.3) for PAD. Twenty-two videos were analysed. Of the 14 videos evaluated as part of the PAD search, the median JAMA score was 2 (2 – 3), the median GQS score was 3 (3 – 3) and the evaluation of content score was 8.5 (7.25 – 11.5). The equivalent scores for the IC search were 2 (2 – 2), 3 (3 – 4), and 5.5 (5 – 8). Conclusion The educational quality and reliability of information both in written and video form on the internet is low. Attention needs to focus on improving the quality of all forms of information delivery to allow proper advocacy for patients.

Ascertainment bias is a well-recognized source of bias in research, but few studies have systematically analyzed sources of ascertainment bias in randomized trials in which blinding is not possible and endpoint assessment is not protocolized. In the current study, we sought to evaluate differences in the clinical practice patterns of trial investigators with respect to bias in the ascertainment of pre-revascularization patient risk and the incidence of secondary endpoints post-revascularization. We conducted a cross-sectional survey of active investigators ( n = 936) from the Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST-CLI) trial. The total survey response rate was 19.6% (183/936). Vascular surgeons were more likely than nonsurgical interventionalists to order tests for cardiac complications after both surgical bypass ( p < 0.001) and endovascular revascularization ( p = 0.038). Post-procedure, investigators were more likely to order additional testing for cardiac complications in open surgery versus endovascular cases (7% vs 16% never, 41% vs 65% rarely, 43% vs 17% sometimes, 9% vs 2% always, respectively; p < 0.0001). Significant variation in practice patterns exist in the pre- and post-procedure assessment of cardiac risk and events for patients with CLI undergoing revascularization. Variation in the ascertainment of risk and outcomes according to the type of revascularization procedure and physician specialty should be considered when interpreting the results of clinical studies, such as the BEST-CLI trial. ClinicalTrials.gov Identifier: NCT02060630

Climate change is the greatest existential challenge to planetary and human health and is dictated by a shift in the Earth's weather and air conditions owing to anthropogenic activity. Climate change has resulted not only in extreme temperatures, but also in an increase in the frequency of droughts, wildfires, dust storms, coastal flooding, storm surges and hurricanes, as well as multiple compound and cascading events. The interactions between climate change and health outcomes are diverse and complex and include several exposure pathways that might promote the development of non-communicable diseases such as cardiovascular disease. A collaborative approach is needed to solve this climate crisis, whereby medical professionals, scientific researchers, public health officials and policymakers should work together to mitigate and limit the consequences of global warming. In this Review, we aim to provide an overview of the consequences of climate change on cardiovascular health, which result from direct exposure pathways, such as shifts in ambient temperature, air pollution, forest fires, desert (dust and sand) storms and extreme weather events. We also describe the populations that are most susceptible to the health effects caused by climate change and propose potential mitigation strategies, with an emphasis on collaboration at the scientific, governmental and policy levels.

Objective: Frailty is a multi-dimensional vulnerability due to age-associated decline. We assessed the impact of frailty on long-term outcomes in a cohort of vascular surgical patients.Methods: Patients aged over 65 years with length of stay (LOS) > 2 days admitted to a tertiary vascular unit over a single calendar year were included. Demographics, mode of admission, diagnosis were recorded alongside a variety of frailty-specific characteristics. Using the previously developed Addenbrookes Vascular Frailty Score (AVFS – 6 point score: anaemia on admission, lack of independent mobility, polypharmacy , Waterlow score > 13, depression and emergency admission) we assessed the effect of frailty on 5-year mortality and readmission rates using multivariate regression techniques. We further refined the AVFS to assess longer term outcomes.Results: In total, 410 patients (median age 77 years) were included and followed up until death or five years since the index admission. One hundred and thirty-four were treated for aortic aneurysm, 75 and 96 for acute and chronic limb ischaemia respectively, 52 for carotid disease and 53 for other pathologies. The in-hospital mortality rate was 3.6%. The 1-, 3- and 5-year survival rates were 83%, 70% and 59%; and the 1-, 3- and 5-year readmission-free survival rates were 47%, 29% and 22% respectively. Independent predictors of 5-year mortality were age, lack of independent mobility, high Charlson score, polypharmacy, evidence of malnutrition and emergency admission (PConclusions: Frailty factors are strong predictors of long-term outcomes in vascular surgery. Further prospective studies are warranted to investigate its utility in clinical decision-making.

Visual Abstract, Highlights • Restenosis limits the efficacy of PTA or stent treatment of atherosclerosis in peripheral and coronary artery disease. • Paclitaxel DCBs effectively reduce restenosis; however, recently, their overall safety profile has been called into question. • In an in vivo molecular-structural imaging study of 25 rabbits with experimental atherosclerosis, DCB-PTA, plain PTA, or sham-PTA was investigated using serial intravascular NIRF-OCT and IVUS. • DCB-PTA reduced lesion inflammation on NIRF-OCT and halted lesion progression on IVUS, compared with PTA or sham-PTA. • These findings indicated the potential for DCBs to serve effectively and safely as a regional anti-atherosclerosis therapy., Summary Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. This study hypothesized that DCBs could lessen inflammation and reduce plaque progression. Using 25 rabbits with cholesterol feeding- and balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon insertion without inflation) was investigated using serial intravascular near-infrared fluorescence−optical coherence tomography and serial intravascular ultrasound. In these experiments, DCB-PTA reduced inflammation and plaque burden in nonobstructive lesions compared with PTA or sham-PTA. These findings indicated the potential for DCBs to serve safely as regional anti-atherosclerosis therapy.

Objectives This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. Background Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. Methods In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. Results Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p, Central Illustration

Lower limb arterial calcification associates with poor cardiovascular outcomes. The gold standard method of assessment is via computed tomography, yet duplex is our primary imaging modality. Currently, there is no standardized objective assessment of lower limb arterial calcification using duplex. We aimed to define the role of duplex in the assessment of lower limb arterial calcification. Initial consensus was achieved between a cohort of vascular scientists on objective imaging specific markers of lower limb arterial calcification severity using duplex. This resulted in objective descriptions to grade calcification from 0 to 3 (no calcification through to severe calcification) which formed the duplex lower limb arterial calcification score. Reproducibility of the duplex lower limb arterial calcification score was assessed and further validation was undertaken by comparing the duplex lower limb arterial calcification with computed tomography–based assessment in a separate cohort of 44 patients investigated with both modalities. The intra- and inter-class correlation coefficient were > 0.87 . The Spearman rank correlation coefficient between the duplex and CT based arterial calcium measurements was (ρ = 0.644, P < .001). The duplex lower limb arterial calcification score provides a standardized and reproducible modality for assessment of lower limb arterial calcification and may aid with risk stratification in patients with peripheral arterial disease.

Introduction Carotid atherosclerosis is a major risk factor for ischaemic stroke, a leading cause of death. Carotid CT angiography (CTA) is commonly performed following a stroke or transient ischaemic attack (TIA) to help guide patient management in secondary prevention of stroke. Deep learning algorithms can help extract greater information from scans. Method The dataset comprised CTA scans from 40 culprit and 40 non-culprit carotid arteries of patients with recent stroke/TIA, and 40 carotid arteries of asymptomatic patients without previous stroke/TIA. A 3D convolutional neural network was trained to classify carotid artery type. Each input comprised 14 axial CTA carotid patches (centred around the carotid artery) concatenated together to form a 3D volume (capturing ∼3cm of artery). 75% of the dataset was used for training and 25% for internal validation. Following training, computer vision operations were applied to input images to assess their impact on the model’s classification decisions. Results The model achieved 100% accuracy on the training set and 67% on the internal validation set. However, after subjecting input images to image operations, vulnerabilities in the deep learning model were revealed, even when using input images from the training set. For example, using a Gaussian blur filter with sigma 1.0 was sufficient to change classification decisions, as was horizontally flipping the image. Conclusions Deep learning has exceptional capabilities for learning, however the risk with such high-capacity models is failure to learn relevant features from the data. Stress testing provides a viable method to further evaluate deep learning models before clinical deployment.

Objective: Near-infrared autofluorescence (NIRAF) of atherosclerosis associates with intraplaque hemorrhage and is detectable in living patients with coronary artery disease. However, further mechanisms underlying NIRAF generation have not been fully characterized. Here, we investigated the role of lipids and oxidative stress in NIRAF generation in atherosclerosis and in vitro in human macrophages. Approach and Results: In N=15 human carotid endarterectomy specimens, we investigated the spatial distribution of lipid, intraplaque hemorrhage, and NIRAF (ex/em 630/650 nm). Plaque NIRAF associated with both Sudan black-positive lipids ( r =0.53, P =0.023) and GPA (glycophorin A)-positive intraplaque hemorrhage ( r =0.48, P =0.043). Plaque NIRAF also localized with lipid and specifically insoluble lipid (ceroid) and iron. Intriguingly, some NIRAF-positive areas were Sudan black-positive but GPA-negative. Studies on human macrophages investigated further the role of lipids in NIRAF generation. OxLDL (Oxidized low-density lipoprotein) and hemoglobin, but not LDL, generated NIRAF in both THP-1 cells and monocyte-derived macrophages. In oxLDL-treated THP-1 cells, higher NIRAF, lipid peroxidation products, and intracellular oxidative stress markers evolved ( P Conclusions: In human atherosclerosis and human macrophages in vitro, NIRAF colocalizes with lipid and specifically insoluble lipid or ceroid. In vitro studies further show that oxidized LDL generates NIRAF, oxidative stress, and lipid peroxidation products. These results demonstrate a new pathway for NIRAF generation through oxidized lipid-driven oxidative stress and support ceroid as a source of NIRAF in human atherosclerosis. These findings may inform future clinical intracoronary NIRAF imaging studies of patients with coronary artery disease.

Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.

Objective Statin therapy is indicated in patients with peripheral arterial disease (PAD). National Institute for Health and Care Excellence guidelines suggest the use of “high intensity” statins, although evidence with PAD specific data are lacking. The effect of statin therapy and dose on outcomes in PAD is investigated. Data Sources Studies measuring statin use in PAD patients and outcomes were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The EMBASE and MEDLINE databases were interrogated from January 1957 until February 2020. Twenty-two observational cohort studies and two randomised control trials were included (n = 268 611). Review Methods Pooled estimates of dichotomous outcome data were calculated using the odds/hazard ratios (OR/HR) and 95% confidence interval (CI). Meta-analysis was conducted using the inverse variance or Mantel–Haenszel method. Outcomes included all cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiac events (MACE), and amputation. Subgroup analysis was performed on studies comparing patients taking high dose vs. combined low and moderate doses of statins. The GRADE criteria assessed the quality of evidence for outcomes. Results Statin therapy (vs. no statins) was significantly protective for ACM: OR 0.68 (95% CI 0.60 – 0.76) (number needed to treat [NNT] = 48), HR 0.74 (95% CI 0.70 – 0.78) (NNT = 10 – 91); MACE: OR 0.84 (95% CI 0.78 – 0.92) (NNT = 53), HR 0.78 (95% CI 0.65 – 0.93) (NNT = 167); and amputations: OR 0.59 (95% CI 0.33 – 1.07) (NNT = 333), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 50). High doses of statins (vs. combined low and moderate doses) were significantly better protective against ACM OR 0.69 (95% CI 0.43 – 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 16 – 200) but work less significantly for MACE OR 0.77 (95% CI 0.49 – 1.21) (NNT = 25). Amputations were less frequent in patients on high doses HR 0.78 (95% CI 0.69 – 0.90) (NNT = 53 – 1 000). Conclusion Higher dosing of statins confers a significant improvement in patient outcomes, especially ACM and amputations, although the quality of the evidence was variable. Such findings require confirmation in larger, PAD specific trials.

Background Carotid artery atherosclerosis is an important cause of ischaemic stroke. In oncology, textural analysis (“radiomics”) of computed tomography (CT) images can predict the metastatic potential and prognosis of several types of malignant tumours. We investigated whether this quantitative approach could be applied in carotid artery disease. Purpose (1) To evaluate the feasibility of computed tomography angiography (CTA) texture analysis in differentiating symptomatic from asymptomatic patients. (2) To investigate whether CTA carotid texture analysis can identify culprit lesions in patients with stroke and transient ischaemic attack (TIA). Methods Carotid CTAs of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CTA imaging. Asymptomatic (ASX) patients had no prior stroke/TIA. Both TexRAD, a research texture analysis software, and PyRadiomics, a Python package for radiomics studies, were used to extract 99 first-order and higher-order texture features from regions-of-interest (ROI) drawn around the outer wall of the carotid artery. Single-slice analysis compared the carotid bifurcations of symptomatic and asymptomatic patients, and of culprit (CC) and non-culprit (NC) arteries in symptomatic patients. Multi-slice analysis was conducted using a 3D volume defined by ROIs drawn on 14 consecutive CT slices of 3mm thickness, covering 3cm of carotid artery. The Mann-Whitney U test was used for inter-subject comparisons (ASX vs CC; ASX vs NC) and the Wilcoxon signed-rank test was used for intra-subject comparisons (CC vs NC). A p value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. Single-slice analysis revealed greater homogeneity in asymptomatic carotids versus symptomatic culprit carotids (Uniformity: ASX 0.11 (0.05); CC 0.08 (0.05), p Conclusion Textural analysis of carotid CTAs reveal significant differences between symptomatic and asymptomatic patients and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could be used to identify patients at high risk of further stroke for aggressive medical therapy and surveillance. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Background Convolutional neural networks (CNNs), part of deep learning, are used widely for computer vision tasks and in some medical domains, such as mammography interpretation. The application of deep learning to carotid artery imaging is scarce. We investigated the ability of deep learning to correctly classify contrast CT images of the carotid arteries without the need for prior feature selection. Purpose (1) To assess the ability of deep learning to differentiate symptomatic patients (had prior stroke or transient ischaemic attack [TIA]) from asymptomatic patients (no prior stroke/TIA) using contrast CT scans alone. (2) To investigate whether deep learning can further discriminate between culprit and non-culprit carotid arteries in symptomatic patients. (3) To assess the interpretability of the deep learning models. Methods Carotid contrast CT scans of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CT imaging, and asymptomatic patients had no prior cerebrovascular events. The dataset comprised 1148 axial symptomatic slices (covering a 3cm area of each carotid artery in 41 patients; 41 culprit and 41 non-culprit carotids) and 700 asymptomatic slices (from the bilateral carotid arteries of 25 patients). The dataset was split such that 75% was used for training and 25% for testing. A 30x30 bounding box was used to create patches of the carotid arteries from these axial slices for use as input to the CNN, a modified VGG16 architecture initialised with ImageNet weights to leverage transfer learning (the application of a model trained in one domain to a different domain) implemented in Python. Data augmentation was applied to the training set and the model was trained for 100 epochs using a cyclic learning rate, the RMSProp optimizer and binary cross-entropy loss. Class activation heatmaps were generated using the GradCAM method to highlight the areas of the image that were most important to the model for making its classification decision. Results The deep learning model was 92% accurate in correctly identifying carotid arteries from symptomatic patients versus those from asymptomatic patients. Discriminating between culprit versus non-culprit carotid arteries in symptomatic patients alone was 71% accurate. The class activation heatmaps demonstrated how the model learnt to localise the carotid artery within the image patch, and to ignore the arterial lumen when making its classification decision. Conclusions Deep learning can be used to differentiate between symptomatic and asymptomatic carotid CT scans from stroke/TIA subjects without the need for prior feature engineering. The model learns to identify relevant features in the image that predict the patients' symptom state. If further validated, this approach could be used to identify high-risk patients for intensive medical therapy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Introduction Carotid atherosclerosis is the main cause of ischaemic stroke. Texture analysis is a radiomic approach used to quantify image heterogeneity which can predict tumour aggression in oncology. We investigated whether this method could be applied to carotid artery disease to differentiate symptomatic from asymptomatic patients and culprit from non-culprit plaques, and then whether machine learning (ML) could correctly classify plaques based on these features. Methods CT angiography (CTA) images from symptomatic patients with carotid artery-related cerebrovascular accidents (CVAs) and from asymptomatic (ASX) patients were studied. Regions-of-interest (ROIs) were drawn on 14 consecutive carotid artery CTA slices with 3mm slice thickness. PyRadiomics was used for isotropic image (1x1x1) resampling and normalisation prior to texture feature extraction from 6 different classes (Table 1). Asymptomatic carotids were compared to culprit carotids (CC), and non-culprit (NC) carotids using the Mann Whitney U test or Wilcoxon signed-rank tests as appropriate, with a p-value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. CC and NC carotids showed significant differences in both first- and second-order features (IH Median: CC 618 (61); NC 646 (97), p Conclusions Textural analysis combined with machine learning on carotid CT scans reveals highly significant differences between symptomatic and asymptomatic patients, and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could help identify patients at high-risk of stroke for aggressive medical therapy and surveillance. Conflict of Interest None

Background Debate surrounds the optimal management of superficial femoral artery (SFA) disease. Randomized trial data rarely reflect real world findings, specifically the consequences to the patient of angioplasty failure. We observed the effect of a failed SFA angioplasty on the need for repeated clinic visits, hospital readmissions, imaging requirements, and reinterventions. Methods We reviewed a consecutive series of 148 patients (94 men, median age 72 years) undergoing solely SFA angioplasty over a 2-year period. Patient preangioplasty demographics and 2-year post-PTA follow-up data were collated, including hospital attendances (inpatient/outpatient), further imaging (including radiation exposure) and revascularization attempts. We defined “failed angioplasty” as presence of clinical symptoms with radiological evidence of significant restenosis after an initial successful primary SFA angioplasty. Results Fifty-four patients represented with a failed angioplasty (median time of 4 months after index PTA). In this group, failure of index angioplasty resulted in a further 185 restenosis-related clinic visits and a total of 537 bed days of inpatient stay. This group underwent a further 149 imaging events and required a further 34 endovascular revascularization procedures and 12 infrainguinal bypass procedures. These interventions and investigations corresponded to overall effective radiation dose across all patients of 190.69 mSv. Of the cohort of 99 patients who did not have a “failed angioplasty,” they required 100 clinic visits, 21 further scans (total radiation dose 6.42 mSv), and 36 bed days of inpatient admission. Conclusions Failed angioplasty results in significant additional consequences for patients and health-care systems. Further work should focus on refining decision-making, providing the right procedure to the right patient at the right time.

ObjectiveUsing combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis.MethodsWe prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores.ResultsIn patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBRmax2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBRmax2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBRmax2.23±0.45 vs 1.68±0.21, pmax2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBRmax thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, pConclusionsThe entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall.

Background: Inflammation and microcalcification are interrelated processes contributing to atherosclerotic plaque vulnerability. Positron-emission tomography can quantify these processes in vivo. This study investigates (1) 18 F-fluorodeoxyglucose (FDG) and 18 F-sodium fluoride (NaF) uptake in culprit versus nonculprit carotid atheroma, (2) spatial distributions of uptake, and (3) how macrocalcification affects this relationship. Methods: Individuals with acute ischemic stroke with ipsilateral carotid stenosis of ≥50% underwent FDG-positron-emission tomography and NaF-positron-emission tomography. Tracer uptake was quantified using maximum tissue-to-background ratios (TBR max ) and macrocalcification quantified using Agatston scoring. Results: In 26 individuals, median most diseased segment TBR max (interquartile range) was higher in culprit than in nonculprit atheroma for both FDG (2.08 [0.52] versus 1.89 [0.40]; P P max was higher in culprit arteries for FDG (1.92 [0.41] versus 1.71 [0.31]; P P =0.10). NaF uptake was concentrated at carotid bifurcations, while FDG was distributed evenly throughout arteries. Correlations between FDG and NaF TBR max differed between bifurcations with low macrocalcification ( r s =0.38; P r s =0.59; P Conclusions: This is the first study to demonstrate increased uptake of both FDG and NaF in culprit carotid plaques, with discrete distributions of pathophysiology influencing vulnerability in vivo. These findings have implications for our understanding of the natural history of the disease and for the clinical assessment and management of carotid atherosclerosis.

PET imaging is able to harness biological processes to characterise high-risk features of atherosclerotic plaque prone to rupture. Current radiotracers are able to track inflammation, microcalcification, hypoxia, and neoangiogenesis within vulnerable plaque. 18 F-fluorodeoxyglucose (18 F-FDG) is the most commonly used radiotracer in vascular studies and is employed as a surrogate marker of plaque inflammation. Increasingly, 18 F-FDG and other PET tracers are also being used to provide imaging endpoints in cardiovascular interventional trials. The evolution of novel PET radiotracers, imaging protocols, and hybrid scanners are likely to enable more efficient and accurate characterisation of high-risk plaque. This review explores the role of PET imaging in atherosclerosis with a focus on PET tracers utilised in clinical research and the applications of PET imaging to cardiovascular drug development.

Background: Fluorine-18 sodium fluoride (NaF), a bone-seeking radiopharmaceutical used to detect osseous metastases, localizes in regions of microcalcification in atherosclerosis. Objectives: To determine if atherosclerosis of penile arteries plays a role in erectile dysfunction (ED), this study analyzed NaF images in prostate cancer patients. Methods: NaF positron emission tomography–computed tomography bone scans were evaluated in 437 prostate cancer patients (age 66.6 ± 8.7 years). Their urologic histories were reviewed for prevalent ED (diagnosed before the scan date) or incident ED (no ED at first scan, but developed during 1-year follow-up); patients with no ED (neither before the scan nor during follow-up) were included as a control group. A semicircular region of interest was set on the dorsal one-half of the penis (to avoid residual excreted activity in the urethra) on 5 contiguous slices at the base of the penis on positron emission tomography–computed tomography coronal reconstructions, and the average standardized uptake value (SUVmax) was described as NaF uptake. Results: Of 437 patients, 336 (76.9%) had prevalent ED, 60 incident ED (13.7%), and 41 had no ED (9.4%). SUVmax in patients with prevalent (median 1.88; interquartile range [IQR]: 1.67 to 2.16) or incident (median 1.86; IQR: 1.72 to 2.08) ED was significantly higher than no ED (median 1.42; IQR: 1.25 to 1.54) patients (p < 0.001). After adjustment for other risk factors, the odds ratio of prevalent or incident ED was 25.2 (95% confidence interval: 9.5 to 67.0) for every 0.5-U increment in SUVmax with receptor operating characteristic area of 0.91 (95% confidence interval: 0.88 to 0.94). Conclusions: NaF uptake in penile vessels suggests that atherosclerosis is associated with ED in prostate cancer patients. The importance of NaF uptake needs to be tested in noncancer subjects and cause-effect relationship needs to be established.

Molecular imaging of cardiovascular disease is a powerful clinical and experimental approach that can inform our understanding of atherosclerosis biology. Complementing cross-sectional imaging techniques that provide detailed anatomical information, molecular imaging can further detect important biological changes occurring within atheroma and refine the prediction of vascular complications. Molecular imaging of atherosclerosis can illuminate underlying pathophysiology and serve as a surrogate endpoint in clinical trials of new drugs. This review showcases promising molecular approaches for imaging atherosclerosis, with a focus on positron emission tomography (PET), magnetic resonance imaging (MRI), and intravascular near-infrared fluorescence (NIRF) imaging methods that are in the clinic or close-to-clinical usage.

Arterial calcification in different arterial beds has been observed to be an independent predictor of mortality. The association of abdominal visceral artery calcium with all-cause mortality remains unexplored. Patients who had undergone contrast-enhanced computerized tomography (CT) imaging for routine assessment of peripheral arterial disease (PAD) were considered for this study. A novel calcium score (abdominal visceral arteries calcium [AVAC]) for the abdominal visceral arteries (celiac axis, superior mesenteric, and renal arteries) was calculated using a modified Agatston score. Cumulative AVAC was defined as sum total of the calcium score of above individual arteries. The primary outcome was all-cause mortality. The association of AVAC with all-cause mortality was assessed. Of the 134 consecutive patients, 89 were included for analysis. Median follow-up duration was 72 (47-91) months since CT imaging; 35 (39%) patients died during this period. Hypertension and cumulative AVAC score had a significant association with all-cause mortality ( P < .05). Cumulative visceral abdominal artery calcification is associated with all-cause mortality in patients with PAD. Future prospective studies are warranted to investigate this relationship in PAD and other patient cohorts.

BACKGROUND: Frailty is a recognized predictor of poor outcome in patients undergoing surgical intervention. Frailty is intricately linked with body morphology, which can be evaluated using morphometric assessment via computerized tomographic (CT) imaging. We aimed to assess the predictive power of such objective assessments in a broad cohort of vascular surgical patients.METHODS: A consecutive series of patients aged over 65 years admitted to a vascular unit, who had undergone CT imaging of the abdomen, were analyzed. Demographic and patient-specific data were collated alongside admission relevant information. Outcomes included mortality, length of stay, health care-related costs, and discharge destination. Images were analyzed for 4 morphometric measurements: (1) psoas muscle area, (2) mean psoas density, (3) subcutaneous fat depth, and (4) intra-abdominal fat depth, all taken at the level of the fourth lumbar vertebra.RESULTS: Two hundred and ten patients were initially analyzed. Forty-four patients had significant retroperitoneal and abdominal abnormalities that limited appropriate CT analysis. Decreased subcutaneous fat depth was significantly associated with mortality, readmission within 12 months, and increased cost of health care (P < 0.01, adjusted for confounders). Psoas muscle area was significantly associated with readmission-free survival.CONCLUSIONS: Morphometric analysis predicts poorer outcome in a broad cohort of vascular surgery patients. Such assessment is likely to enhance patient counseling regarding individual risk as well as enhancing the ability to undertake risk-modified surgical audit.

Lower limb peripheral arterial disease (PAD) is becoming increasingly common. Lower limb perfusion, as determined by the ankle brachial pressure index (ABPI), is a recognised predictor of overall mortality. The increasing role of non-invasive imaging in patient assessment may aid in the ability to predict poor patient outcomes.This study included all patients undergoing a lower limb arterial duplex over a period of 20 months. The site and burden of atherosclerosis within the lower limb was determined using the well validated Bollinger score. Patient demographic data were also collated. The primary outcome measure was all cause mortality.A total of 678 patients were included (median age 74 years). The overall median follow up period was 69.9 months. Of these, 307 patients reached the primary end point, which was death. Independent predictors of all cause mortality included total Bollinger score (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18 [p .001]; OR per 10 points), femoropopliteal Bollinger score (OR 1.34, 95% CI 1.11-1.08 [p = .05]; OR per 10 points), and crural Bollinger score (OR 1.03, 95% CI 1.01-1.03 [p = .03]). There was also a significant association between mortality and age, a prior history of ischaemic heart disease, a history of congestive cardiac failure and chronic renal failure (chronic kidney disease ≥ 3). Statin and antiplatelet therapy were protective.This contemporary study confirms poor long-term outcomes still exist in patients with PAD. The site and severity of lower limb atherosclerosis are independent predictors of long-term mortality.

Introduction Carotid artery dissection is a leading cause of stroke in younger patients, with an associated prevalence of 2.6–3.0 per 100,000 population. This meta-analysis aims to determine whether in patients managed medically, treatment with anticoagulants or antiplatelet agents was associated with a better outcome with respect to mortality, ischaemic stroke, and major bleeding episodes. Patients and methods A comprehensive search strategy was employed of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to March 2015), and EMBASE (January 1980 to March 2015) databases. Primary outcomes were death (all causes) or disability. Secondary outcomes were ischaemic stroke, symptomatic intracranial haemorrhage, and major extracranial haemorrhage during the reported follow-up period. Results No completed randomized trials were found. Comparing antiplatelets with anticoagulants across 38 studies (1,398 patients), there were no significant differences in the odds of death (effects size, ES, −0.007, p = .871), nor in the death and disability comparison or across any secondary outcomes. Conclusion There were no randomised trials comparing either anticoagulants or antiplatelets with control, thus there is no level 1 evidence to support their routine use for the treatment of carotid artery dissection. Also, there were no randomised trials that directly compared anticoagulants with antiplatelet drugs, and the reported non-randomised studies did not show any evidence of a significant difference between the two.

Mechanochemical ablation (MOCA) is a nonthermal nontumescent technique used in the treatment of superficial venous disease. This review analyzed the available data on the efficacy and safety of MOCA. A systematic literature search was performed. Of 101 studies identified, 14 were suitable for inclusion. The studies were found to be heterogeneous in design, and the quality of evidence was found to be low or very low. MOCA was demonstrated to be effective in the short-term with minimal complications. Consensus guidelines and definitions of reporting outcome measures must be standardized to allow comparison with other techniques.

Introduction: Microcalcification is a histopathological feature of atheroma at risk of rupture; so-called “vulnerable plaques.” Positron emission tomography (PET) using 18 F-sodium fluoride (NaF) has been used to detect microcalcification in ex vivo histology, though its use in vivo has been limited. We investigated the utility of NaF-PET to identify culprit carotid artery atheroma non-invasively in vivo in the setting of acute ischemic stroke. Methods: Symptomatic carotid artery stenosis of ≥50% was imaged using NaF-PET within 14 days of ipsilateral ischemic stroke. Symptomatic arteries were compared to contralateral asymptomatic carotid arteries. NaF dose was 125 MBq with 60 minute uptake on a GE Discovery 690 with 64 slice computed tomography. NaF uptake was measured using standardized uptake values for each artery’s single region of maximum uptake (SUVmax) and the mean of the three slices representing the most diseased segment (MDS-SUVmax). Arteries were compared using Wilcoxon signed-rank testing. Results: Fifty-two carotid arteries were analyzed: 26 symptomatic, 26 asymptomatic. Median SUVmax was higher in symptomatic than asymptomatic arteries: 2.16 (IQR 0.76) and 1.88 (IQR 0.94) respectively (p Conclusions: The ability to identify culprit carotid atheroma using NaF-PET in vivo represents an important advance in vascular imaging. This has important implications for understanding atherosclerosis pathophysiology, as well as potential clinical applications to identify and risk-stratify vulnerable carotid atheroma.

Paclitaxel (PTX) drug-coated balloons (DCBs) are effective at reducing restenosis following endovascular arterial revascularization; however, their efficacy is limited in highly calcified/impermeable arteries. However, no in vivo tool exists to guide arterial lesion preparation prior to DCB to

Introduction: The iliac bifurcated device (IBD) is an innovative endovascular device for aortoiliac aneurysm repair. The objective of this study is to provide further evidence on the efficacy and safety of the device. Study Design: Case series study with retrospective analysis of prospectively collected nonrandomized data. Methods: Between 2007 and 2010, all consecutive IBD placements were analyzed. The main outcomes included (1) technical failure; (2) morbidity and mortality; and (3) late outcomes. Prospective follow-up was performed by interval computed tomography scanning. Results: In all, 27 consecutive patients had elective placement of 28 IBDs. Mean operating time was 251.1 ± 65.4 minutes, mean fluoroscopy time was 63.9 ± 27.2 minutes, and mean contrast volume used was 186.2 ± 106.7 mL. Periprocedural type I endoleak occurred in 2 patients. No aneurysm-related adverse events were recorded. Conclusion: We demonstrate that IBDs can be used in patients with aortoiliac aneurysms and are associated with satisfactory medium-term results as expressed by high patency and low reintervention rates.

Acute kidney injury (AKI) is a recognized complication post-endovascular aneurysm repair (EVAR). Neutrophil gelatin-associated lipocalin (NGAL), interleukin 18 (IL-18), and retinol-binding protein are emerging urinary biomarkers that have shown promise in detecting subclinical and clinical renal impairment. In this study, we assessed changes in these urinary biomarkers as well as serum creatinine (SCr) in patients undergoing EVAR. Urine samples were collected prospectively at 5 time points for each recruited patient: pre-EVAR (baseline) and 6, 12, 24, and 48 hours after the procedure for serial assessment of urinary biomarkers. Serum creatinine was quantified preoperatively and at 24 and 48 hours postoperatively. Serial changes of urinary biomarkers and SCr were assessed. A significant increase in NGAL and IL-18 from baseline was observed ( P < .05), as early as 6 hours for NGAL. A significant rise in levels of NGAL and IL-18 precedes the significant rise in SCr. These findings highlight the potential of emerging urinary biomarkers in detecting early AKI following EVAR.

Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([This study tested the efficacy of gallium-68-labeled DOTATATE (We confirmedTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specificWe validated

Atherosclerosis is a leading cause of morbidity and mortality. It is now widely recognized that the disease is more than simply a flow-limiting process and that the atheromatous plaque represents a nidus for inflammation with a consequent risk of plaque rupture and atherothrombosis, leading to myocardial infarction or stroke. However, widely used conventional clinical imaging techniques remain anatomically focused, assessing only the degree of arterial stenosis caused by plaques. Positron emission tomography (PET) has allowed the metabolic processes within the plaque to be detected and quantified directly. The increasing armory of radiotracers has facilitated the imaging of distinct metabolic aspects of atherogenesis and plaque destabilization, including macrophage-mediated inflammatory change, hypoxia, and microcalcification. This imaging modality has not only furthered our understanding of the disease process in vivo with new insights into mechanisms but has also been utilized as a non-invasive endpoint measure in the development of novel treatments for atherosclerotic disease. This review provides grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field.

Current multimodality optical coherence tomography (OCT)-near infrared fluorescence (NIRF) imaging systems have a moderate NIRF lateral resolution (∼100 um). In this study, we developed a high-resolution (HR)-OCT-NIRF imaging system to investigate its potential for providing additional information

OBJECTIVE: Strategies to improve outcomes for patients with ruptured abdominal aortic aneurysm (rAAA) are becoming more evident. The aging population, however, continues to make the decision to intervene often difficult, especially given that traditional risk models do not reflect issues of aging and frailty. This study aimed to integrate measures of function alongside comorbidity- and frailty-specific factors to determine outcome.METHODS: Patients treated for a rAAA between January 2006 and April 2014 were assessed. Demographics, mortality, and requirement for care after discharge as well as a variety of measures of function (physical, social, and psychological) and comorbidity were recorded. The primary outcome was 1-year mortality. Outcome models were generated using multivariate logistic regression and were compared with models of vascular frailty and AAA-related outcome.RESULTS: Of 184 patients treated, 108 (59%) underwent an open surgical repair. The overall 30-day and 1-year mortality were 21.5% and 31.4%, respectively, with an overall median hospital length of stay of 13 days (interquartile range, 6-27 days). An optimal logistic regression model for 12-month mortality used Katz score, Charlson score, number of admission medicines, visual impairment, hearing impairment, hemoglobin level, and statin use as predictors, achieving an area under the receiver operating characteristic curve of 0.84.CONCLUSIONS: This novel rAAA model incorporating function and comorbidity offers good predictive power for mortality. It is quick to calculate and may ultimately become helpful for both counseling and selection of patients and comparative audit at a time when outcome in patients with rAAA increasingly comes under the spotlight.