Neovascularization as a Leading Mechanism of Intraplaque Hemorrhage and Carotid Plaque Destabilization: A Narrative Review.

Intraplaque neovascularization (IPN) is considered a leading mechanism causing carotid plaque destabilization. We provide an objective and comprehensive summary of the biology, imaging techniques, and treatment options related to carotid IPN. Plaque neovascularization has been reported to originate mainly from the adventitial vasa vasorum as a response to hypoxia. The leakage and rupture of neovessels lead to the formation of extravasations and foci of inflammation that destabilize the plaque. Vascular endothelial growth factor and its receptors are key regulators of neoangiogenesis. Neovascularization can be analyzed by advanced computed tomography and magnetic resonance imaging. The basic tools for the ultrasound assessment of IPN are contrast-enhanced ultrasound, superb microvascular imaging, and ultrasound molecular imaging. A promising direction of research seems to be the identification of patients with advanced plaque neovascularization. A simple test assessing low-velocity flow in the IPN can detect patients at risk of stroke before they experience rupture of defective neovessels and intracerebral embolism. In addition to surgical treatment, the stabilization of carotid atherosclerotic plaque can be supported pharmacologically. Statins have the best-documented role in this respect. The ideal moment of intensified therapeutic intervention in patients with previously stable carotid plaque is its increased neovascularization. However, the time frame in which intracerebral embolization may occur is unknown, and therapeutic intervention may be too late. The formation of deficient neovessels can currently be non-invasively evaluated with ultrasound. Superb microvascular imaging may change the clinical approach for asymptomatic patients at risk of cerebral ischemia.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

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

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

Evaluation of factors affecting the healing process of venous ulcers: A 12-week longitudinal study.

The process of healing venous ulcers is complex and influenced by many factors. By identifying the risk factors that influence a slower healing process, it is possible to predict impending delays and plan an individualised care plan. We analysed our database of patients with venous ulcers and identified clinical and demographic factors that delay the healing process. The research analysed the medical records of 754 patients with VLUs at Chronic Wound Treatment Unit of the University Hospital treated between 2001 and 2019. In study, the majority (64.3%) were women, the mean age was 65.7 years. The median duration of Chronic Venous Insufficiency was 24 years, 52% patients had had the disease >20 years, and 296 (39.3%) had experienced ulceration >12 months. Most of the patients (85.8%) had comorbidities, 84% were obese. At 12-week follow-up, 432 of the 754 ulcers had healed. Identified independent predictors of slower ulcer healing rates: wound area greater than 8.25 cm2 , location of the ulceration other than the medial ankle area, underlying disease >20 years, the presence of multiple comorbidities, depth of the ulcer, the presence of an unpleasant smell and alert pathogens. The presence of redness resulted in faster healing of VLUc. Many factors influence the healing process of venous ulceration. The results of the study can help in planning patient care and implementing appropriate early strategies to promote healing.

Lower extremity arterial disease perspective: IUA consensus document on "lead management". Part 1.

Atherosclerotic cardiovascular disease (ASCVD) is defined as coronary heart disease (CHD), cerebrovascular disease, or lower extremity arterial disease (LEAD) also named peripheral arterial disease (PAD). ASCVD is considered to be of atherosclerotic origin and is the leading cause of morbidity and mortality mainly for individuals with diabetes mellitus (DM). In this consensus document of the International Union of Angiology the authors discuss epidemiology, risk factors, primary and secondary prophylaxis, the correlation between diabetes mellitus and LEAD, conservative and surgical treatment.

Enhancing Functional Efficiency and Quality of Life through Revascularization Surgery in Peripheral Arterial Disease: A Comparative Analysis of Objective and Subjective Indicators.

BACKGROUND This study aimed to compare the ankle-brachial index (ABI), maximal claudication distance (MCD), pain-free walking distance (PFWD), claudication pain, and quality of life (intermittent claudication questionnaire [ICQ]) before and 3 months after revascularization surgery in 98 patients diagnosed with peripheral arterial disease (PAD) at a single center in Poland. MATERIAL AND METHODS Ninety-eight patients were examined (77% men, 23% women, 65.65±7.27 years old), diagnosed with PAD, and qualified for revascularization. The diagnosis of PAD was made on the basis of ABI ≤0.9 and medical records. The patients underwent a noninvasive examination, including measurement of ABI (by Doppler with the EZ8 probe), assessment of the quality of life by ICQ, distance of intermittent claudication on a treadmill using the Gardner-Skinner protocol (including PFWD and MCD), and pain intensity during walking (numeric rating scale [NRS11]). The assessment was carried out twice: 1 to 5 days before surgery and 3 months after surgery. RESULTS There was an increase of ABI (0.4 vs 0.62, P<0.001), PFWD (26.64 vs 80.21, P<0.001), MCD (60.08 vs 181.85, P<0.001), and ICQ (79.92 vs 60.23, P<0.001) and reduction of PFWD pain (7.26 vs 6.05, P<0.001) and MCD pain (9.24 vs 8.11, P<0.001). CONCLUSIONS Revascularization surgery improved the ABI and patients functional efficiency expressed in the improvement of subjective indicators PFWD, MCD, NRS11, and ICQ. Patients who had a longer duration of disease had worse outcomes after revascularization. More attention should be paid to increasing access to preventive examinations aimed at early detection of PAD and the possibility of implementing conservative treatment.

Improved Detection of Endoleaks in Virtual Monoenergetic Images in Dual-Energy CT Angiography Following EVAR.

OBJECTIVES: The objective of this prospective study was to evaluate the virtual monoenergetic images (VMI) and virtual noncontrast (VNC) phase in the detection of endoleaks after endovascular abdominal aortic repair (EVAR). The potential dose reduction of abbreviated examination protocols was calculated. MATERIALS AND METHODS: Ninety-seven patients after the EVAR procedure were enrolled in this study. An initial single-source noncontrast acquisition was followed by two dual-energy acquisitions (arterial and 60 s delayed). Fast-kVp switching scanner was used. VNC images were reconstructed from the delayed phase. First examination session (reference) included a full triphasic study protocol consisting of true noncontrast (TNC) images and two postcontrast phases, the latter ones presented as classical polyenergetic reconstructions. Reading sessions II and III were performed by two independent and blinded readers evaluating VMIs in abbreviated protocols-biphasic (VNC + arterial, delayed phase), monophasic (VNC + delayed phase). The diagnostic accuracy of sessions II and III was calculated. RESULTS: The calculated sensitivity of the biphasic protocol with the use of VMIs in endoleak detection was 100%, with a statistically significant increase in the number of endoleaks detected in comparison with the reference study. The monophasic protocol showed 83.33% sensitivity. The use of abbreviated examination protocols led to a decrease in the mean effective dose (ED) of 23.28% (biphasic protocol) and 61.37% (monophasic protocol). CONCLUSION: The use of VMIs increases the number of endoleaks diagnosed with a possible radiation reduction by up to » (biphasic protocol). Further reduction to a monophasic protocol leads to over 60% dose reduction but with a decrease in diagnostic accuracy.

Fluorescence - modern method of the diagnosis of chronic wounds on the example of venous leg ulcer.

Introduction: Fluorescence imaging has become a method for bacterial visualisation in chronic wounds for the last few years. MolecuLight i:X (MolecuLight, Inc, ON, Canada) is a handheld device, which enables quick diagnostics to determine both the type and location of pathogens present in the wound and on the skin. By means of fluorescent light illumination the tissues populated by pathogenic bacteria emit red or cyan fluorescent signatures, depending on the type of the pathogen: red fluorescence signal is emitted by Staphylococcus and Escherichia coli among others, while Pseudomonas aeruginosa produce cyan fluorescence. The fluorescence image also presents the spatial pattern of bacterial load, which creates bacterial mapping of the wound and may be used by a clinician for targeted sampling or debridement, among others. Aim: This study presents the method of microbiological fluorescent imaging and two case studies of patients with venous leg ulcers. Material and methods: In both cases, the sample for microbiological testing was obtained by means of a swab stick. Results: The results obtained from fluorescent imaging showed moderate-to-heavy bacterial load, which corresponded with the results from microbiology laboratory. Thanks to quick diagnostics with the use of MolecuLight i:X device, instant implementation of targeted topical actions such as wound hygiene, skin disinfection, appropriate dressing choice and curative treatment among others was possible. Conclusions: Our observations are consistent with the reports from other facilities.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Optimal periprocedural antithrombotic treatment in carotid interventions: An international, multispecialty, expert review and position statement.

BACKGROUND: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. METHODS: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. RESULTS: For asymptomatic patients, we recommend low-dose aspirin (75-100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. CONCLUSIONS: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

Venous leg ulcers treated with fish collagen gel in a 12-week randomized single-centre study.

Introduction: Venous ulcers are difficult to heal chronic wounds. Most challenging are the non-healing and recurrent ulcers, because of which we are seeking for therapies that stimulate and support their healing. Aim: To assess the efficacy of fish collagen and its impact on the process of healing of venous leg ulcers. Material and methods: This 12-week randomized single-centre study included a total of 97 adults with venous leg ulcer, randomized into two groups: the study group (n = 48) and the control group (n = 49). All patients received specialist medical care including skin and limb care, wound development according to the TIME scheme (tissue debridement, infection and inflammation control, moisture balance, edge) and short-stretch bandage compression (compression class II). In addition, the study group received tropocollagen gel applied to the skin around the wound. Every 2 weeks we evaluated the wound surface and temperature distribution on the shin (average temperature, median, minimum and maximum) - symmetrically on the sick and healthy limb. Results: We observed a greater number of complete ulcer healing in the study group (week 12: 29.2% vs. 22.4%; week 24: 52.1% vs. 36.7%). Faster healing time in the study group was observed in both big and small ulcers. The thermographic analysis showed statistically significant reduction in periwound inflammation among patients from the study group (p < 0.05). Statistically significant reduction in mean as well as maximum values of limb temperature occurred only in the study group (Tx: R = 0.37, p < 0.001; Tmax: R = 0.40, p < 0.001). Conclusions: Thermographic analysis showed better wound healing effects in the group using tropocollagen. Significant impact of collagen on the healing process was observed only after 8 weeks of application.

Clinical Perspectives and Management of Edema in Chronic Venous Disease-What about Ruscus?

Background: Edema is highly prevalent in patients with cardiovascular disease and is associated with various underlying pathologic conditions, making it challenging for physicians to diagnose and manage. Methods: We report on presentations from a virtual symposium at the Annual Meeting of the European Venous Forum (25 June 2021), which examined edema classification within clinical practice, provided guidance on making differential diagnoses and reviewed evidence for the use of the treatment combination of Ruscus extract, hesperidin methyl chalcone and vitamin C. Results: The understanding of the pathophysiologic mechanisms underlying fluid build-up in chronic venous disease (CVD) is limited. Despite amendments to the classic Starling Principle, discrepancies exist between the theories proposed and real-world evidence. Given the varied disease presentations seen in edema patients, thorough clinical examinations are recommended in order to make a differential diagnosis. The recent CEAP classification update states that edema should be considered a sign of CVD. The combination of Ruscus extract, hesperidin methyl chalcone and vitamin C improves venous tone and lymph contractility and reduces macromolecule permeability and inflammation. Conclusions: Data from randomized controlled trials support guideline recommendations for the use of Ruscus extract, hesperidin methyl chalcone and vitamin C to relieve major CVD-related symptoms and edema.

Complex treatment of venous leg ulcers including the use of oral nutritional supplementation: results of 12-week prospective study.

Introduction: Malnutrition is known to impair the wound healing process, contributing to wound chronicity. Venous leg ulcers (VLU) represent the most common chronic leg wounds and become epidemiologically relevant in an ageing society. Aim: This study investigated the effects of a complex treatment, including a specialized oral nutritional supplementation, on the dynamics of the VLU healing. Material and methods: This 12-week prospective study included 35 individuals with VLU. The patients received professional wound care including specialized dressings. To ensure an optimal nutritional status for wound healing, the patients were asked to drink three times per day 200 ml of an energy-dense protein-rich formula containing arginine, zinc, and vitamins. The healing dynamics were assessed by planimetry. Results: Complete wound healing was achieved in 6 patients, and the median ulcer area decreased from 26.5 cm2 to 14.8 cm2 (p = 0.0001). Both the highest healing rates and most marked increase in prealbumin levels were observed in the first 6-8 weeks. The progress in wound healing was associated with a decreased pain intensity and an improved quality of life. Supplementation was well accepted by the patients. Conclusions: This study shows that a complex intervention involving nutritional support contributes to a significant progress in VLU healing and promotes the well-being of affected individuals.

Healing Process, Pain, and Health-Related Quality of Life in Patients with Venous Leg Ulcers Treated with Fish Collagen Gel: A 12-Week Randomized Single-Center Study.

The aim of the study was to assess the effectiveness of fish skin collagen and its impact on healing, pain intensity, and quality of life in patients with venous leg ulcers (VLUs). This study included 100 adults with VLUs. Eligible patients were randomized to either tropocollagen gel treatment (group A, n = 47) or placebo alone (group B, n = 45). We applied the gel to the periwound skin for 12 weeks. All groups received standard wound care, including class 2 compression therapy and wound hygiene procedures. We assessed the healing rate (cm2/week) and quality of life (QoL) using the Skindex-29 and CIVIQ scales. In group A, more ulcers healed, and the healing rate was faster. In both study groups, patients showed a significant improvement in quality of life after the intervention, but there was a greater improvement in the tropocollagen group. In group A, the greatest improvement was related to physical symptoms and the pain dimension. This study showed that the application of fish collagen gel to the periwound skin improves the healing process and QoL in patients with VLUs. The 12-week treatment with collagen reduced the severity of physical complaints, pain, and local skin symptoms, which determined the quality of life in patients with VLUs to the greatest extent.

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.