Inflammation, anti-inflammatory agents, and the role of colchicine in carotid artery stenosis.

Cardiovascular disease is a major cause of morbidity and mortality worldwide. In the last few years, the role of inflammation and inflammatory modulatory medications is investigated for the optimal treatment of coronary artery disease. It can be hypothesized that since inflammation is also involved in carotid artery stenosis development and progression, the same class of medication could be useful. Our objective with this review is to present the available evidence, published studies and promising ongoing trials on the role of anti-inflammatory medications - with a special emphasis on the most commonly used drug of this class: colchicine - in patients with carotid artery stenosis.

Differences between Lower Extremity Arterial Occlusion vs. Stenosis and Predictors of Successful Endovascular Interventions.

Background and Objectives: In patients with peripheral artery disease, there is insufficient understanding of characteristics that predict successful revascularization of the lower extremity (LE) chronic total occlusions (CTOs) and baseline differences in demographic, clinical, and angiographic characteristics in patients with LE CTO vs. non-CTO. We aim to explore these differences and predictors of successful revascularization among CTO patients. Materials and Methods: Two vascular centers enrolled LE-CTO patients who underwent endovascular revascularization. Data on demographics, clinical, angiographic, and interventional characteristics were collected. LE non-CTO arterial stenosis patients were compared. A total of 256 patients with LE revascularization procedures were studied; among them, 120 had CTOs and 136 had LE stenosis but no CTOs. Results: Aspirin use (Odds ratio, OR: 3.43; CI 1.32-8.88; p = 0.011) was a positive predictor whereas a history of malignancy (OR: 0.27; CI 0.09-0.80; p = 0.018) was a negative predictor of successful crossing in the CTO group. The CTO group had a higher history of myocardial infarction (29.2 vs. 18.3%, p = 0.05), end-stage renal disease (19.2 vs. 9.6%, p = 0.03), and chronic limb-threatening ischemia as the reason for revascularization (64.2 vs. 22.8%, p < 0.001). They were more likely to have advanced TransAtlantic Inter-Society Consensus (TASC) stages, multi-vessel revascularization procedures, longer lesions, and urgent treatment. Conclusions: The use of aspirin is a positive predictor whereas a history of malignancy is a negative predictor for successful crossing in CTO lesions. Additionally, LE-CTO patients have a higher incidence of comorbidities, which is expected given their higher disease burden. Successful endovascular re-vascularization can be associated with baseline clinical variables.

Treatment of chronic venous disorder: A comprehensive review.

Chronic venous disorder (CVD) is highly prevalent vascular disorder affecting up to 45% of the general population, with clinical manifestations ranging from teleangiectasias to venous leg ulcers (VLUs). We examined the currently available data in order to provide an updated, comprehensive review on treatment options of CVD. We searched MEDLINE, Cochrane, Scopus, EMBASE, ClinicalTrials, and OpenGrey databases for relevant articles in English published until November 2020. Compression treatment is the mainstay of conservative treatment. Pharmacological treatment can provide significant symptomatic relief and hence it should be considered as part of conservative treatment. Transcutaneous Lacer treatment (TCL) is a safe and effective alternative option to sclerotherapy for treatment of C1 stage. High ligation and stripping (HL/S), ultrasound-guided foam sclerotherapy (UGFS), endovenous thermal ablation (EVTA) systems and non thermal non tumescent ablation (NTNT) systems are safe and efficacious first-line options for treatment of saphenous insufficiency. Interventional treatment of co-existing incompetent perforator veins (IPVs) is not supported by contemporary evidence. Regarding deep venous insufficiency (DVI), treatment of symptomatic femoroiliocaval occlusive venous disease refractory to conservative treatment with percutaneous transluminal venoplasty stenting has produced encouraging results.

KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model.

BACKGROUND: Inflammatory dysregulation of KLF4 is related to atheromatosis. In the present study, we explored the impact of colchicine-based regimens on the development of thoracic aortic atheromatosis and KLF4 expression. METHODS: Twenty-eight New Zealand White rabbits were divided to 4 groups. The control group (n = 6) was fed standard chow, group A (n = 6) was fed chow enriched with 1% w/w cholesterol, group B (n = 8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n = 8) was also fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine. After 7 weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with quantitative RT-PCR. RESULTS: Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49-19.84) and C (MD: 20.29, 95% CI: 14.12-26.47). Colchicine with N-acetylcysteine resulted in more pronounced reduction in the extent of atherosclerotic plaques compared to colchicine/fibrate (MD: 6.62, 95% CI: 0.90-12.34). Group A exhibited significantly greater KLF4 expression compared to group B (MD: 4.94, 95% CI: 1.11-8.77) and C (MD: 9.94, 95% CI: 6.11-13.77). Combining colchicine with N-acetylcysteine instead of fenofibrate (MD: 5.00, 95% CI: 1.45-8.54) led to a more robust reduction in KLF4 expression. CONCLUSIONS: In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas.

Transcervical carotid artery revascularization: A systematic review and meta-analysis of outcomes.

OBJECTIVE: Carotid artery stenosis is considered a determinant factor for cerebrovascular events, estimated to be the cause of 10% to 20% of all ischemic strokes. Transcervical carotid artery revascularization (TCAR) has been offered as an alternative to transfemoral carotid artery stenting and carotid endarterectomy to treat carotid artery stenosis. METHODS: We performed a systematic review and meta-analysis of prospective and retrospective studies reporting the outcomes of patients who had undergone TCAR for carotid artery stenosis. The incidence of periprocedural adverse events was calculated. RESULTS: A total of 45 studies with 14,588 patients met the predefined eligibility criteria and were included in the present meta-analysis. The technical success rate was 99% (95% confidence interval [CI], 98%-99%). The reasons for technical failure included an inability to cross the lesion and/or failure to deploy the stent. Access site complications occurred in 2% of all cases (95% CI, 1%-2%; 30 studies). Overall, the incidence of cranial nerve (CN) injuries was very rare, with only 33 of 8994 patients experiencing neurologic deficits attributed to CN involvement. Bleeding complications were reported by 20 studies and occurred in 2% (95% CI, 1%-3%) of all cases. The overall periprocedural all-cause mortality and stroke rate was 0.5% and 1.3%, respectively. In-stent restenosis was observed in 4 of 260 patients (1.5%; 7 studies), and early (30-day) reocclusion or acute thrombosis of the target lesion occurred in 12 of 1243 patients (∼1%; 11 studies). CONCLUSIONS: The results from the present study have provided significant evidence that TCAR is a very promising and safe carotid revascularization approach with favorable technical success rates associated with low periprocedural stroke and CN injury rates.

Serum lipid abnormalities in migraine: A meta-analysis of observational studies.

BACKGROUND: The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear. OBJECTIVE: To determine-quantify the differences in the serum lipid concentrations between lipid-lowering agents-naïve individuals with migraine and healthy controls (HC). METHODS: The study protocol was not preregistered with an online systematic review-protocol registry. A literature search involving MEDLINE, EMBASE, CENTRAL, Google Scholar, and the OpenGrey database was performed. Case-control, cross-sectional, or cohort studies involving HC and participants with migraine (with and without aura regardless of the use of prophylactic treatment) that quantitatively assessed serum low-density lipoprotein cholesterol (LDL-C) (primary index) and/or total cholesterol (TC) and/or high-density lipoprotein cholesterol (HDL-C) and/or triglycerides (TG) (secondary indices) were retrieved. Articles including participants with known dyslipidemia (or under lipid-lowering medications) or with secondary causes of dyslipidemia (aside from the subjectively assessed lifestyle parameters) were excluded. Studies with abstracts and full texts not published in English and articles reporting the implementation of other study designs (reviews, meta-analyses, commentaries, case reports, etc.) were excluded as well. Conference abstracts and English abstracts from studies with full texts not published in English were evaluated as part of the gray literature. Each step of the review process was performed by two investigators independently, and relevant data were abstracted based on standardized extraction forms. Any discrepancies were resolved by a third investigator. RESULTS: Seventeen studies (16 case-control and 1 cross-sectional) fulfilled the eligibility criteria. Retrieved articles involved adult participants, principally during the fourth decade of life. Results were compatible with higher LDL-C levels in migraine individuals (1370) than in HC (1215) [12 studies, mean difference (MD) = 10.4 mg/dl, 95% confidence interval (CI) = (1.6, 19.2)]. Similarly, higher TC levels were determined in migraine patients [14 studies, migraine = 1325, HC = 1213, MD = 10.6 mg/dl, 95% CI = (1.8, 19.3)], as were TG levels [15 studies, migraine = 1526, HC = 1262, MD = 11.8 mg/dl, 95% CI = (3.6, 20.0)]. HDL-C concentrations were not different between the two groups [14 studies, migraine = 1488, HC = 1328, MD = -0.4 mg/dl, 95% CI = (-2.2, 1.5)]. Prespecified sensitivity analysis following the exclusion of studies not presenting comparable body mass index values between the groups nullified the significant difference regarding LDL-C levels [MD = 5.3 mg/dl, 95% CI = (-0.1, 10.8)]. Subgroup analyses as well as the direct comparison of migraine with aura and migraine without aura individuals were compatible with no difference regarding lipid concentrations, but only a small fraction of the retrieved studies presented relevant figures. CONCLUSIONS: Although our results are of limited generalizability, since most retrieved studies were performed in Turkey (nine studies), TC abnormalities may provide part of the explanation for the unfavorable cardiovascular profile of migraine patients. Lifestyle may be partly or entirely accountable for the determined increased serum TC. Additional studies that will completely address the effect that lifestyle parameters exert on lipid concentrations are required to better capture existing abnormalities.

Repeat Coronary Artery Bypass Grafting: A Meta-Analysis of Off-Pump versus On-Pump Techniques in a Large Cohort of Patients.

BACKGROUND: Redo coronary artery bypass grafting (CABG) can be performed with either the off-pump (OPCAB) or the on-pump (ONCAB) technique. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this meta-analysis compared the safety and efficacy of OPCAB versus ONCAB redo CABG. RESULTS: Twenty-three (23) eligible studies were included (OPCAB, n=2,085; ONCAB, n=3,245). Off-pump CABG significantly reduced the risk of perioperative death (defined as in-hospital or 30-day death rate), myocardial infarction, atrial fibrillation, and acute kidney injury. The two treatment approaches were comparable regarding 30-day stroke and late all-cause mortality. CONCLUSIONS: Off-pump redo CABG resulted in lower perioperative death and periprocedural complication rates. No difference was observed in perioperative stroke rates and long-term survival between the two techniques.

Nutrition, dietary habits, and weight management to prevent and treat patients with peripheral artery disease.

Peripheral artery disease (PAD) affects 3%-10% of the Western population and if remains untreated can have devastating consequences to patients and their families. This review article analyzes how healthy dietary habits can decrease PAD rates when applied in the general population. The aim is to focus on dietary, nutritional and weight management interventions in patients with established PAD. Most adults with PAD are overweight or obese, while three out of four patients are characterized by deficiencies in vitamins and minerals. Weight loss interventions when needed and specialized dietary plans should be routinely recommended in patients with PAD. Appropriate nutritional support is of paramount importance in patients with advanced stages of PAD (critical limb ischemia).

Permanent pacemaker implantation in pediatric heart transplant recipients: A systematic review and evidence quality assessment.

Bradyarrhythmias are a common complication following pediatric OHT and may require permanent pacemaker implantation (PPM). The purpose of this study was to investigate the incidence, predictors, and outcomes of children undergoing PPM implantation following OHT. A PRISMA-compliant systematic literature review was performed using the PubMed database and the Cochrane Library (end-of-search date: January 27, 2019). The Newcastle-Ottawa scale and the Joanna Briggs Institute tool were used to assess the quality of cohort studies and case reports, respectively. We analyzed data from a total of 11 studies recruiting 7198 pediatric patients who underwent heart transplant. PPM implantation was performed in 1.9% (n = 137/7,198; 95% CI: 1.6-2.2) of the patients. Most patients underwent dual-chamber pacing (46%, 95% CI: 32.6-59.7). Male-to-female ratio was 1.3:1. Mean patient age at the time of OHT was 10.1 ± 6.3. Overall, biatrial anastomosis was used in 62.2% (95% CI: 52.8-70.6) of the patients. The bicaval technique was performed in the remaining 37.8% (95% CI: 29.4-47.1). Sinus node dysfunction was the most frequent indication for PPM implantation (54.4%; 95% CI: 42.6-65.7) followed by AV block (45.6%; 95% CI: 34.3-57.3). The median time interval between OHT and PPM implantation ranged from 17 days to 12.5 years. All-cause mortality was 27.9% (95% CI: 18.6-39.6) during a median follow-up of 5 years. PPM implantation is rarely required after pediatric OHT. The most common indication for pacing is sinus node dysfunction, and patients undergoing biatrial anastomosis may be more likely to require PPM.

Increased Serum KLF4 in Severe Atheromatosis and Extensive Aneurysmal Disease.

BACKGROUND: Krüppel-like factor 4 (KLF4) is known to preserve vascular homeostasis. In the present study, we sought to correlate serum KLF4 levels with arterial aneurysm size and their clinical presentation. We also explored the association between serum KLF4 levels and the severity of extracranial carotid and peripheral arterial disease. METHODS: Patients undergoing surgery for various forms of atheromatosis (ATH group) or for arterial aneurysm repair (AA group) were eligible for inclusion. KLF4 levels were measured via enzyme-linked immunosorbent assay. RESULTS: Patients in the atheromatic and aneurysmal groups had significantly higher serum KLF4 levels compared with controls. Patients with permanent end-organ damage (ATH3) had higher serum KLF4 (6.96 ± 0.75 pg/mL) compared with patients with asymptomatic internal carotid stenosis >70% or claudication (ATH1) (2.76 ± 0.68 pg/mL; mean difference [MD], -4.20; 95% confidence interval [95% CI], -5.35 to -3.04; P < 0.01) and those with transient ischemic attack or rest pain (ATH2) (4.47 ± 1.08 pg/mL; MD, -2.48; 95% CI, -3.76 to -1.21). Furthermore, patients with an asymptomatic aneurysm of a diameter 250-300% of that of the normal artery (AA1, 5.01 ± 1.08 pg/mL) had considerably lower serum KLF4 compared with those suffering from either a symptomatic aneurysm or an asymptomatic aneurysm of a diameter >350% of that of normal artery (AA3, 6.63 ± 1.92 pg/mL; MD, -2.61; 95% CI, -5.04 to -0.18; P < 0.01). CONCLUSIONS: Serum KLF4 levels are significantly increased in patients with end-organ damage related to atheromatosis as well as those with extensive aneurysmal disease.

Minimally Invasive Surgery vs Device Closure for Atrial Septal Defects: A Systematic Review and Meta-analysis.

Device closure is the first-line treatment for most atrial septal defects (ASDs). Minimally invasive cardiac surgery (MICS) has been found safe and effective for ASD closure with comparable mortality/morbidity and superior cosmetic results compared to conventional median sternotomy. Our goal was to compare percutaneous versus MICS of ASDs. A systematic review was performed using PubMed and the Cochrane Library (end-of-search date on May 22, 2019). Meta-analyses were conducted using fixed and random effects models. In the present systematic review, we analyzed six studies including 1577 patients with ASDs who underwent either MICS (n = 642) or device closure (n = 935). Treatment efficacy was significantly higher in the MICS (99.8%; 95% CI 98.9-99.9) compared to the device closure group (97.3%; 95% CI 95.6-98.2), (OR 0.1; 95% CI 0.02-0.6). Surgical patients experienced significantly more complications (16.2%; 95% CI 13.0-19.9) compared to those that were treated with a percutaneous approach (7.1%; 95% CI 5.0-9.8), (OR 2.0; 95% CI 1.2-3.2). Surgery was associated with significantly longer length of hospital stay (5.6 ± 1.7 days) compared to device closure (1.3 ± 1.4 days), (OR 4.8; 95% CI 1.1-20.5). Residual shunts were more common with the transcatheter (3.9%; 95% CI 2.7-5.5) compared to the surgical approach (0.95%; 95% CI 0.3-2.4), (OR 0.1; 95% CI 0.06-0.5). There was no difference between the two techniques in terms of major bleeding, hematoma formation, transfusion requirements, cardiac tamponade, new-onset atrial fibrillation, permanent pacemaker placement, and reoperation rates. MICS for ASD is a safe procedure and compares favorably to transcatheter closure. Despite longer hospitalization requirements, the MICS approach is feasible irrespective of ASD anatomy and may lead to a more effective and durable repair.

Correlation of Glycosylated Hemoglobin Levels with Histological and Ultrasound Characteristics of the Carotid Plaque in Diabetic and Nondiabetic Patients.

BACKGROUND: The purpose of this study is to investigate the correlation of glycosylated hemoglobin (HbA1c) levels with histological characters of atherosclerotic plaque that makes it vulnerable, as well as ultrasound (US) criteria that can contribute to the prognosis of carotid disease. MATERIAL AND METHODS: This is a single-center prospective study. Our study population consists of 74 diabetic and nondiabetic patients with carotid atherosclerosis who underwent carotid endarterectomy in our department. Patient categorization was based on the following criteria: levels of HbA1c, gender, and risk factors (smoking, hypertension), carotid stenosis rate, symptomatic or asymptomatic carotid disease, histological examination of the atherosclerotic plaque, and US morphological criteria of the plaque. RESULTS: The mean age of the patients was 68.2 years (standard deviation = 7.8); 58.1% were smokers, 71.6% had arterial hypertension, 37.8% had symptomatic carotid disease, and 64.9% had atherosclerotic plaque type 6. Futhermore, 95.9% of the patients had a carotid stenosis rate more than 70% and 4.1% had from 50% to 69%. Older patients had more frequent type 7 and 8 atherosclerotic plaque based on American Heart Association scoring system than younger patients (P = 0.041). The relative likelihood of atherosclerotic plaque type 7 and 8 was 1.12 times higher in older patients (Odds ratio [OR] = 1.12, P = 0.029). Patients with higher levels of HbA1cwere more likely to have type 6 atherosclerotic plaque than those with atherosclerotic lesions type 7 and 8 (P < 0.001). Specifically, increasing the level of HbA1c by 1 mg/dl increases the likelihood of the presence of vulnerable plaque by 2.55%. Moreover, the relative likelihood of a type 6 atherosclerotic plaque was 10.4 times higher in the older patients (OR = 10.4, P < 0.001). CONCLUSIONS: This study demonstrates that levels of HbA1c and advanced age are 2 factors that may be correlated with the presence of vulnerable carotid plaques in diabetic population. Moreover, HbA1c is an independent factor that could possibly be used as a prognostic marker for carotid artery disease, although further studies are needed to explore this association to elucidate the precise role of HbA1c.

Postoperative cardiac damage after standardized carotid endarterectomy procedures in low- and high-risk patients.

BACKGROUND: We conducted a comparison of postoperative cardiac damage, defined as cardiac troponin I (cTn-I) elevation, after carotid endarterectomy in low- and high-risk patients. METHODS: The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) criteria for stratifying patients considered for carotid endarterectomy into low and high surgical risk groups were used prospectively. All patients had preoperative full cardiologic evaluations and cTn-I value assessments that were repeated on postoperative days 1, 3, and 7. Postoperative cTn-I values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. RESULTS: Mortality was 1.2%, the stroke rate was null, and symptomatic myocardial infarction was null. Among the 56 high-risk patients, 8 had cTn-I values>0.5 ng/mL. Among the 106 low-risk patients, 10 patients had cTn-I value >0.5 ng/mL and 4 patients had cTn-I values that were >0.05 ng/mL and ≤0.5 ng/mL. All patients with increased cTn-I levels were asymptomatic. Concerning all patients, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.438 ng/mL on postoperative day 1 (P=0.017), 0.168 ng/mL on postoperative day 3 (P=0.06), and 0.019 ng/mL on postoperative day 7 (P=0.02). In the high-risk group, the mean preoperative cTn-I value was 0.008 ng/mL, which increased to 0.829 ng/mL on postoperative day 1, 0.270 ng/mL on postoperative day 3, and 0.030 ng/mL on postoperative day 7. In the low-risk group, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.198 ng/mL on postoperative day 1, 0.119 ng/mL on postoperative day 3, and 0.013 ng/mL on postoperative day 7. Patients without cardiac damage showed analogous tendencies in their troponin values. Comparison of troponin values between high- and low-risk patients on each day showed no statistical difference. Electrocardiogram alterations were seen in 20 of the 22 patients with asymptomatic troponin elevation but in none without troponin elevation. CONCLUSIONS: Carotid endarterectomy is followed by an increase in cTn-I value>0.5 ng/mL in 14% of all cases, although symptomatic cardiac ischemia is very low. However, high-risk patients as defined by the SAPPHIRE criteria do not show an increased risk of cardiac damage compared to low-risk patients. Larger studies using cTn-I as a marker of postoperative cardiac damage, after carotid endarterectomy or stenting, are needed.

Obesity and Peripheral Artery Disease: Current Evidence and Controversies.

PURPOSE OF REVIEW: Obesity is a significant public health problem and a major risk factor for the development and progression of atherosclerosis and its cardiovascular manifestations. Lower extremity peripheral artery disease (PAD) affects 3%-10% of the Western population and, if left untreated, can lead to devastating outcomes with both an increased risk of morbidity and mortality. Interestingly, the association between obesity and PAD remains debatable. Whereas it is well known that PAD and obesity frequently overlap in the same patients, many studies have demonstrated a negative association between obesity and PAD and a protective effect of obesity on disease development and progression, a phenomenon described as the "obesity paradox." Possible mechanisms for this paradox may include genetic background, as assessed by mendelian randomization studies, adipose tissue dysfunction, and body fat distribution rather than adiposity, while other factors, such as sex, ethnicity, sarcopenia in the elderly population, or aggressive treatment of co-existing metabolic conditions in individuals with obesity compared to those with normal weight, could have some impact as well. RECENT RINDINGS: Few reviews and meta-analyses examining systematically the relationship between obesity and PAD exist. The impact of PAD development due to the presence of obesity remains largely controversial. However, the most current evidence, backed by a recent meta-analysis, suggests a potential protective role of a higher body mass index on PAD-related complications and mortality. In this review, we discuss the association between obesity and PAD development, progression, and management, and the potential pathophysiologic mechanisms linking the two diseases.

Management of Post-thrombotic Syndrome: A Comprehensive Review.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common long-term complication of acute deep venous thrombosis (DVT). The cumulative incidence of PTS in the first two years after the first acute DVT diagnosis approximates 25%. OBJECTIVE: This study aims to summarize the most recent updates and provide a comprehensive review of the current management of PTS. METHODS: We searched MEDLINE/PMC/NCBI Bookshelf (PubMed), Cochrane, Embase, Scopus, ClinicalTrials, and OpenGrey databases for relevant articles in English published from the establishment of each separate database until February 9, 2021. CONCLUSION: PTS constitutes the most frequent long-term complication of lower limb deep venous thrombosis (DVT). Lifestyle changes and compression treatment represent an integral part of PTS management and have a clear benefit to offer in PTS patients. Pharmacological treatment with phlebotonic and non-phlebotonic medications, such as micronized purified flavonoid fraction (MMPF) and sulodexide, respectively, may have a more central and significant role in PTS management than previously thought. The introduction of percutaneous transluminal venoplasty (PTV) and stenting has again raised our expectations with the field, along with new concerns and considerations. There is a growing number of studies that report promising results on patientoriented outcomes on PTS patients who were treated with PTV and stenting. Moreover, hybrid (endovascular/ surgical) interventions may also represent a safe and efficacious treatment option for a subset of patients with PTS. Patient selection criteria for endovascular and hybrid interventional treatment should be carefully set and standardized. Post-operative care after venoplasty is an important field of future research with potential clinical impact. Management of deep and superficial reflux remains controversial. Hopefully, future prospective studies shall provide more robust evidence on the management of PTS.

Advances in treatment of chronic thromboembolic pulmonary hypertension.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a progressive pulmonary vascular disease which can lead to right heart failure and death, if left untreated. CTEPH is caused by persistent obstruction of large, middle-sized, or distal pulmonary arteries due to limited thromboembolic resolution in the pulmonary vascular arterial tree. Every patient with CTEPH should undergo evaluation for Pulmonary Endarterectomy (PEA) after referral to institutions with an experienced multidisciplinary CTEPH team. Although management of distal thromboembolic lesions with PEA remains a challenge due to their difficult accessibility, limited distal CTEPH is not considered an absolute contraindication for PEA, as more expertise surgical teams operate on them successfully. Furthermore, in up to 30-50% of patients who undergo PEA, curative treatment is not achieved due to incomplete thrombi removal or extensive pulmonary microvascular disease. Medical therapies that target the underlying pulmonary microvascular disease can offer symptomatic and hemodynamic benefits, although they do not deal with the core mechanism of the disease which is the removal of thromboembolic material from pulmonary vasculature. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) is a reasonable treatment option for inoperable CTEPH and recurrent/persistent pulmonary hypertension after PEA. Advancements in diagnostic modalities and refinements of BPA technique have decreased the complication rate and increased its beneficial effects in hemodynamics, symptoms, right ventricular function and long-term survival. Ongoing trials and future prospective cohorts will provide evidence regarding the optimal selection of patients and lesions prone to BPA treatment along with hybrid therapeutic strategies combining pharmacological therapy, PEA and BPA, which can potentially change the standard of care in CTEPH.

Toll-like receptor 4 immunohistochemical expression is enhanced in macrophages of symptomatic carotid atherosclerotic plaques.

BACKGROUND: A growing body of evidence supports a role for Toll-like receptor 4 (TLR4), a primary receptor of the innate immune system, in atherosclerosis initiation and progression. Carotid atheroma macrophages (MACs) and smooth muscle cells (SMCs) express TLR4; nevertheless, correlations with epidemiological and clinical variables and especially cerebrovascular symptomatology remain unsettled. METHODS: Carotid atherosclerotic plaques were obtained by standard carotid endarterectomy on 157 patients with carotid artery disease (84 asymptomatic - 73 symptomatic). TLR4 expression in MACs and SMCs of carotid atheroma was detected by immunohistochemistry techniques. TLR4 positivity, overexpression and intensity of immunostaining in MACs and SMCs were correlated with cerebrovascular symptomatology, epidemiological and clinical variables. RESULTS: MAC TLR4 positivity was noted in 129 (82.2%) patients. Patients receiving statins had significantly lower TLR4 expression. Rates of MAC TLR4 positivity were higher among symptomatic patients (odds ratio, OR = 5.1; 95% confidence interval, CI = 1.8-14.3; p < 0.001); the association was stronger for transient ischemic attacks. TLR4 overexpression was also significantly enhanced among symptomatic patients (OR = 2.3; 95% CI = 1.02-5.03; p < 0.05). No correlations were detected between SMC TLR4 expression and cerebrovascular symptoms. In multivariate models adjusting for age, gender, body mass index, hyperlipidemia and smoking, MAC TLR4 positivity was associated with a cerebrovascular event during the last 6 months (OR = 4; 95% CI = 1.2-13.3; p = 0.02). CONCLUSIONS: Symptomatic carotid artery plaques are characterized by increased expression of TLR4 in macrophages supporting a potential role for TLR4 in the pathophysiology and clinical presentation of cerebrovascular disease. Further investigation is warranted.

Revascularization approaches in patients with radiation-induced carotid stenosis: an updated systematic review and meta-analysis.

BACKGROUND: Ionizing radiation remains a well-known risk factor of carotid artery stenosis. The survival rates of head and neck cancer patients undergoing radiotherapy have risen owing to medical advancements in the field. As a consequence, the incidence of carotid artery stenosis in these high-risk patients has increased. AIMS: In this study we sought to compare the outcomes of carotid endarterectomy (CEA) vs carotid artery stenting (CAS) for radiation-induced carotid artery stenosis. METHODS: This study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Eligible studies were identified through a comprehensive search of PubMed, Scopus and Cochrane Central until July 2020. A random-effects model meta-analysis was conducted, and odds ratios (ORs) were calculated. The I-square statistic was used to assess for heterogeneity. RESULTS: Seven studies and 201 patients were included. Periprocedural stroke, myocardial infarction (MI), and death rates were similar between the two revascularization approaches. However, the risk for cranial nerve (CN) injury was higher in the CEA group (OR, 7.40; 95% CI, 1.58-34.59; I2 = 0%). Analysis revealed no significant difference in terms of long-term mortality (OR, 0.41; 95% CI, 0.14-1.16; I2 = 0%) and restenosis rates (OR, 0.69; 95% CI, 0.29-1.66; I2 = 0%) between CEA and CAS after a mean follow-up of 40.5 months. CONCLUSIONS: CAS and CEA appear to have a similar safety and efficacy profile in patients with radiation-induced carotid artery stenosis. Patients treated with CEA have a higher risk for periprocedural CN injuries. Future prospective studies are warranted to validate these results.

Risk Models and Scores in Patients with Peripheral Artery Disease and Chronic Limb-threatening Ischemia: A Comprehensive Review.

Peripheral artery disease (PAD) affects more than 200 million patients worldwide and chronic limbthreatening ischemia (CLTI) is the most advanced stage of PAD with very high morbidity and mortality rates. Cardiovascular medicine is trending towards a more personalized approach where each individual patient will be managed according to specific risk factors, disease characteristics, expectations related to their disease and individualized assessment of potential outcomes. For this reason, a number of risk models and scores have been developed during the last few years. Our aim in this comprehensive review article is to provide an overview of selected risk models and scores for patients with PAD and CLTI. Given that some of the published scores were of low quality (minimal discriminatory ability), we included scores that were already externally validated or scores that had promising initial findings. Available scoring systems were grouped in the five following categories according to their utility: i) scores that can detect asymptomatic patients who should be screened for PAD, ii) scores for assessment of functional status and quality of life in patients with PAD, iii) scores assessing risk for amputation and other major adverse limb events among patients with CLTI, iv) scores for the optimal revascularization strategy in each patient and scores predicting successful procedural outcomes; v) scores predicting short or long-term cardiovascular and limb related outcomes after either revascularization or at least angiographic assessment. Limitations of available scoring systems include development and validation in specific populations, lack of external validation (for some of them) and also lack of synchrony with current era endovascular technology. However, with further optimization of current scores and the development of new scores, the field of PAD and CLI can be transitioned to a personalized medicine approach.