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Patients undergoing coronary artery bypass grafting (CABG) are at increased risk of perioperative stroke. Carotid atherosclerosis has been identified as an independent risk factor for stroke during and in the early postoperative period of cardiac surgery. However, the pathogenesis of peri-CABG stroke is multifactorial and frequently involves other noncarotid causes, such as cardiac emboli and aortic atheroma. Therefore, routine population-wide screening of carotid stenosis is not recommended, but target screening of patients at high risk of carotid-related perioperative stroke can have benefits. Carotid duplex sonography is recommended as an initial screening tool. Elimination of carotid stenosis before cardiac surgery is indicated in patients in whom carotid atherosclerosis is suspected to be the primary contributor to perioperative stroke. In patients with advanced carotid atherosclerosis, an individualized revascularization approach, including simultaneous or staged procedures, is advocated. The prevailing consensus is that synchronous surgery is safer than staged procedures. Carotid artery stenting represents a less invasive alternative, but its role in high-risk patients requires further investigation. In conclusion, the risk of perioperative stroke in patients undergoing CABG involves different factors, and carotid artery stenosis is involved in its pathogenesis only in some patients. Therefore, individualized approaches and careful consideration of patient risk factors are essential in determining the need for carotid screening and revascularization before CABG., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Disclosures D.P.M. has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. J.F.M. receives funding from the United States National Institute of Neurologic Disorders and Stroke for work related to running the CREST-2 clinical trial (U01NS080168) and the CREST-2 Long-term Observational Extension study (U01NS119169). E.A.S. has received research grants from the United States Food and Drug Administration, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips; has received consulting/speaking fees from Abbott, Bayer, BD, Boston Scientific, Cook, Cordis, CSI, Inari, Infraredx, Medtronic, Philips, Shockwave and VentureMed. H.-H.E. is a local Principal Investigator for the ROADSTER 2 trial and a scientific committee member of SPACE-1, SPACE-2 and ACST-2. T.R. is funded by grants from the National Institutes of Health (R01 MD012467, R01 NS029993, R01NS040807, 1U24NS107267), and the National Center for Advancing Translational Sciences (UL1 TR002736, KL2 TR002737). J.S.M. has received institutional research grants from Abbott, Cook, Endologix, Gore and Medtronic., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Varicose veins (VVs) mostly represent benign disease. However, in some cases, they can lead to serious complications including deep venous thrombosis (DVT) and pulmonary embolism (PE). Besides deteriorated blood flow caused by VVs inflammation is most probably a common denominator of VVs and DVT, which promotes a procoagulant state and thrombus formation also in deep veins. Patients with VVs have increased levels of interleukins, the most specific inflammatory markers of vascular wall inflammation that promote coagulation. The studies showed that VVs may increase the risk for DVT. However, the evidence of the risk and incidence of DVT in patients with VVs and without additional risk factors is poor. The increased risk is associated with previous venous thromboembolism (VTE), malignancy, estrogen use, pregnancy and postpartum, hospitalization in the last 6 months, age, and obesity. Varicose veins represent also an increased risk for VTE during long-term immobilization and long air travel or road trip. Further, superficial venous thrombosis is related to an increased risk for DVT, particularly if the thrombus in the superficial vein extends close to the saphenofemoral or femoropopliteal junction. Increased risk for DVT is increased during and after invasive treatment of VVs. Thromboprophylaxis after invasive procedures is recommended in subjects older than 60 years and those with another thrombophilic state.

Competing Interests: Disclosure: The authors have no conflicts of interest to disclose.

Background: Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk., Methods: We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021. Patients were divided into delayed sternal closure (DSC) and primary sternal closure (PSC) groups. We used chi-squared or Fisher Exact tests, as appropriate, to compare the incidence of postoperative LVAD-related infections (mediastinal/sternal wound) and LVAD-specific infections (driveline and pump pocket) after definitive chest closure between these two groups., Results: A total of 327 patients met eligibility criteria, including 127 (39%) patients that underwent DSC and 200 (61%) patients that had a PSC. Demographic and clinical characteristics were similar except for an overrepresentation of men (87% vs. 75%, p = .016), Interagency Registry of Mechanically Assisted Circulatory Support class I-II patients (89% vs 66%, p < .001), patients with a previous sternotomy (43% vs 13%, p < .001), and patients with chronic kidney disease (55% vs 43%, p = .030) in the DSC group. The median DSC time was 24 (IQR: 24-48) hours. The incidence of LVAD-related mediastinal/sternal wound infection was similar between the DSC and PSC groups (4.7% vs 3.0%, p = .419). There was no difference between DSC and PSC groups in the incidence of driveline infection (6.3% vs 9%, p = .411) and pump pocket infection (1.6% vs 1.5%, p =.901), respectively., Conclusions: DSC does not seem to increase the incidence of LVAD-related or LVAD-specific infection rates in heart failure patients undergoing device implantation surgery., Competing Interests: Disclosure statement The authors report no conflict of interest., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest All authors are members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS; available at www.FACTCATS.org) with the shared goal of optimizing stroke prevention. The views of particular FACTCATS do not necessarily reflect the views of other FACTCATS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Tricuspid valve repair in left ventricular assist device implantation continues to pose a challenge and may impact the occurrence of early and late right heart failure. We investigated the effects of concomitant tricuspid repair on clinical outcomes., Methods: A retrospective, multicentre study enrolled adult patients who received continuous-flow left ventricular assist devices between 2005 and 2017 and compared those who received concomitant tricuspid valve repair to those who did not. Primary outcomes were early right heart failure necessitating temporary ventricular assist devices and right heart failure-related rehospitalizations requiring inotropic or diuretic treatment., Results: Out of 526 patients who underwent left ventricular assist device implantation, 110 (21%) received a concomitant tricuspid valve repair. Those patients were sicker, and most had moderate or severe tricuspid regurgitation. A significantly higher incidence of temporary right ventricular assist devices was observed in the group with concomitant tricupid valve repair (18% vs. 11%, P = 0.049), with a significantly elevated risk for temporary right heart assist device (sHR 1.68, 95% CI 1.04-2.72; P = 0.037). After adjusting for confounders, no significant differences were found in the incidence of and risk for most clinical outcomes, including right heart failure-related rehospitalizations (P = 0.891) and death (P = 0.563)., Conclusions: Concomitant tricuspid valve repair, when deemed necessary in left ventricular assist device implantation, may increase the risk of early right heart failure requiring a temporary right ventricular assist device but does not impact the incidence or risk of death or rehospitalizations due to late right heart failure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation., Methodology and Study Design: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared., Results: We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR ≥ 1) (32% vs. 12%, P = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR ≥ 2R) (32% vs. 40%, P = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, P = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711-1,664], P < 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, P = 0.020). No difference was observed in other outcomes., Conclusion: In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McDonald, Mihalj, Zhao, Nathan, Matejin, Ottaviani, Jezovnik, Radovancevic, Kar, Gregoric and Buja.)

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

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., Competing Interests: Declaration of Competing Interest Dr. Mikhailidis has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. Dr. Chaturvedi reports consulting for Astra Zeneca and BrainGate and serving as an Associate Editor for Stroke, and as an Editorial Board Member of Neurology and Journal of Stroke and Cerebrovascular Diseases. The other authors report no conflicts., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-2021-12/coif). DPM receives royalties and fees from SAGE, Informa and Bentham Science publishers, consulting fees from Novo Nordisk, lecture fees and travel expenses from Amgen and Novo Nordisk. The other authors have no conflicts of interest to declare.

Objectives: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic., Materials and Methods: A literature review was performed with a focus on data from recent studies., Results: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses., Conclusions: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Background: A significant consequence of peripheral arterial disease (PAD) is an impaired functional capacity and deteriorated quality of life. Therefore, our study aimed to investigate the usefulness of a symptom questionnaire and walk tests for the determination of the functional capacity of patients with intermittent claudication. Patients and methods: The study included 53 patients (38 males) with stable claudication distance (50-300m). A detailed history and physical examination, ankle-brachial index (ABI), treadmill exercise test, and 6-minute walk test were performed and compared to walking impairment questionnaire (WIQ). Results: Claudication distance reported from patients' history and 6-minute walk test were significantly correlated with ABI (p=0.033, p=0.044). There were no significant correlations between ABI and treadmill walk test or WIQ. Results of WIQ were significantly correlated with the history and the most of performed walk tests: treadmill initial and maximal claudication distance (p=0.004 and 0.012, respectively) and 6-minute walk test (p=0.026). 6-minute walk test was correlated with maximal claudication distance of treadmill (p=0.018), but not with an initial claudication distance. Conclusions: The validity of WIQ is comparable to walk tests and represents the useful technique for the investigation of the functional capacity of patients with PAD. A self-report based on WIQ enables a longer period of observation. It should be routinely used as a basic diagnostic tool for the estimation of the functional capacity of PAD patients with stable intermittent claudication.

Carotid atherosclerotic lesions are correlated with atherosclerotic deterioration of the arterial wall in other vascular territories and with cardiovascular events. The detection of pre-symptomatic carotid lesions like intima-media thickness (IMT) and asymptomatic carotid plaques is possible by non-invasive ultrasound duplex scanning. Current measurement guidelines suggest an average measurement of IMT within 10 mm of the segment of the common carotid artery. The thickening of intima-media appears in a long subclinical period of atherosclerosis. Therefore, the determination of IMT has emerged as one of the methods for determining early structural deterioration of the arterial wall. A close interrelationship was shown between IMT and risk factors of atherosclerosis, their duration, and intensity. Different studies demonstrated that increased IMT is a powerful predictor of coronary, cerebrovascular, and peripheral arterial occlusive disease and their complication. A recent meta-analysis indicated a minimal improvement in the risk estimation of cardiovascular events after adding IMT to the Framingham Risk Score. These findings influenced the latest ACC/AHA guidelines which again recommend the use of carotid IMT measurement for individual risk assessment. The presence of atherosclerotic plaques indicates that the atherosclerotic process is already ongoing. The findings of different studies are equivocal that carotid plaques independently predict cardiovascular events and improve risk predictions for coronary artery disease when added to the Framingham Risk Score. However, besides the size of plaque and grade of stenosis, the structure of plaque calcification, vascularization, lipid core, and the surface of plaques are important indicators of related risks for cardiovascular events., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-20-5570). The series “Carotid Artery Stenosis and Stroke – Prevention and Treatment Part II” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Peripheral artery disease (PAD) is one of the most frequent manifestations of atherosclerosis with high rates of morbidity and mortality. Platelets and coagulation are involved in the progression of atherosclerosis and thromboembolic complications. PAD patients have increased prothrombotic potential, which includes platelet hyperaggregability and increased pro-coagulant state. Therefore, antithrombotic treatment is of utmost importance for the prevention of cardiovascular events in this group of patients. Aspirin is the basic antiplatelet drug, but with limited efficacy in PAD. In contrast to coronary artery disease, its effect on the prevention of cardiovascular events in PAD has been limited proven. Particularly in asymptomatic PAD, there is no evidence for risk reduction with aspirin. Clopidogrel and ticagrelor are more effective than aspirin. Clopidogrel is thus an effective alternative to aspirin for prevention of cardiovascular events in symptomatic PAD. In patients who are non-responders to clopidogrel, ticagrelor is indicated. Dual antiplatelet treatment (DAPT) with aspirin and ticagrelor in patients with coronary artery disease and concomitant PAD significantly decreased the rate of major adverse cardiovascular events, including adverse limb events. However, in the CHARISMA Trial, aspirin and clopidogrel were not more effective than aspirin alone and increased bleeding complications. Therefore, DAPT seems effective only in PAD accompanied by coronary artery disease. Anticoagulant treatment for symptomatic PAD with vitamin K antagonists alone or in combination with aspirin is not more effective than single antiplatelet treatment but increases the rate of major bleeding. Low dose rivaroxaban combined with aspirin in PAD patients significantly reduces cardiovascular events, including limb-threatening ischemia and limb amputations. Anticoagulation and antiplatelet treatment after percutaneous or surgical revascularization of PAD improve the patency of treated vessels. Aspirin with or without dipyridamole improved patency of infra-inguinal by-pass grafts at one year. The combination of clopidogrel with aspirin was more effective than aspirin alone in the prevention of prosthetic graft occlusions in patients undergoing below-knee by-pass-grafting. Oral vitamin K antagonists were not more effective than aspirin in the prevention of infra-inguinal by-pass occlusion. The combination of low dose rivaroxaban and aspirin was effective in preventing major adverse cardiovascular events and adverse limb events after infrainguinal endovascular or surgical revascularization in patients with intermittent claudication. However, the data on antithrombotic treatment after revascularization for limb-threatening ischemia is scanty and inconclusive. In conclusion: Antithrombotic treatment of PAD is a cornerstone for the management of these patients. Antiplatelet drugs prevent the initiation and progression of atherosclerosis and are effective also in the prevention of thromboembolic events. Simultaneous use of antiplatelet and anticoagulation drugs is accompanied by an increased risk of bleeding. However, combined treatment with aspirin and low-dose rivaroxaban is more effective than single antithrombotic treatment and safer than full-dose combined treatment.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Background: The presence of a left ventricular thrombus (LVT) poses a risk of thromboembolic complications and excludes patients from undergoing left ventricular assist device (LVAD) implantation without the aid of cardiopulmonary bypass (CPB). Transthoracic echocardiography (TTE) and transesophageal echocardiography are used to detect LVT in patients with heart disease; however, the detection validity of these imaging studies has not been definitively elucidated., Methods: A retrospective analysis of patients with end-stage heart failure who underwent LVAD implantation from May 2012 to August 2018 in a single center was completed. To be included, patients' medical records had to have presurgical TTE and transesophageal echocardiographic images, as well as intraoperative digital and visual exploration observations. A total of 301 patients underwent LVAD implantation; 239 of these patients had an LVAD implanted with the use of CPB. A total of 230 patients had complete data sets and were included in the analysis., Results: Preoperative TTE identified LVT in 23 of the 230 patients (10%); 15 patients (6.5%) had LVT confirmed by surgical intraventricular visualization. Of the patients with visual LVT confirmation, preoperative TTE identified an LVT in all but 1 case (93%; 14 of 15). Preoperative TTE of LVT had a high sensitivity (94%) and specificity (96%), as well as high negative predictive value (99%)., Conclusions: The results of this study show that preoperative TTE is highly accurate for LVT detection. The high negative predictive value could have significant implications for the choice of surgical procedure because with TTE, surgeons can reasonably determine whether LVAD placement procedure can be attempted without CPB support., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The endothelium plays a crucial role in maintaining cardiovascular homeostasis. Shear stress generated by flowing blood regulates the release of substances that provide adequate tissue perfusion. The extent of damage to endothelial cells depends on locally disturbed shear stress caused by the deteriorated flow. Patients with heart failure have reduced cardiac output, which results in reduced blood flow and negative shear stress. Reduced shear stress also affects microcirculation and reduces tissue perfusion. Consequently, the production of free oxygen radicals is increased and bioavailability of nitric oxide is additionally decreased. Therefore, endothelial dysfunction is involved in the progression of heart failure and cardiovascular events. Left ventricular assist devices (LVAD) are used for the treatment of patients with advanced heart failure. Older pulsatile flow LVADs were mostly substituted by continuous-flow LVADs (cf-LVADs). Despite the advantages of the cf-LVADs, the loss of pulsatility leads to different complications on the micro- and macrovascular levels. One of the pathogenetic mechanisms of cardiovascular complications with cf-LVADs may be endothelial dysfunction, which after the implantation of the device does not improve and may even deteriorate. In contrast, the pulsatile pattern of LVADs on blood flow could preserve endothelial function.

Our study aimed to investigate the levels and time-course of systemic inflammatory and hemostasis markers in the early postoperative period in patients undergoing total hip replacement (THR). The study included 70 patients of both sexes, average age 68.4 ± 10.9 years. Levels of inflammatory and hemostasis markers were measured before surgery (POD 0), a day after the surgery (POD 1) and 5 days after surgery (POD 5). In the postoperative period inflammatory markers increased. The operation provoked a significant increase of CRP on POD 1 in comparison to POD 0 (68.5 ± 5.4 vs 6.8 ± 2.2 μg/mL, p < 0.001) and the additional increase was registered on POD 5 (87.5 ± 8.1 vs 68.5 ± 5.4 μg/mL, p < 0.001). Interleukin-6 significantly increased on POD 1 (251.5 ± 21.6 vs 14.6 ± 7.1 μg/mL, p < 0.001) and after that (POD 5) decreased. After surgery leukocyte count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher compared to POD 0. Activation of coagulation in the postoperative period was shown by increased peak thrombin on POD 5 in comparison to POD 0 (185 ± 27 vs. 124 ± 31 nM, p < 0.001). D-dimer was increased on POD 1 and an additional rise was observed on POD 5. vWF also progressively increased in the observed period. Results of our study showed that after THR systemic inflammatory markers increased and coagulation function was enhanced. Determination of inflammatory and procoagulant markers could help identify patients at risk for cardiovascular thromboembolic events.

Gastrointestinal (GI) bleeding is a common complication following the placement of continuous-flow left ventricular assist devices (LVADs) in patients with advanced heart failure. Secondary events arising as a result of GI bleeding have not been well-described. Furthermore, attribution of these events to bleeding is complicated by the interruption or de-intensification of antithrombotic therapy, while bleeding is controlled. The purpose of this study was to assess the incidence of pump thrombosis and ischemic stroke in patients with LVADs who experience GI bleeding, while on support. This was a single-center, retrospective, observational cohort study of consecutive patients with LVADs implanted from January 2012 to June 2018. Patients were assigned to comparator groups based on whether they experienced GI bleeding while on LVAD support. The primary endpoint assessed was the composite of pump thrombosis or ischemic stroke. Secondary endpoints assessed included incidence of pump thrombosis or ischemic stroke. A total of 250 patients were included after screening for exclusion criteria, 101 (40.4%) in the GI bleeding group, and 149 (59.6%) in the non-bleeding group. The incidence of pump thrombosis or ischemic stroke was not significantly greater in patients experiencing GI bleeding [23 (22.8%) vs. 21 (14.1%); P = .09]; however, the incidence of ischemic stroke alone was significantly greater [17 (16.8%) vs. 10 (6.7%); P = .01]. We conclude that GI bleeding in LVAD patients may be associated with a greater risk of ischemic stroke., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Carotid atherosclerotic plaques represent a risk for ischemic stroke. The data indicate that the risk for distal embolization from atherosclerotic lesions in internal carotid arteries is not related only to the degree of stenosis but also to the composition of plaques. The stability of atherosclerotic plaque depends on the thickness of the fibrous cap and plaque hemorrhage. Recent research indicated that the inflammatory activity of atherosclerotic lesions is pivotal in the progression of atherosclerotic plaques. It also promotes the development of unstable atherosclerotic lesions and is related to thromboembolic cerebrovascular complications. Inflammation destabilizes atherosclerotic plaques through the degradation of their fibrotic structure. Inflammation of atherosclerotic plaques was confirmed by histopathologic findings and levels of circulating inflammatory markers which were correlated to the intensity of the inflammation in atherosclerotic lesions. Recently, new techniques like fluorodeoxyglucose positron emission tomography (18-FDG PET) were developed for the identification of inflammation of atherosclerotic lesions in the vessel wall in vivo . Systemic inflammatory markers, particularly interleukins, tumor necrosis factor-alpha and metalloproteinases were shown to be related to the intensity of the inflammatory process in atherosclerotic lesions and the cerebrovascular events. Identification of inflamed atherosclerotic plaques may help to identify unstable atherosclerotic lesions and subjects at high risk for cerebrovascular incidents who need intensive preventive measures including anti-inflammatory medication., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-2020-cass-15). The series “Carotid Artery Stenosis and Stroke: Prevention and Treatment Part I” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

In patients with peripheral arterial disease (PAD), the ability to perform physical exercise is an essential and most important indicator of a patient's health and quality of life. In many cases, there exists a discrepancy between lower extremity blood flow, the extent of arterial occlusion shown by morphological investigation and functional impairment. Reversal of lower extremity arterial obstruction with revascularization does not always reverse functional impairment of diseased leg. Further, training exercise and drug treatment can improve functional performance although they are not associated with an improvement in arterial obstruction. Therefore, the determination of functional impairment and its recovery after different therapeutic procedures should be determined using objective tests. The most frequently used functional tests are treadmill exercise testing and a 6-minute walk test. The constant load test, in which results are expressed as a walked distance, does not always permit an accurate assessment of the full range of functional impairment of PAD patients. Recently, as a substitute for a constant-load test, the graded treadmill test is used. With this test, it is possible to identify those individuals with exercise limitations who are not caused only by deterioration of the blood flow of lower limbs. The 6-minute walk test is simple to perform and requires minimal equipment. However, the correlation between the 6-minute walk test and the graded treadmill test is relatively weak, indicating that peak performance on a graded treadmill may reflect different pathophysiological mechanisms of limitations. In conclusion: for the determination of limitations of mobility and quality of life in patients with PAD, objective measures of functional impairment are needed. The determination of functional capacity is related to the quality of life and is a useful tool for investigation of the success of revascularization of peripheral arteries and conservative treatment.

The outcome of a thrombotic vessel occlusion is related to the resolution of thrombus and restitution of blood flow. Thrombus formation simultaneously activates an enzymatic process that mediates endogenous fibrinolysis to maintain vessel patency. The balance between coagulation and fibrinolysis determines the extent of thrombus formation, its resolution, and clinical outcome. Endogenic fibrinolysis is frequently unable to overcome coagulation and to resolve the thrombus. Therefore, for a complete resolution of thrombus in an acute phase, exogenic fibrinolytic agents are needed. Currently, tissue plasminogen activator (tPA) is most frequently used for therapeutic thrombolysis. Also, heparins, particularly low-molecular-weight heparins and direct oral anticoagulants which are known as anticoagulant drugs, have some pro-fibrinolytic properties. Besides the extent and age of a clot, different other factors influence the lysis of thrombus. Thrombus structure is one of the most important determinants of thrombus lysis. The concentration of thrombolytic agent (tPA) around and inside of thrombus importantly determines clot lysis velocity. Further, flow-induced mechanical forces which stimulate the transport of thrombolytic agent into the clot influence thrombolysis. Inflammation most probably represents a basic pathogenetic mechanism of activation of coagulation and influences the activity of the fibrinolytic system. Inflammation increases tissue factor release, platelet activity, fibrinogen concentration and inhibits fibrinolysis by increasing plasminogen activator inhibitor 1. Therefore, recanalization of a thrombotic vessel occlusion is inversely related to levels of some circulating inflammatory agents. Consequently, inhibition of inflammation with anti-inflammatory drugs may improve the efficacy of prevention of thromboembolic events and stimulate recanalization of thrombotic occlusions of veins.

In patients with left ventricular assist devices (LVADs), the association of driveline infection (DLI) and body mass index (BMI) remains controversial. The aim of this study was to explore a potential correlation between BMI and DLI in the LVAD patient population. A retrospective, single-center study evaluated patients who underwent LVAD implantation between May 2012 and July 2016. Driveline infection was evaluated per Interagency Registry for Mechanically Assisted Circulatory Support established criteria. Of 222 included patients, 80% were male, the average age was 55 years, and the main underlying heart failure diagnosis was nonischemic cardiomyopathy (56%). The majority of patients (65%) received LVAD as destination therapy and 35% as a bridge to transplantation. Average time-to-first DLI was 296 days after LVAD implantation. In comparison to non-DLI group (80%, N = 177), patients in DLI group (20%, N = 45) had a higher BMI (33.5 ± 8.3 kg/m in DLI group vs. 28.8 ± 7.5 kg/m in non-DLI group, p = 0.0003) and were younger (51 ± 12 years in DLI group vs. 56 ± 12 years in non-DLI group, p = 0.013). There was a significant correlation between BMI and DLI (p < 0.0001), and age was negatively correlated with DLI (p = 0.01). Analysis revealed no correlation between time-to-first DLI and BMI. Our data confirm that higher BMI is associated with increased prevalence of DLI in LVAD population, particularly in younger patients. Addressing excessive body weight in this patient cohort may significantly reduce DLI and thereby improve long-term outcomes.

Surgery represents an increased risk of different perioperative complications. Endothelial function (EF) is a key mechanism responsible for cardiovascular homeostasis and is involved in thromboembolic complications. We aimed to follow changes of EF in an early postoperative period in patients undergoing total hip replacement (THR). Endothelial function was assessed noninvasively in 70 consecutive patients who underwent an elective THR under spinal anesthesia. Flow-mediated dilation (FMD) and low flow-mediated constriction capability of the brachial artery, which are indicators of EF were measured before the operation (baseline), 24 hours after the operative procedure, and 5 to 7 days postoperatively. Baseline FMD was 12.3% and decreased a day after surgery to 7.3% ( P < .001). After 5 to 7 days, it gradually increased to 9.2%. However, on average, it was lower than before surgery ( P < .001). The median duration of THR was 85.0 (65.0-100.0) minutes, the average hospital length of stay was 7 days. Total hip replacement is associated with an immediate decrease in FMD which remains significantly decreased 5 to 7 days after the surgery compared with the preoperative value. These results indicate that surgery provokes endothelial dysfunction and deteriorates cardiovascular homeostasis. This effect could be involved in cardiovascular complications in the postoperative period.

Thrombosis is a consequence of disbalance between the procoagulant and fibrinolytic activity of blood and is frequently associated with chronic sequelae, which are the consequence of chronic occlusion of affected veins. Treatment of venous thrombosis should not be oriented in the prevention of thrombus progression and associated thromboembolic events, but also in stimulation of thrombolysis and recanalization of occluded veins, which are one of the most important preventive mechanisms of late sequelae, including post-thrombotic syndrome. The treatment of acute venous thrombosis (superficial and deep) is based on drugs with anticoagulant activity, like antagonists of vitamin K, heparins, and new oral anticoagulants. One of the most frequently used anticoagulant drugs is heparin, particularly the low molecular weight heparin (LMWH). It was shown that besides strong anticoagulant activity heparin has pro-fibrinolytic effects, which promote thrombolysis and recanalization of occluded veins. LMWH markedly increases tissue factor pathway inhibitor levels and a release of tissue plasminogen activator from vascular endothelium. Heparins are also capable of increasing the nitrogen oxide level, which is responsible for circulatory homeostasis.

Background: Atherosclerosis is a systemic disease with different faces. Despite similar, or even identical, risk factors and pathogenesis, atherosclerotic lesions and their clinical manifestations vary in different parts of the vasculature. Peripheral arterial disease (PAD) in the superficial femoral artery (SFA) represents a frequent clinical manifestation of atherosclerotic disease. The pathohistological characteristics of plaques in PAD differ from lesions in the coronary arteries. Plaques in the SFA have more fibrotic elements with less lipid and degenerative tissue elements; this makes them more stable and less prone to rupture. The density of vasa vasorum, an important determinant of structure and stability of atherosclerotic lesions, is significantly lower in PAD than in coronary arteries. Further, haemodynamic forces and shear stress vary in different segments of the arterial tree and influence the development of atherosclerotic lesions and their stability. It follows that the clinical consequences differ depending on the vascular territory involved. In the coronary arteries, acute thrombotic occlusion with clinical manifestation of myocardial infarction is one of the most frequent manifestations due to unstable atherosclerotic lesions. Atherosclerotic lesions in SFA progress slowly and are more stable; therefore, clinical manifestations develop more gradually., Conclusion: The atherosclerotic process in SFA is frequently asymptomatic or presents as stable intermittent claudication, and in a relatively low percentage, progresses to critical limb ischaemia. Also, remodelling of the arterial wall in peripheral arteries compensates for the reduction of arterial lumen and provides blood flow in spite of relatively large atherosclerotic lesions. However, arterial restenosis after recanalization procedures in SFA reduces the long-term success of recanalization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The traditional treatment of venous thromboembolism (VTE) with heparin and warfarin has numerous limitations. New oral anticoagulants represent the promising alternative with the potential to overcome the limitations of traditional treatment., Objective: Apixaban is an oral factor Xa inhibitor with a rapid onset of action and predictable pharmacokinetics that allows a fixed dose regimen. With this characteristic apixaban overcomes many limitations and simplifies treatment of VTE eliminating the need for initial parenteral anticoagulant therapy and laboratory monitoring., Results: Fixed-dose regimen of oral apixaban alone is as effective as conventional treatment regimen and is associated with a clinically relevant reduction of major bleeding. Extended anticoagulation with apixaban with either a treatment dose (5 mg twice daily) or thromboprophylactic dose (2.5 mg twice daily) reduces the risk of recurrent venous thromboembolism without increase in the rate of major bleeding., Conclusion: Therefore, apixaban provides a simple, effective and safe alternative to conventional acute or long-term treatment of VTE., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Vascular complications are an important cause of morbidity in patients with diabetes mellitus (DM). Endothelial dysfunction is an early marker of atherosclerosis and has already been shown in macrocirculation of diabetic patients; however, data on endothelial function of microcirculation is scarce. Our aim was to evaluate endothelial function in macro- and microcirculation and their interrelationship in patients with type 1 and 2 DM., Methods: The study included 30 patients with type 1 DM, 30 patients with type 2 DM and 25 healthy controls. The endothelial function of large arteries was studied measuring flow-mediated dilation (FMD). Peripheral arterial tonometry was used for investigation of the endothelial function of microcirculation, measuring Reactive Hyperemia Index (RHI) and Augmentation Index (AI)., Results: In comparison to controls, both DM groups had decreased FMD: type 1 (4.0±5.0% vs. 10.0±7.8%, P=0.005) and type 2 (5.0±0.6% vs. 10.0±7.8%, P=0.007). However, only type 2 DM group had a lower RHI (1.71±0.44 vs. 2.05±0.54, P=0.017) in comparison to controls., Conclusions: Patients with type 1 and 2 DM had deteriorated functional capability of macrocirculation. However, endothelial dysfunction of microcirculation was present only in type 2 DM patients. Type 2 DM patients were also at higher risk for atherosclerosis because of the more frequent presence of risk factors.

Purpose: To investigate the relationship between recanalization rate of occluded veins after deep venous thrombosis (DVT) and development of postthrombotic syndrome (PTS)., Materials and Methods: Patients treated for DVT of the lower limbs were evaluated 12-36 months after acute DVT. Of 100 patients, 34 developed PTS, defined as Villalta score of ≥ 5. Symptoms and signs of PTS were assessed, and ultrasound examination of the veins was performed, checking for residual thrombus and presence of reflux., Results: Patients with PTS were older (64.0 y vs 55.5 y; P = .007) and more frequently experienced recurrent DVT (15% vs 3%; P = .030). Patients with PTS had a lower rate of recanalization. Patients with residual thrombus appeared to be at increased risk for PTS development compared with patients with total recanalization (odds ratio 6.0; 95% confidence interval, 1.7-21.9; P = .006). No difference in the presence of reflux was observed., Conclusions: Incomplete or absent recanalization is associated with a higher incidence of PTS, probably as a consequence of deteriorated blood flow and increased venous pressure. This suggests early recanalization could improve the outcome of DVT treatment in selected patients., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT., Aim: To follow inflammatory parameters in a cohort of patients with idiopathic DVT., Methods: Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS)., Results: The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1., Conclusion: Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT.

Implantation of left ventricular assist devices while avoiding cardiopulmonary bypass (CPB) may decrease bleeding and improve postoperative recovery. To understand the effectiveness of this approach, we reviewed the charts of 26 patients who underwent HeartWare left ventricular assist device (HVAD) implantation without use of CPB (off-CPB group) and 22 patients who had HVAD implanted with CPB (CPB group) with an emphasis on the 30 day postoperative period. Preoperatively, both groups had similar demographic, functional, and hemodynamic characteristics. Off-CPB patients had significantly shorter surgery times than CPB patients, 188.5 (161.5-213.3) min versus 265.0 (247.5-299.5) min, respectively; p < 0.001. Blood transfusion requirements during surgery and within the postoperative 48 hour period were significantly lower in the off-CPB group than in the CPB group (odds ratio: 5.9; 95% confidence interval: 1.1-31.1, p = 0.042). Compared with the CPB group, the off-CPB group patients had a shorter intubation time, 21 (17.4-48.5) hours versus 41 (20.6-258.4) hours; p = 0.042. Intensive care unit stay was 7.0 (4.75-13.5) days for off-CPB versus 10.0 (6.0-19.0) days for CPB (p = 0.256). The off-CPB approach allows HVAD to be implanted quickly with significantly less perioperative bleeding and transfusion requirements and facilitates postoperative rehabilitation.

Aim: Inflammation is highlighted in the pathogenesis and destabilization of atherosclerotic lesions. Noninvasive identification of inflammation of atherosclerotic lesions has been challenging. 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a useful technique for detecting inflamed atherosclerotic plaques in vivo. However, it is time consuming, expensive, and accompanied by radiation. Therefore, we investigated the relationship between levels of circulating inflammatory markers and the degree of inflammation of atherosclerotic plaques shown by 18F-FDG uptake. We aimed to identify high-risk patients with inflamed, unstable atherosclerotic plaques on the basis of the determination of inflammatory markers., Methods: The study included 37 patients, 21 with high-grade stenosis of internal carotid artery (ICA group) and 16 with occlusion of common femoral artery (CFA group), who underwent endarterectomy. Mean age of the study population was 69.43±6.2 years. Eight out of 21 patients with ICA stenosis and all patients with CFA occlusion were symptomatic. In all patients before endarterectomy, 18F-FDG-PET imaging was performed and blood samples were obtained for determination of circulating inflammatory markers: high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukins, and selectins. Both groups were compared with a sex- and age-matched control group composed of 27 healthy volunteers., Results: 18F-FDG uptake, calculated by target-to-background ratio (TBR) was not significantly different between the groups. Levels of inflammatory markers were elevated, and there were no significant differences between ICA and CFA groups, with an exception of interleukin 6 (IL-6) levels, which was higher in the ICA group (3.2±2.5 ng/L vs. 1.8±1.3 ng/L, p＜0.05). There was a positive interrelationship between 18F-FDG-PET and most of the systemic inflammatory markers: hsCRP (r=0.417, p=0.010), IL-6 (r=0.603, p＜0.001), and TNF-α (r=0.374, p=0.023). However, correlation between 18F-FDG-PET and P-selectin, E-selectin, and t-PA was not found., Conclusion: Our study showed that an interrelationship exists between the intensity of inflammatory process of atherosclerotic lesions shown by FDG uptake and circulating inflammatory markers. Therefore, the determination of circulating inflammatory markers can have a potential to identify individuals with unstable, inflamed atherosclerotic plaques., Competing Interests: None.

Background: The prognostic importance of preclinical markers of atherosclerosis and their interrelationship are inconclusive. In this study interrelationship between different methods investigating endothelial function and intima media thickness (IMT) was investigated in patients with polycystic ovary syndrome (PCOS)., Methods: Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), low-flow-mediated constriction (L-FMC) and peripheral arterial tonometry (PAT). Arterial stiffness was determined by pulse wave velocity (PWV) and the Augmentation Index (AI). The IMT of carotid arteries was measured., Results: Twenty-eight obese women were recruited with the diagnosis of PCOS, mean age 27±7.2 years and Body Mass Index 38.8±6.3 kg/m2. A relationship between FMD and NMD (r=0.44, P=0.02) was shown. FMD as well as NMD of the brachial artery were not correlated with L-FMC or PAT. The AI and PWV, indicators of arterial stiffness were not interrelated with FMD, and there was no significant interrelationship between IMT and FMD or NMD. The AI was related only to IMT (r=0.45, P=0.30)., Conclusions: The relationship between available methods for evaluation of endothelial function/dysfunction is weak in PCOS. This indicates that different methods investigate different mechanisms and various sections of the circulatory system.

The estimation of risk for atherosclerotic cardiovascular (CV) events based only on the presence of classical risk factors is often insufficient. Therefore, efforts have been made to find markers that indicate the presence of preclinical or clinical disease. Inflammation mediates all stages of the disease, from initiation to the thrombotic complications of atherosclerosis. Raised levels of several circulating markers, particularly inflammatory mediators, have been reported in subjects with atherosclerosis. Increased risk for CV events is associated with increased levels of cytokines, celladhesion molecules, P-selectin and E-selectin, and acute phase reactants, such a highsensitivity C-reactive protein and serum amyloid-A. Elevation of some of these markers predicts the outcomes of patients with acute coronary syndromes. However, because of their non-specificity, these biomarkers represent only a moderate added predicting value after considering conventional CV risk factors. Consequently, recent research has focused on the detection of vulnerable plaque, using vascular bed-specific biomarkers that can help identify individuals at highest risk and help guide how to intervene to prevent CV events. Considerable progress in the understanding of the role of the inflammation in atherogenesis has opened new possibilities for the management of atherosclerosis. Recently new drugs mediating the direct inhibition of circulating markers of inflammation were developed. These drugs could provide a novel therapeutic approach and further enhance the understanding of the role of inflammation in atherosclerosis.

Objective: Varicose veins represent one of the most frequent vascular diseases and are in most cases benign. However, advanced disease is frequently associated with complications such as chronic venous insufficiency and superficial vein thrombosis. The pathogenic mechanisms are not well understood. Besides increased venous pressure, it is suggested that local blood constituents trigger various mechanisms responsible for the progression of the disease and its complications., Design: The aim of this study was to investigate the changes in the blood in varicose veins and to compare them with the systemic markers of inflammation and endothelial damage., Materials and Methods: Forty patients with primary varicose veins were included in the study. Most patients were class C2. Blood samples were taken from the leg from the tortuous and dilated varicose tributaries of the great saphenous vein and from the cubital vein., Results: The values of basic hematologic tests were comparable between blood samples (varicose vs. systemic). In varicose veins, the following parameters were significantly increased in comparison with systemic blood: hsCRP (3.12 ± 2.18 mg/L vs. 2.04 ± 2.21 mg/L, p = .04), IL-6 (3.54 ± 2.59 pg/mL vs. 2.25 ± 1.27 pg/mL, p = .008), vWF (118.4  ±  27% vs. 83.2  ±  22%, p < .05). D-dimer, in samples taken from the leg varicose veins, was also significantly higher than in the systemic blood (104.3 ± 9.3 ng/mL vs. 89.5 ± 8.3 ng/mL, p = .039)., Conclusions: Some inflammatory markers and indicators of endothelial dysfunction are increased in varicose vein blood. This is most probably the consequence of deteriorated blood flow in dilated and tortuous superficial veins, and increased venous pressure. Damage to the venous wall, which causes a chronic inflammatory response, together with the procoagulant properties of local blood may promote further progression of the disease and thrombotic complications., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Atherosclerosis is considered a generalized disease. Similar or identical etiopathogenetic mechanisms and risk factors are involved in various atherosclerotic diseases, and the positive effects of preventive measures on atherogenesis in different parts of the arterial system were shown. However, until know, great emphasis has been placed on the aggressive pharmacological management of coronary artery disease (CHD), while less attention has been devoted to the management of peripheral arterial disease (PAD), despite its significant morbidity and mortality. Data on the efficacy of preventive measures in PAD patients have mostly been gained from subgroup analyses from studies devoted primarily to the management of coronary patients. These data have shown that treatment of risk factors for atherosclerosis with drugs can reduce cardiovascular events also in patients with PAD. The effects of some preventive procedures in PAD patients differ from coronary patients. Aspirin as a basic antiplatelet drug has been shown to be less effective in PAD patients than in coronary patients. The latest Antithrombotic Trialists' Collaboration (ATC) meta-analysis demonstrates no benefit of aspirin in reducing cardiovascular events in PAD. Statins reduce cardiovascular events in all three of the most frequently presented cardiovascular diseases, including PAD to a comparable extent. Recent studies indicate that in PAD patients, in addition to a reduction in cardiovascular events, statins may have some hemodynamic effects. They prolong walking distance and improve quality of life. Similarly, angiotensin enzyme inhibitors are also effective in the prevention of cardiovascular events in coronary, cerebrovascular, as well as PAD patients and show positive effects on the walking capacity of patients with intermittent claudication. In PAD patients, the treatment of hypertension and diabetes also effectively prevents cardiovascular morbidity and mortality. As PAD patients are at a highest risk of cardiovascular complications, the risk factors of atherosclerosis should be treated intensively in this group of patients. Most of the preventive measures, including the drugs used for prevention of CHD, are also effective in PAD patients.

The aim of this study was to follow the thrombus progression and regression in superficial veins of lower limbs in patients with superficial vein thrombosis (SVT) treated with low-molecular-weight heparin. Patients (n = 68) with a first symptomatic SVT of the lower limbs received 2 different dosages of dalteparin. The primary outcome was a change in the diameter and length of thrombus in the affected veins. The regression of thrombus was not significantly different between the groups (P = .19). The reduction in the length of thrombus as well as thrombus diameter was significantly greater in females. At the end of the observation period, the length of thrombus in the distal part was more reduced than in the proximal segments. It seems that the dosage of anticoagulant drug does not have a significant impact on thrombus resolution., (© The Author(s) 2014.)